bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generalizability of foot-placement control strategies during unperturbed and perturbed gait
Authors: Liu Chang , Valero-Cuevas Francisco J. , Finley James M. 
Published: July 2023

AbstractControl of foot placement is an essential strategy for maintaining balance during walking. During unperturbed, steady-state walking, foot placement can be accurately described as a linear function of the body’s center of mass state at midstance. However, it is uncertain if this mapping from center of mass state to foot placement generalizes to larger perturbations that may be more likely to cause falls. These perturbations may cause balance disturbances and generate reactive control strategies not observed during unperturbed walking. Here, we used unpredictable changes in treadmill speed to assess the generalizability of foot placement mappings identified during unperturbed walking. We found that foot placement mappings generalized poorly from unperturbed to perturbed walking and differed for forward versus backward perturbations. We also used singular value decomposition of the mapping matrix to reveal that people were more sensitive to backward versus forward perturbations. Together, these results indicate that control of foot placement during losses of balance differs from the control strategies used during unperturbed walking. Better characterization of human balance control strategies could improve our understanding of why different neuromotor disorders result in heightened fall risk and inform the design of controllers for balance-assisting devices.
Harnessing the power of whole human liver ex situ normothermic perfusion for preclinical AAV vector evaluation
Authors: Cabanes-Creus Marti , Liao Sophia H.Y. , Navarro Renina Gale , Knight Maddison , Nazareth Deborah , Lau Ngee-Soon , Ly Mark , Zhu Erhua , Roca-Pinilla Ramon , Delgado Ricardo Bugallo , Baltazar Grober , Westhaus Adrian , Merjane Jessica , Crawford Michael , McCaughan Geoffrey W. , Unzu Carmen , González-Aseguinolaza Gloria , Alexander Ian E. , Pulitano Carlo , Lisowski Leszek 
Published: July 2023

AbstractDeveloping clinically predictive model systems for evaluating gene transfer and gene editing technologies has become increasingly important in the era of personalized medicine. Liver-directed gene therapies present a unique challenge due to the complexity of the human liver. In this work, we describe the application of whole human liver explants in anex situnormothermic perfusion system to evaluate a set of fourteen natural and bioengineered adeno-associated viral (AAV) vectors directly in human liver, in the presence and absence of neutralizing human sera. Under non-neutralizing conditions, the recently developed AAV variants, AAV-SYD12 and AAV-LK03, emerged as the most functional variants in terms of cellular uptake and transgene expression. However, when assessed in the presence of human plasma containing anti-AAV neutralizing antibodies (NAbs), vectors of human origin, specifically those derived from AAV2/AAV3b, were extensively neutralized, whereas AAV8-derived variants performed efficiently. This study establishes the use of normothermic liver perfusion as an invaluable preclinical model for evaluating liver-targeted gene therapies and providing guidance for making essential decisions that promote the most effective translational programs.
Petascale Homology Search for Structure Prediction
Authors: Lee Sewon , Kim Gyuri , Karin Eli Levy , Mirdita Milot , Park Sukhwan , Chikhi Rayan , Babaian Artem , Kryshtafovych Andriy , Steinegger Martin 
Published: July 2023

AbstractThe recent CASP15 competition highlighted the critical role of multiple sequence alignments (MSAs) in protein structure prediction, as demonstrated by the success of the top AlphaFold2-based prediction methods. To push the boundaries of MSA utilization, we conducted a petabase-scale search of the Sequence Read Archive (SRA), resulting in gigabytes of aligned homologs for CASP15 targets. These were merged with default MSAs produced by ColabFold-search and provided to ColabFold-predict. By using SRA data, we achieved highly accurate predictions (GDT_TS > 70) for 66% of the non-easy targets, whereas using ColabFold-search default MSAs scored highly in only 52%. Next, we tested the effect of deep homology search and ColabFold’s advanced features, such as more recycles, on prediction accuracy. While SRA homologs were most significant for improving ColabFold’s CASP15 ranking from 11th to 3rd place, other strategies contributed too. We analyze these in the context of existing strategies to improve prediction.
Engineering and Evolution of the Complete Reductive Glycine Pathway inSaccharomyces cerevisiaefor Formate and CO2Assimilation
Authors: Bysani Viswanada R , Alam Ayesha S M , Bar-Even Arren , Machens Fabian 
Published: July 2023

