bluuebunny/crossref_metadata_2025_split huggingface dataset:
ArcheD, a residual neural network for prediction of cerebrospinal fluid amyloid-beta from amyloid PET images
Authors: Tagmazian Arina A. , Schwarz Claudia , Lange Catharina , Pitkänen Esa , Vuoksimaa Eero ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2023

AbstractDetection and measurement of amyloid-beta (Aβ) aggregation in the brain is a key factor for early identification and diagnosis of Alzheimer’s disease (AD). We aimed to develop a deep learning model to predict Aβ cerebrospinal fluid (CSF) concentration directly from amyloid PET images, independent of tracers, brain reference regions or preselected regions of interest. We used 1870 Aβ PET images and CSF measurements to train and validate a convolutional neural network (“ArcheD”). We evaluated the ArcheD performance in relation to episodic memory and the standardized uptake value ratio (SUVR) of cortical Aβ. We also compared the brain region’s relevance for the model’s CSF prediction within clinical-based and biological-based classifications. ArcheD-predicted Aβ CSF values correlated strongly with measured Aβ CSF values (r=0.81;p<0.001) and showed correlations with SUVR and episodic memory measures in all participants except in those with AD. For both clinical and biological classifications, cerebral white matter significantly contributed to CSF prediction (q<0.01), specifically in non-symptomatic and early stages of AD. However, in late-stage disease, brain stem, subcortical areas, cortical lobes, limbic lobe, and basal forebrain made more significant contributions (q<0.01). Considering cortical gray matter separately, the parietal lobe was the strongest predictor of CSF amyloid levels in those with prodromal or early AD, while the temporal lobe played a more crucial role for those with AD. In summary, ArcheD reliably predicted Aβ CSF concentration from Aβ PET scans, offering potential clinical utility for Aβ level determination and early AD detection.
Protein evolvability under rewired genetic codes
Authors: Rozhoňová Hana , Martí-Gómez Carlos , McCandlish David M. , Payne Joshua L. 
Published: June 2023

AbstractThe standard genetic code defines the rules of translation for nearly every life form on Earth. It also determines the amino acid changes accessible via single-nucleotide mutations, thus influencing protein evolvability — the ability of mutation to bring forth adaptive variation in protein function. One of the most striking features of the standard genetic code is its robustness to mutation, yet it remains an open question whether this robustness facilitates or frustrates protein evolvability. To answer this question, we use data from massively-parallel sequence-to-function assays to construct and analyze empirical adaptive landscapes under hundreds of thousands of rewired genetic codes, including those of codon compression schemes relevant to protein engineering and synthetic biology. We find that robust genetic codes tend to enhance protein evolvability by rendering smooth adaptive landscapes with few peaks, which are readily accessible from throughout sequence space. By constructing low-dimensional visualizations of these landscapes, which each comprise more than 16 million mRNA sequences, we demonstrate that alternative genetic codes can radically alter the topological features of the network of high-fitness genotypes. Whereas the genetic codes that optimize evolvability depend to some extent on the detailed relationship between amino acid sequence and protein function, we also uncover general design principles for engineering non-standard genetic codes for enhanced and diminished evolvability, which may facilitate directed protein evolution experiments and the biocontainment of synthetic organisms, respectively. Our findings demonstrate that the standard genetic code, a critical and near-universal cellular information processing system, not only mitigates replication and translation errors as compared to most alternative genetic codes, but also facilitates predictable and directional adaptive evolution by enabling evolving populations to readily find mutational paths to adaptation.
Functional Implications of the Exon 9 Splice Insert in GluK1 Kainate Receptors
Authors: Dhingra Surbhi , Chopade Prachi M. , Vinnakota Rajesh , Kumar Janesh 
Published: June 2023

