bluuebunny/crossref_metadata_2025 huggingface dataset:
Zoonotic pathogens in fluctuating common vole (Microtus arvalis) populations: occurrence and dynamics
Authors: Rodríguez-Pastor Ruth , Escudero Raquel , Lambin Xavier , Vidal Mª Dolors , Gil Horacio , Jado Isabel , Rodríguez-Vargas Manuela , Luque-Larena Juan José , Mougeot François
Published: September 2018

Diseases and host dynamics are linked, but their associations may vary in strength, be time-lagged, and depend on environmental influences. Where a vector is involved in disease transmission, its dynamics are an additional influence, and we often lack a general understanding on how diseases, hosts and vectors interact. We report on the occurrence of six zoonotic arthropod-borne pathogens (Anaplasma, Bartonella, Borrelia, Coxiella, Francisella and Rickettsia) in common voles (Microtus arvalis) throughout a population fluctuation and how their prevalence varies according to host density, seasonality and vector prevalence. We detected Francisella tularensis and four species of Bartonella, but not Anaplasma, Borrelia, Coxiella or Rickettsia. Bartonella taylorii and B. grahamii prevalence increased and decreased with current host (vole and mice) density, respectively, and increased with flea prevalence. Bartonella doshiae prevalence decreased with mice density. These three Bartonella species were also more prevalent during winter. Bartonella rochalimae prevalence varied with current and previous vole density (delayed-density dependence), but not with season. Coinfection with F. tularensis and Bartonella occurred as expected from the respective prevalence of each disease in voles. Our results highlight that simultaneously considering pathogen, vector and host dynamics provide a better understanding of the epidemiological dynamics of zoonoses in farmland rodents.
pH-mediated inhibition of a bumble bee parasite by an intestinal symbiont
Authors: Palmer-Young Evan C. , Raffel Thomas R. , McFrederick Quinn S.
Published: September 2018

Gut symbionts can augment resistance to pathogens by stimulating host-immune responses, competing for space and nutrients, or producing antimicrobial metabolites. Gut microbiota of social bees, which pollinate many crops and wildflowers, protect hosts against diverse infections and might counteract pathogen-related bee declines. Bumble bee gut microbiota, and specifically abundance ofLactobacillus‘Firm-5’ bacteria, can enhance resistance to the trypanosomatid parasiteCrithidia bombi. However, the mechanism underlying this effect remains unknown. We hypothesized that the Firm-5 bacteriumLactobacillus bombicola, which produces lactic acid, inhibitsC. bombi viapH-mediated effects. Consistent with our hypothesis,L. bombicolaspent medium inhibitedC. bombigrowthviareduction in pH that was both necessary and sufficient for inhibition. Inhibition of all parasite strains occurred within the pH range documented in honey bees, though sensitivity to acidity varied among strains. Spent medium was slightly more potent than HCl,d- andl-lactic acids for a given pH, suggesting that other metabolites also contribute to inhibition. Results implicate symbiont-mediated reduction in gut pH as a key determinant of trypanosomatid infection in bees. Future investigation intoin vivoeffects of gut microbiota on pH and infection intensity would test the relevance of these findings for bees threatened by trypanosomatids.
Decision-making ability in psychosis: a systematic review and meta-analysis of the magnitude, specificity and correlates of impaired performance on the Iowa and Cambridge Gambling Tasks
Authors: Woodrow Amanda , Sparks Sarah , Bobrovskaia Valeria , Paterson Charlotte , Murphy Philip , Hutton Paul
Published: September 2018

To identify factors which may help or hinder decision-making ability in people with psychosis, we did a systematic review and meta-analysis of their performance on the Iowa and Cambridge Gambling Tasks. Analysis of 47 samples found they had moderately poorer performance than healthy individuals (N = 4264, g = −0.57, 95% confidence interval (CI) −0.66 to −0.48). Few studies (k = 8) used non-psychotic clinical comparator groups, although very low-quality evidence (k = 3) found people with bipolar disorder may perform better. Negative symptoms (k = 13, N = 648, r = −0.17, 95% CI −0.26 to −0.07) and lower IQ (k = 11, N = 525, r = 0.20, 95% CI 0.29–0.10), but not positive symptoms (k = 10, N = 512, r = −0.01, 95% CI −0.11 to 0.08), each had small-moderate associations with poorer decision-making. Lower quality evidence suggested general symptoms, working memory, social functioning, awareness of emotional responses to information, and attentional bias towards gain are associated with decision-making, but not education, executive functioning or overall symptoms. Meta-regression suggested an inverse association between decision-making and depression severity (k = 6, Q = 6.41, R2 100%, p = 0.01). Those taking first-generation (k = 6, N = 305, g = −0.17, 95% CI −0.40 to 0.06, p = 0.147) or low-dose antipsychotics (k = 5, N = 442, g = −0.19, 95% CI −0.44 to 0.06, p = 0.139) had unimpaired decision-making. Although meta-regression found no linear association between dose and performance, non-reporting of the dose was common and associated with larger impairments (k = 46, Q = 4.71, R2 14%, p = 0.03). Those supporting people with psychosis to make decisions, including treatment decisions, should consider the potential effect of these factors. Interventionist-causal trials are required to test whether reducing antipsychotic dose and treating anxiety and depression can improve decision-making in this group.
Reducing loneliness among older people – who is responsible?
Authors: Agren Axel , Cedersund Elisabet
Published: September 2018

