bluuebunny/crossref_metadata_2025 huggingface dataset:
Human–crocodile conflict in the Indian Sundarban: an analysis of spatio-temporal incidences in relation to people's livelihood
Authors: Das Chandan Surabhi , Jana Rabindranath
Published: August 2017

The incidence of human–crocodile conflict is increasing, and fear of injury and loss of life is affecting public and political support for crocodile conservation. We studied conflicts between people and estuarine crocodiles Crocodylus porosus across socio-economic dimensions, using a spatio-temporal database. We collected data on 127 crocodile attacks that occurred during 2000–2013, through questionnaires including open- and close-ended questions, administered in 30 villages of five blocks of the Indian Sundarban. Most of the attacks (42%) occurred during winter (December–February), followed by the early monsoon (May–July; 27%). Almost 80% of victims were prawn seed collectors and were 11–50 years old, and 61.16% of victims died as a result of the attacks. Female victims accounted for a higher percentage of deaths (55.12%) than male victims (44.88%). Crocodile attacks were more common in the daytime than at night, with 76.35% of the killings occurring during 08.00–17.00. Most of the cases were recorded from Gosaba (34%), followed by Patharpratima (25.24%) and Namkhana (18.45%) blocks. The mean number of incidents per year was 9.07, with vulnerability and mortality rates of 0.07 and 0.04, respectively, per 10,000 persons. Existing management practices are insufficient to eliminate the risk of crocodile attacks and ensure the conservation of the Sundarban ecosystem. A comprehensive management plan for reducing dependency on forest resources is needed to minimize human–crocodile conflict.
The chain of security
Authors: de Goede Marieke
Published: August 2017

Increasingly, private companies – including Twitter, airlines, and banks – find themselves in the frontline of fighting terrorism and other security threats, because they are obliged to mine and expel suspicious transactions. This analytical work of companies forms part of a chain, whereby transactions data are analysed, collected, reported, shared, and eventually deployed as a basis for intervention by police and prosecution. This article develops the notion of theChain of Securityin order to conceptualise the ways in which security judgements are made across public/private domains and on the basis of commercial transactions. Drawing on the work of Bruno Latour, this article understands the security chain as the set of practices whereby commercial transactions are collected, stored, transferred, and analysed, in order to arrive at security facts. Understanding the trajectory of the suspicious transaction as a series of translations across professional domains draws attention to the processes of sequencing, movement, and referral in the production of security judgements. The article uses the chain of financial suspicious transactions reporting as example to show how this research ‘thinking tool’ can work. In doing so, it aims to contribute to debates at the intersection between International Relations (IR) and Science-and-Technology Studies (STS).
The model of the influence of the electron refluxing on the electron transport andKαemission
Authors: Zhao J.C. , Cao L.H. , Zheng J.H. , Zhao Z.Q. , Liu Z.J. , Zheng C.Y. , Zhang H. , Gu Y.Q. , Liu J.
Published: August 2017

In our previous research (Zhaoet al., 2016), we focus on the transport processes from hot electrons toKαX-ray emission in a copper foil and nanobrush target when the electron refluxing effect is not taken into account. In this work, considering the refluxing effect, the transport of hot electrons in a solid target is studied by adding the electric fields both at the front and rear surfaces of the target with Monte Carlo code Geant4. Simulation results show that the electron refluxing has an important influence onKαphoton yield and the size ofKαradiation source.Kαyield from the 10-μm-thick target with the electron refluxing effect is 2.7–3.7 times more than that without the refluxing for the electron temperatures from 0.4 to 1.4 MeV. The laser-to-Kαphoton energy conversion efficiency${\rm \eta} _{L \to K_{\rm \alpha}} $with the refluxing effect is always higher than that without the refluxing, and both of them decrease gradually with laser strengthIλ2. Considering the electron refluxing effect or not, the variations ofKαyield with the target thicknessdare very different. A critical thickness of the targetdc(~30 μm) is achieved to confirm whether the refluxing effect is valid for the target. For the target with the thicknessdless thandc, the refluxing effect can enhanceKαyield with several times, while for the target with the thicknessdlarger thandc, the refluxing effect is not so effective. The full-width at half-maximum increases from 23 to 56 µm after including the refluxing effect by the electron beam with the radius of 10 µm and the temperature of 400 keV.
South Korea's Linguistic Tangle: English vs. Korean vs. Konglish
Authors: McPhail Sean A.
Published: August 2017

Konglish is a blend of Korean and English found throughout South Korea, and often suffers for lack of prestige amongst Koreans. The primary aim of this article is to determine the reasons behind Konglish's low social status in Korea. I begin my investigation by exploring Korean public space as linguistic space, and examining in what social and cultural capacities Koreans use English, Mandarin, Korean, and Konglish. I then shift in part II to discuss perceptions of Korean and English inside Korea. Having analysed Koreans’ attitudes towards Konglish's parent languages, I discuss in part III why Konglish struggles for social legitimacy, despite its ubiquity. In the course of this investigation it will become clear that Koreans often deride Konglish for its ease of use. Because one absorbs it organically through cultural exposure rather than hours of study and millions of won in tuition fees, Konglish accords none of the prestige that comes with Standard English; meanwhile, Konglish's mixed nature means not only that it cannot benefit from the national pride Koreans associate with ‘pure’ Korean, but also that this pride harms Konglish's reception throughout the country.
Molecular survey ofBartonella henselaeandBartonella clarridgeiaein pet cats across Japan by species-specific nested-PCR
Authors: SATO S. , KABEYA H. , NEGISHI A. , TSUJIMOTO H. , NISHIGAKI K. , ENDO Y. , MARUYAMA S.
Published: August 2017

