bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germination behaviour of forbs native to the southwestern United States following exposure to short-term seed bank conditions (−20°C)
Authors: Seglias Alexandra E. , Finch Jessamine , Kramer Andrea T. 
Published: March 2020

AbstractSeeds are increasingly being stored in seed banks for ex situ conservation, food security, and restoration reserves. Although it is hypothesized that seeds of many species can survive the dry, freezer conditions (−20°C) of seed banks for many years, shelf life is unknown for many species. In particular, changes to dormancy and germination requirements following freezer storage have not yet been studied extensively. To improve our understanding of how seed dormancy and germination respond to seed banking conditions, we evaluated seed of six restoration-priority species in the southwestern United States, which is a region of increasing restoration need. Germination tendencies of seeds that were and were not exposed to a −20°C treatment for 4–6 months were evaluated under 22 cold-moist stratification and incubation treatments to broadly assess changes to dormancy and germination requirements and speed. Direct or indirect (via interactions with stratification and/or incubation treatments) differences in dormancy breaking and germination were observed in seeds for four of the six species studied. Specifically, storage temperature accounted for differences in the final germination proportion, germination during stratification, and/or rate of germination in five of the six species. Notably, seeds of the one species that exhibit a combination of physiological and physical dormancy showed significant differences in all germination measures. However, while significant differences were found between seeds exposed to short-term seed bank storage and those that were not, these differences were small and may not be biologically meaningful, indicating that seed banking these species should not change how they are used for restoration or reintroduction purposes.
Seed destruction of weeds in southern US crops using heat and narrow-windrow burning
Authors: Norsworthy Jason K. , Green Jeremy K. , Barber Tom , Roberts Trent L. , Walsh Michael J. 
Published: March 2020

AbstractNarrow-windrow burning has been a successful form of harvest weed seed control in Australian cropping systems, but little is known about the efficacy of narrow-windrow burning on weed seeds infesting U.S. cropping systems. An experiment was conducted using a high-fire kiln that exposed various grass and broadleaf weed seeds to temperatures of 200, 300, 400, 500, and 600 C for 20, 40, 60, and 80 s to determine the temperature and time needed to kill weed seeds. Weeds evaluated included Italian ryegrass, barnyardgrass, johnsongrass, sicklepod, Palmer amaranth, prickly sida, velvetleaf, pitted morningglory, and hemp sesbania. Two field experiments were also conducted over consecutive growing seasons, with the first experiment aimed at determining the amount of heat produced during burning of narrow windrows of soybean harvest residues (chaff and straw) and the effect of this heat on weed seed mortality. The second field experiment aimed to determine the effect of wind speed on the duration and intensity of burning narrow windrows of soybean harvest residues. Following exposure to the highest temperature and longest duration in the kiln, only sicklepod showed any survival (<1% average); however, in most cases, the seeds were completely destroyed (ash). A heat index of only 22,600 was needed to kill all seeds of Palmer amaranth, barnyardgrass, and Italian ryegrass. In the field, all seeds of the evaluated weed species were completely destroyed by narrow-windrow burning of 1.08 to 1.95 kg m−2 of soybean residues. The burn duration of the soybean harvest residues declined as wind speed increased. Findings from the kiln and field experiments show that complete kill is likely for weed seeds concentrated into narrow windrows of burned soybean residues. Given the low cost of implementation of narrow-windrow burning and the seed kill efficacy on various weed species, this strategy may be an attractive option for destroying weed seed.
Treatment response, survival, safety, and predictive factors to chimeric antigen receptor T cell therapy in Chinese relapsed or refractory B cell acute lymphoblast leukemia patients
Authors: Li Limin , Liu Jie , Xu Mengyuan , Yu Hongjuan , Lv Chengfang , Cao Fenglin , Wang Zhenkun , Fu Yueyue , Zhang Mingwen , Meng Hongbin , Zhang Xiaoqian , Kang Liqing , Zhang Zhuo , Li Jinmei , Feng Jiawei , Lian Xin , Yu Lei , Zhou Jin 
Published: March 2020