In the Swedish news-press, loneliness among older people is presented as a severe problem that needs to be solved. The issue of who is responsible for reducing loneliness and how this responsibility is designated is, however, rarely discussed. In this study, we have analysed how responsibility is designated and constructed in articles from the Swedish news-press. Focus has been on identifying responsibility in discourses proceeding from the concept ofsubject positions.This concept has enabled analysis on how responsibility is negotiated and who is positioned as a responsible actor with the ability to perform actions that reduce loneliness. Three dominating discourses were found. In thediscourse of responsibility within politics and the welfare state, the responsibility is both self-taken and designated to other institutions held responsible for not initiating sufficient measures to reduce loneliness. In thediscourse of responsibility within societal and evolutionary perspectives on loneliness, developments beyond the individual's control are considered to contribute to loneliness. At the same time ‘we’ in ‘society’ are considered capable of reducing loneliness, thereby constructing individuals as responsible actors. Within thediscourses of responsibility within senior organisations, both senior organisations and people who participate in activities are constructed as responsible actors. In conclusion, the responsibility for reducing loneliness is, apart from the discourse on senior organisations, designated to those working with older people.
No-Fault Divorce Reform in the 1950s: The Lost History of the “Greatest Project” of the National Association of Women Lawyers
Authors: Oren Laura
Published: September 2018

In the 1950s, the National Association of Women Lawyers (“NAWL”) undertook what it considered its “greatest project,” the drafting and promotion of a model no-fault divorce law. It launched its campaign at a time when post-war realities and the law in practice were putting increasing pressure on the law on the books which lagged behind contemporary sensibilities. NAWL acted two decades before the no-fault divorce “revolution” of the 1970s. It did so in the 1950s when women were said to be both “domestic” and “quiescent.” The Article has three aims. First, it considers NAWL's project as a missing piece in the history of divorce law, the no-fault revolution, and the rise of mass divorce in mid-twentieth century America. Second, it reflects on the implications of NAWL's undertaking for the standard narrative of “domesticity” in the 1950s, an account that has been questioned in recent years. Last, it tells a story of women's activism in the depth of the so-called “doldrums” of the organized women's moveme
Important areas for the conservation of the European Roller Coracias garrulus during the non-breeding season in southern Africa
Authors: RODRÍGUEZ-RUIZ JUAN , MOUGEOT FRANÇOIS , PAREJO DESEADA , PUENTE JAVIER DE LA , BERMEJO ANA , AVILÉS JESÚS M.
Published: September 2018

The identification of threats to migratory species of conservation concern and the relevance of protected areas for them is often biased towards breeding areas. The European Roller Coracias garrulus is a long-distance migrant experiencing a pronounced decline throughout its breeding range, which has been attributed to the degradation of open agricultural habitats. However, its conservation status in non-breeding areas in Africa remains unstudied. Land cover change is a major threat affecting migratory birds in their wintering grounds, therefore identifying important areas for their protection at this stage is a priority. Here we used occurrence data during the wintering season and ecological niche models to identify key land cover and areas used by Rollers in Africa. First, we used 33 filtered locations from six satellite-tracked birds breeding in Spain to describe suitable wintering areas for the Spanish population (westernmost part of the Eurasian breeding range). We also used 1,167 occurrence data in southern Africa from open-access databases and bird atlases to characterise the overall wintering range of the species. The Spanish population occupied a relatively small area in the north-western part of southern Africa, and a narrow range of land covers. Open grassland, less steep areas and those with sparse tree cover are correlated with suitability. In all, 18.06% of suitable wintering areas for the Spanish population overlapped with protected areas. The overall population of Rollers occupied a wider area and range of land cover. Tree cover was the most important variable affecting suitability, with areas without tree cover being the least suitable. We found that 9.58% of suitable wintering areas for the overall population overlapped with protected areas. Our results suggest that Rollers from different origins (breeding populations) use separate, but overlapping, wintering areas and may have different habitat requirements, and therefore, population-specific conservation strategies in these areas might be needed to fully protect the species.
Microstructural Characterization of Carbon Nanotubes (CNTs)-Reinforced Nickel Matrix Nanocomposites
Authors: Simões Sónia , Carneiro Íris , Viana Filomena , Reis Marcos A. L. , Vieira Manuel F.
Published: September 2018

This research focuses on the microstructural characterization of nickel matrix composites reinforced by carbon nanotubes (CNTs). The nanocomposites were produced by a conventional powder metallurgy process and the dispersion of CNTs and mixture with nickel powders was performed in a single step by ultrasonication. Microstructural characterization of Ni–CNT nanocomposites was performed by scanning and transmission electron microscopy, electron backscattered diffraction, high-resolution transmission electron microscopy, selected area electron diffraction, and fast Fourier transform analyses. This characterization revealed CNTs embedded in the nickel grains and mainly presented as clusters at the grain boundaries. CNTs hinder recrystallization during sintering, and dislocation cells and subgrains form as a result of the recovery process.
Bioactivity of cardanol against the rust red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae)
Authors: Buxton Thomas , Owusu E. O. , Kim Chul-Sa
Published: September 2018

