bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular landscape of adrenocortical carcinoma at single-nuclei resolution
Authors: Tourigny David S. , Altieri Barbara , Secener Kerim A. , Sbiera Silviu , Schauer Marc P. , Arampatzi Panagiota , Herterich Sabine , Sauer Sascha , Fassnacht Martin , Ronchi Cristina L. 
Published: October 2023

AbstractAdrenocortical carcinoma (ACC) is a rare yet devastating tumour of the adrenal gland with a molecular pathology that remain incompletely understood. To gain novel insights into the cellular landscape of ACC, we generated single-nuclei RNA sequencing (snRNA-seq) data sets from twelve ACC tumour samples and analysed these alongside a previously published snRNA-seq data set from normal adrenal glands (NAGs). We find the ACC tumour microenvironment to be relatively devoid of immune cells compared to NAG tissues, consistent with known high tumour purity values for ACC as an immunologically “cold” tumour. Our analysis identifies three separate groups of ACC samples that are characterised by different relative compositions of adrenocortical cell types, including two populations (ACC 1 and ACC 2) that are specifically enriched in the most aggressive tumours and display hallmarks of the epithelial to mesenchymal transition (EMT) and dysregulated steroidogenesis, respectively. In addition to cell types associated with hypoxic and metabolic signatures (ACC 3 and ACC 4) prevalent among less-aggressive tumours, we also identified and validated a population of mitotically active adrenocortical cells (ACC M) strongly overexpressing genesPOLQandDIAPH3that possibly supports the expansion of malignant cell lineages. The smallest identified ACC specific cell type, ACC 5, displays characteristics of increased proliferation and growth factor signalling, and is therefore a potential progenitor-like or cell-of-origin candidate for the different lineages involved in adrenocortical carcinogenesis. Intriguingly, linage tracing suggests the fate adopted by malignant adrenocortical cells upon differentiation appears to be at least partly associated with the copy number or allelic balance state of the imprintedDLK1/MEG3genomic locus, which we verified by assessing DNA methylation status among samples from the three groups of tumours defined by their different cell type compositions. Our results therefore provide new insights into the cellular heterogeneity of ACC, indicating that genetic perturbations to a hierarchical cellular differentiation mechanism underlying healthy adrenocortical renewal and zonation may explain the molecular basis for disease pathogenesis.
Inter-Organellar Effects of Defective ER-localized Linolenic Acid Formation on Thylakoid Lipid Composition and Xanthophyll-Cycle Pigment De-epoxidation in the Arabidopsisfad3mutant
Authors: Matzner Monique , Launhardt Larissa , Barth Olaf , Humbeck Klaus , Goss Reimund , Heilmann Ingo 
Published: October 2023

AbstractMonogalactosyldiacylglycerol (MGDG) is the main lipid constituent of thylakoids and a structural component of photosystems and photosynthesis-related proteo-lipid complexes in green tissues. Previously reported changes in MGDG abundance upon stress-treatments are hypothesized to reflect mobilization of MGDG-based polyunsaturated lipid intermediates to maintain extraplastidial membrane integrity. While exchange of lipid intermediates between compartmental membranes is well documented, physiological consequences of mobilizing an essential thylakoid lipid, such as MGDG, for an alternative purpose are not well understood.Arabidopsis seedlings exposed to mild (50 mM) salt-treatment displayed significantly increased abundance of both MGDG and the extraplastidial lipid, phosphatidylcholine (PC). Interestingly, similar increases in MGDG and PC were observed in Arabidopsisfad3mutant seedlings defective in ER-localized linolenic acid formation, in which compensatory plastid-to-ER-directed mobilization of linolenic acid-containing intermediates takes place. The postulated (salt) or evident (fad3) plastid-ER-exchange of intermediates concurred with altered thylakoid function according to parameters of photosynthetic performance. While salt-treatment of wild type seedlings inhibited photosynthetic parameters in a dose-dependent manner, interestingly thefad3mutant did not show overall reduced photosynthetic quantum yield. By contrast, we observed a reduction specifically of non-photochemical quenching (NPQ) under high light, representing only part of observed salt effects. The decreased NPQ in thefad3mutant was accompanied by reduced activity of the xanthophyll cycle, leading to a reduced concentration of the NPQ-effective pigment zeaxanthin. The findings suggest that altered ER-located fatty acid unsaturation and ensuing inter-organellar compensation impacts on aspects of thylakoids related to the function of specific enzymes, rather than globally affecting thylakoid function.Subject Areas(2) Environmental and stress responses(7) Membrane and transport
Cell type-focused compound screen in human organoids reveals CK1 and MAPK11 inhibition protects cone photoreceptors from death
Authors: Spirig Stefan E. , Arteaga-Moreta Valeria J. , Raics Zoltan , Posada-Céspedes Susana , Chreng Stephanie , Galuba Olaf , Galuba Inga , Claerr Isabelle , Renner Steffen , Utz Larissa , Kleindienst P. Timo , Volak Adrienn , Imbach Jannick , Malysheva Svitlana , Siwicki Rebecca A. , Hahaut Vincent , Hou Yanyan , Picelli Simone , Cattaneo Marco , Jüttner Josephine , Cowan Cameron S. , Duckely Myriam , Baeschlin Daniel K. , Renner Magdalena , Unterreiner Vincent , Roska Botond 
Published: October 2023

