bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARATIVE EFFICACY OF HERBICIDES IN WEED CONTROL AND ENHANCEMENT OF PRODUCTIVITY AND PROFITABILITY OF RICE
Authors: SINGH TEEKAM , SATAPATHY BHAWANI SHANKAR , GAUTAM PRIYANKA , LAL BANWARI , KUMAR UPENDRA , SAIKIA KANCHAN , PUN K. B.
Published: March 2017

Weed management is the major challenge to the success of boro rice (rice grown during Dec–Jan to May–Jun, also known as summer rice) in Southern Asia. Herbicide seems to be a cost effective and strategic tool from an agronomic view point to control weeds; however, herbicide application can potentially interfere with soil enzyme activity and microbial biomass carbon (MBC). A field study was conducted in 2012/13 and 2013/14 to evaluate the performance of sole and combined application of different pre-emergence herbicides in comparison to manual weeding in boro rice. Lowest weed density, biomass and highest weed control efficiency (~83%) were recorded with the pyrazosulfuron ethyl, causing higher grain yield (6.7 Mg ha−1 in 2012/13 and 4.5 Mg ha−1 in 2013/14) than treatments with chlorimuron + metsulfuron-methyl, bensulfuron methyl + pretilachlor, butachlor fb 2,4D, butachlor and cono-weeder. Among, the herbicidal treatments butachlor caused lower grain yield and higher weed density and biomass when compared to the others. Although grain yield was highest in weed-free treatments but net returns and (B:C) benefit cost ratio was highest for pyrazosulfuron ethyl due to high cost of hand weeding. After 15 days of herbicide application, lowest microbial biomass carbon was recorded with bensulfuron methyl + pretilachlor, whereas lower values of dehydrogenase and fluorescein diacetate activities were observed with the application of chlorimuron + metsulfuron-methyl at 15 days after herbicide application. Our results suggest that pyrazosulfuron ethyl is one broad-spectrum and economically effective herbicide for controlling weeds as an alternative to labour consuming hand weeding in boro rice cultivation.
Unintended Bigamies: Holy Widowhood, Marriage, andSponsa Christiin Erasmus'sDe Vidua Christiana
Authors: Smith William E.
Published: March 2017

Christ's brides were hell bound by the end of the Middle Ages, when women—in the figure of the witch—were increasingly seen as Satan's spouses. Such is the narrative arc of Dyan Elliott's significant recent study ofsponsa Christi(bride of Christ),The Bride of Christ Goes to Hell. Elliott points toward the incarnational logic of Christianity in general and the type of physically immanent bridal mysticism that flourished among late medieval women in particular to locate some of the dynamic forces that helped make possible the theological ideas about witches that flourished from the fifteenth century onward. Elliott has done much to enrich our understanding of the development of an embodied version of the bride of Christ. Medieval and early modern Christianity held out an option, for women at least, to marry Jesus—to become asponsa Christi—in a literal sense, a form of marriage sustained by such things as legal mechanisms, theological visions, particular emotions, religious rituals, and spiritual practices. But Elliott's argument, stopping as it does right before the tumultuous sixteenth century, lends itself to a reading that the literalizedsponsa Christiwas bound henceforth to the early modern witch craze. Desiderius Erasmus's 1529 treatiseDe vidua christianaprovides us evidence that the literalizedsponsa Christideveloped in alternative ways in the early modern period, including the creation of a distinctive vision of the Christian widow who is, at times, bigamous.De vidua, then, can serve as the basis for expanding upon an alternative historical trajectory for the bride of Christ that Elliott mentions in passing in her study.
Genetic characterization of spotted fever group rickettsiae in questing ixodid ticks collected in Israel and environmental risk factors for their infection
Authors: ROSE JESSICA , NACHUM-BIALA YAARIT , MUMCUOGLU KOSTA Y. , ALKHAMIS MOH A. , BEN-NUN ADI , LENSKY ITAMAR , KLEMENT EYAL , NASEREDDIN ABEDELMAJEED , ABDEEN ZIAD A. , HARRUS SHIMON
Published: March 2017

This study aimed to genetically characterize spotted fever group rickettsiae (SFGR) in questing ixodid ticks from Israel and to identify risk factors associated with SFGR-positive ticks using molecular techniques and geographic information systems (GIS) analysis. 1039 ticks from the genusRhipicephaluswere collected during 2014. 109/1039 (10·49%) carried SFGR-DNA of eitherRickettsia massiliae(95), ‘CandidatusRickettsia barbariae’ (8) orRickettsia conorii(6). Higher prevalence of SFGR was found inRhipicephalus turanicus(18·00%) compared withRhipicephalus sanguineussensu lato (3·22%).Rickettsia massiliaewas the most commonly detected species and the most widely disseminated throughout Israel (87·15% of allRickettsia-positive ticks). GIS analysis revealed that Central and Northern coastal regions are at high risk for SFGR. The presence of ticks was significantly associated with normalized difference vegetation index and temperature variation over the course of the year. The presence of rickettsiae was significantly associated with brown type soils, higher land surface temperature and higher precipitation. The latter parameters may contribute to infection of the tick with SFGR. Health care professionals should be aware of the possible exposure of local communities and travellers toR. massillae. Molecular and geographical information can help professionals to identify areas that are susceptible to SFGR-infected ticks.
Are managers open to involvement in employee retirement? The influence of manager psycho-social characteristics, decision-making environment and older employee situational factors
Authors: DAVIES ELEANOR M. M. , VAN DER HEIJDEN BEATRICE I. J. M. , STEPHENSON JOHN
Published: March 2017

