bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic profiling of retinal cells reveals a subpopulation of microglia/macrophages expressing Rbpms and Spp1 markers of retinal ganglion cells (RGCs) that confound identification of RGCs
Authors: Theune William C. , Trakhtenberg Ephraim F. 
Published: January 2023

ABSTRACTAnalysis of retinal ganglion cells (RGCs) by scRNA-seq is emerging as a state-of-the-art method for studying RGC biology and subtypes, as well as for studying the mechanisms of neuroprotection and axon regeneration in the central nervous system (CNS). Rbpms has been established as a pan-RGC marker, and Spp1 has been established as an αRGC type marker. Here, we analyzed by scRNA-seq retinal microglia and macrophages, and found Rbpms+ and Spp1+ subpopulations of retinal microglia/macrophages, which pose a potential pitfall in scRNA-seq studies involving RGCs. We performed comparative analysis of cellular identity of the presumed RGC cells isolated in recent scRNA-seq studies, and found that Rbpms+ and Spp1+ microglia/macrophages confounded identification of RGCs. We also provide solutions for circumventing this potential pitfall in scRNA-seq studies, by including in RGC and αRGC selection criteria other pan-RGC and αRGC markers.
rRNA intermediates coordinate the multilayered nucleolar phase transition inC. elegans
Authors: Xu Demin , Chen Xiangyang , Kuang Yan , Hong Minjie , Xu Ting , Wang Ke , Fu Chuanhai , Ruan Ke , Zhu Chengming , Feng Xuezhu , Guang Shouhong 
Published: January 2023

AbstractThe nucleolus is the most prominent membraneless organelle within the nucleus and plays essential roles in rRNA transcription and processing and ribosome assembly. How the structure of the nucleolus is maintained and regulated is poorly understood. Here, we identified two types of nucleoli inC. elegans. Type I nucleoli are spherical, and rRNA transcription and processing factors are evenly distributed throughout the nucleolus. In type II nucleoli, rRNA transcription and processing factors exclusively accumulate in the periphery rim, which is named the nucleolar ring. The hollow vacuole inside the nucleolar ring contains proteins that usually localize in the nucleoplasm but are capable of exchanging contents across the ring. The high-order structure of the nucleolus is dynamically regulated inC. elegans. Faithful rRNA processing is important to maintain the spherical structure of the nucleoli. The depletion of a class of rRNA processing factors, for example, class I ribosomal proteins of the large subunit (RPL), which are involved in 27SA2rRNA processing, reshaped spherical nucleoli to a ring-shaped nucleolar structure. The inhibition of RNAP I transcription and depletion of two conserved nucleolar factors, nucleolin and fibrillarin, prohibits the formation of the nucleolar ring. We concluded that the integrity of nucleoli is highly dependent on rRNA processing and maturation, which may provide a mechanism to coordinate structure maintenance and gene expression.
Prefrontal cortical protease TACE/ADAM17 is involved in neuroinflammation and stress-related eating alterations
Authors: Sharafeddin Fransua , Ghaly Mina , Simon Timothy B. , Ontiveros-Ángel Perla , Figueroa Johnny D. 
Published: January 2023

ABSTRACTChildhood traumatic stress profoundly affects prefrontal cortical networks regulating top-down control of eating and body weight. However, the neurobiological mechanisms contributing to trauma-induced aberrant eating behaviors remain largely unknown. Traumatic stress influences brain immune responses, which may, in turn, disrupt prefrontal cortical networks and behaviors. The tumor necrosis factor alpha-converting enzyme / a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and neuroinflammation. This study aimed to determine the role of TACE/ADAM17 on traumatic stress-induced disruption of eating patterns. We demonstrate a novel mechanistic connection between prefrontal cortical TACE/ADAM17 and trauma-induced eating behaviors. Fifty-two (52) adolescent Lewis rats (postnatal day, PND, 15) were injected intracerebrally either with a novel Accell™ SMARTpool ADAM17 siRNA or a corresponding siRNA vehicle. The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Observation cages were used to monitor ethological behaviors in a more naturalistic environment over long periods. We found that traumatic stress blunts startle reactivity and alter eating behaviors (increased intake and disrupted eating patterns). We also found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited decreased eating and increased grooming behaviors compared to controls. These changes were associated with decreased AIF-1 expression (a typical marker of microglia and neuroinflammation). This study demonstrates that prefrontal cortical TACE/ADAM17 is involved in neuroinflammation and may play essential roles in regulating feeding patterns under stress conditions. TACE/ADAM17 represents a promising target to ameliorate inflammation-induced brain and behavior alterations.
Investigating the effect of changes in model parameters on optimal control policies, time to absorption, and mixing times
Authors: Johnson Kathleen , Plaugher Daniel , Murrugarra David 
Published: January 2023

