bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prior indigenous technological species
Authors: Wright Jason T. 
Published: June 2017

AbstractOne of the primary open questions of astrobiology is whether there is extant or extinct life elsewhere the solar system. Implicit in much of this work is that we are looking for microbial or, at best, unintelligent life, even though technological artefacts might be much easier to find. Search for Extraterrestrial Intelligence (SETI) work on searches for alien artefacts in the solar system typically presumes that such artefacts would be of extrasolar origin, even though life is known to have existed in the solar system, on Earth, for eons. But if a prior technological, perhaps spacefaring, species ever arose in the solar system, it might have produced artefacts or other technosignatures that have survived to present day, meaning solar system artefact SETI provides a potential path to resolving astrobiology's question. Here, I discuss the origins and possible locations for technosignatures of such a prior indigenous technological species, which might have arisen on ancient Earth or another body, such as a pre-greenhouse Venus or a wet Mars. In the case of Venus, the arrival of its global greenhouse and potential resurfacing might have erased all evidence of its existence on the Venusian surface. In the case of Earth, erosion and, ultimately, plate tectonics may have erased most such evidence if the species lived Gyr ago. Remaining indigenous technosignatures might be expected to be extremely old, limiting the places they might still be found to beneath the surfaces of Mars and the Moon, or in the outer solar system.
Developing a “toolkit” to measure implementation of concurrent palliative care in rural community cancer centers
Authors: Zubkoff Lisa , Dionne-Odom J. Nicholas , Pisu Maria , Babu Dilip , Akyar Imatullah , Smith Tasha , Mancarella Gisella A. , Gansauer Lucy , Sullivan Margaret Murray , Swetz Keith M. , Azuero Andres , Bakitas Marie A. 
Published: June 2017

ABSTRACTObjective:Despite national guidelines recommending early concurrent palliative care for individuals newly diagnosed with metastatic cancer, few community cancer centers, especially those in underserved rural areas do so. We are implementing an early concurrent palliative care model, ENABLE (Educate, Nurture, Advise, Before Life Ends) in four, rural-serving community cancer centers. Our objective was to develop a “toolkit” to assist community cancer centers that wish to integrate early palliative care for patients with newly diagnosed advanced cancer and their family caregivers.Method:Guided by the RE-AIM (Reach, Effectiveness–Adoption, Implementation, Maintenance) framework, we undertook an instrument-development process based on the literature, expert and site stakeholder review and feedback, and pilot testing during site visits.Results:We developed four instruments to measure ENABLE implementation: (1) the ENABLE RE-AIM Self-Assessment Tool to assess reach, adoption, implementation, and maintenance; (2) the ENABLE General Organizational Index to assess institutional implementation; (3) an Implementation Costs Tool; and (4) an Oncology Clinicians' Perceptions of Early Concurrent Oncology Palliative Care survey.Significance of results:We developed four measures to determine early palliative care implementation. These measures have been pilot-tested, and will be integrated into a comprehensive “toolkit” to assist community cancer centers to measure implementation outcomes. We describe the lessons learned and recommend strategies for promoting long-term program sustainability.
Life-cycle greenhouse gas assessment of Community Supported Agriculture in California's Central Valley
Authors: Christensen Libby O. , Galt Ryan E. , Kendall Alissa 
Published: June 2017

AbstractMany consumers are trying to reduce their food's environmental impact by purchasing more locally sourced food. One choice for local food is Community Supported Agriculture (CSA), in which farmers provide a share of produce on a regular basis to pre-paying farm members. The number of CSAs in the USA has grown from two in the mid-1980s to perhaps as many as 12,617 according to the latest US census of agriculture (2014). We use a case study approach to investigate the greenhouse gas (GHG) emissions associated with five CSA operations in the Sacramento Valley of California. By understanding the GHG emissions of CSAs and the practices that might be improved, we hope to support innovative strategies to reduce GHG emissions in these agricultural production systems. Input, production and distribution data were collected from each farm and reported in CO2e emissions for 1 kg CSA produce at the pickup location. Results show large variation in total emissions, ranging from 1.72 to 6.69 kg CO2e kg−1 of produce with an average of 3.94 kg CO2e kg−1 produce. The largest source of emissions was electricity, contributing over 70% of total CO2e emissions on average. Based on our findings, despite the seemingly similarities between these operations in terms of production site, acreage, customers and production practices, there is still a large amount of variability with regard to total GHG. Thus we argue coming up with a standardized production function for diversified production and deriving GHGs or calculating average total emissions overlooks the heterogeneity of the system. Food systems can never be reduced to a simple binary of local is better and conventional is worse, or its inverse local is worse and conventional is better, because of the complexities of the production and distribution systems and their relationship to GHG emissions. Yet, we can say that localized production systems that are low in electricity use (or use renewable energy sources) and use efficiently-produced compost use have lower GHG emissions than those that do not.
In vitro expansion impaired the stemness of early passage mesenchymal stem cells for treatment of cartilage defects
Authors: Jiang Tongmeng , Xu Guojie , Wang Qiuyan , Yang Lihui , Zheng Li , Zhao Jinmin , Zhang Xingdong 
Published: June 2017

