bluuebunny/crossref_metadata_2025_split huggingface dataset:
A damaged-informed lung ventilator model for ventilator waveforms
Authors: Agrawal Deepak K. , Smith Bradford J. , Sottile Peter D. , Albers David J. 
Published: October 2020

ABSTRACTMotivated by desire to understand pulmonary physiology and pathophysiology, scientists have developed models of pulmonary physiology. However, pathophysiology and interactions between human lungs and ventilators, e.g., ventilator-induced lung injury (VILI), present problems for modeling efforts. Real-world injury is too complex for simple models to capture, and while complex models tend not to be estimable with clinical data, limiting both the clinical utility with existing approaches. To address this gap, we present a damaged-informed lung ventilator (DILV) model to model and quantify patient-ventilator interactions and lung health. This approach relies on systematically mathematizing the pathophysiologic knowledge clinicians use to interpret lung condition from ventilator waveform data. This is achieved by defining clinically relevant features in the ventilator waveform data that contain hypothesis-driven information about pulmonary physiology, patient-ventilator interaction, and ventilator settings. To capture these features, we develop a modelling framework where the model has enough flexibility to reproduce commonly observed variability in waveform data. We infer the model parameters with clinical (human) and laboratory (mouse) data. The DILV model can reproduce essential dynamics of differently damaged lungs for tightly controlled measurements in mice and uncontrolled human intensive care unit data in the absence and presence of respiratory effort. Estimated parameters correlate with known measures of lung physiology, including lung compliance. This method has the potential to translate laboratory physiology experiments to clinical applications, including pathways for high fidelity estimates of lung state and sources of VILI with an end goal of reducing the impact of VILI and acute respiratory distress syndrome.
MADS-box genes galore in wheat genome: phylogenomics, evolution and stress associated functions
Authors: Raza Qasim , Riaz Awais , Atif Rana Muhammad , Hussain Babar , Ali Zulfiqar , Budak Hikmet 
Published: October 2020

AbstractMADS-box gene family members play multifarious roles in regulating the growth and development of crop plants and hold enormous promise for bolstering grain yield potential under changing global environments. Bread wheat (Triticum aestivumL.) is a key stable food crop around the globe. Until now, the available information concerning MADS-box genes in the wheat genome has been insufficient. However, a comprehensive genome-wide analysis identified 300 high confidence MADS-box genes from the latest publicly available reference genome of wheat. Comparative phylogenetic analyses withArabidopsisand rice MADS-box genes classified the wheat genes into 16 distinct subfamilies, without a singleFLOWERING LOCUS Chomolog present in the wheat genome. Gene duplications were mainly identified in subfamilies containing unbalanced homeologs, pointing towards a potential mechanism for gene family expansion. Moreover, a more recent evolutionary origin was inferred for M-type genes, as compared with MIKC-type genes, indicating their significance in understanding the evolutionary history of the wheat genome. We speculate that subfamily-specific distal telomeric duplications in unbalanced homeologs facilitate the rapid adaptation of wheat to changing environments. Furthermore, ourin-silicoexpression data strongly proposed MADS-box genes as active guardians of plants against pathogen insurgency and harsh environmental conditions. In conclusion, we provide an entire complement of MADS-box genes identified in the wheat genome that will accelerate functional genomics efforts and possibly facilitate bridging gaps between genotype-to-phenotype relationships through fine-tuning of agronomically important traits.
Epidemiological dynamics of bacteriocin competition and antibiotic resistance
Authors: Lehtinen Sonja , Croucher Nicholas J. , Blanquart François , Fraser Christophe 
Published: October 2020

