bluuebunny/crossref_metadata_2025_split huggingface dataset:
A third vaccination with a single T cell epitope protects against SARS-CoV-2 infection in the absence of neutralizing antibodies
Authors: Pardieck Iris N. , van der Gracht Esmé T.I. , Veerkamp Dominique M.B. , Behr Felix M. , van Duikeren Suzanne , Beyrend Guillaume , Rip Jasper , Nadafi Reza , van der Sluis Tetje C. , Nejad Elham Beyranvand , Mülling Nils , Brasem Dena J. , Camps Marcel G.M. , Myeni Sebenzile K. , Bredenbeek Peter J. , Kikkert Marjolein , Kim Yeonsu , Cicin-Sain Luka , Abdelaal Tamim , van Gisbergen Klaas P.J.M. , Franken Kees L.M.C. , Drijfhout Jan Wouter , Melief Cornelius J.M. , Zondag Gerben C.M. , Ossendorp Ferry , Arens Ramon 
Published: December 2021

AbstractUnderstanding the mechanisms and impact of booster vaccinations can facilitate decisions on vaccination programmes. This study shows that three doses of the same synthetic peptide vaccine eliciting an exclusive CD8+ T cell response against one SARS-CoV-2 Spike epitope protected all mice against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, while only a second vaccination with this T cell vaccine was insufficient to provide protection. The third vaccine dose of the single T cell epitope peptide resulted in superior generation of effector-memory T cells in the circulation and tissue-resident memory T (TRM) cells, and these tertiary vaccine-specific CD8+ T cells were characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping showed that a substantial fraction of the tertiary effector-memory CD8+ T cells developed from remigrated TRM cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8+ T cell response leading to protection against otherwise lethal SARS-CoV-2 infection.SummaryA third dose with a single T cell epitope-vaccine promotes a strong increase in tissue-resident memory CD8+ T cells and fully protects against SARS-CoV-2 infection, while single B cell epitope-eliciting vaccines are unable to provide protection.
The algal PETC-Pro171-Leu suppresses electron transfer in the cytochrome b6f complex under acidic lumenal condition
Authors: Ozawa Shin-Ichiro , Buchert Felix , Reuys Ruby , Hippler Michael , Takahashi Yuichiro 
Published: December 2021

AbstractLinear photosynthetic electron flow (LEF) produces NADPH and generates a proton electrochemical potential gradient across the thylakoid membrane used to synthesize ATP, both of which are required for CO2 fixation. As cellular demand for ATP and NADPH are variable, cyclic electron flow (CEF) between PSI and cytochrome b6f complex (b6f) produces extra ATP. The b6f regulates LEF and CEF via photosynthetic control, which is a pH-dependent b6f slowdown of plastoquinol oxidation at the lumenal site. This protection mechanism is triggered at more alkaline lumen pH in the pgr1 mutant of the vascular plant Arabidopsis thaliana, carrying Pro194Leu in the b6f Rieske Iron-sulfur protein. In this work, we introduced pgr1 mutation in the green alga Chlamydomonas reinhardtii (PETC-P171L). Consistent with pgr1 phenotype, PETC-P171L displayed an impaired NPQ induction along with slower photoautotrophic growth under high light conditions. Our data provides evidence that the ΔpH component in PETC-P171L is dependent on oxygen availability. Only under low oxygen conditions the ΔpH component was sufficient to trigger a phenotype in algal PETC-P171L where the mutant b6f was more restricted to oxidize the PQ pool and showed a diminished electron flow through the b6f complex.One sentence summaryChange of PETC to P171L via site directed mutagenesis alters the pH dependency of the photosynthetic control mechanism
Characterizing the genetic basis of trait evolution in the Mexican cavefish
Authors: Oliva Camila , Hinz Nicole K. , Robinson Wayne , Barrett Thompson Alexys M. , Booth Julianna , Crisostomo Lina M. , Zanineli Samantha , Tanner Maureen , Lloyd Evan , O’Gorman Morgan , McDole Brittnee , Paz Alexandra , Kozol Rob , Brown Elizabeth B. , Kowalko Johanna E. , Fily Yaouen , Duboue Erik R. , Keene Alex C. 
Published: December 2021

