bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the impact of disease and vaccine mechanisms on the importance of optimal vaccine allocation
Authors: Abell Isobel R. , McCaw James M. , Baker Christopher M. 
Published: July 2022

AbstractVaccination is an important epidemic intervention strategy. Resource limitations and an imperative for efficient use of public resources drives a need for optimal allocation of vaccines within a population. For a disease causing severe illness in particular members of a population, an effective strategy to reduce illness might be to vaccinate those vulnerable with a vaccine that reduces the chance of catching a disease. However, it is not clear that this is the best strategy, and it is generally unclear how the difference between various vaccine strategies changes depending on population characteristics, vaccine mechanisms and allocation objective. In this paper we develop a conceptual mathematical model to consider strategies for vaccine allocation, prior to the establishment of community transmission. By extending the SEIR model to incorporate a range of vaccine mechanisms and disease characteristics, we simulate the impact of vaccination on a population with two sub-groups of differing characteristics. We then compare the outcomes of optimal and suboptimal vaccination strategies for a range of public health objectives using numerical optimisation. Our comparison serves to demonstrate that the difference between vaccinating optimally and suboptimally may be dependent on vaccine mechanism, diseases characteristics, and objective considered. We find that better resources do not guarantee better outcomes. Allocating optimally with lesser vaccine resources can produce a better outcome than allocating good vaccine resources suboptimally, dependent on vaccine mechanisms, disease characteristics and objective considered. Through a principled model-based process, this work highlights the importance of designing effective vaccine allocation strategies. This design process requires models that incorporate known biological characteristics, realistic parameters based on data analysis, etc. Overall, we see that allocation of resources can be just as crucial to the success of a vaccination strategy as the strength of resources available.
Habitual exercise evokes fast and persistent adaptation during split-belt walking
Authors: Brinkerhoff Sarah A. , Sánchez Natalia , Roper Jaimie A. 
Published: July 2022

AbstractChanging movement patterns in response to environmental perturbations is a critical aspect of gait and is related to reducing the energetic cost of the movement. Exercise improves energetic capacity for submaximal exercise and may affect how people adapt movement to reach an energetic minimum. The purpose of this study was to determine whether self-reported exercise behavior influences gait adaptation in young adults. Young adults who met the optimal volume of exercise according to the Physical Activity Guidelines for Americans (MOVE; n=19) and young adults who did not meet the optimal volume of exercise (notMOVE; n=13) walked on a split-belt treadmill with one belt moving twice the speed of the other belt for 10 minutes. Step length asymmetry (SLA) and mechanical work done by each leg were measured. Nonlinear mixed effects models compared the time course of adaptation between MOVE and notMOVE, andt-tests compared net work at the end of adaptation between MOVE and notMOVE. Compared to notMOVE, MOVE had a faster initial response to the split belt treadmill, and continued to adapt over the duration of split-belt treadmill walking. Young adults who engage in sufficient amounts of exercise responded more quickly to the onset of a perturbation, and throughout the perturbation they continued to explore movement strategies, which might be related to reduction of energetic cost. Our findings provide insights into the multisystem positive effects of exercise, including walking adaptation.
Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe
Authors: Kerner Gaspard , Neehus Anna-Lena , Abel Laurent , Casanova Jean-Laurent , Patin Etienne , Laval Guillaume , Quintana-Murci Lluis 
Published: July 2022

ABSTRACTAncient genomics can directly detect human genetic adaptation to environmental cues. However, it remains unclear how pathogens have exerted selective pressures on human genome diversity across different epochs and affected present-day inflammatory disease risk. Here, we use an ancestry-aware approximate Bayesian computation framework to estimate the nature, strength, and time of onset of selection acting on 2,879 ancient and modern European genomes from the last 10,000 years. We found that the bulk of genetic adaptation occurred after the start of the Bronze Age, <4,500 years ago, and was enriched in genes relating to host-pathogen interactions. Furthermore, we detected directional selection acting on specific leukocytic lineages and experimentally demonstrated that the strongest negatively selected immunity gene variant — the lipopolysaccharide-binding protein gene (LBP) D283G — is hypomorphic. Finally, our analyses suggest that the risk of inflammatory disorders has progressively increased in post-Neolithic Europeans, partly due to antagonistic pleiotropy following genetic adaptation to pathogens.
The pH-sensing Rim101 pathway regulates cell size in budding yeast
Authors: Shimasawa Masaru , Sakamaki Jun-ichi , Mizushima Noboru 
Published: July 2022

