bluuebunny/crossref_metadata_2025 huggingface dataset:
WHAT’S IN THE TEXTBOOK AND WHAT’S IN THE MIND
Authors: Marsden Heather , Whong Melinda , Gil Kook-Hee
Published: May 2017

This paper presents an experimental study of the rarely explored question of how input through instruction interacts with L2 acquisition at the level of modular linguistic knowledge. The investigation focuses on L2 knowledge of the English polarity itemany, whose properties are only partially covered by typical language-teaching materials. We investigate Najdi-Saudi Arabic-speaking learners’ knowledge of the distribution ofanyin contexts that are taught, contexts that are not taught but may be observable in the input, and contexts that are neither taught nor observable. We further test whether conscious awareness of instructed rules aboutanycorrelates with performance. Our findings suggest a role for instruction and for internal, UG-constrained acquisition, and that these two paths interact. We explore our findings in terms of Sharwood Smith and Truscott’s (2014a, 2014b) framework of modular online growth and use of language, in which cognitive development is driven by processing.
John Gay and the Birth of Utilitarianism
Authors: LUSTILA GETTY L.
Published: May 2017

This article concerns John Gay's 1731 essay ‘Preliminary Dissertation Concerning the Fundamental Principle of Virtue or Morality’. Gay undertakes two tasks here, the first of which is to supply a criterion of virtue. I argue that he is the first modern philosopher to claim that universal happiness is the aim of moral action. In other words: Gay is the first utilitarian. His second task is to explain the source of moral motivation. He draws upon the principles of association to argue (a) that we develop benevolent motives by associating the idea of our happiness with that of others and (b) that we come to approve of benevolence by recognizing that our happiness is inextricably connected with the general happiness. While some scholars have taken an interest in Gay's essay, a sustained treatment of its contents does not exist, despite its acknowledged influence on Hume, Hartley, James Mill, and John Stuart Mill.
Development and Evaluation of Acceptance and Commitment Therapy Delivered by Psychologists and Non-Psychologists in an NHS Community Adult Mental Health Service: a Preliminary Analysis
Authors: Richardson Thomas , Bell Lorraine , Bolderston Helen , Clarke Sue
Published: May 2017

Background: Previous studies have demonstrated that acceptance and commitment therapy (ACT) is effective for depression and may be useful for complex transdiagnostic clients. Aims: To conduct a preliminary evaluation of whether ACT is feasible and effective when delivered by psychologists and non-psychologists for complex clients in a National Health Service (NHS) community mental health service for adults. Method: Staff were trained in ACT and conducted one-to-one therapy with clients. Measures on general mental health, depression, fusion and values were given pre-therapy, post-therapy and at 3-month follow-up. Results: Standardized measures showed significant improvements post-therapy for global mental health, depression, cognitive fusion and values post-treatment. These were partially maintained at follow-up and remained after an intent-to-treat analysis. There were no differences in outcomes between psychologists and non-psychologists. Conclusions: ACT may be delivered effectively with limited training for complex cases in secondary care, though further research is needed.
Regular monitoring of breast-feeding rates: feasible and sustainable. The Emilia-Romagna experience
Authors: Di Mario Simona , Borsari Silvana , Verdini Eleonora , Battaglia Sergio , Cisbani Luca , Sforza Stefano , Cuoghi Chiara , Basevi Vittorio
Published: May 2017

Objective

An efficient breast-feeding monitoring system should be in place in every country to assist policy makers and health professionals plan activities to reach optimal breast-feeding rates.

Design/Setting/Subjects

From March to June 2015, breast-feeding rates at 3 and 5 months of age were monitored in Emilia-Romagna, an Italian region, using four questions added to a newly developed paediatric immunization database with single records for each individual. Data were collected at primary-care centres. Breast-feeding definitions and 24 h recall as recommended by the WHO were used. Direct age standardization was applied to breast-feeding rates. Record linkage with the medical birth database was attempted to identify maternal, pregnancy and delivery factors associated with full breast-feeding rates at 3 and 5 months of age.

Results

Data on breast-feeding were collected for 14044 infants. The mean regional full breast-feeding rate at 3 months was 52 %; differences between local health authorities ranged from 42 to 62 %. At 5 months of age, the mean regional full breast-feeding rate dropped to 33 % (range between local health authorities: 26 to 46 %). Record linkage with the birth certificate database was successful for 93 % of records. Total observations more than doubled with respect to the previous regional survey.

Conclusions

The new monitoring system implemented in 2015 in Emilia-Romagna region, totally integrated with the immunization database, has proved to be feasible, sustainable and more efficient than the previous one. This system can be a model for other regions and countries where the vast majority of mothers obtain vaccinations from public health facilities and that already have an immunization database in place.
Alternatives to antibiotics for maximizing growth performance and feed efficiency in poultry: a review
Authors: Gadde U. , Kim W. H. , Oh S. T. , Lillehoj Hyun S.
Published: May 2017