The changing retirement landscape calls on employers to develop practices that respond to individuals’ retirement needs. Line managers are a key stakeholder in managing retirement and this study focuses on how they respond to employee retirement scenarios. This empirical work examines manager openness to involvement in retirement, focusing on three sets of explanatory variables: manager psycho-social characteristics (experience of managing older workers, intention to work past 65), their decision-making environment (influence, discretion and decision-making support) and older employee situational factors (performance, ease of replacement, retirement affect and attitude to work). Data were collected from 129 managers in the United Kingdom's university sector using survey items and a factorial vignette design. The multi-level analysis found support for each category of variables in predicting manager openness to involvement in employee retirement. Managers with more experience of managing older workers were more likely to be open to involvement although managers’ own retirement intentions were not significant as a predictor. Decision-making environment variables were significant predictors of manager openness to involvement. The only older employee situational factor that was associated with manager openness to involvement was employee performance. Practically, organisations need to recognise the potential influence that managers have on employee retirement decisions and this study's findings show that managers may need training to help them understand their own role in supporting older employee retirement.
The ‘Development’ Discourse in Multilateral Trade Lawmaking
Authors: LAMP NICOLAS
Published: March 2017

The impact of the idea of ‘development’ in multilateral trade lawmaking is often reduced to the principle of ‘special and differential treatment’, which exempts developing countries from certain obligations imposed by the trade regime. The article shows that ‘development’ has always presented a much wider challenge to the vision of the trade regime championed by the major trading nations. The development discourse has conceived the trade regime's historical significance, the regime's aims, and the relationships among its members in ways that were often fundamentally at odds with the conception preferred by most developed countries. The article explores how the development discourse has informed lawmaking initiatives by developing countries throughout the history of the trade regime. While not all of these initiatives were successful or necessarily fruitful, they show that the pursuit of development in trade lawmaking has always been more than an effort to seek exemption from trade rules.
Social, economic and environmental impacts of organic cotton production on the livelihood of smallholder farmers in Odisha, India
Authors: Altenbuchner Christine , Vogel Stefan , Larcher Manuela
Published: March 2017

Cotton is an important source of income for smallholder farmers in India, usually grown very intensively. To counteract negative impacts of cotton cultivation in India, such as environmental degradation and financial dependency due to high input costs, organic cotton cultivation is being promoted by non-governmental organizations in the country. This study examines how the conversion to organic cotton cultivation influences the livelihood of smallholder farmers in rural India. Interviews with organic farmers were conducted in Odisha, India, complemented by expert interviews and observations in the field. Results show that farmers profit from organic agriculture, mainly due to soil improvements, through reduced exposure to toxic chemicals and lower input costs, which in turn reduces dependency on money lenders. Organic agriculture enables smallholder farmers in the study region to improve their livelihood by providing access to training and by organizing in groups. Important social impacts identified in this study were capacity building and strengthened communities, through training and institution building. However, a higher workload, due to the higher work intensity of organic farming practices, was also observed, with this impacting women more than men. Environmental conditions and gender aspects still remain challenging.
Development assistance for health: what criteria do multi- and bilateral funders use?
Authors: Ottersen Trygve , Kamath Aparna , Moon Suerie , Martinsen Lene , Røttingen John-Arne
Published: March 2017

After years of unprecedented growth in development assistance for health (DAH), the system is challenged on several fronts: by the economic downturn and stagnation of DAH, by the epidemiological transition and increase in non-communicable diseases, and by the economic transition and rise of the middle-income countries. This raises questions about which countries should receive DAH and how much, and, fundamentally, what criteria that promote fair and effective allocation. Yet, no broad comparative assessment exists of the criteria used today. We reviewed the allocation criteria stated by five multilateral and nine bilateral funders of DAH. We found that several funders had only limited information about concrete criteria publicly available. Moreover, many funders not devoted to health lacked specific criteria for DAH or criteria directly related to health, and no funder had criteria directly related to inequality. National income per capita was emphasised by many funders, but the associated eligibility thresholds varied considerably. These findings and the broad overview of criteria can assist funders in critically examining and revising the criteria they use, and inform the wider debate about what the optimal criteria are.
Business As Usual:Maya and Merchants on Yucatán-Belize border at the Onset of the Caste War
Authors: Dutt Rajeshwari
Published: March 2017

On September 13, 1849, Yucatecan forces at Chac Creek, near the port city of Bacalar (in present-day Quintana Roo), stopped and searched a vessel namedFour Sisters, owned by the Belizean merchant, Austin W. Cox. Inside they uncovered kegs containing 73arrobas(25-pound kegs) of gunpowder and 16 arrobas of lead. Manned by three black men, the vessel also carried a Maya on whom the search party found incriminating evidence, in the form of a letter from Cox to Maya rebel leader Jacinto Pat. The letter made it clear that the gunpowder was meant for the Maya insurgents who were fighting against Mexican authorities in the Yucatán's raging Caste War. Historians of the Caste War period have consistently recognized that the Belizean authorities ignored the munitions trade that flourished between Mexico and Belize during the conflict. Largely unexplored has been the critical role that merchants and munitions traders played in shaping the British government's attitude, and consequently its policies, toward Maya groups during this volatile period.
Using the Errors-in-Variables Method in Two-Group Pretest-Posttest	Designs
Authors: Counsell Alyssa , Cribbie Robert A.
Published: March 2017

