bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perfusion reduces bispecific antibody aggregation via mitigating mitochondrial dysfunction-induced glutathione oxidation and ER stress in CHO cells
Authors: Sinharoy Pritam , Aziz Aaron H. , Majewska Natalia I. , Ahuja Sanjeev , Handlogten Michael W. 
Published: October 2020

AbstractOne major challenge observed for the expression of therapeutic bispecific antibodies (BisAbs) is high product aggregates. Aggregates increase the risk of immune responses in patients and therefore must be removed at the expense of purification yields. BisAbs contain engineered disulfide bonds, which have been demonstrated to form product aggregates, if mispaired. However, the underlying intracellular mechanisms leading to product aggregate formation remain unknown. We demonstrate that impaired glutathione regulation underlies BisAb aggregation formation in a CHO cell process. Aggregate formation was evaluated for the same clonal CHO cell line producing a BisAb using fed-batch and perfusion processes. The perfusion process produced significantly lower BisAb aggregates compared to the fed-batch process. Perfusion bioreactors attenuated mitochondrial dysfunction and ER stress resulting in a favorable intracellular redox environment as indicated by improved reduced to oxidized glutathione ratio. Conversely, mitochondrial dysfunction-induced glutathione oxidation and ER stress disrupted the intracellular redox homeostasis, leading to product aggregation in the fed-batch process. Combined, our results demonstrate that mitochondrial dysfunction and ER stress impaired glutathione regulation leading to higher product aggregates in the fed-batch process. This is the first study to utilize perfusion bioreactors as a tool to demonstrate the intracellular mechanisms underlying product aggregation formation.
A global class reunion with multiple groups feasting on the declining insect smorgasbord
Authors: Vesterinen Eero J. , Kaunisto Kari M. , Lilley Thomas M. 
Published: October 2020

AbstractWe report a detection of a surprising similarity in the diet of predators across distant phyla. Though just a first glimpse into the subject, our discovery contradicts traditional aspects of biology, as the earliest notions in ecology have linked the most severe competition of resources with evolutionary relatedness. We argue that our finding deserves more research, and propose a plan to reveal more information on the current biodiversity loss around the world. While doing so, we expand the recently proposed conservation roadmaps into a parallel study of global interaction networks.
A simple RNA preparation method for SARS-CoV-2 detection by RT-qPCR
Authors: Wozniak Aniela , Cerda Ariel , Ibarra-Henríquez Catalina , Sebastian Valentina , Armijo Grace , Lamig Liliana , Miranda Carolina , Lagos Marcela , Solari Sandra , Guzmán Ana María , Quiroga Teresa , Hitschfeld Susan , Riveras Eleodoro , Ferrés Marcela , Gutiérrez Rodrigo A. , García Patricia 
Published: October 2020

AbstractThe technique RT-qPCR for viral RNA detection is the current worldwide strategy used for early detection of the novel coronavirus SARS-CoV-2. RNA extraction is a key pre-analytical step in RT-qPCR, often achieved using commercial kits. However, the magnitude of the COVID-19 pandemic is causing disruptions to the global supply chains used by many diagnostic laboratories to procure the commercial kits required for RNA extraction. Shortage in these essential reagents is even more acute in developing countries with no means to produce kits locally. We sought to find an alternative procedure to replace commercial kits using common reagents found in molecular biology laboratories. Here we report a method for RNA extraction that takes about 40 min to complete ten samples, and is not more laborious than current commercial RNA extraction kits. We demonstrate that this method can be used to process nasopharyngeal swab samples and yields RT-qPCR results comparable to those obtained with commercial kits. Most importantly, this procedure can be easily implemented in any molecular diagnostic laboratory. Frequent testing is crucial for individual patient management as well as for public health decision making in this pandemic. Implementation of this method could maintain crucial testing going despite commercial kit shortages.
HMGR overexpression and interference affect the expression of steroidogenic genes and cholesterol content in bovine intramuscular adipocytes
Authors: Lin Haichao , Wei Chen , Zhang Xianglun , You Wei , Jin Qing , Tan Xiuwen , Zhao Hongbo , Zhang Chen , Liu Xiaomu , Liu Guifen 
Published: October 2020

