bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure, activity, and stability of metagenome‐derived glycoside hydrolase family 9 endoglucanase with an N‐terminal Ig‐like domain
Authors: Okano Hiroyuki , Kanaya Eiko , Ozaki Masashi , Angkawidjaja Clement , Kanaya Shigenori 
Published: December 2014

AbstractA metagenome‐derived glycoside hydrolase family 9 enzyme with an N‐terminal immunoglobulin‐like (Ig‐like) domain, leaf‐branch compost (LC)‐CelG, was characterized and its crystal structure was determined. LC‐CelG did not hydrolyze p‐nitrophenyl cellobioside but hydrolyzed CM‐cellulose, indicating that it is endoglucanase. LC‐CelG exhibited the highest activity at 70°C and >80% of the maximal activity at a broad pH range of 5–9. Its denaturation temperature was 81.4°C, indicating that LC‐CelG is a thermostable enzyme. The structure of LC‐CelG resembles those of CelD from Clostridium thermocellum (CtCelD), Cel9A from Alicyclobacillus acidocaldarius (AaCel9A), and cellobiohydrolase CbhA from C. thermocellum (CtCbhA), which show relatively low (29–31%) amino acid sequence identities to LC‐CelG. Three acidic active site residues are conserved as Asp194, Asp197, and Glu558 in LC‐CelG. Ten of the thirteen residues that form the substrate binding pocket of AaCel9A are conserved in LC‐CelG. Removal of the Ig‐like domain reduced the activity and stability of LC‐CelG by 100‐fold and 6.3°C, respectively. Removal of the Gln40‐ and Asp99‐mediated interactions between the Ig‐like and catalytic domains destabilized LC‐CelG by 5.0°C without significantly affecting its activity. These results suggest that the Ig‐like domain contributes to the stabilization of LC‐CelG mainly due to the Gln40‐ and Asp99‐mediated interactions. Because the LC‐CelG derivative lacking the Ig‐like domain accumulated in Escherichia coli cells mostly in an insoluble form and this derivative accumulated in a soluble form exhibited very weak activity, the Ig‐like domain may be required to make the conformation of the active site functional and prevent aggregation of the catalytic domain.
Synthesizing Environmental Flow Needs Data for Water Management in a Water‐Scarce State: The Arizona Environmental Water Demands Database
Authors: Mott Lacroix K. E. , Xiu B. C. , Nadeau J. B. , Megdal S. B. 
Published: December 2014

AbstractWater rights for environmental flows are not universal, and oftentimes, legal tools used to incorporate the environment into water management only require new users to consider their impact. It can be difficult to include the needs of riparian and aquatic ecosystems in new plans when relevant information is not always available, especially when other existing uses already outstrip available supplies. There is a need for easily accessible and understandable science on the water requirements for riparian and aquatic species, so managers can make informed decisions about whether or not to include riparian and aquatic species in their community's water management future. In this paper, we describe the current understanding of the link between hydrology and Arizona's riparian and aquatic ecosystems through the creation of a geospatial Environmental Water Demands database that can be used to determine the water needs to maintain habitat. Analysis of 121 studies reveals that there are very few analyses of the surface water and groundwater requirements for intermittent or ephemeral river systems, and there are only limited generalizable data for aquatic species. Except for a few species, such as Cottonwood (Populous fremontii) and Willow (Salix gooddingii), few data are available on the flow requirements for vegetation. The Environmental Water Demands database can be used to identify critical geographic and topical knowledge gaps where further research is needed, as well as serve as a single place for water and land managers to assess and use the most currently available information to make more informed management decisions and recommendations. Copyright © 2014 John Wiley & Sons, Ltd.
Signalling Through Retinoic Acid Receptors is Required for Reprogramming of Both Mouse Embryonic Fibroblast Cells and Epiblast Stem Cells to Induced Pluripotent Stem Cells
Authors: Yang Jian , Wang Wei , Ooi Jolene , Campos Lia S. , Lu Liming , Liu Pentao 
Published: December 2014