Cats are known to be the main reservoir forBartonella henselaeandBartonella clarridgeiae, which are the agents of ‘cat-scratch disease’ in humans. In the present study, we investigated the prevalence of the twoBartonellaspecies on 1754 cat bloods collected from all prefectures in Japan during 2007–2008 by a nested-polymerase chain reaction (PCR) targeting the 16S–23S rRNA internal transcribed spacer region. Overall,BartonellaDNA was detected in 4·6% (80/1754) of the cats examined. The nested-PCR showed that 48·8% (39/80) of the positive cats were infected withB. henselaemono-infection, 33·8% (27/80) withB. clarridgeiaemono-infection and 17·5% (14/80) were infected with both species. The prevalence (5·9%; 65/1103) ofBartonellainfection in the western part of Japan was significantly higher than that (2·3%; 15/651) of eastern Japan (P< 0·001). Statistical analysis of the cats examined suggested a significant association betweenBartonellainfection and FeLV infection (OR = 1·9; 95% CI = 1·1–3·4), but not with FIV infection (OR = 1·6; 95% CI = 1·0–2·6).
Reassessment of the distribution and population size of Spizella wortheni
Authors: SCOTT-MORALES LAURA M. , VELA-COIFFIER PATRICIA , COTERA-CORREA MAURICIO , ALMEJO-RAMOS MIRNA , CANALES-DELGADILLO JULIO
Published: August 2017

Information deficit constrains our capacity to assess the status of threatened species in regional and global contexts. In this study of the endangered Worthen’s Sparrow Spizella wortheni, we first review its current and potential distribution using the species distribution software, Maxent. An initial basic model was constructed using historical records, and used to guide a subsequent search for additional populations in summer 2013. Using the information gathered from our survey, we built a second, breeding model, to update the current and potential species distribution. Population size was estimated using line transects of variable length to count singing males and calculate densities per 10 ha. We found 10 new small reproductive populations dispersed south of the established core area, increasing the extent of occurrence of the species from 25 km2 to almost 17,000 km2. Suitable habitat across the species’ range was more than threefold higher in the breeding compared with the basic model. We counted 316 males, with a mean density of four individuals per 10 ha. Our results demonstrate that conservation assessment based on limited records can exaggerate the vulnerability of species, and confirm that the Worthen’s Sparrow population and geographic distribution range are larger than previously determined, indicating that the Red List status of this species should be reconsidered. The use of niche models was successful in enhancing species information data quantity (e.g. range extensions) and quality (e.g. more precise habitat requirements), facilitating improved understanding of needs and conservation status in the wild.
Neo-oogenesis in mammals
Authors: Porras-Gómez Tania Janeth , Moreno-Mendoza Norma
Published: August 2017

Recently, the existence of a mechanism for neo-oogenesis in the ovaries of adult mammals has generated much controversy within reproductive biology. This mechanism, which proposes that the ovary has cells capable of renewing the follicular reserve, has been described for various species of mammals. The first evidence was found in prosimians and humans. However, these findings were not considered relevant because the predominant dogma for reproductive biology at the time was that of Zuckerman. This dogma states that female mammals are born with finite numbers of oocytes that decline throughout postnatal life. Currently, the concept of neo-oogenesis has gained momentum due to the discovery of cells with mitotic activity in adult ovaries of various mammalian species (mice, humans, rhesus monkeys, domestic animals such as pigs, and wild animals such as bats). Despite these reports, the concept of neo-oogenesis has not been widely accepted by the scientific community, generating much criticism and speculation about its accuracy because it has been impossible to reproduce some evidence. This controversy has led to the creation of two positions: one in favour of neo-oogenesis and the other against it. Various animal models have been used in support of both camps, including both classic laboratory animals and domestic and wild animals. The aim of this review is to critically present the current literature on the subject and to evaluate the arguments pro and contra neo-oogenesis in mammals.
Post-transplant lymphoproliferative disease is associated with early sternotomy and left ventricular hypoplasia during infancy: a population-based retrospective review
Authors: Ekman-Joelsson Britt-Marie , Wåhlander Håkan , Synnergren Mats , Sager Madeleine , Mellgren Karin
Published: August 2017

Background

Heart transplantation has been an option for children in Sweden since 1989. As our unit faced an increased rate of post-transplant lymphoproliferative disorder, the objective of the study was to identify possible risk factors.

Methods

This is a retrospective study of all children aged 0–18 years who underwent heart transplantation in Gothenburg from 1989 to 2014.

Results

A total of 71 children underwent heart transplantation. The overall incidence of post-transplant lymphoproliferative disorder was 14% (10/71); however, 17% (6/36) of those undergoing transplantation after 2007 developed lymphoma, compared with only 10% (4/35) of transplantation cases before 2007 (p=0.85). The mean age at transplantation was 9 years (0–17). The mean post-transplant follow-up time was 5.5 years (0.5–21.9) in the group that developed post-transplant lymphoproliferative disorder, compared with 10.2 years (0.02–25.2) in those who did not. In our study group, risk factors for post-transplant lymphoproliferative disorder were surgically palliated CHD (p=0.0005), sternotomy during infancy (p⩽0.0001), hypoplastic left ventricle (p=0.0001), number of surgical events (p=0.0022), mismatch concerning Epstein–Barr virus infection – that is, a positive donor–negative recipient (p⩽0.0001) – and immunosuppressive treatment with tacrolimus compared with ciclosporine (p=0.028).

