bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboplatin response in preclinical models for ovarian cancer: comparison of 2D monolayers, spheroids, ex vivo tumors and in vivo models
Authors: Brodeur Melica Nourmoussavi , Simeone Kayla , Leclerc-Deslauniers Kim , Fleury Hubert , Carmona Euridice , Provencher Diane M. , Mes-Masson Anne-Marie 
Published: September 2021

AbstractEpithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Among the key challenges in developing effective therapeutics is the poor translation of preclinical models used in the drug discovery pipeline. This leaves drug attrition rates and costs at an unacceptably high level. Previous work has highlighted the discrepancies in therapeutic response between current in vitro and in vivo models. To address this, we conducted a comparison study to differentiate the carboplatin chemotherapy response across four different model systems including 2D monolayers, 3D spheroids, 3D ex vivo tumors and mouse xenograft models. We used six previously characterized EOC cell lines of varying chemosensitivity and performed viability assays for each model. In vivo results from the mouse model correlated with 2D response in 3/6 cell lines while they correlated with 3D spheroids and the ex vivo model in 4/6 and 5/5 cell lines, respectively. Our results emphasize the variability in therapeutic response across models and demonstrate that the carboplatin response in EOC cell lines cultured in a 3D ex vivo model correlates best with the in vivo response. These results highlight a more feasible, reliable, and cost-effective preclinical model with the highest translational potential for drug screening and prediction studies in EOC.
Improving weather forecasting by assimilation of water vapor isotopes
Authors: Tada Masataka , Yoshimura Kei , Toride Kinya 
Published: September 2021

AbstractStable water isotopes, which depend on meteorology and terrain, are important indicators of global water circulation. During the past 10 years, major advances have been made in general circulation models that include water isotopes, and the understanding of water isotopes has greatly progressed as a result of innovative, improved observation techniques. However, no previous studies have combined modeled and observed isotopes using data assimilation, nor have they investigated the impacts of real observations of isotopes. This is the first study to assimilate real satellite observations of isotopes using a general circulation model, then investigate the impacts on global dynamics and local phenomena. The results showed that assimilating isotope data improved not only the water isotope field but also meteorological variables such as air temperature and wind speed. Furthermore, the forecast skills of these variables were improved by a few percent, compared with a model that did not assimilate isotope observations.
The gene repertoire of the main cysteine protease of Trypanosoma cruzi, cruzipain, reveals four sub-types with distinct active sites
Authors: Santos Viviane Corrêa , Oliveira Antonio Edson Rocha , Campos Augusto César Broilo , Reis-Cunha João Luís , Bartholomeu Daniella Castanheira , Teixeira Santuza Maria Ribeiro , Lima Ana Paula C. A. , Ferreira Rafaela Salgado 
Published: September 2021

AbstractCruzipains are the main papain-like cysteine proteases of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. Encoded by a multigenic family, previous studies have estimated the presence of dozens of copies spread over multiple chromosomes in different parasite strains. Here, we describe the complete gene repertoire of cruzipain in three parasite strains, their genomic organization, and expression pattern throughout the parasite life cycle. Furthermore, we have analyzed primary sequence variations among distinct family members as well as structural differences between the main groups of cruzipains. Based on phylogenetic inferences and residue positions crucial for enzyme function and specificity, we propose the classification of cruzipains into two families (I and II), whose genes are distributed in two or three separate clusters in the parasite genome, according with the strain. Family I comprises nearly identical copies to the previously characterized cruzipain 1/cruzain, whereas Family II encompasses three structurally distinct sub-types, named cruzipain 2, cruzipain 3, and cruzipain 4. RNA-seq data derived from the CL Brener strain indicates that Family I genes are mainly expressed by epimastigotes, whereas trypomastigotes mainly express Family II genes. Significant differences in the active sites among the enzyme sub-types were also identified, which may play a role in their substrate selectivity and impact their inhibition by small molecules.
The role of DNA-binding and ARNT dimerization on the nucleo-cytoplasmic translocation of the aryl hydrocarbon receptor
Authors: Haidar Rashad , Henkler Frank , Kugler Josephine , Rosin Aline , Genkinger Doris , Laux Peter , Luch Andreas 
Published: September 2021