Abstract. Culpepper and Aguinis (2011) highlighted the benefit of using the errors-in-variables (EIV) method to control for measurement error and obtain unbiased regression estimates. The current study investigated the EIV method and compared it to change scores and analysis of covariance (ANCOVA) in a two-group pretest-posttest design. Results indicated that the EIV method’s estimates were unbiased under many conditions, but the EIV method consistently demonstrated lower power than the change score method. An additional risk with using the EIV method is that one must enter the covariate reliability into the EIV model, and results highlighted that estimates are biased if a researcher chooses a value that differs from the true covariate reliability. Obtaining unbiased results also depended on sample size. Our conclusion is that there is no additional benefit to using the EIV method over change score or ANCOVA methods for comparing the amount of change in pretest-posttest designs.
Molecular insights of Gas6/TAM in cancer development and therapy
Authors: Wu Guiling , Ma Zhiqiang , Hu Wei , Wang Dongjin , Gong Bing , Fan Chongxi , Jiang Shuai , Li Tian , Gao Jianyuan , Yang Yang
Published: March 2017

Since growth arrest-specific gene 6 (Gas6) was discovered in 1988, numerous studies have highlighted the role of the Gas6 protein and its receptors Tyro3, Axl and Mer (collectively referred to as TAM), in proliferation, apoptosis, efferocytosis, leukocyte migration, sequestration and platelet aggregation. Gas6 has a critical role in the development of multiple types of cancers, including pancreatic, prostate, oral, ovarian and renal cancers. Acute myelocytic leukaemia (AML) is a Gas6-dependent cancer, and Gas6 expression predicts poor prognosis in AML. Interestingly, Gas6 also has a role in establishing tumour dormancy in the bone marrow microenvironment and in suppressing intestinal tumorigenesis. Numerous studies regarding cancer therapy have targeted Gas6 and TAM receptors with good results. However, some findings have suggested that Gas6 is associated with the development of resistance to cancer therapies. Concerning these significant effects of Gas6 in numerous cancers, we discuss the roles of Gas6 in cancer development in this review. First, we introduce basic knowledge on Gas6 and TAM receptors. Next, we describe and discuss the involvement of Gas6 and TAM receptors in cancers from different organ systems. Finally, we highlight the progress in therapies targeting Gas6 and TAM receptors. This review presents the significant roles of Gas6 in cancers from different systems and may contribute to the continued promotion of Gas6 as a therapeutic target.
Solute carrier family 12 member 5 promotes tumor invasion/metastasis of bladder urothelial carcinoma by enhancing NF-κB/MMP-7 signaling pathway
Authors: Liu J Y , Dai Y B , Li X , Cao K , Xie D , Tong Z T , Long Z , Xiao H , Chen M K , Ye Y L , Liu B , Tan J , Tang J , Xu Z Z , Gan Y , Zhou Y H , Deng F , He L Y
Published: March 2017

Solute carrier family 12 member 5 (SLC12A5), an integral membrane KCl cotransporter, which maintains chloride homeostasis in neurons, is aberrantly expressed and involved in the tumorigenesis of certain cancers. However, the clinical significance and biological role of SLC12A5 in human bladder urothelial carcinoma (BUC) remains unclear. In this study, the expression of SLC12A5 was examined in clinical specimens of primary BUC and in BUC cell lines using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). The prognostic value of SLC12A5 expression and its correlation with the clinicopathological features of patients with BUC were analyzed statistically. A series of in vitro and in vivo assays were performed to elucidate the effect of SLC12A5 in BUC and its underlying mechanisms. The present results showed that SLC12A5 expression was significantly increased in BUC tissues. SLC12A5 expression significantly correlated with the tumor node metastasis (TNM) stage. Kaplan–Meier survival curves showed that high SLC12A5 expression was associated with poor survival in patients with BUC. Multivariate analysis indicated that SLC12A5 expression was an independent prognostic marker for the survival of patients. Downregulation of SLC12A5 inhibited the migratory and invasive abilities of BUC cells in vitro, and knocking down SLC12A5 diminished BUC metastasis in vivo. Moreover, we identified that SLC12A5 promoted the migration and invasion of BUC by enhancing MMP-7 expression via NF-κB-dependent transcription. Taken together, our findings indicated that SLC12A5 might function as a tumor metastasis promoting factor in the development and progression of BUC by regulating the NF-κB/MMP-7 signaling pathway. Thus, SLC12A5 might be a prognostic marker as well as a therapeutic target for BUC.
Inhibition of autophagy prevents irradiation-induced neural stem and progenitor cell death in the juvenile mouse brain
Authors: Wang Yafeng , Zhou Kai , Li Tao , Xu Yiran , Xie Cuicui , Sun Yanyan , Zhang Yaodong , Rodriguez Juan , Blomgren Klas , Zhu Changlian
Published: March 2017

Radiotherapy is an effective tool in the treatment of malignant brain tumors. However, damage to brain stem and progenitor cells constitutes a major problem and is associated with long-term side effects. Autophagy has been shown to be involved in cell death, and the purpose of this study was to evaluate the effect of autophagy inhibition on neural stem and progenitor cell death in the juvenile brain. Ten-day-old selective Atg7 knockout (KO) mice and wild-type (WT) littermates were subjected to a single 6Gy dose of whole-brain irradiation. Cell death and proliferation as well as microglia activation and inflammation were evaluated in the dentate gyrus of the hippocampus and in the cerebellum at 6 h after irradiation. We found that cell death was reduced in Atg7 KO compared with WT mice at 6 h after irradiation. The number of activated microglia increased significantly in both the dentate gyrus and the cerebellum of WT mice after irradiation, but the increase was lower in the Atg7 KO mice. The levels of proinflammatory cytokines and chemokines decreased, especially in the cerebellum, in the Atg7 KO group. These results suggest that autophagy might be a potential target for preventing radiotherapy-induced neural stem and progenitor cell death and its associated long-term side effects.
NPAS2 promotes cell survival of hepatocellular carcinoma by transactivating CDC25A
Authors: Yuan Peng , Li Jibin , Zhou Feng , Huang Qichao , Zhang Jiansheng , Guo Xu , Lyu Zhuomin , Zhang Hongxin , Xing Jinliang
Published: March 2017

