bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterologous prime-boost immunization with CoronaVac and Convidecia
Authors: Li Jingxin , Hou Lihua , Guo Xiling , Jin Pengfei , Wu Shipo , Zhu Jiahong , Pan Hongxing , Wang Xue , Song Zhizhou , Wan Jingxuan , Cui Lunbiao , Li Junqiang , Wang Xuewen , Jin Lairun , Liu Jingxian , Shi Fengjuan , Xu Xiaoyu , Chen Yin , Zhu Tao , Chen Wei , Zhu Fengcai 
Published: September 2021

ABSTRACTBackgroundThe safety and immunogenicity of heterologous prime-boost COVID-19 vaccine regimens with one shot of a recombinant adenovirus type-5-vectored COVID-19 vaccine Convidecia has not been reported.MethodsWe conducted a randomized, controlled, observer-blinded trial of heterologous prime-boost immunization with CoronaVac and Convidecia in healthy adults 18-59 years of age. Eligible participants who were primed with one or two doses of CoronaVac were randomly assigned at a 1:1 ratio to receive a booster dose of Convidecia or CoronaVac. Participants were masked to the vaccine received but not to the three-dose or two-dose regimen. The occurrences of adverse reactions within 28 days after the vaccination were documented. The geometric mean titers of neutralizing antibodies against live SARS-CoV-2 virus were measured at 14 and 28 days after the booster vaccination.ResultsBetween May 25 and 26, 2021, a total of 300 participants were enrolled. Participants who received a booster shot with a heterologous dose of Convidecia reported increased frequencies of solicited injection-site reactions than did those received a homogeneous dose of CoronaVac, but frequencies of systemic reactions. The adverse reactions were generally mild to moderate. The heterologous immunization with Convidecia induced higher live viral neutralizing antibodies than did the homogeneous immunization with CoronaVac (197.4[167.7, 232.4] vs. 33.6[28.3, 39.8] and 54.4[37. 9, 78.0] vs. 12.8[9.3, 17.5]) at day 14 in the three- and two-dose regimen cohort, respectively.ConclusionsThe heterologous prime-boost regimen with Convidecia after the priming with CoronaVac was safe and significantly immunogenic than a homogeneous boost with CoronaVac (ClinicalTrials.gov, numberNCT04892459).
Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health
Authors: Gadd Danni A , Hillary Robert F , McCartney Daniel L , Shi Liu , Stolicyn Aleks , Robertson Neil , Walker Rosie M , McGeachan Robert I , Campbell Archie , Xueyi Shen , Barbu Miruna C , Green Claire , Morris Stewart W , Harris Mathew A , Backhouse Ellen V , Wardlaw Joanna M , Steele J Douglas , Oyarzún Diego A , Muniz-Terrera Graciela , Ritchie Craig , Nevado-Holgado Alejo , Chandra Tamir , Hayward Caroline , Evans Kathryn L , Porteous David J , Cox Simon R , Whalley Heather C , McIntosh Andrew M , Marioni Riccardo E 
Published: September 2021

AbstractCharacterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4,058 plasma proteins are performed (N=774), identifying 2,928 CpG-protein associations after adjustment for multiple testing. These were independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N=1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health.
Functional respiratory capacity in the elderly after COVID-19 – a pilot study
Authors: Pereira Filipe Alexandre , Tomás Maria Teresa 
Published: September 2021