AbstractThe human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. Binding to endogenous or xenobiotic ligands terminates the basal nucleo-cytoplasmic shuttling and stabilizes an exclusive nuclear population. The precise mechanisms that facilitate such stable nuclear accumulation remain to be clarified as essential step in the activation cascade. In this study, we have tested whether the sustained nuclear compartmentalization of ligand-bound or basal AHR might further require heterodimerization with the AHR-nuclear translocator (ARNT) and binding to the cognate XRE-motif. Mutagenesis of the DNA-binding motif or of selected individual residues in the ARNT-binding motif did not lead to any variation in AHR’s nucleo-cytoplasmic distribution. In response to ligands, all mutants were retained in the nucleus demonstrating that the stable compartmentalization of activated AHR in the nucleus is neither dependent on interactions with DNA, nor ARNT. Knocking down the ARNT gene using small interfering RNA confirmed that ARNT does not play any role in the intracellular trafficking of AHR.
Stochastic binary synapses having sigmoidal cumulative distribution functions for unsupervised learning with spike timing-dependent plasticity
Authors: Nishi Yoshifumi , Nomura Kumiko , Marukame Takao , Mizushima Koichi 
Published: September 2021

AbstractSpike timing-dependent plasticity (STDP), which is widely studied as a fundamental synaptic update rule for neuromorphic hardware, requires precise control of continuous weights. From the viewpoint of hardware implementation, a simplified update rule is desirable. Although simplified STDP with stochastic binary synapses was proposed previously, we find that it leads to degradation of memory maintenance during learning, which is unfavourable for unsupervised online learning. In this work, we propose a stochastic binary synaptic model where the cumulative probability of the weight change evolves in a sigmoidal fashion with potentiation or depression trials, which can be implemented using a pair of switching devices consisting of serially connected multiple binary memristors. As a benchmark test we perform simulations of unsupervised learning of MNIST images with a two-layer network and show that simplified STDP in combination with this model can outperform conventional rules with continuous weights not only in memory maintenance but also in recognition accuracy. Our method achieves 97.3% in recognition accuracy, which is higher than that reported with standard STDP in the same framework. We also show that the high performance of our learning rule is robust against device-to-device variability of the memristor's probabilistic behaviour.
Selective 13C labelling reveals the electronic structure of flavocoenzyme radicals
Authors: Schleicher Erik , Rein Stephan , Illarionov Boris , Lehmann Ariane , Al Said Tarek , Kacprzak Sylwia , Bittl Robert , Bacher Adelbert , Fischer Markus , Weber Stefan 
Published: September 2021

AbstractFlavocoenzymes are nearly ubiquitous cofactors that are involved in the catalysis and regulation of a wide range of biological processes including some light-induced ones, such as the photolyase-mediated DNA repair, magnetoreception of migratory birds, and the blue-light driven phototropism in plants. One of the factors that enable versatile flavin-coenzyme biochemistry and biophysics is the fine-tuning of the cofactor’s frontier orbital by interactions with the protein environment. Probing the singly-occupied molecular orbital (SOMO) of the intermediate radical state of flavins is therefore a prerequisite for a thorough understanding of the diverse functions of the flavoprotein family. This may be ultimately achieved by unravelling the hyperfine structure of a flavin by electron paramagnetic resonance. In this contribution we present a rigorous approach to obtaining a hyperfine map of the flavin’s chromophoric 7,8-dimethyl isoalloxazine unit at an as yet unprecedented level of resolution and accuracy. We combine powerful high-microwave-frequency/high-magnetic-field electron–nuclear double resonance (ENDOR) with 13C isotopologue editing as well as spectral simulations and density functional theory calculations to measure and analyse 13C hyperfine couplings of the flavin cofactor in DNA photolyase. Our data will provide the basis for electronic structure considerations for a number of flavin radical intermediates occurring in blue-light photoreceptor proteins.
Effect of disconnection of deformable units on the mobility and stiffness of 3D prismatic modular origami structures using angular kinematics
Authors: Xiao Kai , Zhou Xiang , Ju Jaehyung 
Published: September 2021

