bluuebunny/crossref_metadata_2025_split huggingface dataset:
DAXX safeguards heterochromatin formation in embryonic stem cells
Authors: Canat Antoine , Veillet Adeline , Batrin Renaud , Dubourg Clara , Illingworth Robert , Fabre Emmanuelle , Therizols Pierre 
Published: April 2021

AbstractGenomes comprise a large fraction of repetitive sequences folded into constitutive heterochromatin to protect genome integrity and cell identity.De novoformation of heterochromatin during preimplantation development is an essential step for preserving the ground-state of pluripotency and the self-renewal capacity of embryonic stem cells (ESCs). Yet, the molecular mechanisms responsible for the remodeling of constitutive heterochromatin are largely unknown. Here, we find that DAXX, an H3.3 chaperone, is essential for ESCs maintenance in the ground-state of pluripotency. DAXX accumulates at pericentromeric regions, and recruits PML and SETDB1, thereby promoting heterochromatin formation. In absence of DAXX or PML, the 3D-architecture and physical properties of pericentric and peripheral heterochromatin are disrupted, resulting in derepression of major satellite DNA, transposable elements and genes associated with the nuclear lamina. Using epigenome editing tools, we observe that H3.3, and specifically H3.3K9 modification, directly contribute to maintaining pericentromeric chromatin conformation. Altogether, our data reveal that DAXX is crucial for the maintenance and 3D-organization of the heterochromatin compartment and protects ESCs viability.
Mechanism and role of astrogliosis in the pathogenesis of HIV-associated pain One Sentence Summary: Neuron-to-astrocyte Wnt5a signaling-activated astrogliosis is essential for the development of pathological pain induced by HIV-1 gp120
Authors: Liu Xin , Bae Chilman , Gelman Benjamin , Chung Jin Mo , Tang Shao-Jun 
Published: April 2021

ABSTRACTPathological pain is the most common neurological disorder in people living with HIV-1/AIDS (PLWHA), and rationale-based effective treatment is not available. Multiple neuropathologies develop in the pain transmission pathways in of HIV patients, consistent with their nociceptive dysfunction1,2. One of the prominent neuropathologies associating with the manifestation of pain in HIV patients is astrogliosis (a.k.a. reactive astrocytes) in the spinal dorsal horn (SDH)1, the spinal center for the transmission of pain signals from peripheral organs to the brain. However, the pathogenic role and the activation mechanism of astrogliosis are unclear. Here, we show that the astrogliosis is crucial for the pain pathogenesis induced by HIV-1 gp120, a key etiologically relevant protein2, and that a neuron-to-astrocyte Wnt5a signal controls the astrogliosis. We found that ablation of astrogliosis blocked the development of gp120-induced mechanical hyperalgesia, and concomitantly the expression of neural circuit polarization (NCP) in the SDH. In addition, we demonstrated that conditional knockout (CKO) of either Wnt5a in neurons or its receptor ROR2 in astrocytes abolished not only gp120-induced astrogliosis but also the hyperalgesia and the NCP. Furthermore, we found that the astrogliosis promoted expression of the NCP and the hyperalgesia via IL-1β regulated by a Wnt5a-ROR2-MMP2 axis. Our results elucidate an important role and a novel mechanism of astrogliosis in the pathogenesis of HIV-associated pain. Targeting reactive astrocytes by manipulating the mechanistic processes identified here may lead to the development of effective therapy to treat the pain syndrome in HIV patients.
Co-Infection of cattle in Virginia withTheileria orientalis ikedagenotype andAnaplasma marginale
Authors: Oakes Vanessa J. , Todd S. Michelle , Carbonello Amanda A. , Michalak Pawel , Lahmers Kevin K. 
Published: April 2021