SUMMARYHuman organoids that mirror their corresponding organs in cell-type diversity present an opportunity to perform large-scale screens for compounds that protect disease-affected or damage healthy cell types. However, such screens have not yet been performed. Here, we generated 20,000 human retinal organoids with GFP-labeled cone photoreceptors. Since degeneration of cones is a leading cause of blindness, we induced cone death and screened 2,707 compounds with known targets, for those that saved cones or those that further damaged cones. We identified inhibitors of CK1 or MAPK11 that protected cones, HSP90 inhibitors that saved cones in the short term but damaged them in the longer term, and broad HDAC inhibition by many compounds that significantly damaged cones. This work provides a database for cone-damaging compounds and describes compounds that can be starting points to develop neuroprotection for cones in diseases such as macular degeneration.
ASCT2 is the primary serine transporter in cancer cells
Authors: Conger Kelly O. , Chidley Christopher , Ozgurses Mete Emir , Zhao Huiping , Kim Yumi , Semina Svetlana E. , Burns Philippa , Rawat Vipin , Sheldon Ryan , Ben-Sahra Issam , Frasor Jonna , Sorger Peter K. , DeNicola Gina M. , Coloff Jonathan L. 
Published: October 2023

SUMMARYThe non-essential amino acid serine is a critical nutrient for cancer cells due to its diverse biosynthetic functions. While some tumors can synthesize serinede novo, others are auxotrophic for serine and therefore reliant on the uptake of exogenous serine. Importantly, however, the transporter(s) that mediate serine uptake in cancer cells are not known. Here, we characterize the amino acid transporter ASCT2 (coded for by the geneSLC1A5) as the primary serine transporter in cancer cells. ASCT2 is well-known as a glutamine transporter in cancer, and our work demonstrates that serine and glutamine compete for uptake through ASCT2. We further show that ASCT2-mediated serine uptake is essential for purine nucleotide biosynthesis and that ERα promotes serine uptake by directly activatingSLC1A5transcription. Together, our work defines an additional important role for ASCT2 as a serine transporter in cancer and evaluates ASCT2 as a potential therapeutic target in serine metabolism.
A maternal-effectPadi6variant results in abnormal nuclear localization of DNMT1 and failure of epigenetic reprogramming and zygotic genome activation in mouse embryos
Authors: Giaccari Carlo , Cecere Francesco , Argenziano Lucia , Galvao Antonio , Acampora Dario , Rossi Gianna , Mele Bruno Hay , Cubellis Maria Vittoria , Cerrato Flavia , Andrews Simon , Cecconi Sandra , Kelsey Gavin , Riccio Andrea 
Published: October 2023