Cashew nut shell liquid (CNSL) is an economically important by-product obtained from the cashew nut Anacardium occidentale L. The liquid has been found to be versatile with a wide range of uses, including as a raw material in the polymer industry, in the development of drugs (antioxidants) and in pest control. One important chemical component of CNSL known for its bioactivity is cardanol. We isolated (8Z,11Z)-3-(8,11,14-pentadecatrienyl)phenol, a cardanol from CNSL, and determined its insecticidal and progeny growth and development inhibition activities against Tribolium castaneum Hebst. We used a bioassay-guided approach for the isolation. Exposure to cardanol produced 80% mortality of adult T. castaneum in the insecticidal bioassay. In the progeny growth and development inhibition bioassay, 46.7% of larvae were killed, and only 20.7% of adults emerged without deformities after the cardanol treatment. The amount of isolated cardanol from the 1 g equivalent/ml extracted CNSL was found to be 36.55 mg with LC50 value of 47.88 mg/ml and 13.28 mg/ml against adult T. castaneum and its larvae, respectively. We conclude that cardanol can potentially be useful in managing stored product insect pests, especially T. castaneum, but with the prerequisite that one should take much care when handling and when applying the compound.
Effect of host plants on life history traits of Phenacoccus solenopsis (Homoptera: Pseudococcidae)
Authors: Dogar Abdul Manan , Ayyaz Mahmood , Abbas Naeem , Shad Sarfraz Ali , Naeem Afifa
Published: September 2018

Cotton mealybug,Phenacoccus solenopsisTinsley is an important polyphagous insect pest and causes severe losses to different crops worldwide. In the current study, we investigated the effect of different host plants, such asCaesalpinia pulcherrima,Plumeria rubra, Anthurium andraeanum, Jasminum sambac, andHibiscus rosasinensis, on the biological parameters ofP. solenopsis. The survival rate from crawler to adult, female nymphal duration, development time from crawler to female adult, and female adult weight were significantly different on the different hosts. Male nymphal duration, development time from crawler to male adult, pupal weight, emergence rate of male adults, and mean relative growth rate for male were similar on all the tested host plants. Pupal duration and generation time of male and female onH. rosasinensiswere significantly shorter than on the other hosts. Adult male and femaleP. solenopsislongevity was significantly shorter onH. rosasinensiscompared to other hosts. The fecundity was lower onC. pulcherrimaandA. andraeanumand hatchability was lower onC. pulcherrimathan on the other hosts. The net reproductive rate, the intrinsic rate of natural increase, and biotic potential and mean relative growth rate for female ofP. solenopsiswere significantly different on the tested hosts. Our results point to the role of host plants in increasing the populations ofP. solenopsisand could help to design cultural management strategies.
Fruits of Icacinaceae Miers from the Palaeocene of the Paris Basin (Oise, France)
Authors: Del Rio Cédric , Thomas Romain , De Franceschi Dario
Published: September 2018

Icacinaceae Miers are a family of trees, shrubs, and lianas with a current pantropical distribution. The family is well known in the fossil record, especially from the Palaeogene of Europe and North America, with the modern genus Iodes being particularly well represented. Here, we describe five new species of Iodes based on fossil endocarps with horn-like protrusions from the late Palaeocene Rivecourt deposits (Oise, France). Moreover, we propose a new combination for Iodes israelii Soudry & Gregor, as Icacinicarytes israelii (Soudry & Gregor) Del Rio, Thomas & De Franceschi, because it lacks the diagnostic morphological and anatomical characters of the genus Iodes. The significance of papillae, which has been emphasised in the literature, is discussed in light of new data, and a more standardised system of terminology is proposed. Given that, among modern members of Iodes, horn-like protrusions are only known from Asian species; the fossils described here suggest an affinity between the late Palaeocene flora of Europe and the modern flora of Asia. Finally, this study represents the first detailed investigation of Icacinaceae from the Paris Basin, where palaeocarpology remains understudied.
Evaporation From Layered Porous Medium in the Presence of Infrared Heating
Authors: Kumar Navneet , Arakeri Jaywant H.
Published: September 2018

We report an experimental study of evaporation of two configurations of layered porous media that are heated from above by infrared (IR) radiation having ~1,000 W/m2 intensity. We used nearly monodisperse glass beads in each of the layers. The two configurations are (1) coarse and fine beads, stacked side by side and (2) fine beads over coarse beads (FoC). The IR heater mimics the natural evaporation process in soils, and the aim is to study, using three diagnostic tools, how the layering affects the evaporation process, and compare it with the homogeneous porous medium case. For each experiment we use three diagnostics simultaneously, evaporation rate measurement using a precision balance, surface temperature imaging using an IR camera, and visualization of the evaporation process with fluorescein dye. The constant (evaporation) rate period (CRP) regime, found in homogeneous porous media, is drastically changed for the two layered configurations. We show new results for side‐by‐side configuration. In the FoC configuration we show that the near‐surface water content in the finer particles does not change in CRP and a true constant evaporation rate is possible. The average water depth at end of CRP in the porous medium, for a wide range of diameter ratios for the FoC configuration are compared with the predictions from theoretical relations proposed by Shokri et al. (2010, https://doi.org/10.1029/2009JB006743) and Assouline et al. (2014, https://doi.org/10.1002/2013WR014489). Using a simple surface energy budget, we show that knowing the surface temperature, the evaporation rate can be estimated with reasonable accuracy (±5%) during drying of a porous medium.
Climate Change and Women's Health: Impacts and Opportunities in India
Authors: Sorensen Cecilia , Saunik Sujata , Sehgal Meena , Tewary Anwesha , Govindan Mini , Lemery Jay , Balbus John
Published: September 2018