AbstractUsing captured CO2and C1-feedstocks like formate and methanol derived from electrochemical activation of CO2are key solutions for transforming industrial processes towards a circular carbon economy. Engineering formate and CO2-based growth in the biotechnologically relevant yeastSaccharomyces cerevisiaecould boost the emergence of a formate-mediated circular bio-economy. This study adopts a growth-coupled selection scheme for modular implementation of the Reductive Glycine Pathway (RGP) and subsequent Adaptive Laboratory Evolution (ALE) to enable formate and CO2assimilation for biomass formation in yeast. We first constructed a serine biosensor strain and then implemented the serine synthesis module of the RGP into yeast, establishing glycine and serine synthesis from formate and CO2. ALE improved the RGP-dependent growth by 8-fold. 13C-labeling experiments reveal glycine, serine, and pyruvate synthesis via the RGP, demonstrating the complete pathway activity. Further, we reestablished formate and CO2-dependent growth in non-evolved biosensor strains via reverse-engineering a mutation inGDH1identified from ALE. This mutation led to significantly more 13C-formate assimilation than in WT without any selection or overexpression of the RGP. Overall, we demonstrated the activity of the complete RGP, showing evidence for carbon transfer from formate to pyruvate coupled with CO2assimilation.
Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis
Authors: Herruzo Esther , Sánchez-Díaz Estefanía , González-Arranz Sara , Santos Beatriz , Carballo Jesús A. , San-Segundo Pedro A. 
Published: July 2023

AbstractThe meiotic recombination checkpoint reinforces the order of events during meiotic prophase I, ensuring the accurate distribution of chromosomes to the gametes. The AAA+ ATPase Pch2 remodels the Hop1 axial protein enabling adequate levels of Hop1-T318 phosphorylation to support the ensuing checkpoint response. While these events are focalized at chromosome axes, the checkpoint activating function of Pch2 relies on its cytoplasmic population. In contrast, forced nuclear accumulation of Pch2 leads to checkpoint inactivation. Here, we reveal the mechanism by which Pch2 travels from the cell nucleus to the cytoplasm to maintain Pch2 cellular homeostasis. Leptomycin B treatment provokes the nuclear accumulation of Pch2, indicating that its nucleocytoplasmic transport is mediated by the Crm1 exportin recognizing proteins containing Nuclear Export Signals (NESs). Consistently, leptomycin B leads to checkpoint inactivation and impaired Hop1 axial localization. Pch2 nucleocytoplasmic traffic is independent of its association with Zip1 and Orc1. We also identify a conserved functional NES in the non-catalytic N-terminal domain of Pch2 that is required for its nucleocytoplasmic traffic and proper checkpoint activity. In sum, we unveil another layer of control of Pch2 function during meiosis involving the nuclear export via the exportin pathway that is crucial to maintain the critical balance of Pch2 distribution among different cellular compartments.
Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in vertebrates
Authors: Ishibashi Kota , Shichino Yuichi , Han Peixun , Wakabayashi Kimi , Inada Toshifumi , Kimura Seisuke , Iwasaki Shintaro , Mishima Yuichiro 
Published: July 2023

AbstractQuality control of translation is crucial for maintaining cellular and organismal homeostasis. Obstacles in translation elongation induce ribosome collision, which is monitored by multiple sensor mechanisms in eukaryotes. The E3 ubiquitin ligase Znf598 recognizes collided ribosomes, triggering ribosome-associated quality control (RQC) to rescue stalled ribosomes and no-go decay (NGD) to degrade stall-prone mRNAs. However, the impact of RQC and NGD on maintaining the translational homeostasis of endogenous mRNAs has remained unclear. In this study, we investigated the endogenous substrate mRNAs of NGD during the maternal-to-zygotic transition (MZT) of zebrafish development. RNA-Seq analysis of zebrafishznf598mutant embryos revealed that Znf598 downregulates mRNAs encoding the C2H2-type zinc finger domain (C2H2-ZF) during the MZT. Reporter assays and disome profiling indicated that ribosomes stall and collide while translating tandem C2H2-ZFs, leading to mRNA degradation by Znf598. We further showed that mRNAs encoding C2H2-ZF were degraded in a ZNF598-dependent manner in HEK293T cells. Our results suggest that NGD maintains the quality of the translatome by mitigating the risk of ribosome collision at the abundantly present C2H2-ZF sequences in the vertebrate genome.
High-resolution map of the Fc-functions mediated by COVID-19 neutralizing antibodies
Authors: Paciello Ida , Maccari Giuseppe , Pantano Elisa , Andreano Emanuele , Rappuoli Rino 
Published: July 2023