AbstractPADI6 belongs to the multi-protein sub-cortical maternal complex (SCMC) that is present specifically in mammalian oocytes and early embryos. Maternal inactivation of SCMC genes generally results in early embryo lethality. In humans, variants in a subset of SCMC genes have been found in the healthy mothers of children affected by genomic imprinting disorders and characterized by multi-locus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly defined. To address this issue, we generated a mouse line carrying aPadi6missense variant that had been identified in the mother of two sisters affected by Beckwith-Wiedemann syndrome and MLID. We found that if homozygous in female mice this variant resulted in interruption of embryo development at the 2-cell stage. Single-cell DNA methylation and RNA analyses demonstrated genomic hypermethylation, down-regulation of zygotic genome activation (ZGA) genes and up-regulation of maternal decay genes in 2-cell embryos from homozygous females. In addition, immunofluorescence analysis showed abnormal localization of DNMT1 and UHRF1 in mutant oocytes and zygotes. Taken together, this study demonstrates that PADI6 controls the subcellular localization of DNMT1 that is necessary for pre-implantation epigenetic reprogramming and ZGA.
Breeding and identification of promising Mauritius x Kew pineapple hybrids with high heterosis for fruit and plant traits
Authors: Dhurve Lalit , Kumar K. Ajith , Bhaskar Jyothi , Sobhana A. , Francies Rose Mary , Mathew Deepu 
Published: October 2023

AbstractLeading cultivars of pineapple Mauritius and Kew were hybridized and 25 hybrids were evaluated under open field conditions, using randomized block design with two replications. Performance of the female parent cum check variety Mauritius, male parent Kew and check variety in Kerala state, India, Amritha, were also evaluated and compared. Based on the performance, heterobeltiosis, average heterosis and standard heterosis over two check varieties, in each hybrid, for 10 plant growth traits and 24 fruit traits, were calculated. For fruit weight, hybrid H35 had the highest heterobeltiosis and standard heterosis over Amritha whereas H62 had highest standard heterosis over Mauritius and average heterosis. For pulp weight, hybrid H17 had the highest values for all heterosis parameters. For TSS, hybrid H62 had the highest heterobeltiosis and other parameters were highest in H43. For days to attain physiological maturity, crown weight, peel weight and acidity, H27, H30, H77 and H43, respectively were lowest in all heterosis parameters. Based on the selection criterion [∑average heterosis (fruit weight, TSS, pulp weight) – ∑average heterosis (crown weight, peel weight, eye profile, eye relative surface, time taken for physiological maturity, acidity)] developed using the average heterosis values for desirable and undesirable fruit traits, six hybrids H66, H17, H59, H43, H70 and H35 were identified for further evaluation. The identified hybrids also satisfied the requirements in fruit weight (≥1.0 kg), pulp weight (≥750.58 g), TSS (≥14.49○Brix), days to attain physiological maturity (≤185.70 days), crown weight (≤305.50 g), peel weight (≤159.27 g) and acidity (≤1.05).
Hippocampal mechanisms resolve competition in memory and perception
Authors: Favila Serra E. , Aly Mariam 
Published: October 2023

AbstractBehaving adaptively requires selection of relevant memories and sensations and suppression of competing ones. We hypothesized that these mechanisms are linked, such that hippocampal computations that resolve competition in memory also shape the precision of sensory representations to guide selective attention. We leveraged fMRI-based pattern similarity, receptive field modeling, and eye tracking to test this hypothesis in humans performing a memory-dependent visual search task. In the hippocampus, differentiation of competing memories predicted the precision of memory-guided eye movements. In visual cortex, preparatory coding of remembered target locations predicted search successes, whereas preparatory coding of competing locations predicted search failures due to interference. These effects were linked: stronger hippocampal memory differentiation was associated with lower competitor activation in visual cortex, yielding more precise preparatory representations. These results demonstrate a role for memory differentiation in shaping the precision of sensory representations, highlighting links between mechanisms that overcome competition in memory and perception.
De novoassembling a high-quality genome sequence of Amur grape (Vitis amurensisRupr.) gives insight intoVitisdivergence and sex determination
Authors: Wang Pengfei , Meng Fanbo , Yang Yiming , Mu Qian , Ding Tingting , Liu Huiping , Wang Fengxia , Li Ao , Zhang Qingtian , Fan Shutian , Li Bo , Ma Zhiyao , Zhang Tianhao , Zhou Yongfeng , Zhao Hongjun , Wang Xiyin 
Published: October 2023

