bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revealing electronic state-switching at conical intersections in alkyl iodides by ultrafast XUV transient absorption spectroscopy
Authors: Chang Kristina F. , Reduzzi Maurizio , Wang Han , Poullain Sonia M. , Kobayashi Yuki , Barreau Lou , Prendergast David , Neumark Daniel M. , Leone Stephen R. 
Published: August 2020

AbstractConical intersections between electronic states often dictate the chemistry of photoexcited molecules. Recently developed sources of ultrashort extreme ultraviolet (XUV) pulses tuned to element-specific transitions in molecules allow for the unambiguous detection of electronic state-switching at a conical intersection. Here, the fragmentation of photoexcited iso-propyl iodide and tert-butyl iodide molecules (i-C3H7I and t-C4H9I) through a conical intersection between 3Q0/1Q1 spin–orbit states is revealed by ultrafast XUV transient absorption measuring iodine 4d core-to-valence transitions. The electronic state-sensitivity of the technique allows for a complete mapping of molecular dissociation from photoexcitation to photoproducts. In both molecules, the sub-100 fs transfer of a photoexcited wave packet from the 3Q0 state into the 1Q1 state at the conical intersection is captured. The results show how differences in the electronic state-switching of the wave packet in i-C3H7I and t-C4H9I directly lead to differences in the photoproduct branching ratio of the two systems.
Children’s family income is associated with cognitive function and volume of anterior not posterior hippocampus
Authors: Decker Alexandra L. , Duncan Katherine , Finn Amy S. , Mabbott Donald J. 
Published: August 2020

AbstractChildren from lower income backgrounds tend to have poorer memory and language abilities than their wealthier peers. It has been proposed that these cognitive gaps reflect the effects of income-related stress on hippocampal structure, but the empirical evidence for this relationship has not been clear. Here, we examine how family income gaps in cognition relate to the anterior hippocampus, given its high sensitivity to stress, versus the posterior hippocampus. We find that anterior (but not posterior) hippocampal volumes positively correlate with family income up to an annual income of ~$75,000. Income-related differences in the anterior (but not posterior) hippocampus also predicted the strength of the gaps in memory and language. These findings add anatomical specificity to current theories by suggesting a stronger relationship between family income and anterior than posterior hippocampal volumes and offer a potential mechanism through which children from different income homes differ cognitively.
Neural mechanisms underlying the effects of physical fatigue on effort-based choice
Authors: Hogan Patrick S. , Chen Steven X. , Teh Wen Wen , Chib Vikram S. 
Published: August 2020

AbstractPhysical fatigue crucially influences our decisions to partake in effortful action. However, there is a limited understanding of how fatigue impacts effort-based decision-making at the level of brain and behavior. We use functional magnetic resonance imaging to record markers of brain activity while human participants engage in uncertain choices for prospective physical effort, before and after bouts of exertion. Using computational modeling of choice behavior we find that fatiguing exertions cause participants to increase their subjective cost of effort, compared to a baseline/rested state. We describe a mechanism by which signals related to motor cortical state in premotor cortex influence effort value computations, instantiated by insula, thereby increasing an individual’s subjective valuation of prospective physical effort while fatigued. Our findings provide a neurobiological account of how information about bodily state modulates decisions to engage in physical activity.
A high-content image-based drug screen of clinical compounds against cell transmission of adenovirus
Authors: Georgi Fanny , Kuttler Fabien , Murer Luca , Andriasyan Vardan , Witte Robert , Yakimovich Artur , Turcatti Gerardo , Greber Urs F. 
Published: August 2020

AbstractHuman adenoviruses (HAdVs) are fatal to immuno-suppressed individuals, but no effective anti-HAdV therapy is available. Here, we present a novel image-based high-throughput screening (HTS) platform, which scores the full viral replication cycle from virus entry to dissemination of progeny and second-round infections. We analysed 1,280 small molecular weight compounds of the Prestwick Chemical Library (PCL) for interference with HAdV-C2 infection in a quadruplicate, blinded format, and performed robust image analyses and hit filtering. We present the entire set of the screening data including all images, image analyses and data processing pipelines. The data are made available at the Image Data Resource (IDR, idr0081). Our screen identified Nelfinavir mesylate as an inhibitor of HAdV-C2 multi-round plaque formation, but not single round infection. Nelfinavir has been FDA-approved for anti-retroviral therapy in humans. Our results underscore the power of image-based full cycle infection assays in identifying viral inhibitors with clinical potential.
RNA N6-methyladenosine modification is required for miR-98/MYCN axis-mediated inhibition of neuroblastoma progression
Authors: Cheng Junmei , Xu Lingling , Deng Liqiang , Xue Lan , Meng Qingmei , Wei Furong , Wang Jinghua 
Published: August 2020

