bluuebunny/crossref_metadata_2025_split huggingface dataset:
The revised reference genome of the leopard gecko (Eublepharis macularius) provides insight into the considerations of genome phasing and assembly
Authors: Pinto Brendan J. , Gamble Tony , Smith Chase H. , Keating Shannon E. , Havird Justin C. , Chiari Ylenia 
Published: January 2023

AbstractGenomic resources across squamate reptiles (lizards and snakes) have lagged behind other vertebrate systems and high-quality reference genomes remain scarce. Of the 23 chromosome-scale reference genomes across the order, only 12 of the ~60 squamate families are represented. Within geckos (infraorder Gekkota), a species-rich clade of lizards, chromosome-level genomes are exceptionally sparse representing only two of the seven extant families. Using the latest advances in genome sequencing and assembly methods, we generated one of the highest quality squamate genomes to date for the leopard gecko,Eublepharis macularius(Eublepharidae). We compared this assembly to the previous, short-read only,E. maculariusreference genome published in 2016 and examined potential factors within the assembly influencing contiguity of genome assemblies using PacBio HiFi data. Briefly, the read N50 of the PacBio HiFi reads generated for this study was equal to the contig N50 of the previousE. maculariusreference genome at 20.4 kilobases. The HiFi reads were assembled into a total of 132 contigs, which was further scaffolded using HiC data into 75 total sequences representing all 19 chromosomes. We identified that 9 of the 19 chromosomes were assembled as single contigs, while the other 10 chromosomes were each scaffolded together from two or more contigs. We qualitatively identified that percent repeat content within a chromosome broadly affects its assembly contiguity prior to scaffolding. This genome assembly signifies a new age for squamate genomics where high-quality reference genomes rivaling some of the best vertebrate genome assemblies can be generated for a fraction previous cost estimates. This newE. maculariusreference assembly is available on NCBI at JAOPLA010000000. The genome version and its associated annotations are also available via this Figshare repositoryhttps://doi.org/10.6084/m9.figshare.20069273.
StratoMod: Predicting sequencing and variant calling errors with interpretable machine learning
Authors: Dwarshuis Nathan , Tonner Peter , Olson Nathan D. , Sedlazeck Fritz J , Wagner Justin , Zook Justin M. 
Published: January 2023

AbstractDespite the variety in sequencing platforms, mappers, and variant callers, no single pipeline is optimal across the entire human genome. Therefore, developers, clinicians, and researchers need to make tradeoffs when designing pipelines for their application. Currently, assessing such tradeoffs relies on intuition about how a certain pipeline will perform in a given genomic context. We present Stratomod, which addresses this problem using an interpretable machine-learning classifier to predict variant calling errors in a data-driven manner. We showed Stratomod can precisely quantify the likelihood of missing variants using Hifi or Illumina, and leveraged Stratomod’s interpretability to measure contributions from difficult-to-map and homopolymer regions for each respective outcome. Furthermore, we used Statomod to assess the likelihood of missing variants due to mismapping using linear vs. graph-based references, and identified the hard-to-map regions where graph-based methods excelled and by how much. For these we utilized our new benchmark based on the Q100 HG002 assembly, which contains previously-inaccessible difficult regions. Furthermore, Stratomod presents a new method of finding likely false negatives, which is an improvement over current pipelines which only filter false positives. We anticipate this being useful for performing precise risk-reward analyses when designing variant calling pipelines.
Dopamine D2 receptors in nucleus accumbens cholinergic interneurons increase impulsive choice
Authors: Cavallaro Julianna , Yeisley Jenna , Akdoǧan Başak , Floeder Joseph , Balsam Peter D. , Gallo Eduardo F. 
Published: January 2023

