bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural Stem Cell Tumorigenicity and Biodistribution Assessment for Phase I Clinical Trial in Parkinson’s Disease
Authors: Garitaonandia Ibon , Gonzalez Rodolfo , Christiansen-Weber Trudy , Abramihina Tatiana , Poustovoitov Maxim , Noskov Alexander , Sherman Glenn , Semechkin Andrey , Snyder Evan , Kern Russell 
Published: September 2016

AbstractHuman pluripotent stem cells (PSC) have the potential to revolutionize regenerative medicine. However undifferentiated PSC can form tumors and strict quality control measures and safety studies must be conducted before clinical translation. Here we describe preclinical tumorigenicity and biodistribution safety studies that were required by the US Food and Drug Administration (FDA) and Australian Therapeutic Goods Administration (TGA) prior to conducting a Phase I clinical trial evaluating the safety and tolerability of human parthenogenetic stem cell derived neural stem cells ISC-hpNSC for treating Parkinson’s disease (ClinicalTrials.gov Identifier NCT02452723). To mitigate the risk of having residual PSC in the final ISC-hpNSC population, we conducted sensitive in vitro assays using flow cytometry and qRT-PCR analyses and in vivo assays to determine acute toxicity, tumorigenicity and biodistribution. The results from these safety studies show the lack of residual undifferentiated PSC, negligible tumorigenic potential by ISC-hpNSC and provide additional assurance to their clinical application.
Adaptive pattern of nectar volume within inflorescences: bumblebee foraging behavior and pollinator-mediated natural selection
Authors: Zhao Zhigang , Lu Ningna , Conner Jeffrey K. 
Published: September 2016

AbstractLarger floral displays increase pollinator visitation as well as among-flower self-pollination (geitonogamy) in self-compatible species. Dichogamy (temporal separation of gender expression) can limit geitonogamy and increase outcrossing but this depends on pollinator behavior within inflorescences. Declining nectar volume from lower to upper flowers is a hypothesized adaptation to increase outcrossing and pollen export by encouraging the upward movment of pollinators from female to male flowers and by reducing the number of flowers probed per inflorescence, but supporting evidence has been equivocal. We tested this hypothesis in Aconitum gymnandrum by studying floral display and rewards, pollinator visitation, and pollinator-mediated selection on floral traits. We found that larger inflorescences of A. gymnandrum attracted more pollinators, but did not increase the number of flowers probed per visit. Nectar production declined with increasing flower height on average, but the opposite pattern was also common. Bumblebees responded strongly to the nectar pattern, moving from higher to lower nectar concentration. Finally, there was significant pollinator-mediated direct selection for this pattern of declining nectar volume after correcting for correlations with flower size, number, and mean nectar volume. Together, the results strongly suggest that declining nectar production in higher flowers is an adaptation to enhance outcrossing in A. gymnandrum.
Wnt/β-catenin signaling pathway activation is required for proliferation of chicken primordial germ cells in vitro
Authors: Lee Hyung Chul , Lim Sumi , Han Jae Yong 
Published: September 2016

AbstractHere, we investigated the role of the Wnt/β-catenin signaling pathway in chicken primordial germ cells (PGCs) in vitro. We confirmed the expression of Wnt signaling pathway-related genes and the localization of β-catenin in the nucleus, revealing that this pathway is potentially activated in chicken PGCs. Then, using the single-cell pick-up assay, we examined the proliferative capacity of cultured PGCs in response to Wnt ligands, a β-catenin-mediated Wnt signaling activator (6-bromoindirubin-3′-oxime [BIO]) or inhibitor (JW74), in the presence or absence of basic fibroblast growth factor (bFGF). WNT1, WNT3A, and BIO promoted the proliferation of chicken PGCs similarly to bFGF, whereas JW74 inhibited this proliferation. Meanwhile, such treatments in combination with bFGF did not show a synergistic effect. bFGF treatment could not rescue PGC proliferation in the presence of JW74. In addition, we confirmed the translocation of β-catenin into the nucleus by the addition of bFGF after JW74 treatment. These results indicate that there is signaling crosstalk between FGF and Wnt, and that β-catenin acts on PGC proliferation downstream of bFGF. In conclusion, our study suggests that Wnt signaling enhances the proliferation of chicken PGCs via the stabilization of β-catenin and activation of its downstream genes.
High expression of MAP7 predicts adverse prognosis in young patients with cytogenetically normal acute myeloid leukemia
Authors: Fu Lin , Fu Huaping , Zhou Lei , Xu Keman , Pang Yifan , Hu Kai , Wang Jing , Tian Lei , Liu Yuanyuan , Wang Jijun , Jing Hongmei , Huang Wenrong , Ke Xiaoyan , Shi Jinlong 
Published: September 2016