Emerging evidences show that disruption of the circadian rhythm is associated with tumor initiation and progression. Neuronal PAS domain protein 2 (NPAS2), one of the core circadian molecules, has been proved to be a potential prognostic biomarker in colorectal and breast cancers. However, to date, the potential functional roles and molecular mechanisms by which NPAS2 affects cancer cell survival are greatly unclear, especially in hepatocellular carcinoma (HCC). We first investigated the expression of NPAS2 and its clinical significance in HCC. We then systematically explored the role of NPAS2 in HCC cell survival both in vitro and in vivo and the underlying mechanism. NPAS2 was frequently upregulated in HCC, which significantly facilitated cell survival both in vitro and in vivo mainly by promoting cell proliferation and inhibiting mitochondria-dependent intrinsic apoptosis, and thus contributed to poor prognosis of HCC patients. Mechanistically, the survival-promoting role of NPAS2 was mediated by transcriptional upregulation of the CDC25A phosphatase and subsequent dephosphorylation of CDK2/4/6 and Bcl-2, which induced cell proliferation and inhibited cell apoptosis in HCC, respectively. Moreover, BMAL1, another core clock transcription factor, was identified to heterodimerize with NPAS2 to bind to the E-box element in the promoter of CDC25A and be associated with the NPAS2-mediated tumor cell survival in HCC. Our findings demonstrate that NPAS2 has a critical role in HCC cell survival and tumor growth, which is mainly mediated by transcriptional upregulation of CDC25A. Thereby, NPAS2 may serve as a potential therapeutic target in HCC patients.
Hydrogen sulfide promotes autophagy of hepatocellular carcinoma cells through the PI3K/Akt/mTOR signaling pathway
Authors: Wang Shanshan S , Chen Yuhan H , Chen Ning , Wang Lijun J , Chen Dexi X , Weng Honglei L , Dooley Steven , Ding Huiguo G
Published: March 2017

Hydrogen sulfide (H2S), in its gaseous form, plays an important role in tumor carcinogenesis. This study investigated the effects of H2S on the cell biological functions of hepatocellular carcinoma (HCC). HCC cell lines, HepG2 and HLE, were treated with NaHS, a donor of H2S, and rapamycin, a classic autophagy inducer, for different lengths of time. Western blotting, immunofluorescence, transmission electron microscopy (TEM), scratch assay, CCK-8 and flow cytometric analysis were carried out to examine the effects of H2S on HCC autophagy, cell behavior and PI3K/Akt/mTOR signaling. Treatment with NaHS upregulated expression of LC3-II and Atg5, two autophagy-related proteins, in HepG2 and HLE cells. TEM revealed increased numbers of intracellular double-membrane vesicles in those cells treated with NaHS. Like rapamycin, NaHS also significantly inhibited expression of p-PI3K, p-Akt and mTOR proteins in HCC cells. Interestingly, the expression of LC3-II was further increased when the cells were treated with NaHS together with rapamycin. In addition, NaHS inhibited HCC cell migration, proliferation and cell division. These findings show that H2S can induce HCC cell apoptosis. The biological function of the gasotransmitter H2S in HCC cells was enhanced by the addition of rapamycin. Hydrogen sulfide influences multiple biological functions of HCC cells through inhibiting the PI3K/Akt/mTOR signaling pathway.
Upregulation of miR-665 promotes apoptosis and colitis in inflammatory bowel disease by repressing the endoplasmic reticulum stress components XBP1 and ORMDL3
Authors: Li Manying , Zhang Shenghong , Qiu Yun , He Yao , Chen Baili , Mao Ren , Cui Yi , Zeng Zhirong , Chen Minhu
Published: March 2017

MicroRNAs are critical post-transcriptional regulators of gene expression and key mediators of pathophysiology of inflammatory bowel disease (IBD). This study is aimed to study the role of miR-665 in the progression of IBD. Real-time PCR analysis was used to determine miR-665 expression in 89 freshly isolated IBD samples and dextran sulfate sodium (DSS)-induced colonic mucosal tissues. The role of miR-665 in inducing apoptosis and colitis were examined by Annexin V, TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining, colony formation in vitro and DSS-induced colitis mice model in vivo. Moreover, luciferase reporter assay, western blot analysis and microribonucleoprotein immunoprecipitation were performed to determine that miR-665 directly repressed XBP1 (X-box-binding protein-1) and ORMDL3 expression. Herein, our results revealed that miR-665 was markedly upregulated in active colitis. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-665 promoted apoptosis under different inflammatory stimuli. Importantly, delivery of miR-665 mimic promoted, while injection of antagomiR-665 markedly impaired DSS-induced colitis in vivo. Mechanistically, we demonstrated that miR-665 induced apoptosis by inhibiting XBP1 and ORMDL3. Taken together, our findings reveal a new regulatory mechanism for ER stress signaling and suggest that miR-665 might be a potential target in IBD therapy.
BRE modulates granulosa cell death to affect ovarian follicle development and atresia in the mouse
Authors: Yeung Cheung Kwan , Wang Guang , Yao Yao , Liang Jianxin , Tenny Chung Cheuk Yiu , Chuai Manli , Lee Kenneth Ka Ho , Yang Xuesong
Published: March 2017