ABSTRACTImpulsive choice, often characterized by excessive preference for small, short-term rewards over larger, long-term rewards, is a prominent feature of substance use and other neuropsychiatric disorders. The neural mechanisms underlying impulsive choice are not well understood, but growing evidence implicates nucleus accumbens (NAc) dopamine and its actions on dopamine D2 receptors (D2Rs). Because several NAc cell types and afferents express D2Rs, it has been difficult to determine the specific neural mechanisms linking NAc D2Rs to impulsive choice. Of these cell types, cholinergic interneurons (CINs) of the NAc, which express D2Rs, have emerged as key regulators of striatal output and local dopamine release. Despite these relevant functions, whether D2Rs expressed specifically in these neurons contribute to impulsive choice behavior is unknown. Here, we show that D2R upregulation in CINs of the mouse NAc increases impulsive choice as measured in a delay discounting task without affecting reward magnitude sensitivity or interval timing. Conversely, mice lacking D2Rs in CINs showed decreased delay discounting. Furthermore, CIN D2R manipulations did not affect probabilistic discounting, which measures a different form of impulsive choice. Together, these findings suggest that CIN D2Rs regulate impulsive decision-making involving delay costs, providing new insight into the mechanisms by which NAc dopamine influences impulsive behavior.
Incorporating fire-smartness into agricultural policies minimises suppression costs and ecosystem services damages from wildfires
Authors: Lecina-Diaz Judit , Chas-Amil María-Luisa , Aquilué Núria , Sil Ângelo , Brotons Lluís , Regos Adrián , Touza Julia 
Published: January 2023

AbstractGlobal climate warming is expected to increase wildfire hazard in many regions of the world. In southern Europe, land abandonment and an unbalanced investment toward fire suppression instead of prevention has gradually increased wildfire risk, which calls for a paradigm change in fire management policies. Here we combined scenario analysis, fire landscape modelling, and economic tools to identify which land-use policies would minimise the expected wildfire-related losses in a representative mountainous area of the northwestern Iberian Peninsula (the Transboundary Biosphere Reserve ‘Gerês-Xurés’, between Spain and Portugal). To do so, we applied the least-cost-plus-net-value-change approach and estimated net changes in wildfire damages based on their implications for the ecosystem services that affect financial returns to landowners in the study area (i.e. agriculture, pasture, and timber) and the wider economic benefits (i.e. recreation and climate regulation) for the 2010-2050 period. Four land-use scenarios were considered: (1) Business as Usual (BAU); (2) fire-smart, fostering more fire-resistant (less flammable) and/or fire-resilient landscapes (fire-smart); (3) High Nature Value farmlands (HNVf), wherein the abandonment of extensive agriculture is reversed; and (4) a combination of HNVf and fire-smart. We found the highest net value change (i.e. the difference between damages and avoided damages) in BAU for timber and pasture provision, and in fire-smart for recreation and climate regulation. HNVf was the best for suppression cost savings, but it generated the lowest expected present value for climate regulation. In fact, the best scenarios related to fire suppression are HNVf and HNVf combined with fire-smart, which also generate the lowest net value change plus net suppression costs in the entire study area (i.e. considering all ecosystem services damages and suppression costs). Therefore, reverting land abandonment through recultivation and promoting fire-resistant tree species is the most efficient way to reduce wildfire hazard. In this sense, payments for ecosystem services should reward farmers for their role in wildfire prevention. This study improves the understanding of the financial and societal benefits derived from reducing fire suppression spending and ecosystem services damage by undertaking fire-smart land-use strategies, which can be essential to enhance local stakeholders’ support for wildfire prevention policies.HighlightsLand-use changes impact wildfire ecosystem services (ES) damages and suppression costsPromoting agriculture generates significant suppression cost savingsAgriculture + fire-resistant forests is the best to reduce wildfire ES damagesLand-use policies should balance trade-offs between climate and wildfire regulationPayments for ES should reward farmers for their role in wildfire prevention
Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate
Authors: Oichi Takeshi , Kodama Joe , Wilson Kimberly , Tian Hongying , Imamura Yuka , Usami Yu , Oshima Yasushi , Saito Taku , Tanaka Sakae , Iwamoto Masahiro , Otsuru Satoru , Iwamoto-Enomoto Motomi 
Published: January 2023