AbstractMicrotubule-associated protein 7 (MAP7) plays an important role in cancer cells. In this study, we identified the prognostic significance of MAP7 expression in cytogenetically normal acute myeloid leukemia (CN-AML) patients (aged <60 years) based on several microarray datasets. In the first group (n = 129), high MAP7 expression (MAP7high) was associated with adverse overall survival (OS; P = 0.0441) and event-free survival (EFS; P = 0.0114) compared with low MAP7 expression (MAP7low). In addition, the prognostic significance of MAP7 was confirmed by European Leukemia Net (ELN) intermediate-I genetic categories and multivariable analysis. In the second independent group of CN-AML patients (aged <60 years), MAP7high was also associated with adverse OS (n = 88, OS; P = 0.00811). To understand the inherent mechanisms of MAP7’s prognosis, we investigated genome-wide gene/microRNA expression signatures associated with MAP7 expression. Several known oncogenic genes/microRNAs and anti-oncogenic genes/microRNAs were disordered in MAP7high CN-AML patients. In conclusion, MAP7high is an adverse prognostic biomarker for CN-AML, which may be attributed to the distinctive genome-wide gene/microRNA expression and related cell signaling pathways.
Comparison of standard, quantitative and digital PCR in the detection of enterotoxigenic Bacteroides fragilis
Authors: Purcell Rachel V. , Pearson John , Frizelle Frank A. , Keenan Jacqueline I. 
Published: September 2016

AbstractGut colonization with enterotoxigenic Bacteroides fragilis (ETBF) appears to be associated with the development of colorectal cancer. However, differences in carriage rates are seen with various testing methods and sampling sites. We compared standard PCR, SYBR green and TaqMan quantitative PCR (qPCR) and digital PCR (dPCR) in detecting the B. fragilis toxin (bft) gene from cultured ETBF, and from matched luminal and faecal stool samples from 19 colorectal cancer patients. Bland-Altman analysis found that all three quantitative methods performed comparably in detecting bft from purified bacterial DNA, with the same limits of detection (<1 copy/μl). However, SYBR qPCR under-performed compared to TaqMan qPCR and dPCR in detecting bft in clinical stool samples; 13/38 samples were reported positive by SYBR, compared to 35 and 36 samples by TaqMan and dPCR, respectively. TaqMan qPCR and dPCR gave bft copy numbers that were 48-fold and 75-fold higher for the same samples than SYBR qPCR, respectively (p < 0.001). For samples that were bft-positive in both fecal and luminal stools, there was no difference in relative abundance between the sites, by any method tested. From our findings, we recommend the use of TaqMan qPCR as the preferred method to detect ETBF from clinical stool samples.
The impact of P2Y12 promoter DNA methylation on the recurrence of ischemic events in Chinese patients with ischemic cerebrovascular disease
Authors: Li Xin-Gang , Ma Ning , Wang Bo , Li Xiao-Qing , Mei Sheng-Hui , Zhao Kun , Wang Yong-Jun , Li Wei , Zhao Zhi-Gang , Sun Shu-Sen , Miao Zhong-Rong 
Published: September 2016

AbstractThe primary mechanism of clopidogrel resistance is still unclear. We aimed to investigate whether the methylation status of the P2Y12 promoter has effects on platelet function and clinical ischemic events. Patients with ischemic cerebrovascular disease were enrolled into our study. Venous blood samples were drawn for thrombelastograpy (TEG) and active metabolite assay. Patients were divided into a case- or control-group based on the occurrence of ischemic events during a one year follow-up. Two TEG parameters between the case and control groups were statistically significant [ADP inhibition rate (ADP%): P = 0.018; ADP-induced platelet-fibrin clot strength (MAADP): P = 0.030]. The concentrations of clopidogrel active metabolite had no significant difference (P = 0.281). Sixteen CpG dinucleotides on P2Y12 promoter were tested. Three CpG sites (CpG11 and CpG12 + 13) showed lower methylation status, which correlated with a strong association with increased risk of clinical events. Changes of MAADP and ADP% were also associated with methylation levels of CpG 11 and CpG 12 + 13. Hypomethylation of the P2Y12 promoter is associated with a higher platelet reactivity and increased risk of ischemic events in our patients. Methylation analysis of peripheral blood samples might be a novel molecular marker to help early identification of patients at high risk for clinical ischemic events.
Rhythmic displays of female gibbons offer insight into the origin of dance
Authors: Fan Peng-Fei , Ma Chang-Yong , Garber Paul A. , Zhang Wen , Fei Han-Lan , Xiao Wen 
Published: September 2016