AbstractNeuroblastoma (NB) is one of the most common malignant tumors of the sympathetic nervous system in childhood. NB severely threatens patient’s health and life. However, more effective diagnosis and treatment methods are badly needed in clinics all over the world. MYCN is well recognized as a genetic biomarker of high risk and poor outcome in NB. miRNAs are small RNAs and miR-98 involved in the pathogenesis of various cancers. The role and mechanism of miR-98 in NB remains to be investigated. Here we found that miR-98 was decreased in human MYCN-high-expression NB tissues, and its down-regulation was associated with poor prognosis of NB. Over-expression of miR-98 inhibited cell proliferation, migration and invasion of NB cells. The analysis by employing the software of miRanda predicted the possible binding sites of miR-98 in the 3′-UTR of MYCN, and experimental data illustrated that miR-98 directly bound to MYCN 3′-UTR and decreased MYCN expression. Over-expression of MYCN rescued the decreased malignant phenotype caused by over-expression of miR-98 in NB. N6-methyladenosine modification in 3′-UTR of MYCN promoted its interaction with miR-98. The data collectively demonstrated that RNA m6A modification was required for miR-98/MYCN axis-mediated inhibition of neuroblastoma progression, and miR-98 might be novel targets for NB detection and treatment.
Identification and the potential involvement of miRNAs in the regulation of artemisinin biosynthesis in A. annua
Authors: Khan Shazia , Ali Athar , Saifi Monica , Saxena Parul , Ahlawat Seema , Abdin Malik Zainul 
Published: August 2020

AbstractMicro RNAs (miRNAs) play crucial regulatory roles in multiple biological processes. Recently they have garnered the attention for their strong influence on the secondary metabolite production in plants. Their role in the regulation of artemisinin (ART) biosynthesis is, however, not fully elucidated. ART is a potent anti-malarial compound recommended by WHO for the treatment of drug-resistant malaria. It is produced by Artemisia annua (A. annua). The lower in planta content of ART necessitates a deep understanding of regulatory mechanisms involved in the biosynthesis of this metabolite. In this study, using modern high throughput small RNA-sequencing by Illumina Nextseq 500 platform for identification and stem-loop RT PCR for validation, miRNAs were identified in the leaf sample of A. annua plant. Here, we report a total of 121 miRNAs from A. annua that target several important genes and transcription factors involved in the biosynthesis of ART. This study revealed the presence of some important conserved miRNA families, miR396, miR319, miR399, miR858, miR5083 and miR6111 not identified so far in A. annua. The expression patterns and correlation between miRNAs and their corresponding targets at different developmental stages of the plant using real-time PCR indicate that they may influence ART accumulation. These findings thus, open new possibilities for the rational engineering of the secondary metabolite pathways in general and ART biosynthesis in particular.
Influence of 16S rRNA target region on the outcome of microbiome studies in soil and saliva samples
Authors: Soriano-Lerma Ana , Pérez-Carrasco Virginia , Sánchez-Marañón Manuel , Ortiz-González Matilde , Sánchez-Martín Victoria , Gijón Juan , Navarro-Mari José María , García-Salcedo José Antonio , Soriano Miguel 
Published: August 2020

AbstractNext generation sequencing methods are widely used in evaluating the structure and functioning of microbial communities, especially those centered on 16S rRNA subunit. Since Illumina Miseq, the most used sequencing platform, does not allow the full sequencing of 16S rRNA gene, this study aims to evaluate whether the choice of different target regions might affect the outcome of microbiome studies regarding soil and saliva samples. V1V3, V3V4, V4V5 and V6V8 domains were studied, finding that while some regions showed differences in the detection of certain bacterial taxa and in the calculation of alpha diversity, especially in soil samples, the overall effect did not compromise the differentiation of any sample type in terms of taxonomic analysis at the genus level. 16S rRNA target regions did affect the detection of specific bacteria related to soil quality and development, and microbial genera used as health biomarkers in saliva. V1V3 region showed the closest similarity to internal sequencing control mock community B, suggesting it might be the most preferable choice regarding data reliability.
Distribution of estrogen receptor in the rabbit cervix during pregnancy with special reference to stromal elements: an immunohistochemical study
Authors: Mustafa Fatma El-Zahraa A. , Elhanbaly Ruwaida 
Published: August 2020

