bluuebunny/crossref_metadata_2025 huggingface dataset:
Geology, biostratigraphy and carbon isotope chemostratigraphy of the Palaeogene fossil-bearing Dakhla sections, southwestern Moroccan Sahara
Authors: BENAMMI MOULOUD , ADNET SYLVAIN , MARIVAUX LAURENT , YANS JOHAN , NOIRET CORENTIN , TABUCE RODOLPHE , SURAULT JÉRÔME , EL KATI IMAD , ENAULT SÉBASTIEN , BAIDDER LAHSSEN , SADDIQI OMAR , BENAMMI MOHAMED
Published: October 2017

New Palaeogene vertebrate localities were recently reported in the southern Dakhla area (southwestern Morocco). The Eocene sediment strata crops out on cliffs along the Atlantic Ocean coast. Vertebrate remains come from five conglomeratic sandstone beds and are principally represented by isolated teeth belonging to micromammals, selachians and bony fishes, a proboscidean assigned to ?Numidotheriumsp. and many remains of archaeocete whales (Basilosauridae). From fieldwork five lithostratigraphic sections were described, essentially based on the lithological characteristic of sediments. Despite the lateral variations of facies, correlations between these five sections were possible on the basis of fossil-bearing beds (A1, B1, B2, C1 and C2) and five lithological units were identified. The lower part of the section consists of rhythmically bedded, chert-rich marine siltstones and marls with thin black phosphorite with organic matter at the base. The overlying units include coarse-grained to microconglomeratic sandstones interbedded with silts, indicating deposition in a shallow-marine environment with fluvial influence. The natural remanence magnetization of a total of 50 samples was measured; the intensity of most of the samples is too weak however, before or after the first step of demagnetization. The palaeomagnetic data from the samples are very unstable, except for eight from three similar sandstone levels which show a normal polarity. Matched with biostratigraphic data on rodents, primates, the selachian, sirenian and cetacean faunas, the new carbon isotope chemostratigraphy on organics (1) refines the age of the uppermost C2 fossil-bearing bed to earliest Oligocene time and (2) confirms the Priabonian age of the B1 to C1 levels.
Alive but not well: the limited validity but continued utility of the concept of schizophrenia
Authors: Zoghbi Anthony W. , Lieberman Jeffrey A.
Published: October 2017

Guloksuz & van Os boldly challenge the status quo as pertains to schizophrenia. In ‘The Slow Death of the Concept of Schizophrenia, and the Painful Birth of the Psychosis Spectrum’ (Guloksuz & van Os, 2017) they thoughtfully review long-standing concerns about this diagnostic category and present a new conceptualization. The authors question the validity of the schizophrenia concept citing variable clinical outcomes, transdiagnostic manifestations of psychosis, and the difficulty in identifying biomarkers, among other concerns. They also point toward the over-representation of schizophrenia in the psychosis literature and lament that patients and clinicians have come to associate this illness with predominantly poor outcomes. Finally, they propose removing the diagnosis of schizophrenia from the diagnostic nomenclature and instituting a broad new classification system, ‘psychosis spectrum disorder’ (PSD), to capture the many manifestations of psychosis. In this commentary, we advise against the institution of a psychosis spectrum due to the potential negative effects this framework would have on clinical care and progress in biological research.
Observation and interpretation of neutron origin prior to hard X rays and pinch in a hundred joules plasma focus device
Authors: Jain J. , Moreno J. , Morales D. , Davis S. , Bora B. , Avaria G. , Inestrosa-Izurieta M.J. , Soto L.
Published: October 2017

The temporal correlation between neutron and hard X-ray (HXR) emissions from a hundred joules plasma focus device (PF-400J) was studied. A method, time history analysis, to estimate the time of origin of neutrons with respect to HXRs is applied. In most of the discharges, it was found that neutrons are originated before HXRs in the axial direction and after HXRs in the radial direction. In some discharges, the time difference between HXRs and neutrons origin was found large enough, so that it can be interpreted that those neutrons would have been originated before the pinch. A qualitative discussion is conjectured to explain the experimental observations.
WEAK CONVERGENCE TO STOCHASTIC INTEGRALS UNDER PRIMITIVE CONDITIONS IN NONLINEAR ECONOMETRIC MODELS
Authors: Peng Jiangyan , Wang Qiying
Published: October 2017

Limit theory with stochastic integrals plays a major role in time series econometrics. In earlier contributions on weak convergence to stochastic integrals, the literature commonly uses martingale and semi-martingale structures. Liang, Phillips, Wang, and Wang (2016) (see also Wang (2015), Chap. 4.5) currently extended weak convergence to stochastic integrals by allowing for a linear process or a α-mixing sequence in innovations. While these martingale, linear process and α-mixing structures have wide relevance, they are not sufficiently general to cover many econometric applications that have endogeneity and nonlinearity. This paper provides new conditions for weak convergence to stochastic integrals. Our frameworks allow for long memory processes, causal processes, and near-epoch dependence in innovations, which have applications in a wide range of econometric areas such as TAR, bilinear, and other nonlinear models.
An asymptotic for the average number of amicable pairs for elliptic curves
Authors: PARKS JAMES
Published: October 2017