AbstractPreviously, we found that mevalonic acid stimulates 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR) expression in bovine intramuscular adipocytes to influence adipocyte differentiation. However, any direct links among HMGR, steroidogenic genes, and cholesterol content remain unclear. RNA-Seq was conducted to determine the differences between the gene expression profiles of bovine adipocytes containing different HMGR expression constructs. In total, 10,234 differentially expressed genes (DEGs) were found. Of these, 35 and 6 DEGs between the control and the overexpression groups were functionally related to lipid and energy metabolism, respectively. In addition, 43 and 8 DEGs between the control and the HMGR inhibition groups were related to lipid and energy metabolism, respectively. Several DEGs related to lipid and energy metabolism were also identified between the HMGR overexpression group and the HMGR interference group, and many DEGs were correlated positively or negatively with the overexpression or inhibition of HMGR. We also found that, following the activation or inhibition of the HMGR gene, AMP-activated protein kinase (AMPK) and sirtuin type 1 (SIRT1) had opposite expression patterns in bovine intramuscular adipocytes. Interestingly, the HMGR gene was downregulated when HMGR was overexpressed, and upregulated when HMGR was inhibited. Our findings establish a theoretical understanding of signaling pathways involved in cholesterol synthesis by elucidating the relationships between key genes.
The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: a randomized placebo-controlled clinical trial
Authors: Minakuchi Hitoshi , Wakino Shu , Urai Hidenori , Kurokochi Arata , Hasegawa Kazuhiro , Kanda Takeshi , Tokuyama Hirobumi , Itoh Hiroshi 
Published: October 2020

AbstractThe progression of chronic kidney disease (CKD) cannot be completely inhibited. We first explored factors contributing to CKD progression in patients with CKD in a prospective observational study. In the next phase, we focused on the effects of aldosterone, conducting a single-blinded placebo-controlled study using the selective mineralocorticoid receptor antagonist (MRA), eplerenone (25 mg/day). We recruited patients with CKD stage 2 and 3 whose plasma aldosterone concentration was above 15 ng/dL based on the prior data of a prospective observational study. In the CKD cohort study (n = 141), baseline plasma aldosterone concentration was identified as an independent contributory factor for the future rate of change in estimated glomerular filtration rate (eGFR). When the cut-off value for aldosterone was set at 14.5 ng/dL, the decline rate was significantly higher in patients with higher plasma aldosterone concentration (− 1.22 ± 0.39 ml/min/1.73 m2/year vs. 0.39 ± 0.40 ml/min/1.73 m2/year, p = 0.0047). In the final intervention study, in the eplerenone group, eGFR dropped at 6 months after the initiation of the study, and thereafter eGFR was maintained until the end of the study. At 24 months and 36 months, eGFR was significantly higher in the eplerenone group than in the placebo group. In conclusion, MRA can be an effective strategy in preventing CKD progression, especially in patients with high plasma aldosterone.
Extensive fragmentation and re-organization of transcription in Systemic Lupus Erythematosus
Authors: Ntasis Vasilis F. , Panousis Nikolaos I. , Tektonidou Maria G. , Dermitzakis Emmanouil T. , Boumpas Dimitrios T. , Bertsias George K. , Nikolaou Christoforos 
Published: October 2020