Discussion

This study has three major findings. First, post-transplant lymphoproliferative disorder only developed in subjects born with CHD. Second, the vast majority (9/10) of the subjects developing the disorder had undergone sternotomy as infants. Third, the number of surgical events correlated with a higher risk for developing post-transplant lymphoproliferative disorder.
To use or not to use: Feature selection for sentiment analysis of highly imbalanced data
Authors: KÜBLER SANDRA , LIU CAN , SAYYED ZEESHAN ALI
Published: August 2017

We investigate feature selection methods for machine learning approaches in sentiment analysis. More specifically, we use data from the cooking platform Epicurious and attempt to predict ratings for recipes based on user reviews. In machine learning approaches to such tasks, it is a common approach to use word or part-of-speech n-grams. This results in a large set of features, out of which only a small subset may be good indicators for the sentiment. One of the questions we investigate concerns the extension of feature selection methods from a binary classification setting to a multi-class problem. We show that an inherently multi-class approach, multi-class information gain, outperforms ensembles of binary methods. We also investigate how to mitigate the effects of extreme skewing in our data set by making our features more robust and by using review and recipe sampling. We show that over-sampling is the best method for boosting performance on the minority classes, but it also results in a severe drop in overall accuracy of at least 6 per cent points.
Assessment of cognitive function in patients with metastatic cancer: Are we using the right tools?
Authors: Kurita Geana Paula , Sandvad Marlene , Lundorff Lena , De Mattos-Pimenta Cibele Andrucioli , Højsted Jette , Sjøgren Per
Published: August 2017

Objective:

This study aimed at analyzing the validity and reliability of the continuous reaction time (CRT) test, the finger-tapping test (FTT), the Digit Span Test (DST), the Trail Making Test – part B (TMTB), and the Mini-Mental State Examination (MMSE) in patients with metastatic cancer.

Method:

Eighty adult patients and 81 healthy controls were assessed between July of 2010 and November of 2015. The neuropsychological tests were analyzed regarding construct/discriminant/criterion validity and reliability.

Results:

In terms of construct validity, it was not possible to estimate a model for the MMSE because of a skewed response distribution. For discriminant validity, patients were slower on two measures of the CRT (p= 0.00483,p= 0.00030) and FTT dominant hand (p= 0.00306). Regarding sensitivity and specificity, only the DST and TMTB seemed to predict cognitive deficit; however, the ROC curve areas were ≤ 0.73. In terms of criterion validity, there were few significant correlations between the tests and the sociodemographic and clinical variables, and for the most part were very weak. Reliability was deemed to be adequate for the TMTB, DST, and FTT.

Significance of results:

The findings of the full validation analyses were not clear-cut. However, CRT test, DST, FTT, and TMTB demonstrated partial positive results, indicating that these tests have good potential for use in clinical settings and require further study.
Exercise during pregnancy and its impact on mothers and offspring in humans and mice
Authors: Ferrari N. , Bae-Gartz I. , Bauer C. , Janoschek R. , Koxholt I. , Mahabir E. , Appel S. , Alejandre Alcazar M. A. , Grossmann N. , Vohlen C. , Brockmeier K. , Dötsch J. , Hucklenbruch-Rother E. , Graf C.
Published: August 2017

Exercise during pregnancy has beneficial effects on maternal and offspring’s health in humans and mice. The underlying mechanisms remain unclear. This comparative study aimed to determine the long-term effects of an exercise program on metabolism, weight gain, body composition and changes in hormones [insulin, leptin, brain-derived neurotrophic factor (BDNF)]. Pregnant women (n=34) and mouse dams (n=44) were subjected to an exercise program compared with matched controls (period I). Follow-up in the offspring was performed over 6 months in humans, corresponding to postnatal day (P) 21 in mice (period II). Half of the mouse offspring was challenged with a high-fat diet (HFD) for 6 weeks between P70 and P112 (period III). In period I, exercise during pregnancy led to 6% lower fat content, 40% lower leptin levels and an increase of 50% BDNF levels in humans compared with controls, which was not observed in mice. After period II in humans and mice, offspring body weight did not differ from that of the controls. Further differences were observed in period III. Offspring of exercising mouse dams had significantly lower fat mass and leptin levels compared with controls. In addition, at P112, BDNF levels in offspring were significantly higher from exercising mothers while this effect was completely blunted by HFD feeding. In this study, we found comparable effects on maternal and offspring’s weight gain in humans and mice but different effects in insulin, leptin and BDNF. The long-term potential protective effects of exercise on biomarkers should be examined in human studies.
Lysine demethylase KDM2A inhibits TET2 to promote DNA methylation and silencing of tumor suppressor genes in breast cancer
Authors: Chen J-Y , Luo C-W , Lai Y-S , Wu C-C , Hung W-C
Published: August 2017