AbstractThis study aimed to evaluate treatment response, survival, safety profiles, and predictive factors to chimeric antigen receptor T cell (CAR-T) therapy in Chinese patients with relapsed or refractory B cell acute lymphoblast leukemia (R/R B-ALL). 39R/R B-ALL patients who underwent CAR-T therapy were included. Baseline data were collected from patients’ electronic medical records. Patients’ peripheral bloods, bone marrow aspirates, and biopsies were obtained for routine examination, and treatment response and survival profiles as well as adverse events were evaluated. The rates of complete remission (CR), CR with minimal residual disease (MRD) negative/positive, and bridging to hematopoietic stem-cell transplantation (HSCT) were 92.3%, 76.9%, 15.4%, and 43.6%, respectively. The median event-free survival (EFS) was 11.6 months (95% confidence interval (CI): 4.0–19.2 months) and median overall survival (OS) was 14.0 months (95% CI: 10.9–17.1 months). Bridging to HSCT independently predicted better EFS and OS, while high bone marrow blasts level independently predicted worse EFS. The incidence of cytokine release syndrome (CRS) was 97.4%, and refractory disease as well as decreased white blood cell independently predicted higher risk of severe CRS. Other common adverse events included hematologic toxicities (grade I: 5.1%, grade II: 7.7%, grade III: 17.9%, grade IV: 69.2%), neurotoxicity (28.2%), infection (38.5%), and admission for intensive care unit (10.3%). In conclusion, CAR-T therapy presents with promising treatment response, survival and safety profiles, and higher disease burden predicts worse survival as well as increased risk of severe CRS in Chinese R/R B-ALL patients.
Atorvastatin-induced senescence of hepatocellular carcinoma is mediated by downregulation of hTERT through the suppression of the IL-6/STAT3 pathway
Authors: Wang Sin-Ting , Huang Shi-Wei , Liu Kuang-Ting , Lee Teng-Yu , Shieh Jeng-Jer , Wu Chun-Ying 
Published: March 2020

AbstractHepatocellular carcinoma (HCC), a hepatic malignancy, has a poor prognosis and contributes to cancer-related death worldwide. Cellular senescence is an anticancer therapeutic strategy that causes irreversible cell cycle arrest and enables immune-mediated clearance of cancer cells. Atorvastatin, an HMG-CoA reductase inhibitor, has been shown to inhibit tumor growth and induce apoptosis or autophagy in malignant tumors. However, whether atorvastatin can induce HCC cell senescence and the mechanisms involved are poorly understood. The effects of atorvastatin-induced senescence were examined in both HCC cells and mouse xenograft models. The phenomenon and mechanism of senescence were examined by cell cycle analysis, senescence-associated β-galactosidase (SA-β-gal) staining and western blotting in HCC cells, and HCC tissues from mice were analyzed by immunohistochemical (IHC) staining. We demonstrated that atorvastatin induced cell growth inhibition and G0/G1 phase cell cycle arrest, leading to senescence in HCC cells. Atorvastatin-induced senescence was independent of p53, p14, and p16, and atorvastatin not only decreased the secretion of IL-6, a major senescence-associated secretory phenotype (SASP) factor, and the phosphorylation of STAT3 but also inhibited the expression of hTERT, a catalytic subunit of telomerase. Supplementation with exogenous IL-6 reversed both atorvastatin-induced suppression of STAT3 phosphorylation and hTERT expression and atorvastatin-induced senescence. Overexpression of constitutively activated STAT3 rescued HCC cells from atorvastatin-induced hTERT suppression and senescence. Moreover, atorvastatin decreased tumor growth in mouse xenograft models. Consistent with these results, atorvastatin decreased the IL-6, p-STAT3, and hTERT levels and increased β-gal expression in tumor sections. Taken together, these data indicate that atorvastatin can induce atypical cellular senescence in HCC cells to inhibit tumor growth, an effect mediated by downregulation of hTERT through suppression of the IL-6/STAT3 pathway.
Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion
Authors: Xia Shuai , Liu Meiqin , Wang Chao , Xu Wei , Lan Qiaoshuai , Feng Siliang , Qi Feifei , Bao Linlin , Du Lanying , Liu Shuwen , Qin Chuan , Sun Fei , Shi Zhengli , Zhu Yun , Jiang Shibo , Lu Lu 
Published: March 2020