AbstractAlthough cell size regulation is crucial for cellular functions in a variety of organisms, from bacteria to humans, the underlying mechanisms remain elusive. Here, we identify Rim21, a component of the pH-sensing Rim101 pathway, as a positive regulator of cell size through a genome-wide screen of Saccharomyces cerevisiae deletion mutants. We found that mutants defective in the Rim101 pathway were consistently smaller than wild-type cells in the log and stationary phases. The expression of the active form of Rim101 increased the size of wild-type cells. Furthermore, the size of wild-type cells increased in response to external alkalization, which was associated with changes in both vacuolar and cytoplasmic volume. These volume changes were dependent on Rim21 and Rim101. A mutant lacking Vph1, a component of V-ATPase that is transcriptionally regulated by Rim101, was also smaller than wild-type cells, with no increase in size in response to alkalization. The loss of Vph1 suppressed the Rim101-induced increase in cell size under physiological pH conditions. Our results suggest that the cell size of budding yeast is regulated by the Rim101 and V-ATPase axis under physiological conditions as well as in response to alkaline stresses.
A systematic investigation of lactic acid bacteria-derived biosynthetic gene clusters reveals diverse antagonistic bacteriocins in the human microbiome
Authors: Zhang Dengwei , Zhang Jian , Kalimuthu Shanthini , Liu Jing , Song Zhiman , He Beibei , Cai Peiyan , Zhong Zheng , Feng Chenchen , Neelakantan Prasanna , Li Yong-Xin 
Published: July 2022

AbstractLactic acid bacteria (LAB) produce various bioactive secondary metabolites (SMs), which endow LAB with a protective role for the host. However, the biosynthetic potentials of LAB-derived SMs remain elusive, particularly in their diversity, abundance, and distribution in the human microbiome. To gain an insight into the biosynthetic capacity of LAB, we analyzed the biosynthetic gene clusters (BGCs) from 31,977 LAB genomes and 748 human microbiome metagenomes, identifying 130,051 BGCs. The found BGCs were clustered into 2,849 gene cluster families (GCFs), most of which are species-specific, niche-specific, and uncharacterized yet. We found that most LAB BGCs encoded bacteriocins with pervasive antagonistic activities predicted by machine learning models, potentially playing protective roles in the human microbiome. Class II bacteriocins, the most abundant LAB SMs, are particularly enriched and predominant in vaginal microbiomes. Together with experimental validation, our metagenomic and metatranscriptomic analysis showed that class II bacteriocins with antagonistic potential might regulate microbial communities in the vagina, thereby contributing to homeostasis. These discoveries of the diverse and prevalent antagonistic SMs are expected to stimulate the mechanism study of LAB’s protective roles in the host and highlight the potential of LAB as a new source of antibacterial SMs.
In-depth investigation of microRNA-mediated cross-kingdom regulation between Asian honey bee and microsporidian
Authors: Fan Xiaoxue , Zhang Wende , Zhang Kaiyao , Zhang Jiaxin , Long Qi , Wu Ying , Zhang Kuihao , Zhu Leran , Chen Dafu , Guo Rui 
Published: July 2022