ABSTRACTBackgroundThe pandemic spread of SARS-CoV-2 has led to an unprecedented outbreak of viral pneumonia. Despite the current focus of worldwide research being the characterization of post-COVID-19 sequelae, the level of functional impact that this disease causes in the elderly who have presented moderate, severe or critical manifestations is still unknown.ObjectiveTo identify the main consequences/sequelae on functional respiratory capacity in the elderly after CoViD-19.MethodologyA cross-sectional study was carried out in the community. Functional aerobic capacity (2min step test), dyspnea perception (modified Medical Research Council Dyspnea Questionnaire), respiratory and peripheral muscle strength (maximum inspiratory and expiratory pressure, grip strength) and the Frailty Index (Clinical Fragility Scale) were assessed in 25 community-dwelling individuals aged ≥65 years, who have had a diagnosis of CoViD-19 for up to 6 months, and in an equal number of elderly people with the same characteristics without a known diagnosis of CoViD-19.ResultsThe elderly with a diagnosis of CoViD-19 up to 6 months presented a decrease in the values of maximum inspiratory pressure (p=0.001) and maximum expiratory pressure (p=0.015), in aerobic capacity (p<0.001) with significant presence of desaturation on exertion (p<0.001), and increased values of dyspnea perception (p=0.001) and Frailty Index (p=0.026).ConclusionSignificant changes were found in the functional respiratory capacity of elderly patients diagnosed with CoViD-19 for up to 6 months, when compared with elderly individuals without a known diagnosis of CoViD-19. It is not possible to extrapolate the results obtained to the Portuguese population, however these results may be an important indicator in the characterization of sequelae in the elderly after infection by SARS-CoV-2.
Is life-course neighbourhood deprivation associated with frailty and frailty progression from age 70 to 82 in the Lothian Birth Cohort 1936?
Authors: Baranyi Gergő , Welstead Miles , Corley Janie , Deary Ian J. , Muniz-Terrera Graciela , Redmond Paul , Shortt Niamh , Taylor Adele , Ward Thompson Catharine , Cox Simon , Pearce Jamie 
Published: September 2021

ABSTRACTBackgroundNeighbourhood features have been postulated as key predictors of frailty. However, evidence is mainly limited to cross-sectional studies without indication of long-term impact and developmental timing of the exposures. This study explored how neighbourhood social deprivation (NSD) across the life course is associated with frailty and frailty progression among older Scottish adults.MethodsParticipants (n=323) were from the Lothian Birth Cohort 1936 with historical measures of NSD in childhood (1936-1955), early adulthood (1956-1975) and mid-to-late adulthood (1976-2014). Frailty was measured five times between the ages of 70 and 82 years using the Frailty Index. Confounder-adjusted life-course models were assessed using a structured modelling approach with least angle regression; associations were estimated for frailty at baseline using linear regression, and for frailty progression using linear mixed-effects models.ResultsAccumulation was the most appropriate life-course model for males; greater accumulated NSD was associated with higher frailty at age 70 (b=0.017; 95%CI: 0.005, 0.029;P=0.007) with dominant exposure times in childhood and mid-to-late adulthood. Among females, mid-to-late adulthood sensitive period was the best-fit life-course model and higher NSD in this period was associated with widening frailty trajectories between age 70 and 82 (b=0.005; 95%CI: 0.0004, 0.009,P=0.033).ConclusionsThis is the first investigation of the life-course impact of neighbourhood deprivation on frailty in a cohort of older adults with residential information across their lives. Future research should explore neighbourhood mechanisms linking deprivation to frailty. Policies designed to address neighbourhood deprivation and inequalities across the full life course may support healthy ageing.Key messagesNeighbourhood context might be associated with old-age frailty, but existing investigations are mainly based on cross-sectional data with limited understanding of the relative importance of exposure timing during the life course.Using a structured approach, we investigated how neighbourhood social deprivation across the life course is associated with frailty, and frailty progression, in a sample of older Scottish adults.Among males, accumulated neighbourhood social deprivation was moderately associated with frailty at age 70 but not with subsequent frailty trajectories; widening frailty trajectories between age 70 and 82 conditional on deprivation during mid-to-late adulthood were identified among females.Gendered experiences of living in deprived areas from childhood onwards may contribute to frailty which should be considered in policies supporting healthy ageing.
Effective connectivity reveals distinctive patterns in response to others’ genuine affective experience of disgust as compared to pain
Authors: Zhao Yili , Zhang Lei , Rütgen Markus , Sladky Ronald , Lamm Claus 
Published: September 2021