AbstractMany processes in biology and medicine have been modeled using Markov decision processes which provides a rich algorithmic theory for model analysis and optimal control. An optimal control problem for stochastic discrete systems consists of deriving a control policy that dictates how the system will move from one state to another such that the probability of reaching a desired state is maximized. In this paper, we focus on the class of Markov decision processes that is obtained by considering stochastic Boolean networks equipped with control actions. Here, we study the effect of changes in model parameters on optimal control policies. Specifically, we conducted a sensitivity analysis on optimal control policies for a Boolean model of the T-cell large granular lymphocyte (T-LGL). For this model, we quantified how the choice of propensity parameters impacts the effectiveness of the optimal policy and then we provide thresholds at which the effectiveness is guaranteed. We also examined the effect on the optimal control policies of the level of noise that is usually added for simulations. Finally, we studied the effect on changes in the propensity parameters on the time to absorption and the mixing time for a Boolean model of the Repressilator.
Protein semisynthesis underscores role of a conserved lysine in activation and desensitization of acid-sensing ion channels
Authors: Sarkar Debayan , Galleano Iacopo , Heusser Stephanie Andrea , Ou Sofie Yuewei , Refika Uzun Gül , Khoo Keith K. , van der Heden van Noort Gerbrand Jan , Harrison Joseph Scott , Pless Stephan Alexander 
Published: January 2023

ABSTRACTAcid-sensing ion channels (ASICs) are trimeric ion channels that open a cation-conducting pore in response to proton binding. Excessive ASIC activation during prolonged acidosis in conditions such as inflammation and ischemia is linked to pain and stroke. A conserved lysine in the extracellular domain (Lys211 in mASIC1a) is suggested to play a key role in ASIC function. However, the precise contributions are difficult to dissect with conventional mutagenesis, as replacement of Lys211 with naturally occurring amino acids invariably changes multiple physico-chemical parameters. Here, we study the contribution of Lys211 to mASIC1a function using tandem protein-trans splicing (tPTS) to incorporate non-canonical lysine analogs. We conduct optimization efforts to improve splicing and functionally interrogate semisynthetic mASIC1a. In combination with molecular modeling, we show that Lys211 charge and side chain length are crucial to activation and desensitization, thus emphasizing that tPTS can enable atomic-scale interrogations of membrane proteins in live cells.
Structures of two main components of the virophage and Marseilleviridae virions extend the range of unrelated viruses using fiber head as common receptor binding fold
Authors: Jeudy Sandra , Garcin Elsa , Schmitt Alain , Abergel Chantal 
Published: January 2023

ABSTRACTThe detailed proteomic analysis ofMarseilleviridaeicosahedral capsids revealed that the two most abundant protein components of the virions were the Major Capsid Protein (MCP) and the product of an ORFan gene conserved in allMarseilleviridae. The noumeavirus NMV_189 3D structure revealed a common fold with fiber head proteins used by a variety of viruses to recognize their cellular receptor. However, the trimeric structure of NMV_189 uniquely lacking a tail domain, presented a deep concave site suggesting it could be directly anchored to the pseudo-hexagonal capsomers of the virion. This was confirmed by the unambiguous fit of the structure in the melbournevirus 4.4 Å cryo-EM map. In parallel, our structural genomic study of zamilon vitis virophage capsid proteins revealed that Zav_19 shared the same trimeric fiber head fold, but presented an N-terminal tail with a unique β-prism fold. The fiber head fold thus appears to be conserved in all types of non-enveloped icosahedral virions independently of their genomic contents (dsDNA, ssRNA, dsRNA). This could be a testimony of a common origin or the result of convergent evolution for receptor binding function.IMPORTANCEGiant viruses and their associated virophages exhibit a large proportion (≥60%) of orphan genes,i.e. genes without homologs in databases, and thus a vast majority of their proteins are of unknown function. The structural characterization of two ORFans, NMV_189 and Zav_19, both major components of noumeavirus and zamilon virophage capsids, respectively, revealed that despite a total lack of sequence homology, the two proteins share a common trimeric fold typical of viral receptor binding proteins and could be responsible for host receptor recognition. These two structures extend the range of unrelated viruses using fiber head structures as common receptor binding fold.
Metachronal coordination enables omnidirectional swimming via spatially distributed propulsion
Authors: Herrera-Amaya Adrian , Byron Margaret L. 
Published: January 2023