AbstractLongitudinal bone growth relies on endochondral ossification in the cartilaginous growth plate where chondrocytes accumulate and synthesize the matrix scaffold that is replaced by bone. The chondroprogenitors in the resting zone maintain the continuous turnover of chondrocytes in the growth plate. Malnutrition is a leading cause of growth retardation in children; however, after recovery from nutrient deprivation, bone growth is accelerated beyond the normal rate, a phenomenon termed catch-up growth. Though nutritional status is a known regulator of long bone growth, it is largely unknown if and how chondroprogenitor cells respond to deviations in nutrient availability. Here, using fate-mapping analysis inAxin2CreERT2mice, we showed that dietary restriction increased the number of Axin2+ chondroprogenitors in the resting zone and simultaneously inhibited their differentiation. Once nutrient deficiency was resolved, the accumulated chondroprogenitor cells immediately restarted differentiation and formed chondrocyte columns, contributing to accelerated growth. Furthermore, we showed that nutrient deprivation reduced the level of phosphorylated Akt in the resting zone, and that exogenous IGF-1 canceled this reduction and stimulated differentiation of the pooled chondroprogenitors, decreasing their numbers. Our study ofAxin2CreERT2revealed that nutrient availability regulates the balance between accumulation and differentiation of chondroprogenitors in the growth plate, and further demonstrated that IGF-1 partially mediates this regulation by promoting the committed differentiation of the chondroprogenitor cells.
Characterizing Mineral Ellipsoids in New Bone Formation at the Interface of Ti6Al4V Porous Implants
Authors: Deering Joseph , Chen Jianyu , Mahmoud Dalia , Tang Tengteng , Lin Yujing , Fang Qiyin , Wohl Gregory R. , Elbestawi Mohamed , Grandfield Kathryn 
Published: January 2023

AbstractThe hierarchy of newly formed bone contains elements of disorder within an ordered multiscale structure, spanning from the macroscale to below the nanoscale. With mineralized structures presenting in the shape of ellipsoids in mature and mineralizing tissue, this work characterizes the heterogeneity in mineral ellipsoid packing at the interface of porous titanium implants. The characterization of mineral at the bone-implant interface offers insight into the osseointegration of titanium implants and the mechanical properties of the interfacial bone tissue. Using scanning transmission electron microscopy and plasma focused ion beam - scanning electron microscopy, mineral ellipsoids are characterized at the implant interface in both 2D and 3D. Heterogeneous in their size and shape within the newly formed bone tissue, ellipsoids are observed with alternating orientations corresponding to unique lamellar packets within 2-3 μm of the titanium implant interface – although this motif is not universal, and a mineral-dense zone can also appear at the implant interface. Short-order ellipsoid orientation shifts are also present in the 3D probe of the implant interface, where an approximate 90° misorientation angle between neighbouring packets of mineral ellipsoid resolves with increasing distance from the titanium, possibly providing a strengthening mechanism to prevent crack propagation in the peri-implant bone.Graphical Abstract
Sleep specific changes in infra-slow and respiratory frequency drivers of cortical EEG rhythms
Authors: Väyrynen Tommi , Helakari Heta , Korhonen Vesa , Tuunanen Johanna , Huotari Niko , Piispala Johanna , Kallio Mika , Raitamaa Lauri , Kananen Janne , Järvelä Matti , Palva J. Matias , Kiviniemi Vesa 
Published: January 2023