AbstractBacteriocins, toxic peptides involved in the competition between bacterial strains, are extremely diverse. Previous work on bacteriocin dynamics has highlighted the role of non-transitive ‘rock-paper-scissors’ competition in maintaining the coexistence of different bacteriocin profiles. The focus to date has primarily been on bacteriocin interactions at the within-host scale. Yet, in species such asStreptococcus pneumoniaewith relatively short periods of colonisation and limited within-host diversity, ecological outcomes are also shaped by processes at the epidemiological (between-host) scale. Here, we first investigate bacteriocin dynamics and diversity in epidemiological models. We find that in these models, bacteriocin diversity is more readily maintained than in within-host models, and with more possible combinations of coexisting bacteriocin profiles. Indeed, maintenance of diversity in epidemiological models does not require rock-paper-scissors dynamics; it can also occur through a competition-colonisation trade-off. Second, we investigate the link between bacteriocin diversity and diversity at antibiotic resistance loci. Previous work has proposed that bacterial duration of colonisation modulates the fitness of antibiotic resistance. Due to their inhibitory effects, bacteriocins are a plausible candidate for playing a role in the duration of colonisation episodes. We extend the epidemiological model of bacteriocin dynamics to incorporate an antibiotic resistance locus and demonstrate that bacteriocin diversity can indeed maintain the coexistence of antibiotic sensitive and resistant strains.
Limited and strain-specific transcriptional and growth responses to acquisition of a multidrug resistance plasmid in genetically diverseEscherichia colilineages
Authors: Dunn Steven , Carrilero Laura , Brockhurst Michael , McNally Alan 
Published: October 2020

AbstractMulti-drug resistant (MDR)Escherichia coliare a major global threat to human health, wherein multi-drug resistance is primarily spread by MDR plasmid acquisition. MDR plasmids are not widely distributed across the entireE. colispecies, but instead are concentrated in a small number of clones. Here, we test if diverseE. colistrains vary in their ability to acquire and maintain MDR plasmids, and if this relates to their transcriptional response following plasmid acquisition. We used strains from across the diversity ofE. coli,including the common MDR lineage ST131, and the IncF plasmid, pLL35, encoding multiple antibiotic resistance genes. Strains varied in their ability to acquire pLL35 by conjugation, but all were able to stably maintain the plasmid. The effects of pLL35 acquisition on cefotaxime resistance and growth also varied among strains, with growth responses ranging from a small decrease to a small increase in growth of the plasmid-carrier relative to the parental strain. Transcriptional responses to pLL35 acquisition were limited in scale and highly strain specific. We observed significant transcriptional responses at the operon or regulon level, possibly due to stress responses or interactions with resident MGEs. Subtle transcriptional responses consistent across all strains were observed affecting functions, such as anaerobic metabolism, previously shown to be under negative frequency dependent selection in MDRE. coli.Overall, there was no correlation between the magnitude of the transcriptional and growth responses across strains. Together these data suggest that fitness costs arising from transcriptional disruption are unlikely to act as a barrier to dissemination of this MDR plasmid inE. coli.ImportancePlasmids play a key role in bacterial evolution by transferring niche adaptive functions between lineages, including driving the spread of antibiotic resistance genes. Fitness costs of plasmid acquisition arising from the disruption of cellular processes could limit the spread of multidrug resistance plasmids. However, the impacts of plasmid acquisition are typically measured in lab-adapted strains rather than in more ecologically relevant natural isolates. Using a clinical multidrug resistance plasmid and a diverse collection ofE. colistrains isolated from clinical infections and natural environments, we show that plasmid acquisition had only limited and highly strain-specific effects on bacterial growth and transcription. These findings suggest that fitness costs arising from transcriptional disruption are unlikely to act as a barrier to transmission of this plasmid in natural populations ofE. coli.
Synthetic model ecosystem of 12 cryopreservable microbial species allowing for a noninvasive approach
Authors: Hosoda Kazufumi , Seno Shigeto , Murakami Naomi , Matsuda Hideo , Osada Yutaka , Kamiura Rikuto , Kondoh Michio 
Published: October 2020