AbstractAquatic organisms often employ maneuverable and agile swimming behavior to escape from predators, find prey, or navigate through complex environments. Many of these organisms use metachronally coordinated appendages to execute complex maneuvers. However, though metachrony is used across body sizes ranging from microns to tens of centimeters, it is understudied compared to the swimming of fish, cetaceans, and other groups. In particular, metachronal coordination and control of multiple appendages for three-dimensional maneuvering is not fully understood. To explore the maneuvering capabilities of metachronal swimming, we combine 3D high-speed videography of freely swimming ctenophores (Bolinopsis vitrea) with reduced-order mathematical modeling. Experimental results show that ctenophores can quickly reorient, and perform tight turns while maintaining forward swimming speeds close to 70% of their observed maximum — performance comparable to or exceeding that of many vertebrates with more complex locomotor systems. We use a reduced-order model to investigate turning performance across a range of beat frequencies and appendage control strategies, and reveal that ctenophores are capable of near-omnidirectional turning. Based on both recorded and modeled swimming trajectories, we conclude that the ctenophore body plan enables a high degree of maneuverability and agility, and may be a useful starting point for future bioinspired aquatic vehicles.Author summaryMetachronal swimming—the sequential, coordinated beating of appendages arranged in a row— exists across a wide range of sizes, from unicellular organisms (micrometers) to marine crustaceans (tens of centimeters). While metachronal swimming is known to be scalable and efficient, the level of maneuverability and agility afforded by this strategy is not well understood. This study explores the remarkable 3D maneuverability of ctenophores (comb jellies), and the appendage control strategies they use to achieve it. Ctenophores have eight rows of appendages (instead of the one or two found in crustaceans and other organisms). This higher number of appendages, their distribution along the body, and the independent frequency control between paired rows enables near-omnidirectional swimming and turning performance, placing ctenophores among the most maneuverable swimmers. We use experiments and mathematical modeling to explore both the real and theoretical performance landscape of the ctenophore body plan, and show that ctenophores are capable of executing tight turns at high speeds in nearly any plane. This omnidirectional swimming capability gives insight into the ecology and behavior of an important taxonomic group, and shows the potential of metachronal swimming as a source of design inspiration for robotic vehicles (particularly those that must navigate complex environments).
Clinical manifestation and laboratory parameters associated with progression to severe dengue in children: a systematic review and meta-analysis
Authors: Sandinirwan Indra , Muslim Bani , Leo Henry , Hasanah Hasanah , Karina Permata Putri 
Published: January 2023

AbstractBackgroundThe ingenuity to predict the progression to severe dengue is crucial in managing dengue patients. The previous meta-analysis has been performed on adults, and none has been performed specifically on children. We conducted a systematic review and meta-analysis to determine the clinical manifestations and laboratory parameters associated with the progression to severe dengue according to WHO criteria.MethodsWe focused on searching six medical databases for studies published from Jan 1, 2000, to Dec 31, 2020. The meta-analysis used random-effects or fixed-effects models to estimate pooled effect sizes. We also assessed the heterogeneity and publication bias. This study was registered with PROSPERO, CRD42021224439.ResultsWe included 49 of papers in the systematic review, and we encased the final selected 39 papers comprising 23 potential predictors in the meta-analyses. Among 23 factors studied, seven clinical manifestations demonstrated association with disease progression in children, including neurological signs, gastrointestinal bleeding, clinical fluid accumulation, hepatomegaly, vomiting, abdominal pain, and petechiae. Six laboratory parameters are associated during the early days of illness, including elevated hematocrit, elevated aspartate aminotransferase [AST], elevated alanine aminotransferase [ALT], low platelet count, low albumin levels, and elevated activated partial thromboplastin time. Dengue virus serotype 2 (DENV-2) and secondary infections were also associated with severe disease progression.ConclusionThis finding supports the use of the warning signs described in the WHO 2009 guidelines. In addition, monitoring serum albumin, AST/ALT levels, identifying infecting dengue serotypes, and immunological status could improve the risk prediction of disease progression.
Building a genome-based understanding of bacterial pH preferences
Authors: Ramoneda Josep , Stallard-Olivera Elias , Hoffert Michael , Winfrey Claire C. , Stadler Masumi , Niño-García Juan Pablo , Fierer Noah 
Published: January 2023