AbstractThe estrogen plays a critical role during pregnancy through their receptors. Although the rabbit is one of the most important lab animal estrogen receptor alpha (ERA) localization on basic cells, newly discovered cells including telocyte and neuroendocrine cells, vascular compartments and interstitium during pregnancy not been described. At 0 day pregnancy, the most prominent immunoreactivity was moderate to ERA and observed on the ciliated cells, secretory cells, blood plasma, and interstitium. The smooth muscles and the endothelial cells showed mild immunoreactivity to ERA. Lymphocytes only exhibited strong immunoreactivity to ERA. At 7 days pregnancy moderate immunoreactivity to ERA observed on ciliated cells, secretory cells, smooth muscles, interstitium, and lymphocytes. Strong immunoreactivity to ERA detected on endothelial cells and blood plasma. At 14 days of pregnancy, the most prominent immunoreactivity was strong and detected on ciliated cells, smooth muscles, lymphocytes, and interstitium. Moderate immunoreactivity detected on endothelial cells and blood plasma. Secretory cells only exhibited mild immunoreactivity to ERA. At 21 days of pregnancy, the immunoreactivity to ERA ranged between mild on ciliated cells, smooth muscles, blood plasma and interstitium and negative on secretory cells, endothelial cells and lymphocytes. Our results indicated that the frequency and intensity of ERA immunostaining in the rabbit cervix varied on different structural compartments of the cervix during different pregnancy stages.
Unlike Zika, Chikungunya virus interferes in the viability of Aedes aegypti eggs, regardless of females’ age
Authors: Resck Maria Eduarda Barreto , Padilha Karine Pedreira , Cupolillo Aline Possati , Talyuli Octávio A. C. , Ferreira-de-Brito Anielly , Lourenço-de-Oliveira Ricardo , Farnesi Luana Cristina , Bruno Rafaela Vieira 
Published: August 2020

AbstractChikungunya and Zika are arboviruses transmitted by the mosquitoAedes aegypti. Mosquito fecundity and egg viability are important parameters of vectorial capacity. Here we aim to understand, comparatively, the effects of Chikungunya virus (CHIKV) and Zika virus (ZIKV) infections on the fecundity and fertility of young and oldAedes aegyptifemales. Using artificial infection blood feeding experiments we observed that both CHIKV and ZIKV do not alter the number of eggs laid when compared to uninfected females, although the egg fertility significantly decreases in both young and old CHIKV-infected females. There is an upward trend of null females (infertile females) from 2.1% in young to 6.8% in old ZIKV-infected females. Together, our data revealed that CHIKV and ZIKV affects differentlyAe. aegyptiphysiology, that may be related to different viral spread in nature.
Radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate for PET imaging of folate receptor β-positive macrophages
Authors: Moisio Olli , Palani Senthil , Virta Jenni , Elo Petri , Liljenbäck Heidi , Tolvanen Tuula , Käkelä Meeri , Miner Maxwell G. , Herre Erika Atencio , Marjamäki Päivi , Örd Tiit , Heinäniemi Merja , Kaikkonen Minna U. , Zhang Fenghua , Srinivasarao Madduri , Knuuti Juhani , Low Philip S. , Saraste Antti , Li Xiang-Guo , Roivainen Anne 
Published: August 2020

AbstractFolate receptor β (FR-β), a marker expressed on macrophages, is a promising target for imaging of inflammation. Here, we report the radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate (68Ga-FOL). After determining the affinity of 68Ga-FOL using cells expressing FR-β, we studied atherosclerotic mice with 68Ga-FOL and 18F-FDG PET/CT. In addition, we studied tracer distribution and co-localization with macrophages in aorta cryosections using autoradiography, histology, and immunostaining. The specificity of 68Ga-FOL was assessed in a blocking study with folate glucosamine. As a final step, human radiation doses were extrapolated from rat PET data. We were able to produce 68Ga-FOL with high radiochemical purity and moderate molar activity. Cell binding studies revealed that 68Ga-FOL had 5.1 nM affinity for FR-β. Myocardial uptake of 68Ga-FOL was 20-fold lower than that of 18F-FDG. Autoradiography and immunohistochemistry of the aorta revealed that 68Ga-FOL radioactivity co-localized with Mac-3–positive macrophage-rich atherosclerotic plaques. The plaque-to-healthy vessel wall ratio of 68Ga-FOL was significantly higher than that of 18F-FDG. Blocking studies verified that 68Ga-FOL was specific for FR. Based on estimations from rat data, the human effective dose was 0.0105 mSv/MBq. Together, these findings show that 68Ga-FOL represents a promising new FR-β–targeted tracer for imaging macrophage-associated inflammation.
A single-center retrospective safety analysis of cyclin-dependent kinase 4/6 inhibitors concurrent with radiation therapy in metastatic breast cancer patients
Authors: Guerini Andrea Emanuele , Pedretti Sara , Salah Emiliano , Simoncini Edda Lucia , Maddalo Marta , Pegurri Ludovica , Pedersini Rebecca , Vassalli Lucia , Pasinetti Nadia , Peretto Gloria , Triggiani Luca , Costantino Gianluca , Figlia Vanessa , Alongi Filippo , Magrini Stefano Maria , Buglione Michela 
Published: August 2020

