bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chiral phosphoric acid catalyzed aminative dearomatization of α-naphthols/Michael addition sequence
Authors: Xia Zi-Lei , Zheng Chao , Xu Ren-Qi , You Shu-Li 
Published: July 2019

AbstractAsymmetric dearomatization reactions have recently emerged as a powerful tool for the rapid build-up of the molecular complexity. Chiral three-dimensional polycyclic molecules bearing contiguous stereogenic centers can be synthesized from readily available planar aromatic feedstocks. Here we report that an intermolecular asymmetric dearomatization reaction ofα-naphthols bearing a tethered nucleophile at the C4 position of the naphthol ring is achieved by a chiral phosphoric acid. The reaction proceeds via a highly chemo- and regioselective aminative dearomatization/Michael addition sequence, affording a wide array of functionalized cyclic ketones in good yields (up to 93%) with excellent enantioselectivity (up to >99% ee). The catalyst loading can be reduced to 0.1 mol%. Preliminary mechanistic investigations identify that the enantioselectivity is established in the dearomatization step, while the Michael addition is the rate-limiting step. A working model accounting for the origin of the stereochemistry is proposed based on DFT calculations.
Pulse control protocols for preserving coherence in dipolar-coupled nuclear spin baths
Authors: Waeber A. M. , Gillard G. , Ragunathan G. , Hopkinson M. , Spencer P. , Ritchie D. A. , Skolnick M. S. , Chekhovich E. A. 
Published: July 2019

AbstractCoherence of solid state spin qubits is limited by decoherence and random fluctuations in the spin bath environment. Here we develop spin bath control sequences which simultaneously suppress the fluctuations arising from intrabath interactions and inhomogeneity. Experiments on neutral self-assembled quantum dots yield up to a five-fold increase in coherence of a bare nuclear spin bath. Numerical simulations agree with experiments and reveal emergent thermodynamic behaviour where fluctuations are ultimately caused by irreversible conversion of coherence into many-body quantum entanglement. Simulations show that for homogeneous spin baths our sequences are efficient with non-ideal control pulses, while inhomogeneous bath coherence is inherently limited even under ideal-pulse control, especially for strongly correlated spin-9/2 baths. These results highlight the limitations of self-assembled quantum dots and advantages of strain-free dots, where our sequences can be used to control the fluctuations of a homogeneous nuclear spin bath and potentially improve electron spin qubit coherence.
The genome assembly of asparagus bean, Vigna unguiculata ssp. sesquipedialis
Authors: Xia Qiuju , Pan Lei , Zhang Ru , Ni Xuemei , Wang Yangzi , Dong Xiao , Gao Yun , Zhang Zhe , Kui Ling , Li Yong , Wang Wen , Yang Huanming , Chen Chanyou , Miao Jianhua , Chen Wei , Dong Yang 
Published: July 2019

AbstractAsparagus bean (Vigna. unguiculata ssp. sesquipedialis), known for its very long and tender green pods, is an important vegetable crop broadly grown in the developing Asian countries. In this study, we reported a 632.8 Mb assembly (549.81 Mb non-N size) of asparagus bean based on the whole genome shotgun sequencing strategy. We also generated a linkage map for asparagus bean, which helped anchor 94.42% of the scaffolds into 11 pseudo-chromosomes. A total of 42,609 protein-coding genes and 3,579 non-protein-coding genes were predicted from the assembly. Taken together, these genomic resources of asparagus bean will help develop a pan-genome of V. unguiculata and facilitate the investigation of economically valuable traits in this species, so that the cultivation of this plant would help combat the protein and energy malnutrition in the developing world.
Speckle modulation enables high-resolution wide-field human brain tumor margin detection and in vivo murine neuroimaging
Authors: Yecies Derek , Liba Orly , SoRelle Elliott D. , Dutta Rebecca , Yuan Edwin , Vogel Hannes , Grant Gerald A. , de la Zerda Adam 
Published: July 2019

