bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANISEED 2019: 4D exploration of genetic data for an extended range of tunicates
Authors: Dardaillon Justine , Dauga Delphine , Simion Paul , Faure Emmanuel , Onuma Takeshi A , DeBiasse Melissa B , Louis Alexandra , Nitta Kazuhiro R , Naville Magali , Besnardeau Lydia , Reeves Wendy , Wang Kai , Fagotto Marie , Guéroult-Bellone Marion , Fujiwara Shigeki , Dumollard Rémi , Veeman Michael , Volff Jean-Nicolas , Roest Crollius Hugues , Douzery Emmanuel , Ryan Joseph F , Davidson Bradley , Nishida Hiroki , Dantec Christelle , Lemaire Patrick 
Published: October 2019

AbstractANISEED (https://www.aniseed.cnrs.fr) is the main model organism database for the worldwide community of scientists working on tunicates, the vertebrate sister-group. Information provided for each species includes functionally-annotated gene and transcript models with orthology relationships within tunicates, and with echinoderms, cephalochordates and vertebrates. Beyond genes the system describes other genetic elements, including repeated elements and cis-regulatory modules. Gene expression profiles for several thousand genes are formalized in both wild-type and experimentally-manipulated conditions, using formal anatomical ontologies. These data can be explored through three complementary types of browsers, each offering a different view-point. A developmental browser summarizes the information in a gene- or territory-centric manner. Advanced genomic browsers integrate the genetic features surrounding genes or gene sets within a species. A Genomicus synteny browser explores the conservation of local gene order across deuterostome. This new release covers an extended taxonomic range of 14 species, including for the first time a non-ascidian species, the appendicularian Oikopleura dioica. Functional annotations, provided for each species, were enhanced through a combination of manual curation of gene models and the development of an improved orthology detection pipeline. Finally, gene expression profiles and anatomical territories can be explored in 4D online through the newly developed Morphonet morphogenetic browser.
Cigarette Smokers Versus Cousers of Cannabis and Cigarettes: Exposure to Toxicants
Authors: Meier Ellen , Vandrey Ryan , Rubin Nathan , Pacek Lauren R , Jensen Joni A , Donny Eric C , Hecht Stephen S , Carmella Steven G , Murphy Sharon E , Luo Xianghua , Stepanov Irina , Ikuemonisan Joshua , Severson Herb , Al’absi Mustafa , Hatsukami Dorothy K 
Published: October 2019

AbstractIntroductionCannabis and tobacco couse is common and could expose users to higher levels of toxicants. No studies have examined biomarkers of toxicant exposure in cousers of cannabis and cigarettes, compared with cigarette smokers (CS).Aims and MethodsAdult daily CS were recruited from 10 US sites for a study of reduced nicotine cigarettes. In this analysis of baseline data, participants were categorized as either cousers of cannabis and tobacco (cousers; N = 167; urine positive for 11-nor-9-carboxy-Δ 9-tetrahydrocannnabinol and self-reported cannabis use ≥1×/week), or CS (N = 911; negative urine and no self-reported cannabis use). Participants who did not meet either definition (N = 172) were excluded. Self-reported tobacco and cannabis use and tobacco and/or combustion-related biomarkers of exposure were compared between groups.ResultsCompared to CS, cousers were younger (couser Mage = 38.96, SD = 13.01; CS Mage = 47.22, SD = 12.72; p &lt; .001) and more likely to be male (cousers = 67.7%, CS = 51.9%, p &lt; .001). There were no group differences in self-reported cigarettes/day, total nicotine equivalents, or breath carbon monoxide, but cousers had greater use of non-cigarette tobacco products. Compared to CS, cousers had higher concentrations of 3-hydroxypropylmercapturic acid, 2-cyanoethylmercapturic acid, S-phenylmercapturic acid, 3-hydroxy-1-methylpropylmercapturic acid (ps &lt; .05), and phenanthrene tetraol (p &lt; .001). No biomarkers were affected by number of cannabis use days/week or days since last cannabis use during baseline (ps &gt; .05).ConclusionsCousers had higher concentrations of biomarkers of exposure than CS, but similar number of cigarettes per day and nicotine exposure. Additional studies are needed to determine whether cannabis and/or alternative tobacco products are driving the increased toxicant exposure.ImplicationsCousers of cannabis and tobacco appear to be exposed to greater levels of harmful chemicals (ie, volatile organic compounds and polycyclic aromatic hydrocarbons), but similar levels of nicotine as CS. It is unclear if the higher levels of toxicant exposure in cousers are due to cannabis use or the increased use of alternative tobacco products compared with CS. It is important for studies examining biomarkers of exposure among CS to account for cannabis use as it may have a significant impact on outcomes. Additionally, further research is needed examining exposure to harmful chemicals among cannabis users.
Characterization of Anti–Interferon-γ Antibodies in HIV-Negative Patients Infected With Disseminated Talaromyces marneffei and Cryptococcosis
Authors: Zeng Wen , Qiu Ye , Tang Shudan , Zhang Jianquan , Pan Mianluan , Zhong Xiaoning 
Published: October 2019