AbstractIn vitrocultured autologous mesenchymal stem cells (MSCs) within passage 5 have been approved for clinical application in stem cell-based treatment of cartilage defects. However, their chondrogenic potential has not yet been questioned or verified. In this study, the chondrogenic potential of bone marrow MSCs at passage 3 (P3 BMSCs) was investigated both in cartilage repair andin vitro,with freshly isolated bone marrow mononuclear cells (BMMNCs) as controls. The results showed that P3 BMSCs were inferior to BMMNCs not only in their chondrogenic differentiation ability but also as candidates for long-term repair of cartilage defects. Compared with BMMNCs, P3 BMSCs presented a decay in telomerase activity and a change in chromosomal morphology with potential anomalous karyotypes, indicating senescence. In addition, interindividual variability in P3 BMSCs is much higher than in BMMNCs, demonstrating genomic instability. Interestingly, remarkable downregulation in cell cycle, DNA replication and mismatch repair (MMR) pathways as well as in multiple genes associated with telomerase activity and chromosomal stability were found in P3 BMSCs. This result indicates that telomerase and chromosome anomalies might originate from expansion, leading to impaired stemness and pluripotency of stem cells.In vitroculture and expansion are not recommended for cell-based therapy, and fresh BMMNCs are the first choice.
The novel hypoxia-inducible factor-1α inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth
Authors: Ban Hyun Seung , Kim Bo-Kyung , Lee Hongsub , Kim Hwan Mook , Harmalkar Dipesh , Nam Miso , Park Song-Kyu , Lee Kiho , Park Joon-Tae , Kim Inhyub , Lee Kyeong , Hwang Geum-Sook , Won Misun 
Published: June 2017

AbstractHIF-1 is associated with poor prognoses and therapeutic resistance in cancer patients. We previously developed a novel hypoxia-inducible factor (HIF)-1 inhibitor, IDF-11774, a clinical candidate for cancer therapy. We also reported that IDF-1174 inhibited HSP70 chaperone activity and suppressed accumulation of HIF-1α. In this study, IDF-11774 inhibited the accumulation of HIF-1α in vitro and in vivo in colorectal carcinoma HCT116 cells under hypoxic conditions. Moreover, IDF-11774 treatment suppressed angiogenesis of cancer cells by reducing the expression of HIF-1 target genes, reduced glucose uptake, thereby sensitizing cells to growth under low glucose conditions, and decreased the extracellular acidification rate (ECAR) and oxygen consumption rate of cancer cells. Metabolic profiling of IDF-11774-treated cells revealed low levels of NAD+, NADP+, and lactate, as well as of intermediates in glycolysis and the tricarboxylic acid cycle. In addition, we observed elevated AMP and diminished ATP levels, resulting in a high AMP/ATP ratio. The level of AMP-activated protein kinase phosphorylation also increased, leading to inhibition of mTOR signaling in treated cells. In vivo xenograft assays demonstrated that IDF-11774 exhibited substantial anticancer efficacy in mouse models containing KRAS, PTEN, or VHL mutations, which often occur in malignant cancers. Collectively, our data indicate that IDF-11774 suppressed hypoxia-induced HIF-1α accumulation and repressed tumor growth by targeting energy production-related cancer metabolism.
Loss of epidermal AP1 transcription factor function reduces filaggrin level, alters chemokine expression and produces an ichthyosis-related phenotype
Authors: Young Christina A , Rorke Ellen A , Adhikary Gautam , Xu Wen , Eckert Richard L 
Published: June 2017