AbstractThe environmental preferences of many microbes remain undetermined. This is the case for bacterial pH preferences, which can be difficult to predicta prioridespite the importance of pH as a factor structuring bacterial communities in many systems. We compiled data on bacterial distributions from five datasets spanning pH gradients in soil and freshwater systems (1470 samples in total), quantified the pH preferences of bacterial taxa across these datasets, and compiled genomic data from representative bacterial taxa. While taxonomic and phylogenetic information were generally poor predictors of bacterial pH preferences, we identified genes consistently associated with pH preference across environments. We then developed and validated a machine learning model to estimate bacterial pH preferences from genomic information alone, a model which could aid in the selection of microbial inoculants, improve species distribution models, or help design effective cultivation strategies. More generally, we demonstrate the value of combining biogeographic and genomic data to infer and predict the environmental preferences of diverse bacterial taxa.
Distribution and genetic diversity of South FloridaTephrosiashed light on past cultural use
Authors: von Wettberg Eric JB , Sadle Jimi , Ogutcen Ezgi , Possley Jennifer , Lange James , Carrasquila-Garcia Noelia , Chang Peter L. 
Published: January 2023

SummaryThe genusTephrosia(Fabaceae), the hoary peas, contain high levels of rotenone, which has a long history of human use as a fish poison. We examine the distribution ofTephrosia angustissima, in South Florida to clarify patterns of genetic relatedness and shed light on human plant movement before European contact. Several populations ofTephrosia angustissimawith a history of taxonomic uncertainty exist in South Florida and the neighboring Caribbean Islands.To clarify relationships in this group, and to elucidate the conservation status of populations in Everglades National Park and Big Cypress National Preserve, we used restriction site associated DNA sequencing (RAD-SEQ) on 94 samples from South Florida and three locations in southwest Puerto Rico.Analysis of variation in SNP markers by the Bayesian STRUCTURE algorithm and principal coordinate analysis both separated the samples into three groups. These three groups were likely separate colonization events of Florida. Genetic diversity is moderate in all of the groups, with only limited evidence of a bottleneck in some of the disjunct South Florida populations.Overall, the human association of this group is consistent with a history of human use, suggesting conservation efforts for these taxa should consider their pre-Columbian human associations.Societal impact statementA great many endangered plant taxa exhibit patterns of edaphic specialization, occurring on particular substrates such as karst or serpentine soils. Human activities, such as the construction of shell middens, can create edaphically unique substrates. In the Americas, post-Columbian land use changes coupled with extensive loss of indigenous cultural knowledge, has created areas where associations of cultivated plants with human-generated habitats may be lost. Here we use population genetic approaches to examine rareTephrosia(hoary pea) taxa from South Florida, a group of plants that produce rotenone that has been used by many indigenous groups as a fish poison. We find evidence of multiple introductions from the broader Caribbean region and an association with anthropogenic habitats such as shell middens. In efforts to conserve rare hoary peas in Florida, an understanding of past use of the landscape by native Americans is essential.
ciRS-7 and miR-7 regulate ischemia induced neuronal death via glutamatergic signaling
Authors: Scoyni Flavia , Sitnikova Valeriia , Giudice Luca , Korhonen Paula , Trevisan Davide M , Hernandez de Sande Ana , Gomez-Budia Mireia , Giniatullina Raisa , Ugidos Irene F , Dhungana Hiramani , Pistono Cristiana , Korvenlaita Nea , Välimäki Nelli-Noora , Kangas Salla M , Hiltunen Anniina E , Gribchenko Emma , Kaikkonen-Määttä Minna U , Koistinaho Jari , Ylä-Herttuala Seppo , Hinttala Reetta , Venø Morten T , Su Junyi , Stoffel Markus , Schaefer Anne , Rajewsky Nikolaus , Kjems Jørgen , LaPierre Mary P , Piwecka Monika , Jolkkonen Jukka , Giniatullin Rashid , Hansen Thomas B , Malm Tarja 
Published: January 2023

