bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emerging models and trends in mental health crisis care in England: a national investigation of crisis care systems
Authors: Dalton-Locke Christian , Johnson Sonia , Harju-Seppänen Jasmine , Lyons Natasha , Rains Luke Sheridan , Stuart Ruth , Campbell Amelia , Clark Jeremy , Clifford Aisling , Courtney Laura , Dare Ceri , Kathleen Kelly , Lynch Chris , McCrone Paul , Nairi Shilpa , Newbigging Karen , Nyikavaranda Patrick , Osborn David , Persaud Karen , Stefan Martin , Lloyd-Evans Brynmor 
Published: July 2021

AbstractBackgroundInpatient psychiatric care is unpopular and expensive, and development and evaluation of alternatives is a long-standing policy and research priority around the world. In England, the three main models documented over the past fifty years (teams offering crisis assessment and treatment at home; acute day services; and residential crisis services in the community) have recently been augmented by several new service models. These are intended to enhance choice and flexibility within catchment area acute care systems, but remain largely undocumented in the research literature. We therefore aimed to describe the types and distribution of crisis care models across England through a national survey.MethodsWe carried out comprehensive mapping of crisis resolution teams (CRTs) using previous surveys, websites and multiple official data sources. Managers of CRTs were invited to participate as key informants who were familiar with the provision and organisation of crisis care services within their catchment area. The survey could be completed online or via telephone interview with a researcher, and elicited details about types of crisis care delivered in the local catchment area.ResultsWe mapped a total of 200 adult CRTs and completed the survey with 184 (92%). Of the 200 mapped adult CRTs, there was a local (i.e., within the adult CRT catchment area) children and young persons CRT for 84 (42%), and an older adults CRT for 73 (37%). While all but one health region in England provided CRTs for working age adults, there was high variability regarding provision of all other community crisis service models and system configurations. Crisis cafes, street triage teams and separate crisis assessment services have all proliferated since a similar survey in 2016, while provision of acute day units has reduced.ConclusionsThe composition of catchment area crisis systems varies greatly across England and popularity of models seems unrelated to strength of evidence. A group of emerging crisis care models with varying functions within service systems are increasingly prevalent: they have potential to offer greater choice and flexibility in managing crises, but an evidence base regarding impact on service user experiences and outcomes is yet to be established.
Highly versatile antibody binding assay for the detection of SARS-CoV-2 infection
Authors: Datta Pratik , Ukey Rahul , Bruiners Natalie , Honnen William , Carayannopoulos Mary O. , Reichman Charles , Choudhary Alok , Onyuka Alberta , Handler Deborah , Guerrini Valentina , Mishra Pankaj K. , Dewald Hannah K. , Lardizabal Alfred , Lederer Leeba , Leiser Aliza L. , Hussain Sabiha , Jagpal Sugeet K. , Radbel Jared , Bhowmick Tanaya , Horton Daniel B. , Barrett Emily S. , Xie Yingda L. , Fitzgerald-Bocarsly Patricia , Weiss Stanley H. , Woortman Melissa , Parmar Heta , Roy Jason , Dominguez-Bello Maria Gloria , Blaser Martin J. , Carson Jeffrey L. , Panettieri Reynold A. , Libutti Steven K. , Raymond Henry F. , Pinter Abraham , Gennaro Maria Laura 
Published: July 2021

AbstractMonitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and COVID-19 vaccination.We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.
Dual effects of presynaptic membrane mimetics on α-synuclein amyloid aggregation
Authors: Lin Yuxi , Ito Dai , Yoo Je Min , Lim Mi Hee , Yu Woo Kyung , Kawata Yasushi , Lee Young-Ho 
Published: July 2021