AbstractAP1 transcription factors are important controllers of epidermal differentiation. Multiple family members are expressed in the epidermis in a differentiation-dependent manner, where they function to regulate gene expression. To study the role of AP1 factor signaling, TAM67 (dominant-negative c-jun) was inducibly expressed in the suprabasal epidermis. The TAM67-positive epidermis displays keratinocyte hyperproliferation, hyperkeratosis and parakeratosis, delayed differentiation, extensive subdermal vasodilation, nuclear loricrin localization, tail and digit pseudoainhum and reduced filaggrin level. These changes are associated with increased levels of IFNγ, CCL3, CCL5, CXCL9, CXCL10, and CXCL11 (Th1-associated chemokines), and CCL1, CCL2, CCL5 and CCL11 (Th2-associated chemokines) in the epidermis and serum. S100A8 and S100A9 protein levels are also markedly elevated. These changes in epidermal chemokine level are associated with increased levels of the corresponding chemokine mRNA. The largest increases were observed for CXCL9, CXCL10, CXCL11, and S100A8 and S100A9. To assess the role of CXCL9, CXCL10, CXCL11, which bind to CXCR3, on phenotype development, we expressed TAM67 in CXCR3 knockout mice. Using a similar strategy, we examine the role of S100A8 and S100A9. Surprisingly, loss of CXCR3 or S100A8/A9 did not attenuate phenotype development. These studies suggest that interfering with epidermal AP1 factor signaling initiates a loss of barrier function leading to enhanced epidermal chemokine production, but that CXCR3 and S100A8/A9 do not mediate the phenotypic response.
The putative tumor suppressor microRNA-30a-5p modulates clear cell renal cell carcinoma aggressiveness through repression of ZEB2
Authors: Chen Zhenhua , Zhang Jiaxing , Zhang Zhiling , Feng Zihao , Wei Jinhuan , Lu Jun , Fang Yong , Liang Yanping , Cen Junjie , Pan Yihui , Huang Yong , Zhou Fangjian , Chen Wei , Luo Junhang 
Published: June 2017

AbstractClear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, can easily invade local tissues and metastasize, and is resistant to currently available treatments. Recent studies profiling microRNA expression in ccRCC have suggested miR-30a-5p may be deregulated in these cancer cells. To determine its role and mechanism of action in ccRCC, miR-30-5p expression levels were quantified and functions were analyzed usingin vitroandin vivoexperiments and bioinformatics. A decrease in miR-30a-5p expression was frequently noted in ccRCC cells and tissues. Importantly, low miR-30a-5p levels were significantly associated with a poor ccRCC patient prognosis. Stable overexpression of miR-30a-5p in 769-P cells was sufficient to prevent cellular proliferation and invasionin vitroandin vivo. Upon further examination, it was found that miR-30a-5p directly targeted the 3′-UTR of ZEB2 and suppressed ccRCC cell epithelial–mesenchymal transition. In addition, miR-30a-5p may be downregulated by the long non-coding RNA DLEU2. Taken together, these data reveal an important role for miR-30a-5p in the regulation of ccRCC proliferation and invasion, and indicate the potential for miR-30a-5p in applications furthering ccRCC prognostics and therapeutics.
Knockdown of miR-128a induces Lin28a expression and reverts myeloid differentiation blockage in acute myeloid leukemia
Authors: De Luca Luciana , Trino Stefania , Laurenzana Ilaria , Tagliaferri Daniela , Falco Geppino , Grieco Vitina , Bianchino Gabriella , Nozza Filomena , Campia Valentina , D'Alessio Francesca , La Rocca Francesco , Caivano Antonella , Villani Oreste , Cilloni Daniela , Musto Pellegrino , Del Vecchio Luigi 
Published: June 2017