The BRE (brain and reproductive expression) gene, highly expressed in nervous and reproductive system organs, plays an important role in modulating DNA damage repair under stress response and pathological conditions. Folliculogenesis, a process that ovarian follicle develops into maturation, is closely associated with the interaction between somatic granulosa cell and oocyte. However, the regulatory role of BRE in follicular development remains undetermined. In this context, we found that BRE is normally expressed in the oocytes and granulosa cells from the primordial follicle stage. There was a reduction in follicles number of BRE mutant (BRE−/−) mice. It was attributed to increase the follicular atresia in ovaries, as a result of retarded follicular development. We established that cell proliferation was inhibited, while apoptosis was markedly increased in the granulosa cells in the absence of BRE. In addition, expressions of γ-H2AX (marker for showing DNA double-strand breaks) and DNA damage-relevant genes are both upregulated in BRE−/− mice. In sum, these results suggest that the absence of BRE, deficiency in DNA damage repair, causes increased apoptosis in granulosa cells, which in turn induces follicular atresia in BRE−/− mice.
Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells
Authors: Bassey-Archibong Blessing I , Rayner Lyndsay G A , Hercules Shawn M , Aarts Craig W , Dvorkin-Gheva Anna , Bramson Jonathan L , Hassell John A , Daniel Juliet M
Published: March 2017

Triple negative breast cancers (TNBC) are highly aggressive and lack specific targeted therapies. Recent studies have reported high expression of the transcription factor Kaiso in triple negative tumors, and this correlates with their increased aggressiveness. However, little is known about the clinical relevance of Kaiso in the growth and survival of TNBCs. Herein, we report that Kaiso depletion attenuates TNBC cell proliferation, and delays tumor onset in mice xenografted with the aggressive MDA-231 breast tumor cells. We further demonstrate that Kaiso depletion attenuates the survival of TNBC cells and increases their propensity for apoptotic-mediated cell death. Notably, Kaiso depletion downregulates BRCA1 expression in TNBC cells expressing mutant-p53 and we found that high Kaiso and BRCA1 expression correlates with a poor overall survival in breast cancer patients. Collectively, our findings reveal a role for Kaiso in the proliferation and survival of TNBC cells, and suggest a relevant role for Kaiso in the prognosis and treatment of TNBCs.
Plant cysteine oxidases are dioxygenases that directly enable arginyl transferase-catalysed arginylation of N-end rule targets
Authors: White Mark D. , Klecker Maria , Hopkinson Richard J. , Weits Daan A. , Mueller Carolin , Naumann Christin , O’Neill Rebecca , Wickens James , Yang Jiayu , Brooks-Bartlett Jonathan C. , Garman Elspeth F. , Grossmann Tom N. , Dissmeyer Nico , Flashman Emily
Published: March 2017

Crop yield loss due to flooding is a threat to food security. Submergence-induced hypoxia in plants results in stabilization of group VII ETHYLENE RESPONSE FACTORs (ERF-VIIs), which aid survival under these adverse conditions. ERF-VII stability is controlled by the N-end rule pathway, which proposes that ERF-VII N-terminal cysteine oxidation in normoxia enables arginylation followed by proteasomal degradation. The PLANT CYSTEINE OXIDASEs (PCOs) have been identified as catalysts of this oxidation. ERF-VII stabilization in hypoxia presumably arises from reduced PCO activity. We directly demonstrate that PCO dioxygenase activity produces Cys-sulfinic acid at the N terminus of an ERF-VII peptide, which then undergoes efficient arginylation by an arginyl transferase (ATE1). This provides molecular evidence of N-terminal Cys-sulfinic acid formation and arginylation by N-end rule pathway components, and a substrate of ATE1 in plants. The PCOs and ATE1 may be viable intervention targets to stabilize N-end rule substrates, including ERF-VIIs, to enhance submergence tolerance in agriculture.
Pharmacokinetic-Pharmacodynamic modelling of intracellular Mycobacterium tuberculosis growth and kill rates is predictive of clinical treatment duration
Authors: Aljayyoussi Ghaith , Jenkins Victoria A. , Sharma Raman , Ardrey Alison , Donnellan Samantha , Ward Stephen A. , Biagini Giancarlo A.
Published: March 2017

Tuberculosis (TB) treatment is long and complex, typically involving a combination of drugs taken for 6 months. Improved drug regimens to shorten and simplify treatment are urgently required, however a major challenge to TB drug development is the lack of predictive pre-clinical tools. To address this deficiency, we have adopted a new high-content imaging-based approach capable of defining the killing kinetics of first line anti-TB drugs against intracellular Mycobacterium tuberculosis (Mtb) residing inside macrophages. Through use of this pharmacokinetic-pharmacodynamic (PK-PD) approach we demonstrate that the killing dynamics of the intracellular Mtb sub-population is critical to predicting clinical TB treatment duration. Integrated modelling of intracellular Mtb killing alongside conventional extracellular Mtb killing data, generates the biphasic responses typical of those described clinically. Our model supports the hypothesis that the use of higher doses of rifampicin (35 mg/kg) will significantly reduce treatment duration. Our described PK-PD approach offers a much needed decision making tool for the identification and prioritisation of new therapies which have the potential to reduce TB treatment duration.
Reinterpretation of oceanic 230Th profiles based on decadal export productivity (2003–2010)
Authors: Luo Yiming
Published: March 2017