Amicable pairs for a fixed elliptic curve defined over ℚ were first considered by Silverman and Stange where they conjectured an order of magnitude for the function that counts such amicable pairs. This was later refined by Jones to give a precise asymptotic constant. The author previously proved an upper bound for the average number of amicable pairs over the family of all elliptic curves. In this paper we improve this result to an asymptotic for the average number of amicable pairs for a family of elliptic curves.
Protectionist Empire: Trade, Tariffs, and United States Foreign Policy, 1890–1914
Authors: Fordham Benjamin O.
Published: October 2017

Between 1890 and 1914, the United States acquired overseas colonies, built a battleship fleet, and intervened increasingly often in Latin America and East Asia. This activism is often seen as the precursor to the country's role as a superpower after 1945 but actually served very different goals. In contrast to its pursuit of a relatively liberal international economic order after 1945, the United States remained committed to trade protection before 1914. Protectionism had several important consequences for American foreign policy on both economic and security issues. It led to a focus on less developed areas of the world that would not export manufactured goods to the United States instead of on wealthier European markets. It limited the tactics available for promoting American exports, forcing policymakers to seek exclusive bilateral agreements or unilateral concessions from trading partners instead of multilateral arrangements. It inhibited political cooperation with other major powers and implied an aggressive posture toward these states. The differences between this foreign policy and the one the United States adopted after 1945 underscore the critical importance not just of the search for overseas markets but also of efforts to protect the domestic market.
How to fight terrorism? Political and strategic aspects
Authors: Vad Erich
Published: October 2017

“Fighting terrorism is like eating soup with a fork” (Shimon Peres). Peres’s quote symbolically captures the key problem of countering terrorism. 9/11 proved to be a hallmark in the global perception of modern terrorism. The following questions form the framework of the present essay: What is the essence of modern terrorism? How did it develop during the past two decades? Who are the key players within the terror framework? What are the root causes for global terrorism? How are we to deal appropriately with the global phenomenon of terrorism? Are there any solutions (short-, medium-, long-term) to terrorism? If yes, where do we have to look for them? The underlying essay provides a strategic overview of antiterrorism policy that is based on the author’s years-long experience as a high-level expert and advisor within the security policy framework. For this reason, citations are expressly not included. The key target audience comprises laypersons interested in the phenomenon of global terrorism and its social interplay.
Diversification and labor productivity on US permaculture farms
Authors: Ferguson Rafter Sass , Lovell Sarah Taylor
Published: October 2017

The relationship between diversification and labor productivity is a pressing issue for diversified farming systems (DFS), which must compete with the high labor productivity of specialized and mechanized industrial farming systems. Synergies between multiple production systems represent an alternative pathway for enhancing labor productivity, contrasting with the economies of scale achieved by industrial farming. Facing a lack of technical and institutional support for managing diversified systems, DFS turn to grassroots agroecological networks for support. Permaculture is a grassroots network with an emphasis on diversified production that—despite its international scope and high public profile—has received little scholarly attention. In this exploratory study we assessed the relationship between diversification, labor productivity and involvement with permaculture, using data from 196 enterprises (i.e., distinct sources of income or aspects of a farm business) on 36 permaculture farms in the USA. We characterized diversification in two ways: by income at the level of the whole farm, and by labor for production enterprises only. By fitting a multilevel model of labor productivity (enterprises nested within farms) we assessed the evidence for synergies in production, i.e., positive relationships between diversification and returns to labor. Results indicated that both production diversity and level of involvement in the permaculture network had significant positive effects on labor productivity. This effect disappeared, however, when both diversity and participation were at their highest levels. Results also indicate that high levels of diversification shift tree crops from the lowest labor productivity of any type of production enterprise to the highest. Through this first ever (to our knowledge) systematic investigation of permaculture farms, our results provide support for the presence of production synergies in DFS, and for the role of permaculture in helping farmers achieve these synergies.
The impact of tillage regime and row cover use on insect pests and yield in organic cucurbit production
Authors: Skidmore Amanda , Wilson Neil , Williams Mark , Bessin Ricardo
Published: October 2017

Control of cucurbit pests, such as striped cucumber beetle (Acalymma vittatum), spotted cucumber beetle (Diabrotica undecimpunctata howardi) and squash bug (Anasa tristis), in organic systems is difficult due to a lack of effective insecticide options. This has led to the development of many integrated pest management techniques, such as use of row covers, crop rotation and cover crops. This study explored the novel use of strip tillage and row covers to reduce pest pressure in summer squash (Cucurbita pepe) and muskmelon (Cucumis melo) production systems. Results showed that although strip tillage reduced striped cucumber beetle and squash bug numbers, there was a yield reduction in both crops compared with the plasticulture system. Row cover increased marketable yield in both systems, with the highest yield being in the plasticulture system. Unmarketable fruit directly attributed to insect damage was higher in the plasticulture systems, but was not significantly different when compared with the strip tillage system. Although there are many documented positive attributes of strip tillage, results from this study indicate that a combination of plasticulture and row cover may be a superior system for organic cucurbit production.
A Question of Control? Examining the Role of Control Conditions in Experimental Psychopathology using the Example of Cognitive Bias Modification Research
Authors: Blackwell Simon E. , Woud Marcella L. , MacLeod Colin
Published: October 2017