AbstractArchitected modular origami structures show potential for future robotic matter owing to their reconfigurability with multiple mobilities. Similar to modular robots, the units of modular origami structures do not need to be assembled in a fully packed fashion; in fact, disconnection can provide more freedom for the design of mobility and functionality. Despite the potential of expanded design freedom, the effect of the disconnection of units on the mobility and physical properties has not yet been explored in modular origami structures. Determining the mobility and weak spots of modular origami structures is significant to enable transformation with minimum energy. Herein, we investigate the effect of the disconnection of units on the mobility and stiffness of architected modular origami structures with deformable units using angular kinematics of geometry and topology of units and closed loops. Angular kinematics provides a valuable tool for investigating the complex mobility of architected modular origami structures with the disconnection of loops. The mobility of the network structure is a function not only of the number of disconnections but also of the topology of the loop. In contrast to the conventional negative perception of defects or disconnection in these materials, the disconnection can potentially be used to expand the design space of mobility for future robotic matter. Our findings can be used to develop powerful design guidelines for topologically reconfigurable structures for soft modular robots, active architected materials, implanted modular devices, deployable structures, thermal metamaterials, and active acoustic metamaterials.
Cruciate ligament force of knees following mobile-bearing unicompartmental knee arthroplasty is larger than the preoperative value
Authors: Kono Kenichi , Inui Hiroshi , Tomita Tetsuya , D’Lima Darryl D. , Yamazaki Takaharu , Konda Shoji , Taketomi Shuji , Yamagami Ryota , Kawaguchi Kohei , Sameshima Shin , Kage Tomofumi , Tanaka Sakae 
Published: September 2021

AbstractWe analyzed the implantation effects on cruciate ligament force in unicompartmental knee arthroplasty (UKA) and determined whether kinematics is associated with the cruciate ligament force. We examined 16 patients (17 knees) undergoing medial UKA. Under fluoroscopy, each participant performed a deep knee bend before and after UKA. A two-dimensional/three-dimensional registration technique was employed to measure tibiofemoral kinematics. Forces in the anteromedial and posterolateral bundles of both the anterior cruciate ligament (aACL and pACL) and the anterolateral and posteromedial bundles of the posterior cruciate ligament (aPCL and pPCL) during knee flexion were analyzed pre- and post-UKA. Correlations between changes in kinematics and ligament forces post-UKA were also analyzed. Preoperatively, the aACL forces were highly correlated with anteroposterior (AP) translation of the lateral condyles (Correlation coefficient [r] = 0.59). The pPCL forces were highly correlated with the varus–valgus angulation (r =  − 0.57). However, postoperatively, the PCL forces in both bundles were highly correlated with the AP translation of the medial femoral condyle (aPCL: r = 0.62, pPCL: r = 0.60). The ACL and PCL forces of the knees post-UKA were larger than those of the knees pre-UKA. Kinematic changes were significantly correlated with the cruciate ligament force changes.
Genome-wide identification, evolution, and transcript profiling of Aldehyde dehydrogenase superfamily in potato during development stages and stress conditions
Authors: Islam Md. Sifatul , Hasan Md. Soyib , Hasan Md. Nazmul , Prodhan Shamsul H. , Islam Tahmina , Ghosh Ajit 
Published: September 2021

AbstractThe Aldehyde dehydrogenase (ALDH) superfamily comprises a group of enzymes involved in the scavenging of toxic aldehyde molecules by converting them into their corresponding non-toxic carboxylic acids. A genome-wide study in potato identified a total of 22 ALDH genes grouped into ten families that are presented unevenly throughout all the 12 chromosomes. Based on the evolutionary analysis of ALDH proteins from different plant species, ALDH2 and ALDH3 were found to be the most abundant families in the plant, while ALDH18 was found to be the most distantly related one. Gene expression analysis revealed that the expression of StALDH genes is highly tissue-specific and divergent in various abiotic, biotic, and hormonal treatments. Structural modelling and functional analysis of selected StALDH members revealed conservancy in their secondary structures and cofactor binding sites. Taken together, our findings provide comprehensive information on the ALDH gene family in potato that will help in developing a framework for further functional studies.
P16INK4A expression might be associated with a favorable prognosis for cervical adenocarcinoma via dysregulation of the RB pathway
Authors: Ishikawa Masako , Nakayama Kentaro , Nakamura Kohei , Yamashita Hitomi , Ishibashi Tomoka , Minamoto Toshiko , Sawada Kiyoka , Yoshimura Yuki , Iida Kouji , Razia Sultana , Ishikawa Noriyoshi , Nakayama Satoru , Otsuki Yoshiro , Kyo Satoru 
Published: September 2021