AbstractCurrentin vivoneuroimaging techniques provide limited field of view or spatial resolution and often require exogenous contrast. These limitations prohibit detailed structural imaging across wide fields of view and hinder intraoperative tumor margin detection. Here we present a novel neuroimaging technique, speckle-modulating optical coherence tomography (SM-OCT), which allows us to image the brains of live mice andex vivohuman samples with unprecedented resolution and wide field of view using only endogenous contrast. The increased visibility provided by speckle elimination reveals white matter fascicles and cortical layer architecture in brains of live mice. To our knowledge, the data reported herein represents the highest resolution imaging of murine white matter structure achievedin vivoacross a wide field of view of several millimeters. When applied to an orthotopic murine glioblastoma xenograft model, SM-OCT readily identifies brain tumor margins with resolution of approximately 10 μm. SM-OCT ofex vivohuman temporal lobe tissue reveals fine structures including cortical layers and myelinated axons. Finally, when applied to anex vivosample of a low-grade glioma resection margin, SM-OCT is able to resolve the brain tumor margin. Based on these findings, SM-OCT represents a novel approach for intraoperative tumor margin detection andin vivoneuroimaging.
Telomere length in early childhood is associated with sex and ethnicity
Authors: Ly Kien , Walker Caroline , Berry Sarah , Snell Russell , Marks Emma , Thayer Zaneta , Atatoa-Carr Polly , Morton Susan 
Published: July 2019

AbstractTelomeres are repetitive DNA sequences at the end of chromosomes that function to protect chromosomes from degradation. Throughout the life course, telomere length decreases with age and is influenced by environmental factors and health conditions. This study aimed to determine the relative telomere lengths in a diverse cohort of about 4000 four-year-old children in New Zealand. Linear regression was used to investigate the relationship between telomere length, child gender, ethnicity, paternal age and deprivation. We observed substantial variation in telomere length according to sex and self-identified ethnicity. Telomere length was longer in females compared to males (coefficient of 0.042, 95% confidence interval (CI) 0.024–0.060). European children had shorter telomere than both the indigenous Māori (coefficient of 0.03, CI 0.007–0.055) and Pacific children (coefficient of 0.15, CI 0.12–0.18). The data suggest that telomere lengths are highly variable and variability between individuals arise from early age, influenced partly by sex and ethnicity. Longer telomeres in indigenous Māori and Pacific children may reflect the heritability of telomere length in genetically less complex populations. This study increases our understanding of telomere dynamics in young children since the majority of telomere studies are conducted in adults.
A novel approach for geographical risk mapping of morbidity and mortality rates: the case of Val D’Agri, Italy
Authors: Duggento Andrea , Toschi Nicola , Pietroiusti Antonio , Musmeci Loredana , Buonomo Ersilia , Moramarco Stefania , Lucaroni Francesca , Boffetta Paolo , Palombi Leonardo 
Published: July 2019

AbstractWhile associations between exposure to air pollutants and increased morbidity and mortality are well established, few rigorous studies on this issue are available. The aim of the current study is to implement a new approach to the spatial analysis of mortality and morbidity, based on testing for the presence of the same association in other areas of similar size. Additionally, we perform a case study in Val d’Agri (VA), an area of Basilicata Region, Southern Italy, where oil and natural gas extraction began in 1998. In order to examine the spatial distribution of morbidity and mortality in the region of interest, Hospital discharge (2001–2013) and mortality (2003–2014) rates for the main environment-related diseases were calculated. In addition, a comparison between the period 1980–1998 and the period 1999–2014 was performed for cardiovascular disease mortality. For the period under study, a neutral scenario emerged for cancer and respiratory diseases, where we found no differences in morbidity and mortality as compared to the national benchmark. In some cases significantly lower values (as compared to the nation-wide benchmark) were found. Conversely, a slight excess in morbidity and mortality (as compared to the nation-wide benchmark) emerged for cardiovascular diseases. Still, this excess was common to a number of municipalities in the surroundings of VA, and appeared to be already present in 1980. Higher rates of cardiovascular diseases, lower rates of neoplastic disorders no differences in mortality for respiratory causes (as compared to the nation-wide benchmark) were found in multiple areas of the region, and were therefore not specific to VA. In summary, our data do not support the hypothesis of a role of industrial activities related to oil extraction in VA in determining mortality and morbidity patterns and trends.
Crucial Role of NLRP3 Inflammasome in the Development of Peritoneal Dialysis-related Peritoneal Fibrosis
Authors: Hishida Erika , Ito Homare , Komada Takanori , Karasawa Tadayoshi , Kimura Hiroaki , Watanabe Sachiko , Kamata Ryo , Aizawa Emi , Kasahara Tadashi , Morishita Yoshiyuki , Akimoto Tetsu , Nagata Daisuke , Takahashi Masafumi 
Published: July 2019