While control conditions are vitally important in research, selecting the optimal control condition can be challenging. Problems are likely to arise when the choice of control condition is not tightly guided by the specific question that a given study aims to address. Such problems have become increasingly apparent in experimental psychopathology research investigating the experimental modification of cognitive biases, particularly as the focus of this research has shifted from theoretical questions concerning mechanistic aspects of the association between cognitive bias and emotional vulnerability, to questions that instead concern the clinical efficacy of ‘cognitive bias modification’ (CBM) procedures. We discuss the kinds of control conditions that have typically been employed in CBM research, illustrating how difficulties can arise when changes in the types of research questions asked are not accompanied by changes in the control conditions employed. Crucially, claims made on the basis of comparing active and control conditions within CBM studies should be restricted to those conclusions allowed by the specific control condition employed. CBM studies aiming to establish clinical utility are likely to require quite different control conditions from CBM studies aiming to illuminate mechanisms. Further, conclusions concerning the clinical utility of CBM interventions cannot necessarily be drawn from studies in which the control condition has been chosen to answer questions concerning mechanisms. Appreciating the need to appropriately alter control conditions in the transition from basic mechanisms-focussed investigations to applied clinical research could greatly facilitate the translational process.
Positive Technologies for Understanding and Promoting Positive Emotions
Authors: Baños Rosa María , Carrillo Alba , Etchemendy Ernestina , Botella Cristina
Published: October 2017

Information and Communication Technologies (ICTs) have become increasingly present in our lives, and their use has spread considerably. This paper presents a review of the way ICTs can help practitioners and researchers to study, promote, and train positive emotions. It is framed within the field of Positive Technologies: the applied scientific approach to the study of the use of technology to improve the quality of personal experience, with the goal of increasing wellbeing. First, the article presents an introduction to the topic of technologies and positive emotions. Then, it describes how ICTs can aid in monitoring, assessing, promoting, modifying, and training positive emotions. Finally, implications and future directions of the role of Positive Technologies in positive emotions are discussed. The authors conclude that, in the near future, Positive Technologies and the field of positive emotions will interact synergistically, producing an exponential growth in the understanding and promotion of positive emotions.
Burnout und chronischer beruflicher Stress
Authors: Hillert Andreas , Koch Stefan , Lehr Dirk
Published: October 2017

Angesichts der aktuellen, von zunehmendem Druck dominierten Arbeitswelt, erleben viele berufstätige Menschen andauernden Stress, nicht wenige fühlen sich überlastet und „ausgebrannt“. Chronischer beruflicher Stress und Erschöpfungszustände beeinträchtigen die Lebensqualität und sind u.a. ein Risikofaktor dafür, psychisch zu erkranken. Der Ratgeber informiert über die Zusammenhänge von beruflicher Belastung sowie von Stress- und Burnouterleben. Er stellt wissenschaftlich fundierte und praktisch bewährte Strategien vor, wie chronischem Stress begegnet werden kann.
Chronischer beruflicher Stress weist darauf hin, dass etwas aus der Balance gekommen ist. Nach dem Modell der beruflichen Gratifikationskrise ist die Balance zwischen beruflichem Engagement und den dafür erhaltenen Gratifikationen, z. B. von Gehalt und Wertschätzung, für die körperliche und psychische Gesundheit von zentraler Bedeutung. Im Ratgeber werden die Leser anhand von Fallbeispielen und konkreten Anleitungen darin unterstützt, die eigene Gratifikationsbalance zu überprüfen und zu verändern. Es werden Strategien vorgestellt, wie mit Arbeitsbedingungen umgegangen werden kann, die zu hohe Verausgabung erfordern oder wie das eigene Engagement so angepasst werden kann, dass die Gesundheit einen höheren Stellenwert bekommt. Zur Balance tragen ebenso Anleitungen bei, wie mit ausbleibender Wertschätzung umgegangen werden kann, die Fähigkeit zur gedanklichen Distanzierung nach der Arbeit gestärkt und die Erholungskompetenz verbessert werden kann. Der Ratgeber eignet sich sowohl als persönlicher Einstieg in die Thematik als auch als Ergänzung zu Coaching oder ambulanter Psychotherapie.
Confirmatory Factor Analysis of the Coalitional Mate Retention	Inventory (CMRI) and Evidence for Two Superordinate Domains
Authors: Barbaro Nicole , Sela Yael , Lopes Guilherme S. , Shackelford Todd K.
Published: October 2017

Abstract. The Coalitional Mate Retention Inventory (CMRI; Pham, Barbaro, Mogilski, & Shackelford, 2015 ) assesses the frequency with which individuals solicit allies to assist with mate retention efforts. The current study subjected the CMRI to confirmatory factor analyses (CFAs). A model comparison approach was employed using data from a large community sample of participants currently in a heterosexual romantic relationship ( n = 1,003, 54% male). The seven-factor structure of the CMRI demonstrates good model fit and provides significantly better fit than an alternative single-factor structure. The results also demonstrate that the seven tactics of the CMRI are subsumed by two superordinate domains of Benefit-Provisioning and Cost-Inflicting coalitional mate retention. Correlational analyses with the superordinate domains of coalitional mate retention are presented and highlight their predictive utility. We recommend the continued use of the CMRI in psychological research.
The Evolutionary Life History Model of Externalizing Personality: Bridging Human and Animal Personality Science to Connect Ultimate and Proximate Mechanisms Underlying Aggressive Dominance, Hostility, and Impulsive Sensation Seeking
Authors: Hengartner Michael P.
Published: October 2017