AbstractAsian honey bee Apis cerana is the original host for Nosema ceranae, a unicellular fungal parasite that causes bee nosemosis throughout the world. Currently, interaction between A. cerana and N. ceranae is largely unknown. Here, based on our previously gained high-quality RNA-seq and small RNA-seq data from N. ceranae-infected A. c. cerana workers’ midguts and clean spores, differentially expressed mRNAs (DEmiRNAs) in N. ceranae targeted by DEmiRNAs in host midguts and A. c. cerana DEmRNAs targeted by microsporidian DEmiRNAs were predicted using bioinformatics, and then target DEmRNAs in microsporidian and host were annotated and investigated, with a focus on targets involved in N. ceranae glycolysis/glyconeogenesis and virulence factors as well as A. c. cerana energy mechanism and immune response. It’s found that 97 down-regulated (60 up-regulated) mRNAs in NcCKM vs NcTM1 were potentially targeted by eight up-regulated (six down-regulated) miRNAs in AcCKMI1 vs AcTMI1, 44 down-regulated (15 up-regulated) mRNAs in NcCKM vs NcTM2 were putative targets of seven up-regulated (two down-regulated) miRNAs in AcCKMI2 vs AcTMI2. Additionally, miR-60-y and miR-676-y were found to up-regulate in AcCKMI1 vs AcTMI1 and target genes engaged in spore wall protein and glycolysis/gluconeogenesis, while miR-60-y in AcCKMI1 vs AcTMI1 was up-regulated and potentially targeted a glycolysis/gluconeogenesis-associated gene. Comparatively, 343 down-regulated (138 up-regulated) mRNAs in AcCKM1 vs AcTM1 were putative targets of 121 up-regulated (112 down-regulated) miRNAs in NcCKMI vs NcTMI1, 247 down-regulated (110 up-regulated) mRNAs were putatively targeted by 110 up-regulated (104 down-regulated) miRNAs in NcCKMI vs NcTMI2. Further analysis showed that 31 up-regulated miRNAs in NcCKMI vs NcTMI1 potentially targeted 12 down-regulated mRNAs in AcCKM1 vs AcTM1, which were involved in five immune-related pathways such as phagasome and Jak-STAT signaling pathway, whereas nine up-regulated miRNAs in NcCKMI vs NcTMI2 putatively targeted five down-regulated mRNAs in AcCKM2 vs AcTM2, which were engaged in three immune-related pathways including endocytosis, lysosomes, and regulation of autophagy. In addition, miR-21-x was observed to up-regulate in NcCKMI vs NcTMI1 and target a oxidative phosphorylation-related gene. Finally, potential targeting relationship between two host DEmiRNAs-microsporidian DEmRNAs pairs and two microsporidian DEmiRNAs-host DEmRNAs pairs were verified on basis of RT-qPCR. Our findings not only lay a foundation for exploring the molecular mechanism underlying cross-kingdom regulation between A. c. cerana workers and N. ceranae, but also offer valuable insights into Asian honey bee-microsporidian interaction.
Signatures of contextual interference in implicit sensorimotor adaptation
Authors: Tsay Jonathan S. , Irving Carolyn , Ivry Richard B. 
Published: July 2022

AbstractContextual interference refers to the phenomenon whereby a blocked practice schedule results in faster acquisition but poorer retention of new motor skills compared to a random practice schedule. While contextual interference has been observed under a broad range of tasks, it remains unclear if this effect generalizes to the implicit and automatic recalibration of an overlearned motor skill. To address this question, we compared blocked and random practice schedules on a reaching task in which we used a feedback perturbation method that isolates implicit adaptation. The degree of implicit adaptation was quantified as the change in hand angle in the opposite direction of the perturbation, and retention was quantified as the percent of adaptation remaining after visual feedback was extinguished. In two experiments, participants tested under a random practice schedule exhibited slower implicit adaptation, but better retention compared to participants tested under a blocked practice schedule, the signature of contextual interference. These results indicate that contextual interference is not limited to the acquisition of new motor skills but also applies to the implicit adaptation of established motor skills.
Environmental pH signals the release of monosaccharides from cell wall in coral symbiotic alga
Authors: Ishii Yuu , Ishii Hironori , Kuroha Takeshi , Yokoyama Ryusuke , Deguchi Ryusaku , Nishitani Kazuhiko , Minagawa Jun , Kawata Masakado , Takahashi Shunichi , Maruyama Shinichiro 
Published: July 2022