ABSTRACTBrain functionality relies on finely tuned regulation of gene expression by networks of non-coding RNAs (ncRNAs) such as the one composed by the circular RNA ciRS-7 (also known as CDR1as), the microRNA miR-7 and the long non-coding RNA Cyrano. Here we describe ischemia induced alterations in the ncRNA network bothin vitroandin vivoand in transgenic mice lacking ciRS-7 or miR-7. Our data show that cortical neurons downregulate ciRS-7 and Cyrano and upregulate miR-7 expression upon ischemic insults. Mice lacking ciRS-7 show reduced lesion size and motor impairment, whilst the absence of miR-7 alone leads to an increase in the ischemia induced neuronal death. Moreover, miR-7 levels in pyramidal excitatory neurons regulate dendrite morphology and glutamatergic signaling suggesting a potential molecular link to thein vivophenotype. Our data reveal that ciRS-7 and miR-7 contribute to the outcome of ischemic stroke and shed new light into the pathophysiological roles of intracellular networks of non-coding RNAs in the brain.
Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome
Authors: Johnson Kelsey E. , Heisel Timothy , Allert Mattea , Fürst Annalee , Yerabandi Nikhila , Knights Dan , Jacobs Katherine M. , Lock Eric F. , Bode Lars , Fields David A. , Rudolph Michael C. , Gale Cheryl A. , Albert Frank W. , Demerath Ellen W. , Blekhman Ran 
Published: January 2023

AbstractHuman milk is a complex mix of nutritional and bioactive components that provide complete nutrition for the infant. However, we lack a systematic knowledge of the factors shaping milk composition and how milk variation influences infant health. Here, we used multi-omic profiling to characterize interactions between maternal genetics, milk gene expression, milk composition, and the infant fecal microbiome in 242 exclusively breastfeeding mother-infant pairs. We identified 487 genetic loci associated with milk gene expression unique to the lactating mammary gland, including loci that impacted breast cancer risk and human milk oligosaccharide concentration. Integrative analyses uncovered connections between milk gene expression and infant gut microbiome, including an association between the expression of inflammation-related genes with IL-6 concentration in milk and the abundance ofBifidobacteriain the infant gut. Our results show how an improved understanding of the genetics and genomics of human milk connects lactation biology with maternal and infant health.
A new web resource to predict the impact of missense variants at protein interfaces using 3D structural data: Missense3D-PPI
Authors: Pennica Cecilia , Hanna Gordon , Islam Suhail A , Sternberg Michael JE , David Alessia 
Published: January 2023

ABSTRACTIn 2019, we released Missense3D which identifies stereochemical features that are disrupted by a missense variant, such as introducing a buried charge. Missense3D analyses the effect of a missense variant on a single structure and thus may fail to identify as damaging surface variants disrupting a protein interface i.e., a protein-protein interaction (PPI) site. Here we present Missense3D-PPI designed to predict missense variants at PPI interfaces.Our development dataset comprised of 1,279 missense variants (pathogenic n=733, benign n=546) in 434 proteins and 545 experimental structures of PPI complexes. Benchmarking of Missense3D-PPI was performed after dividing the dataset in training (320 benign and 320 pathogenic variants) and testing (226 benign and 413 pathogenic). Structural features affecting PPI, such as disruption of interchain bonds and introduction of unbalanced charged interface residues, were analysed to assess the impact of the variant at PPI.Missense3D-PPI’s performance was superior to that of Missense3D: sensitivity 42% versus 8% and accuracy 58% versus 40%, p=4.23×10−16However, the specificity of Missense3D-PPI was slightly lower compared to Missense3D (84% versus 98%). On our dataset, Missense3D-PPI’s accuracy was superior to BeAtMuSiC (p=2.3×10−5), mCSM-PPI2 (p=3.2×10−12) and MutaBind2 (p=0.003).Missense3D-PPI represents a valuable tool for predicting the structural effect of missense variants on biological protein networks and is available at the Missense3D web portal (http://missense3d.bc.ic.ac.uk/missense3d/indexppi.html).