AbstractCyclin dependent kinases 4/6 (CDK4/6) inhibitors gained an essential role in the treatment of metastatic breast cancer. Nevertheless, data regarding their use in combination with radiotherapy are still scarce. We performed a retrospective preliminary analysis of breast cancer patients treated at our Center with palliative radiation therapy and concurrent CDK4/6 inhibitors. Toxicities were measured according to CTCAE 4.0, local response according to RECIST 1.1 or PERCIST 1.0 and pain control using verbal numeric scale. 18 patients (32 treated sites) were identified; 50% received palbociclib, 33.3% ribociclib and 16.7% abemacliclib. Acute non-hematologic toxicity was fair, with the only exception of a patient who developed G3 ileitis. During 3 months following RT, 61.1% of patients developed G 3–4 neutropenia; nevertheless no patient required permanent suspension of treatment. Pain control was complete in 88.2% of patients three months after radiotherapy; 94.4% of patients achieved and maintained local control of disease. Radiotherapy concomitant to CDK4/6 inhibitors is feasible and characterized by a fair toxicity profile, with isolated episodes of high-grade reversible intestinal toxicity. Rate of G 3–4 neutropenia was comparable with that measured for CDK4/6 inhibitors alone. Promising results were reported in terms of pain relief and local control of disease.
Incidence, determinants and prognostic relevance of dyspnea at admission in patients with Takotsubo syndrome: results from the international multicenter GEIST registry
Authors: Arcari Luca , Musumeci Maria Beatrice , Stiermaier Thomas , El-Battrawy Ibrahim , Möller Christian , Guerra Federico , Novo Giuseppina , Mariano Enrica , Limite Luca Rosario , Cacciotti Luca , Semeraro Raffaella , Volpe Massimo , Romeo Francesco , Caldarola Pasquale , Thiele Holger , Akin Ibrahim , Brunetti Natale Daniele , Eitel Ingo , Santoro Francesco 
Published: August 2020

AbstractClinical presentation of Takotsubo syndrome (TTS) may range from acute chest pain to dyspnea: the prognostic role of clinical onset is still controversial. Aim of this study was therefore to investigate the prognostic relevance of dyspnea at presentation in patients with TTS. We analyzed 1,071 TTS patients (median age 72 years, 90% female) enrolled in the international multicenter GEIST registry. Patients were divided according to the presence or absence of dyspnea at hospital admission, as clinically assessed by the accepting physician. The primary endpoint was occurrence of in-hospital complications defined as a composite of pulmonary edema, cardiogenic shock and death. Overall, 316 (30%) patients presented with dyspnea at hospital admission. Diabetes, lower left ventricular ejection fraction and presence of pulmonary disease or atrial fibrillation were independently associated with dyspnea. In-hospital pulmonary edema, cardiogenic shock and death (17% vs. 3%, p < 0.001; 12% vs. 7%, p = 0.009; 5% vs. 2%, p = 0.004 respectively) and long-term overall mortality (22% vs. 11%, p < 0.001) occurred more frequently in patients with dyspnea than in those without. At multivariable analysis, dyspnea at presentation remained independently associated to both the composite primary endpoint [odds ratio 2.98 (95% confidence interval (CI) 1.95–4.59, p < 0.001] and all-cause mortality [hazard ratio 2.03 (95% CI 1.37–2.99), p < 0.001]. Dyspnea at presentation is common in TTS and is independently associated with in-hospital complications and impaired long-term prognosis. Thorough symptom assessment including dyspnea therefore represents a valuable tool to potentially optimize risk-stratification models for TTS patients.
Identification of substances which regulate activity of corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus
Authors: Mukai Yasutaka , Nagayama Ayako , Itoi Keiichi , Yamanaka Akihiro 
Published: August 2020