AbstractReef-building corals thrive in oligotrophic environments due to their possession of endosymbiotic algae. Confined to the low pH interior of the symbiosome within the cell, the algal symbiont provides the coral host with photosynthetically fixed carbon. However, it remains unknown how carbon is released from the algal symbiont for uptake by the host. Here we show, using cultured symbiotic dinoflagellate, Breviolum sp., that decreases in pH directly accelerates the release of monosaccharides, i.e., glucose and galactose, into the ambient environment. Under low pH conditions, the cell surface structures were deformed and genes related to cellulase were significantly upregulated in Breviolum. Importantly, the release of monosaccharides was suppressed by the cellulase inhibitor, glucopyranoside, linking the release of carbon to degradation of the agal cell wall. Our results suggest that the low pH signals the cellulase-mediated release of monosaccharides from the algal cell wall as an environmental response in coral reef ecosystems.
Zbtb14 regulates monocyte and macrophage development through inhibiting pu.1 expression in zebrafish
Authors: Deng Yun , Wang Haihong , Liu Xiaohui , Yuan Hao , Xu Jin , de Thé Hugues , Zhou Jun , Zhu Jun 
Published: July 2022

AbstractMacrophages and their precursor cells, monocytes, are the first line of defense of the body against foreign pathogens and tissue damage. Although the origins of macrophages are diverse, some common transcription factors (such as PU.1) are required to ensure proper development of monocytes/macrophages. Here we report that the deficiency of zbtb14, a transcription repressor gene belonging to ZBTB family, leads to an aberrant expansion of monocyte/macrophage population in zebrafish. Mechanistically, Zbtb14 functions as a negative regulator of pu.1, and SUMOylation on a conserved lysine is essential for the repression activity of Zbtb14. Moreover, a serine to phenylalanine mutation found in an acute myeloid leukemia (AML) patient could target ZBTB14 protein to autophagic degradation. Hence, ZBTB14 is a newly identified gene implicated in both normal and malignant myelopoiesis.
Process-based modelling of microbial community dynamics in the human colon
Authors: Kettle Helen , Louis Petra , Flint Harry J. 
Published: July 2022

AbstractThe human colon contains a dynamic microbial community whose composition has important implications for human health. In this work we build a process-based model of the colonic microbial ecosystem and compare with general empirical observations and the results of in-vivo experiments. Based our previous work (Kettle et al., 2015), the microbial model consists of 10 microbial functional groups, 4 substrates and 10 metabolites; to this we add the interaction with a human host to give simulations of the in-situ colonic microbial ecosystem. This model incorporates absorption of short chain fatty acids (SCFA) and water by the host through the gut wall, variations in incoming dietary substrates (in the form of “meals” whose composition varies in time), bowel movements, feedback on microbial growth from changes in pH resulting from SCFA production, and multiple compartments to represent the proximal, transverse and distal colon. We verify our model against a number of observed criteria, e.g. total SCFA concentrations, SCFA ratios, mass of bowel movements, pH and water absorption over the transit time; and then run simulations investigating the effect of colonic transit time, and the composition and amount of indigestible carbohydrate in the host diet, which we compare with in-vivo studies. Gut microbiota are highly complex and poory understood yet our work shows that it is nevertheless possible to develop predictive models of the key components of the dynamics of this ecological system. The code is available as an R package (microPopGut) to aid future research.Author SummaryKettle wrote the model code and led the writing of the manuscript. Louis and Flint both contributed to writing the manuscript and all aspects of microbiolgy. All authors contributed critically to the drafts and gave final approval for publication.
Zyxin contributes to coupling between cell junctions and contractile actomyosin networks during apical constriction
Authors: Slabodnick Mark M. , Tintori Sophia C. , Prakash Mangal , Zhang Pu , Higgins Christopher D. , Chen Alicia H. , Cupp Timothy D. , Wong Terrence , Bowie Emily , Jug Florian , Goldstein Bob 
Published: July 2022