AbstractEvolution in response to a change in ecology often coincides with various morphological, physiological, and behavioral traits. For most organisms little is known about the genetic and functional relationship between evolutionarily derived traits, representing a critical gap in our understanding of adaptation The Mexican tetra, Astyanax mexicanus, consists of largely independent populations of fish that inhabit at least 30 caves in Northeast Mexico, and a surface fish population, that inhabits the rivers of Mexico and Southern Texas. The recent application of molecular genetic approaches combined with behavioral phenotyping have established A. mexicanus as a model for studying the evolution of complex traits. Cave populations of A. mexicanus are interfertile with surface populations and have evolved numerous traits including eye degeneration, insomnia, albinism and enhanced mechanosensory function. The interfertility of different populations from the same species provides a unique opportunity to define the genetic relationship between evolved traits and assess the co-evolution of behavioral and morphological traits with one another. To define the relationships between morphological and behavioral traits, we developed a pipeline to test individual fish for multiple traits. This pipeline confirmed differences in locomotor activity, prey capture, and startle reflex between surface and cavefish populations. To measure the relationship between traits, individual F2 hybrid fish were characterized for locomotor behavior, prey-capture behavior, startle reflex and morphological attributes. Analysis revealed an association between body length and slower escape reflex, suggesting a trade-off between increased size and predator avoidance in cavefish. Overall, there were few associations between individual behavioral traits, or behavioral and morphological traits, suggesting independent genetic changes underlie the evolution of behavioral and morphological traits. Taken together, this approach provides a novel system to identify genes that underlie naturally occurring genetic variation in morphological and behavioral traits.
Neural signature of everyday function in older adults at-risk of cognitive impairment
Authors: De Sanctis Pierfilippo , Wagner Johanna , Molholm Sophie , Foxe John J. , Blumen Helena M. , Horsthuis Douwe J. 
Published: December 2021

AbstractAssessment of everyday activities are central to the diagnosis of pre-dementia and dementia. Yet, little is known about the brain substrates and processes that contribute to everyday functional impairment, particularly during early stages of cognitive decline. We investigated everyday function using a complex gait task in normal older adults stratified by risk of cognitive impairment. We applied a novel EEG approach, which combines electroencephalographic with 3D-body tracking technology to measure brain-gait dynamics with millisecond precision while participants are in motion. Twenty-six participants (mean age = 74.9 years) with cognitive and everyday functional profiles within the normal range for their age and sex were ranked for risk of cognitive impairment. We used the Montreal Cognitive Assessment battery, a global index of cognition with a range from 0 to 30, to classify individuals as being at higher (22-26) and lower risk (27+). Individuals walking on a treadmill were exposed to visual perturbation designed to destabilize gait. Assuming that brain changes precede behavioral decline, we predicted that older adults increase step width to gain stability, yet the underlying neural signatures would be different for lower versus higher risk individuals. When pooling across risk groups, we found that step width increased and fronto-parietal activation shifted from transient, during swing phases, to sustained across the gait cycle during visually perturbed input. As predicted, step width increased in both groups but underlying neural signatures were different. Fronto-medial theta (3-7Hz) power of gait-related brain oscillations were increased in higher risk individuals during both perturbed and unperturbed inputs. On the other hand, left central gyri beta (13-28Hz) power was decreased in lower risk individuals, specifically during visually perturbed input. Finally, relating MoCA scores to spectral power pooled across fronto-parietal regions, we found associations between increased theta power and worse MoCA scores and between decreased beta power and better MoCA scores.Able-bodied older adults at-risk of cognitive impairment are characterized by unique neural signatures of mobility. Stronger reliance on frontomedial theta activation in at-risk individuals may reflect higher-order compensatory responses for deterioration of basic sensorimotor processes. Region and spectral-specific signatures of mobility may provide brain targets for early intervention against everyday functional decline.
The first Miocene fossils from coastal woodlands in the southern East African Rift
Authors: Bobe René , Aldeias Vera , Alemseged Zeresenay , Archer Will , Aumaître Georges , Bamford Marion K. , Biro Dora , Bourlès Didier L. , Braun David R. , Capelli Cristian , d’Oliveira Coelho João , Habermann Jörg M. , Head Jason J. , Keddadouche Karim , Kupczik Kornelius , Lebatard Anne-Elisabeth , Lüdecke Tina , Macôa Amélia , Martínez Felipe I. , Mathe Jacinto , Mendes Clara , Meira Paulo Luis , Pinto Maria , Püschel Thomas A. , Tátá Regala Frederico , Sier Mark , Ferreira da Silva Maria Joana , Stalmans Marc , Carvalho Susana 
Published: December 2021