AbstractTheileria orientalis ikedais a newly identified agent of bovine infectious anemia in the United States. Although it is transmitted by separate tick hosts thanAnaplasma marginale– a bacterial etiology of bovine infectious anemia –the geographic distributions of these two infectious organisms overlap, with co-infection reported in some cattle. Only anaplasmosis has approved effective treatment in the United States. To provide rapid diagnostic information for producers with anemic animals, we developed a duplex qPCR forA. marginaleandT. orientalis. With a cut-off of 38 cycles, the duplex assay has a sensitivity of 96.97% and a specificity of 100% forA. marginale; with a cut-off of 45 cycles, the duplex assay has a sensitivity and a specificity of 100% forT. orientalis. In addition to providing a tool for improved clinical decision-making for veterinarians and producers, this qPCR facilitates the study of co-infection rate of cattle in Virginia. Of 1,359 blood samples analyzed, 174 were positive for the presence ofT. orientalis, 125 were positive for the presence ofA. marginale, and 12 samples were positive for bothT. orientalisandA. marginale.This indicated that co-infection of both of these etiologies of bovine infectious anemia does occur within the state of Virginia. It is likely that this pattern of infection will be seen in regions whereT. orientalisandA. marginaleare endemic, despite the difference in tick vectors.
A Dual-Site Inhibitor of CBP/p300 KIX is a Selective and Effective Modulator of Myb
Authors: Joy Stephen T. , Henley Matthew J. , De Salle Samantha N. , Beyersdorf Matthew S. , Vock Isaac W. , Huldin Allison J.L. , Mapp Anna K. 
Published: April 2021

AbstractThe protein-protein interaction between the KIX motif of the transcriptional coactivator CBP/p300 and the transcriptional activator Myb is a high value target due to its established role in certain acute myeloid leukemias (AML) and potential contributions to other cancers. However, the CBP/p300 KIX domain has multiple binding sites, several structural homologues, many binding partners, and substantial conformational plasticity, making it challenging to specifically target using small molecule inhibitors. Here, we report a picomolar dual-site inhibitor (MybLL-tide) of the Myb-CBP/p300 KIX interaction. MybLL-tide has higher affinity for CBP/p300 KIX than any previously reported compounds while also possessing 16,000-fold selectivity for the CBP/p300 KIX domain over other coactivator domains. MybLL-tide blocks the association of CBP and p300 with Myb in the context of the proteome leading to inhibition of key Myb•KIX-dependent genes in AML cells. These results show that MybLL-tide is an effective, modifiable tool to selectively target the KIX domain and assess transcriptional effects in AML cells and potentially other cancers featuring aberrant Myb behavior. Additionally, the dual-site design has applicability to the other challenging coactivators that bear multiple binding surfaces
Gonadal hormones and sex chromosome complement differentially contribute to ethanol intake, preference, and relapse-like behavior in Four Core Genotypes mice
Authors: Sneddon Elizabeth A. , Rasizer Lindsay N. , Cavalco Natalie G. , Jaymes Asa H. , Ostlie Noah J. , Minshall Brianna L. , Masters Brianna M. , Hrncir Haley , Arnold Arthur P. , Radke Anna K. 
Published: April 2021

AbstractAlcohol use and high-risk alcohol drinking behaviors among women are rapidly rising. In rodent models, females typically consume more ethanol (EtOH) than males. Here, we used the Four Core Genotypes (FCG) mouse model to investigate the influence of gonadal hormones and sex chromosome complement on EtOH drinking behaviors. FCG mice were given access to escalating concentrations of EtOH in a two-bottle, 24-h continuous access drinking paradigm to assess consumption and preference. Relapse-like behavior was measured by assessing escalated intake following repeated cycles of deprivation and re-exposure. Twenty-four hour EtOH consumption was greater in mice with ovaries (Sry-), relative to those with testes, and in mice with the XX chromosome complement, relative to those with XY sex chromosomes. EtOH preference was higher in XX vs. XY mice. Escalated intake following repeated cycles of deprivation and re-exposure emerged only in XX mice (vs. XY). Mice with ovaries (Sry-FCG mice and C57Bl/6J females) were also found to consume more water than mice with testes. These results demonstrate that aspects of EtOH drinking behavior may be independently regulated by sex hormones and chromosomes and inform our understanding of the neurobiological mechanisms which contribute to EtOH dependence in male and female mice. Future investigation of the contribution of sex chromosomes to EtOH drinking behaviors is warranted.
Tributyltin Protects Against Ovariectomy-Induced Trabecular Bone Loss in C57BL/6J Mice with an Attenuated Effect in High Fat Fed Mice
Authors: Freid Rachel , Hussein Amira I , Schlezinger Jennifer J 
Published: April 2021