The present work proposes an evolutionary model of externalizing personality that defines variation in this broad psychobiological phenotype resulting from genetic influences and a conditional adaptation to high-risk environments with high extrinsic morbidity-mortality. Due to shared selection pressure, externalizing personality is coadapted to fast life history strategies and maximizes inclusive fitness under adverse environmental conditions by governing the major trade-offs between reproductive versus somatic functions, current versus future reproduction, and mating versus parenting efforts. According to this model, externalizing personality is a regulatory device at the interface between the individual and its environment that is mediated by 2 overlapping psychobiological systems, that is, the attachment and the stress-response system. The attachment system coordinates interpersonal behavior and intimacy in close relationships and the stress-response system regulates the responsivity to environmental challenge and both physiological and behavioral reactions to stress. These proximate mechanisms allow for the integration of neuroendocrinological processes underlying interindividual differences in externalizing personality. Hereinafter I further discuss the model's major implications for personality psychology, psychiatry, and public health policy.
Inhibition of Caspase-8 does not protect from alcohol-induced liver apoptosis but alleviates alcoholic hepatic steatosis in mice
Authors: Hao Fengjie , Cubero Francisco Javier , Ramadori Pierluigi , Liao Lijun , Haas Ute , Lambertz Daniela , Sonntag Roland , Bangen Jörg- Martin , Gassler Nikolaus , Hoss Mareike , Streetz Konrad L , Reissing Johanna , Zimmermann Henning W , Trautwein Christian , Liedtke Christian , Nevzorova Yulia A
Published: October 2017

Hepatic apoptosis is involved in the progression of alcoholic liver disease (ALD). Caspase-8, the apical initiator in death receptor-mediated apoptosis, has been implicated in acute liver injury and in non-alcoholic steatohepatitis. However, the relevance of Caspase-8 in the pathogenesis of ALD remains unclear. In the present study, we investigated the impact of Caspase-8 in human and murine alcohol-induced apoptosis and in ALD. We investigated human samples from ALD patients, primary mouse hepatocytes, and hepatocyte-specific Caspase-8 knockout (Casp8Δhepa) mice in acute and chronic models of ethanol (EtOH) administration. Caspase-8 activation was detected in liver biopsies from ALD patients, as well as in livers of wild-type (WT) mice after chronic ethanol feeding for 8 weeks using the Lieber-DeCarli model. Lack of Caspase-8 expression in Casp8Δhepa animals failed to prevent alcohol-induced liver damage and apoptosis. Instead, inhibition of Caspase-8 shifted the ethanol-induced death signals towards pronounced activation of the intrinsic, mitochondria-dependent apoptosis pathway in Casp8Δhepa livers involving enhanced release of cytochrome c, stronger Caspase-9 activation and specific morphological changes of mitochondria. In vitro and in vivo intervention using a pan-caspase inhibitor markedly attenuated alcohol-induced hepatocyte damage in a Caspase-8-independent manner. Surprisingly, EtOH-fed Casp8Δhepa mice displayed significantly attenuated steatosis and reduced hepatic triglyceride and free fatty acids content. Caspase-8 is dispensable for alcohol-induced apoptosis, but plays an unexpected role for alcohol-dependent fat metabolism. We provide evidence that simultaneous inhibition of extrinsic and intrinsic apoptosis signaling using pan-caspase inhibitors in vivo might be an optimal approach to treat alcohol-induced liver injury.
Glucocorticoid mediates prenatal caffeine exposure-induced endochondral ossification retardation and its molecular mechanism in female fetal rats
Authors: Shangguan Yangfan , Jiang Hongqiang , Pan Zhengqi , Xiao Hao , Tan Yang , Tie Kai , Qin Jun , Deng Yu , Chen Liaobin , Wang Hui
Published: October 2017

Our previous studies discovered that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) and long-bone dysplasia in offspring rats, accompanied by maternal glucocorticoid over-exposure. This study is to explore whether intrauterine high glucocorticoid level can cause endochondral ossification retardation and clarify its molecular mechanism in PCE fetal rats. Pregnant Wistar rats were intragastrically administered 30 and 120 mg/kg day of caffeine during gestational days (GDs) 9–20, then collected fetal serum and femurs at GD20. In vitro, primary chondrocytes were treated with corticosterone (0–1250 nM), caffeine (0–100 μM), mitogen-inducible gene 6 (Mig-6) siRNA and epidermal growth factor receptor (EGFR) siRNA, respectively, or together. Results showed that the hypertrophic chondrocytes zone (HZ) of PCE fetal femur was widened. Meanwhile, the expression levels of chondrocytes terminal differentiation genes in the HZ were decreased, and the chondrocytes apoptosis rate in the HZ was decreased too. Furthermore, PCE upregulated Mig-6 and suppressed EGFR expression in the HZ. In vitro, a high-concentration corticosterone (1250 nM) upregulated Mig-6 expression, inhibit EGFR/c-Jun N-terminal kinase (JNK) signaling pathway and terminal differentiation genes expression in chondrocytes and reduced cell apoptosis, and these above alterations could be partly reversed step-by-step after Mig-6 and EGFR knockdown. However, caffeine concentration dependently increased chondrocyte apoptosis without significant changes in the expression of terminal differentiation genes. Collectively, PCE caused endochondral ossification retardation in the female fetal rats, and its main mechanism was associated with glucocorticoid (rather than caffeine)-mediated chondrocyte terminal differentiation suppression by the upregulation of Mig-6 and then inhibition of EGFR/JNK pathway-mediated chondrocyte apoptosis.
Calreticulin promotes EGF-induced EMT in pancreatic cancer cells via Integrin/EGFR-ERK/MAPK signaling pathway
Authors: Sheng Weiwei , Chen Chuanping , Dong Ming , Wang Guosen , Zhou Jianping , Song He , Li Yang , Zhang Jian , Ding Shuangning
Published: October 2017