With the increase in regulations regarding the use of antibiotic growth promoters and the rise in consumer demand for poultry products from ‘Raised Without Antibiotics’ or ‘No Antibiotics Ever’ flocks, the quest for alternative products or approaches has intensified in recent years. A great deal of research has focused on the development of antibiotic alternatives to maintain or improve poultry health and performance. This review describes the potential for the various alternatives available to increase animal productivity and help poultry perform to their genetic potential under existing commercial conditions. The classes of alternatives described include probiotics, prebiotics, synbiotics, organic acids, enzymes, phytogenics, antimicrobial peptides, hyperimmune egg antibodies, bacteriophages, clay, and metals. A brief description of the mechanism of action, efficacy, and advantages and disadvantages of their uses are also presented. Though the beneficial effects of many of the alternatives developed have been well demonstrated, the general consensus is that these products lack consistency and the results vary greatly from farm to farm. Furthermore, their mode of action needs to be better defined. Optimal combinations of various alternatives coupled with good management and husbandry practices will be the key to maximize performance and maintain animal productivity, while we move forward with the ultimate goal of reducing antibiotic use in the animal industry.
Two Islamic Movements in conflict in terms of linguistic nationalism
Authors:   ANONYMOUS
Published: May 2017

Religion and nationalism are not only two distinctive but also closely related concepts when it comes to nation-building. Their role in language policy and linguistic nationalism is pervasive. Today, in Turkey, two religious movements of the same origin play a key role in linguistic nationalism and decision-making in language policy: the Gülen movement and the Med-Zehra movement. These two non-governmental affinities are important groups in the Nur movement. The Gülen movement is supportive of Turkish nationalism and thereby Turkish language and identity, while the Med-Zehra group emphasizes Kurdish identity and separatism. This study makes a comparison between the two movements and investigates in detail their role in language policy and linguistic nationalism.
The Planetary Nebula Luminosity Function and its Issues
Authors: Ciardullo Robin
Published: May 2017

The bright-end cutoff of the [O III] λ5007 planetary nebula luminosity function (PNLF) is insensitive to population age and metallicity, making it an excellent extragalactic standard candle. We review our knowledge of the function and discuss the challenges related to modeling it. We show that, while there has been a great deal of progress in understanding the nuances of its shape, there is still no solid theory which explains the luminosity of the PNLF cutoff in old stellar populations. This is an extremely serious problem, as it affects a myriad of astrophysical issues, from the determination of the stellar masses of galaxies to our understanding of alternative channels of stellar evolution.
Plant Development and Seed Biology of Windmillgrass (Chloris truncata) in Southern Australia
Authors: Ngo The D. , Boutsalis Peter , Preston Christopher , Gill Gurjeet
Published: May 2017

Windmillgrass is a major weed in agricultural systems in northern Australia, and it has now become more common in southern Australia. Because little information is available on the biology of this weed species in southern Australia, studies were conducted to investigate plant development and seed biology. Under irrigated field conditions in South Australia, windmillgrass required 748 to 786 growing degree days from emergence to mature seed production. Freshly harvested seed had low dormancy with 16% to 40% germination. Seeds required light exposure for germination and less than 2% germination was observed in complete darkness. Seed could germinate over a wide temperature range (10 to 40 C) with maximum germination at 20 to 25 C. At 25 to 30 C, 50% germination occurred within 27.3 to 45.5 h, and the predicted base temperature for germination of the two populations investigated ranged from 9.2 to 11.2 C. The sodium chloride concentration and osmotic potential required to inhibit germination by 50% were 51 to 73 mM and −0.27 MPa, respectively. Seedling emergence was completely inhibited by burial of seed, which is consistent with its absolute requirement for light exposure to begin germination. Under field conditions, there was no clear effect of burial depth on seed viability in the first 2 yr with average rainfall, and seeds were completely nonviable after 12 mo. However, in the third year, with low spring–summer rainfall, buried seeds (37% viability after 14 mo) persisted longer than those left on the soil surface (6% viability after 14 mo). This study provides important information on plant development and seed biology of windmillgrass that will contribute to the development of a management program for this weed species in southern Australia.
Using Metaphor to Find Meaning in Life
Authors: Landau Mark J.
Published: May 2017

Pursuing meaning in life confronts the individual with abstract ideas about the connections between experiences and identities over time ( continuity), the ends that life serves ( purpose), and its worth ( value). Conceptual metaphor theory is helpful to explain the cognitive strategies people use to understand these ideas. This theory posits that metaphor is a cognitive tool for understanding abstractions in terms of superficially dissimilar, relatively more concrete concepts. Early empirical tests of this claim focused on how activated metaphors influence judgments of other people, events, and social issues. Going further, an emerging area of research examines metaphor's roles in perceptions of life's continuity, purpose, and value. This article provides the first overview of this development. Specific aims are to organize previous findings, identify questions for future research, and discuss theoretical implications for the meaning of meaning.
Finding Meaning in Nostalgia
Authors: Sedikides Constantine , Wildschut Tim
Published: May 2017

Nostalgia—defined as sentimental longing for one's past—is a self-relevant, albeit deeply social, and an ambivalent, albeit more positive than negative, emotion. As nostalgia brings the past into present focus, it has existential implications. Nostalgia helps people find meaning in their lives, and it does so primarily by increasing social connectedness (a sense of belongingness and acceptance), and secondarily by augmenting self-continuity (a sense of connection between one's past and one's present). Also, nostalgia-elicited meaning facilitates the pursuit of one's important goals. Moreover, nostalgia acts as a buffer against existential threats. In particular, it shields against meaning threat, and buffers the impact of mortality salience on meaning, collective identity, accessibility of mortality-related thoughts, and death anxiety. Finally, nostalgia confers psychological benefits to individuals with chronic or momentary meaning deficits. These benefits are higher subjective vitality, lower stress, and regulation of meaning-seeking in response to boredom. Taken together, nostalgia helps people attain a more meaningful life, protects from existential threat, and contributes to psychological equanimity.
Sclerostin activity plays a key role in the negative effect of glucocorticoid signaling on osteoblast function in mice
Authors: Beier Eric E , Sheu Tzong-Jen , Resseguie Emily A , Takahata Masahiko , Awad Hani A , Cory-Slechta Deborah A , Puzas J Edward
Published: May 2017