Abstract
We previously demonstrated that coexpressing retinoic acid (RA) receptor gamma and liver receptor homolog-1 (LRH1 or NR5A2) with OCT4, MYC, KLF4, and SOX2 (4F) rapidly reprograms mouse embryonic fibroblast cells (MEFs) into induced pluripotent stem cells (iPSCs). Here, we further explore the role of RA in reprogramming and report that the six factors (6F) efficiently and directly reprogram MEFs into integration-free iPSCs in defined medium (N2B27) in the absence of feeder cells. Through genetic and chemical approaches, we find that RA signalling is essential, in a highly dose-sensitive manner, for MEF reprogramming. The removal of exogenous RA from N2B27, the inhibition of endogenous RA synthesis or the expression of a dominant-negative form of RARA severely impedes reprogramming. By contrast, supplementing N2B27 with various retinoids substantially boosts reprogramming. In addition, when coexpressed with LRH1, RA receptors (RARs) can promote reprogramming in the absence of both exogenous and endogenously synthesized RA. Remarkably, the reprogramming of epiblast stem cells into embryonic stem cell-like cells also requires low levels of RA, which can modulate Wnt signalling through physical interactions of RARs with β-catenin. These results highlight the important functions of RA signalling in reprogramming somatic cells and primed stem cells to naïve pluripotency. Stem Cells 2015;33:1390–1404
Contrasting Roles for C/EBPα and Notch in Irradiation-Induced Multipotent Hematopoietic Progenitor Cell Defects
Authors: Fleenor Courtney Jo , Rozhok Andrii Ivan , Zaberezhnyy Vadym , Mathew Divij , Kim Jihye , Tan Aik-Choon , Bernstein Irwin David , DeGregori James 
Published: December 2014

Abstract
Ionizing radiation (IR) is associated with reduced hematopoietic function and increased risk of hematopoietic malignancies, although the mechanisms behind these relationships remain poorly understood. Both effects of IR have been commonly attributed to the direct induction of DNA mutations, but evidence supporting these hypotheses is largely lacking. Here we demonstrate that IR causes long-term, somatically heritable, cell-intrinsic reductions in hematopoietic stem cell (HSC) and multipotent hematopoietic progenitor cell (mHPC) self-renewal that are mediated by C/EBPα and reversed by Notch. mHPC from previously irradiated (&gt;9 weeks prior), homeostatically restored mice exhibit gene expression profiles consistent with their precocious differentiation phenotype, including decreased expression of HSC-specific genes and increased expression of myeloid program genes (including C/EBPα). These gene expression changes are reversed by ligand-mediated activation of Notch. Loss of C/EBPα expression is selected for within previously irradiated HSC and mHPC pools and is associated with reversal of IR-dependent precocious differentiation and restoration of self-renewal. Remarkably, restoration of mHPC self-renewal by ligand-mediated activation of Notch prevents selection for C/EBPα loss of function in previously irradiated mHPC pools. We propose that environmental insults prompt HSC to initiate a program limiting their self-renewal, leading to loss of the damaged HSC from the pool while allowing this HSC to temporarily contribute to differentiated cell pools. This “programmed mediocrity” is advantageous for the sporadic genotoxic insults animals have evolved to deal with but becomes tumor promoting when the entire HSC compartment is damaged, such as during total body irradiation, by increasing selective pressure for adaptive oncogenic mutations. Stem Cells 2015;33:1345–1358
Hematopoietic Stem/Progenitor Cells Directly Contribute to Arteriosclerotic Progression via Integrin β2
Authors: Wang Xuhong , Gao Mingming , Schouteden Sarah , Roebroek Anton , Eggermont Kristel , van Veldhoven Paul P. , Liu George , Peters Thorsten , Scharffetter-Kochanek Karin , Verfaillie Catherine M. , Feng Yingmei 
Published: December 2014

Abstract
Recent studies described the association between hematopoietic stem/progenitor cell (HSPC) expansion in the bone marrow (BM), leukocytosis in the peripheral blood, and accelerated atherosclerosis. We hypothesized that circulating HSPC may home to inflamed vessels, where they might contribute to inflammation and neointima formation. We demonstrated that Lin− Sca-1+ cKit+ (LSK cells) in BM and peripheral blood of LDLr−/− mice on high fat diet expressed significantly more integrin β2, which was responsible for LSK cell adhesion and migration toward ICAM-1 in vitro, and homing to injured arteries in vivo, all of which were blocked with an anti-CD18 blocking antibody. When homed LSK cells were isolated from ligated artery and injected to irradiated recipients, they resulted in BM reconstitution. Injection of CD18+/+ LSK cells to immunodeficient Balb/C Rag2− ɣC−/− recipients resulted in more severe inflammation and reinforced neointima formation in the ligated carotid artery, compared to mice injected with PBS and CD18−/− LSK cells. Hypercholesterolemia stimulated ERK phosphorylation (pERK) in LSK cells of LDLr−/− mice in vivo. Blockade of pERK reduced ARF1 expression, leading to decreased integrin β2 function on HSPC. In addition, integrin β2 function could be regulated via ERK-independent LRP1 pathway. Integrin β2 expression on HSPC is regulated by hypercholesterolemia, specifically LDL, in pERK-dependent and -independent manners, leading to increased homing and localization of HSPC to injured arteries, which is highly correlated with arteriosclerosis. Stem Cells 2015;33:1230–1240
The RUNX1 +24 Enhancer and P1 Promoter Identify a Unique Subpopulation of Hematopoietic Progenitor Cells Derived from Human Pluripotent Stem Cells
Authors: Ferrell Patrick I. , Xi Jiafei , Ma Chao , Adlakha Mitali , Kaufman Dan S. 
Published: December 2014