AbstractKainate receptors are key modulators of synaptic transmission and plasticity in the central nervous system. Different kainate receptor isoforms with distinct spatiotemporal expressions have been identified in the brain. The GluK1-1 splice variant receptors, which are abundant in the adult brain, have an extra fifteen amino acids inserted in the amino-terminal domain (ATD) of the receptor resulting from alternative splicing of exon 9. However, the functional implications of this post-transcriptional modification are not yet clear. We employed a multi-pronged approach using cryogenic electron microscopy, electrophysiology, and other biophysical and biochemical tools to understand the structural and functional impact of this splice insert in the extracellular domain of GluK1 receptors. Our study reveals that the splice insert alters the key gating properties of GluK1 receptors and their modulation by the cognate auxiliary Neuropilin and tolloid-like (Neto) proteins 1 and 2. Mutational analysis identified the role of crucial splice residues that influence receptor properties and their modulation. Furthermore, the cryoEM structure of the variant shows that the presence of exon 9 in GluK1 does not affect the receptor architecture or domain arrangement in the desensitized state. Our study thus provides the first detailed structural and functional characterization of GluK1-1a receptors, highlighting the role of the splice insert in modulating receptor properties and their modulation.
ParSe 2.0: A web application that enables proteome-scale searches for sequences that drive protein-mediated phase separation
Authors: Wilson Colorado , Lewis Karen A. , Fitzkee Nicholas C. , Hough Loren E. , Whitten Steven T. 
Published: June 2023

AbstractWe have developed an algorithm, ParSe, that accurately identifies from the primary sequence those protein regions likely to exhibit physiological phase separation behavior. Originally, ParSe was designed to test the hypothesis that, for flexible proteins, phase separation potential is correlated to hydrodynamic size. While our results were consistent with that idea, we also found that many different descriptors could successfully differentiate between three classes of protein regions: folded, intrinsically disordered, and phase-separating intrinsically disordered. Consequently, numerous combinations of amino acid property scales can be used to make robust predictions of protein phase separation. Built from that finding, ParSe 2.0 uses an optimal set of property scales to predict domain-level organization and compute a sequence-based prediction of phase separation potential. The algorithm is fast enough to scan the whole of the human proteome in minutes on a single computer and is equally or more accurate than other published predictors in identifying proteins and regions within proteins that drive phase separation. Here, we describe a web application for ParSe 2.0 that may be accessed through a browser by visitinghttps://stevewhitten.github.io/Parse_v2_FASTAto quickly identify phase-separating proteins within large sequence sets, or by visitinghttps://stevewhitten.github.io/Parse_v2_webto evaluate individual protein sequences.
Blood flow directionality establishes the SCN as source and OVLT as target within a new vascular portal pathway
Authors: Roy Ranjan K. , Yao Yifan , Green Isabella K. , Silver Rae , Stern Javier E. 
Published: June 2023

SUMMARYThe suprachiasmatic nucleus (SCN) is the locus of a brain clock that sets the phase of oscillation in cells throughout the brain and body. Anatomical evidence reveals a portal system linking the SCN and the OVLT (here termed SCN-OVLTp). This discovery begs the question of the direction of blood flow and the nature of diffusible signals that flow in this specialized vasculature. Here we show unequivocally that the direction of blood flow is from the SCN to the OVLT, that the rate of flow is under circadian regulation, and that vasopressin (AVP) is present in portal vessels following systemic injection. These findings highlight a previously unknown CNS communication pathway. It is well established that the SCN is required for circadian regulation of AVP in the CSF and that the OVLT bears AVP receptors. Specifically, SCN neurons are necessary for time-stamped signals such as the peptide AVP, that can travel via portal veins to a target in the OVLT. The OVLT, a circumventricular organ offering a “window to the brain,” can relay neural and diffusible signals to broad brain areas via its efferent connections and via the CSF. We conclude that the SCN-OVLTp, like that of the pituitary portal system, discovered almost a century ago, allows neurosecretions to reach nearby specialized target sites, thereby avoiding dilution in the systemic blood. In both of these brain portal pathways, the target site, namely the pituitary and OVLT respectively, relay signals broadly, to both the brain and the rest of the body.
ShinyMultiome.UiO: An interactive open-source framework utilizing Seurat Objects for visualizing single-cell Multiomes
Authors: Akshay Akshay , Sharma Ankush , Eskeland Ragnhild 
Published: June 2023