Our previous study showed that Calreticulin (CRT) promoted the development of pancreatic cancer (PC) through ERK/MAPK pathway. We next investigate whether CRT promotes EGF-induced epithelial–mesenchymal transition (EMT) in PC via Integrin/EGFR-ERK/MAPK signaling, which has not been reported yet to our knowledge. EGF simultaneously induced EMT and activated Integrin/EGFR–ERK/MAPK signaling pathway in 3 PC cells. However, CRT silencing significantly inhibited EGF function, including inhibiting EGF-induced EMT-like cell morphology, EGF-enhanced cell invasion and migration, and EGF induced the decrease of E-cadherin, ZO-1, and β-catenin and the increase of the key proteins in Integrin/EGFR-ERK/MAPK signaling (pEGFR-tyr1173, Fibronectin, Integrinβ1, c-Myc and pERK). Conversely, CRT overexpression rescued the change of EMT-related proteins induced by EGF in CRT silencing PC cells. Additionally, CRT was co-stained with pEGFR1173 (with EGF), Fibronectin and Integrinβ1 by IF under confocal microscopy and was co-immunoprecipitated with Fibronectin, Integrinβ1 and c-Myc in both PC cells, all of which indicating a close interaction of CRT with Integrin/EGFR–ERK/MAPK signaling pathway in PC. In vivo, CRT silencing inhibited subcutaneous tumor growth and liver metastasis of pancreatic tumor. A positive relationship of CRT with Fibronectin, Integrinβ1, c-Myc and pERK and a negative association of CRT with E-cad was also observed in vivo and clinical samples. Meanwhile, overexpression of the above proteins was closely associated with multiple aggressive clinicopathological characteristics and the poor prognosis of PC patients. CRT promotes EGF-induced EMT in PC cells via Integrin/EGFR-ERK/MAPK signaling pathway, which would be a promising therapy target for PC.
CITED2 affects leukemic cell survival by interfering with p53 activation
Authors: Mattes Katharina , Berger Gerbrig , Geugien Marjan , Vellenga Edo , Schepers Hein
Published: October 2017

CITED2 (CBP/p300-interacting-transactivator-with-an-ED-rich-tail 2) is a regulator of the acetyltransferase CBP/p300 and elevated CITED2 levels are shown in a number of acute myeloid leukemia (AML). To study the in vivo role of CITED2 in AML maintenance, AML cells were transduced with a lentiviral construct for RNAi-mediated knockdown of CITED2. Mice transplanted with CITED2-knockdown AML cells (n=4) had a significantly longer survival compared to mice transplanted with control AML cells (P<0.02). In vitro, the reduction of CITED2 resulted in increased p53-mediated apoptosis and CDKN1A expression, whereas BCL2 levels were reduced. The activation of p53 upon CITED2 knockdown is not a direct consequence of increased CBP/p300-activity towards p53, since no increased formation of CBP/p300/p53 complexes was demonstrated and inhibition of CBP/p300-activity could not rescue the phenotype of CITED2-deficient cells. Instead, loss of CITED2 had an inhibitory effect on the AKT-signaling pathway, which was indicated by decreased levels of phosphorylated AKT and altered expression of the AKT-pathway regulators PHLDA3 and SOX4. Notably, simultaneous upregulation of BCL2 or downregulation of the p53-target gene PHLDA3 rescued the apoptotic phenotype in CITED2-knockdown cells. Furthermore, knockdown of CITED2 led to a decreased interaction of p53 with its inhibitor MDM2, which results in increased amounts of total p53 protein. In summary, our data indicate that CITED2 functions in pathways regulating p53 activity and therefore represents an interesting target for AML therapy, since de novo AML cases are characterized by an inactivation of the p53 pathway or deregulation of apoptosis-related genes.
PLOD2 regulated by transcription factor FOXA1 promotes metastasis in NSCLC
Authors: Du Hongzhi , Chen Yulong , Hou Xiaoying , Huang Yue , Wei Xiaohui , Yu Xiaowen , Feng Shuyun , Wu Yao , Zhan Meixiao , Shi Xin , Lin Sensen , Lu Ligong , Yuan Shengtao , Sun Li
Published: October 2017

In multiple types of tumors, fibrotic collagen is regarded as the 'highway' for cancer cell migration, which is mainly modified by lysyl hydroxylase 2 (PLOD2). The previous findings have demonstrated that the expression of PLOD2 was regulated by multiple factors, including HIF-1α, TGF-β and microRNA-26a/b. Although PLOD2 was confirmed to be related to poor prognosis in lung adenocarcinoma, the regulatory mechanism and function of PLOD2 in human lung adenocarcinoma is poorly understood. On the other hand, upregulation or hyperactivation of epidermal growth factor receptor is considered as a prognostic marker in many cancers, especially in non-small-cell lung cancer (NSCLC). In this study, we found that PLOD2 was elevated in NSCLC specimens and positively links to NSCLC poor prognosis. Gain- and loss-of-function studies and orthotopic implantation metastasis model pinpointed that PLOD2 promotes NSCLC metastasis directly by enhancing migration and indirectly by inducing collagen reorganization. In addition, we revealed that PLOD2 was regulated by PI3K/AKT-FOXA1 axis. The transcription factor FOXA1 directly bound to the PLOD2 promoter, and turned on PLOD2 transcription. In summary, our findings revealed a regulatory mechanism of NSCLC metastasis through EGFR-PI3K/AKT-FOXA1-PLOD2 pathway, and provided PLOD2 as a therapeutic target for NSCLC treatment.
The non-invasive serum biomarker soluble Axl accurately detects advanced liver fibrosis and cirrhosis
Authors: Staufer Katharina , Dengler Mirko , Huber Heidemarie , Marculescu Rodrig , Stauber Rudolf , Lackner Carolin , Dienes Hans-Peter , Kivaranovic Danijel , Schachner Christian , Zeitlinger Markus , Wulkersdorfer Beatrix , Rauch Peter , Prager Gerhard , Trauner Michael , Mikulits Wolfgang
Published: October 2017