AbstractThe Miocene is a key time in the evolution of African mammals and their ecosystems witnessing the origin of the African apes and the isolation of eastern coastal forests through an expanding biogeographic arid corridor. Until recently, however, Miocene sites from the southeastern regions of the continent were unknown. Here we report discovery of the first Miocene fossil teeth from the shoulders of the Urema Rift in Gorongosa National Park, Mozambique, at the southern East African Rift System. We provide the first 1) radiometric age determinations of the fossiliferous Mazamba Formation, 2) reconstructions of past vegetation in the region based on pedogenic carbonates and fossil wood, and 3) description of fossil teeth from the southern rift. Gorongosa is unique in the East African Rift System in combining marine invertebrates, marine vertebrates, terrestrial mammals, and fossil woods in coastal paleoenvironments. The Gorongosa fossil sites offer the first evidence of persistent woodlands and forests on the coastal margins of southeastern Africa during the Miocene, and an exceptional assemblage of fossil vertebrates including new species. Further work will allow the testing of hypotheses positing the formation of a northeast-southwest arid corridor isolating species on the eastern coastal forests from those elsewhere in Africa.BriefThe Miocene is a key time in the evolution of African mammals and their ecosystems encompassing hominine origins and the establishment of an arid corridor that isolated eastern Africa’s coastal forests. Until now, however, Miocene sites from southeastern Africa have been unknown. We report the discovery of the first Miocene fossil sites from Gorongosa National Park, Mozambique, and show that these sites formed in coastal settings. We provide radiometric ages for the fossiliferous sediments, reconstructions of past vegetation based on stable isotopes and fossil wood, and a description of the first fossil teeth from the region. Gorongosa is the only paleontological site in the East African Rift that combines fossil woods, marine invertebrates, marine vertebrates, and terrestrial mammals. Gorongosa offers the first evidence of persistent woodlands and forests on the coastal margins of southeastern Africa during the Miocene.
Structure of EPCR in a non-canonical conformation
Authors: Erausquin Elena , Rodríguez-Fernández Adela , López-Sagaseta Jacinto 
Published: December 2021

AbstractStructural motion and conformational flexibility are often linked to biological functions of proteins. Whether the endothelial protein C receptor (EPCR), like other molecules, is vulnerable to folding transitions or might adopt alternative conformations remains unknown. The current understanding points to a rigid molecular structure suitable for binding of its ligands, like the anticoagulant protein C, or the CIDRα1 domains of Plasmodium falciparum. In this study, we have identified a novel conformation of EPCR, captured by X-ray diffraction analyses, whereby Tyr154 shows a dramatically altered structural arrangement, likely incompatible with protein C binding. Biolayer interferometry analysis confirms previous results supporting a critical role for this position in protein C binding. Importantly, the conformational change has no apparent effect in the bound lipid. We conclude these findings reveal a site of conformational vulnerability in EPCR and inform a highly malleable region that could modulate EPCR functions.
Low Frequency Oscillations drive EEG’s complexity changes during wakefulness and sleep
Authors: González Joaquín , Mateos Diego , Cavelli Matias , Mondino Alejandra , Pascovich Claudia , Torterolo Pablo , Rubido Nicolás 
Published: December 2021

AbstractRecently, the sleep-wake states have been analysed using novel complexity measures, complementing the classical analysis of EEGs by frequency bands. This new approach consistently shows a decrease in EEG’s complexity during slow-wave sleep, yet it is unclear how cortical oscillations shape these complexity variations. In this work, we analyse how the frequency content of brain signals affects the complexity estimates in freely moving rats. We find that the low-frequency spectrum – including the Delta, Theta, and Sigma frequency bands – drives the complexity changes during the sleep-wake states. This happens because low-frequency oscillations emerge from neuronal population patterns, as we show by recovering the complexity variations during the sleep-wake cycle from micro, meso, and macroscopic recordings. Moreover, we find that the lower frequencies reveal synchronisation patterns across the neocortex, such as a sensory-motor decoupling that happens during REM sleep. Overall, our works shows that EEG’s low frequencies are critical in shaping the sleep-wake states’ complexity across cortical scales.
Proteolytic cleavage of the extracellular domain affects signaling of parathyroid hormone receptor 1
Authors: Klenk Christoph , Hommers Leif , Lohse Martin J. 
Published: December 2021