Climate change impacts on health, including increased exposures to heat, poor air quality, extreme weather events, and altered vector‐borne disease transmission, reduced water quality, and decreased food security, affect men and women differently due to biologic, socioeconomic, and cultural factors. In India, where rapid environmental changes are taking place, climate change threatens to widen existing gender‐based health disparities. Integration of a gendered perspective into existing climate, development, and disaster‐risk reduction policy frameworks can decrease negative health outcomes. Modifying climate risks requires multisector coordination, improvement in data acquisition, monitoring of gender specific targets, and equitable stakeholder engagement. Empowering women as agents of social change can improve mitigation and adaptation policy interventions.
Changes in Marine Fog Over the North Pacific Under Different Climates in CMIP5 Multimodel Simulations
Authors: Kawai Hideaki , Koshiro Tsuyoshi , Endo Hirokazu , Arakawa Osamu
Published: September 2018

In this study, the changes in the occurrence of marine fog over the summer North Pacific in warmer sea surface temperature (SST) or increased CO2 climates were investigated based on atmospheric model simulations by using the fifth phase of the Climate Model Intercomparison Project (CMIP5) multimodel data. Initially, the marine fog representation in CMIP5 multimodels was briefly evaluated globally. We found that the simulated marine fog occurrence was represented relatively well in boreal summer but poorly in other seasons. The results indicated that the changes in the North Pacific high‐pressure system accompanied by changes in horizontal wind patterns control the changes in marine fog occurrence in the North Pacific. The magnitude of contrasting pair changes in marine fog occurrence in the western and eastern North Pacific are primarily determined by the magnitude of changes in the North Pacific high‐pressure system. Global‐scale changes in the vertical profiles of the atmosphere (stability changes) can also affect the marine fog changes. These changes in marine fog over the North Pacific were consistent among most CMIP5 models.
Wastewater treatment plant resistomes are shaped by bacterial composition, genetic exchange, and upregulated expression in the effluent microbiomes
Authors: Ju Feng , Beck Karin , Yin Xiaole , Maccagnan Andreas , McArdell Christa S , Singer Heinz P , Johnson David R , Zhang Tong , Bürgmann Helmut
Published: September 2018

Wastewater treatment plants (WWTPs) are implicated as hotspots for the dissemination of antibacterial resistance into the environment. However, the in situ processes governing removal, persistence, and evolution of resistance genes during wastewater treatment remain poorly understood. Here, we used quantitative metagenomic and metatranscriptomic approaches to achieve a broad-spectrum view of the flow and expression of genes related to antibacterial resistance to over 20 classes of antibiotics, 65 biocides, and 22 metals. All compartments of 12 WWTPs share persistent resistance genes with detectable transcriptional activities that were comparatively higher in the secondary effluent, where mobility genes also show higher relative abundance and expression ratios. The richness and abundance of resistance genes vary greatly across metagenomes from different treatment compartments, and their relative and absolute abundances correlate with bacterial community composition and biomass concentration. No strong drivers of resistome composition could be identified among the chemical stressors analyzed, although the sub-inhibitory concentration (hundreds of ng/L) of macrolide antibiotics in wastewater correlates with macrolide and vancomycin resistance genes. Contig-based analysis shows considerable co-localization between resistance and mobility genes and implies a history of substantial horizontal resistance transfer involving human bacterial pathogens. Based on these findings, we propose future inclusion of mobility incidence (M%) and host pathogenicity of antibiotic resistance genes in their quantitative health risk ranking models with an ultimate goal to assess the biological significance of wastewater resistomes with regard to disease control in humans or domestic livestock.
SP1-induced lncRNA-ZFAS1 contributes to colorectal cancer progression via the miR-150-5p/VEGFA axis
Authors: Chen Xiaoxiang , Zeng Kaixuan , Xu Mu , Hu Xiuxiu , Liu Xiangxiang , Xu Tao , He Bangshun , Pan Yuqin , Sun Huiling , Wang Shukui
Published: September 2018

Increasing long non-coding RNAs (lncRNAs) have been reported to play key roles in the development and progression of various malignancies. ZNFX1 antisense RNA1 (ZFAS1) has been reported to be aberrant expression and suggested as a tumor suppressor or oncogene in many cancers. However, the biological role and underlying molecular mechanism of ZFAS1, especially the miRNA sponge role of which in CRC remain largely unknown. We found that ZFAS1 expression was higher in CRC tissues, where it was associated with poor overall survival (OS), we also showed that ZFAS1 upregulation was induced by nuclear transcription factor SP1. Moreover, ZFAS1 and VEGFA are both targets of miR-150-5p, while ZFAS1 binds to miR-150-5p in an AGO2-dependent manner. Additionally, ZFAS1 upregulation markedly promoted as well as ZFAS1 knockdown significantly suppressed CRC cell proliferation, migration, invasion and angiogenesis, and the inhibitory effect caused by ZFAS1 knockdown could be reversed by antagomiR-150-5p. Lastly, we demonstrated that ZFAS1 knockdown inhibited EMT process and inactivated VEGFA/VEGFR2 and downstream Akt/mTOR signaling pathway in CRC. Our data demonstrated that SP1-induced ZFAS1 contributed to CRC progression by upregulating VEGFA via competitively binding to miR-150-5p, which acts as a tumor suppressor by targeting VEGFA in CRC.
Loperamide, pimozide, and STF-62247 trigger autophagy-dependent cell death in glioblastoma cells
Authors: Zielke Svenja , Meyer Nina , Mari Muriel , Abou-El-Ardat Khalil , Reggiori Fulvio , van Wijk Sjoerd J. L. , Kögel Donat , Fulda Simone
Published: September 2018