AbstractRisk factors for poor bone quality include estrogen loss at menopause, a high fat diet and exposures to drugs/chemicals that activate peroxisome proliferator activated receptor gamma (PPARγ). We observed that the PPARγ and retinoid X receptor dual ligand, tributyltin (TBT), repressed periosteal bone formation but enhanced trabecular bone formation in female C57BL6/J mice. Here, we examined the interaction of diet, ovariectomy (OVX) and TBT exposure on bone structure. C57BL/6J mice underwent either sham surgery or OVX at 10 weeks of age. At 12 weeks of age, they were placed on a low (10% kcal) or high (45% kcal) fat, sucrose-matched diet and treated with Vh or TBT (1 or 5 mg/kg) for 14 weeks. OVX increased body weight gain in mice on either diet. TBT enhanced body weight gain in intact mice fed a high fat diet, but decreased weight gain in OVX mice. Elemental tin concentrations increased dose-dependently in bone. TBT had marginal effects on cortical and trabecular bone in intact mice fed a low- or high- fat diet. OVX caused a reduction in cortical and trabecular bone, regardless of diet. In high-fat fed OVX mice, TBT further reduced cortical thickness, bone area and total area. Interestingly, TBT protected against OVX-induced trabecular bone loss in low fat fed mice. The protective effect of TBT was nullified by the high fat diet and accompanied by a significant decrease in serum bone formation markers. Our novel observations will provide new information on basic bone biology, potential therapeutic targets and toxicological pathways.
Using total RNA quality metrics for time since deposition estimates in degrading bloodstains
Authors: Elliott Colin I. , Stotesbury Theresa E. , Shafer Aaron B.A. 
Published: April 2021

ABSTRACTDetermining the time since deposition (TSD) of bloodstains would provide forensic scientists with critical information regarding the timeline of the events involving bloodshed. The physicochemical changes occurring to biomolecules as a bloodstain degrades can be used to approximate the TSD of bloodstains. Our study aims to quantify the timewise degradation trends and temperature dependence found in total RNA from bloodstains without the use of amplification, expanding the scope of the RNA TSD research which has previously targeted mRNA molecules. Whole bovine blood was stored in plastic microcentrifuge tubes at 21°C or 4°C and tested over different timepoints spanning one week. Nine RNA metrics were visually assessed and quantified using linear and mixed models; the RNA Integrity Number equivalent (RINe) and the DV200 demonstrated strong negative trends over time and statistical independence. The RINe model fit was high (R2= 0.60), and while including the biological replicate as a random effect increased the fit for all RNA metrics, no significant differences were found between biological replicates stored at the same temperature for the RINe and DV200 metrics. Importantly, this suggests that these standardized metrics can likely be directly compared between scenarios and individuals, with DV200 having an inflection point at ∼28 hrs. This study provides a novel approach for blood TSD estimates, producing metrics that are not affected by inter-individual variation and improving our understanding of the rapid degradation occurring in bloodstains.HIGHLIGHTSAmplification-free analysis of total RNA in degrading bloodstains.Short-term RNA degradation assessment using high-resolution size measurements.Total RNA quality and quantity metrics were assessed across a one-week.Total RNA quality metrics demonstrated the strongest timewise trends.Biological replicates produced similar results for RNA quality metrics.
Automating UbiFast for High-throughput and Multiplexed Ubiquitin Enrichment
Authors: Rivera Keith D. , Olive Meagan E. , Bergstrom Erik J. , Nelson Alissa J. , Lee Kimberly A. , Satpathy Shankha , Carr Steven A. , Udeshi Namrata D. 
Published: April 2021