AbstractParathyroid hormone 1 receptor (PTH1R) is a member of the class B family of G protein-coupled receptors, which are characterized by a large extracellular domain required for ligand binding. We have previously shown that the extracellular domain of PTH1R is subject to metalloproteinase cleavage in vivo that is regulated by ligand-induced receptor trafficking and leads to impaired stability of PTH1R. In this work, we localize the cleavage site in the first loop of the extracellular domain using amino-terminal protein sequencing of purified receptor and by mutagenesis studies. We further show, that a receptor mutant not susceptible to proteolytic cleavage exhibits reduced signaling to Gs and increased activation of Gq compared to wild-type PTH1R. These findings indicate that the extracellular domain modulates PTH1R signaling specificity, and that its cleavage affects receptor signaling.
Accumulation of Treg cells is detrimental in late-onset (aged) mouse model of multiple sclerosis
Authors: Wang Weikan , Thomas Rachel , Oh Jiyoung , Su Dong-Ming 
Published: December 2021

AbstractAlthough typically associated with onset in young adults, multiple sclerosis (MS) also attacks aged people, which is termed late-onset MS. The disease can be recapitulated and studied in the aged mouse model of experimental autoimmune encephalomyelitis (EAE). The onset of induced EAE is delayed in aged mice, but the disease severity is increased relative to standard EAE in young mice. Given that CD4+FoxP3+ regulatory T (Treg) cells play an ameliorative role in MS/EAE severity and the aged immune system accumulates Treg cells, failure of these cells to prevent or ameliorate EAE disease is enigmatic. When analyzing the distribution of Treg cells in EAE mice, the aged mice exhibited a higher proportion of polyclonal(pan) Treg cells and a lower proportion of antigen-specific-Treg cells in their periphery, but lower proportions of pan- and antigen-specific-Treg cells in the central nervous system (CNS). Furthermore, in the aged CNS, Treg cells exhibited a higher plasticity and T effector (Teff) cells exhibited a greater clonal expansion, which disrupted the Treg/Teff balance. Transiently inhibiting FoxP3 expression in peripheral Treg cells partially ameliorated the disease and corrected Treg distribution in the aged mice. These results provide evidence that accumulated aged Treg cells play a detrimental role in neuronal inflammation of aged MS.HighlightsQuestionCD4+ regulatory T (Treg) cells typically play an ameliorative role in multiple sclerosis (MS) onset and severity. However, why aged immune system has accumulated peripheral Treg cells, but the elderly has more severe MS symptoms?FindingsAged Treg cells cannot easily distribute to the CNS of aged EAE mice, and those aged Treg cells that did enter the CNS exhibited increased plastic features. However, transient inhibition of peripherally accumulated Treg cells corrected Treg distribution and partially ameliorated the disease in the aged mice.Conclusion and mechanistic insightsAccumulated aged Treg cells within an “inflammaging” condition do not play an ameliorative role but are potentially detrimental for inflamed CNS repair processes in aged EAE mice due to impeding the trafficking of immune cells into the inflamed CNS.
LY6S, a New Interferon-Inducible Human Member of the Ly6a-Subfamily Expressed by Spleen Cells and Associated with Inflammation and Viral Resistance
Authors: Shmerling Moriya , Chalik Michael , Smorodinsky Nechama I. , Meeker Alan , Roy Sujayita , Sagi-Assif Orit , Meshel Tsipi , Danilevsky Artem , Shomron Noam , Levinger Shmuel , Nishry Bar , Baruchi David , Shargorodsky Avital , Ziv Ravit , Sarusi-Portuguez Avital , Lahav Maoz , Ehrlich Marcelo , Braschi Bryony , Bruford Elspeth , Witz Isaac P. , Wreschner Daniel H. 
Published: December 2021