AbstractInfra-slow fluctuations (ISFs, 0.008-0.1 Hz) characterize hemodynamic and electric potential signals from the human brain. ISFs are known to correlate with the amplitude dynamics of fast (> 1 Hz) neuronal oscillations, and may arise from permeability fluctuations of the blood-brain barrier (BBB). Slow physiological pulsations such as respiration may also influence the amplitude dynamics of fast oscillations, but it remains uncertain if these processes track the fluctuations of fast cortical oscillations or act as their drivers. Moreover, possible effects of sleep and associated BBB permeability changes on such coupling are unknown. Here, we used non-invasive high-density full-band electroencephalography (EEG) in healthy human volunteers (N=21) to measure concurrently the ISFs, respiratory pulsations, and fast neuronal oscillations during periods of wakefulness and sleep, and to assess the strength and direction of their phase-amplitude coupling. The phases of ISFs and respiration were both coupled with the amplitude of fast neuronal oscillations, with stronger ISF coupling evident during sleep. Causality analysis robustly showed that the phase of ISF and respiration drove the amplitude dynamics of fast oscillations in sleeping and waking states. However, the net direction of modulation was stronger during the awake state, despite the stronger power and phase-amplitude coupling of slow signals during sleep. These findings show that the ISFs in slow cortical potentials and respiration together significantly determine the dynamics of fast cortical oscillations. We propose that these slow physiological phases are involved in coordinating cortical excitability, which is a fundamental aspect of brain function.Significance StatementPreviously disregarded EEG infra-slow fluctuations (0.008-0.1 Hz) and slow physiological pulsations such as respiration have been attracting increasing research interest, which shows that both of these signals correlate with fast (> 1 Hz) neuronal oscillations. However, little has been known about the mechanisms underlying these interactions; for example, the direction of causality in this interaction has not hitherto been studied. Therefore, we investigated full-band EEG in healthy volunteers during wakefulness and sleep to determine if ISF and respiration phases drive neuronal amplitudes. Results showed that ISF and respiration are phase-amplitude coupled, and predict neuronal EEG rhythms. Thus, we conclude that fast neuronal rhythms in human brain are modulated by slower non-neural phenomena.
Performing Roux-N Y Gastric Bypass on Rabbits: Perspective Report to Evaluate Body Weight Changes Food Consumption, And the Malabsorption of Vitamin D3
Authors: Al Meanazel Osaid , Alanazi Fars K. , Hailat Mohammad , Dayyih Wael Abu , Al-Shdefat Ramadan , Assab Mohammad Abu , Awad Riad , Al-Ani Israa , Shakeel Faiyaz , Alshora Doaa H. , Ibrahim Mohamed A. 
Published: January 2023

AbstractIn 1998, Dr. Scopinaro published the first-ever known bariatric surgery, followed by reports by Buchwald and Oien in 2003 and 2013 [1,2]. Bariatric surgery (BS) is the most effective therapy against obesity, and recently it was recommended for type 2 diabetes as a therapeutic plan [3]. BS includes; Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy, and laparoscopic adjustable gastric banding has gained the attention of most healthcare providers in elevation of the issue of obesity for its ease and fast results, especially with patients with mobility problems and those with high risk to develop chronic diseases [1,2]. Gastric bypass is considered the most common BS and a gold standard for weight loss, also known as Roux-en-Y gastric bypass (RYGB). The procedure of this BS is by creating a small pouch of the stomach (300 mL capacity) connected directly to the jejunum by bypassing the duodenum. RYGB has many advantages, such as; the alteration of guts hormones, which reduces appetite and hunger feeling, increases energy expenditure, causes significant long-term weight loss (60-80% of the excess body weight), decreases the amount of food consumed, and preserves 50% of the weight loss during this procedure. However, RYGB has some disadvantages. The most critical issue regarding this BS is altering the absorption of many medicines and nutrients, such as; vitamin D3 (Vit D3) [4,5]. (American Society for Metabolic and Bariatric Surgery. Bariatric Surgery Procedures.https://asmbs.org/patients/bariatric-surgery-procedures(accessed Feb 15, 2020). RYGB was performed on rodents before [6] but was never applied to rabbits. To determine the malabsorption procedure after the RYGB, the pharmacokinetics of the substance must be attained, and data must be calculated, such as; Cmaxand Tmax, to determine the absorption mutation. It was reported that pharmacokinetic studies on rodents could not be accurate due to the erratic absorption of the rodents [7]; thus, many studies have suggested using larger animals, such as rabbits, that do not address the same problem [8]. The current study investigates the ability to perform RYGB on rabbits and tests the effect of the surgery on body weight, food consumption, and the absorption of Vit D3.
Visualization and review of reads alignment on the graphical pan-genome with VAG
Authors: Li Fangping , Hu Haifei , Xiao Zitong , Wang Jingming , Liu Jieying , Zhao Deshu , Fu Yu , Wang Yijun , Yuan Xue , Bu Suhong , Zhou Xiaofan , Zhao Junliang , Wang Shaokui 
Published: January 2023