AbstractBackgroundFew reports of Talaromyces marneffei (TM) or cryptococcosis infections among HIV-negative patients with high-titeranti–IFN-γautoantibodies (nAIGAs) have been published. We investigated the clinical manifestations of patients with nAIGAs and TM infections.MethodsHIV-negative adults (≥18 years) were enrolled if they haddisseminated TM infection (group 1; further divided into nAIGAs positive [group 1P] and negative [group 1N]); cryptococcosis(pulmonary cryptococcosis and/or cryptococcosis of the brain)(group 2); pulmonary tuberculosis (group 3); and healthy controls (group 4) with nAIGAs detected. Complete histories, physical examinations, and routine clinical laboratory tests were obtained at baseline.ResultsOverall, 88 participants were in the four groups (20,13,23, and 32 in groups 1 to 4, respectively). Significant differences occurred between groups with higher nAIGAs titers (P &lt; 0.001), and higher total white-cell and absolute neutrophil counts (P &lt; 0.001) in group1. Lungs (90.0%), lymph nodes (60.0%), skin (55.0%), and bones (50.0%) were most common sites of involvement. Significant differences in total white-cell and absolute neutrophil counts occurred between groups IP and 1N.Patients with recurrent TM infections, particularly group 1P, had higher initial nAIGA titer.ConclusionsPatients with persistent infection who died tended to have positive initial nAIGA titer. It suggests that nAIGAs may play a critical role in the pathogenesis of TM infections, and may be associated with more severe, refractory infection.
Bridging the Knowledge Gap: An Examination of the Ideal Postoperative Autologous Breast Reconstruction Educational Material with A/B Testing
Authors: Fan Kenneth L. , Black Cara K. , DeFazio Michael V. , Luvisa Kyle , Camden Rachel , Song David H. 
Published: October 2019

Background:
Poor health literacy is an epidemic in the United States, associated with higher mortality rates and poor postoperative care. Autologous breast reconstruction is highly complex, and the identification of complications is difficult even for non–plastic surgeon practitioners. The authors sought to explore the problem of health literacy in this context and identify the ideal postoperative patient education materials.

Methods:
Available online postoperative patient education materials for autologous breast reconstruction and corresponding readability scores were assessed. To derive the ideal formula for materials, the authors crowd-sourced quizzes with A/B testing, a method to examine the outcome of two versions of a single variable. The authors implemented their findings and compared performance on postoperative quizzes with and without oral reinforcement.

Results:
Of the 12 postoperative flap complication patient education materials found through an Internet search, the average grade level readability level was 9.9. Only one of 12 (8.3 percent) mentioned symptoms and signs of flap compromise. The A/B tests result revealed that text approximately 400 to 800 words written on a sixth-grade level led to the highest quiz scores. Patients scored significantly higher on the postoperative day–2 quiz when patient education materials, modeled after these findings, were reinforced with oral presentation (p = 0.0059). Retention of high quiz scores remained at postoperative day 10.