Understanding 230Th distributions in the global ocean is important to support and guide the use of this important radioactive nuclide in multiple aspects of oceanographic research, and this issue is now revisited. Based on estimates of export productivity (EP) over 2003–2010 and assuming 230Th scavenging at equilibrium at seven Pacific stations where linear 230Th profiles are found, an empirical equilibrium-state 230Th-scavenging versus EP correlation is established. This correlation demonstrates the relationship between 230Th-scavenging intensity and EP in the absence of advection. With this correlation, other 230Th profiles from global oceans are reinterpreted. My findings provide alternative explanations of signals carried by 230Th distributions with regard to advection, by a reassessment of the 230Th deficits in deep waters. Such an equilibrium-state 230Th-scavenging versus EP correlation provides a basis for convenient parameterization for use in 3D modeling studies of the 230Th distributions.
Correction: Corrigendum: Towards ultrasensitive malaria diagnosis using surface enhanced Raman spectroscopy
Authors: Chen Keren , Yuen Clement , Aniweh Yaw , Preiser Peter , Liu Quan
Published: March 2017

Scientific Reports 6: Article number: 20177; published online: 09 February 2016; updated: 23 March 2017 In this Article, Yaw Aniweh and Peter Preiser are incorrectly listed as being affiliated with the ‘School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637457’.
Mass coral mortality under local amplification of 2 °C ocean warming
Authors: DeCarlo Thomas M. , Cohen Anne L. , Wong George T. F. , Davis Kristen A. , Lohmann Pat , Soong Keryea
Published: March 2017

A 2 °C increase in global temperature above pre-industrial levels is considered a reasonable target for avoiding the most devastating impacts of anthropogenic climate change. In June 2015, sea surface temperature (SST) of the South China Sea (SCS) increased by 2 °C in response to the developing Pacific El Niño. On its own, this moderate, short-lived warming was unlikely to cause widespread damage to coral reefs in the region, and the coral reef “Bleaching Alert” alarm was not raised. However, on Dongsha Atoll, in the northern SCS, unusually weak winds created low-flow conditions that amplified the 2 °C basin-scale anomaly. Water temperatures on the reef flat, normally indistinguishable from open-ocean SST, exceeded 6 °C above normal summertime levels. Mass coral bleaching quickly ensued, killing 40% of the resident coral community in an event unprecedented in at least the past 40 years. Our findings highlight the risks of 2 °C ocean warming to coral reef ecosystems when global and local processes align to drive intense heating, with devastating consequences.
Effect of probe diffusion on the SOFI imaging accuracy
Authors: Vandenberg Wim , Dedecker Peter
Published: March 2017

Live-cell super-resolution fluorescence imaging is becoming commonplace for exploring biological systems, though sample dynamics can affect the imaging quality. In this work we evaluate the effect of probe diffusion on super-resolution optical fluctuation imaging (SOFI), using a theoretical model and numerical simulations based on the imaging of live cells labelled with photochromic fluorescent proteins. We find that, over a range of physiological conditions, fluorophore diffusion results in a change in the amplitude of the SOFI signal. The magnitude of this change is approximately proportional to the on-time ratio of the fluorophores. However, for photochromic fluorescent proteins this effect is unlikely to present a significant distortion in practical experiments in biological systems. Due to this lack of distortions, probe diffusion strongly enhances the SOFI imaging by avoiding spatial undersampling caused by the limited labeling density.
Age of Complementary Foods Introduction and Risk of Anemia in Children Aged 4–6 years: A Prospective Birth Cohort in China
Authors: Wang Fenglei , Liu Huijuan , Wan Yi , Li Jing , Chen Yu , Zheng Jusheng , Huang Tao , Li Duo
Published: March 2017

Age of complementary foods introduction is associated with childhood anemia, but the ideal age for the introduction of complementary foods to infants is a continuing topic of debate. We examined the longitudinal association between complementary foods introduction age and risk of anemia in 18,446 children from the Jiaxing Birth Cohort, who had detailed complementary feeding records at 3 and 6 months of age and had hemoglobin concentrations measured at 4–6 years. Early introduction of complementary foods at 3–6 months of age was significantly associated with a higher risk of anemia (odds ratio = 1.14; 95% confidence interval: 1.01–1.28) and a lower hemoglobin concentration of −0.84 g/L (95% confidence interval: −1.33 to −0.35) in children aged 4–6 years, compared with those fed complementary foods starting at 6 months of age. When it comes to the specific type of complementary foods, early introduction of all plant-based foods was associated with increased anemia risks and lower hemoglobin concentrations, while early introduction of most animal-based foods was not. These findings may be informative regarding the appropriate time to introduce complementary foods in infants.
Enzyme IIANtr Regulates Salmonella Invasion Via 1,2-Propanediol And Propionate Catabolism
Authors: Yoo Woongjae , Kim Dajeong , Yoon Hyunjin , Ryu Sangryeol
Published: March 2017