The coupling between DNA methylation and histone modification contributes to aberrant expression of oncogenes or tumor suppressor genes that leads to tumor development. Our previous study demonstrated that lysine demethylase 2A (KDM2A) functions as an oncogene in breast cancer by promoting cancer stemness and angiogenesis via activation of the Notch signaling. Here, we demonstrate that knockdown of KDM2A significantly increases the 5′-hydroxymethylcytosine (5′-hmc) level in genomic DNA and expression of tet-eleven translocation 2 (TET2) in various breast cancer cell lines. Conversely, ectopic expression of KDM2A inhibits TET2 expression in KDM2A-depleted cells suggesting TET2 is a transcriptional repression target of KDM2A. Our results show that KDM2A interacts with RelA to co-occupy at the TET2 gene promoter to repress transcription and depletion of RelA or KDM2A restores TET2 expression. Upregulation of TET2 in the KDM2A-depleted cells induces the re-activation of two TET downstream tumor suppressor genes, epithelial cell adhesion molecule (EpCAM) and E-cadherin, and inhibits migration and invasion. On the contrary, knockdown of TET2 in these cells decreases EpCAM and E-cadherin and increases cell invasiveness. More importantly, TET2 expression is negatively associated KDM2A in triple-negative breast tumor tissues, and its expression predicts a better survival. Taken together, we demonstrate for the first time that TET2 is a direct repression target of KDM2A and reveal a novel mechanism by which KDM2A promotes DNA methylation and breast cancer progression via the inhibition of a DNA demethylase.
Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine
Authors: Marsian Johanna , Fox Helen , Bahar Mohammad W. , Kotecha Abhay , Fry Elizabeth E. , Stuart David I. , Macadam Andrew J. , Rowlands David J. , Lomonossoff George P.
Published: August 2017

Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus. Such a sVLP would retain the native antigenic conformation and the repetitive structure of the original virus particle, but lack infectious genomic material. In this study, we report the production of synthetically stabilized PV VLPs in plants. Mice carrying the gene for the human PV receptor are protected from wild-type PV when immunized with the plant-made PV sVLPs. Structural analysis of the stabilized mutant at 3.6 Å resolution by cryo-electron microscopy and single-particle reconstruction reveals a structure almost indistinguishable from wild-type PV3.
Sparse orthogonal population representation of spatial context in the retrosplenial cortex
Authors: Mao Dun , Kandler Steffen , McNaughton Bruce L. , Bonin Vincent
Published: August 2017

Sparse orthogonal coding is a key feature of hippocampal neural activity, which is believed to increase episodic memory capacity and to assist in navigation. Some retrosplenial cortex (RSC) neurons convey distributed spatial and navigational signals, but place-field representations such as observed in the hippocampus have not been reported. Combining cellular Ca2+ imaging in RSC of mice with a head-fixed locomotion assay, we identified a population of RSC neurons, located predominantly in superficial layers, whose ensemble activity closely resembles that of hippocampal CA1 place cells during the same task. Like CA1 place cells, these RSC neurons fire in sequences during movement, and show narrowly tuned firing fields that form a sparse, orthogonal code correlated with location. RSC ‘place’ cell activity is robust to environmental manipulations, showing partial remapping similar to that observed in CA1. This population code for spatial context may assist the RSC in its role in memory and/or navigation.
Two-magnon scattering in the 5d all-in-all-out pyrochlore magnet Cd2Os2O7
Authors: Nguyen Thi Minh Hien , Sandilands Luke J. , Sohn C. H. , Kim C. H. , Wysocki Aleksander L. , Yang In-Sang , Moon S. J. , Ko Jae-Hyeon , Yamaura J. , Hiroi Z. , Noh Tae Won
Published: August 2017

5d pyrochlore oxides with all-in-all-out magnetic order are prime candidates for realizing strongly correlated, topological phases of matter. Despite significant effort, a full understanding of all-in-all-out magnetism remains elusive as the associated magnetic excitations have proven difficult to access with conventional techniques. Here we report a Raman spectroscopy study of spin dynamics in the all-in-all-out magnetic state of the 5d pyrochlore Cd2Os2O7. Through a comparison between the two-magnon scattering and spin-wave theory, we confirm the large single ion anisotropy in this material and show that the Dzyaloshinskii–Moriya and exchange interactions play a significant role in the spin-wave dispersions. The Raman data also reveal complex spin–charge–lattice coupling and indicate that the metal–insulator transition in Cd2Os2O7 is Lifshitz-type. Our work establishes Raman scattering as a simple and powerful method for exploring the spin dynamics in 5d pyrochlore magnets.
Membrane-free culture and real-time barrier integrity assessment of perfused intestinal epithelium tubes
Authors: Trietsch Sebastiaan J. , Naumovska Elena , Kurek Dorota , Setyawati Meily C. , Vormann Marianne K. , Wilschut Karlijn J. , Lanz Henriëtte L. , Nicolas Arnaud , Ng Chee Ping , Joore Jos , Kustermann Stefan , Roth Adrian , Hankemeier Thomas , Moisan Annie , Vulto Paul
Published: August 2017