AbstractMotivationSingle-cell genomics has been revolutionized by the advent of single-cell Multiome sequencing which allows for simultaneous profiling of chromatin accessibility and gene expression in individual nuclei. The analysis and interpretation of large and often complex scMultiome datasets requires in-depth knowledge of computational programming.ResultsWe present ShinyMultiome.UiO, a user-friendly, integrative, and opensource web-based tool that supports Seurat objects for visualization of single-cell Multiome. The ShinyMultiome.UiO facilitates interactive reporting and comprehensive characterization of cellular heterogeneity and regulatory landscapes. With ShinyMultiome.UiO, users can facilitate collaborative efforts for interpre-tation of single-cell Multiome data and make it available to the public.Availability and implementationhttps://github.com/EskelandLab/ShinyMultiomeUiOand demo server,https://cancell.medisin.uio.no/ShinyMultiome.UiO/set up with a PBMC reference dataset.ContactAnkush.Sharma@medisin.uio.no&Ragnhild.Eskeland@medisin.uio.no
Maintaining task performance levels under cognitive load while walking requires widespread reallocation of neural resources: A Mobile Brain-Body Imaging (MoBI) study
Authors: Patelaki Eleni , Foxe John J. , McFerren Amber L. , Freedman Edward G. 
Published: June 2023

ABSTRACTThe neural underpinnings of increasing cognitive load during walking, despite being ubiquitous in everyday life, is still not fully understood. This study elucidates the neural mechanisms underlying increased cognitive load while walking, by employing 2 versions of a Go/NoGo response inhibition task, namely the 1-back Go/NoGo task and the more cognitively demanding 2-back Go/NoGo task, during sitting or walking on a treadmill. By using the Mobile Brain/Body Imaging (MoBI) modality, electroencephalographic (EEG) activity, three-dimensional (3D) gait kinematics and task-related behavioral responses were collected from 34 young adults for the 1-back Go/NoGo task and 34 young adults for the 2-back Go/NoGo task. Interestingly, increasing cognitive-inhibitory load from 1-back to 2-back Go/NoGo during walking was not associated with any detectable costs in response accuracy, response speed, or gait consistency; however, it came with attenuations in walking-related EEG amplitude changes during both successful inhibitions (correct rejections) and successful executions (hits) of the ‘Go’ motor response. During correct rejections, such attenuations were detected over frontal regions, during latencies related to sensory gain control, conflict monitoring and working memory storage and processing. During hits, attenuations were found over left-parietal regions, during latencies related to orienting attention to and selecting the ‘Go’ motor plan, as well as over central regions, during latencies linked to executing the ‘Go’ motor response. The pattern of attenuation in walking-related EEG amplitude changes, manifested by the 2-back Go/NoGo group, is thought to reflect more effortful recalibration of the above neural processes, a mechanism which might be a key driver of performance maintenance in the face of increased cognitive demands while walking. Overall, the present findings shed light on the extent of the neurocognitive capacity of young adults, thus revealing the employed methodology as promising for better understanding how factors such as aging or neurological disorders could impinge on this capacity.
Assembly archetypes in ecological communities
Authors: Flores-Arguedas Hugo , Antolin-Camarena Omar , Saavedra Serguei , Angulo Marco Tulio 
Published: June 2023

AbstractAn instrumental discovery in comparative and developmental biology is the existence of assembly archetypes that synthesize the vast diversity of organisms’ body plans—from legs and wings to human arms—into simple, interpretable, and general design principles. Here we combine a novel mathematical formalism based on Category Theory with experimental data to show that similar “assembly archetypes” exist at the larger organization scale of ecological communities when assembling a species pool across diverse environmental contexts, particularly when species interactions are highly structured. We applied our formalism to clinical data discovering two assembly archetypes that differentiate between healthy and unhealthy human gut microbiota. The concept of assembly archetypes and the methods to synthesize them can pave the way to discovering the general assembly principles of the ecological communities we observe in nature.
Recombinase-Independent AAV for Anterograde Transsynaptic Tracing
Authors: Faress Islam , Khalil Valentina , Yamamoto Haruka , Sajgo Szilard , Yonehara Keisuke , Nabavi Sadegh 
Published: June 2023