Many Proteobacteria possess a nitrogen-metabolic phosphotransferase system (PTSNtr) consisting of EINtr, NPr, and EIIANtr (encoded by ptsP, ptsO, and ptsN, respectively). The PTSNtr plays diverse regulatory roles, but the substrate phosphorylated by EIIANtr and its primary functions have not yet been identified. To comprehensively understand the roles of PTSNtr in Salmonella Typhimurium, we compared the whole transcriptomes of wild-type and a ΔptsN mutant. Genome-wide RNA sequencing revealed that 3.5% of the annotated genes were up- or down-regulated by three-fold or more in the absence of EIIANtr. The ΔptsN mutant significantly down-regulated the expression of genes involved in vitamin B12 synthesis, 1,2-propanediol utilization, and propionate catabolism. Moreover, the invasiveness of the ΔptsN mutant increased about 5-fold when 1,2-propanediol or propionate was added, which was attributable to the increased stability of HilD, the transcriptional regulator of Salmonella pathogenicity island-1. Interestingly, an abundance of 1,2-propanediol or propionate promoted the production of EIIANtr, suggesting the possibility of a positive feedback loop between EIIANtr and two catabolic pathways. These results demonstrate that EIIANtr is a key factor for the utilization of 1,2-propanediol and propionate as carbon and energy sources, and thereby modulates the invasiveness of Salmonella via 1,2-propanediol or propionate catabolism.
Cheetahs have a stronger constitutive innate immunity than leopards
Authors: Heinrich Sonja K. , Hofer Heribert , Courtiol Alexandre , Melzheimer Jörg , Dehnhard Martin , Czirják Gábor Á. , Wachter Bettina
Published: March 2017

As a textbook case for the importance of genetics in conservation, absence of genetic variability at the major histocompatibility complex (MHC) is thought to endanger species viability, since it is considered crucial for pathogen resistance. An alternative view of the immune system inspired by life history theory posits that a strong response should evolve in other components of the immune system if there is little variation in the MHC. In contrast to the leopard (Panthera pardus), the cheetah (Acinonyx jubatus) has a relatively low genetic variability at the MHC, yet free-ranging cheetahs are healthy. By comparing the functional competence of the humoral immune system of both species in sympatric populations in Namibia, we demonstrate that cheetahs have a higher constitutive innate but lower induced innate and adaptive immunity than leopards. We conclude (1) immunocompetence of cheetahs is higher than previously thought; (2) studying both innate and adaptive components of immune systems will enrich conservation science.
Phenotype of postural instability/gait difficulty in Parkinson disease: relevance to cognitive impairment and mechanism relating pathological proteins and neurotransmitters
Authors: Zuo Li-Jun , Piao Ying-Shan , Li Li-Xia , Yu Shu-Yang , Guo Peng , Hu Yang , Lian Teng-Hong , Wang Rui-Dan , Yu Qiu-Jin , Jin Zhao , Wang Ya-Jie , Wang Xiao-Min , Chan Piu , Chen Sheng-Di , Wang Yong-Jun , Zhang Wei
Published: March 2017

Parkinson disease (PD) is identified as tremor-dominant (TD) and postural instability and gait difficulty (PIGD) phenotypes. The relationships between motor phenotypes and cognitive impairment and the underlying mechanisms relating pathological proteins and neurotransmitters in cerebrospinal fluid (CSF) are unknown. We evaluated the motor symptoms and cognitive function by scales, and detected the levels of pathological proteins and neurotransmitters in CSF. TD group and PIGD group had significantly higher levels of total tau, tau phosphorylated at the position of threonine 181(P-tau181t), threonine 231, serine 396, serine 199 and lower β amyloid (Aβ)1–42 level in CSF than those in control group; PIGD group had significantly higher P-tau181t level and lower Aβ1–42 level than those in TD group. In PD group, PIGD severity was negatively correlated with MoCA score and Aβ1–42 level in CSF, and positively correlated with Hoehn-Yahr stage and P-tau181t level in CSF. In PIGD group, PIGD severity was negatively correlated with homovanillic acid (HVA) level in CSF, and HVA level was positively correlated with Aβ1–42 level in CSF. PIGD was significantly correlated with cognitive impairment, which underlying mechanism might be involved in Aβ1–42 aggregation in brain and relevant neurochemical disturbance featured by the depletion of HVA in CSF.
Inertial bioluminescence rhythms at the Capo Passero (KM3NeT-Italia) site, Central Mediterranean Sea
Authors: Aguzzi J. , Fanelli E. , Ciuffardi T. , Schirone A. , Craig J. ,   KM3NeT-Italia/NEMO Collaboration, Aiello S. , Ameli F. , Anghinolfi M. , Barbarino G. , Barbarito E. , Beverini N. , Biagi S. , Biagioni A. , Bouhadef B. , Bozza C. , Cacopardo G. , Calamai M. , Calì C. , Capone A. , Caruso F. , Cecchini S. , Ceres A. , Chiarusi T. , Circella M. , Cocimano R. , Coniglione R. , Costa M. , Cuttone G. , D’Amato C. , D’Amico A. , De Bonis G. , De Luca V. , Deniskina N. , Distefano C. , Di Mauro L. S. , Fermani P. , Ferrara G. , Flaminio V. , Fusco L. A. , Garufi F. , Giordano V. , Gmerk A. , Grasso R. , Grella G. , Hugon C. , Imbesi M. , Kulikovskiy V. , Larosa G. , Lattuada D. , Leismüller K. P. , Leonora E. , Litrico P. , Lonardo A. , Longhitano F. , Presti D. Lo , Maccioni E. , Margiotta A. , Marinelli A. , Martini A. , Masullo R. , Mele R. , Migliozzi P. , Migneco E. , Miraglia A. , Mollo C. M. , Mongelli M. , Morganti M. , Musico P. , Musumeci M. , Nicolau C. A. , Orlando A. , Orzelli A. , Papaleo R. , Pellegrino C. , Pellegriti M. G. , Perrina C. , Piattelli P. , Poma E. , Pulvirenti S. , Raffaelli F. , Randazzo N. , Riccobene G. , Rovelli A. , Sanguineti M. , Sapienza P. , Sciacca V. , Sgura I. , Simeone F. , Sipala V. , Speziale F. , Spitaleri A. , Spurio M. , Stellacci S. M. , Taiuti M. , Terreni G. , Trasatti L. , Trovato A. , Versari F. , Vicini P. , Viola S. , Vivolo D.
Published: March 2017