Stress during prenatal development is correlated with detrimental cognitive and behavioral outcomes in offspring. However, the long-term impact of prenatal stress (PS) and disrupted glucocorticoid signaling on bone mass and strength is not understood. In contrast, the detrimental effect of lead (Pb) on skeletal health is well documented. As stress and Pb act on common biological targets via glucocorticoid signaling pathways and co-occur in the environment, this study first sought to assess the combined effect of stress and Pb on bone quality in association with alterations in glucocorticoid signaling. Bone parameters were evaluated using microCT, histomorphometry, and strength determination in 8-month-old male mouse offspring subjected to PS on gestational days 16 and 17, lifetime Pb exposure (100 p.p.m. Pb in drinking water), or to both. Pb reduced trabecular bone mass and, when combined with PS, Pb unmasked an exaggerated decrement in bone mass and tensile strength. Next, to characterize a mechanism of glucocorticoid effect on bone, prednisolone was implanted subcutaneously (controlled-release pellet, 5 mg·kg−1 per day) in 5-month-old mice that decreased osteoblastic activity and increased sclerostin and leptin levels. Furthermore, the synthetic glucocorticoid dexamethasone alters the anabolic Wnt signaling pathway. The Wnt pathway inhibitor sclerostin has several glucocorticoid response elements, and dexamethasone administration to osteoblastic cells induces sclerostin expression. Dexamethasone treatment of isolated bone marrow cells decreased bone nodule formation, whereas removal of sclerostin protected against this decrement in mineralization. Collectively, these findings suggest that bone loss associated with steroid-induced osteoporosis is a consequence of sclerostin-mediated restriction of Wnt signaling, which may mechanistically facilitate glucocorticoid toxicity in bone.
Cold-inducible RNA-binding protein through TLR4 signaling induces mitochondrial DNA fragmentation and regulates macrophage cell death after trauma
Authors: Li Zhigang , Fan Erica K , Liu Jinghua , Scott Melanie J , Li Yuehua , Li Song , Xie Wen , Billiar Timothy R , Wilson Mark A , Jiang Yong , Wang Ping , Fan Jie
Published: May 2017

Trauma is a major cause of systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Macrophages (Mφ) direct trauma-induced inflammation, and Mφ death critically influences the progression of the inflammatory response. In the current study, we explored an important role of trauma in inducing mitochondrial DNA (mtDNA) damage in Mφ and the subsequent regulation of Mφ death. Using an animal pseudo-fracture trauma model, we demonstrated that tissue damage induced NADPH oxidase activation and increased the release of reactive oxygen species via cold-inducible RNA-binding protein (CIRP)–TLR4–MyD88 signaling. This in turn, activates endonuclease G, which serves as an executor for the fragmentation of mtDNA in Mφ. We further showed that fragmented mtDNA triggered both p62-related autophagy and necroptosis in Mφ. However, autophagy activation also suppressed Mφ necroptosis and pro-inflammatory responses. This study demonstrates a previously unidentified intracellular regulation of Mφ homeostasis in response to trauma.
The novel long intergenic noncoding RNA UCC promotes colorectal cancer progression by sponging miR-143
Authors: Huang Feng-Ting , Chen Wen-Ying , Gu Zhi-Qiang , Zhuang Yan-Yan , Li Chu-Qiang , Wang Ling-Yun , Peng Juan-Fei , Zhu Zhe , Luo Xin , Li Yuan-Hua , Yao He-Rui , Zhang Shi-Neng
Published: May 2017

The human genome contains thousands of long intergenic noncoding RNAs (lincRNAs). However, the functional roles of these transcripts and the mechanisms responsible for their deregulation in colorectal cancer (CRC) remain elusive. A novel lincRNA termed upregulated in CRC (UCC) was found to be highly expressed in human CRC tissues and cell lines. UCC levels correlated with lymph node metastasis, Dukes’ stage, and patient outcomes. In SW480 and SW620 cells, knockdown of UCC inhibited proliferation, invasion, and cell cycle progression and induced apoptosis in vitro. Xenograft tumors grown from UCC-silenced SW620 cells had smaller mean volumes and formed more slowly than xenograft tumors grown from control cells. Inversely, overexpression of UCC in HCT116 promoted cell growth and invasion in vitro. Bioinformatics analysis, dual-luciferase reporter assays, and RNA immunoprecipitation assays showed that miR-143 can interact with UCC, and we found that UCC expression inversely correlates with miR-143 expression in CRC specimens. Moreover, mechanistic investigations showed that UCC may act as an endogenous sponge by competing for miR-143, thereby regulating the targets of this miRNA. Our results suggest that UCC and miR-143 may be promising molecular targets for CRC therapy.
All-trans retinoic acid and arsenic trioxide fail to derepress the monocytic differentiation driver Irf8 in acute promyelocytic leukemia cells
Authors: Liu XiangZhen , Chen Juan , Yu ShanHe , Yan Li , Guo HeZhou , Dai JianMin , Zhang Wu , Zhu Jiang
Published: May 2017