AbstractViral transsynaptic labeling has become indispensable for investigating the functional connectivity of neural circuits. Adeno-associated virus serotype 1 (AAV1) allows for anterograde transneuronal labeling and manipulation of postsynaptic neurons. However, it is limited to delivering an AAV1 expressing a recombinase which relies on using transgenic animals or genetic access to postsynaptic neurons. We reasoned that a strong expression level could overcome this limitation. To this end, we used a self-complementary AAV1 (scAAV1) under a strong promoter (CAG). We demonstrated the anterograde transneuronal efficiency of scAAV1 by delivering a fluorescent marker in mouse retina-superior colliculus and thalamic-amygdala pathways in a recombinase-independent manner. In addition to investigating neuronal connectivity, scAAV1.CAG may be suitable for functional manipulation and imaging.
Rat Deconvolution as Knowledge Miner for Immune Cell Trafficking from Toxicogenomics Databases
Authors: Morita Katsuhisa , Mizuno Tadahaya , Azuma Iori , Suzuki Yutaka , Kusuhara Hiroyuki 
Published: June 2023

ABSTRACTToxicogenomics databases are useful for understanding biological responses in individuals because they include a diverse spectrum of biological responses. Although these databases contain no information regarding immune cells in the liver, which are important in the progression of liver injury, deconvolution that estimates cell-type proportions from bulk transcriptome could extend immune information. However, deconvolution has been mainly applied to humans and mice and less often to rats, which are the main target of toxicogenomics databases. Here, we developed a deconvolution method for rats to retrieve information regarding immune cells from toxicogenomics databases. The rat-specific deconvolution showed high correlations for several types of immune cells between spleen and blood, and between liver treated with toxicants compared with those based on human and mouse data. Additionally, we found 4 clusters of compounds in Open TG-GATEs database based on estimated immune cell trafficking, which are different from those based on transcriptome data itself. The contributions of this work are three-fold. First, we obtained the gene expression profiles of 6 rat immune cells necessary for deconvolution. Second, we clarified the importance of species differences on deconvolution. Third, we retrieved immune cell trafficking from toxicogenomics databases. Accumulated and comparable immune cell profiles of massive data of immune cell trafficking in rats could deepen our understanding of enable us to clarify the relationship between the order and the contribution rate of immune cells, chemokines and cytokines, and pathologies. Ultimately, these findings will lead to the evaluation of organ responses in Adverse Outcome Pathway.
Direct quantification of unicellular algae sinking velocities reveals cell size, light, and nutrient-dependence
Authors: Miettinen Teemu P. , Gomez Annika L. , Wu Yanqi , Wu Weida , Usherwood Thomas R. , Hwang Yejin , Roller Benjamin R.K. , Polz Martin F. , Manalis Scott R. 
Published: June 2023

ABSTRACTEukaryotic phytoplankton, also known as algae, form the basis of marine food webs and drive marine carbon sequestration when their biomass sinks to the ocean floor. Algae must regulate their vertical movement, as determined by motility and gravitational sinking, to balance access to light at the surface and nutrients in deeper layers. However, the regulation of gravitational sinking velocities remains largely unknown, especially in motile species. Here, we directly quantify single-cell masses and volumes to calculate sinking velocities according to Stokes’ law in diverse clades of unicellular marine microalgae. Our results reveal the cell size, light, and nutrient-dependency of sinking velocities. We identify motile dinoflagellate and green algal species that increase their sinking velocity in response to starvation. Mechanistically, this increased cell sinking is achieved by photosynthesis-driven accumulation of carbohydrates, which increases cell mass and density. Moreover, cell sinking velocities correlate inversely with proliferation rates, and the mechanism regulating cell sinking velocities integrates signals from multiple nutrients. Our findings suggest that the regulation of cell composition according to environmental conditions contributes to the vertical movement of motile cells in the oceans. More broadly, our approach for sinking velocity measurements expands the study of gravitational sinking to motile cells and supports the modeling of marine carbon pump and nutrient cycles.
Study protocol for a cluster randomized controlled trial for 16 weeks to assess the effect of almond consumption on glycemic control and gut health in prediabetes adults in rural settings of India
Authors: Vaidya Ruchi , Chaudhury Nayanjeet , Kalra Pramila , Nair Sreekumaran , Prabhakar Bellur S. 
Published: June 2023

