bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRKAR2B‐HIF‐1α loop promotes aerobic glycolysis and tumour growth in prostate cancer
Authors: Xia Lei , Sun Jian , Xie Shaowei , Chi Chenfei , Zhu Yinjie , Pan Jiahua , Dong Baijun , Huang Yiran , Xia Weiliang , Sha Jianjun , Xue Wei 
Published: October 2020

AbstractObjectivesReprogramming of cellular metabolism is profoundly implicated in tumorigenesis and can be exploited to cancer treatment. Cancer cells are known for their propensity to use glucose‐dependent glycolytic pathway instead of mitochondrial oxidative phosphorylation for energy generation even in the presence of oxygen, a phenomenon known as Warburg effect. The type II beta regulatory subunit of protein kinase A (PKA), PRKAR2B, is highly expressed in castration‐resistant prostate cancer (CRPC) and contributes to tumour growth and metastasis. However, whether PRKAR2B regulates glucose metabolism in prostate cancer remains largely unknown.Materials and methodsLoss‐of‐function and gain‐of‐function studies were used to investigate the regulatory role of PRKAR2B in aerobic glycolysis. Real‐time qPCR, Western blotting, luciferase reporter assay and chromatin immunoprecipitation were employed to determine the underlying mechanisms.ResultsPRKAR2B was sufficient to enhance the Warburg effect as demonstrated by glucose consumption, lactate production and extracellular acidification rate. Mechanistically, loss‐of‐function and gain‐of‐function studies showed that PRKAR2B was critically involved in the tumour growth of prostate cancer. PRKAR2B was able to increase the expression level of hypoxia‐inducible factor 1α (HIF‐1α), which is a key mediator of the Warburg effect. Moreover, we uncovered that HIF‐1α is a key transcription factor responsible for inducing PRKAR2B expression in prostate cancer. Importantly, inhibition of glycolysis by the glycolytic inhibitor 2‐deoxy‐d‐glucose (2‐DG) or replacement of glucose in the culture medium with galactose (which has a much lower rate than glucose entry into glycolysis) largely compromised PRKAR2B‐mediated tumour‐promoting effect. Similar phenomenon was noticed by genetic silencing of HIF‐1α.ConclusionsOur study identified that PRKAR2B‐HIF‐1α loop enhances the Warburg effect to enable growth advantage in prostate cancer.
Histone H3K79 demethylation by KDM2B facilitates proper DNA replication through PCNA dissociation from chromatin
Authors: Kang Joo‐Young , Park Jin Woo , Hahm Ja Young , Jung Hyeonsoo , Seo Sang‐Beom 
Published: October 2020

AbstractObjectivesThe level of histone H3 lysine 79 methylation is regulated by the cell cycle and involved in cell proliferation. KDM2B is an H3K79 demethylase. Proliferating cell nuclear antigen (PCNA) is a component of the DNA replication machinery. This study aimed at elucidating a molecular link between H3K79me recognition of PCNA and cell cycle control.Materials and methodsWe generated KDM2B‐depleted 293T cells and histone H3‐K79R mutant‐expressing 293T cells. Western blots were primarily utilized to examine the H3K79me level and its effect on subsequent PCNA dissociation from chromatin. We applied IP, peptide pull‐down, isothermal titration calorimetry (ITC) and ChIP experiments to show the PCNA binding towards methylated H3K79 and DNA replication origins. Flow cytometry, MTT, iPOND and DNA fibre assays were used to assess the necessity of KDM2B for DNA replication and cell proliferation.ResultsWe revealed that KDM2B‐mediated H3K79 demethylation regulated cell cycle progression. We found that PCNA bound chromatin in an H3K79me‐dependent manner during S phase. KDM2B was responsible for the timely dissociation of PCNA from chromatin, allowing to efficient DNA replication. Depletion of KDM2B aberrantly enriched chromatin with PCNA and caused slow dissociation of residual PCNA, leading to a negative effect on cell proliferation.ConclusionsWe suggested a novel interaction between PCNA and H3K79me. Thus, our findings provide a new mechanism of KDM2B in regulation of DNA replication and cell proliferation.
Impact of censusing and research on wildlife populations
Authors: Kilpatrick A. Marm , Hoyt Joseph R. , King R. Andrew , Kaarakka Heather M. , Redell Jennifer A. , White J. Paul , Langwig Kate E. 
Published: October 2020