ABSTRACTA growing body of evidence shows that Fc-dependent antibody effector functions play an important role in protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To unravel the mechanisms that drive these responses, we analyzed the phagocytosis and complement deposition mediated by a panel of 482 human monoclonal antibodies (nAbs) neutralizing the original Wuhan virus, expressed as recombinant IgG1. Our study confirmed that nAbs no longer neutralizing SARS-CoV-2 Omicron variants can retain their Fc-functions. Surprisingly, we found that nAbs with the most potent Fc-function recognize the N- terminal domain, followed by those targeting Class 3 epitopes in the receptor binding domain. Interestingly, nAbs direct against the Class 1/2 epitopes in the receptor binding motif, which are the most potent in neutralizing the virus, were the weakest in Fc-functions. The divergent properties of the neutralizing and Fc- function mediating antibodies were confirmed by the use of different B cell germlines and by the observation that Fc-functions of polyclonal sera differ from the profile observed with nAbs, suggesting that not-neutralizing antibodies also contribute to Fc-functions. These data provide a high-resolution picture of the Fc-antibody response to SARS-CoV-2 and suggest that the Fc contribution should be considered for the design of improved vaccines, the selection of therapeutic antibodies and the evaluation of correlates of protection.
Highly pathogenic avian influenza A(H5N1) virus clade 2.3.4.4b in domestic ducks, Indonesia, 2022
Authors: Wibawa Hendra , Wibowo Putut Eko , Supriyadi Arif , Lestari  , Silaban Jessiaman , Fuadi Aziz Ahmad , Fiqri Anna Januar , Handayani Retno Wulan , Irianingsih Sri Handayani , Fahmia Zaza , Mulyawan Herdiyanto , Idris Syafrison , Zainuddin Nuryani 
Published: July 2023

AbstractHighly pathogenic avian influenza A(H5N1) clade 2.3.4.4b viruses were detected and isolated from domestic ducks in South Kalimantan, Indonesia during April 2022. The viruses were genetically similar to clade 2.3.4.4b H5N1 viruses recently detected in East Asia from 2021-2022. Further investigation is necessary to determine the source of virus incursion.
Transposable element insertions are associated with Batesian mimicry in the pantropical butterflyHypolimnas misippus
Authors: Orteu Anna , Kucka Marek , Katili Eunice , Ngumbao Charo , Gordon Ian J. , Ng’iru Ivy , van der Heijden Eva , Talavera Gerard , Warren Ian A. , Collins Steve , ffrench-Constant Richard H. , Martins Dino J. , Chan Yingguang Frank , Jiggins Chris D. , Martin Simon H. 
Published: July 2023

AbstractHypolimnas misippusis a Batesian mimic of the toxic African Queen butterfly(Danaus chrysippus). FemaleH. misippusbutterflies use two major wing patterning loci (M and A) to imitate the four colour morphs ofD. chrysippusfound in different regions of Africa. In this study, we examine the evolution of the M locus and identify it as an example of adaptive atavism. This phenomenon involves a morphological reversion to an ancestral character that results in an adaptive phenotype. We show thatH. misippushas re-evolved a wing pattern present in otherHypolimnasspecies for Batesian mimicry of aD. chrysippusmorph. Using haplotagging, a linked-read sequencing technology, we discover two large transposable element (TE) insertions located at the M locus and establish that these insertions are present in the dominant allele responsible for producing the ancestral and mimetic phenotype. By conducting a comparative analysis involving additionalHypolimnasspecies, we demonstrate that the dominant allele is derived. This suggests that the TEs disrupt a cis-regulatory element, leading to the reversion to an ancestral phenotype that is then utilized for Batesian mimicry of a distinct model, a different morph ofD. chrysippus. Our findings present a compelling instance of convergent evolution and adaptive atavism, in which the same pattern element has independently evolved multiple times inHypolimnasbutterflies, repeatedly playing a role in Batesian mimicry of diverse model species.
Sustained hippocampal theta-oscillations reflect experience-dependent learning in backward temporal order memory retrieval
Authors: Jiang Hongjie , Cai Jing , Santos-Pata Diogo , Shi Lei , Zhu Xuanlong , Tong Jiaona , Cai Yudian , Li Chenyang , Wang Rui , Yin Jia , Zhang Shaomin , Kwok Sze Chai 
Published: July 2023