Abstract
Derivation of hematopoietic stem cells (HSCs) from human pluripotent stem cells remains a key goal for the fields of developmental biology and regenerative medicine. Here, we use a novel genetic reporter system to prospectively identify and isolate early hematopoietic cells derived from human embryonic stem cells (hESCs) and human induced pluripotent cells (iPSCs). Cloning the human RUNX1c P1 promoter and +24 enhancer to drive expression of tdTomato (tdTom) in hESCs and iPSCs, we demonstrate that tdTom expression faithfully enriches for RUNX1c-expressing hematopoietic progenitor cells. Time-lapse microscopy demonstrated the tdTom+ hematopoietic cells to emerge from adherent cells. Furthermore, inhibition of primitive hematopoiesis by blocking Activin/Nodal signaling promoted the expansion and/or survival of the tdTom+ population. Notably, RUNX1c/tdTom+ cells represent only a limited subpopulation of the CD34+CD45+ and CD34+CD43+ cells with a unique genetic signature. Using gene array analysis, we find significantly lower expression of Let-7 and mir181a microRNAs in the RUNX1c/tdTom+ cell population. These phenotypic and genetic analyses comparing the RUNX1c/tdTom+ population to CD34+CD45+ umbilical cord blood and fetal liver demonstrate several key differences that likely impact the development of HSCs capable of long-term multilineage engraftment from hESCs and iPSCs. Stem Cells 2015;33:1130–1141
Ciliary Neurotrophic Factor Promotes the Activation of Corneal Epithelial Stem/Progenitor Cells and Accelerates Corneal Epithelial Wound Healing
Authors: Zhou Qingjun , Chen Peng , Di Guohu , Zhang Yangyang , Wang Yao , Qi Xia , Duan Haoyun , Xie Lixin 
Published: December 2014

Abstract
Ciliary neurotrophic factor (CNTF), a well-known neuroprotective cytokine, has been found to play an important role in neurogenesis and functional regulations of neural stem cells. As one of the most innervated tissue, however, the role of CNTF in cornea epithelium remains unclear. This study was to explore the roles and mechanisms of CNTF in the activation of corneal epithelial stem/progenitor cells and wound healing of both normal and diabetic mouse corneal epithelium. In mice subjecting to mechanical removal of corneal epithelium, the corneal epithelial stem/progenitor cell activation and wound healing were promoted by exogenous CNTF application, while delayed by CNTF neutralizing antibody. In cultured corneal epithelial stem/progenitor cells, CNTF enhanced the colony-forming efficiency, stimulated the mitogenic proliferation, and upregulated the expression levels of corneal epithelial stem/progenitor cell-associated transcription factors. Furthermore, the promotion of CNTF on the corneal epithelial stem/progenitor cell activation and wound healing was mediated by the activation of STAT3. Moreover, in diabetic mice, the content of CNTF in corneal epithelium decreased significantly when compared with that of normal mice, and the supplement of CNTF promoted the diabetic corneal epithelial wound healing, accompanied with the advanced activation of corneal epithelial stem/progenitor cells and the regeneration of corneal nerve fibers. Thus, the capability of expanding corneal epithelial stem/progenitor cells and promoting corneal epithelial wound healing and nerve regeneration indicates the potential application of CNTF in ameliorating limbal stem cell deficiency and treating diabetic keratopathy. Stem Cells 2015;33:1566–1576
Inexpensive, Clean, Reliable Energy Will Require Engineered Systems
Authors: Pavlak Alex 
Published: December 2014