All-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) administration leads to granulocytic maturation and/or apoptosis of acute promyelocytic leukemia (APL) cells mainly by targeting promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα). Yet, ~10–15% of APL patients are not cured by ATRA- and ATO-based therapies, and a potential failure of ATRA and ATO in completely reversing PML/RARα-driven oncogenic alterations has not been comprehensively examined. Here we characterized the in vivo primary responses of dysregulated genes in APL cells treated with ATRA and ATO using a GFP-labeled APL model. Although induced granulocytic differentiation of APL cells was evident after ATRA or ATO administration, the expression of the majority of dysregulated genes in the c-Kit+ APL progenitors was not consistently corrected. Irf8, whose expression increased along with spontaneous differentiation of the APL progenitors in vivo, represented such a PML/RARα-dysregulated gene that was refractory to ATRA/ATO signaling. Interestingly, Irf8 induction, but not its knockdown, decreased APL leukemogenic potential through driving monocytic maturation. Thus, we reveal that certain PML/RARα-dysregulated genes that are refractory to ATRA/ATO signaling are potentially crucial regulators of the immature status and leukemogenic potential of APL cells, which can be exploited for the development of new therapeutic strategies for ATRA/ATO-resistant APL cases.
A balance of Mad and Myc expression dictates larval cell apoptosis and adult stem cell development during Xenopus intestinal metamorphosis
Authors: Okada Morihiro , Miller Thomas C , Wen Luan , Shi Yun-Bo
Published: May 2017

The Myc/Mad/Max network has long been shown to be an important factor in regulating cell proliferation, death and differentiation in diverse cell types. In general, Myc–Max heterodimers activate target gene expression to promote cell proliferation, although excess of c-Myc can also induce apoptosis. In contrast, Mad competes against Myc to form Mad–Max heterodimers that bind to the same target genes to repress their expression and promote differentiation. The role of the Myc/Mad/Max network during vertebrate development, especially, the so-called postembryonic development, a period around birth in mammals, is unclear. Using thyroid hormone (T3)-dependent Xenopus metamorphosis as a model, we show here that Mad1 is induced by T3 in the intestine during metamorphosis when larval epithelial cell death and adult epithelial stem cell development take place. More importantly, we demonstrate that Mad1 is expressed in the larval cells undergoing apoptosis, whereas c-Myc is expressed in the proliferating adult stem cells during intestinal metamorphosis, suggesting that Mad1 may have a role in cell death during development. By using transcription activator-like effector nuclease-mediated gene-editing technology, we have generated Mad1 knockout Xenopus animals. This has revealed that Mad1 is not essential for embryogenesis or metamorphosis. On the other hand, consistent with its spatiotemporal expression profile, Mad1 knockout leads to reduced larval epithelial apoptosis but surprisingly also results in increased adult stem cell proliferation. These findings not only reveal a novel role of Mad1 in regulating developmental cell death but also suggest that a balance of Mad and Myc controls cell fate determination during adult organ development.
Halofuginone dually regulates autophagic flux through nutrient-sensing pathways in colorectal cancer
Authors: Chen Guo-Qing , Gong Rui-Hong , Yang Da-Jian , Zhang Ge , Lu Ai-Ping , Yan Siu-Cheong , Lin Shu-Hai , Bian Zhao-Xiang
Published: May 2017

Autophagy has a key role in metabolism and impacts on tumorigenesis. Our previous study found that halofuginone (HF) exerts anticancer activity in colorectal cancer (CRC) by downregulating Akt/mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway. But whether and how HF regulates autophagy and metabolism to inhibit cancer growth remains an open question. Here, we unveil that HF activates ULK1 by downregulation of its phosphorylation site at Ser757 through Akt/mTORC1 signaling pathway, resulting in induction of autophagic flux under nutrient-rich condition. On the other hand, HF inactivates ULK1 by downregulation of its phosphorylation sites at Ser317 and Ser777 through LKB1/AMPK signaling pathway, resulting in autophagic inhibition under nutrient-poor condition. Furthermore, Atg7-dependent autophagosome formation is also induced under nutrient-rich condition or blocked in nutrient-poor environment, respectively, upon HF treatment. More interestingly, we also found that HF inhibits glycolysis under nutrient-rich condition, whereas inhibits gluconeogenesis under nutrient-poor condition in an Atg7-dependent manner, suggesting that autophagy has a pivotal role of glucose metabolism upon HF treatment. Subsequent studies showed that HF treatment retarded tumor growth in xenograft mice fed with either standard chow diet or caloric restriction through dual regulation of autophagyin vivo. Together, HF has a dual role in autophagic modulation depending on nutritional conditions for anti-CRC.
Control of type III protein secretion using a minimal genetic system
Authors: Song Miryoung , Sukovich David J. , Ciccarelli Luciano , Mayr Julia , Fernandez-Rodriguez Jesus , Mirsky Ethan A. , Tucker Alex C. , Gordon D. Benjamin , Marlovits Thomas C. , Voigt Christopher A.
Published: May 2017