AbstractAggregation of intrinsically disordered α-synuclein (αSN) under various conditions is closely related to synucleinopathies. Although various biological membranes have shown to alter the structure and aggregation propensity of αSN, a thorough understanding of the molecular and mechanical mechanism of amyloidogenesis in membranes remains unanswered. Herein, we examined the structural changes, binding properties, and amyloidogenicity of three variations of αSN mutants under two types of liposomes, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and presynaptic vesicle mimetic (Mimic) membranes. While neutrally charged DOPC membranes elicited marginal changes in the structure and amyloid fibrillation of αSNs, negatively charged Mimic membranes induced dramatic helical folding and biphasic amyloid generation. At low concentration of Mimic membranes, the amyloid fibrillation of αSNs was promoted in a dose-dependent manner. However, further increases in the concentration constrained the fibrillation process. These results suggest the dual effect of Mimic membranes on regulating the amyloidogenesis of αSN, which is rationalized by the amyloidogenic structure of αSN and condensation-dilution of local αSN concentration. Finally, we propose physicochemical properties of αSN and membrane surfaces, and their propensity to drive electrostatic interactions as decisive factors of amyloidogenesis.
Engineering sorghum for higher 4-hydroxybenzoic acid content
Authors: Lin Chien-Yuan , Tian Yang , Nelson-Vasilchik Kimberly , Hague Joel , Kakumanu Ramu , Lee Mi Yeon , Trinh Jessica , Northen Trent R. , Baidoo Edward E. K. , Kausch Albert P. , Scheller Henrik V. , Eudes Aymerick 
Published: July 2021

AbstractLignocellulosic biomass represents a renewable source of sugars for the manufacturing of bioproducts such as biofuels. The high cost associated with deconstruction of plant biomass to simple sugars remains one of the challenges preventing the deployment of economically sustainable advanced bioproducts. The accumulationin-plantaof value-added coproducts such as platform chemicals can improve the economics of biofuels. Among other crops, sorghum is an ideal bioenergy feedstock due to its low input requirements, efficient nitrogen recycling, and high water use efficiency and biomass yields. In this work, we engineered sorghum to overproduce the valuable chemical 4-hydroxybenzoic acid (4-HBA) by co-expressing plastid-targeted versions ofEscherichia colichorismate pyruvate-lyase (UbiC) and feedback-resistant 3-deoxy-D-arabino-heptulonate-7-phosphate synthase (AroG*). Two independent lines containing the dualaroG*-ubiCconstruct were selected for characterization in the T2 generation. Using liquid chromatography-mass spectrometry, analysis of methanolic extracts obtained from biomass samples revealed an accumulation of 4-HBA in the two transgenic lines (corresponding to 1.56% and 1.72% dry weight, respectively), with 4-HBA glucose conjugates representing major forms. Measurements of biomass composition and several agronomic traits showed no significant difference between transgenic and wild-type control plants grown under controlled environment. This work demonstrates the transferability of theubiCengineering approach to sorghum; generated lines will be useful to assess the agronomic performance of modified 4-HBA-rich sorghum under natural conditions.
Gene-Specific Nonsense-Mediated mRNA Decay Targeting for Cystic Fibrosis Therapy
Authors: Kim Young Jin , Nomakuchi Tomoki , Papaleonidopoulou Foteini , Krainer Adrian R. 
Published: July 2021

AbstractLow CFTR mRNA expression due to nonsense-mediated mRNA decay (NMD) is a major hurdle in developing a therapy for cystic fibrosis (CF) caused by the W1282X mutation in the CFTR gene. CFTR-W1282X truncated protein retains partial function, so increasing its levels by inhibiting NMD of its mRNA will likely be beneficial. Because NMD regulates the normal expression of many genes, gene-specific stabilization of CFTR-W1282X mRNA expression is more desirable than general NMD inhibition. Synthetic antisense oligonucleotides (ASOs) designed to prevent binding of exon junction complexes (EJC) downstream of premature termination codons (PTCs) attenuate NMD in a gene-specific manner. We developed a cocktail of three ASOs that specifically increases the expression of CFTR W1282X mRNA and CFTR protein in ASO-transfected human bronchial epithelial cells. This treatment increased the CFTR-mediated chloride current. These results set the stage for clinical development of an allele-specific therapy for CF caused by the W1282X mutation.
Prolactin and prolactin receptor expression in the HPG axis and crop during parental care in both sexes of a biparental bird (Columba livia)
Authors: Farrar Victoria S. , Harris Rayna M. , Austin Suzanne H. , Nava Ultreras Brandon M. , Booth April M. , Angelier Frédéric , Lang Andrew S. , Feustel Tanner , Lee Candice , Bond Annie , MacManes Matthew D. , Calisi Rebecca M. 
Published: July 2021