Autophagy is a well-described degradation mechanism that promotes cell survival upon nutrient starvation and other forms of cellular stresses. In addition, there is growing evidence showing that autophagy can exert a lethal function via autophagic cell death (ACD). As ACD has been implicated in apoptosis-resistant glioblastoma (GBM), there is a high medical need for identifying novel ACD-inducing drugs. Therefore, we screened a library containing 70 autophagy-inducing compounds to induce ATG5-dependent cell death in human MZ-54 GBM cells. Here, we identified three compounds, i.e. loperamide, pimozide, and STF-62247 that significantly induce cell death in several GBM cell lines compared to CRISPR/Cas9-generated ATG5- or ATG7-deficient cells, pointing to a death-promoting role of autophagy. Further cell death analyses conducted using pharmacological inhibitors revealed that apoptosis, ferroptosis, and necroptosis only play minor roles in loperamide-, pimozide- or STF-62247-induced cell death. Intriguingly, these three compounds induce massive lipidation of the autophagy marker protein LC3B as well as the formation of LC3B puncta, which are characteristic of autophagy. Furthermore, loperamide, pimozide, and STF-62247 enhance the autophagic flux in parental MZ-54 cells, but not in ATG5 or ATG7 knockout (KO) MZ-54 cells. In addition, loperamide- and pimozide-treated cells display a massive formation of autophagosomes and autolysosomes at the ultrastructural level. Finally, stimulation of autophagy by all three compounds is accompanied by dephosphorylation of mammalian target of rapamycin complex 1 (mTORC1), a well-known negative regulator of autophagy. In summary, our results indicate that loperamide, pimozide, and STF-62247 induce ATG5- and ATG7-dependent cell death in GBM cells, which is preceded by a massive induction of autophagy. These findings emphasize the lethal function and potential clinical relevance of hyperactivated autophagy in GBM.
Proscillaridin A exerts anti-tumor effects through GSK3β activation and alteration of microtubule dynamics in glioblastoma
Authors: Berges Raphael , Denicolai Emilie , Tchoghandjian Aurélie , Baeza-Kallee Nathalie , Honore Stephane , Figarella-Branger Dominique , Braguer Diane
Published: September 2018

Glioblastoma (GBM) is characterized by highly aggressive growth and invasive behavior. Due to the highly lethal nature of GBM, new therapies are urgently needed and repositioning of existing drugs is a promising approach. We have previously shown the activity of Proscillaridin A (ProA), a cardiac glycoside inhibitor of the Na(+)/K(+) ATPase (NKA) pump, against proliferation and migration of GBM cell lines. ProA inhibited tumor growth in vivo and increased mice survival after orthotopic grafting of GBM cells. This study aims to decipher the mechanism of action of ProA in GBM tumor and stem-like cells. ProA displayed cytotoxic activity on tumor and stem-like cells grown in 2D and 3D culture, but not on healthy cells as astrocytes or oligodendrocytes. Even at sub-cytotoxic concentration, ProA impaired cell migration and disturbed EB1 accumulation at microtubule (MT) plus-ends and MT dynamics instability. ProA activates GSK3β downstream of NKA inhibition, leading to EB1 phosphorylation on S155 and T166, EB1 comet length shortening and MT dynamics alteration, and finally inhibition of cell migration and cytotoxicity. Similar results were observed with digoxin. Therefore, we disclosed here a novel pathway by which ProA and digoxin modulate MT-governed functions in GBM tumor and stem-like cells. Altogether, our results support ProA and digoxin as potent candidates for drug repositioning in GBM.
POFUT1 promotes colorectal cancer development through the activation of Notch1 signaling
Authors: Du Yuheng , Li Daojiang , Li Nanpeng , Su Chen , Yang Chunxing , Lin Changwei , Chen Miao , Wu Runliu , Li Xiaorong , Hu Gui
Published: September 2018

Copy number variations (CNVs) are key drivers of colorectal cancer (CRC). Our previous studies revealed that protein O-fucosyltransferase 1 (POFUT1) overexpression is driven by CNVs during CRC development. The potential role and underlying mechanisms of POFUT1 in CRC were not investigated. In this study, we analyzed the expression of POFUT1 in CRC from cosmic and TCGA databases and confirmed that POFUT1 is highly expressed in CRC. We used well characterized CRC cell lines, including SW620 and HCT116 to establish a model POFUT1 knockdown cell line. Using these cells, we investigated the role of POFUT1 in CRC. Our data revealed that silencing POFUT1 in CRC cells inhibits cell proliferation, decreases cell invasion and migration, arrests cell cycle progression, and stimulates CRC cell apoptosis in vitro. We further demonstrate that POFUT1 silencing dramatically suppresses CRC tumor growth and transplantation in vivo. We additionally reveal new mechanistic insights into the role of POFUT1 during CRC, through demonstrating that POFUT1 silencing inhibits Notch1 signaling. Taken together, our findings demonstrate that POFUT1 is a tumor activating gene during CRC development, which positively regulates CRC tumor progression through activating Notch1.
SIRT3 deficiency leads to induction of abnormal glycolysis in diabetic kidney with fibrosis
Authors: Srivastava Swayam Prakash , Li Jinpeng , Kitada Munehiro , Fujita Hiroki , Yamada Yuichiro , Goodwin Julie E. , Kanasaki Keizo , Koya Daisuke
Published: September 2018