AbstractTo date, there is no high-quality sequence for genomes of the East Asian grape species, hindering biological and breeding research efforts to improve grape cultivars. This study presents a ∼522 Mb of theVitis amurensis(Va) genome sequence containing 27,635 coding genes. Phylogenetic analysis indicated thatV. riparia(Vr) may firstly split from the other two species,Va,V. Vinifera(Vv; Pinot Noir: PN40024 and Cabernet Sauvignon). Much divergent gene reservation among three grape duplicated gene sets suggests that the core eudicot common hexaploidy (ECH), 130 million years ago (Mya), has still played a non-negligible role in grape species divergence and biological innovation. Prominent accumulation of sequence variants might have improved cold resistance inVa, resulting in a more robust cold resistance gene regulatory network than those inVvandVr. In contrast,Vapreserved much fewer NBS disease resistance genes than the other grapes. Notably, multi-omics analysis identified one trans-cinnamate 4-monooxygenase gene positively correlated to the resveratrol accumulated duringVaberry development. A selective sweep analysis revealed a hypotheticalVasex-determination region (SDR). Besides, a PPR-containing protein-coding gene in the hypothetical SDR may be related with sex determination inVa. The content and arrangement order of genes in the putative SDR of femaleVawere similar to the SDR of femaleVv. However, the putative SDR of femaleValost one Flavin-containing monooxygenases (FMO) and contained one extra uncharacterized protein-coding gene. These findings will improve the understanding ofVitisbiology and contribute to the improvement of grape breeding.
A K-mer based Bulked Segregant Analysis approach to map seed traits in unphased heterozygous potato genomes
Authors: Sonsungsan Pajaree , Nganga Mwaura Livingstone , Lieberman Meric , Amundson Kirk , Stewart Victoria , Plaimas Kitiporn , Comai Luca , Henry Isabelle 
Published: October 2023

AbstractHigh-throughput sequencing-based methods for bulked segregant analysis (BSA) allow for the rapid identification of genetic markers associated with traits of interest. BSA studies have successfully identified qualitative (binary) and quantitative trait loci using QTL mapping. However, most traditional QTL mapping approaches require a reference genome. Here, we combine high throughput short read sequencing with bulk segregant analysis of k-mers (BSA-k-mer). This method can be applied to any organism and is particularly useful for species with genomes too different from the closest sequenced genome. It is also instrumental when dealing with highly heterozygous and polyploid genomes without phased haplotype assemblies and for which a single haplotype can control a trait. Finally, it is flexible in terms of population structure. Here, we present the application of the BSA-k-mer method for the rapid identification of candidate regions related to seed spot and seed size in diploid potato. While conventional QTL mapping of parental genotypes did not generate any signal, candidate loci were identified for each trait using the BSA-k-mer approach. The seed spot loci match with previously identified loci associated with pigmentation in potato. The loci associated with seed size are novel. Both sets of loci are potentially instrumental in future breeding towards true seeds in potato.Article SummaryIdentifying genes linked to agronomic traits in potatoes is challenging because potato genomes are complex and variable. We are investigating the genetic basis of seed size and color. Seeds were categorized as large or small, or spotted or not, based on simple visual observation. Next, DNA sequences from each individual were mined for association between random short sequences (k-mers) and those two traits. This more flexible method allowed us to identify regions of the potato genome associated with both traits.
Value-Based Integrated Care: A Systematic Literature Review
Authors: van Hoorn Evelien S. , Ye Lizhen , van Leeuwen Nikki , Raat Hein , Lingsma Hester F. 
Published: October 2023