AbstractLong-term peritoneal dialysis (PD) therapy leads to peritoneal inflammation and fibrosis. However, the mechanism underlying PD-related peritoneal inflammation and fibrosis remains unclear. NLRP3 inflammasome regulates the caspase-1-dependent release of interleukin-1β and mediates inflammation in various diseases. Here, we investigated the role of NLRP3 inflammasome in a murine model of PD-related peritoneal fibrosis induced by methylglyoxal (MGO). Inflammasome-related proteins were upregulated in the peritoneum of MGO-treated mice. MGO induced parietal and visceral peritoneal fibrosis in wild-type mice, which was significantly reduced in mice deficient in NLRP3, ASC, and interleukin-1β (IL-1β). ASC deficiency reduced the expression of inflammatory cytokines and fibrotic factors, and the infiltration of macrophages. However, myeloid cell-specific ASC deficiency failed to inhibit MGO-induced peritoneal fibrosis. MGO caused hemorrhagic ascites, fibrin deposition, and plasminogen activator inhibitor-1 upregulation, but all of these manifestations were inhibited by ASC deficiency. Furthermore, in vitro experiments showed that MGO induced cell death via the generation of reactive oxygen species in vascular endothelial cells, which was inhibited by ASC deficiency. Our results showed that endothelial NLRP3 inflammasome contributes to PD-related peritoneal inflammation and fibrosis, and provide new insights into the mechanisms underlying the pathogenesis of this disorder.
Quantifying hexagonal stacking in diamond
Authors: Murri Mara , Smith Rachael L. , McColl Kit , Hart Martin , Alvaro Matteo , Jones Adrian P. , Németh Péter , Salzmann Christoph G. , Corà Furio , Domeneghetti Maria C. , Nestola Fabrizio , Sobolev Nikolay V. , Vishnevsky Sergey A. , Logvinova Alla M. , McMillan Paul F. 
Published: July 2019

AbstractDiamond is a material of immense technological importance and an ancient signifier for wealth and societal status. In geology, diamond forms as part of the deep carbon cycle and typically displays a highly ordered cubic crystal structure. Impact diamonds, however, often exhibit structural disorder in the form of complex combinations of cubic and hexagonal stacking motifs. The structural characterization of such diamonds remains a challenge. Here, impact diamonds from the Popigai crater were characterized with a range of techniques. Using the MCDIFFaX approach for analysing X-ray diffraction data, hexagonality indices up to 40% were found. The effects of increasing amounts of hexagonal stacking on the Raman spectra of diamond were investigated computationally and found to be in excellent agreement with trends in the experimental spectra. Electron microscopy revealed nanoscale twinning within the cubic diamond structure. Our analyses lead us to propose a systematic protocol for assigning specific hexagonality attributes to the mineral designated as lonsdaleite among natural and synthetic samples.
Eye tracking in an everyday environment reveals the interpersonal distance that affords infant-parent gaze communication
Authors: Yamamoto Hiroki , Sato Atsushi , Itakura Shoji 
Published: July 2019

AbstractThe unique morphology of human eyes enables gaze communication at various ranges of interpersonal distance. Although gaze communication contributes to infants’ social development, little is known about how infant-parent distance affects infants’ visual experience in daily gaze communication. The present study conducted longitudinal observations of infant-parent face-to-face interactions in the home environment as 5 infants aged from 10 to 15.5 months. Using head-mounted eye trackers worn by parents, we evaluated infants’ daily visual experience of 3138 eye contact scenes recorded from the infants’ second-person perspective. The results of a hierarchical Bayesian statistical analysis suggest that certain levels of interpersonal distance afforded smooth interaction with eye contact. Eye contacts were not likely to be exchanged when the infant and parent were too close or too far apart. The number of continuing eye contacts showed an inverse U-shaped pattern with interpersonal distance, regardless of whether the eye contact was initiated by the infant or the parent. However, the interpersonal distance was larger when the infant initiated the eye contact than when the parent initiated it, suggesting that interpersonal distance affects the infant’s and parent’s social look differently. Overall, the present study indicates that interpersonal distance modulates infant-parent gaze communication.
Hypoxia-induced Downregulation of SRC-3 Suppresses Trophoblastic Invasion and Migration Through Inhibition of the AKT/mTOR Pathway: Implications for the Pathogenesis of Preeclampsia
Authors: He Chengjin , Shan Nan , Xu Ping , Ge Huisheng , Yuan Yu , Liu Yangming , Zhang Pu , Wen Li , Zhang Fumei , Xiong Liling , Peng Chuan , Qi Hongbo , Tong Chao , Baker Philip N. 
Published: July 2019