AbstractDuring breeding, multiple circulating hormones, including prolactin, facilitate reproductive transitions in species that exhibit parental care. Prolactin underlies parental behaviors and related physiological changes across many vertebrates, including birds and mammals. While circulating prolactin levels often fluctuate across breeding, less is known about how relevant target tissues vary in their prolactin responsiveness via prolactin receptor (PRLR) expression. Recent studies have also investigated prolactin (PRL) gene expression outside of the pituitary (i.e., extra-pituitaryPRL), but howPRLgene expression varies during parental care in non-pituitary tissue (e.g., hypothalamus, gonads) remains largely unknown. Further, it is unclear if and how tissue-specificPRLandPRLRvary between the sexes during biparental care. To address this, we measuredPRLandPRLRgene expression in tissues relevant to parental care, the endocrine reproductive hypothalamic-pituitary-gonadal (HPG) axis and the crop (a tissue with a similar function as the mammalian mammary gland), across various reproductive stages in both sexes of a biparental bird, the rock dove (Columba livia). We also assessed how these genes responded to changes in offspring presence by adding chicks mid-incubation, simulating an early hatch when prolactin levels were still moderately low. We found that pituitaryPRLexpression showed similar increases as plasma prolactin levels, and detected extra-pituitaryPRLin the hypothalamus, gonads and crop. Hypothalamic and gonadalPRLRexpression also changed as birds began incubation. CropPRLRexpression correlated with plasma prolactin, peaking when chicks hatched. In response to replacing eggs with a novel chick mid-incubation, hypothalamic and gonadalPRLandPRLRgene expression differed significantly compared to mid-incubation controls, even when plasma prolactin levels did not differ. We also found sex differences inPRLandPRLRthat suggest gene expression may allow males to compensate for lower levels in prolactin by upregulatingPRLRin all tissues. Overall, this study advances our understanding of how tissue-specific changes in responsiveness to parental hormones may differ across key reproductive transitions, in response to offspring cues, and between the sexes.
Dicamba drift alters plant-herbivore interactions at the agro-ecological interface
Authors: Johnson Nia M , Baucom Regina S 
Published: July 2021

AbstractNatural populations evolve in response to biotic and abiotic changes in their environment, which shape species interactions and ecosystem dynamics. Agricultural systems can introduce novel conditions via herbicide exposure to non-crop habitats in surrounding fields. While herbicide drift is known to produce a variety of toxic effects in plants, little is known about its impact on non-target wildlife species interactions. In a two-year study, we investigated the impact of herbicide drift on plant-herbivore interactions with common weed velvetleaf (Abutlion theophrasti) as the focal species. The findings reveal a significant increase in the phloem feeding silverleaf whitefly (Bermisia tabaci) abundance on plants exposed to herbicide at drift rates of 0.5% and 1% of the field dose. We also identified a significant phenotypic tradeoff between whitefly resistance and herbicide resistance in addition to whitefly resistance and relative growth rate in the presence of dicamba drift after increasing the populations grown in year two. In a follow-up greenhouse study, we found evidence that dicamba drift at 0.5% of the field dose significantly increased average chlorophyll content (mg/cm2) along with a positive correlation between whitefly abundance and chlorophyll content. Overall, these findings suggest herbicide exposure to non-target communities can significantly alter herbivore populations, potentially impacting biodiversity and community dynamics of weed populations found at the agro-ecological interface.
Infinite re-reading of single proteins at single-amino-acid resolution using nanopore sequencing
Authors: Brinkerhoff Henry , Kang Albert S. W. , Liu Jingqian , Aksimentiev Aleksei , Dekker Cees 
Published: July 2021