AbstractThe stress response is a physiological system for adapting to various internal and external stimuli. Corticotropin-releasing factor-producing neurons in the paraventricular nucleus of the hypothalamus (PVN-CRF neurons) are known to play an important role in the stress response as initiators of the hypothalamic–pituitary–adrenal axis. However, the mechanism by which activity of PVN-CRF neurons is regulated by other neurons and bioactive substances remains unclear. Here, we developed a screening method using calcium imaging to identify how physiological substances directly affect the activity of PVN-CRF neurons. We used acute brain slices expressing a genetically encoded calcium indicator in PVN-CRF neurons using CRF-Cre recombinase mice and an adeno-associated viral vector under Cre control. PVN-CRF neurons were divided into ventral and dorsal portions. Bath application of candidate substances revealed 12 substances that increased and 3 that decreased intracellular calcium concentrations. Among these substances, angiotensin II and histamine mainly increased calcium in the ventral portion of the PVN-CRF neurons via AT1 and H1 receptors, respectively. Conversely, carbachol mainly increased calcium in the dorsal portion of the PVN-CRF neurons via both nicotinic and muscarinic acetylcholine receptors. Our method provides a precise and reliable means of evaluating the effect of a substance on PVN-CRF neuronal activity.
Construct a circRNA/miRNA/mRNA regulatory network to explore potential pathogenesis and therapy options of clear cell renal cell carcinoma
Authors: Bai Shuheng , Wu YinYing , Yan Yanli , Shao Shuai , Zhang Jiangzhou , Liu Jiaxin , Hui Beina , Liu Rui , Ma Hailin , Zhang Xiaozhi , Ren Juan 
Published: August 2020

AbstractClear cell renal cell carcinoma (ccRCC) is the most representative subtype of renal cancer. CircRNA acts as a kind of ceRNA to play a role in regulating microRNA (miRNA) in many cancers. However, the potential pathogenesis role of the regulatory network among circRNA/miRNA/mRNA is not clear and has not been fully explored. CircRNA expression profile data were obtained from GEO datasets, and the differentially expressed circRNAs (DECs) were identified through utilizing R package (Limma) firstly. Secondly, miRNAs that were regulated by these circRNAs were predicted by using Cancer-specific circRNA database and Circular RNA Interactome. Thirdly, some related genes were identified by intersecting targeted genes, which was predicted by a web tool (miRWalk) and differentially expressed genes, which was obtained from TCGA datasets. Function enrichment was analyzed, and a PPI network was constructed by Cytoscape software and DAVID web set. Subsequently, ten hub-genes were screened from the network, and the overall survival time in patients of ccRCC with abnormal expression of these hub-genes were completed by GEPIA web set. In the last, a circRNA/miRNA/mRNA regulatory network was constructed, and potential compounds and drug which may have the function of anti ccRCC were forecasted by taking advantage of CMap and PharmGKB datasets. Six DECs (hsa_circ_0029340, hsa_circ_0039238, hsa_circ_0031594, hsa_circ_0084927, hsa_circ_0035442, hsa_circ_0025135) were obtained and six miRNAs (miR-1205, miR-657, miR-587, miR-637, miR-1278, miR-548p) which are regulated by three circRNAs (hsa_circ_0084927, hsa_circ_0035442, hsa_circ_0025135) were also predicted. Then 497 overlapped genes regulated by these six miRNAs above had been predicted, and function enrichment analysis revealed these genes are mainly linked with some regulation functions of cancers. Ten hub-genes (PTGER3, ADCY2, APLN, CXCL5, GRM4, MCHR1, NPY5R, CXCR4, ACKR3, MTNR1B) have been screened from a PPI network. PTGER3, ADCY2, CXCL5, GRM4 and APLN were identified to have a significant effect on the overall survival time of patients with ccRCC. Furthermore, one compound (josamycin) and four kinds of drugs (capecitabine, hmg-coa reductase inhibitors, ace Inhibitors and bevacizumab) were confirmed as potential therapeutic options for ccRCC by CMap analysis and pharmacogenomics analysis. This study implies the potential pathogenesis of the regulatory network among circRNA/miRNA/mRNA and provides some potential therapeutic options for ccRCC.