AbstractEmpathy is significantly influenced by the identification of others’ emotions. In a recent study, we have found increased activation in the anterior insular cortex (aIns) that could be attributed to affect sharing rather than perceptual saliency, when seeing another person genuinely experiencing pain as opposed to merely acting to be in pain. In that prior study, effective connectivity between aIns and the right supramarginal gyrus (rSMG) was revealed to track what another person really feels. In the present study, we used a similar paradigm to investigate the corresponding neural signatures in the domain of empathy for disgust - with participants seeing others genuinely sniffing unpleasant odors as compared to pretending to smell something disgusting. Consistent with the previous findings on pain, we found stronger activations in aIns associated with affect sharing for genuine disgust compared with pretended disgust. However, instead of rSMG we found engagement of the olfactory cortex. Using dynamic causal modeling (DCM), we estimated the neural dynamics of aIns and the olfactory cortex between the genuine and pretended conditions. This revealed an increased excitatory modulatory effect for genuine disgust compared to pretended disgust. For genuine disgust only, brain-to-behavior regression analyses highlighted a link between the observed modulatory effect and the perspective-taking empathic trait. Altogether, the current findings complement and expand our previous work, by showing that perceptual saliency alone does not explain responses in the insular cortex. Moreover, it reveals that different brain networks are implicated in a modality-specific way when sharing the affective experiences associated with pain vs. disgust.
Community science designed ribosomes with beneficial phenotypes
Authors: Krüger Antje , Watkins Andrew M. , Wellington-Oguri Roger , Romano Jonathan , Kofman Camila , DeFoe Alysse , Kim Yejun , Anderson-Lee Jeff , Fisker Eli , Townley Jill , participants Eterna , d’Aquino Anne E. , Das Rhiju , Jewett Michael C. 
Published: September 2021

ABSTRACTFunctional design of ribosomes with mutant ribosomal RNA (rRNA) could expand opportunities for understanding molecular translation, building cells from the bottom-up, and engineering ribosomes with altered capabilities. However, such efforts have been hampered by cell viability constraints, an enormous combinatorial sequence space, and limitations on large-scale, 3D design of RNA structures and functions. To address these challenges, we developed an integrated community science and experimental screening approach for rational design of ribosomes. This approach couples Eterna, an online video game that crowdsources RNA sequence design to community scientists in the form of puzzles, within vitroribosome synthesis, assembly, and translation in multiple design-build-test-learn cycles. We applied our framework to discover mutant rRNA sequences that improve protein synthesisin vitroand cell growthin vivo, relative to wild type ribosomes, under diverse environmental conditions. This work provides new insights into ribosome rRNA sequence-function relationships, with implications for synthetic biology.
Machine learning techniques to derive bioclimatic classifications for Colombia ☆
Authors: Rios Richard , Noguera-Urbano Elkin A. , Espinosa Jairo , Ochoa Jose Manuel 
Published: September 2021

AbstractBioclimatic classifications seek to divide a study region into geographic areas with similar bioclimatic characteristics. In this study we proposed two bioclimatic classifications for Colombia using machine learning techniques. We firstly characterized the precipitation space of Colombia using principal component analysis. Based on Lang classification, we then projected all background sites in the precipitation space with their corresponding categories. We sequentially fit logistic regression models to reclassify all background sites in the precipitation space with six redefined Lang categories. New categories were the used to define a new modified Lang and Caldas-Lang classifications.
Serine Starvation Silences Estrogen Receptor Signaling through Histone Hypoacetylation
Authors: Li Albert M. , Li Yang , He Bo , Jiang Haowen , Ramirez Yaniel , Zhou Meng-Ning , Lu Chao , Gruber Joshua J. , Rankin Erinn B. , Ye Jiangbin 
Published: September 2021

ABSTRACTEstrogen receptor (ER) plays important roles in regulating normal development and female reproductive system function. Loss of ER pathway activity is a hallmark of breast cancer progression, associated with accelerated tumor proliferation and resistance to endocrine therapy. How ER loss occurs remains poorly understood. Here, we show that serine starvation, a metabolic stress often found in solid tumors, downregulates estrogen receptor alpha (ERα) expression, represses transcriptional targets such as progesterone receptor (PR), and reduces sensitivity to antiestrogens, suggesting a transition of ER-positive (ER+) breast cancer cells to an ER/PR-negative (ER-/PR-) state. ER downregulation under serine starvation is accompanied by a global loss of histone acetylation. These chromatin changes are driven by metabolic reprogramming triggered by serine starvation, particularly lower glucose flux through glycolysis and the TCA cycle, leading to reduced acetyl-CoA levels and histone hypoacetylation. Supplementation with acetate or glycerol triacetate (GTA), precursors of acetyl-CoA, restores H3K27 acetylation and ERα expression under serine starvation. Therefore, a major consequence of serine starvation in breast cancer could be global chromatin changes that influence lineage-specific gene expression.
A hybrid capture RNA bait set for resolving genetic and evolutionary relationships in angiosperms from deep phylogeny to intraspecific lineage hybridization
Authors: Waycott Michelle , van Dijk Kor-jent , Biffin Ed 
Published: September 2021