AbstractSystemic Lupus Erythematosus (SLE) is the prototype of autoimmune diseases, characterized by extensive gene expression perturbations in peripheral blood immune cells. Circumstantial evidence suggests that these perturbations may be due to altered epigenetic profiles and chromatin accessibility but the relationship between transcriptional deregulation and genome organization remains largely unstudied. In this work we propose a genomic approach that leverages patterns of gene coexpression from genome-wide transcriptome profiles in order to identify statistically robust Domains of Co-ordinated gene Expression (DCEs). Application of this method on a large transcriptome profiling dataset of 148 SLE patients and 52 healthy individuals enabled the identification of significant disease-associated alterations in gene co-regulation patterns, which also correlate with SLE activity status. Low disease activity patient genomes are characterized by extensive fragmentation leading to overall fewer DCEs of smaller size. High disease activity genomes display extensive redistribution of co-expression domains with expanded and newly-appearing (emerged) DCEs. The dynamics of domain fragmentation and redistribution are associated with SLE clinical endophenotypes, with genes of the interferon pathway being highly enriched in DCEs that become disrupted and with functions associated to more generalized symptoms, being located in domains that emerge anew in high disease activity genomes. Our results suggest strong links between the SLE phenotype and the underlying genome structure and underline an important role for genome organization in shaping gene expression in SLE.
Best diagnostic accuracy of sepsis combining SIRS criteria or qSOFA score with Procalcitonin and Mid-Regional pro-Adrenomedullin outside ICU
Authors: Spoto Silvia , Nobile Edoardo , Carnà Emanuele Paolo Rafano , Fogolari Marta , Caputo Damiano , De Florio Lucia , Valeriani Emanuele , Benvenuto Domenico , Costantino Sebastiano , Ciccozzi Massimo , Angeletti Silvia 
Published: October 2020

AbstractEarly diagnosis and treatment significantly reduce sepsis mortality. Currently, no gold standard has been yet established to diagnose sepsis outside the ICU. The aim of the study was to evaluate the diagnostic accuracy of sepsis defined by SIRS Criteria of 1991,
Second Consensus Conference Criteria of 2001, modified Second Consensus Conference Criteria of 2001 (obtaining SIRS Criteria and SOFA score), Third Consensus Conference of 2016, in addition to the dosage of Procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM). In this prospective study, 209 consecutive patients with clinical diagnosis of sepsis were enrolled (May 2014–June 2018) outside intensive care unit (ICU) setting. A diagnostic protocol could include SIRS criteria or qSOFA score evaluation, rapid testing of PCT and MR-proADM, and SOFA score calculation for organ failure definition. Using this approach outside the ICU, a rapid diagnostic and prognostic evaluation could be achieved, also in the case of negative SIRS, qSOFA or SOFA scores with high post-test probability to reduce mortality and improve outcomes.
Molecular changes associated with spontaneous phenotypic variation of Paenibacillus polymyxa, a commonly used biocontrol agent, and temperature-dependent control of variation
Authors: Lee Younmi , Kim Young Soo , Balaraju Kotnala , Seo Young-Su , Park Jungwook , Ryu Choong-Min , Park Seung-Hwan , Kim Jihyun F. , Kang Seogchan , Jeon Yongho 
Published: October 2020

AbstractThere has been a growing interest in deploying plant growth-promoting rhizobacteria (PGPR) as a biological control agent (BCA) to reduce the use of agrochemicals. Spontaneous phenotypic variation of PGPR, which causes the loss of traits crucial for biocontrol, presents a large obstacle in producing commercial biocontrol products. Here, we report molecular changes associated with phenotypic variation in Paenibacillus polymyxa, a PGPR widely used for biocontrol worldwide, and a simple cultural change that can prevent the variation. Compared to B-type (non-variant) cells of P. polymyxa strain E681, its phenotypic variant, termed as F-type, fails to form spores, does not confer plant growth-promoting effect, and displays altered colony and cell morphology, motility, antagonism against other microbes, and biofilm formation. This variation was observed in all tested strains of P. polymyxa, but the frequency varied among them. RNA-seq analysis revealed differential regulation of many genes involved in sporulation, flagella synthesis, carbohydrate metabolism, and antimicrobial production in F-type cells, consistent with their pleiotropic phenotypic changes. F-type cells's sporulation was arrested at stage 0, and the key sporulation gene spo0A was upregulated only in B-type cells. The phenotypic variation could be prevented by altering the temperature for growth. When E681 was cultured at 20 °C or lower, it exhibited no variation for 7 days and still reached ~ 108 cfu/mL, the level sufficient for commercial-scale production of biocontrol products.
Continental-scale patterns of hyper-cryptic diversity within the freshwater model taxon Gammarus fossarum (Crustacea, Amphipoda)
Authors: Wattier Remi , Mamos Tomasz , Copilaş-Ciocianu Denis , Jelić Mišel , Ollivier Anthony , Chaumot Arnaud , Danger Michael , Felten Vincent , Piscart Christophe , Žganec Krešimir , Rewicz Tomasz , Wysocka Anna , Rigaud Thierry , Grabowski Michał 
Published: October 2020