ABSTRACTIntroductionAlmonds have prebiotic potential to maintain gut health and regulate glycemia. Western studies have shown their positive effects in preventing non-communicable diseases like diabetes and CVDs. However, there is a lack of well-designed studies involving Asian Indians, who have a higher predisposition to diabetes due to their unique ‘Asian phenotype’. Therefore, this study aims to evaluate the impact of almond supplementation on glycemic control and gut health in prediabetic adults in rural India through a randomized clinical trial.Methods and AnalysisA parallel cluster randomized controlled trial with 178 prediabetic participants aged 20-50, both genders, with a BMI of 18.9-25 kg/m2, will be conducted in rural areas of Chikkaballapur, Kolar, and rural Bangalore districts in India. The intervention group will receive 56g of almonds as mid-morning snacks for 16 weeks, while the control group will receive cereal pulse based traditional isocaloric snacks under the closed supervision of the study investigators. Anthropometry, clinical, and biochemical parameters will be measured at 0, 8th, and 16th weeks, and a subgroup of 120 participants will undergo gut health analysis. GLP 1 analysis will be conducted on 30 participants at 0 and 16th week. Statistical analysis will be performed using SPSS for Windows V 27.0, and both ITT and per-protocol analyses will be conducted.Ethics and DisseminationEthics approval was obtained from the Institutional Ethics Committee at Ramaiah Medical College, Bangalore, Karnataka, India (DRPEFP7672021). Results from this trial will be disseminated through publication in peer-reviewed journals, national and international presentations.Trial Registration NumberThe trial is registered in the clinical trial registry of India (CTRI/2023/03/050421).ARTICLE SUMMARYStrengths and Limitations:-The study is the first field-based trial in rural settings to assess the effect of almond consumption versus traditional cereal pulse-based snacks on prediabetes adults’ glycemic control and gut health.-The compliance management is crucially designed by performing an intervention on one-to-one closed supervision, assessment of serum tocopherol levels, and regular follow up of any adverse events.-The upcoming metagenomic analysis and the gut metabolites like short chain fatty acids (SCFA) and GLP 1 will significantly advance our understanding of the impact of almonds on the gut health of prediabetes adults.-A potential limitation of the study is that it will not be feasible to follow the participants after the post intervention period.
A case study ofWhirly1(WHY1) evolution in the angiosperms: altered sequence, splicing, and expression in a clade of early-transitional mycoheterotrophic orchids
Authors: Muti Rachel M. , Barrett Craig F. , Sinn Brandon T. 
Published: June 2023

AbstractThe plastid-targeted transcription factorWhirly1(WHY1) has been implicated in chloroplast biogenesis, plastid genome stability, and fungal defense response, which together represent characteristics of interest for the study of autotrophic losses across the angiosperms. While gene loss in the plastid and nuclear genomes has been well studied in mycoheterotrophic plants, the evolution of the molecular mechanisms impacting genome stability are completely unknown. Here we characterize the evolution ofWHY1in four early-transitional mycoheterotrophic orchid species in the genusCorallorhizaby synthesizing the results of phylogenetic, transcriptomic, and comparative genomic analyses withWHY1genomic sequences sampled from 21 orders of angiosperms. We found an increased number of non-canonicalWHY1isoforms assembled from all but the greenestCorallorhizaspecies, including intron retention in some isoforms. WithinCorallorhiza, phylotranscriptomic analyses revealed the presence of tissue-specific differential expression ofWHY1in only the most photosynthetically capable species and a coincident increase in the number of non-canonicalWHY1isoforms assembled from fully mycoheterotrophic species. Gene- and codon-level tests ofWHY1selective regimes did not infer significant signal of either relaxed selection or episodic diversifying selection inCorallorhiza, but did so for relaxed selection in the late-stage full mycoheterotrophic orchidsEpipogium aphyllumandGastrodia elata. Taken together, this study provides the most comprehensive view ofWHY1evolution in angiosperms to date. Our analyses reveal that splicing alteration and decreased expression ofWHY1are coincident with deceased plastome stability in a group of early-transitional mycoheterotrophic orchids and that these changes may precede the selective shifts observed in late-stage mycoheterotrophic species.