AbstractLin28A is a highly conserved RNA-binding protein that concurs to control the balance between stemness and differentiation in several tissue lineages. Here, we report the role of miR-128a/Lin28A axis in blocking cell differentiation in acute myeloid leukemia (AML), a genetically heterogeneous disease characterized by abnormally controlled proliferation of myeloid progenitor cells accompanied by partial or total inability to undergo terminal differentiation. First, we found Lin28A underexpressed in blast cells from AML patients and AML cell lines as compared with CD34+ normal precursors. In vitro transfection of Lin28A in NPM1-mutated OCI-AML3 cell line significantly triggered cell-cycle arrest and myeloid differentiation, with increased expression of macrophage associate genes (EGR2, ZFP36 and ANXA1). Furthermore, miR-128a, a negative regulator of Lin28A, was found overexpressed in AML cells compared with normal precursors, especially in acute promyelocytic leukemia (APL) and in ‘AML with maturation’ (according to 2016 WHO classification of myeloid neoplasms and acute leukemia). Its forced overexpression by lentiviral infection in OCI-AML3 downregulated Lin28A with ensuing repression of macrophage-oriented differentiation. Finally, knockdown of miR-128a in OCI-AML3 and in APL/AML leukemic cells (by transfection and lentiviral infection, respectively) induced myeloid cell differentiation and increased expression of Lin28A, EGR2, ZFP36 and ANXA1, reverting myeloid differentiation blockage. In conclusion, our findings revealed a new mechanism for AML differentiation blockage, suggesting new strategies for AML therapy based upon miR-128a inhibition.
Interferon-γ derived from cytotoxic lymphocytes directly enhances their motility and cytotoxicity
Authors: Bhat Purnima , Leggatt Graham , Waterhouse Nigel , Frazer Ian H 
Published: June 2017

AbstractInterferon gamma (IFNγ) is a key moderator of cell-mediated immunity with diverse, mainly pro-inflammatory actions on immunocytes and target tissue. Recent studies have shown it may enhance anti-tumor and antiviral effects of CD8 T cells. Here we investigate the mechanisms by which IFNγ mediates CD8 T-cell cytotoxic function. We show that in vivo, antigen-specific CD8 T cells that produce INFγ are necessary to effect rejection of skin grafts expressing OVA as a transgene in keratinocytes. The ability of CD8 T cells to produce IFNγ enhanced their ability to migrate to the site of antigen-presenting skin cells. By in vivo imaging, we show that CTL motility, particularly speed, during graft rejection was enhanced by locally available IFNγ. We then used a reductionist two-cell model of CTL effectors and keratinocyte targets to investigate the effects of locally available (paracrine) and CTL-producing (autocrine) IFNγ on the motility behavior and killing ability of the CTL. Using live-cell imaging by prolonged time-lapse microscopy of primary effector CD8 T cells and antigen-expressing primary keratinocyte targets, we show that CD8 T-cell cytotoxic function and motility is enhanced by locally available IFNγ. Conversely, deprivation of either autocrine or paracrine IFNγ, or blockade of IFNγ signaling to CTL markedly reduced their cytotoxic function, their kinematics, and effector cell survival. We conclude that in vitro and in vivo, autocrine production of IFNγ by CTL enhances their motility and promotes killing of primary target keratinocytes. The absolute need for local IFNγ to enable cytotoxic CD8 T-cell function is of significance for immunotherapy for chronic viral infection and for cancer.
Ants regulate colony spatial organization using multiple chemical road-signs
Authors: Heyman Yael , Shental Noam , Brandis Alexander , Hefetz Abraham , Feinerman Ofer 
Published: June 2017

AbstractCommunication provides the basis for social life. In ant colonies, the prevalence of local, often chemically mediated, interactions introduces strong links between communication networks and the spatial distribution of ants. It is, however, unknown how ants identify and maintain nest chambers with distinct functions. Here, we combine individual tracking, chemical analysis and machine learning to decipher the chemical signatures present on multiple nest surfaces. We present evidence for several distinct chemical ‘road-signs’ that guide the ants’ movements within the dark nest. These chemical signatures can be used to classify nest chambers with different functional roles. Using behavioural manipulations, we demonstrate that at least three of these chemical signatures are functionally meaningful and allow ants from different task groups to identify their specific nest destinations, thus facilitating colony coordination and stabilization. The use of multiple chemicals that assist spatiotemporal guidance, segregation and pattern formation is abundant in multi-cellular organisms. Here, we provide a rare example for the use of these principles in the ant colony.
The critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis
Authors: Qiu Cong , Wang Yuewen , Zhao Haige , Qin Lingfeng , Shi Yanna , Zhu Xiaolong , Song Lin , Zhou Xiaofei , Chen Jian , Zhou Hong , Zhang Haifeng , Tellides George , Min Wang , Yu Luyang 
Published: June 2017