Gram-negative bacteria secrete proteins using a type III secretion system (T3SS), which functions as a needle-like molecular machine. The many proteins involved in T3SS construction are tightly regulated due to its role in pathogenesis and motility. Here, starting with the 35 kb Salmonella pathogenicity island 1 (SPI-1), we eliminated internal regulation and simplified the genetics by removing or recoding genes, scrambling gene order and replacing all non-coding DNA with synthetic genetic parts. This process results in a 16 kb cluster that shares no sequence identity, regulation or organizational principles with SPI-1. Building this simplified system led to the discovery of essential roles for an internal start site (SpaO) and small RNA (InvR). Further, it can be controlled using synthetic regulatory circuits, including under SPI-1 repressing conditions. This work reveals an incredible post-transcriptional robustness in T3SS assembly and aids its control as a tool in biotechnology.
Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine inhibits osteoarthritis progression
Authors: Corciulo Carmen , Lendhey Matin , Wilder Tuere , Schoen Hanna , Cornelissen Alexander Samuel , Chang Gregory , Kennedy Oran D. , Cronstein Bruce N.
Published: May 2017

Osteoarthritis (OA) is characterized by cartilage destruction and chondrocytes have a central role in this process. With age and inflammation chondrocytes have reduced capacity to synthesize and maintain ATP, a molecule important for cartilage homeostasis. Here we show that concentrations of ATP and adenosine, its metabolite, fall after treatment of mouse chondrocytes and rat tibia explants with IL-1β, an inflammatory mediator thought to participate in OA pathogenesis. Mice lacking A2A adenosine receptor (A2AR) or ecto-5′nucleotidase (an enzyme that converts extracellular AMP to adenosine) develop spontaneous OA and chondrocytes lacking A2AR develop an ‘OA phenotype’ with increased expression ofMmp13andCol10a1. Adenosine replacement by intra-articular injection of liposomal suspensions containing adenosine prevents development of OA in rats. These results support the hypothesis that maintaining extracellular adenosine levels is an important homeostatic mechanism, loss of which contributes to the development of OA; targeting adenosine A2A receptors might treat or prevent OA.
Unconventional double-bended saturation of carrier occupation in optically excited graphene due to many-particle interactions
Authors: Winzer Torben , Mittendorff Martin , Winnerl Stephan , Mittenzwey Henry , Jago Roland , Helm Manfred , Malic Ermin , Knorr Andreas
Published: May 2017

Saturation of carrier occupation in optically excited materials is a well-established phenomenon. However, so far, the observed saturation effects have always occurred in the strong-excitation regime and have been explained by Pauli blocking of the optically filled quantum states. On the basis of microscopic theory combined with ultrafast pump-probe experiments, we reveal a new low-intensity saturation regime in graphene that is purely based on many-particle scattering and not Pauli blocking. This results in an unconventional double-bended saturation behaviour: both bendings separately follow the standard saturation model exhibiting two saturation fluences; however, the corresponding fluences differ by three orders of magnitude and have different physical origin. Our results demonstrate that this new and unexpected behaviour can be ascribed to an interplay between time-dependent many-particle scattering and phase-space filling effects.
Identification of mouse cochlear progenitors that develop hair and supporting cells in the organ of Corti
Authors: Xu Jinshu , Ueno Hiroo , Xu Chelsea Y. , Chen Binglai , Weissman Irving L. , Xu Pin-Xian
Published: May 2017

The adult mammalian cochlear sensory epithelium houses two major types of cells, mechanosensory hair cells and underlying supporting cells, and lacks regenerative capacity. Recent evidence indicates that a subset of supporting cells can spontaneously regenerate hair cells after ablation only within the first week postparturition. Here in vivo clonal analysis of mouse inner ear cells during development demonstrates clonal relationship between hair and supporting cells in sensory organs. We report the identification in mouse of a previously unknown population of multipotent stem/progenitor cells that are capable of not only contributing to the hair and supporting cells but also to other cell types, including glia, in cochlea undergoing development, maturation and repair in response to damage. These multipotent progenitors originate from Eya1-expressing otic progenitors. Our findings also provide evidence for detectable regenerative potential in the postnatal cochlea beyond 1 week of age.
Phf8 loss confers resistance to depression-like and anxiety-like behaviors in mice
Authors: Walsh Ryan M. , Shen Erica Y. , Bagot Rosemary C. , Anselmo Anthony , Jiang Yan , Javidfar Behnam , Wojtkiewicz Gregory J. , Cloutier Jennifer , Chen John W. , Sadreyev Ruslan , Nestler Eric J. , Akbarian Schahram , Hochedlinger Konrad
Published: May 2017

PHF8 is a histone demethylase with specificity for repressive modifications. While mutations of PHF8 have been associated with cognitive defects and cleft lip/palate, its role in mammalian development and physiology remains unexplored. Here, we have generated a Phf8 knockout allele in mice to examine the consequences of Phf8 loss for development and behaviour. Phf8 deficient mice neither display obvious developmental defects nor signs of cognitive impairment. However, we report a striking resiliency to stress-induced anxiety- and depression-like behaviour on loss of Phf8. We further observe misregulation of serotonin signalling within the prefrontal cortex of Phf8 deficient mice and identify the serotonin receptors Htr1a and Htr2a as direct targets of PHF8. Our results clarify the functional role of Phf8 in mammalian development and behaviour and establish a direct link between Phf8 expression and serotonin signalling, identifying this histone demethylase as a potential target for the treatment of anxiety and depression.
The digestive and defensive basis of carcass utilization by the burying beetle and its microbiota
Authors: Vogel Heiko , Shukla Shantanu P. , Engl Tobias , Weiss Benjamin , Fischer Rainer , Steiger Sandra , Heckel David G. , Kaltenpoth Martin , Vilcinskas Andreas
Published: May 2017