Soluble Axl (sAxl) was recently shown to be strongly released into the blood during liver fibrogenesis and hepatocellular carcinoma suggesting sAxl as a biomarker of liver diseases. In this study we are the first to evaluate sAxl in human serum in comparison to Enhanced Liver Fibrosis (ELF) test and transient elastography (TE; Fibroscan) for its value to detect significant (F≥2), advanced fibrosis (F≥3), and cirrhosis (F4) in different liver disease etiologies and healthy controls. To properly determine the diagnostic accuracy of sAxl, a test cohort as well as a validation cohort was employed using liver biopsy as a reference method. Most notably, sAxl was confirmed to be an accurate biomarker of liver fibrosis and cirrhosis. Its accuracy was increased, if total serum albumin was added to build a sAxl/albumin ratio. Thereby an AUC of 0.763, 0.776, 0.826, and 0.832 was achieved corresponding to histological fibrosis stages F≥2, F≥3, F4 with liver biopsy as a reference method, and cirrhosis according to imaging techniques, respectively. With a cut-off of 1.29, a sensitivity, specificity, PPV, and NPV of 78.5%, 80.1%, 44%, 94.9% for the detection of cirrhosis was achieved. In comparison, ELF test and TE showed an AUC of 0.910, and 0.934, respectively, for the detection of cirrhosis. However, performance of TE was not possible in 14.4% of patients and both, ELF™ test and TE bear the disadvantage of high costs. In conclusion, the sAxl/albumin ratio is suggested as an accurate biomarker of liver fibrosis and cirrhosis. Due to its easy applicability and low costs it is suitable as screening parameter for significant to advanced liver fibrosis and cirrhosis, especially if TE is not available or not applicable.
Requirement for CCNB1 in mouse spermatogenesis
Authors: Tang Ji-Xin , Li Jian , Cheng Jin-Mei , Hu Bian , Sun Tie-Cheng , Li Xiao-Yu , Batool Aalia , Wang Zhi-Peng , Wang Xiu-Xia , Deng Shou-Long , Zhang Yan , Chen Su-Ren , Huang Xingxu , Liu Yi-Xun
Published: October 2017

Spermatogenesis, which involves mitosis and meiosis of male germ cells, is a highly complicated and coordinately ordered process. Cyclin B1 (CCNB1), an important regulator in cell cycle machinery, is proved essential for mouse embryonic development. However, the role of CCNB1 in mammalian spermatogenesis remains unclear. Here we tested the requirement for CCNB1 using conditional knockout mice lacking CCNB1 in male germ cells. We found that ablation of CCNB1 in gonocytes and spermatogonia led to mouse sterile caused by the male germ cells’ depletion. Gonocyte and spermatogonia without CCNB1 is unable to proliferate normally and apoptosis increased. Moreover, CCNB1 ablation in spermatogonia may promote their differentiation by downregulating Lin28a and upregulating let-7 miRNA. However, ablation of CCNB1 in premeiotic male germ cells did not have an effect on meiosis of spermatocytes and male fertility, suggesting that CCNB1 may be dispensable for meiosis of spermatocytes. Collectively, these results indicate that CCNB1 is critically required for the proliferation of gonocytes and spermatogonia but may be redundant in meiosis of spermatocytes in mouse spermatogenesis.
Corrigendum: NDRG1 inhibition sensitizes osteosarcoma cells to combretastatin A-4 through targeting autophagy
Authors: Wang Hongsheng , Li Wen , Xu Jing , Zhang Tao , Zuo Dongqing , Zhou Zifei , Lin Binhui , Wang Gangyang , Wang Zhuoying , Sun Wei , Sun Mengxiong , Chang Shimin , Cai Zhengdong , Hua Yingqi
Published: October 2017

Correction to: Cell Death and Disease (2017) 8 (9):e3048. doi: 10.1038/cddis.2017.438; published online 14 September 2017 Since the publication of this paper, the authors have noted that there was an error in Figure 1d, in that, the GAPDH for combination treatment with CA-4 and CQ in SJSA cells by mistake duplicated for CQ alone treatment (Figure 3e).
SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity
Authors: Liu Jingxin , Li Dan , Zhang Tian , Tong Qiang , Ye Richard Dequan , Lin Ligen
Published: October 2017