The regulation of aberrant glucose metabolism in diabetes associated-kidney fibrosis is not well known. In this study we found the suppression of SIRT3 protein level in diabetic kidney, displays responsibility in fibrogenic programming associated with aberrant glycolysis and such abnormal glycolysis is the therapeutic target in diabetes associated-kidney fibrosis. When analyzing different strains of streptozotocin-induced diabetic mice model (fibrotic model: CD-1, less fibrotic model: C57Bl6), we found SIRT3 suppression was associated with kidney fibrosis in fibrotic CD-1; further SIRT3 suppression by systemic administration of SIRT3 siRNA in the diabetic mice, showed profound fibrogenic phenotype in the kidney. Such suppression in SIRT3 was associated with the induction of transforming growth factor-β (TGF-β)/smad signaling, higher level of HIF1α accumulation and PKM2 dimer formation; these alterations subsequently led to abnormal glycolysis and linked abnormal mesenchymal transformations in vivo and in vitro. Inhibition of such aberrant glycolysis suppressed fibrogenic programming and restored SIRT3 level as well. Such aberrant glycolysis was confirmed in the KK/Ta-Ins2Akita mouse, the mouse model of progressive diabetic kidney disease. These data demonstrate that SIRT3 deficiency promotes abnormal glycolysis which is responsible for the fibrogenic pathway in diabetic kidney. Restoration of SIRT3 could be an alternative strategy in combating diabetes associated-kidney fibrosis via inhibition of aberrant glycolysis.
Pharmacological activation of SIRT6 triggers lethal autophagy in human cancer cells
Authors: Iachettini Sara , Trisciuoglio Daniela , Rotili Dante , Lucidi Alessia , Salvati Erica , Zizza Pasquale , Di Leo Luca , Del Bufalo Donatella , Ciriolo Maria Rosa , Leonetti Carlo , Steegborn Clemens , Mai Antonello , Rizzo Angela , Biroccio Annamaria
Published: September 2018

Sirtuin 6 (SIRT6) is a member of the NAD+-dependent class III deacetylase sirtuin family, which plays a key role in cancer by controlling transcription, genome stability, telomere integrity, DNA repair, and autophagy. Here we analyzed the molecular and biological effects of UBCS039, the first synthetic SIRT6 activator. Our data demonstrated that UBCS039 induced a time-dependent activation of autophagy in several human tumor cell lines, as evaluated by increased content of the lipidated form of LC3B by western blot and of autophagosomal puncta by microscopy analysis of GFP-LC3. UBCS039-mediated activation of autophagy was strictly dependent on SIRT6 deacetylating activity since the catalytic mutant H133Y failed to activate autophagy. At the molecular level, SIRT6-mediated autophagy was triggered by an increase of ROS levels, which, in turn, resulted in the activation of the AMPK-ULK1-mTOR signaling pathway. Interestingly, antioxidants were able to completely counteract UBCS039-induced autophagy, suggesting that ROS burst had a key role in upstream events leading to autophagy commitment. Finally, sustained activation of SIRT6 resulted in autophagy-related cell death, a process that was markedly attenuated using either a pan caspases inhibitor (zVAD-fmk) or an autophagy inhibitor (CQ). Overall, our results identified UBCS039 as an efficient SIRT6 activator, thereby providing a proof of principle that modulation of the enzyme can influence therapeutic strategy by enhancing autophagy-dependent cell death.
Temporal genetic association and temporal genetic causality methods for dissecting complex networks
Authors: Lin Luan , Chen Quan , Hirsch Jeanne P. , Yoo Seungyeul , Yeung Kayee , Bumgarner Roger E. , Tu Zhidong , Schadt Eric E. , Zhu Jun
Published: September 2018

A large amount of panomic data has been generated in populations for understanding causal relationships in complex biological systems. Both genetic and temporal models can be used to establish causal relationships among molecular, cellular, or phenotypical traits, but with limitations. To fully utilize high-dimension temporal and genetic data, we develop a multivariate polynomial temporal genetic association (MPTGA) approach for detecting temporal genetic loci (teQTLs) of quantitative traits monitored over time in a population and a temporal genetic causality test (TGCT) for inferring causal relationships between traits linked to the locus. We apply MPTGA and TGCT to simulated data sets and a yeast F2 population in response to rapamycin, and demonstrate increased power to detect teQTLs. We identify a teQTL hotspot locus interacting with rapamycin treatment, infer putative causal regulators of the teQTL hotspot, and experimentally validate RRD1 as the causal regulator for this teQTL hotspot.
Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis
Authors: Driller Ronja , Janke Sophie , Fuchs Monika , Warner Evelyn , Mhashal Anil R. , Major Dan Thomas , Christmann Mathias , Brück Thomas , Loll Bernhard
Published: September 2018

Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C–C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are capable of chaperoning highly reactive carbocation intermediates through an enzyme-specific reaction. Due to the instability of carbocation intermediates, the proteins’ structural dynamics and enzyme:substrate interactions during TPS catalysis remain elusive. Here, we present the structure of the diterpene synthase CotB2, in complex with an in crystallo cyclised abrupt reaction product and a substrate-derived diphosphate. We captured additional snapshots of the reaction to gain an overview of CotB2’s catalytic mechanism. To enhance insights into catalysis, structural information is augmented with multiscale molecular dynamic simulations. Our data represent fundamental TPS structure dynamics during catalysis, which ultimately enable rational engineering towards tailored terpene macrocycles that are inaccessible by conventional chemical synthesis.
Genus-wide sequencing supports a two-locus model for sex-determination in Phoenix
Authors: Torres Maria F. , Mathew Lisa S. , Ahmed Ikhlak , Al-Azwani Iman K. , Krueger Robert , Rivera-Nuñez Diego , Mohamoud Yasmin A. , Clark Andrew G. , Suhre Karsten , Malek Joel A.
Published: September 2018