AbstractDance is a universal art form practiced by all human societies and has many functions including sexual attraction, social cohesion, and the therapeutic release of energy. Dance also has been reported in a small number of non-human primate species, in particular apes. However, its function has not been systematically evaluated. We observed 357 intentional, rhythmic, and nonverbal dance displays performed by four adult female cao vit gibbons (Nomascus nasutus) residing in four polygynous groups during 3000 h of observation in Bangliang, Guangxi, China. Females used dance to solicit copulations, as well as to promote a social bond with the group’s lone adult male. In addition, this display appears to represent a form of non-aggressive competition among adult females living in the same group. We found that a female who had a weaker social relationship with the breeding male increased her social and sexual access to the male by an increase in dancing frequency. Given that gibbons dance in various behavioral contexts, and appears to serve several important social and sexual functions, a greater understanding of this form of gestural communication offers an instructive model for examining the origin and evolution of dance in humans and other apes.
Simple and rapid direct cloning and heterologous expression of natural product biosynthetic gene cluster in Bacillus subtilis via Red/ET recombineering
Authors: Liu Qingshu , Shen Qiyao , Bian Xiaoying , Chen Hanna , Fu Jun , Wang Hailong , Lei Ping , Guo Zhaohui , Chen Wu , Li Dingjun , Zhang Youming 
Published: September 2016

AbstractHeterologous expression of biosynthetic pathways is an important way to research and discover microbial natural products. Bacillus subtilis is a suitable host for the heterologous production of natural products from bacilli and related Firmicutes. Existing technologies for heterologous expression of large biosynthetic gene clusters in B. subtilis are complicated. Herein, we present a simple and rapid strategy for direct cloning based heterologous expression of biosynthetic pathways in B. subtilis via Red/ET recombineering, using a 5.2 kb specific direct cloning vector carrying homologous sequences to the amyE gene in B. subtilis and CcdB counterselection marker. Using a two-step procedure, two large biosynthetic pathways for edeine (48.3 kb) and bacillomycin (37.2 kb) from Brevibacillus brevis X23 and B. amyloliquefaciens FZB42, respectively, were directly cloned and subsequently integrated into the chromosome of B. subtilis within one week. The gene cluster for bacillomycin was successfully expressed in the heterologous host, although edeine production was not detectable. Compared with similar technologies, this method offers a simpler and more feasible system for the discovery of natural products from bacilli and related genera.
Orphan nuclear receptor SHP regulates iron metabolism through inhibition of BMP6-mediated hepcidin expression
Authors: Kim Don-Kyu , Kim Yong-Hoon , Jung Yoon Seok , Kim Ki-Sun , Jeong Jae-Ho , Lee Yong-Soo , Yuk Jae-Min , Oh Byung-Chul , Choy Hyon E. , Dooley Steven , Muckenthaler Martina U. , Lee Chul-Ho , Choi Hueng-Sik 
Published: September 2016

AbstractSmall heterodimer partner (SHP) is a transcriptional corepressor regulating diverse metabolic processes. Here, we show that SHP acts as an intrinsic negative regulator of iron homeostasis. SHP-deficient mice maintained on a high-iron diet showed increased serum hepcidin levels, decreased expression of the iron exporter ferroportin as well as iron accumulation compared to WT mice. Conversely, overexpression of either SHP or AMP-activated protein kinase (AMPK), a metabolic sensor inducing SHP expression, suppressed BMP6-induced hepcidin expression. In addition, an inhibitory effect of AMPK activators metformin and AICAR on BMP6-mediated hepcidin gene expression was significantly attenuated by ablation of SHP expression. Interestingly, SHP physically interacted with SMAD1 and suppressed BMP6-mediated recruitment of the SMAD complex to the hepcidin gene promoter by inhibiting the formation of SMAD1 and SMAD4 complex. Finally, overexpression of SHP and metformin treatment of BMP6 stimulated mice substantially restored hepcidin expression and serum iron to baseline levels. These results reveal a previously unrecognized role for SHP in the transcriptional control of iron homeostasis.
Defining the extreme substrate specificity of Euonymus alatus diacylglycerol acetyltransferase, an unusual membrane-bound O-acyltransferase
Authors: Bansal Sunil , Durrett Timothy P. 
Published: September 2016

Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) synthesizes the unusually structured 3-acetyl-1,2-diacylglycerols (acetyl-TAG) found in the seeds of a few plant species. A member of the membrane-bound O-acyltransferase (MBOAT) family, EaDAcT transfers the acetyl group from acetyl-CoA to sn-1,2-diacylglycerol (DAG) to produce acetyl-TAG. In vitro assays demonstrated that the enzyme is also able to utilize butyryl-CoA and hexanoyl-CoA as acyl donors, though with much less efficiency compared with acetyl-CoA. Acyl-CoAs longer than eight carbons were not used by EaDAcT. This extreme substrate specificity of EaDAcT distinguishes it from all other MBOATs which typically catalyze the transfer of much longer acyl groups. In vitro selectivity experiments revealed that EaDAcT preferentially acetylated DAG molecules containing more double bonds over those with less. However, the enzyme was also able to acetylate saturated DAG containing medium chain fatty acids, albeit with less efficiency. Interestingly, EaDAcT could only acetylate the free hydroxyl group of sn-1,2-DAG but not the available hydroxyl groups in sn-1,3-DAG or in monoacylglycerols (MAG). Consistent with its similarity to the jojoba wax synthase, EaDAcT could acetylate fatty alcohols in vitro to produce alkyl acetates. Likewise, when coexpressed in yeast with a fatty acyl-CoA reductase capable of producing fatty alcohols, EaDAcT synthesized alkyl acetates although the efficiency of production was low. This improved understanding of EaDAcT specificity confirms that the enzyme preferentially utilizes acetyl-CoA to acetylate sn-1,2-DAGs and will be helpful in engineering the production of acetyl-TAG with improved functionality in transgenic plants.
Rawlsian maximin rule operates as a common cognitive anchor in distributive justice and risky decisions
Authors: Kameda Tatsuya , Inukai Keigo , Higuchi Satomi , Ogawa Akitoshi , Kim Hackjin , Matsuda Tetsuya , Sakagami Masamichi 
Published: September 2016

Significance
Distributive justice is a highly controversial issue across many societies. Compared with the accumulation of various normative (“ought”) theories by philosophers over the centuries, our empirical (“is”) understanding of people’s distributive judgments remains insufficient. In a series of experiments, we show that the “maximin” concern (maximizing the minimum possible payoff) operates as a strong cognitive anchor in both distributive decisions for others and economic decisions for self, and that the right temporoparietal junction, associated with perspective taking, plays a key role in this linkage. Our approach illustrates how rigorous methods from behavioral, cognitive, and neural sciences can be combined to shed light on functional elements of distributive justice in our minds, and potential neural underpinnings shared by other nonsocial decisions.
Dysregulation of Notch and ERα signaling in AhR−/−male mice
Authors: Huang Bo , Butler Ryan , Miao Yifei , Dai Yubing , Wu Wanfu , Su Wen , Fujii-Kuriyama Yoshiaki , Warner Margaret , Gustafsson Jan-Åke 
Published: September 2016

SignificanceThe aryl hydrocarbon receptor (AhR), in addition to its well-known role in repressing ER signaling, has now been shown to have a physiological function in regulating Notch signaling. Thus, in AhR−/−male mice, there is growth of mammary ducts and degenerative changes in the testes. There is germ cell apoptosis, reduction of expression of Notch1 and Notch3 in Sertoli cells and slightly reduced serum testosterone level. Male infertility (affecting approximately 7% of all men) and gynecomastia (benign growth of the mammary gland in men) are two disorders for which there is need for better intervention. The study suggests that the AhR may be targeted to treat these disorders.
Habitat Use in a Depleted Population of Winter Flounder: Insights into Impediments to Population Recovery
Authors: Howell Penelope T. , Pereira Jose J. , Schultz Eric T. , Auster Peter J. 
Published: September 2016