AbstractNovel multi-gene targeted capture probes have been developed with the objective of obtaining multi-locus high quality sequence reads across any angiosperm lineage. Using existing genomic and transcriptomic data, two independent single assay probe/bait sets have been developed, the first targeting conserved exons from 20 low copy nuclear genes (OzBaits_NR V1.0) and the second, 19 plastid gene regions (OZBaits_CP V1.0). These ‘universal’ bait sets can efficiently generate DNA sequence data that are suitable for systematics and evolutionary studies of flowering plants. The bait sets can be ordered as Daicel-Arbor Sciences custom myBaits. We demonstrate the utility of the bait set in consistently recovering the targeted genomic regions across an evolutionarily broad range of angiosperm taxa.
Sequence conservation and structural features that are common within TRP channels
Authors: Cabezas-Bratesco Deny , Colenso Charlotte K. , Zavala Katina , Granata Danielle , Carnevale Vincenzo , Opazo Juan C. , Brauchi Sebastian E. 
Published: September 2021

ABSTRACTTRP proteins are a large family of cation selective channels, surpassed in variety only by voltage-gated potassium channels. Detailed molecular mechanisms governing how membrane voltage, ligand binding, or temperature can induce conformational changes promoting the open state of the channel are still missing for TRP channels. Aiming to unveil distinctive structural features common to the transmembrane domains within the TRP family, we performed bioinformatic analyses over a large set of TRP channel genes. Here we report a discrete and exceptionally conserved set of residues. This fingerprint is composed of eleven residues localized at equivalent three-dimensional positions in TRP channels from the different subtypes. Moreover, these amino acids are arranged in three groups, connected by a set of aromatics located at the core of the transmembrane structure. We hypothesize that differences in the connectivity between these different groups of residues harbors the apparent differences in coupling strategies used by TRP subgroups.
Evidence of structural rearrangements and variability in pESI(like) megaplasmids of S.Infantis by resolving the pESI-like ESBL-producing variants
Authors: Alba Patricia , Carfora Virginia , Feltrin Fabiola , Iurescia Manuela , Diaconu Elena Lavinia , Cordaro Gessica , Dell’Aira Elena , Marani Ilaria , Giacomi Angelo , Franco Alessia , Battisti Antonio 
Published: September 2021

AbstractThe increasing prevalence of pESI(like)-positive, multidrug-resistant (MDR) S. Infantis in Europe is a cause of major concern. As previously demonstrated, the pESI(like) megaplasmid is not only a carrier of antimicrobial resistant (AMR) genes (at least tet, dfr and sul genes), but also harbours several virulence and fitness genes, and toxin/antitoxin systems that enhance its persistence in the S. Infantis host.In this study, five prototype pESI(like) plasmids, of either CTX-M-1 or CTX-M-65 ESBL producing strains, were long-read sequenced using Oxford Nanopore Technology (ONT) and their complete sequences were resolved. Comparison of the structure and gene content of the five sequenced plasmids, and further comparison with previously published pESI(like) sequences, indicated that although the sequence of such pESI(like) “mosaic” plasmids remains almost identical, their structures appear different and composed of regions inserted or transposed after different events.The results obtained in this study are essential to better understand the plasticity and the evolution of the pESI(like) megaplasmid, and therefore to better address risk management options and policy decisions to fight against AMR and MDR in Salmonella and other food-borne pathogens.
SETDB1 Fuels the Lung Cancer Phenotype by Modulating Epigenome, 3D Genome Organization and Chromatin Mechanical Properties
Authors: Zakharova Vlada V. , Magnitov Mikhail D. , Del-Maestro Laurence , Ulianov Sergey V. , Glentis Alexandros , Ulyanik Burhan , Williart Alice , Karpukhina Anna , Demidov Oleg , Joliot Veronique , Vassetzky Yegor S. , Mège René-Marc , Piel Matthieu , Razin Sergey V. , Ait-Si-Ali Slimane 
Published: September 2021