AbstractAs identifying proteins is of paramount importance for cell biology and applications, it is of interest to develop a protein sequencer with the ultimate sensitivity of decoding individual proteins. Here, we demonstrate a nanopore-based single-molecule sequencing approach capable of reliably detecting single amino-acid substitutions within individual peptides. A peptide is linked to a DNA molecule that is pulled through the biological nanopore MspA by a DNA helicase in single amino-acid steps. The peptide sequence yields clear stepping ion current signals which allows to discriminate single-amino-acid substitutions in single reads. Molecular dynamics simulations show these signals to result from size exclusion and pore binding. Notably, we demonstrate the capability to ‘rewind’ peptide reads, obtaining indefinitely many independent reads of the same individual molecule, yielding virtually 100% read accuracy in variant identification, with an error rate less than 10−6. These proof-of-concept experiments constitute a promising basis for developing a single-molecule protein sequencer.One-sentence summaryThis paper presents proof-of-concept experiments and simulations of a nanopore-based approach to sequencing individual proteins.
Temporal Analyses of Postnatal Liver Development and Maturation by Single Cell Transcriptomics
Authors: Liang Yan , Kaneko Kota , Xin Bing , Lee Jin , Sun Xin , Zhang Kun , Feng Gen-Sheng 
Published: July 2021

SUMMARYLiver is the major metabolic organ, although its postnatal development and maturation are inadequately understood. We analyzed 52,834 single cell transcriptomes and identified 31 cell types or states in mouse livers at postnatal day 1, 3, 7, 21 and 56. We observed unexpectedly high levels of hepatocyte heterogeneity in the developing liver and progressive construction of the zonated metabolic functions from pericentral to periportal hepatocytes, which was orchestrated with development of sinusoid endothelial, stellate and Kupffer cells. Trajectory and gene regulatory analyses captured 36 transcription factors, including a circadian regulator Bhlhe40, in programming liver development. Remarkably, we identified a special group of macrophages enriched at day 7 with a hybrid phenotype of macrophages and endothelial cells, which may regulate sinusoidal construction and Treg cell function. This study provides a comprehensive atlas that covers all hepatic cell types instrumental for further dissection of liver development, metabolic functions and diseases.In BriefSingle cell transcriptomics of all hepatic cell types in neonatal and adult liversConcerted development of zonated metabolic functions in hepatocytes and NPCsTransient emergence of a distinct group of macrophages at postnatal day 7Hepatic cell-cell communications that program postnatal liver development
Cellular resolution anatomical and molecular atlases for prenatal human brains
Authors: Ding Song-Lin , Royall Joshua J. , Lesnar Phil , Facer Benjamin A.C. , Smith Kimberly A. , Wei Yina , Brouner Kristina , Dalley Rachel A. , Dee Nick , Dolbeare Tim A. , Ebbert Amanda , Glass Ian A. , Glattfelter Katie , Keller Nika H. , Lee Felix , Lemon Tracy A. , Nyhus Julie , Pendergraft Julie , Reid Robert , Sarreal Melaine , Shapovalova Nadiya V. , Szafer Aaron , Phillips John W. , Sunkin Susan M. , Hohmann John G. , Jones Allan R. , Hawrylycz Michael J. , Hof Patrick R. , Ng Lydia , Bernard Amy , Lein Ed S. 
Published: July 2021