AbstractPopulation monitoring and research are essential for conserving wildlife, but these activities may directly impact the populations under study. These activities are often restricted to minimize disturbance, and impacts must be weighed against knowledge gained. However, few studies have quantified the effects of research or census‐related visitation frequency on populations, and low visitation rates have been hypothesized to have little effect. Hibernating bats have been hypothesized to be especially sensitive to visitation because they have limited energetic stores to survive winter, and disturbance may partly deplete these stores. We examined the effect of site visitation frequency on population growth rates of three species of hibernating bats, little brown bats (Myotis lucifugus), Indiana bats (Myotis sodalis) and tri‐colored bats (Perimyotis subflavus), both before and after detection of the disease white‐nose syndrome. We found no evidence that more frequent visits decreased population growth rates for any of these species. Estimated coefficients were either the opposite sign as hypothesized (population growth rates increased with visitation frequency) or were very small (difference in population growth rates 0.067% [SE 2.5%]–1.8% [SE 9.8%]) relative to spatial and temporal variation (5.9–32%). In contrast, white‐nose syndrome impacts on population growth rates were easily detected and well‐characterized statistically (effect sizes 4.4–8.0; severe population declines occurred in the second and third years after pathogen detection) indicating that we had sufficient power to detect effects. These results indicate that visitation frequency (for M. sodalis: annual vs. semi‐annual counts; for M. lucifugus and P. subflavus: 1–3 three research visits per year) had undetectable impacts on bat population growth rates both with and without the additional stress of an emerging infectious disease. Knowledge gained from censuses and research may outweigh disturbance due to human visitation if it can be used to understand and conserve the species.
Co‐designing behavior change interventions to conserve biodiversity
Authors: Bowie Matthew J. , Dietrich Timo , Cassey Phillip , Veríssimo Diogo 
Published: October 2020

AbstractMany threats to biodiversity are the result of human actions, which means that changing human behavior can positively alter the trajectory of our current biodiversity crisis. While there is an increasing number of behavior change interventions being implemented in biodiversity conservation, their design is rarely informed by the people they try to influence, thereby lowering the probability of success. Building successful interventions requires substantial audience research, but this can be challenging for conservation projects with perennially limited time and resources. Here, we critically discuss co‐design as a useful and effective approach for gathering audience insights relatively quickly, allowing conservation practitioners to integrate end‐user voices when they would otherwise be excluded from intervention design. Specifically, we present a seven‐step co‐design process, providing an outline and guidance for how to generate more user‐centric intervention ideas and transform them into feasible prototype interventions. Further, we show how we applied this seven‐step process with coffee consumers in a sustainable conservation context. This study outlines contributions that showcase the value of user‐centered design approaches to behavior change interventions for biodiversity conservation.
Functional connectivity in the developing language network in 4‐year‐old children predicts future reading ability
Authors: Jasińska Kaja K. , Shuai Lan , Lau Airey N. L. , Frost Stephen , Landi Nicole , Pugh Kenneth R. 
Published: October 2020

AbstractUnderstanding how pre‐literate children's language abilities and neural function relate to future reading ability is important for identifying children who may be at‐risk for reading problems. Pre‐literate children are already proficient users of spoken language and their developing brain networks for language become highly overlapping with brain networks that emerge during literacy acquisition. In the present longitudinal study, we examined language abilities, and neural activation and connectivity within the language network in pre‐literate children (mean age = 4.2 years). We tested how language abilities, brain activation, and connectivity predict children's reading abilities 1 year later (mean age = 5.2 years). At Time 1, children (n = 37) participated in a functional near infrared spectroscopy (fNIRS) experiment of speech processing (listening to words and pseudowords) and completed a standardized battery of language and cognitive assessments. At Time 2, children (n = 28) completed standardized reading assessments. Using psychophysiological interaction (PPI) analyses, we observed significant connectivity between the left IFG and right STG in pre‐literate children, which was modulated by task (i.e., listening to words). Neural activation in left IFG and STG and increased task‐modulated connectivity between the left IFG and right STG was predictive of multiple reading outcomes. Increased connectivity was associated later with increased reading ability.
Action prediction during real‐time parent‐infant interactions
Authors: Monroy Claire , Chen Chi‐Hsin , Houston Derek , Yu Chen 
Published: October 2020