AbstractThe recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell–cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs.
Optical quantum nondemolition measurement of a single rare earth ion qubit
Authors: Raha Mouktik , Chen Songtao , Phenicie Christopher M. , Ourari Salim , Dibos Alan M. , Thompson Jeff D. 
Published: March 2020

AbstractOptically-interfaced spins in the solid state are a promising platform for quantum technologies. A crucial component of these systems is high-fidelity, projective measurement of the spin state. Here, we demonstrate single-shot spin readout of a single rare earth ion qubit, Er3+, which is attractive for its telecom-wavelength optical transition and compatibility with silicon nanophotonic circuits. In previous work with laser-cooled atoms and ions, and solid-state defects, spin readout is accomplished using fluorescence on an optical cycling transition; however, Er3+ and other rare earth ions generally lack strong cycling transitions. We demonstrate that modifying the electromagnetic environment around the ion can increase the strength and cyclicity of the optical transition by several orders of magnitude, enabling single-shot quantum nondemolition readout of the ion’s spin with 94.6% fidelity. We use this readout to probe coherent dynamics and relaxation of the spin.
Gut, oral and skin microbiome of Indian patrilineal families reveal perceptible association with age
Authors: Chaudhari Diptaraj S. , Dhotre Dhiraj P. , Agarwal Dhiraj M. , Gaike Akshay H. , Bhalerao Devika , Jadhav Parmeshwar , Mongad Dattatray , Lubree Himangi , Sinkar Vilas P. , Patil Ulhas K. , Salvi Sundeep , Bavdekar Ashish , Juvekar Sanjay K. , Shouche Yogesh S. 
Published: March 2020

AbstractThe human microbiome plays a key role in maintaining host homeostasis and is influenced by age, geography, diet, and other factors. Traditionally, India has an established convention of extended family arrangements wherein three or more generations, bound by genetic relatedness, stay in the same household. In the present study, we have utilized this unique family arrangement to understand the association of age with the microbiome. We characterized stool, oral and skin microbiome of 54 healthy individuals from six joint families by 16S rRNA gene-based metagenomics. In total, 69 (1.03%), 293 (2.68%) and 190 (8.66%) differentially abundant OTUs were detected across three generations in the gut, skin and oral microbiome, respectively. Age-associated changes in the gut and oral microbiome of patrilineal families showed positive correlations in the abundance of phyla Proteobacteria and Fusobacteria, respectively. Genera Treponema and Fusobacterium showed a positive correlation with age while Granulicatella and Streptococcus showed a negative correlation with age in the oral microbiome. Members of genus Prevotella illustrated high abundance and prevalence as a core OTUs in the gut and oral microbiome. In conclusion, this study highlights that precise and perceptible association of age with microbiome can be drawn when other causal factors are kept constant.
Identification of Small Molecule Enhancers of Immunotherapy for Melanoma
Authors: Dextras Christopher , Dashnyam Myagmarjav , Griner Lesley A. Mathews , Sundaresan Janani , Chim Bryan , Yu Zhiya , Vodnala Suman , Lee Chyi-Chia Richard , Hu Xin , Southall Noel , Marugan Juan J. , Jadhav Ajit , Restifo Nicholas P. , Acquavella Nicolas , Ferrer Marc , Singh Anju 
Published: March 2020