AbstractNavigating within our neighborhood, learning a set of concepts, or memorizing a story, requires remembering the relationship between individual items that are presented sequentially. Theta activity in the mammalian hippocampus has been related to the encoding and recall of relational structures embedding episodic memories. However, how theta oscillations are involved in retrieving temporal order information in opposing directionality (forward vs backward) has not been characterized. Here, using intracranial recordings from 10 human epileptic patients of both genders with hippocampal electrodes, we tested the patients with a temporal order memory task in which they learned the spatial relationship among individual items arranged along a circular track and were tested on both forward-cued and backward-cued retrieval conditions. We found that sustained high-power oscillatory events in the hippocampal theta (2-8 Hz) band, as quantified by Pepisoderate, were higher for the backward conditions during the later stage but not in the earlier stage. The theta Pepisoderesults are consistent with the behavioral memory performance. In contrast, we observed a stronger effect of forward than backward retrieval for the gamma (30-70 Hz) Pepisoderate irrespective of stages. Our results revealed differential roles of theta vs. gamma oscillations in the retrieval of temporal order and how theta oscillations are specifically implicated in the learning process for efficient retrieval of temporal order memories under opposing directionality.Significance statementWhile the hippocampus is critical to link events into unitary episodes, the effect of repeated experiences, or learning, on these processes is not entirely clear. We discovered that hippocampal theta oscillation in humans is modulated by repeated experiences, which in turn increases the efficacy of backward-cued memory retrieval of temporal order. This study revealed an important physiological signature characterizing the role of experiences and learning in bidirectional temporal memory retrieval.Journal sectionBehavioral/Cognitive
Remodeling of the secretory pathway is coordinated withde novomembrane formation in budding yeast gametogenesis
Authors: Suda Yasuyuki , Tachikawa Hiroyuki , Suda Tomomi , Kurokawa Kazuo , Nakano Akihiko , Irie Kenji 
Published: July 2023

AbstractGametogenesis in budding yeast involves a large-scale rearrangement of membrane traffic to allowde novoformation of a membrane, called the prospore membrane (PSM). However, the mechanism underlying this event is not fully elucidated. Here, we show that the number of endoplasmic reticulum exit sites (ERES) per cell fluctuates and switches from decreasing to increasing upon the onset of PSM formation. Reduction in ERES number, presumably accompanying a transient stall in membrane traffic, resulting in the loss of preexisting Golgi apparatus from the cell, was followed by local ERES regeneration, leading to Golgi reassembly in nascent spores. We have revealed that protein phosphatase-1 (PP-1) and its development-specific subunit, Gip1, promote ERES regeneration through Sec16 foci formation. Furthermore,sed4Δ, a mutant with impaired ERES formation, showed defects in PSM growth and spore formation. Thus, ERES regeneration in nascent spores facilitates the segregation of membrane traffic organelles, leading to PSM growth.
Identification of the yeast mannoprotein geneHZY1as a key genetic determinant for yeast-derived haze in beer
Authors: Lacy Keith , Mormando Rita , Smith Jeremy R. , Gibney Patrick A. , Shaner Lance M. , Burns Laura T. 
Published: July 2023