AbstractSocial interactions provide a crucial context for early learning and cognitive development during infancy. Action prediction—the ability to anticipate an observed action—facilitates successful, coordinated interaction and is an important social‐cognitive skill in early development. However, current knowledge about infant action prediction comes largely from screen‐based laboratory tasks. We know little about what infants’ action prediction skills look like during real‐time, free‐flowing interactions with a social partner. In the current study, we used head‐mounted eyetracking to quantify 9‐month‐old infants’ visual anticipations of their parents’ actions during free‐flowing parent–child play. Our findings reveal that infants do anticipate their parents’ actions during dynamic interactions at rates significantly higher than would be expected by chance. In addition, the frequency with which they do so is associated with child‐led joint attention and hand‐eye coordination. These findings are the first to reveal infants’ action prediction behaviors in a more naturalistic context than prior screen‐based studies, and they support the idea that action prediction is inherently linked to motor development and plays an important role in infants’ social‐cognitive development. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=9HrmcicfiqE
Aortic valve area calculation using 3D transesophageal echocardiography: Implications for aortic stenosis severity grading
Authors: Beneduce Alessandro , Capogrosso Cristina , Moroni Francesco , Ancona Francesco , Falasconi Giulio , Pannone Luigi , Stella Stefano , Ingallina Giacomo , Melillo Francesco , Ancona Marco Bruno , Romano RT Vittorio , Palmisano Anna , Latib Azeem , Colombo Antonio , Montorfano Matteo , Esposito Antonio , Agricola Eustachio 
Published: October 2020

AbstractAimsAortic stenosis (AS) grading by 2D‐transthoracic echocardiography (2D‐TTE) aortic valve area (AVA) calculation is limited by left ventricular outflow tract (LVOT) area underestimation. The combination of Doppler parameters with 3D LVOT area obtained by multidetector computed tomography (MDCT) can improve AS grading, reconciling discordant 2D‐TTE findings. This study aimed to systematically evaluate the role of 3D‐transesophageal echocardiography (3D‐TEE) in AS grading using MDCT as reference standard.Methods and results288 patients (81 ± 6.3 years, 52.4% female) with symptomatic AS underwent 2D‐TTE, 3D‐TEE, and MDCT for transcatheter aortic valve implantation. Doppler parameters were combined with 3D LVOT areas measured by manual and semi‐automated software 3D‐TEE and by MDCT to calculate AVA, reassessing AS severity. Both 3D‐TEE modalities demonstrated good correlation with MDCT, with excellent intra‐observer and inter‐observer variability. Compared to MDCT, 3D‐TEE measurements significantly underestimated AVA (PANOVA < .0001), although the difference was clinically acceptable. Compared to 2D‐TTE, 3D‐TEE manual and semi‐automated software reclassified severe AS in 21.9% and 25.2% of cases, respectively (P < .0001), overcame grading parameters discordance in more than 40% of cases in patients with low‐gradient AS (P < .0001) and reduced the proportion of low‐flow states in nearly 75% of cases when combined to stroke volume index assessment (P < .0001). 3D‐TEE imaging modalities showed a reduction in the proportion of patients with low‐gradient and pathological AVA as defined by 2D‐TTE, and improved AVA and mean pressure gradient agreement with current guidelines cutoff values.Conclusion3D‐TEE AVA calculation is a reliable tool for AS grading with excellent reproducibility and good correlation with MDCT measurements.
Preparing the hair follicle canal for hair shaft emergence
Authors: Mesler Arlee L. , Benedeck Rachel E. , Wong Sunny Y. 
Published: October 2020