AbstractData from clinical research and our previous study have suggested the potential involvement of SENP1, the major protease of post-translational SUMOylation, in cardiovascular disorders. Here, we investigate the role of SENP1-mediated SUMOylation in graft arteriosclerosis (GA), the major cause of allograft failure. We observe an endothelial-specific induction of SENP1 and GATA2 in clinical graft rejection specimens that show endothelial activation-mediated vascular remodelling. In mouse aorta transplantation GA models, endothelial-specific SENP1 knockout grafts demonstrate limited neointima formation with attenuated leukocyte recruitment, resulting from diminished induction of adhesion molecules in the graft endothelium due to increased GATA2 SUMOylation. Mechanistically, inflammation-induced SENP1 promotes the deSUMOylation of GATA2 and IκBα in endothelial cells, resulting in increased GATA2 stability, promoter-binding capability and NF-κB activity, which leads to augmented endothelial activation and inflammation. Therefore, upon inflammation, endothelial SENP1-mediated SUMOylation drives GA by regulating the synergistic effect of GATA2 and NF-κB and consequent endothelial dysfunction.
Fetal and postnatal metal dysregulation in autism
Authors: Arora Manish , Reichenberg Abraham , Willfors Charlotte , Austin Christine , Gennings Chris , Berggren Steve , Lichtenstein Paul , Anckarsäter Henrik , Tammimies Kristiina , Bölte Sven 
Published: June 2017

AbstractGenetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings.
Multicentennial record of Labrador Sea primary productivity and sea-ice variability archived in coralline algal barium
Authors: Chan P. , Halfar J. , Adey W. , Hetzinger S. , Zack T. , Moore G.W.K. , Wortmann U. G. , Williams B. , Hou A. 
Published: June 2017

AbstractAccelerated warming and melting of Arctic sea-ice has been associated with significant increases in phytoplankton productivity in recent years. Here, utilizing a multiproxy approach, we reconstruct an annually resolved record of Labrador Sea productivity related to sea-ice variability in Labrador, Canada that extends well into the Little Ice Age (LIA; 1646 AD). Barium-to-calcium ratios (Ba/Ca) and carbon isotopes (δ13C) measured in long-lived coralline algae demonstrate significant correlations to both observational and proxy records of sea-ice variability, and show persistent patterns of co-variability broadly consistent with the timing and phasing of the Atlantic Multidecadal Oscillation (AMO). Results indicate reduced productivity in the Subarctic Northwest Atlantic associated with AMO cool phases during the LIA, followed by a step-wise increase from 1910 to present levels—unprecedented in the last 363 years. Increasing phytoplankton productivity is expected to fundamentally alter marine ecosystems as warming and freshening is projected to intensify over the coming century.
Large spin accumulation and crystallographic dependence of spin transport in single crystal gallium nitride nanowires
Authors: Park Tae-Eon , Park Youn Ho , Lee Jong-Min , Kim Sung Wook , Park Hee Gyum , Min Byoung-Chul , Kim Hyung-jun , Koo Hyun Cheol , Choi Heon-Jin , Han Suk Hee , Johnson Mark , Chang Joonyeon 
Published: June 2017

AbstractSemiconductor spintronics is an alternative to conventional electronics that offers devices with high performance, low power and multiple functionality. Although a large number of devices with mesoscopic dimensions have been successfully demonstrated at low temperatures for decades, room-temperature operation still needs to go further. Here we study spin injection in single-crystal gallium nitride nanowires and report robust spin accumulation at room temperature with enhanced spin injection polarization of 9%. A large Overhauser coupling between the electron spin accumulation and the lattice nuclei is observed. Finally, our single-crystal gallium nitride samples have a trigonal cross-section defined by the (001), ("Equation missing") and ("Equation missing") planes. Using the Hanle effect, we show that the spin accumulation is significantly different for injection across the (001) and ("Equation missing") (or ("Equation missing")) planes. This provides a technique for increasing room temperature spin injection in mesoscopic systems.