The date palm tree is a commercially important member of the genus Phoenix whose 14 species are dioecious with separate male and female individuals. To identify sex determining genes we sequenced the genomes of 15 female and 13 male Phoenix trees representing all 14 species. We identified male-specific sequences and extended them using phased single-molecule sequencing or BAC clones. We observed that only four genes contained sequences conserved in all analyzed Phoenix males. Most of these sequences showed similarity to a single genomic locus in the closely related monoecious oil palm. CYP703 and GPAT3, two single copy genes present in males and critical for male flower development in other monocots, were absent in females. A LOG-like gene appears translocated into the Y-linked region and is suggested to play a role in suppressing female flowers. Our data are consistent with a two-mutation model for the evolution of dioecy in Phoenix.
Remote sensing of geomagnetic fields and atomic collisions in the mesosphere
Authors: Pedreros Bustos Felipe , Bonaccini Calia Domenico , Budker Dmitry , Centrone Mauro , Hellemeier Joschua , Hickson Paul , Holzlöhner Ronald , Rochester Simon
Published: September 2018

Magnetic-field sensing has contributed to the formulation of the plate-tectonics theory, mapping of underground structures on Earth, and the study of magnetism of other planets. Filling the gap between space-based and near-Earth observations, we demonstrate a remote measurement of the geomagnetic field at an altitude of 85–100 km. The method consists of optical pumping of atomic sodium in the mesosphere with an intensity-modulated laser beam, and ground-based observation of the resultant magneto-optical resonance near the Larmor precession frequency. Here we validate this technique and measure the Larmor precession frequency of sodium and the corresponding magnetic field with an accuracy level of 0.28 mG Hz−1/2. These observations allow the characterization of atomic-collision processes in the mesosphere. Remote detection of mesospheric magnetic fields has potential applications such as mapping magnetic structures in the lithosphere, monitoring space weather, and electric currents in the ionosphere.
An iris diaphragm mechanism to gate a cyclic nucleotide-gated ion channel
Authors: Marchesi Arin , Gao Xiaolong , Adaixo Ricardo , Rheinberger Jan , Stahlberg Henning , Nimigean Crina , Scheuring Simon
Published: September 2018

Cyclic nucleotide-gated (CNG) ion channels are non-selective cation channels key to signal transduction. The free energy difference of cyclic-nucleotide (cAMP/cGMP) binding/unbinding is translated into mechanical work to modulate the open/closed probability of the pore, i.e., gating. Despite the recent advances in structural determination of CNG channels, the conformational changes associated with gating remain unknown. Here we examine the conformational dynamics of a prokaryotic homolog of CNG channels, SthK, using high-speed atomic force microscopy (HS-AFM). HS-AFM of SthK in lipid bilayers shows that the CNBDs undergo dramatic conformational changes during the interconversion between the resting (apo and cGMP) and the activated (cAMP) states: the CNBDs approach the membrane and splay away from the 4-fold channel axis accompanied by a clockwise rotation with respect to the pore domain. We propose that these movements may be converted by the C-linker to pull the pore helices open in an iris diaphragm-like mechanism.
A sustained change in the supply of parental care causes adaptive evolution of offspring morphology
Authors: Jarrett Benjamin J. M. , Evans Emma , Haynes Hannah B. , Leaf Miranda R. , Rebar Darren , Duarte Ana , Schrader Matthew , Kilner Rebecca M.
Published: September 2018

Although cooperative social interactions within species are considered an important driver of evolutionary change, few studies have experimentally demonstrated that they cause adaptive evolution. Here we address this problem by studying the burying beetle Nicrophorus vespilloides. In this species, parents and larvae work together to obtain nourishment for larvae from the carrion breeding resource: parents feed larvae and larvae also self-feed. We established experimentally evolving populations in which we varied the assistance that parents provided for their offspring and investigated how offspring evolved in response. We show that in populations where parents predictably supplied more care, larval mandibles evolved to be smaller in relation to larval mass, and larvae were correspondingly less self-sufficient. Previous work has shown that antagonistic social interactions can generate escalating evolutionary arms races. Our study shows that cooperative interactions can yield the opposite evolutionary outcome: when one party invests more, the other evolves to invest less.
Spin-momentum locking and spin-orbit torques in magnetic nano-heterojunctions composed of Weyl semimetal WTe2
Authors: Li Peng , Wu Weikang , Wen Yan , Zhang Chenhui , Zhang Junwei , Zhang Senfu , Yu Zhiming , Yang Shengyuan A. , Manchon A. , Zhang Xi-xiang
Published: September 2018