AbstractWith the sustained popularity of hazy IPAs, brewers have explored multiple approaches to maximizing stable haze that will remain in suspension throughout the shelf life of the beer. Our recent investigations into yeast-dependent haze have uncovered specific brewing yeast strains that promote the formation of haze in heavily dry-hopped beer styles. These brewing strains have been termed “haze-positive” and furthermore, the timing of dry hop additions has been found to be another key factor in producing this stable haze. Classical genetics have identified YIL169C (herein referred to asHZY1) as both necessary and sufficient for the haze-positive phenotype in the yeast strain most widely used for Hazy IPAs.HZY1encodes a candidate glycoprotein and our recent findings suggest it is localized to the cell wall through a GPI anchor. Surprisingly, using long-read sequencing data we uncovered extensive genetic variation inHZY1across brewing strains. The haze-positive phenotype correlates with an expansion in the N-terminal serine-rich region. We propose that the Hzy1 glycoprotein is a critical component to yeast-dependent colloidal haze and the genetic variation in this locus contributes the range of haze phenotypes observed across industrial brewing strains.
Regulatory preconditioning for the evolution of C4photosynthesis revealed by low CO2treatment of Arabidopsis thaliana
Authors: Miao Fenfen , Haq Noor UI , Lyu Ming-Ju Amy , Zhu Xin-Guang 
Published: July 2023

AbstractLow CO2condition was considered a preconditioning or selection pressure for C4evolution. However, it remains elucidated how low CO2condition contribute to the evolutionary assembly of the C4pathway. We conducted a systematic transcriptomics and metabolomics analysis under short-term low CO2condition and found thatArabidopsisgrown under this condition showed increased expression of most genes encoding C4- related enzymes and transporters. Low CO2condition increased NH4+content in leaves; as expected, photorespiratory and ammonia refixing pathways were enhanced. Furthermore, we found that compared to low CO2condition, in vitro treatment with NH4+induced a similar pattern of changes in C4related genes and genes involved in ammonia refixation. This supports that increased expression of C4genes induced by low CO2condition can supply carbon skeleton for ammonia recycling. This study provides new insight into the regulatory preconditioning which may have facilitated the evolution of C4photosynthesis under low atmospheric CO2environments.
Effects of aluminum-salt, CpG and emulsion adjuvants on the stability and immunogenicity of a virus-like particle displaying the SARS-CoV-2 receptor-binding domain (RBD)
Authors: Kumru Ozan S. , Bajoria Sakshi , Kaur Kawaljit , Hickey John M. , Van Slyke Greta , Doering Jennifer , Berman Katherine , Richardson Charles , Lien Hans , Kleanthous Harry , Mantis Nicholas J. , Joshi Sangeeta B. , Volkin David B. 
Published: July 2023

AbstractSecond-generation COVID-19 vaccines with improved immunogenicity (e.g., breadth, duration) and availability (e.g., lower costs, refrigerator stable) are needed to enhance global coverage. In this work, we formulated a clinical-stage SARS-CoV-2 receptor binding domain (RBD) virus-like particle (VLP) vaccine candidate (IVX-411) with widely available adjuvants. Specifically, we assessed thein vitrostorage stability andin vivomouse immunogenicity of IVX-411 formulated with aluminum-salt adjuvants (Alhydrogel™, AH and Adjuphos™, AP), without or with the TLR-9 agonist CpG-1018™ (CpG), and compared these profiles to IVX-411 adjuvanted with an oil-in-water nano-emulsion (AddaVax™, AV). Although IVX-411 bound both AH and AP, lower binding strength of antigen to AP was observed by Langmuir binding isotherms. Interestingly, AH- and AP-adsorbed IVX-411 had similar storage stability profiles as measured by antigen binding assays (competitive ELISAs), but the latter displayed higher pseudovirus neutralizing titers (pNT) in mice, at levels comparable to titers elicited by AV-adjuvanted IVX-411. CpG addition to alum (AP or AH) resulted in a marginal trend of improved pNTs in stressed samples only, yet did not impact the storage stability profiles of IVX-411. In contrast, previous work with AH-formulations of a monomeric RBD antigen showed greatly improved immunogenicity and decreased stability upon CpG addition to alum. At elevated temperatures (25, 37°C), IVX-411 formulated with AH or AP displayed decreasedin vitrostability compared to AV-formulated IVX-411and this rank-ordering correlated within vivoperformance (mouse pNT values). This case study highlights the importance of optimizing antigen-adjuvant interactions to develop low cost, aluminum-salt adjuvanted recombinant subunit vaccine candidates.