AbstractSimultaneous understanding of both individual and ecosystem dynamics is crucial in an era marked by the degradation of ecosystem services. Herein, we present a high-throughput synthetic microcosm system comprising 12 functionally and phylogenetically diverse microbial species. These species are axenically culturable, cryopreservable, and can be measured noninvasively via microscopy, aided by machine learning. This system includes prokaryotic and eukaryotic producers and decomposers, and eukaryotic consumers to ensure functional redundancy. Our model system displayed both positive and negative interspecific interactions and higher-order interactions that surpassed the scope of any two-species interaction. Although complete species coexistence was not our primary objective, we identified several conditions under which at least one species from the producers, consumers, and decomposers groups, and one functionally redundant species, persisted for over six months. These conditions set the stage for detailed investigations in the future. Given its designability and experimental replicability, our model ecosystem offers a promising platform for deeper insights into both individual and ecosystem dynamics, including evolution and species interactions.
EEG alpha-theta dynamics during mind wandering in the context of breath focus meditation: an experience sampling approach with novice meditation practitioners
Authors: Rodriguez-Larios Julio , Alaerts Kaat 
Published: October 2020

ABSTRACTMeditation practice entails moments of distraction dominated by self-generated thoughts (i.e. mind wandering). Initial studies assessing the neural correlates of mind wandering in the context of meditation practice have identified an important role of theta (4-8 Hz) and alpha (8-14 Hz) neural oscillations. In this study, we use a probe-caught experience sampling paradigm to assess spectral changes in the theta-alpha frequency range during mind wandering in the context of breath focus meditation. Electroencephalography (EEG) was measured in 25 novice meditation practitioners during a breath focus task in which they were repeatedly probed to report whether they were focusing on their breath or thinking about something else. Mind wandering episodes were associated with an increase in the amplitude and a decrease in the frequency of theta (4-8 Hz) oscillations. Conversely, alpha oscillations (8-14 Hz) were shown to decrease in amplitude and increase in frequency during mind wandering relative to breath focus. In addition, mind wandering episodes were shown to be accompanied by increased harmonicity and phase synchrony between alpha and theta rhythms. Because similar spectral changes in the theta-alpha frequency range have been reported during controlled cognitive processes involving memory and executive control, we speculate that mind wandering and controlled processes could share some neurocognitive mechanisms. From a translational perspective, this study indicates that oscillatory activity in the theta-alpha frequency range could form adequate parameters for developing EEG-neurofeedback protocols aimed at facilitating the detection of mind wandering during meditation practice.
mRNA based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus neutralizing antibodies and mediates protection in rodents
Authors: Rauch Susanne , Roth Nicole , Schwendt Kim , Fotin-Mleczek Mariola , Mueller Stefan O. , Petsch Benjamin 
Published: October 2020

AbstractmRNA technologies have recently proven clinical efficacy against coronavirus disease 2019 (COVID-19) and are among the most promising technologies to address the current pandemic. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle encapsulated mRNA vaccine that encodes full length, pre-fusion stabilised severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Spike protein. In contrast to previously published approaches, CVnCoV is exclusively composed of naturally occurring nucleotides. Immunisation with CVnCoV induced strong humoral responses with high titres of virus neutralizing antibodies and robust T cell responses. CVnCoV vaccination protected hamsters from challenge with wild type SARS-CoV-2, demonstrated by the absence of viral replication in the lungs. Hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication exhibited no evidence of vaccine enhanced disease. Overall, data presented here provide evidence that CVnCoV represents a potent and safe vaccine candidate against SARS-CoV-2.
Establishment of a simplified preparation method for single-nucleus RNA-sequencing and its application to long-term frozen tumor tissues
Authors: Ernst Kati J. , Okonechnikov Konstantin , Bageritz Josephine , Mallm Jan-Philipp , Wittmann Andrea , Maaß Kendra K. , Leible Svenja , Boutros Michael , Pfister Stefan M. , Zuckermann Marc , Jones David T.W. 
Published: October 2020