Insects that use ephemeral resources must rapidly digest nutrients and simultaneously protect them from competitors. Here we use burying beetles (Nicrophorus vespilloides), which feed their offspring on vertebrate carrion, to investigate the digestive and defensive basis of carrion utilization. We characterize gene expression and microbiota composition in the gut, anal secretions, and on carcasses used by the beetles. We find a strict functional compartmentalization of the gut involving differential expression of immune effectors (antimicrobial peptides and lysozymes), as well as digestive and detoxifying enzymes. A distinct microbial community composed of Firmicutes, Proteobacteria and a clade of ascomycetous yeasts (genus Yarrowia) is present in larval and adult guts, and is transmitted to the carcass via anal secretions, where the yeasts express extracellular digestive enzymes and produce antimicrobial compounds. Our results provide evidence of potential metabolic cooperation between the host and its microbiota for digestion, detoxification and defence that extends from the beetle’s gut to its nutritional resource.
Proline metabolism supports metastasis formation and could be inhibited to selectively target metastasizing cancer cells
Authors: Elia Ilaria , Broekaert Dorien , Christen Stefan , Boon Ruben , Radaelli Enrico , Orth Martin F. , Verfaillie Catherine , Grünewald Thomas G. P. , Fendt Sarah-Maria
Published: May 2017

Metastases are the leading cause of mortality in patients with cancer. Metastasis formation requires cancer cells to adapt their cellular phenotype. However, how metabolism supports this adaptation of cancer cells is poorly defined. We use 2D versus 3D cultivation to induce a shift in the cellular phenotype of breast cancer cells. We discover that proline catabolism via proline dehydrogenase (Prodh) supports growth of breast cancer cells in 3D culture. Subsequently, we link proline catabolism to in vivo metastasis formation. In particular, we find that PRODH expression and proline catabolism is increased in metastases compared to primary breast cancers of patients and mice. Moreover, inhibiting Prodh is sufficient to impair formation of lung metastases in the orthotopic 4T1 and EMT6.5 mouse models, without adverse effects on healthy tissue and organ function. In conclusion, we discover that Prodh is a potential drug target for inhibiting metastasis formation.
Regulation of cardiomyocyte behavior in zebrafish trabeculation by Neuregulin 2a signaling
Authors: Rasouli S. Javad , Stainier Didier Y. R.
Published: May 2017

Trabeculation is crucial for cardiac muscle growth in vertebrates. This process requires the Erbb2/4 ligand Neuregulin (Nrg), secreted by the endocardium, as well as blood flow/cardiac contractility. Here, we address two fundamental, yet unresolved, questions about cardiac trabeculation: why does it initially occur in the ventricle and not the atrium, and how is it modulated by blood flow/contractility. Using loss-of-function approaches, we first show that zebrafish Nrg2a is required for trabeculation, and using a protein-trap line, find that it is expressed in both cardiac chambers albeit with different spatiotemporal patterns. Through gain-of-function experiments, we show that atrial cardiomyocytes can also respond to Nrg2a signalling, suggesting that the cardiac jelly, which remains prominent in the atrium, represents a barrier to Erbb2/4 activation. Furthermore, we find that blood flow/contractility is required for Nrg2a expression, and that while non-contractile hearts fail to trabeculate, non-contractile cardiomyocytes are also competent to respond to Nrg2a/Erbb2 signalling.
Effects of the non-parabolic kinetic energy on non-equilibrium polariton condensates
Authors: Pinsker F. , Ruan X. , Alexander T. J.
Published: May 2017

In the study of non-equilibrium polariton condensates it is usually assumed that the dispersion relation of polaritons is parabolic in nature. We show that considering the true non-parabolic kinetic energy of polaritons leads to significant changes in the behaviour of the condensate due to the curvature of the dispersion relation and the possibility of transfer of energy to high wavenumber components in the condensate spatial profile. We present explicit solutions for plane waves and linear excitations, and identify the differences in the theoretical predictions between the parabolic and non-parabolic mean-field models, showing the possibility of symmetry breaking in the latter. We then consider the evolution of wavepackets and show that self-localisation effects may be observed due to the curvature of the dispersion relation. Finally, we revisit the dynamics of dark soliton trains and show that additional localized density excitations may emerge in the dynamics due to the excitation of high frequency components, mimicking the appearance of near-bright solitary waves over short timescales.
Construction of genotyping-by-sequencing based high-density genetic maps and QTL mapping for fusarium wilt resistance in pigeonpea
Authors: Saxena Rachit K. , Singh Vikas K. , Kale Sandip M. , Tathineni Revathi , Parupalli Swathi , Kumar Vinay , Garg Vanika , Das Roma R. , Sharma Mamta , Yamini K. N. , Muniswamy S. , Ghanta Anuradha , Rathore Abhishek , Kumar C. V. Sameer , Saxena K. B. , Kishor P. B. Kavi , Varshney Rajeev K.
Published: May 2017