AbstractOne of the most common cell shape changes driving morphogenesis in diverse animals is the constriction of the apical cell surface. Apical constriction depends on contraction of an actomyosin network in the apical cell cortex, but such actomyosin networks have been shown to undergo continual, conveyor belt-like contractions before the shrinking of an apical surface begins. This finding suggests that apical constriction is not necessarily triggered by the contraction of actomyosin networks, but rather can be triggered by unidentified, temporally-regulated mechanical links between actomyosin and junctions. Here, we usedC. elegansgastrulation as a model to seek genes that contribute to such dynamic linkage. We found that α-catenin and β-catenin initially failed to move centripetally with contracting cortical actomyosin networks, suggesting that linkage is regulated between intact cadherin-catenin complexes and actomyosin. We used proteomic and transcriptomic approaches to identify new players, including the candidate linkers AFD-1/afadin and ZYX-1/zyxin, as contributing toC. elegansgastrulation. We found that ZYX-1/zyxin is among a family of LIM domain proteins that have transcripts that become enriched in multiple cells just before they undergo apical constriction. We developed a semi-automated image analysis tool to describe rates of myosin and membrane movement, which we then used to discover that ZYX-1/zyxin contributes to cell-cell junctions’ centripetal movement in concert with contracting actomyosin networks. These results identify several new genes that contribute toC. elegansgastrulation, and they identify zyxin as a key protein important for actomyosin networks to effectively pull cell-cell junctions inward during apical constriction. The transcriptional upregulation of ZYX-1/zyxin in specific cells inC. eleganspoints to one way that developmental patterning spatiotemporally regulates cell biological mechanismsin vivo. Because zyxin and related proteins contribute to membrane-cytoskeleton linkage in other systems, we anticipate that its roles in regulating apical constriction in this manner may be conserved.
Pervasive approximate periodic symmetry in organic P1 structures
Authors: Brock Carolyn Pratt 
Published: July 2022

The goal of this project was to identify the prevalence of approximate symmetry in organic P1 structures. In the November 2019 version of the Cambridge Structural Database (CSD), there are 2592 organic, P1, R ≤ 0.050 structures; complete, unique entries are available for 1407 Z = Z′ > 1 and 1049 Z = Z′ = 1 structures. All the Z > 1 structures can have approximate symmetry; the Z = 1 structures were scanned to find those composed of molecules or ions that might lie on a special position and those that have two or more large molecules or ions that are very similar. The number of Z = 1 structures so identified was 285, of which 49 were grouped with the Z > 1 structures because Z
effective > 1. The packing in each of the 1407 + 285 = 1692 structures was investigated. The 144 that should almost certainly have been described in a smaller or higher-symmetry unit cell were removed from the list; 120 of the 144 are composed of achiral or racemic material. (About half of the Z = 1 and 89% of the Z > 1 structures are composed of enantiopure material.) Approximate periodic symmetry was found in 86% of the 1337 remaining Z > 1 structures and in 72% of the 211 remaining Z = 1 structures. About a third of the enantiomerically pure structures mimic inversion symmetry; 38% have approximate rotational symmetry. For the structures of achiral and racemic material, distorted glide or mirror symmetry is more common than is distorted inversion symmetry. Approximate rotational and glide symmetry was found to be periodic in two dimensions considerably more often than in three. In 4% of the structures, different layer types alternate or layers are related by approximate local rotations, as well as by small translations. In 5% of the structures, different parts of the molecule are segregated into two-dimensional regions that have different approximate symmetries. More than a third of the structures that are a distorted version of a higher-symmetry structure were determined at T ≥ 288 K.
Electric supply and demand forecasting using seasonal grey model based on PSO-SVR
Authors: Yao Xianting , Mao Shuhua 
Published: July 2022

PurposeGiven the effects of natural and social factors, data on both the supply and demand sides of electricity will produce obvious seasonal fluctuations. The purpose of this article is to propose a new dynamic seasonal grey model based on PSO-SVR to forecast the production and consumption of electric energy.Design/methodology/approachIn the model design, firstly, the parameters of the SVR are initially optimized by the PSO algorithm for the estimation of the dynamic seasonal operator. Then, the seasonal fluctuations in the electricity demand data are eliminated using the dynamic seasonal operator. After that, the time series after eliminating of the seasonal fluctuations are used as the training set of the DSGM(1, 1) model, and the corresponding fitted, and predicted values are calculated. Finally, the seasonal reduction is performed to obtain the final prediction results.FindingsThis study found that the electricity supply and demand data have obvious seasonal and nonlinear characteristics. The dynamic seasonal grey model based on PSO-SVR performs significantly better than the comparative model for hourly and monthly data as well as for different time durations, indicating that the model is more accurate and robust in seasonal electricity forecasting.Originality/valueConsidering the seasonal and nonlinear fluctuation characteristics of electricity data. In this paper, a dynamic seasonal grey model based on PSO-SVR is established to predict the consumption and production of electric energy.