AbstractImbalance in the finely orchestrated system of chromatin-modifying enzymes is a hallmark of many pathologies such as cancers, since causing the affection of the epigenome and transcriptional reprogramming. Here, we demonstrate that a loss-of-function mutation (LOF) of the major histone lysine methyltransferase SETDB1 possessing oncogenic activity in lung cancer cells leads to broad changes in the overall architecture and mechanical properties of the nucleus through genome-wide redistribution of heterochromatin, which perturbs chromatin spatial compartmentalization. Together with the enforced activation of the epithelial expression program, cytoskeleton remodeling, reduced proliferation rate and restricted cellular migration, this leads to the reversed oncogenic potential of lung adenocarcinoma cells. These results emphasize an essential role of chromatin architecture in the determination of oncogenic programs and illustrate a relationship between gene expression, epigenome, 3D genome and nuclear mechanics.
eIF6 rebinding dynamically couples ribosome maturation and translation
Authors: Jaako Pekka , Faille Alexandre , Tan Shengjiang , Wong Chi C. , Escudero-Urquijo Norberto , Castro-Hartmann Pablo , Wright Penny , Hilcenko Christine , Adams David J. , Warren Alan J. 
Published: September 2021

ABSTRACTProtein synthesis is a cyclical process consisting of translation initiation, elongation, termination and ribosome recycling. The release factors SBDS and EFL1 (both mutated in the leukaemia predisposition disorder Shwachman-Diamond syndrome) license entry of nascent 60S ribosomal subunits into active translation by evicting the anti-association factor eIF6 from the 60S intersubunit face. Here, we show that in mammalian cells, eIF6 holds all free cytoplasmic 60S subunits in a translationally inactive state and that SBDS and EFL1 are the minimal components required to recycle these 60S subunits back into additional rounds of translation by evicting eIF6. Increasing the dose of eIF6 in mice in vivo impairs terminal erythropoiesis by sequestering post-termination 60S subunits in the cytoplasm, disrupting subunit joining and attenuating global protein synthesis. Our data reveal that ribosome maturation and recycling are dynamically coupled by a mechanism that is disrupted in an inherited leukaemia predisposition disorder.
Phase-amplitude coupling and phase synchronization between medial temporal, frontal and posterior brain regions support episodic autobiographical memory recall
Authors: Roehri Nicolas , Bréchet Lucie , Seeber Martin , Pascual-Leone Alvaro , Michel Christoph M. 
Published: September 2021

AbstractEpisodic autobiographical memory (EAM) is a complex cognitive function that emerges from the coordination of specific and distant brain regions. Specific brain rhythms, namely theta and gamma oscillations and their synchronization, are thought of as putative mechanisms enabling EAM. Yet, the mechanisms of inter-regional interaction in the EAM network remain unclear in humans at the whole brain level. To investigate this, we analyzed EEG recordings of participants instructed to retrieve autobiographical episodes. EEG recordings were projected in the source space, and time-courses of atlas-based brain regions-of-interest (ROIs) were derived. Directed phase synchrony in high theta (7-10 Hz) and gamma (30-80 Hz) bands and high theta-gamma phase-amplitude coupling were computed between each pair of ROIs. Using network-based statistics, a graph-theory method, we found statistically significant networks for each investigated mechanism. In the gamma band, two sub-networks were found, one between the posterior cingulate cortex (PCC) and the medial temporal lobe (MTL) and another within the medial frontal areas. In the high theta band, we found a PCC to ventromedial prefrontal cortex (vmPFC) network. In phase-amplitude coupling, we found the high theta phase of the left MTL biasing the gamma amplitude of posterior regions and the vmPFC. Other regions of the temporal lobe and the insula were also phase biasing the vmPFC. These findings suggest that EAM, rather than emerging from a single mechanism at a single frequency, involves precise spatio-temporal signatures mapping on distinct memory processes. We propose that the MTL orchestrates activity in vmPFC and PCC via precise phase-amplitude coupling, with vmPFC and PCC interaction via high theta phase synchrony and gamma synchronization contributing to bind information within the PCC-MTL sub-network or valuate the candidate memory within the medial frontal sub-network.