AbstractPreeclampsia (PE) is characterized by poor placentation, consequent on aberrant extravillous trophoblast (EVT) cell function during placental development. The SRC family of proteins is important during pregnancy, especially SRC-3, which regulates placental morphogenesis and embryo survival. Although SRC-3 expression in mouse trophoblast giant cells has been documented, its role in the functional regulation of extravillous trophoblasts and the development of PE remains unknown. This study found that SRC-3 expression was significantly lower in placentas from PE pregnancies as compared to uncomplicated pregnancies. Additionally, both CoCl2-mimicked hypoxia and suppression of endogenous SRC-3 expression by lentivirus short hairpin RNA attenuated the migration and invasion abilities of HTR-8/SVneo cells. Moreover, we demonstrated that SRC-3 physically interacts with AKT to regulate the migration and invasion of HTR-8 cells, via the AKT/mTOR pathway. We also found that the inhibition of HTR-8 cell migration and invasion by CoCl2-mimicked hypoxia was through the SRC-3/AKT/mTOR axis. Our findings indicate that, in early gestation, accumulation of HIF-1α inhibits the expression of SRC-3, which impairs extravillous trophoblastic invasion and migration by directly interacting with AKT. This potentially leads to insufficient uterine spiral artery remodeling and placental hypoperfusion, and thus the development of PE.
Knockout of glucosidase II beta subunit inhibits growth and metastatic potential of lung cancer cells by inhibiting receptor tyrosine kinase activities
Authors: Khaodee Worapong , Udomsom Suruk , Kunnaja Phraepakaporn , Cressey Ratchada 
Published: July 2019

AbstractGlucosidase II (GluII) plays a major role in regulating post-translation modification of N-linked glycoproteins. We have previously reported that the expression of glucosidase II beta subunit (GluIIβ) was significantly increased in lung tumor tissues and its suppression triggers autophagy and/or apoptosis. Here, we investigated the role of GluIIβ in cell growth, metastatic potential, and receptor tyrosine kinases (RTKs) signaling activity in lung carcinoma cell lines. CRISPR-CAS9 technology was used to knockout the GluIIβ encoding gene (PRKSH) in lung carcinoma cells. GluIIβ knockout cells exhibited drastically slower growth rates in comparison to non-target transfected cells, particularly with lower concentrations of fetal bovine serum, indicating impairment of their ability to survive under nutritional deprivation. Cell migration and anchorage-independent growth, the fundamental components of cancer cell metastasis, were significantly decreased in GluIIβ knockout cells. Knockout of GluIIβ increased the sensitivity of lung cancer cells to cisplatin but reduced their sensitivity to gefitinib. Interestingly, knocking out of GluIIβ lowered overall RTK signaling activities to less than half of those in non-target transfected cells, which could represent a novel strategy for blocking multiple RTKs in tumor cells in an effort to improve lung cancer treatment.
Discrete Changes in Glucose Metabolism Define Aging
Authors: Ravera Silvia , Podestà Marina , Sabatini Federica , Dagnino Monica , Cilloni Daniela , Fiorini Samuele , Barla Annalisa , Frassoni Francesco 
Published: July 2019