ABSTRACTIncreasing interest in studies of prenatal human brain development, particularly using new single-cell genomics and anatomical technologies to create cell atlases, creates a strong need for accurate and detailed anatomical reference atlases. In this study, we present two cellular-resolution digital anatomical atlases for prenatal human brain at post-conceptional weeks (PCW) 15 and 21. Both atlases were annotated on sequential Nissl-stained sections covering brain-wide structures on the basis of combined analysis of cytoarchitecture, acetylcholinesterase staining and an extensive marker gene expression dataset. This high information content dataset allowed reliable and accurate demarcation of developing cortical and subcortical structures and their subdivisions. Furthermore, using the anatomical atlases as a guide, spatial expression of 37 and 5 genes from the brains respectively at PCW 15 and 21 was annotated, illustrating reliable marker genes for many developing brain structures. Finally, the present study uncovered several novel developmental features, such as the lack of an outer subventricular zone in the hippocampal formation and entorhinal cortex, and the apparent extension of both cortical (excitatory) and subcortical (inhibitory) progenitors into the prenatal olfactory bulb. These comprehensive atlases provide useful tools for visualization, targeting, imaging and interpretation of brain structures of prenatal human brain, and for guiding and interpreting the next generation of cell census and connectome studies.
Biological action at a distance: Correlated pattern formation in adjacent tessellation domains without communication
Authors: Brooke John M. , James Sebastian S. , Jimenez-Rodriguez Alejandro , Wilson Stuart P. 
Published: July 2021

AbstractTessellations emerge in many natural systems, and the constituent domains often contain regular patterns, raising the intriguing possibility that pattern formation within adjacent domains might be correlated by the geometry, without the direct exchange of information between parts comprising either domain. We confirm this paradoxical effect, by simulating pattern formation via reaction-diffusion in domains whose boundary shapes tessellate, and showing that correlations between adjacent patterns are strong compared to controls that self-organise in domains with equivalent sizes but unrelated shapes. The effect holds in systems with linear and non-linear diffusive terms, and for boundary shapes derived from regular and irregular tessellations. Based on the prediction that correlations between adjacent patterns should be bimodally distributed, we develop methods for testing whether a given set of domain boundaries constrained pattern formation within those domains. We then confirm such a prediction by analysing the development of ‘subbarrel’ patterns, which are thought to emerge via reaction-diffusion, and whose enclosing borders form a Voronoi tessellation on the surface of the rodent somatosensory cortex. In more general terms, this result demonstrates how causal links can be established between the dynamical processes through which biological patterns emerge and the constraints that shape them.
Transcriptional regulation of neural stem cell expansion in adult hippocampus
Authors: Guo Nannan , McDermott Kelsey D. , Shih Yu-Tzu , Zanga Haley , Ghosh Debolina , Herber Charlotte , Coleman James , Zagouras Alexia , Meara William R. , Wong Lai Ping , Sadreyev Ruslan , Gonçalves J. Tiago , Sahay Amar 
Published: July 2021

AbstractExperience governs neurogenesis from radial-glial neural stem cells (RGLs) in the adult hippocampus to support memory. Transcription factors in RGLs integrate physiological signals to dictate self-renewal division mode. Whereas asymmetric RGL divisions drive neurogenesis during favorable conditions, symmetric divisions prevent premature neurogenesis while amplifying RGLs to anticipate future neurogenic demands. The identities of transcription factors regulating RGL symmetric self-renewal, unlike those that regulate RGL asymmetric self-renewal, are not known. Here, we show that the transcription factor Kruppel-like factor 9 (Klf9) is elevated in quiescent RGLs and inducible, deletion of Klf9 promotes RGL activation state. Clonal analysis and longitudinal intravital 2-photon imaging directly demonstrate that Klf9 functions as a brake on RGL symmetric self-renewal. In vivo translational profiling of RGLs lacking Klf9 generated a blueprint of RGL symmetric self-renewal for stem cell community. Together, these observations identify Klf9 as a transcriptional regulator of neural stem cell expansion in the adult hippocampus.