In vitro models that better reflect in vivo epithelial barrier (patho-)physiology are urgently required to predict adverse drug effects. Here we introduce extracellular matrix-supported intestinal tubules in perfused microfluidic devices, exhibiting tissue polarization and transporter expression. Forty leak-tight tubules are cultured in parallel on a single plate and their response to pharmacological stimuli is recorded over 125 h using automated imaging techniques. A study comprising 357 gut tubes is performed, of which 93% are leak tight before exposure. EC50-time curves could be extracted that provide insight into both concentration and exposure time response. Full compatibility with standard equipment and user-friendly operation make this Organ-on-a-Chip platform readily applicable in routine laboratories.
Time-lapse crystallography snapshots of a double-strand break repair polymerase in action
Authors: Jamsen Joonas A. , Beard William A. , Pedersen Lars C. , Shock David D. , Moon Andrea F. , Krahn Juno M. , Bebenek Katarzyna , Kunkel Thomas A. , Wilson Samuel H.
Published: August 2017

DNA polymerase (pol) μ is a DNA-dependent polymerase that incorporates nucleotides during gap-filling synthesis in the non-homologous end-joining pathway of double-strand break repair. Here we report time-lapse X-ray crystallography snapshots of catalytic events during gap-filling DNA synthesis by pol μ. Unique catalytic intermediates and active site conformational changes that underlie catalysis are uncovered, and a transient third (product) metal ion is observed in the product state. The product manganese coordinates phosphate oxygens of the inserted nucleotide and PPi. The product metal is not observed during DNA synthesis in the presence of magnesium. Kinetic analyses indicate that manganese increases the rate constant for deoxynucleoside 5′-triphosphate insertion compared to magnesium. The likely product stabilization role of the manganese product metal in pol μ is discussed. These observations provide insight on structural attributes of this X-family double-strand break repair polymerase that impact its biological function in genome maintenance.
The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation
Authors: Wang Jing , Ge Pupu , Qiang Lihua , Tian Feng , Zhao Dongdong , Chai Qiyao , Zhu Mingzhao , Zhou Rongbin , Meng Guangxun , Iwakura Yoichiro , Gao George Fu , Liu Cui Hua
Published: August 2017

Mycobacterium tuberculosisPtpA is a secreted effector protein that dephosphorylates several proteins in the host cell cytoplasm, such as p-JNK, p-p38, and p-VPS33B, leading to suppression of host innate immunity. Here we show that, in addition, PtpA enters the nucleus of host cells and regulates the expression of host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration (such asGADD45A). PtpA can bind directly to the promoter region ofGADD45Ain vitro. Both phosphatase activity and DNA-binding ability of PtpA are important in suppressing host innate immune responses. Furthermore, PtpA-expressingMycobacterium bovisBCG promotes proliferation and migration of human lung adenoma A549 cells in vitro and in a mouse xenograft model. Further research is needed to test whether mycobacteria, via PtpA, might affect cell proliferation or migration in humans.
Reduced and unstratified crust in CV chondrite parent body
Authors: Ganino Clément , Libourel Guy
Published: August 2017

Early Solar System planetesimal thermal models predict the heating of the chondritic protolith and the preservation of a chondritic crust on differentiated parent bodies. Petrological and geochemical analyses of chondrites have suggested that secondary alteration phases formed at low temperatures (<300 °C) by fluid-rock interaction where reduced and oxidized Vigarano type Carbonaceous (CV) chondrites witness different physicochemical conditions. From a thermodynamical survey of Ca-Fe-rich secondary phases in CV3 chondrites including silica activity (aSiO2), here we show that the classical distinction between reduced and oxidized chondrites is no longer valid and that their Ca-Fe-rich secondary phases formed in similar reduced conditions near the iron-magnetite redox buffer at low aSiO2 (log(aSiO2) <−1) and moderate temperature (210–610 °C). The various lithologies in CV3 chondrites are inferred to be fragments of an asteroid percolated heterogeneously via porous flow of hydrothermal fluid. Putative ‘onion shell’ structures are not anymore a requirement for the CV parent body crust.
Lyn and Fyn function as molecular switches that control immunoreceptors to direct homeostasis or inflammation
Authors: Mkaddem Sanae Ben , Murua Amaya , Flament Héloise , Titeca-Beauport Dimitri , Bounaix Carine , Danelli Luca , Launay Pierre , Benhamou Marc , Blank Ulrich , Daugas Eric , Charles Nicolas , Monteiro Renato C.
Published: August 2017

Immunoreceptors can transduce either inhibitory or activatory signals depending on ligand avidity and phosphorylation status, which is modulated by the protein kinases Lyn and Fyn. Here we show that Lyn and Fyn control immune receptor signaling status. SHP-1 tyrosine 536 phosphorylation by Lyn activates the phosphatase promoting inhibitory signaling through the immunoreceptor. By contrast, Fyn-dependent phosphorylation of SHP-1 serine 591 inactivates the phosphatase, enabling activatory immunoreceptor signaling. These SHP-1 signatures are relevant in vivo, as Lyn deficiency exacerbates nephritis and arthritis in mice, whereas Fyn deficiency is protective. Similarly, Fyn-activating signature is detected in patients with lupus nephritis, underlining the importance of this Lyn–Fyn balance. These data show how receptors discriminate negative from positive signals that respectively result in homeostatic or inflammatory conditions.
Human microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles
Authors: Chen Hsin-Yi , Wu Chien-Ting , Tang Chieh-Ju C. , Lin Yi-Nan , Wang Won-Jing , Tang Tang K.
Published: August 2017