AbstractBackgroundHealthcare services worldwide are transforming themselves into value-based organizations. Integrated care is an important aspect of value-based healthcare (VBHC), but practical evidence-based recommendations for the successful implementation of integrated care within a VBHC context are lacking. This systematic review aims to identify how value-based integrated care (VBIC) is defined in literature, and to summarize the literature regarding the effects of VBIC, and the facilitators and barriers for its implementation.MethodsEmbase, Medline ALL, Web of Science Core Collection and Cochrane Central Register of Controlled Trails databases were searched from inception until January 2022. Empirical studies that implemented and evaluated an integrated care intervention within a VBHC context were included. Non-empirical studies were included if they described either a definition of VBIC or facilitators and barriers for its implementation. The Rainbow Model of Integrated Care (RMIC) was used to analyse the VBIC interventions. The quality of the articles was assessed using the Mixed Methods Appraisal Tool.ResultsAfter screening 1328 titles/abstract and 485 full-text articles, 24 articles were included. No articles were excluded based on quality. One article provided a definition of VBIC. Eleven studies reported -mostly positive-effects of VBIC, on clinical outcomes, patient-reported outcomes, and healthcare utilization. Nineteen studies reported facilitators and barriers for the implementation of VBIC; factors related to reimbursement and IT infrastructure were reported most frequently.ConclusionThe concept of VBIC is not well defined. The effect of VBIC seems promising, but the exact interpretation of effect evaluations is challenged by the precedence of multicomponent interventions, multiple testing and generalizability issues. For successful implementation of VBIC, it is imperative that healthcare organizations consider investing in adequate IT infrastructure and new reimbursement models.
Scaling COVID-19 rates with population size in the United States
Authors: Cruz Austin R. , Enquist Brian J. , Burger Joseph R. 
Published: October 2023

AbstractWe assessed Urban Scaling Theory using time-series data by quantifying allometric scaling relationships of coronavirus disease (COVID-19) cases, deaths, and demographic cohorts within and across three major variant waves of the pandemic (first, delta, omicron). Results indicate that with county-level population size in the United States, the burden of cases disproportionately impacted larger-sized counties. In contrast, the burden of deaths disproportionately impacted smaller counties, which may be partially due to a higher proportion of older adults who live in smaller counties. Future infectious disease burden across populations might be attenuated by applying Urban Scaling Theory to epidemiological efforts through identifying disease allometry and concomitant allocation of medical interventions.
Studying the context of psychoses to improve outcomes in Ethiopia (SCOPE): protocol paper
Authors: Hanlon Charlotte , Roberts Tessa , Misganaw Eleni , Malla Ashok , Cohen Alex , Shibre Teshome , Fekadu Wubalem , Teferra Solomon , Kebede Derege , Mulushoa Adiyam , Girma Zerihun , Tsehay Mekonnen , Kiross Dessalegn , Lund Crick , Fekadu Abebaw , Morgan Craig , Alem Atalay 
Published: October 2023

AbstractBackgroundGlobal evidence on psychosis is dominated by studies conducted in Western, high-income countries. The objectives of the Study of Context Of Psychoses to improve outcomes in Ethiopia (SCOPE) are (1) to generate rigorous evidence of psychosis experience, epidemiology and impacts in Ethiopia that will illuminate aetiological understanding and (2) inform development and testing of interventions for earlier identification and improved first contact care that are scalable, inclusive of difficult-to-reach populations and optimise recovery.MethodsThe setting is sub-cities of Addis Ababa and rural districts in south-central Ethiopia covering 1.1 million people and including rural, urban and homeless populations. SCOPE comprises (i) formative work to understand care pathways and community resources (resource mapping); examine family context and communication (ethnography); develop valid measures of family communication and personal recovery; and establish platforms for community engagement and involvement of people with lived experience; (ii) a population-based incidence study, case-control study and cohort study with 12 months follow-up involving 440 people with psychosis (390 rural/Addis Ababa; 50 who are homeless), 390 relatives and 390 controls. We will test hypotheses about incidence rates in rural vs. urban populations and men vs. women; potential aetiological role of khat (a commonly chewed plant with amphetamine-like properties) and traumatic exposures in psychosis; determine profiles of needs at first contact and predictors of outcome; (iii) participatory workshops to develop programme theory and inform co-development of interventions, (iv) evaluation of the impact of early identification strategies on engagement with care (interrupted time series study); (v) a feasibility cluster randomised controlled trial of interventions for people with recent-onset psychosis in rural settings (10-12 clusters; n=80 participants) with 6 months follow-up to inform a future large-scale trial and investigate implementation processes and outcomes, and (vi) two uncontrolled pilot studies to test acceptability, feasibility of co-developed interventions in urban and homeless populations.