Conclusions:
Currently available patient education materials are at a high reading level and lack specific information on the identification of flap compromise. The authors propose the most effective postoperative instructions to be approximately 400 to 800 words written on a grade-six level with images and oral reinforcement.
Genome-wide investigation of DNA methylation in congenital adrenal hyperplasia
Authors: Karlsson Leif , Barbaro Michela , Ewing Ewoud , Gomez-Cabrero David , Lajic Svetlana 
Published: October 2019

AbstractBackgroundPatients with congenital adrenal hyperplasia (CAH) are at risk of long-term cognitive and metabolic sequelae with some of the effects being attributed to the chronic glucocorticoid treatment that they receive. This study investigates genome-wide DNA methylation in patients with CAH to determine whether there is evidence for epigenomic reprogramming as well as any relationship to patient outcome.MethodsWe analysed CD4+ T cell DNA from 28 patients with CAH (mean age=18.5 ±6.5 years [y]) and 37 population controls (mean age=17.0 ±6.1 y) with the Infinium-HumanMethylation450 BeadChip array to measure genome-wide locus-specific DNA methylation levels. Effects of CAH, phenotype and CYP21A2 genotype on methylation were investigated as well as the association between differentially methylated CpGs, glucose homeostasis, blood lipid profile and cognitive functions. In addition, we report data on a small cohort of 11 patients (mean age=19.1, ±6.0 y) with CAH who were treated prenatally with dexamethasone (DEX) in addition to postnatal glucocorticoid treatment.ResultsWe identified two CpGs to be associated with patient phenotype: cg18486102 (located in the FAIM2 gene; rho=0.58, adjusted p=0.027) and cg02404636 (located in the SFI1 gene; rho=0.58, adjusted p=0.038). cg02404636 was also associated with genotype (rho=0.59, adjusted p=0.024). Higher levels of serum C-peptide was also observed in patients with CAH (p=0.044). Additionally, levels of C-peptide and HbA1c were positively correlated with patient phenotype (p=0.044 and p=0.034) and genotype (p=0.044 and p=0.033), respectively. No significant association was found between FAIM2 methylation and cognitive or metabolic outcome. However, SFI1 TSS methylation was associated with fasting plasma HDL cholesterol levels (p=0.035).ConclusionIn conclusion, higher methylation levels in CpG sites covering FAIM2 and SFI1 were associated with disease severity. Hypermethylation in these genes may have implications for long-term cognitive and metabolic outcome in patients with CAH.
Homeostatic regulation of perisynaptic MMP9 activity in the amblyopic visual cortex
Authors: Murase Sachiko , Winkowski Daniel E. , Liu Ji , Kanold Patrick O. , Quinlan Elizabeth M. 
Published: October 2019

AbstractDark exposure (DE) followed by light reintroduction (LRx) reactivates robust synaptic plasticity in adult mouse V1, which allows recovery from amblyopia. Previously we showed that LRx-induced perisynaptic proteolysis of extracellular substrates by MMP9 mediates the enhanced plasticity in binocular adult mice (Murase et al., 2017). However, it is unknown if a visual system compromised by amblyopia could engage this pathway. Here we show that LRx to adult amblyopic mice induces perisynaptic MMP2/9 activity and degradation of ECM in the deprived and non-deprived V1. LRx restricted to the amblyopic eye induces equally robust MMP2/9 activity at thalamo-cortical synapses and ECM degradation in deprived V1. Two-photon live imaging demonstrates that the history of visual experience regulates MMP2/9 activity in V1, and that DE lowers the threshold for the proteinase activation. This homeostatic reduction of MMP2/9 activation threshold by DE enables the visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis.
Numerous post-translational modifications of RNA polymerase II subunit Rpb4 link transcription to post-transcriptional mechanisms
Authors: Richard Stephen , Gross Lital , Fischer Jonathan , Bendalak Keren , Ziv Tamar , Urim Shira , Choder Mordechai 
Published: October 2019