Mutations in many centriolar protein-encoding genes cause primary microcephaly. Using super-resolution and electron microscopy, we find that the human microcephaly protein, RTTN, is recruited to the proximal end of the procentriole at early S phase, and is located at the inner luminal walls of centrioles. Further studies demonstrate that RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly. CRISPR/Cas9-mediated RTTN gene knockout in p53-deficient cells induce amplification of primitive procentriole bodies that lack the distal-half centriolar proteins, POC5 and POC1B. Additional analyses show that RTTN serves as an upstream effector of CEP295, which mediates the loading of POC1B and POC5 to the distal-half centrioles. Interestingly, the naturally occurring microcephaly-associated mutant, RTTN (A578P), shows a low affinity for STIL binding and blocks centriole assembly. These findings reveal that RTTN contributes to building full-length centrioles and illuminate the molecular mechanism through which the RTTN (A578P) mutation causes primary microcephaly.
Bias induced up to 100% spin-injection and detection polarizations in ferromagnet/bilayer-hBN/graphene/hBN heterostructures
Authors: Gurram M. , Omar S. , Wees B. J. van
Published: August 2017

We study spin transport in a fully hBN encapsulated monolayer-graphene van der Waals heterostructure at room temperature. A top-layer of bilayer-hBN is used as a tunnel barrier for spin-injection and detection in graphene with ferromagnetic cobalt electrodes. We report surprisingly large and bias-induced (differential) spin-injection (detection) polarizations up to 50% (135%) at a positive voltage bias of + 0.6 V, as well as sign inverted polarizations up to −70% (−60%) at a reverse bias of −0.4 V. This demonstrates the potential of bilayer-hBN tunnel barriers for practical graphene spintronics applications. With such enhanced spin-injection and detection polarizations, we report a record two-terminal (inverted) spin-valve signals up to 800 Ω with a magnetoresistance ratio of 2.7%, and achieve spin accumulations up to 4.1 meV. We propose how these numbers can be increased further, for future technologically relevant graphene based spintronic devices.
Genome re-sequencing reveals the history of apple and supports a two-stage model for fruit enlargement
Authors: Duan Naibin , Bai Yang , Sun Honghe , Wang Nan , Ma Yumin , Li Mingjun , Wang Xin , Jiao Chen , Legall Noah , Mao Linyong , Wan Sibao , Wang Kun , He Tianming , Feng Shouqian , Zhang Zongying , Mao Zhiquan , Shen Xiang , Chen Xiaoliu , Jiang Yuanmao , Wu Shujing , Yin Chengmiao , Ge Shunfeng , Yang Long , Jiang Shenghui , Xu Haifeng , Liu Jingxuan , Wang Deyun , Qu Changzhi , Wang Yicheng , Zuo Weifang , Xiang Li , Liu Chang , Zhang Daoyuan , Gao Yuan , Xu Yimin , Xu Kenong , Chao Thomas , Fazio Gennaro , Shu Huairui , Zhong Gan-Yuan , Cheng Lailiang , Fei Zhangjun , Chen Xuesen
Published: August 2017

Human selection has reshaped crop genomes. Here we report an apple genome variation map generated through genome sequencing of 117 diverse accessions. A comprehensive model of apple speciation and domestication along the Silk Road is proposed based on evidence from diverse genomic analyses. Cultivated apples likely originate fromMalus sieversiiin Kazakhstan, followed by intensive introgressions fromM. sylvestris.M. sieversiiin Xinjiang of China turns out to be an “ancient” isolated ecotype not directly contributing to apple domestication. We have identified selective sweeps underlying quantitative trait loci/genes of important fruit quality traits including fruit texture and flavor, and provide evidences supporting a model of apple fruit size evolution comprising two major events with one occurring prior to domestication and the other during domestication. This study outlines the genetic basis of apple domestication and evolution, and provides valuable information for facilitating marker-assisted breeding and apple improvement.
Dirac point induced ultralow-threshold laser and giant optoelectronic quantum oscillations in graphene-based heterojunctions
Authors: Haider Golam , Ravindranath Rini , Chen Tzu-Pei , Roy Prathik , Roy Pradip Kumar , Cai Shu-Yi , Chang Huan-Tsung , Chen Yang-Fang
Published: August 2017

The occurrence of zero effective mass of electrons at the vicinity of the Dirac point is expected to create new paradigms for scientific research and technological applications, but the related discoveries are rather limited. Here, we demonstrate that a simple architecture composed of graphene quantum dots sandwiched by graphene layers can exhibit several intriguing features, including the Dirac point induced ultralow-threshold laser, giant peak-to-valley ratio (PVR) with ultra-narrow spectra of negative differential resistance and quantum oscillations of current as well as light emission intensity. In particular, the threshold of only 12.4 nA cm−2 is the lowest value ever reported on electrically driven lasers, and the PVR value of more than 100 also sets the highest record compared with all available reports on graphene-based devices. We show that all these intriguing phenomena can be interpreted based on the unique band structures of graphene quantum dots and graphene as well as resonant quantum tunneling.
The mTORC1-4E-BP-eIF4E axis controls de novo Bcl6 protein synthesis in T cells and systemic autoimmunity
Authors: Yi Woelsung , Gupta Sanjay , Ricker Edd , Manni Michela , Jessberger Rolf , Chinenov Yurii , Molina Henrik , Pernis Alessandra B.
Published: August 2017