Fusarium wilt (FW) is one of the most important biotic stresses causing yield losses in pigeonpea. Genetic improvement of pigeonpea through genomics-assisted breeding (GAB) is an economically feasible option for the development of high yielding FW resistant genotypes. In this context, two recombinant inbred lines (RILs) (ICPB 2049 × ICPL 99050 designated as PRIL_A and ICPL 20096 × ICPL 332 designated as PRIL_B) and one F2 (ICPL 85063 × ICPL 87119) populations were used for the development of high density genetic maps. Genotyping-by-sequencing (GBS) approach was used to identify and genotype SNPs in three mapping populations. As a result, three high density genetic maps with 964, 1101 and 557 SNPs with an average marker distance of 1.16, 0.84 and 2.60 cM were developed in PRIL_A, PRIL_B and F2, respectively. Based on the multi-location and multi-year phenotypic data of FW resistance a total of 14 quantitative trait loci (QTLs) including six major QTLs explaining >10% phenotypic variance explained (PVE) were identified. Comparative analysis across the populations has revealed three important QTLs (qFW11.1, qFW11.2 and qFW11.3) with upto 56.45% PVE for FW resistance. This is the first report of QTL mapping for FW resistance in pigeonpea and identified genomic region could be utilized in GAB.
Non-alcoholic fatty liver disease, vascular inflammation and insulin resistance are exacerbated by TRAIL deletion in mice
Authors: Cartland Siân P. , Harith Hanis H. , Genner Scott W. , Dang Lei , Cogger Victoria C. , Vellozzi Melissa , Di Bartolo Belinda A. , Thomas Shane R. , Adams Leon A. , Kavurma Mary M.
Published: May 2017

Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is protective of CVD. We aimed to determine whether TRAIL protects against insulin resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail−/− mice had increased plasma cholesterol, insulin and glucose compared to wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt, GLUT4 expression and glucose uptake in skeletal muscle. Hepatic triglyceride content, inflammation and fibrosis were increased with TRAIL-deletion, with elevated expression of genes regulating lipogenesis and gluconeogenesis. Moreover, Trail−/− mice exhibited reduced aortic vasorelaxation, impaired insulin signaling, and >20-fold increased mRNA expression for IL-1β, IL-6, and TNF-α. In vitro, palmitate treatment of hepatocytes increased lipid accumulation, inflammation and fibrosis, with TRAIL mRNA significantly reduced. TRAIL administration inhibited palmitate-induced hepatocyte lipid uptake. Finally, patients with NASH had significantly reduced plasma TRAIL compared to control, simple steatosis or obese individuals. These findings suggest that TRAIL protects against insulin resistance, NAFLD and vascular inflammation. Increasing TRAIL levels may be an attractive therapeutic strategy, to reduce features of diabetes, as well as liver and vascular injury, so commonly observed in individuals with NAFLD.
Integrin beta8 (ITGB8) activates VAV-RAC1 signaling via FAK in the acquisition of endometrial epithelial cell receptivity for blastocyst implantation
Authors: Kumar Vijay , Soni Upendra Kumar , Maurya Vineet Kumar , Singh Kiran , Jha Rajesh Kumar
Published: May 2017

Integrin beta8 (ITGB8) is involved in the endometrial receptivity. The blastocyst first interacts with the luminal endometrial epithelial cells during its implantation; therefore, we have investigated the signaling of ITGB8 via FAK and VAV-RAC1 in the endometrial epithelial cells. Integrin beta8 was found elevated in epithelial cells at late-pre-receptive (day4, 1600 h) and receptive (day5, 0500 h) stages of endometrial receptivity period in the mouse. Integrins downstream molecule FAK has demonstrated an increased expression and phosphorylation (Y397) in the endometrium as well as in the isolated endometrial epithelial cells during receptive and post-receptive stages. Integrin beta8 can functionally interact with FAK, VAV and RAC1 as the levels of phosphorylated-FAK, and VAV along with the RAC-GTP form was reduced after ITGB8 knockdown in the endometrial epithelial cells and uterus. Further, VAV and RAC1 were seen poorly active in the absence of FAK activity, suggesting a crosstalk of ITGB8 and FAK for VAV and RAC1 activation in the endometrial epithelial cells. Silencing of ITGB8 expression and inhibition of FAK activity in the Ishikawa cells rendered poor attachment of JAr spheroids. In conclusion, ITGB8 activates VAV-RAC1 signaling axis via FAK to facilitate the endometrial epithelial cell receptivity for the attachment of blastocyst.
Exploring optoelectronic properties and mechanisms of layered ferroelectric K4Nb6O17 nanocrystalline films and nanolaminas
Authors: Deng Qinglin , Li Mengjiao , Wang Junyong , Zhang Peng , Jiang Kai , Zhang Jinzhong , Hu Zhigao , Chu Junhao
Published: May 2017

Two-dimensional layered K4Nb6O17 (KN) was easily formed as a secondary phase caused by the volatilization of alkali metal ions, when preparing ferroelectric K
x
Na1−x
NbO3 based ceramics and films. In this work, it was believed that KN film is with weak ferroelectricity and has a little effect on the ferroelectric properties of K
x
Na1−x
NbO3 based films. Moreover, temperature dependent (77–500 K) dielectric functions of KN film have been firstly extracted by fitting ellipsometric spectra with the Adachi dielectric function model and a four-phase layered model. The high-frequency dielectric constant linearly increases and optical band gap slightly decreases with increasing the temperature. We also research its photoelectrochemical properties and its application in high-efficient light-induced H2 evolution. In addition, X-ray photoelectron spectroscopy, Raman scattering, temperature dependent transmittance and infrared reflectance spectra, and first-principles calculation were conjointly performed to further reveal the intrinsic optoelectronic features and relevant mechanisms of KN.
Physicochemical properties of dietary phytochemicals can predict their passive absorption in the human small intestine
Authors: Selby-Pham Sophie N. B. , Miller Rosalind B. , Howell Kate , Dunshea Frank , Bennett Louise E.
Published: May 2017