AbstractAging is a physiological process in which multifactorial processes determine a progressive decline. Several alterations contribute to the aging process, including telomere shortening, oxidative stress, deregulated autophagy and epigenetic modifications. In some cases, these alterations are so linked with the aging process that it is possible predict the age of a person on the basis of the modification of one specific pathway, as proposed by Horwath and his aging clock based on DNA methylation. Because the energy metabolism changes are involved in the aging process, in this work, we propose a new aging clock based on the modifications of glucose catabolism. The biochemical analyses were performed on mononuclear cells isolated from peripheral blood, obtained from a healthy population with an age between 5 and 106 years. In particular, we have evaluated the oxidative phosphorylation function and efficiency, the ATP/AMP ratio, the lactate dehydrogenase activity and the malondialdehyde content. Further, based on these biochemical markers, we developed a machine learning-based mathematical model able to predict the age of an individual with a mean absolute error of approximately 9.7 years. This mathematical model represents a new non-invasive tool to evaluate and define the age of individuals and could be used to evaluate the effects of drugs or other treatments on the early aging or the rejuvenation.
IL-17C-mediated innate inflammation decreases the response to PD-1 blockade in a model of Kras-driven lung cancer
Authors: Ritzmann Felix , Jungnickel Christopher , Vella Giovanna , Kamyschnikow Andreas , Herr Christian , Li Dong , Menger Michael M. , Angenendt Adrian , Hoth Markus , Lis Annette , Bals Robert , Beisswenger C. 
Published: July 2019

AbstractChronic obstructive pulmonary disease (COPD) is associated with neutrophilic lung inflammation and CD8 T cell exhaustion and is an important risk factor for the development of non-small cell lung cancer (NSCLC). The clinical response to programmed cell death-1 (PD-1) blockade in NSCLC patients is variable and likely affected by a coexisting COPD. The pro-inflammatory cytokine interleukin-17C (IL-17C) promotes lung inflammation and is present in human lung tumors. Here, we used a Kras-driven lung cancer model to examine the function of IL-17C in inflammation-promoted tumor growth. Genetic ablation of Il-17c resulted in a decreased recruitment of inflammatory cells into the tumor microenvironment, a decreased expression of tumor-promoting cytokines (e.g. interleukin-6 (IL-6)), and a reduced tumor proliferation in the presence of Haemophilus influenzae- (NTHi) induced COPD-like lung inflammation. Chronic COPD-like inflammation was associated with the expression of PD-1 in CD8 lymphocytes and the membrane expression of the programmed death ligand (PD-L1) independent of IL-17C. Tumor growth was decreased in Il-17c deficient mice but not in wildtype mice after anti-PD-1 treatment. Our results suggest that strategies targeting innate immune mechanisms, such as blocking of IL-17C, may improve the response to anti-PD-1 treatment in lung cancer patients.
Notch Inhibition Prevents Differentiation of Human Limbal Stem/Progenitor Cells in vitro
Authors: González Sheyla , Uhm Heui , Deng Sophie X. 
Published: July 2019

AbstractNotch signaling has been shown to regulate the homeostasis and wound healing of the corneal epithelium. We investigated the effect of Notch inhibition in the human limbal stem/progenitor cells (LSCs) in vitro by using small molecules. Treatment of the LSCs with DAPT and SAHM1 reduced the proliferation rate and maintained the undifferentiated state of the LSCs in a concentration dependent manner. Stratification and differentiation of the corneal epithelium were not reduced after Notch inhibition, indicating that the function of the corneal basal cells is retained. Our findings suggest that Notch signaling plays a role in the proliferation and maintenance of LSCs.
Improved detection of common variants in coronary artery disease and blood pressure using a pleiotropy cFDR method
Authors: Mao Xiang-Jie , Zhang Qiang , Xu Fei , Gao Pan , Sun Nan , Wang Bo , Tang Qi-Xin , Hao Yi-Bin , Sun Chang-Qing 
Published: July 2019

AbstractPlenty of genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms (SNPs) for coronary artery disease (CAD) and blood pressure (BP). However, these SNPs only explain a small proportion of the heritability of two traits/diseases. Although high BP is a major risk factor for CAD, the genetic intercommunity between them remain largely unknown. To recognize novel loci associated with CAD and BP, a genetic-pleiotropy-informed conditional false discovery rate (cFDR) method was applied on two summary statistics of CAD and BP from existing GWASs. Stratified Q-Q and fold enrichment plots showed a high pleiotropic enrichment of SNPs associated with two traits. Adopting a cFDR of 0.05 as a threshold, 55 CAD-associated loci (25 variants being novel) and 47 BP loci (18 variants being novel) were identified, 25 of which were pleiotropic loci (13 variants being novel) for both traits. Among the 32 genes these 25 SNPs were annotated to, 20 genes were newly detected compared to previous GWASs. This study showed the cFDR approach could improve gene discovery by incorporating GWAS datasets of two related traits. These findings may provide novel understanding of etiology relationships between CAD and BP.