AbstractThe distribution and demographics of a population of Winter Flounder Pseudopleuronectes americanus were examined for changes related to habitat quality over a fishery‐independent survey period of 29 years, encompassing an 82% decline in abundance. We tested for spatial and temporal variation in indicators of fitness to determine whether they revealed likely processes that resulted in the observed patterns of habitat use. We also assessed temporal changes in fitness and inferred changes in habitat quality associated with population decline. We focused on the condition of postspawn (resting) mature and immature fish of both sexes during a critical period of spring feeding prior to summer migration. Analysis of variance of individual condition indices (log10[length]–log10[weight] regression residuals) by sex/maturity group and time period identified consistent and significant differences among six survey strata. Highest condition indices were observed for fish that were captured in shallow (<18‐m) mud, sand, and transitional bottom sediment and deep (>18‐m) mud areas, collectively classified as high‐quality habitat. The proportion of the population that occupied high‐quality habitat remained unchanged at approximately 60% over the time series. As abundance decreased, condition decreased in mature females, increased in immature fish of both sexes, and was mixed in mature males. Additionally, the proportion mature at length shifted significantly upward for both sexes, the back‐calculated lengths at ages 2 and 3 increased for mature individuals, and the estimated winter growth declined for age‐3 mature and immature females. The results suggested increased competition for prey among mature fish and increased predation pressure on smaller fish. This Winter Flounder population may be responding to an increase in the abundance of competing mid‐Atlantic species, which was brought about by increasing water temperature. These second‐order effects may have chronically hindered Winter Flounder reproduction and therefore stock rebuilding, especially in areas of low‐quality habitat.Received September 23, 2015; accepted July 18, 2016 Published online September 30, 2016
Reproductive Status and Blood Plasma Indicators of Sex and Gonad Maturation Status for Yelloweye Rockfish Following Barotrauma and Recompression Events
Authors: Blain Brittany J. , Sutton Trent M. 
Published: September 2016

AbstractDiscard mortality of rockfishes Sebastes spp. is a management concern along the West Coast of North America. Although many rockfish species survive after barotrauma and forced recompression, it is unclear whether these mechanisms affect reproductive success. We examined whether (1) Yelloweye Rockfish S. ruberrimus in Prince William Sound, Alaska, could reproduce up to 2 years after one or more barotrauma and recompression events; and (2) blood plasma indicators (i.e., vitellogenin [VTG] and calcium [Ca2+]) could be used to identify sex and gonad maturation stage. In 2010, we captured and examined Yelloweye Rockfish that had been tagged in 2008 and 2009, and all mature females were gravid or spent. The most common barotrauma sign was esophageal eversion, with females and males exhibiting this injury 50% and 90% of the time, respectively. All other injuries, except swim bladder ruptures and tears, occurred at low frequencies and (with the exception of esophageal eversion) increased in frequency with capture depth. Mean plasma VTG concentrations for females were greater than those for males; with the exception of stage‐0 females, there were no differences in VTG among female gestation stages. Mean plasma Ca2+ concentrations for stage‐2 females differed from those of males, stage‐0 recruits, and immature fish. However, there was no difference in mean Ca2+ among female reproductive stages. These results indicate that reproduction of Yelloweye Rockfish is not affected after barotrauma and recompression events and that blood plasma measures show variable success as indicators of sex and female reproductive status.Received March 16, 2016; accepted August 12, 2016 Published online September 30, 2016
Economic Value of Angling on the Colorado River at Lees Ferry: Using Secondary Data to Estimate the Influence of Seasonality
Authors: Bair Lucas S. , Rogowski David L. , Neher Chris 
Published: September 2016

Abstract
Glen Canyon Dam (GCD) on the Colorado River in northern Arizona provides water storage, flood control, and power system benefits to approximately 40 million people who rely on water and energy resources in the Colorado River basin. Downstream resources (e.g., angling, whitewater floating) in Glen Canyon National Recreation Area (GCNRA) and Grand Canyon National Park are impacted by the operation of GCD. The GCD Adaptive Management Program was established in 1997 to monitor and research the effects of dam operations on the downstream environment. We utilized secondary survey data and an individual observation travel cost model to estimate the net economic benefit of angling in GCNRA for each season and each type of angler. As expected, the demand for angling decreased with increasing travel cost; the annual value of angling at Lees Ferry totaled US$2.7 million at 2014 visitation levels. Demand for angling was also affected by season, with per-trip values of $210 in the summer, $237 in the spring, $261 in the fall, and $399 in the winter. This information provides insight into the ways in which anglers are potentially impacted by seasonal GCD operations and adaptive management experiments aimed at improving downstream resource conditions.
Received October 7, 2015; accepted June 13, 2016 Published online September 30, 2016