A diet high in phytochemical-rich plant foods is associated with reducing the risk of chronic diseases such as cardiovascular and neurodegenerative diseases, obesity, diabetes and cancer. Oxidative stress and inflammation (OSI) is the common component underlying these chronic diseases. Whilst the positive health effects of phytochemicals and their metabolites have been demonstrated to regulate OSI, the timing and absorption for best effect is not well understood. We developed a model to predict the time to achieve maximal plasma concentration (Tmax) of phytochemicals in fruits and vegetables. We used a training dataset containing 67 dietary phytochemicals from 31 clinical studies to develop the model and validated the model using three independent datasets comprising a total of 108 dietary phytochemicals and 98 pharmaceutical compounds. The developed model based on dietary intake forms and the physicochemical properties lipophilicity and molecular mass accurately predicts Tmaxof dietary phytochemicals and pharmaceutical compounds over a broad range of chemical classes. This is the first direct model to predict Tmaxof dietary phytochemicals in the human body. The model informs the clinical dosing frequency for optimising uptake and sustained presence of dietary phytochemicals in circulation, to maximise their bio-efficacy for positively affect human health and managing OSI in chronic diseases.
Multivariate EEG analyses support high-resolution tracking of feature-based attentional selection
Authors: Fahrenfort Johannes Jacobus , Grubert Anna , Olivers Christian N. L. , Eimer Martin
Published: May 2017

The primary electrophysiological marker of feature-based selection is the N2pc, a lateralized posterior negativity emerging around 180–200 ms. As it relies on hemispheric differences, its ability to discriminate the locus of focal attention is severely limited. Here we demonstrate that multivariate analyses of raw EEG data provide a much more fine-grained spatial profile of feature-based target selection. When training a pattern classifier to determine target position from EEG, we were able to decode target positions on the vertical midline, which cannot be achieved using standard N2pc methodology. Next, we used a forward encoding model to construct a channel tuning function that describes the continuous relationship between target position and multivariate EEG in an eight-position display. This model can spatially discriminate individual target positions in these displays and is fully invertible, enabling us to construct hypothetical topographic activation maps for target positions that were never used. When tested against the real pattern of neural activity obtained from a different group of subjects, the constructed maps from the forward model turned out statistically indistinguishable, thus providing independent validation of our model. Our findings demonstrate the power of multivariate EEG analysis to track feature-based target selection with high spatial and temporal precision.
PICK1 Genetic Variation and Cognitive Function in Patients with Schizophrenia
Authors: Chen Yi-Ting , Lin Chieh-Hsin , Huang Chiung-Hsien , Liang Wen-Miin , Lane Hsien-Yuan
Published: May 2017

The gene of protein interacting with C kinase 1 alpha (PICK1) has been implicated in schizophrenia, nevertheless, conflicting results existed. However, its role in cognitive function remains unclear. Besides, cognitive deficits impair the long-term outcome. We explored whether the polymorphisms of PICK1 (rs2076369, rs3952) affected cognitive functions in schizophrenic patients. We analyzed 302 patients and tested the differences of cognitive functions, clinical symptoms between genetic groups. We also used general linear model to analyze the effect of PICK1 genetic polymorphisms on cognitive functions. After adjustment for gender, age, education, the patients with rs2076369 G/T genotype showed better performance than T/T homozygotes in the summary score, global composite score, neurocognitive composite score, category fluency subtest, WAIS-III-Digit Symbol Coding subtest, working memory, WMS-III-Spatial Span (backward) subtest, MSCEIT-managing emotions branch (p = 0.038, 0.025, 0.046, 0.036, 0.025, 0.027, 0.035, 0.028, respectively). G/G homozygotes performed better than T/T in category fluency subtest (p = 0.049). A/A homozygotes of rs3952 performed better than G/G in trail making A subtest (p = 0.048). To our knowledge, this is the first study to indicate that PICK1 polymorphisms may associate with cognitive functions in schizophrenic patients. Further replication studies in healthy controls or other ethnic groups are warranted.
Overcoming thermal noise in non-volatile spin wave logic
Authors: Dutta Sourav , Nikonov Dmitri E. , Manipatruni Sasikanth , Young Ian A. , Naeemi Azad
Published: May 2017

Spin waves are propagating disturbances in magnetically ordered materials, analogous to lattice waves in solid systems and are often described from a quasiparticle point of view as magnons. The attractive advantages of Joule-heat-free transmission of information, utilization of the phase of the wave as an additional degree of freedom and lower footprint area compared to conventional charge-based devices have made spin waves or magnon spintronics a promising candidate for beyond-CMOS wave-based computation. However, any practical realization of an all-magnon based computing system must undergo the essential steps of a careful selection of materials and demonstrate robustness with respect to thermal noise or variability. Here, we aim at identifying suitable materials and theoretically demonstrate the possibility of achieving error-free clocked non-volatile spin wave logic device, even in the presence of thermal noise and clock jitter or clock skew.