AbstractRobust methods for deep-scale enrichment and site-specific identification of ubiquitylation sites is necessary for characterizing the myriad roles of protein ubiquitylation. To this end we previously developed UbiFast, a sensitive method for highly multiplexed ubiquitylation profiling where K-ε-GG peptides are enriched with anti-K-ε-GG antibody and labeled on-antibody with isobaric labeling reagents for sample multiplexing. Here, we present robotic automation of the UbiFast method using a magnetic bead-conjugated K-ε-GG antibody (mK-ε-GG) and a magnetic particle processor. We report the identification of ∼20,000 ubiquitylation sites from a TMT10-plex with 500 μg input per sample processed in ∼2 hours. Automation of the UbiFast method greatly increased the number of identified and quantified ubiquitylation sites, improved reproducibility and significantly reduced processing time. The workflow enables processing of up to 96 samples in a single day making it suitable to study ubiquitylation in large sample sets. Here we demonstrate the applicability of this method to profile small amounts of tissue using breast cancer patient-derived xenograft (PDX) tissue samples.
Systematic over-crediting in California’s forest carbon offsets program
Authors: Badgley Grayson , Freeman Jeremy , Hamman Joseph J. , Haya Barbara , Trugman Anna T. , Anderegg William R.L. , Cullenward Danny 
Published: April 2021

AbstractCarbon offsets are widely used by individuals, corporations, and governments to mitigate their greenhouse gas emissions on the assumption that offsets reflect equivalent climate benefits achieved elsewhere. These climate-equivalence claims depend on offsets providing “additional” climate benefits beyond what would have happened, counterfactually, without the offsets project. Here, we evaluate the design of California’s prominent forest carbon offsets program and demonstrate that its climate-equivalence claims fall far short on the basis of directly observable evidence. By design, California’s program awards large volumes of offset credits to forest projects with carbon stocks that exceed regional averages. This paradigm allows for adverse selection, which could occur if project developers preferentially select forests that are ecologically distinct from unrepresentative regional averages. By digitizing and analyzing comprehensive offset project records alongside detailed forest inventory data, we provide direct evidence that comparing projects against coarse regional carbon averages has led to systematic over-crediting of 30.0 million tCO2e (90% CI: 20.5 to 38.6 million tCO2e) or 29.4% of the credits we analyzed (90% CI: 20.1 to 37.8%). These excess credits are worth an estimated $410 million (90% CI: $280 to $528 million) at recent market prices. Rather than improve forest management to store additional carbon, California’s offsets program creates incentives to generate offset credits that do not reflect real climate benefits.Significance StatementForest carbon offsets are increasingly prominent in corporate and government “net zero” emission strategies, but face growing criticism about their efficacy. California’s forest offsets program is frequently promoted as a high-quality approach that improves on the failures of earlier efforts. Our analysis demonstrates, however, that substantial ecological and statistical shortcomings in the design of California’s forest offset protocol generate offset credits that do not reflect real climate benefits. Looking globally, our results illustrate how protocol designs with easily exploitable rules can undermine policy objectives and highlight the need for stronger governance in carbon offset markets.
Fragmentation of macrophages during isolation confounds analysis of single cell preparations from mouse hematopoietic tissues
Authors: Millard Susan M , Heng Ostyn , Opperman Khatora S , Sehgal Anuj , Irvine Katharine M , Kaur Simranpreet , Summers Kim M , Sandrock Cheyenne J , Wu Andy C , Magor Graham W , Batoon Lena , Perkins Andrew C , Noll Jacqueline E , Zannettino Andrew CW , Sester David P , Levesque Jean-Pierre , Hume David A , Raggatt Liza J , Pettit Allison R 
Published: April 2021