AbstractRecent advances allowing the genomic analysis of individual cells from a bulk population have provided intriguing new insights into areas such as developmental processes and tumor heterogeneity. Most approaches to date, however, rely on the availability of fresh surgical specimens, thereby dramatically reducing the ability to profile particularly rare tissue types. Pediatric central nervous system tumors – the leading cause of childhood cancer deaths – represent one such example, where often only frozen rather than native material is available. Due to an increasing need for advanced techniques to understand the heterogeneity of these tumors, we optimized a method to isolate intact nuclei from long-term frozen pediatric glioma tissues. We performed a technical comparison between different single nucleus RNA-sequencing (snRNA-seq) systems using a patient-derived xenograft model as a test sample. Further, we applied the established nucleus isolation method to analyze frozen primary tissue from two pediatric central nervous system tumors – one pilocytic astrocytoma and one glioblastoma – allowing the identification of distinct tumor cell populations and infiltrating microglia. The results show that our fast, simple and low-cost nuclear isolation protocol provides intact nuclei, which can be used in both droplet-based 3’ transcriptome amplification (10X Genomics) and plate-based whole transcriptome amplification (Fluidigm C1) single-cell sequencing platforms, thereby dramatically increasing the potential for application of such methods to rare entities.
Oral immunization of broilers with chitosan nano-encapsulated extracellular and cell wall proteins of necrotic enteritis-inducedClostridium perfringens
Authors: Ramadan Nour Muinis , Akerele Gabriel , Renu Sankar , Renukaradhya Gourapura , Selvaraj Ramesh 
Published: October 2020

AbstractCurrently, there is no commercial vaccine to controlClostridium perfringens(CP) or necrotic enteritis – a clinically and economically devastating disease. Two chitosan-nanoparticle encapsulated CP (CNP-CP) vaccines using extracellular proteins (ECP) and cell wall proteins (CWP) were synthesized: a CNP-CP ECP + CWP vaccine (SC vaccine) and a CNP-CP ECP + CWP surface-adsorbed CWP vaccine (SCC vaccine). The experiment comprised a complete randomized design of 3 treatments replicated 5 times: SC, SCC and nonimmunized control. Broilers orally gavaged with SC or SCC vaccine were primed and boosted with 70μg dose at 3- and 14-days post-hatch (dph). SDS-PAGE analysis revealed bands at 54.7 and 84.7 kDa in the ECP and 17 bands for CWP fraction. There were no differences in body weight gain, feed conversion ratio and mortality rate between treatments. At 17dph, serum of birds in the SC and SCC groups had higher neutralizing antibodies (P<0.01) compared to the control group. At 17dph, there was an increase in bile anti-ECP IgA levels in the SC vaccinated birds and a non-significant increase in SCC vaccinated birds compared to control. At 17dph, bile specific anti-CP CWP IgA levels were greater (P<0.05) in both immunized groups compared to control. At 17 and 21dph, serum anti-ECP and anti-CP CWP IgY levels in SC and SCC birds were comparable to the control. At 21dph, CD4+/CD8+ T-cell ratio in SC and SCC vaccinated groups were elevated (P≤0.01) compared to control. At 17dph, SC and SCC vaccinated birds had a significant reduction(P≤0.001)in α-toxin levels in caecal contents compared to control. Caecal α-toxin levels remained reduced at 21dph(P<0.05)in SC birds and numerically reduced in SCC vaccinated birds compared to control. Jejunal CP load in SCC birds was significantly reduced by 1.4 Log10copy numbers of CP/g compared to control and no differences were observed in liver CP load between immunized and non-immunized birds. SC and SCC immunization did not alter TNF-α, IL-10, iNOS, IL-6 or IL-17 mRNA expression. At 17 and 21dph, SC and SCC immunized birds demonstrated greater sera bactericidal activity compared to control. CNP-SC and CNP-SCC immunization induced specific immune response againstC. perfringensand reduced CP colonization via oral route of administration.
Lactate transport at the uteroplacental unit- A theoretical study
Authors: Barta Efrath 
Published: October 2020