AbstractTraditional morphological diagnoses of taxonomic status remain widely used while an increasing number of studies show that one morphospecies might hide cryptic diversity, i.e. lineages with unexpectedly high molecular divergence. This hidden diversity can reach even tens of lineages, i.e. hyper cryptic diversity. Even well-studied model-organisms may exhibit overlooked cryptic diversity. Such is the case of the freshwater crustacean amphipod model taxon Gammarus fossarum. It is extensively used in both applied and basic types of research, including biodiversity assessments, ecotoxicology and evolutionary ecology. Based on COI barcodes of 4926 individuals from 498 sampling sites in 19 European countries, the present paper shows (1) hyper cryptic diversity, ranging from 84 to 152 Molecular Operational Taxonomic Units, (2) ancient diversification starting already 26 Mya in the Oligocene, and (3) high level of lineage syntopy. Even if hyper cryptic diversity was already documented in G. fossarum, the present study increases its extent fourfold, providing a first continental-scale insight into its geographical distribution and establishes several diversification hotspots, notably south-eastern and central Europe. The challenges of recording hyper cryptic diversity in the future are also discussed.
The age distribution of mortality from novel coronavirus disease (COVID-19) suggests no large difference of susceptibility by age
Authors: Omori Ryosuke , Matsuyama Ryota , Nakata Yukihiko 
Published: October 2020

AbstractAmong Italy, Spain, and Japan, the age distributions of COVID-19 mortality show only small variation even though the number of deaths per country shows large variation. To understand the determinant for this situation, we constructed a mathematical model describing the transmission dynamics and natural history of COVID-19 and analyzed the dataset of mortality in Italy, Spain, and Japan. We estimated the parameter which describes the age-dependency of susceptibility by fitting the model to reported data, including the effect of change in contact patterns during the epidemics of COVID-19, and the fraction of symptomatic infections. Our study revealed that if the mortality rate or the fraction of symptomatic infections among all COVID-19 cases does not depend on age, then unrealistically different age-dependencies of susceptibilities against COVID-19 infections between Italy, Japan, and Spain are required to explain the similar age distribution of mortality but different basic reproduction numbers (R0). Variation of susceptibility by age itself cannot explain the robust age distribution in mortality by COVID-19 infections in those three countries, however it does suggest that the age-dependencies of (i) the mortality rate and (ii) the fraction of symptomatic infections among all COVID-19 cases determine the age distribution of mortality by COVID-19.
Robustness of sex-differences in functional connectivity over time in middle-aged marmosets
Authors: Nephew Benjamin C. , Febo Marcelo , Cali Ryan , Workman Kathryn P. , Payne Laurellee , Moore Constance M. , King Jean A. , Lacreuse Agnès 
Published: October 2020

AbstractNonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5–6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations were characterized by greater node strength and/or degree values in several prefrontal, premotor and temporal regions, as well as stronger intra PFC connectivity, in males compared to females. The current study supports the existence of robust sex differences in prefrontal and striatal resting state networks that may contribute to differences in cognitive function and offers insight on the neural systems that may be compromised in cognitive aging and age-related conditions such as mild cognitive impairment and Alzheimer’s disease.
Antiviral activity of a novel mixture of natural antimicrobials, in vitro, and in a chicken infection model in vivo
Authors: Balta Igori , Stef Lavinia , Pet Ioan , Ward Patrick , Callaway Todd , Ricke Steven C. , Gundogdu Ozan , Corcionivoschi Nicolae 
Published: October 2020