Post-transcriptional modifications can control protein abundance, but the extent to which these alterations contribute to the expression of T helper (TH) lineage-defining factors is unknown. Tight regulation of Bcl6 expression, an essential transcription factor for T follicular helper (TFH) cells, is critical as aberrant TFH cell expansion is associated with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here we show that lack of the SLE risk variant Def6 results in deregulation of Bcl6 protein synthesis in T cells as a result of enhanced activation of the mTORC1–4E-BP–eIF4E axis, secondary to aberrant assembly of a raptor–p62–TRAF6 complex. Proteomic analysis reveals that this pathway selectively controls the abundance of a subset of proteins. Rapamycin or raptor deletion ameliorates the aberrant TFH cell expansion in mice lacking Def6. Thus deregulation of mTORC1-dependent pathways controlling protein synthesis can result in T-cell dysfunction, indicating a mechanism by which mTORC1 can promote autoimmunity.
Formation pathways of mesoporous silica nanoparticles with dodecagonal tiling
Authors: Sun Yao , Ma Kai , Kao Teresa , Spoth Katherine A. , Sai Hiroaki , Zhang Duhan , Kourkoutis Lena F. , Elser Veit , Wiesner Ulrich
Published: August 2017

Considerable progress in the fabrication of quasicrystals demonstrates that they can be realized in a broad range of materials. However, the development of chemistries enabling direct experimental observation of early quasicrystal growth pathways remains challenging. Here, we report the synthesis of four surfactant-directed mesoporous silica nanoparticle structures, including dodecagonal quasicrystalline nanoparticles, as a function of micelle pore expander concentration or stirring rate. We demonstrate that the early formation stages of dodecagonal quasicrystalline mesoporous silica nanoparticles can be preserved, where precise control of mesoporous silica nanoparticle size down to <30 nm facilitates comparison between mesoporous silica nanoparticles and simulated single-particle growth trajectories beginning with a single tiling unit. Our results reveal details of the building block size distributions during early growth and how they promote quasicrystal formation. This work identifies simple synthetic parameters, such as stirring rate, that may be exploited to design other quasicrystal-forming self-assembly chemistries and processes.
Inference and interrogation of a coregulatory network in the context of lipid accumulation in Yarrowia lipolytica
Authors: Trébulle Pauline , Nicaud Jean-Marc , Leplat Christophe , Elati Mohamed
Published: August 2017

Complex phenotypes, such as lipid accumulation, result from cooperativity between regulators and the integration of multiscale information. However, the elucidation of such regulatory programs by experimental approaches may be challenging, particularly in context-specific conditions. In particular, we know very little about the regulators of lipid accumulation in the oleaginous yeast of industrial interest Yarrowia lipolytica. This lack of knowledge limits the development of this yeast as an industrial platform, due to the time-consuming and costly laboratory efforts required to design strains with the desired phenotypes. In this study, we aimed to identify context-specific regulators and mechanisms, to guide explorations of the regulation of lipid accumulation in Y. lipolytica. Using gene regulatory network inference, and considering the expression of 6539 genes over 26 time points from GSE35447 for biolipid production and a list of 151 transcription factors, we reconstructed a gene regulatory network comprising 111 transcription factors, 4451 target genes and 17048 regulatory interactions (YL-GRN-1) supported by evidence of protein–protein interactions. This study, based on network interrogation and wet laboratory validation (a) highlights the relevance of our proposed measure, the transcription factors influence, for identifying phases corresponding to changes in physiological state without prior knowledge (b) suggests new potential regulators and drivers of lipid accumulation and (c) experimentally validates the impact of six of the nine regulators identified on lipid accumulation, with variations in lipid content from +43.2% to −31.2% on glucose or glycerol.
β1-adrenergic receptor O-glycosylation regulates N-terminal cleavage and signaling responses in cardiomyocytes
Authors: Park Misun , Reddy Gopireddy R. , Wallukat Gerd , Xiang Yang K. , Steinberg Susan F.
Published: August 2017

β1-adrenergic receptors (β1ARs) mediate catecholamine actions in cardiomyocytes by coupling to both Gs/cAMP-dependent and Gs-independent/growth-regulatory pathways. Structural studies of the β1AR define ligand-binding sites in the transmembrane helices and effector docking sites at the intracellular surface of the β1AR, but the extracellular N-terminus, which is a target for post-translational modifications, typically is ignored. This study identifies β1AR N-terminal O-glycosylation at Ser37/Ser41 as a mechanism that prevents β1AR N-terminal cleavage. We used an adenoviral overexpression strategy to show that both full-length/glycosylated β1ARs and N-terminally truncated glycosylation-defective β1ARs couple to cAMP and ERK-MAPK signaling pathways in cardiomyocytes. However, a glycosylation defect that results in N-terminal truncation stabilizes β1ARs in a conformation that is biased toward the cAMP pathway. The identification of O-glycosylation and N-terminal cleavage as novel structural determinants of β1AR responsiveness in cardiomyocytes could be exploited for therapeutic advantage.
Conductance fluctuations in InAs quantum wells possibly driven by Zitterbewegung
Authors: Iwasaki Yu , Hashimoto Yoshiaki , Nakamura Taketomo , Katsumoto Shingo
Published: August 2017