AbstractSmall molecule based targeted therapies for the treatment of metastatic melanoma hold promise but responses are often not durable, and tumors frequently relapse. Response to adoptive cell transfer (ACT)-based immunotherapy in melanoma patients are durable but patients develop resistance primarily due to loss of antigen expression. The combination of small molecules that sustain T cell effector function with ACT could lead to long lasting responses. Here, we have developed a novel co-culture cell-based high throughput assay system to identify compounds that could potentially synergize or enhance ACT-based immunotherapy of melanoma. A BRAFV600E mutant melanoma cell line, SB-3123p which is resistant to Pmel-1-directed ACT due to low gp100 expression levels was used to develop a homogenous time resolve fluorescence (HTRF), screening assay. This high throughput screening assay quantitates IFNγ released upon recognition of the SB-3123p melanoma cells by Pmel-1 CD8+ T-cells. A focused collection of approximately 500 small molecules targeting a broad range of cellular mechanisms was screened, and four active compounds that increased melanoma antigen expression leading to enhanced IFNγ production were identified and their in vitro activity was validated. These four compounds may provide a basis for enhanced immune recognition and design of novel therapeutic approaches for patients with BRAF mutant melanoma resistant to ACT due to antigen downregulation.
Validation of Calprotectin As a Novel Biomarker For The Diagnosis of Pleural Effusion: a Multicentre Trial
Authors: Botana-Rial Maribel , Vázquez-Iglesias Lorena , Casado-Rey Pedro , Cadena María Páez de la , Andrade-Olivié María Amalia , Abal-Arca José , García-Nimo Laura , Ferreiro-Fernández Lucía , Valdés-Cuadrado Luis , San-José María Esther , Rodríguez-Berrocal Francisco Javier , Fernández-Villar Alberto 
Published: March 2020

AbstractDiscriminating between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains difficult. Thus, novel and efficient biomarkers are required for the diagnosis of pleural effusion (PE). The aim of this study was to validate calprotectin as a diagnostic biomarker of PE in clinical settings. A total of 425 patients were recruited, and the pleural fluid samples collected had BPE in 223 cases (53.7%) or MPE in 137 patients (33%). The samples were all analysed following the same previously validated clinical laboratory protocols and methodology. Calprotectin levels ranged from 772.48 to 3,163.8 ng/mL (median: 1,939 ng/mL) in MPE, and 3,216–24,000 ng/mL in BPE (median: 9,209 ng/mL; p < 0.01), with an area under the curve of 0.848 [95% CI: 0.810–0.886]. For a cut-off value of ≤ 6,233.2 ng/mL, we found 96% sensitivity and 60% specificity, with a negative and positive predictive value, and negative and positive likelihood ratios of 96%, 57%, 0.06, and 2.4, respectively. Multivariate analysis showed that low calprotectin levels was a better discriminator of PE than any other variable [OR 28.76 (p < 0.0001)]. Our results confirm that calprotectin is a new and useful diagnostic biomarker in patients with PE of uncertain aetiology which has potential applications in clinical practice because it may be a good complement to cytological methods.
The depletion of ubiquilin in Drosophila melanogaster disturbs neurochemical regulation to drive activity and behavioral deficits
Authors: Jantrapirom Salinee , Enomoto Yosuke , Karinchai Jirarat , Yamaguchi Mizuki , Yoshida Hideki , Fukusaki Eiichiro , Shimma Shuichi , Yamaguchi Masamitsu 
Published: March 2020