AbstractSyntenic genomic loci on human chromosome 8 (hChr8) and mouse chromosome 15 (mChr15) code for LY6/Ly6 (lymphocyte antigen 6) family proteins. The 23 murine Ly6 family genes include eight genes that are flanked by the murine Ly6e and Ly6l genes and form an Ly6 subgroup referred to here as the Ly6a subfamily gene cluster. Ly6a, also known as Sca1 (Stem Cell Antigen-1) and TAP (T-cell activating protein), is a member of the Ly6a subfamily gene cluster. No LY6 genes have been annotated within the syntenic LY6E to LY6L human locus. We report here on LY6S, a solitary human LY6 gene that is syntenic with the murine Ly6a subfamily gene cluster, and with which it shares a common ancestry. LY6S codes for the interferon-inducible GPI-linked LY6S-iso1 protein that contains only 9 of the 10 consensus LY6 cysteine residues and is most highly expressed in a non-classical cell population. Its expression leads to distinct shifts in patterns of gene expression, particularly of genes coding for inflammatory and immune response proteins, and LY6S-iso1 expressing cells show increased resistance to viral infection. Our findings reveal the presence of a previously un-annotated human interferon-stimulated gene, LY6S, which has a one to eight ortholog relationship with the genes of the Ly6a subfamily gene cluster, is most highly expressed in spleen cells of a non-classical cell-lineage and whose expression induces viral resistance and is associated with an inflammatory phenotype and with the activation of genes that regulate immune responses.One Sentence SummaryLY6S is a newly discovered human interferon-inducible gene associated with inflammation and with resistance to viral replication.
Characterizing the variation in chromosome structure ensembles in the context of the nuclear microenvironment
Authors: Das Priyojit , Shen Tongye , McCord Rachel Patton 
Published: December 2021

ABSTRACTInside the nucleus, chromosomes are subjected to direct physical interaction between different components, active forces, and thermal noise, leading to the formation of an ensemble of three-dimensional structures. However, it is still not well understood to what extent and how the structural ensemble varies from one chromosome region or cell-type to another. We designed a statistical analysis technique and applied it to single-cell chromosome imaging data to reveal the heterogeneity of individual chromosome structures. By analyzing the resulting structural landscape, we find that the largest dynamic variation is the overall radius of gyration of the chromatin region, followed by domain reorganization within the region. By comparing different human cell-lines and experimental perturbation data using this statistical analysis technique and a network-based similarity quantification approach, we identify both cell-type and condition-specific features of the structural landscapes. We identify a relationship between epigenetic state and the properties of chromosome structure fluctuation and validate this relationship through polymer simulations. Overall, our study suggests that the types of variation in a chromosome structure ensemble are cell-type as well as region-specific and can be attributed to constraints placed on the structure by factors such as variation in epigenetic state.
Water soluble polysaccharides from Spirulina platensis exhibited cyto/DNA protection and suppress the growth of gastric cancer cells via modulation of galectin-3
Authors: Uppin Vinayak , Dharmesh Shylaja M , Sarada R 
Published: December 2021

AbstractPolysaccharides from natural sources play a significant role in the management of different cancer types including gastric cancer. In this study, we reported the effect of spirulina polysaccharide (Sp) on galectin-3 modulatory activity on gastric cancer cells. The polysaccharide was isolated from the spirulina biomass, characterized, and the in silico, in vitro studies are carried out to assess the bioactivities. The isolated Sp possessed average molecular weight of 1457 kDa, and galactose (42%) as major sugar along with Rhamnose, Arabinose, Xylose, and Mannose. Further, characterization of Sp by FT-IR and NMR spectrum indicated the presence of (β1-4D) galactose sugar with galactoarabinorhamnoglycan backbone. Among the monosaccharides, galactose showed highest binding affinity with galectin-3 protein as evidenced by the in silico interaction study. The obtained Sp, inhibited the proliferation of AGS gastric cancer cells by 48 % without affecting normal NIH/3T3 cells as opposed to doxorubicin, a known anticancer drug. Also, Sp exhibited galectin-3 mediated haemagglutination inhibition with MIC of 9.37 μg/mL compared to galactose 6.25 μg/mL, sugar specific to galectin-3. The Sp treatment significantly (p<0.05) lowered the expression of galectin-3 by 32 % compared to untreated control cells. In addition, Sp exhibited the potent cytoprotection in RBCs, Buccal cells, and DNA exposed to oxidants. Thus, the findings suggest that the polysaccharide from spirulina offer a promising therapeutic strategy in the management of gastric cancer in addition to its currently known nutritional and pharmaceutical applications.