Spin–orbit torque has recently been intensively investigated for the purposes of manipulating the magnetization in magnetic nano-devices and understanding fundamental physics. Therefore, the search for novel materials or material combinations that exhibit a strong enough spin-torque effect has become one of the top priorities in this field of spintronics. Weyl semimetal, a new topological material that features open Fermi arc with strong spin–orbit coupling and spin–momentum locking effect, is naturally expected to exhibit an enhanced spin-torque effect in magnetic nano-devices. Here we observe a significantly enhanced spin conductivity, which is associated with the field-like torque at low temperatures. The enhancement is obtained in the b-axis WTe2/Py bilayers of nano-devices but not observed in the a-axis of WTe2/Py nano-devices, which can be ascribed to the enhanced spin accumulation by the spin–momentum locking effect of the Fermi arcs of the Weyl semimetal WTe2.
Bacterial dynamin-like proteins reveal mechanism for membrane fusion
Authors: Bramkamp Marc
Published: September 2018

The dynamin superfamily of large GTPases comprises specialized members that catalyze fusion and fission of biological membranes. While fission-specific proteins such as dynamin work as homo-oligomeric complexes, many fusion catalysts such as mitofusins or bacterial dynamin-like proteins (DLPs) act as hetero-oligomers. However, so far it was unclear how these hetero-oligomeric DLPs assemble and how they function in membrane remodeling. The group of Harry Low report now on the structure of a DLP pair from Campylobacter jejuni, allowing detailed insight into the assembly mechanism and membrane tethering activity.
Diagnosis and treatment of schizotypal personality disorder: evidence from a systematic review
Authors: Kirchner Sophie K. , Roeh Astrid , Nolden Jana , Hasan Alkomiet
Published: September 2018

The main objective of this review was to evaluate studies on the diagnosis, treatment, and course of schizotypal personality disorder and to provide a clinical guidance on the basis of that evaluation. A systematic search in the PubMed/MEDLINE databases was conducted. Two independent reviewers extracted and assessed the quality of the data. A total of 54 studies were eligible for inclusion: 18 were on diagnostic instruments; 22, on pharmacological treatment; 3, on psychotherapy; and 13, on the longitudinal course of the disease. We identified several suitable and reliable questionnaires for screening (PDQ-4+ and SPQ) and diagnosing (SIDP, SIDP-R, and SCID-II) schizotypal personality disorder. Second-generation antipsychotics (mainly risperidone) were the most often studied drug class and were described as beneficial. Studies on the longitudinal course described a moderate remission rate and possible conversion rates to other schizophrenia spectrum disorders. Because of the heterogeneity of the studies and the small sample sizes, it is not yet possible to make evidence-based recommendations for treatment. This is a systematic evaluation of diagnostic instruments and treatment studies in schizotypal personality disorder. We conclude that there is currently only limited evidence on which to base treatment decisions in this disorder. Larger interventional trials are needed to provide the data for evidence-based recommendations.
Shikonin Inhibits Tumor Growth in Mice by Suppressing Pyruvate Kinase M2-mediated Aerobic Glycolysis
Authors: Zhao Xiaoyue , Zhu Yanan , Hu Jianhua , Jiang Longwei , Li Limin , Jia Shaochang , Zen Ke
Published: September 2018

Shift metabolism profile from mitochondrial oxidative phosphorylation to aerobic glycolysis (Warburg effect) is a key for tumor cell growth and metastasis. Therefore, suppressing the tumor aerobic glycolysis shows a great promise in anti-tumor therapy. In the present study, we study the role of shikonin, a naphthoquinone isolated from the traditional Chinese medicine Lithospermum, in inhibiting tumor aerobic glycolysis and thus tumor growth. We found that shikonin dose-dependently inhibited glucose uptake and lactate production in Lewis lung carcinoma (LLC) and B16 melanoma cells, confirming the inhibitory effect of shikonin on tumor aerobic glycolysis. Treatment of shikonin also decreased tumor cell ATP production. Furthermore, pyruvate kinase M2 (PKM2) inhibitor or activator respectively altered the effect of shikonin on tumor cell aerobic glycolysis, suggesting that suppression of cell aerobic glycolysis by shikonin is through decreasing PKM2 activity. Western blot analysis confirmed that shikonin treatment reduced tumor cell PKM2 phosphorylation though did not reduce total cellular PKM2 level. In vitro assay also showed that shikonin treatment significantly promoted tumor cell apoptosis compared to untreated control cells. Finally, when mice implanted with B16 cells were administered with shikonin or control vehicle, only shikonin treatment significantly decreased B16 tumor cell growth. In conclusion, this study demonstrates that shikonin inhibits tumor growth in mice by suppressing PKM2-mediated aerobic glycolysis.
Large-scale 3-D interconnected Ni nanotube networks with controlled structural and magnetic properties
Authors: de la Torre Medina Joaquín , da Câmara Santa Clara Gomes Tristan , Velázquez Galván Yenni G. , Piraux Luc
Published: September 2018

Large-scale, electrically interconnected three-dimensional (3-D) Ni crossed nanotube networks have been fabricated using an electrochemical dealloying method within the crossed nanopores of polymer host membranes. This method paves the way for the easy and cost-effective fabrication of 3-D magnetic NT networks with precise spatial arrangement and diameter and wall thickness of 10–100 nm controlled individually. The excellent control over geometrical parameters and morphological features of the Ni crossed nanotube networks leads to tunable magnetic and magneto-transport properties. Particularly, the low field magneto-transport behavior is consistent with the expected vortex-like states formed in different segments of the nanotube scaffold, whereas nucleation of domain walls at the intersection of the nanowire segments play a dominant role in the solid crossed nanowire networks counterpart. The present 3-D networks of nanomagnets are of special interest due to their potential for memory devices, computing architectures, sensing and biomedical applications.