Evidences of oxidative stress and mitochondrial dysfunction have been recognized in most of clinical and experimental liver diseases. SIRT3, a member of NAD+-dependent deacetylases, is mainly localized in mitochondria. So far, the role of SIRT3 in protecting hepatocytes against oxidative stress remains elusive. Herein, we found SIRT3 protein expression is decreased in tert-butyl hydroperoxide (t-BHP)-treated AML12 cells in vitro and primary hepatocytes from CCl4-injured mice in vivo. To further verify the role of SIRT3 in protecting hepatocytes from t-BHP-induced injury, SIRT3 overexpressed AML12 cell line and primary hepatocytes were generated. SIRT3 overexpressed hepatocytes showed improved cell viability upon t-BHP challenge, with less intracellular reactive oxygen species (ROS) accumulation. SIRT3 overexpression reduced superoxide dismutase 2 acetylation level and stimulated nuclear factor erythroid 2-related factor 2 nuclear translocation to enhance anti-oxidative capacity. Moreover, SIRT3 deacetylated peroxisome proliferator-activated receptor γ coactivator 1α to promote mitochondrial biogenesis, and 8-oxoguanine DNA glycosylase 1 to orchestrate DNA repair, resulting in improved mitochondrial function. Through deacetylating Ku70, SIRT3 also abated mitochondrial translocation of dynamin-related protein 1, to attenuate mitochondrial fragmentation in t-BHP-injured hepatocytes. These results suggested that SIRT3 protected hepatocytes against oxidative stress by enhancing ROS scavenging and maintaining mitochondrial integrity.
Carbon dioxide capture and conversion by an acid-base resistant metal-organic framework
Authors: Liang Linfeng , Liu Caiping , Jiang Feilong , Chen Qihui , Zhang Linjie , Xue Hui , Jiang Hai-Long , Qian Jinjie , Yuan Daqiang , Hong Maochun
Published: October 2017

Considering the rapid increase of CO2 emission, especially from power plants, there is a constant need for materials which can effectively eliminate post-combustion CO2 (the main component: CO2/N2 = 15/85). Here, we show the design and synthesis of a Cu(II) metal-organic framework (FJI-H14) with a high density of active sites, which displays unusual acid and base stability and high volumetric uptake (171 cm3 cm−3) of CO2 under ambient conditions (298 K, 1 atm), making it a potential adsorbing agent for post-combustion CO2. Moreover, CO2 from simulated post-combustion flue gas can be smoothly converted into corresponding cyclic carbonates by the FJI-H14 catalyst. Such high CO2 adsorption capacity and moderate catalytic activity may result from the synergistic effect of multiple active sites.
E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning
Authors: Rübsam Matthias , Mertz Aaron F. , Kubo Akiharu , Marg Susanna , Jüngst Christian , Goranci-Buzhala Gladiola , Schauss Astrid C. , Horsley Valerie , Dufresne Eric R. , Moser Markus , Ziegler Wolfgang , Amagai Masayuki , Wickström Sara A. , Niessen Carien M.
Published: October 2017

Generation of a barrier in multi-layered epithelia like the epidermis requires restricted positioning of functional tight junctions (TJ) to the most suprabasal viable layer. This positioning necessitates tissue-level polarization of junctions and the cytoskeleton through unknown mechanisms. Using quantitative whole-mount imaging, genetic ablation, and traction force microscopy and atomic force microscopy, we find that ubiquitously localized E-cadherin coordinates tissue polarization of tension-bearing adherens junction (AJ) and F-actin organization to allow formation of an apical TJ network only in the uppermost viable layer. Molecularly, E-cadherin localizes and tunes EGFR activity and junctional tension to inhibit premature TJ complex formation in lower layers while promoting increased tension and TJ stability in the granular layer 2. In conclusion, our data identify an E-cadherin-dependent mechanical circuit that integrates adhesion, contractile forces and biochemical signaling to drive the polarized organization of junctional tension necessary to build an in vivo epithelial barrier.
Developmental increases in white matter network controllability support a growing diversity of brain dynamics
Authors: Tang Evelyn , Giusti Chad , Baum Graham L. , Gu Shi , Pollock Eli , Kahn Ari E. , Roalf David R. , Moore Tyler M. , Ruparel Kosha , Gur Ruben C. , Gur Raquel E. , Satterthwaite Theodore D. , Bassett Danielle S.
Published: October 2017

As the human brain develops, it increasingly supports coordinated control of neural activity. The mechanism by which white matter evolves to support this coordination is not well understood. Here we use a network representation of diffusion imaging data from 882 youth ages 8–22 to show that white matter connectivity becomes increasingly optimized for a diverse range of predicted dynamics in development. Notably, stable controllers in subcortical areas are negatively related to cognitive performance. Investigating structural mechanisms supporting these changes, we simulate network evolution with a set of growth rules. We find that all brain networks are structured in a manner highly optimized for network control, with distinct control mechanisms predicted in child vs. older youth. We demonstrate that our results cannot be explained by changes in network modularity. This work reveals a possible mechanism of human brain development that preferentially optimizes dynamic network control over static network architecture.
The amplifying influence of increased ocean stratification on a future year without a summer
Authors: Fasullo J. T. , Tomas R. , Stevenson S. , Otto-Bliesner B. , Brady E. , Wahl E.
Published: October 2017