AbstractDeciphering the lactate transport within the uteroplacental unit should be aided by a theoretical model in light of the insurmountable difficulties involved with in-vivo relevant measurements. Here we formulate a boundary value problem that predicts the direction and extent of lactate fluxes within the human placenta under various physiological conditions. It accounts for metabolic processes within the placenta and transporters’ activity at the two membranes that confine the terminal villi. Lactate concentration inside the terminal villi and its fluxes at the membranes are being computed. Under normal conditions lactate flux from fetal arterioles to the placenta surpasses the flux to the fetus via the umbilical vein. Within the placenta, it adds to the lactate that originates in the glycolysis, some of it degrades to pyruvate and surpluses are delivered to the maternal circulation. The apparent permeabilities of the placental membranes with respect to lactate as well as the specific characterizations of the placental lactate production, hitherto unknown, are being estimated. We determine the range of parameter values that induce sustainable, healthy fetal lactate levels and demonstrate the versatility of lactate exchange between the placenta and the fetus by computing the effect of extreme conditions (e.g., cesarean section, intrauterine growth restriction) on lactate fluxes.
Human mobility at Tell Atchana (Alalakh) during the 2nd millennium BC: integration of isotopic and genomic evidence
Authors: Ingman Tara , Eisenmann Stefanie , Skourtanioti Eirini , Akar Murat , Ilgner Jana , Gnecchi Ruscone Guido Alberto , le Roux Petrus , Shafiq Rula , Neumann Gunnar U. , Keller Marcel , Freund Cäcilia , Marzo Sara , Lucas Mary , Krause Johannes , Roberts Patrick , Yener K. Aslıhan , Stockhammer Philipp W. 
Published: October 2020

AbstractThe Middle and Late Bronze Age Near East, a period roughly spanning the second millennium BC (ca. 2000-1200 BC), is frequently referred to as the first ‘international age’, characterized by intense and far-reaching contacts between different entities from the eastern Mediterranean to the Near East and beyond. In a large-scale tandem study of stable isotopes and ancient DNA of individuals excavated at Tell Atchana (Alalakh), situated in the northern Levant, we explore the role of mobility at the capital of a regional kingdom. We generated strontium isotope data for 53 individuals, oxygen isotope data for 77 individuals, and added ancient DNA data from 9 new individuals to a recently published dataset of 28 individuals. A dataset like this, from a single site in the Near East, is thus far unparalleled in terms of both its breadth and depth, providing the opportunity to simultaneously obtain an in-depth view of individual mobility and also broader demographic insights into the resident population. The DNA data reveals a very homogeneous gene pool, with only one outlier. This picture of an overwhelmingly local ancestry is consistent with the evidence of local upbringing in most of the individuals indicated by the isotopic data, where only five were found to be ‘non-local’. High levels of contact, trade, and exchange of ideas and goods in the Middle and Late Bronze Ages, therefore, seem not to have translated into high levels of individual mobility detectable at Tell Atchana.
FUNGI DIVERSITY IN THE RHIZOSPHERE OFAspilia prulisetaSchweif. ext Schweif IN THE SEMI-ARID EASTERN KENYA
Authors: Muchoka James Peter , Mugendi Daniel Njiru , Njiruh Paul Nthakanio , Mbugua Paul Kamau , Njeru Ezekiel Mugendi , Ghilamicael Amanuel Menghs , Mutiga Mariciano Iguna 
Published: October 2020

AbstractSemi-arid eastern Kenya is a fragile ecosystem with continuous cultivation of dryland pulses and grains. Farmers use artificial fertilizers most of which are deleterious to the environment. Previous studies have shown that soil microbes in the rhizosphere could be used to sustainably enhance levels of soil mineral nutrients and soil health. However, few studies have examined fungal diversity in the rhizosphere of wild and nativeAspilia prulisetashrub. In this study, amplicons of Internal Transcribed Spacer (ITS) region on Total Community DNA using Illumina sequencing were used to explore the fungal community composition within the rhizosphere. Operational taxonomic units (OTUs) were analyzed using QIIME 1.8.0, taxonomy assigned via BLASTn against SILVA 119 database. Hierarchical clustering was done using R programming software. 72,093, 50,539 and 43,506 sequence reads were obtained from samples MC1a, MC2aand MC3arespectively representing rhizosphere depth 0-20 cm, 21-40 cm and 41-60 cm. A total of 373 OTUs were realized at 3% genetic distance. Taxonomic analysis revealed that the generaGlomuswas most prevalent in all soil depths with 85.60 % of the OTUs in depth 0-20 cm, 69.04 % in depth 21-40 cm and 48.45 % in depth 41-60 cm. The results revealed high levels of obligate arbuscular mycorrhiza fungi that if commercially cultured could enhance phosphates uptake in crops.