AbstractThe emergence of hair is a defining event during mammalian skin development, but the cellular mechanisms leading to the opening of the hair follicle canal remain poorly characterized. Our previous studies have shown that early hair buds possess a central column of differentiated keratinocytes expressing Keratin 79 (K79), which marks the future hair follicle opening. Here, we report that during late embryogenesis and early postnatal development, K79+ cells at the distal tips of these columns downregulate E‐cadherin, change shape, recede and undergo cell death. These changes likely occur independently of sebaceous glands and the growing hair shaft, and serve to create an orifice for hair to subsequently emerge. Defects in this process may underlie phenomena such as ingrown hair or may potentially contribute to upper hair follicle pathologies including acne, hidradenitis suppurativa and infundibular cysts.
In silico assessment of the potential of basalt amendments to reduce N2O emissions from bioenergy crops
Authors: Blanc‐Betes Elena , Kantola Ilsa B. , Gomez‐Casanovas Nuria , Hartman Melennie D. , Parton William J. , Lewis Amy L. , Beerling David J. , DeLucia Evan H. 
Published: October 2020

AbstractThe potential of large‐scale deployment of basalt to reduce N2O emissions from cultivated soils may contribute to climate stabilization beyond the CO2‐removal effect from enhanced weathering. We used 3 years of field observations from maize (Zea mays) and miscanthus (Miscanthus × giganteus) to improve the nitrogen (N) module of the DayCent model and evaluate the potential of basalt amendments to reduce N losses and increase yields from two bioenergy crops. We found 20%–60% improvement in our N2O flux estimates over previous model descriptions. Model results predict that the application of basalt would reduce N2O emissions by 16% in maize and 9% in miscanthus. Lower N2O emissions responded to increases in the N2:N2O ratio of denitrification with basalt‐induced increases in soil pH, with minor contributions from the impact of P additions (a minor component of some basalts) on N immobilization. The larger reduction of N2O emissions in maize than in miscanthus was likely explained by a synergistic effect between soil pH and N content, leading to a higher sensitivity of the N2:N2O ratio to changes in pH in heavily fertilized maize. Basalt amendments led to modest increases in modeled yields and the nitrogen use efficiency (i.e., fertilizer‐N recover in crop production) of maize but did not affect the productivity of miscanthus. However, enhanced soil P availability maintained the long‐term productivity of crops with high nutrient requirements. The alleviation of plant P limitation led to enhanced plant N uptake, thereby contributing to lower microbial N availability and N2O emissions from crops with high nutrient requirements. Our results from the improved model suggest that the large‐scale deployment of basalt, by reducing N2O fluxes of cropping systems, could contribute to the sustainable intensification of agriculture and enhance the climate mitigation potential of bioenergy with carbon capture and storage strategies.
Root canal treatment of compromised teeth as alternative treatment for patients receiving bisphosphonates: 60‐month results of a prospective clinical study
Authors: Zamparini F. , Pelliccioni G. A. , Spinelli A. , Gissi D. B. , Gandolfi M. G. , Prati C. 
Published: October 2020

AbstractAimThis 60‐month prospective study aimed to evaluate tooth survival and healing rates after root canal treatment in patients taking bisphosphonates (BPs). Secondary outcomes were complications and clinical variables observed during and after treatment.MethodsRoot canal treatment was performed using manual K‐file canal instrumentation and a carrier‐based filling technique with an epoxy resin‐based sealer. Teeth without adequate root/crown integrity were restored by trained operators at the tissue level (TL group) to prevent occlusal/mechanical stress and to enable periapical lesion healing without the risk of root fracture. Other teeth were restored with normal occlusal contacts (OC group). Healthy patients who had undergone one or more root canal treatments of the same type constituted the control group. The relationships of the following variables to survival and health status were examined (chi‐squared test and multivariate analysis, P = 0.05): age, gender, smoking habit, tooth location, treatment type, BPs treatment, BPs exposure, initial periapical index (PAI) and occlusal restoration. Survival curves were constructed using Kaplan–Meier analysis, with extraction serving as the end‐point.ResultsIn total, 65 patients with 109 root canal‐treated teeth who were taking BPs were included. At 60 months, data from 57 patients (52F, 5M; median age 65.7 ± 8.6 years) who had undergone 96 root canal treatments were analysed (drop‐out rate = 16.9%). The survival rate was 85%, and the success rate was 76%. The control group consisted of 46 patients (21F, 25M; median age 60.3 ± 7.2 years) who had undergone 102 root canal treatments. The survival rate was 88%, with 12 teeth lost during follow‐up. The success rate was 73%. In the BP group, 55 teeth were restored normally (OC group) and 41 teeth were restored at the tissue level (TL group). No difference in the success or survival rate was observed between the BP and control groups (P > 0.05). Univariate Kaplan–Meier analysis revealed that only tooth type significantly affected survival status in the BP group. The analysis revealed the clinical relevance of smoking, tooth location and initial PAI on patients’ health status (P < 0.05).ConclusionRoot canal treatments and post‐endodontic restoration with tissue‐level filling procedures represent a safe approach for severely damaged teeth in patients receiving BPs having comparable results to root filled teeth restored with occlusal contacts and to the control group.
Fracture resistance of human roots filled with mineral trioxide aggregate mixed with phosphate‐buffered saline, with and without calcium hydroxide pre‐medication
Authors: Żuk‐Grajewska E. , Saunders W. P. , Chadwick R. G. 
Published: October 2020