In 1816, the coldest summer of the past two centuries was observed over northeastern North America and western Europe. This so-called Year Without a Summer (YWAS) has been widely attributed to the 1815 eruption of Indonesia’s Mt. Tambora and was concurrent with agricultural failures and famines worldwide. To understand the potential impacts of a similar future eruption, a thorough physical understanding of the YWAS is crucial. Climate model simulations of both the 1815 Tambora eruption and a hypothetical analogous future eruption are examined, the latter occurring in 2085 assuming a business-as-usual climate scenario. Here, we show that the 1815 eruption drove strong responses in both the ocean and cryosphere that were fundamental to driving the YWAS. Through modulation of ocean stratification and near-surface winds, global warming contributes to an amplified surface climate response. Limitations in using major volcanic eruptions as a constraint on cloud feedbacks are also found.
Using a quantum work meter to test non-equilibrium fluctuation theorems
Authors: Cerisola Federico , Margalit Yair , Machluf Shimon , Roncaglia Augusto J. , Paz Juan Pablo , Folman Ron
Published: October 2017

Work is an essential concept in classical thermodynamics, and in the quantum regime, where the notion of a trajectory is not available, its definition is not trivial. For driven (but otherwise isolated) quantum systems, work can be defined as a random variable, associated with the change in the internal energy. The probability for the different values of work captures essential information describing the behaviour of the system, both in and out of thermal equilibrium. In fact, the work probability distribution is at the core of “fluctuation theorems” in quantum thermodynamics. Here we present the design and implementation of a quantum work meter operating on an ensemble of cold atoms, which are controlled by an atom chip. Our device not only directly measures work but also directly samples its probability distribution. We demonstrate the operation of this new tool and use it to verify the validity of the quantum Jarzynksi identity.
Identifying host regulators and inhibitors of liver stage malaria infection using kinase activity profiles
Authors: Arang Nadia , Kain Heather S. , Glennon Elizabeth K. , Bello Thomas , Dudgeon Denali R. , Walter Emily N. F. , Gujral Taranjit S. , Kaushansky Alexis
Published: October 2017

Plasmodiumparasites have extensive needs from their host hepatocytes during the obligate liver stage of infection, yet there remains sparse knowledge of specific host regulators. Here we assess 34 host-targeted kinase inhibitors for their capacity to eliminatePlasmodium yoelii-infected hepatocytes. Using pre-existing activity profiles of each inhibitor, we generate a predictive computational model that identifies host kinases, which facilitatePlasmodium yoeliiliver stage infection. We predict 47 kinases, including novel and previously described kinases that impact infection. The impact of a subset of kinases is experimentally validated, including Receptor Tyrosine Kinases, members of the MAP Kinase cascade, and WEE1. Our approach also predicts host-targeted kinase inhibitors of infection, including compounds already used in humans. Three of these compounds, VX-680, Roscovitine and Sunitinib, each eliminate >85% of infection. Our approach is well-suited to uncover key host determinants of infection in difficult model systems, including field-isolated parasites and/or emerging pathogens.
Nonlinear dynamic characterization of two-dimensional materials
Authors: Davidovikj D. , Alijani F. , Cartamil-Bueno S. J. , van der Zant H. S. J. , Amabili M. , Steeneken P. G.
Published: October 2017

Owing to their atomic-scale thickness, the resonances of two-dimensional (2D) material membranes show signatures of nonlinearities at forces of only a few picoNewtons. Although the linear dynamics of membranes is well understood, the exact relation between the nonlinear response and the resonator’s material properties has remained elusive. Here we show a method for determining the Young’s modulus of suspended 2D material membranes from their nonlinear dynamic response. To demonstrate the method, we perform measurements on graphene and MoS2 nanodrums electrostatically driven into the nonlinear regime at multiple driving forces. We show that a set of frequency response curves can be fitted using only the cubic spring constant as a fit parameter, which we then relate to the Young’s modulus of the material using membrane theory. The presented method is fast, contactless, and provides a platform for high-frequency characterization of the mechanical properties of 2D materials.
Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma
Authors: Abdalla Moustafa , Tran-Thanh Danh , Moreno Juan , Iakovlev Vladimir , Nair Ranju , Kanwar Nisha , Abdalla Mohamed , Lee Jennifer P. Y. , Kwan Jennifer Yin Yee , Cawthorn Thomas R. , Warren Keisha , Arneson Nona , Wang Dong-Yu , Fox Natalie S. , Youngson Bruce J. , Miller Naomi A. , Easson Alexandra M. , McCready David , Leong Wey L. , Boutros Paul C. , Done Susan J.
Published: October 2017

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development.
Multifunctional nanocomposite hollow fiber membranes by solvent transfer induced phase separation
Authors: Haase Martin F. , Jeon Harim , Hough Noah , Kim Jong Hak , Stebe Kathleen J. , Lee Daeyeon
Published: October 2017

The decoration of porous membranes with a dense layer of nanoparticles imparts useful functionality and can enhance membrane separation and anti-fouling properties. However, manufacturing of nanoparticle-coated membranes requires multiple steps and tedious processing. Here, we introduce a facile single-step method in which bicontinuous interfacially jammed emulsions are used to form nanoparticle-functionalized hollow fiber membranes. The resulting nanocomposite membranes prepared via solvent transfer-induced phase separation and photopolymerization have exceptionally high nanoparticle loadings (up to 50 wt% silica nanoparticles) and feature densely packed nanoparticles uniformly distributed over the entire membrane surfaces. These structurally well-defined, asymmetric membranes facilitate control over membrane flux and selectivity, enable the formation of stimuli responsive hydrogel nanocomposite membranes, and can be easily modified to introduce antifouling features. This approach forms a foundation for the formation of advanced nanocomposite membranes comprising diverse building blocks with potential applications in water treatment, industrial separations and as catalytic membrane reactors.