ABSTRACTAlthough small emission reductions are easy, large reductions will demand engineered systems. Classical system engineering (SE) development begins with ultimate goals such as big (>90%) reductions in greenhouse gas emissions. The first SE phase, concept development, consists of system tradeoffs to clarify feasible concepts and focus development efforts. These system studies begin with simple concept models and then build complexity in stages to elucidate principles, interfaces, and requirements. The concept definition phase is classically concluded with a critical review followed by a management decision, a value choice. Overall, classical SE starts with the ultimate goals, then works backward to allocate requirements and figure out how to get there from here. Contrast this with today's forward migration approach. Migrating forward without a clear path to an ultimate goal runs the risk of dead end development, stuck with concepts that cannot reach the ultimate goal. This paper illustrates concept development needs for both wind systems and for civilian nuclear power.
Selective element fission approach for fast FEM simulation of incremental sheet forming based on dual-mesh system
Authors: Zhang M. H. , Lu B. , Chen J. , Long H. , Ou H. 
Published: December 2014

Abstract
Incremental sheet forming (ISF) is a highly versatile and flexible process for producing low batches of sheet metal parts. Although finite element (FE) method is a key approach in the study of material deformation in metal forming processes, the application of FE in ISF process is still limited. This is due to the enormous simulation time required for ISF processes. Focusing on this problem, this paper presents a new selective element fission (SEF) approach for simulation of ISF process based on LS-DYNA. In the approach, the computational efficiency is improved by reducing the unnecessary calculations of elements outside the localized deformation zone in the ISF process. The introduction of a background mesh for simulation data storage and a separate simulation mesh with varied mesh density for simulation ensures both the efficiency of computation and accuracy of results. To verify the proposed SEF method, two ISF case problems including a hyperbolic cone part and a pyramid part are studied by comparing to the conventional FE approach and the H-adaptive approach in terms of the CPU time, the forming load, the final part profile, and thickness distribution. The influence of two key factors: element size ratio and toolpath segment length is also studied. The results suggested that the developed SEF approach can save the CPU time by up to 74 % with satisfactory accuracy as compared to conventional FE method, which demonstrates both the effectiveness and robustness of the developed SEF approach.
How many rodents die on the road? Biological and methodological implications from a small mammals’ roadkill assessment on a Spanish motorway
Authors: Ruiz‐Capillas Pablo , Mata Cristina , Malo Juan E. 
Published: December 2014

AbstractSome small mammal species use road verges as a habitat for sheltering. As a result, their populations suffer mortality from roadkill in an unknown extent. We analysed the road mortality of small mammals and the population impact of roadkill on wood mouse along 1 year on a 4‐km motorway stretch. To account for potential bias in carcass sampling, we conducted walking surveys with the traffic interrupted and we performed three carcass persistence experiments to estimate total number of roadkills. The estimations were contrasted with previous studies and the population abundance on the road verges. The spatial pattern and the effects of seasonality and traffic volume on roadkill were analysed. We recorded 84 rodent carcasses with a mean carcass persistence of 6.65 days (SE = 0.41). The estimations of roadkill ranged between 190.2 and 238.3 individuals km−1year−1, with a mean value close to a monthly 6 % mortality for the most common specie. Roadkill was more frequent during the hottest and driest months, and showed a unimodal relation with traffic peaking at 8100 vehicles day−1. A spatial aggregation of roadkill was detected with 80–190 m clustering. Our results suggest that, although rodents suffer greater roadkill mortality than previously reported, it affects a small percentage of the wood mouse population in our study area. This source of mortality is unlikely to affect population viability in the short term. Our results show that roadkill surveys should be specifically designed for small mammals to have a more accurate analysis of the effects of roadkill on their populations.
Individual trans 18:1 Isomers are Metabolised Differently and Have Distinct Effects on Lipogenesis in 3T3‐L1 Adipocytes
Authors: Vahmani P. , Meadus W. J. , Turner T. D. , Duff P. , Rolland D. C. , Mapiye C. , Dugan M. E. R. 
Published: December 2014