AbstractRpb4/7 binds RNA Polymerase II (Pol II) transcripts co-transcriptionally and accompanies them throughout their lives. By virtue of its capacity to interact with key regulators (e.g., Pol II, eIF3, Pat1) both temporarily and spatially, Rpb4/7 regulates the major stages of the mRNA lifecycle. Here we show that Rpb4/7 can undergo over 100 combinations of post-translational modifications (PTMs). Remarkably, the Rpb4/7 PTMs repertoire changes as the mRNA/Rpb4/7 complex progresses from one stage to the next. A mutagenesis approach in residues that undergo PTMs suggests that temporal Rpb4 PTMs regulate its interactions with key regulators of gene expression that control transcriptional and post-transcriptional stages. Moreover, one mutant type specifically affects mRNA synthesis despite its normal association with Pol II, whereas the other affects both mRNA synthesis and decay; both types disrupt the balance between mRNA synthesis and decay (‘mRNA buffering’) and the cell’s capacity to respond to the environment. Taken together, we propose that temporal Rpb4/7 PTMs are involved in cross talks among the various stages of the mRNA lifecycle.
Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform specific start-loss mutations of essential genes can cause genetic diseases
Authors: Perenthaler Elena , Nikoncuk Anita , Yousefi Soheil , Berdowski Woutje M. , Capo Ivan , van der Linde Herma C. , van den Berg Paul , Jacobs Edwin H. , Putar Darija , Ghazvini Mehrnaz , Aronica Eleonora , van IJcken Wilfred F.J. , de Valk Walter G. , Medici-van den Herik Evita , van Slegtenhorst Marjon , Brick Lauren , Kozenko Mariya , Kohler Jennefer N. , Bernstein Jonathan A. , Monaghan Kristin G. , Begtrup Amber , Torene Rebecca , Futaisi Amna Al , Murshedi Fathiya Al , Mani Renjith , Azri Faisal Al , Kamsteeg Erik-Jan , Mojarrad Majid , Eslahi Atieh , Khazaei Zaynab , Darmiyan Fateme Massinaei , Doosti Mohammad , Karimiani Ehsan Ghayoor , Vandrovcova Jana , Zafar Faisal , Rana Nuzhat , Kandaswamy Krishna K. , Hertecant Jozef , Bauer Peter , Efthymiou Stephanie , Houlden Henry , Bertoli-Avella Aida M. , Maroofian Reza , Retterer Kyle , Brooks Alice S. , van Ham Tjakko J. , Barakat Tahsin Stefan 
Published: October 2019

AbstractDevelopmental and/or epileptic encephalopathies (DEEs) are a group of devastating genetic disorders, resulting in early onset, therapy resistant seizures and developmental delay. Here we report on 12 individuals from 10 families presenting with a severe form of intractable epilepsy, severe developmental delay, progressive microcephaly and visual disturbance. Whole exome sequencing identified a recurrent, homozygous variant (chr2:64083454A>G) in the essentialUDP-glucose pyrophosphorylase(UGP2) gene in all probands. This rare variant results in a tolerable Met12Val missense change of the longer UGP2 protein isoform but causes a disruption of the start codon of the shorter isoform. We show that the absence of the shorter isoform leads to a reduction of functional UGP2 enzyme in brain cell types, leading to altered glycogen metabolism, upregulated unfolded protein response and premature neuronal differentiation, as modelled during pluripotent stem cell differentiationin vitro. In contrast, the complete lack of all UGP2 isoforms leads to differentiation defects in multiple lineages in human cells. Reduced expression of Ugp2a/Ugp2bin vivoin zebrafish mimics visual disturbance and mutant animals show a behavioral phenotype. Our study identifies a recurrent start codon mutation inUGP2as a cause of a novel autosomal recessive DEE. Importantly, it also shows that isoform specific start-loss mutations causing expression loss of a tissue relevant isoform of an essential protein can cause a genetic disease, even when an organism-wide protein absence is incompatible with life. We provide additional examples where a similar disease mechanism applies.
A hierarchical model of perceptual multistability involving interocular grouping
Authors: Wang Yunjiao , Kilpatrick Zachary P , Josić Krešimir 
Published: October 2019

AbstractAmbiguous visual images can generate dynamic and stochastic switches in perceptual interpretation known as perceptual rivalry. Such dynamics have primarily been studied in the context of rivalry between two percepts, but there is growing interest in the neural mechanisms that drive rivalry between more than two percepts. In recent experiments, we showed that split images presented to each eye lead to subjects perceiving four stochastically alternating percepts (Jacot-Guillarmod et al., 2017): two single eye images and two interocularly grouped images. Here we propose a hierarchical neural network model that exhibits dynamics consistent with our experimental observations. The model consists of two levels, with the first representing monocular activity, and the second representing activity in higher visual areas. The model produces stochastically switching solutions, whose dependence on task parameters is consistent with four generalized Levelt Propositions. Our neuromechanistic model also allowed us to probe the roles of inter-actions between populations at the network levels. Stochastic switching at the lower level representing alternations between single eye percepts dominated, consistent with experiments.
Zonation-dependent single-endothelial cell transcriptomic changes in the aged brain
Authors: Zhao Lei , Li Zhongqi , Vong Joaquim S. L. , Chen Xinyi , Lai Hei-Ming , Yan Leo Y. C. , Huang Junzhe , Sy Samuel K. H. , Tian Xiaoyu , Huang Yu , Chan Ho Yin Edwin , So Hon-Cheong , Ng Wai-Lung , Tang Yamei , Lin Wei-Jye , Mok Vincent C.T. , Ko Ho 
Published: October 2019