The highly successful Dirac equation predicts peculiar phenomena such as Klein tunnelling and Zitterbewegung (ZB) of electrons. From its conception by Erwin Schrödinger, ZB has been considered key in understanding relativistic quantum mechanics. However, observing the ZB of electrons has proved difficult, and instead various emulations of the phenomenon have been proposed producing several successes. Concerning charge transport in semiconductors and graphene, expectations were high but little has been reported. Here, we report a surprisingly large ZB effect on charge transport in a semiconductor nanostructure playing “flat pinball”. The setup is a narrow strip of InAs two-dimensional electron gas with strong Rashba spin–orbit coupling. Six quantum point contacts act as pinball pockets. In transiting between two contacts, ZB appears as a large reproducible conductance fluctuation that depends on the in-plane magnetic field. Numerical simulations successfully reproduced our experimental observations confirming that ZB causes this conductance fluctuation.
Reconstruction of a Genome-scale Metabolic Network of Komagataeibacter nataicola RZS01 for Cellulose Production
Authors: Zhang Heng , Ye Chao , Xu Nan , Chen Chuntao , Chen Xiao , Yuan Fanshu , Xu Yunhua , Yang Jiazhi , Sun Dongping
Published: August 2017

Bacterial cellulose (BC) is widely used in industries owing to its high purity and strength. Although Komagataeibacter nataicola is a representative species for BC production, its intracellular metabolism leading to BC secretion is unclear. In the present study, a genome-scale metabolic network of cellulose-producing K. nataicola strain RZS01 was reconstructed to understand its metabolic behavior. This model iHZ771 comprised 771 genes, 2035 metabolites, and 2014 reactions. Constraint-based analysis was used to characterize and evaluate the critical intracellular pathways. The analysis revealed that a total of 71 and 30 genes are necessary for cellular growth in a minimal medium and complex medium, respectively. Glycerol was identified as the optimal carbon source for the highest BC production. The minimization of metabolic adjustment algorithm identified 8 genes as potential targets for over-production of BC. Overall, model iHZ771 proved to be a useful platform for understanding the physiology and BC production of K. nataicola.
Fermentative hydrogen production from Jerusalem artichoke by Clostridium tyrobutyricum expressing exo-inulinase gene
Authors: Jiang Ling , Wu Qian , Xu Qing , Zhu Liying , Huang He
Published: August 2017

Clostridium tyrobutyricum ATCC25755 has been reported as being able to produce significant quantities of hydrogen. In this study, the exo-inulinase encoding gene cloned from Paenibacillus polymyxa SC-2 was into the expression plasmid pSY6 and expressed in the cells of C. tyrobutyricum. The engineered C. tyrobutyricum strain efficiently fermented the inulin-type carbohydrates from Jerusalem artichoke, without any pretreatment being necessary for the production of hydrogen. A comparatively high hydrogen yield (3.7 mol/mol inulin-type sugar) was achieved after 96 h in a batch process with simultaneous saccharification and fermentation (SSF), with an overall volumetric productivity rate of 620 ± 60 mL/h/L when the initial total sugar concentration of the inulin extract was increased to 100 g/L. Synthesis of inulinase in the batch SSF culture was closely associated with strain growth until the end of the exponential phase, reaching a maximum activity of 28.4 ± 0.26 U/mL. The overall results show that the highly productive and abundant biomass crop Jerusalem artichoke can be a good substrate for hydrogen production, and that the application of batch SSF for its conversion has the potential to become a cost-effective process in the near future.
Magnetic moment evolution and spin freezing in doped BaFe2As2
Authors: Pelliciari Jonathan , Huang Yaobo , Ishii Kenji , Zhang Chenglin , Dai Pengcheng , Chen Gen Fu , Xing Lingyi , Wang Xiancheng , Jin Changqing , Ding Hong , Werner Philipp , Schmitt Thorsten
Published: August 2017

Fe-K
β
X-ray emission spectroscopy measurements reveal an asymmetric doping dependence of the magnetic moments μbare in electron- and hole-doped BaFe2As2. At low temperature, μbare is nearly constant in hole-doped samples, whereas it decreases upon electron doping. Increasing temperature substantially enhances μbare in the hole-doped region, which is naturally explained by the theoretically predicted crossover into a spin-frozen state. Our measurements demonstrate the importance of Hund’s-coupling and electronic correlations, especially for hole-doped BaFe2As2, and the inadequacy of a fully localized or fully itinerant description of the 122 family of Fe pnictides.
A dynamical framework for complex fractional killing
Authors: Ballweg Richard , Paek Andrew L. , Zhang Tongli
Published: August 2017

When chemotherapy drugs are applied to tumor cells with the same or similar genotypes, some cells are killed, while others survive. This fractional killing contributes to drug resistance in cancer. Through an incoherent feedforward loop, chemotherapy drugs not only activate p53 to induce cell death, but also promote the expression of apoptosis inhibitors which inhibit cell death. Consequently, cells in which p53 is activated early undergo apoptosis while cells in which p53 is activated late survive. The incoherent feedforward loop and the essential role of p53 activation timing makes fractional killing a complex dynamical challenge, which is hard to understand with intuition alone. To better understand this process, we have constructed a representative model by integrating the control of apoptosis with the relevant signaling pathways. After the model was trained to recapture the observed properties of fractional killing, it was analyzed with nonlinear dynamical tools. The analysis suggested a simple dynamical framework for fractional killing, which predicts that cell fate can be altered in three possible ways: alteration of bifurcation geometry, alteration of cell trajectories, or both. These predicted categories can explain existing strategies known to combat fractional killing and facilitate the design of novel strategies.