In the deep sea, the sense of time is dependent on geophysical fluctuations, such as internal tides and atmospheric-related inertial currents, rather than day-night rhythms. Deep-sea neutrino telescopes instrumented with light detecting Photo-Multiplier Tubes (PMT) can be used to describe the synchronization of bioluminescent activity of abyssopelagic organisms with hydrodynamic cycles. PMT readings at 8 different depths (from 3069 to 3349 m) of the NEMO Phase 2 prototype, deployed offshore Capo Passero (Sicily) at the KM3NeT-Italia site, were used to characterize rhythmic bioluminescence patterns in June 2013, in response to water mass movements. We found a significant (p < 0.05) 20.5 h periodicity in the bioluminescence signal, corresponding to inertial fluctuations. Waveform and Fourier analyses of PMT data and tower orientation were carried out to identify phases (i.e. the timing of peaks) by subdividing time series on the length of detected inertial periodicity. A phase overlap between rhythms and cycles suggests a mechanical stimulation of bioluminescence, as organisms carried by currents collide with the telescope infrastructure, resulting in the emission of light. A bathymetric shift in PMT phases indicated that organisms travelled in discontinuous deep-sea undular vortices consisting of chains of inertially pulsating mesoscale cyclones/anticyclones, which to date remain poorly known.
Dairy cows value access to pasture as highly as fresh feed
Authors: von Keyserlingk Marina A. G. , Amorim Cestari Andressa , Franks Becca , Fregonesi Jose A. , Weary Daniel M.
Published: March 2017

Many dairy cows in the developed world are now housed exclusively indoors with fewer than 5% of the 10 million lactating cows in the United States having access to pasture during the grazing season. Indoor housing systems are designed to meet biological needs for food, water, hygiene, and shelter, but surveys of public and farmer opinion suggest that people think that pasture access is also important for the well-being of dairy cows. To determine if pasture access is important to the cows themselves, we investigated to what extent cows will work to access pasture (by pushing on a weighted gate), and compared it to the motivation to access fresh feed. Cows worked at least as hard to access pasture as they did to access the fresh feed and worked hardest for outdoor access in the evening hours. Echoing public views on what allows for a good life for cattle, these results show that cows are highly motivated for outdoor access.
Erratum: Laser-Driven Ion Acceleration from Plasma Micro-Channel Targets
Authors: Zou D. B. , Pukhov A. , Yi L. Q. , Zhuo H. B. , Yu T. P. , Yin Y. , Shao F. Q.
Published: March 2017

Scientific Reports 7: Article number: 42666; published online: 20 February 2017; updated: 23 March 2017 The original version of this Article contained a typographical error in the spelling of the author H. B. Zhuo, which was incorrectly given as H. B. Zhou. This has now been corrected in the PDF andHTML versions of the Article.
Correction: Corrigendum: NF-kappaB-inducing kinase regulates stem cell phenotype in breast cancer
Authors: Vazquez-Santillan Karla , Melendez-Zajgla Jorge , Jimenez-Hernandez Luis Enrique , Gaytan-Cervantes Javier , Muñoz-Galindo Laura , Piña-Sanchez Patricia , Martinez-Ruiz Gustavo , Torres Javier , Garcia-Lopez Patricia , Gonzalez-Torres Carolina , Ruiz Victor , Avila-Moreno Federico , Velasco-Velazquez Marco , Perez-Tapia Mayra , Maldonado Vilma
Published: March 2017

Scientific Reports 6: Article number: 37340; published online: 23 November 2016; updated: 23 March 2017 The Acknowledgements section in this Article is incomplete. “Karla Itzel Vazquez Santillan was supported by a fellowship from CONACYT (165306), and this study is part of her doctoral thesis from the Biomedical Sciences Doctorate Program, Faculty of Medicine, Universidad Nacional Autonoma de Mexico.
A new class of inhibitors of the AraC family virulence regulator Vibrio cholerae ToxT
Authors: Woodbrey Anne K. , Onyango Evans O. , Pellegrini Maria , Kovacikova Gabriela , Taylor Ronald K. , Gribble Gordon W. , Kull F. Jon
Published: March 2017

Vibrio choleraeis responsible for the diarrheal disease cholera that infects millions of people worldwide. While vaccines protecting against cholera exist, and oral rehydration therapy is an effective treatment method, the disease will remain a global health threat until long-term solutions such as improved sanitation and access to clean water become widely available. Because of this, there is a pressing need for potent therapeutics that can either mitigate cholera symptoms, or act prophylactically to prevent the virulent effects of a cholera infection. Here we report the design, synthesis, and characterization of a set of compounds that bind and inhibit ToxT, the transcription factor that directly regulates the two primaryV. choleraevirulence factors. Using the folded structure of the monounsaturated fatty acid observed in the X-ray structure of ToxT as a template, we designed ten novel compounds that inhibit the virulence cascade to a greater degree than any known inhibitor. Our findings provide a structural and functional basis for the development of viable antivirulence therapeutics that combat cholera and, potentially, other forms of bacterial pathogenic disease.