AbstractThe aim of this study was to test in vitro the ability of a mixture of citrus extract, maltodextrin, sodium chloride, lactic acid and citric acid (AuraShield L) to inhibit the virulence of infectious bronchitis, Newcastle disease, avian influenza, porcine reproductive and respiratory syndrome (PRRS) and bovine coronavirus viruses. Secondly, in vivo, we have investigated its efficacy against infectious bronchitis using a broiler infection model. In vitro, these antimicrobials had expressed antiviral activity against all five viruses through all phases of the infection process of the host cells. In vivo, the antimicrobial mixture reduced the virus load in the tracheal and lung tissue and significantly reduced the clinical signs of infection and the mortality rate in the experimental group E2 receiving AuraShield L. All these effects were accompanied by a significant reduction in the levels of pro-inflammatory cytokines and an increase in IgA levels and short chain fatty acids (SCFAs) in both trachea and lungs. Our study demonstrated that mixtures of natural antimicrobials, such AuraShield L, can prevent in vitro viral infection of cell cultures. Secondly, in vivo, the efficiency of vaccination was improved by preventing secondary viral infections through a mechanism involving significant increases in SCFA production and increased IgA levels. As a consequence the clinical signs of secondary infections were significantly reduced resulting in recovered production performance and lower mortality rates in the experimental group E2.
A glance at the gut microbiota of five experimental animal species through fecal samples
Authors: Xiang Zhiguang , Zhu Hua , Yang Bochao , Fan Hang , Guo Jianguo , Liu Jiangning , Kong Qi , Teng Qingfeng , Shang Haiquan , Su Lei , Qin Chuan 
Published: October 2020

AbstractExperimental animals including the ferret, marmoset, woodchuck, mini pig, and tree shrew have been used in biomedical research. However, their gut microbiota have not been fully investigated. In this study, the gut microbiota of these five experimental animals were analyzed with 16S rRNA sequencing. The phyla Firmicutes, Bacteroidetes, and Fusobacteria were present in the gut microbiota of all the species. Specific phyla were present in different animals: Proteobacteria in the ferret, Tenericutes in the marmoset, and Spirochaetes in the mini pig. Fusobacterium and unidentified Clostridiales were the dominant genera in the ferret, whereas Libanicoccus, Lactobacillus, Porphyromonas, and Peptoclostridium were specific to marmoset, mini pig, woodchuck, and tree shrew, respectively. A clustering analysis showed that the overall distribution of microbial species in the guts of these species mirrored their mammalian phylogeny, and the microbiota of the marmoset and tree shrew showed the closest bray_curtis distances to that of humans. PICRUSt functional prediction separated the woodchuck from the other species, which may reflect its herbivorous diet. In conclusion, both the evolutionary phylogeny and daily diet affect the gut microbiota of these experimental animals, which should not be neglected for their usage in biomedical research.
Effects of Fundamental Frequency Contours on Sentence Recognition in Mandarin-Speaking Children With Cochlear Implants
Authors: Huang Wanting , Wong Lena L. N. , Chen Fei , Liu Haihong , Liang Wei 
Published: October 2020

PurposeFundamental frequency (F0) is the primary acoustic cue for lexical tone perception in tonal languages but is processed in a limited way in cochlear implant (CI) systems. The aim of this study was to evaluate the importance of F0 contours in sentence recognition in Mandarin-speaking children with CIs and find out whether it is similar to/different from that in age-matched normal-hearing (NH) peers.MethodAge-appropriate sentences, with F0 contours manipulated to be either natural or flattened, were randomly presented to preschool children with CIs and their age-matched peers with NH under three test conditions: in quiet, in white noise, and with competing sentences at 0 dB signal-to-noise ratio.ResultsThe neutralization of F0 contours resulted in a significant reduction in sentence recognition. While this was seen only in noise conditions among NH children, it was observed throughout all test conditions among children with CIs. Moreover, the F0 contour-induced accuracy reduction ratios (i.e., the reduction in sentence recognition resulting from the neutralization of F0 contours compared to the normal F0 condition) were significantly greater in children with CIs than in NH children in all test conditions.ConclusionsF0 contours play a major role in sentence recognition in both quiet and noise among pediatric implantees, and the contribution of the F0 contour is even more salient than that in age-matched NH children. These results also suggest that there may be differences between children with CIs and NH children in how F0 contours are processed.