AbstractThe objective of this research was to study the metabolism of individual trans fatty acids (FAs) that can be found in ruminant fat or partially hydrogenated vegetable oils (PHVO) and determine their effects on FA composition and lipogenic gene expression in adipocytes. Differentiated 3T3‐L1 adipocytes were treated with 200 µM of either trans‐9‐18:1, trans‐11‐18:1, trans‐13‐18:1, cis‐9‐18:1 or BSA vehicle control for 120 h. Trans‐9‐18:1 increased total cell FA content (µmole/well) compared to other FA treatments, which was mainly related to the accumulation of trans‐9‐18:1 in the cells. Adipocytes were able to desaturate a significant proportion of absorbed trans‐11‐18:1 and trans‐13‐18:1 (~20 and 30 % respectively) to cis‐9,trans‐11‐18:2 and cis‐9,trans‐13‐18:2, whereas trans‐9‐18:1 was mostly incorporated intact resulting in a greater lipophilic index (i.e. decreased mean FA fluidity) of adipocytes. Trans‐9‐18:1 up‐regulated (P < 0.05) the expression of lipogenic genes including acetyl‐CoA carboxylase (1.65 fold), FA synthase (1.45 fold), FA elongase‐5 (1.52 fold) and stearoyl‐CoA desaturase‐1 (1.49 fold), compared to the control, whereas trans‐11‐18:1 and trans‐13‐18:1 did not affect the expression of these genes compared to control. Our results suggest that the metabolism and lipogenic properties of trans‐11‐18:1 and trans‐13‐18:1, typically the most abundant trans FA in beef from cattle fed forage‐based diets, are similar and are different from those of trans‐9‐18:1, the predominant trans FA in PHVO.
A Maternal High Fat Diet Has Long‐Lasting Effects on Skeletal Muscle Lipid and PLIN Protein Content in Rat Offspring at Young Adulthood
Authors: MacPherson Rebecca E. K. , Castelli Laura M. , Miotto Paula M. , Frendo‐Cumbo Scott , Milburn Amanda , Roy Brian D. , LeBlanc Paul J. , Ward Wendy E. , Peters Sandra J. 
Published: December 2014

AbstractA maternal high fat diet (HFD) can have adverse effects on skeletal muscle development. Skeletal muscle PLIN proteins (PLIN2, 3 and 5) are thought to play critical roles in lipid metabolism, however effects of HFD on PLIN and lipases (HSL, ATGL, CGI‐58) in mothers as well as their offspring have yet to be investigated. The primary objective of this study was to determine whether maternal HFD would influence skeletal muscle lipase and PLIN protein content in offspring at weaning (19d) and young adulthood (3mo). Female rats (28d old, n = 9/group) were fed control (CON, AIN93G, 7 % soybean oil) or HFD (AIN93G, 20 % lard) for 10 weeks prior to mating and throughout pregnancy and lactation. All offspring were weaned to CON [n = 18/group, 1 female and 1 male pup per litter were studied at weaning (19d) and 3mo of age]. There was no effect of sex for the main outcomes measured in plantaris, therefore male and female data was combined. Maternal HFD resulted in higher triacylglycerol content in pups at 3mo (p < 0.05), as well as in the dams (p = 0.015). Maternal HFD resulted in higher PLIN5 content in pups at weaning and 3mo (p = 0.05). PLIN2 and PLIN5 content decreased at 3mo versus weaning (p < 0.001). HFD dams had a higher PLIN3 content (p = 0.016). Diet had no effect on ATGL, CGI‐58, or HSL content. In conclusion, exposure to a maternal HFD resulted in higher skeletal muscle lipid and PLIN5 content in plantaris of offspring through to young adulthood.
Impact of the introduction of neuraxial labor analgesia on mode of delivery at an urban maternity hospital in China
Authors: Hu Ling‐Qun , Zhang Jin , Wong Cynthia A. , Cao Qinying , Zhang Guohua , Rong Huijuan , Li Xia , McCarthy Robert J. 
Published: December 2014

AbstractObjectiveTo evaluate the association between the introduction of neuraxial (epidural) labor analgesia and mode of delivery in a large urban maternity hospital in China.MethodsA single‐intervention impact study was conducted at Shijiazhuang Obstetrics and Gynecology Hospital in Shijiazhuang. Baseline data collection occurred between August 1 and December 31, 2009, when no analgesic method was routinely employed during labor. An intervention was then implemented, consisting of a neuraxial labor analgesia service. The service was fully operational from September 1, 2010, and data were collected to August 31, 2011. The mode of delivery was compared between the different periods.ResultsNeuraxial analgesia rate was used in none of the 3787 deliveries during the baseline period and 3429 (33.5%) of 10 230 in the implementation period. Cesareans were performed in 1533 (40.5%) deliveries in the baseline period and 3441 (33.6%) in the implementation period (difference −6.8%, 99.8% confidence interval [CI] −9.7% to −3.9%; P < 0.0017). The proportion of vaginal deliveries in which forceps were used was unchanged (difference −0.8%, 99.8% CI −0.7% to 2.2%; P = 0.92).ConclusionThe introduction of epidural analgesia reduced the frequency of cesarean delivery, which improved obstetric and neonatal outcomes.