AbstractPrevious studies have largely failed to clarify the relationship between p16INK4A status and cervical adenocarcinoma prognosis. The current study aimed to examine the clinical and pathological significance of p16INK4A expression in several cervical adenocarcinoma subtypes. Eighty-two samples collected from patients with cervical adenocarcinoma were formalin fixed and paraffin embedded. Next, p16INK4A levels were analyzed with immunohistochemistry. Additionally, the relationship between p16INK4A expression and clinicopathological factors as well as prognosis was evaluated. The expression of p16INK4A was mostly detected in all usual cervical adenocarcinoma subtypes. In the gastric type, only a few cases were positive for p16INK4A expression. Results of the Kaplan–Meier analysis indicated that the positive p16INK4A expression in tumor cells was significantly associated with favorable progression-free survival and overall survival in patients with cervical adenocarcinoma (p = 0.018 and p = 0.047, respectively, log-rank test). Our findings suggest that the status of p16INK4A expression may influence prognosis. Thus, p16INK4A expression could be used as a biomarker for improving the prognosis of patients with cervical adenocarcinoma.
Association between diabetes status and subsequent onset of glaucoma in postmenopausal women
Authors: Jung Younhea , Han Kyungdo , Ohn Kyoung , Kim Da Ran , Moon Jung II 
Published: September 2021

AbstractThe purpose of this study was to analyze the risk of glaucoma based on diabetes status using a large nationwide longitudinal cohort of postmenopausal women. This study included 1,372,240 postmenopausal women aged ≥ 40 years who underwent National Health Screening Program in 2009. Subjects were classified into the following 5 categories based on diabetes status: no diabetes, impaired fasting glucose (IFG), new onset diabetes, diabetes treated with oral hypoglycemic medication, and diabetes treated with insulin. Subjects were followed from 2005 through 2018, and hazard ratios of glaucoma onset were calculated for each group. Subgroup analyses of subjects stratified by age, smoking, drinking, hypertension, and dyslipidemia were performed. During the follow up period, 42,058 subjects developed glaucoma. The adjusted hazard ratio was 1.061 (95% CI, 1.036–1.086) in the IFG group, 1.151 (95% CI, 1.086–1.220) in the new onset diabetes group, 1.449 (95% CI, 1.406–1.493) in the diabetes treated with oral hypoglycemic medication group, and 1.884(95% CI, 1.777–1.999) in the diabetes treated with insulin group compared to the no diabetes group. The results were consistent in subgroup analyses after stratifying by age, lifestyle factors (smoking and drinking), and comorbidities (hypertension and dyslipidemia). Diabetes status is associated with increased risk of glaucoma development in postmenopausal women.
Functions of the ventromedial prefrontal cortex in emotion regulation under stress
Authors: Suzuki Yukihiro , Tanaka Saori C. 
Published: September 2021

AbstractRecent neuroimaging studies suggest that the ventromedial prefrontal cortex (vmPFC) contributes to regulation of emotion. However, the adaptive response of the vmPFC under acute stress is not understood. We used fMRI to analyse brain activity of people viewing and rating the emotional strength of emotional images after acute social stress. Here, we show that the vmPFC is strongly activated by highly emotional images, indicating its involvement in emotional regulation, and that the midbrain is activated as a main effect of stress during the emotional response. vmPFC activation also exhibits individual differences in behavioural scores reflecting individual reactions to stress. Moreover, functional connectivity between the vmPFC and midbrain under stress reflects stress-induced emotion regulation. Those results suggest that the functions of the network including the vmPFC in emotion regulation is affected by stress depending on the individuals' level of reaction to the stress.
Characteristics of pulmonary microvascular structure in postnatal yaks
Authors: Wan Ruidong , Zhao Ziqi , Zhao Min , Hu Ke , Zhai Jiaxin , Yu Hongxian , Wei Qing 
Published: September 2021