AbstractDrosophila melanogaster is a useful and highly tractable model organism for understanding the molecular mechanisms of human diseases. We previously characterized a new dUbqn knockdown model that induces learning-memory and locomotive deficits mediated by impaired proteostasis. Although proteinopathies are the main causes of neurodegenerative diseases, limited information is currently available on the relationship between proteostasis and neurodegenerative-related behavioral perturbations, such as locomotion, wakefulness, and sexual activities. Thus, the present study aimed to elucidate the mechanisms by which dUbqn depletion which is known to cause proteinopathies, affects neurodegenerative-related behavioral perturbations. Pan-neuronal dUbqn-depleted flies showed significantly reduced evening activity along with altered pre- and postsynaptic structural NMJ’s proteins by attenuating signals of Bruchpilot puncta and GluRIIA clustering. In addition, the neurochemical profiles of GABA, glutamate, dopamine, and serotonin were disturbed and these changes also affected courtship behaviors in dUbqn-depleted flies. Collectively, these results extend our understanding on how dUbqn depletion affects neurochemical regulation to drive behavioral disturbances that are generally found in the early stage of neurodegenerative diseases. Moreover, the present study may contribute a novel finding to the design of new agents that prevent disease progression or even treat diseases related to neurodegeneration.
Connexin-43 reduction prevents muscle defects in a mouse model of manifesting Duchenne muscular dystrophy female carriers
Authors: Nouet Julie , Himelman Eric , Lahey Kevin C. , Zhao Qingshi , Fraidenraich Diego 
Published: March 2020

AbstractDuchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder that affects males. However, 8% of female carriers are symptomatic and underrepresented in research due to the lack of animal models. We generated a symptomatic mouse model of DMD carriers via injection ofmdx(murine DMD) embryonic stem cells (ESCs) into wild-type (WT) blastocysts (mdx/WT chimera).mdx/WT chimeras developed cardiomyopathic features and dystrophic skeletal muscle phenotypes including elevated mononuclear invasion, central nucleation, fibrosis and declined forelimb grip strength. The disease was accompanied by connexin-43 (Cx43) aberrantly enhanced in both cardiac and skeletal muscles and remodeled in the heart. Genetic reduction of Cx43-copy number inmdx/WT-Cx43(+/−) chimeras protected them from both cardiac and skeletal muscle fiber damage. In dystrophic skeletal muscle, Cx43 expression was not seen in the fibers but in adjacent F4/80+ mononuclear cells. Ethidium Bromide uptake in purified F4/80+/CD11b+mdxmacrophages revealed functional activity of Cx43, which was inhibited by administration of Gap19 peptide mimetic, a Cx43 hemichannel-specific inhibitor. Thus, we suggest that Cx43 reduction in symptomatic DMD carrier mice leads to prevention of Cx43 remodeling in the heart and prevention of aberrant Cx43 hemichannel activity in the skeletal muscle macrophages neighboring Cx43 non-expressing fibers.
Catalpol protects rat ovarian granulosa cells against oxidative stress and apoptosis through modulating the PI3K/Akt/mTOR signaling pathway
Authors: Yan Jin , Deng Disi , Wu Yeke , Wu Keming , Qu Jie , Li Fei 
Published: March 2020

Abstract
Disrupted follicular development may result in increased follicular atresia, which is a crucial mechanism of various ovarian pathologies. It has been demonstrated that oxidative stress is associated with disrupted follicular development. Catalpol is a natural compound that has been found to possess antioxidative stress. However, the effects of catalpol on oxidative stress-induced disrupted follicular development remain unclear. In the present study, we evaluated the protective effect of catalpol on hydrogen peroxide (H2O2)-induced oxidative damage in granulosa cells (GCs), which play crucial roles in the follicular development. Our results showed that catalpol significantly improved cell viability, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) production, and elevated superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in H2O2-induced GCs. Catalpol treatment caused significant increase in bcl-2 expression, and decreases in bax and caspase-9 expressions. Compared with the H2O2-induced GCs, caspase-3 activity in catalpol-treated cells was markedly decreased. Furthermore, catalpol caused significant activation of PI3K/Akt/mTOR pathway in GCs in response to H2O2 stimulation. Additionally, inhibition of this pathway reversed the inhibitory effects of catalpol on H2O2-induced oxidative injury and apoptosis in GCs. In conclusion, these findings suggested that catalpol protected GCs from H2O2-induced oxidative injury and apoptosis via activating PI3K/Akt/mTOR signaling pathway. Thus, catalpol might serve as a therapeutic approach for regulating disrupted follicular development.