AbstractWith advances in single-cell genomics, molecular signatures of cells comprising the brain vasculature are revealed in unprecedented detail1,2, yet the ageing-associated cell subtype transcriptomic changes which may contribute to neurovascular dysfunction in neurodegenerative diseases3–7 remain elusive. Here, we performed single-cell transcriptomic profiling of brain endothelial cells (EC) in young adult and aged mice to characterize their ageing-associated genome-wide expression changes. We identified zonation-dependent transcriptomic changes in aged brain EC subtypes, with capillary ECs exhibiting the most transcriptomic alterations. Pathway enrichment analysis revealed altered immune/cytokine signaling in ECs of all vascular segments, while functional changes impacting the blood-brain barrier (BBB) and glucose/energy metabolism were most prominently implicated in ECs of the capillary bed – the primary site where ECs and other neurovascular unit (NVU) cell types closely interact and coordinate to regulate BBB and cerebral blood flow in health and diseased conditions8–17. Furthermore, an overrepresentation of Alzheimer’s disease (AD)-associated genes identified from GWAS studies was evident among the human orthologs of differentially expressed genes of aged capillary ECs but not other EC subtypes. Importantly, for numerous EC-enriched differentially expressed genes with important functional roles at the BBB and/or association with AD, we found concordant expression changes in human aged or AD brains. Finally, we demonstrated that treatment with exenatide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, strongly reverses transcriptomic changes in ECs and largely reduces BBB leakage in the aged brain. Thus, our study provides insights into detailed transcriptomic alterations underlying brain EC ageing that are complex with subtype specificity yet amenable to pharmacological interventions.
Heterosis indices: What do they really measure?
Authors: de Vienne Dominique , Fiévet Julie B. 
Published: October 2019

AbstractHeterosis (hybrid vigour) is a universal phenomenon of crucial agro-economic and evolutionary importance. We show that the most common heterosis indices do not properly measure deviation from additivity because they include both a component accounting for “real” heterosis and a term that is not related to heterosis since it is derived solely from parental values. Therefore, these indices are inadequate when the aim of the study is to compare heterosis levels between different traits, environments, genetic backgrounds or developmental stages, as these factors may affect not only heterosis but also parental values. The only relevant index for such comparisons is the so-called “potence ratio”. These observations argue for the careful choice of heterosis indices depending on the purpose of the work.HighlightUnlike dominance indices, heterosis indices, with one exception, do not properly measure the level of deviation from additivity, thus making them unsuitable for comparative analyses.
Genetic diversity and thermal performance in invasive and native populations of African fig flies
Authors: Comeault Aaron A. , Wang Jeremy , Tittes Silas , Isbell Kristin , Ingley Spencer , Hurlbert Allen H. , Matute Daniel R. 
Published: October 2019

AbstractDuring biological invasions, alien populations can suffer losses of genetic diversity that are predicted to negatively impact their fitness/performance. Using genome sequences, we show that invasive populations of the African fig fly,Zaprionus indianus, have lower levels of genetic diversity compared to native populations, and that genetic diversity is lost more in regions of the genome with low recombination rates. However, genetic diversity remains as high or higher in invasive populations than in populations of non-invasive congeneric species. We then use parameter estimates from thermal performance curves measured for 13 species ofZaprionusto show thatZ. indianushas the broadest thermal niche of measured species, and that performance does not differ between invasive and native populations. These results illustrate how aspects of genetic diversity in invasive species can be decoupled from measures of fitness, and that a broad thermal niche may have helped facilitateZ. indianus’srange expansion.