AbstractYaks are typical plateau-adapted animals, however the microvascular changes and characteristics in their lungs after birth are still unclear. Pulmonary microvasculature characteristics and changes across age groups were analysed using morphological observation and molecular biology detection in yaks aged 1, 30 and 180 days old in addition to adults. Results: Our experiments demonstrated that yaks have fully developed pulmonary alveolar at birth but that interalveolar thickness increased with age. Immunofluorescence observations showed that microvessel density within the interalveolar septum in the yak gradually increased with age. In addition, transmission electron microscopy (TEM) results showed that the blood–air barrier of 1-day old and 30-days old yaks was significantly thicker than that observed at 180-days old and in adults (P < 0.05), which was caused by the thinning of the membrane of alveolar epithelial cells. Furthermore,VegfaandEpas1expression levels in 30-day old yaks were the highest in comparison to the other age groups (P < 0.05), whilst levels in adult yaks were the lowest (P < 0.05). The gradual increase in lung microvessel density can effectively satisfy the oxygen requirements of ageing yaks. In addition, these results suggest that the key period of yak lung development is from 30 to 180 days.
The nose is the best niche for detection of experimental pneumococcal colonisation in adults of all ages, using nasal wash
Authors: Nikolaou Elissavet , German Esther L. , Blizard Annie , Howard Ashleigh , Hitchins Lisa , Chen Tao , Chadwick Jim , Pojar Sherin , Mitsi Elena , Solórzano Carla , Sunny Syba , Dunne Felicity , Gritzfeld Jenna F. , Adler Hugh , Hinds Jason , Gould Katherine A. , Rylance Jamie , Collins Andrea M. , Gordon Stephen B. , Ferreira Daniela M. 
Published: September 2021

AbstractPrevious studies have suggested that the pneumococcal niche changes from the nasopharynx to the oral cavity with age. We use an Experimental Human Pneumococcal Challenge model to investigate pneumococcal colonisation in different anatomical niches with age. Healthy adults (n = 112) were intranasally inoculated with Streptococcus pneumoniae serotype 6B (Spn6B) and were categorised as young 18–55 years (n = 57) or older > 55 years (n = 55). Colonisation status (frequency and density) was determined by multiplex qPCR targeting the lytA and cpsA-6A/B genes in both raw and culture-enriched nasal wash and oropharyngeal swab samples collected at 2-, 7- and 14-days post-exposure. For older adults, raw and culture-enriched saliva samples were also assessed. 64% of NW samples and 54% of OPS samples were positive for Spn6B in young adults, compared to 35% of NW samples, 24% of OPS samples and 6% of saliva samples in older adults. Many colonisation events were only detected in culture-enriched samples. Experimental colonisation was detected in 72% of young adults by NW and 63% by OPS. In older adults, this was 51% by NW, 36% by OPS and 9% by saliva. The nose, as assessed by nasal wash, is the best niche for detection of experimental pneumococcal colonisation in both young and older adults.
Effects of different salt sources and salinity levels on emergence and seedling growth of faba bean genotypes
Authors: Bimurzayev Nurlykhan , Sari Hatice , Kurunc Ahmet , Doganay Kıvanc Hayri , Asmamaw Mulat 
Published: September 2021

AbstractSuitability of poor quality water for irrigation depends on salinity level and solute concentration in the water and selected crop. Salt stress is a major potential constraint for faba bean. The present study aimed to investigate the effects of different Cl- and SO4-containing salt sources in irrigation water with different salinity levels on emergence, early seedling growth and photosynthetic capacity of six faba bean genotypes. The negative effect order of salinity level was high (3 dS/m) > medium (2 dS/m) > low (1 dS/m) > control (0.05 dS/m) for all investigated parameters except dry root weight. The negative effects of Cl-containing salt sources were higher than that of SO4-containing salt sources. The worst and the best performing genotypes were determined as III-28 and III-29 on emergence percentage at 10th DAS, I-29 and III-1 on mean emergence time, III-22 and III-1 on shoot height, III-1 and I-29 on fresh biomass weight, III-22 and III-28 on fresh shoot weight, III-29 and I-29 on fresh root weight, respectively. This study showed that faba bean genotypes have different behaviors in terms of response to the increasing salinity levels artificially makeup by using different salt sources indicating that salt response of faba bean is genotype-specific.