AbstractRecent advances in pangenomics have led to the rapid development of graph-based pangenomes that code genetic variant as nodes and edges preserve the contiguity of the sequence and structural variation between individuals. Data visualization is an essential component of genomic data analysis. However, the further application of the graph-based pangenome is still suffered from lacking bioinformatics tools to visualize graph format pangenomes and understand the reads alignment on graph pangenomes. In this research, we developed a novel bioinformatics platform, VAG (Visualizing read alignments in graph genomes), to overcome these challenges. VAG includes multifunctional modules integrated into a single command line and an online visualization platform supported through a web server. This tool can extract specific sequence regions from a graph pangenome and display read alignments on different paths of a graph pangenome. In addition, VAG provides population-level presence/absence variations frequency analysis and sequence path navigation to identify the population differentiation regions. To demonstrate the usage, we investigated genetic variations using a rice graph pangenome with population-level sequencing data to identify important genes and gene clusters underlying theindica–japonicadifferentiation with VAG. After investigating read alignments on the graph pangenome, we identified many false-positive alignments due to TE insertions. To reduce the impact of these misleading alignments, we developed a navigation module to determine and filter those false-positive alignments based on the pair-end alignment information. The utilization of mate-pair information in VAG provides a reliable reference for variation identification. Additionally, we developed a VAG web server to provide a user-friendly and interactive platform to visualize the read alignment data. VAG was also applied to SV discovery in the cucumber and soybean graph-based pangenome and details of VAG can be accessed by the following website (https://ricegenomichjx.xiaomy.net/VAG/sequenceextraction.php).
Gene networks driven by genetic variation for plasma cortisol in hepatic and adipose tissues implicate corticosteroid binding globulin in modulating tissue glucocorticoid action and cardiovascular risk
Authors: Bankier Sean , Wang Lingfei , Crawford Andrew , Morgan Ruth A , Ruusalepp Arno , Andrew Ruth , Björkegren Johan LM , Walker Brian R , Michoel Tom 
Published: January 2023

AbstractGenome wide association meta-analyses (GWAMA) by the CORtisol NETwork (CORNET) consortium identified genetic variants spanning theSERPINA6/ SERPINA1locus on chromosome 14 associated with morning plasma cortisol, cardiovascular disease (CVD), andSERPINA6mRNA expression encoding corticosteroid binding globulin (CBG) in liver. These and other findings indicate that higher plasma cortisol levels are causally associated with cardiovascular disease, however, the mechanisms by which variations in CBG lead to CVD are undetermined. Using genomic and transcriptomic data from The Stockholm Tartu Atherosclerosis Reverse Networks Engineering Task (STARNET) study, we identified plasma cortisol linked Single Nucleotide Polymorphisms (SNPs) that are trans-associated with genes from 7 different vascular and metabolic tissues, finding the highest representation of transgenes in liver, subcutaneous adipose and visceral abdominal adipose tissue (FDR = 15%). We identified a sub-set of cortisol-associated trans-genes that are putatively regulated by the Glucocorticoid Receptor (GR), the primary transcription factor activated by cortisol. Using causal inference, we identified GR-regulated trans-genes that are responsible for the regulation of tissue specific gene networks. Cis-expression Quantitative Trait Loci (eQTLs) were used as genetic instruments for identification of pairwise causal relationships from which gene networks could be reconstructed. Gene networks were identified in liver, subcutaneous fat and visceral abdominal fat, including a high confidence gene network specific to subcutaneous adipose (FDR = 10%) under the regulation of the interferon regulatory transcription factor,IRF2. These data identify a plausible pathway through which variation in liver CBG production perturbs cortisol-regulated gene networks in peripheral tissues and thereby promote CVD.