AbstractAimTo compare the fracture strength of extracted human roots with apical plugs of mineral trioxide aggregate (MTA) mixed with either Ca‐ and Mg‐free phosphate‐buffered saline (PBS) or water, with and without calcium hydroxide (CH) canal pre‐medication.MethodologyA total of 180 single‐rooted human teeth were prepared to resemble immature roots and divided into groups (n = 20). The negative control received canal irrigation only, and the positive control received intracanal treatment with CH for either two or twelve weeks. MTA mixed with water was used in Group 1: (i) without CH pre‐medication – MTA(W); (ii) after 2 weeks CH pre‐medication – 2/52CH + MTA(W); and (iii) after 12‐week CH pre‐medication – 12/52 CH + MTA(W). MTA mixed with PBS was used in Group 2: (i) without CH pre‐medication – MTA(PBS); (ii) after 2‐week CH pre‐medication – 2/52CH + MTA(PBS); and (iii) after 12‐week CH pre‐medication – 12/52 CH + MTA(PBS). A compressive force was applied to each root until the point of fracture. The results were analysed by the Kruskal–Wallis and Dunn’s multiple comparisons tests (P < 0.05).ResultsThere was no significant difference between groups MTA(W), MTA(PBS) and 2/52CH + MTA(PBS), and all three groups were significantly (P < 0.01, P < 0.05 and P < 0.05, respectively) more resistant to fracture than the negative control. Within Group 1, the samples that received two‐ (P < 0.01) and twelve‐week (P < 0.001) CH pre‐treatment were more prone to fracture than those which did not. No difference was found amongst the control groups. The roots of the MTA(PBS) group had a higher dependability (P < 0.05) than the MTA(W) group when compared by the Weibull modulus. The difference was also present when a 2‐week CH pre‐medication was used.ConclusionsMineral trioxide aggregate mixed with Ca‐ and Mg‐free phosphate‐buffered saline had a significant strengthening effect on the fracture resistance of structurally weak roots, even when short‐term calcium hydroxide pre‐medication had been used. MTA mixed with water lost its strengthening effect on human roots when 2‐ or 12‐week CH pre‐treatment had been used. Use of CH dressing for up to 12 weeks had no negative effect on fracture resistance of human roots.
Pretreatment eliminates throat irritation by water yam and facilitates the development of functional cookies
Authors: Najeeb Fyroos , Theagarajan Radhika , Dutta Sayantani , Moses Jeyan A. , Anandharamakrishnan Chinnaswamy 
Published: October 2020

SummaryWater yam (Dioscoreaalata) provides sufficient nutrients in terms of protein (10.075 ± 0.02%), fibre (3.40 ± 0.03%) and minerals (potassium and phosphorous). However, due to the presence of anti‐nutritional factors such as saponins, water yam causes throat irritation. Consequently, it is less preferred among consumers, and thus, the commercial importance of yam tubers has been limited. The current investigation aims to reduce the saponin content of water yam by pretreatment of yam tubers at the optimised conditions (blanching with 0.2% potassium metabisulphite, 0.5% tartaric acid and 0.5% citric acid) that rendered a 50% reduction in the saponin content (1.65% to 0.86%). The said nutritious yam flour was utilised as a replacement of refined wheat flour (13%) in the development of functional cookies. The yam cookies showed higher mineral content (phosphorous: 116.20 ± 0.80 mg/100 g; potassium: 221.11 ± 0.98 mg/100 g). Reduced water activity and incorporation of antioxidants in yam cookies decreased the peroxide value of the same during storage attesting its higher shelf‐life.