SummaryMouse hematopoietic tissues contain abundant and heterogeneous populations of tissue-resident macrophages attributed trophic functions in control of immunity, hematopoiesis and bone homeostasis. A systematic strategy to characterise macrophage subsets in mouse bone marrow (BM), spleen and lymph node, unexpectedly revealed macrophage surface marker staining typically emanated from membrane-bound subcellular remnants associated with unrelated cell types. Remnant-restricted macrophage-specific membrane markers, cytoplasmic fluorescent reporters and mRNA were all detected in non-macrophage cell populations including isolated stem and progenitor cells. The profile of macrophage remnant association reflects adhesive interactions between macrophages and other cell types in vivo. Applying this knowledge, reduced macrophage remnant attachment to BM granulocytes inSiglec1deficient mice was associated with compromised emergency granulocytosis, revealing a function forSiglec1-dependent granulocyte-macrophage interactions. Analysis of published RNA-seq data for purified macrophage and non-macrophage populations indicates that macrophage fragmentation is a general phenomenon that confounds bulk and single cell analysis of disaggregated tissues.
Expression of a CO2-permeable aquaporin enhances mesophyll conductance in the C4speciesSetaria viridis
Authors: Ermakova Maria , Osborn Hannah , Groszmann Michael , Bala Soumi , McGaughey Samantha , Byrt Caitlin , Alonso-Cantabrana Hugo , Tyerman Steve , Furbank Robert T. , Sharwood Robert E. , von Caemmerer Susanne 
Published: April 2021

AbstractA fundamental limitation of photosynthetic carbon fixation is the availability of CO4. In C4plants, primary carboxylation occurs in mesophyll cytosol, and little is known about the role of CO2diffusion in facilitating C4photosynthesis. We have examined the expression, localization, and functional role of selected plasma membrane intrinsic aquaporins (PIPs) fromSetaria italica(foxtail millet) and discovered thatSiPIP2;7 isCO2-permeable. When ectopically expressed in mesophyll cells ofS. viridis(green foxtail), SiPIP2;7 was localized to the plasma membrane and caused no marked changes in leaf biochemistry. Gas-exchange and C18O16O discrimination measurements revealed that targeted expression of SiPIP2;7 enhanced the conductance to CO2diffusion from the intercellular airspace to the mesophyll cytosol. Our results demonstrate that mesophyll conductance limits C4photosynthesis at lowpCO2and that SiPIP2;7 is a functional CO2permeable aquaporin that can improve CO2diffusion at the airspace/mesophyll interface and enhance C4photosynthesis.
Transplantation of high fat fed mouse microbiota into zebrafish larvae identifies MyD88-dependent acceleration of hyperlipidaemia by Gram positive cell wall components
Authors: Cholan Pradeep Manuneedhi , Morris Simone , Luo Kaiming , Chen Jinbiao , Boland Jade A , McCaughan Geoff W , Britton Warwick J , Oehlers Stefan H 
Published: April 2021

AbstractGut dysbiosis is an important modifier of pathologies including cardiovascular disease but our understanding of the role of individual microbes is limited. Here, we have used transplantation of mouse microbiota into microbiota-deficient zebrafish larvae to study the interaction between members of a mammalian high fat diet-associated gut microbiota with a lipid rich diet challenge in a tractable model species. We find zebrafish larvae are more susceptible to hyperlipidaemia when exposed to the mouse high fat-diet-associated microbiota and that this effect can be driven by two individual bacterial species fractionated from the mouse high fat-diet-associated microbiota. We findStenotrophomonas maltophiliaincreases the hyperlipidaemic potential of chicken egg yolk to zebrafish larvae independent of direct interaction betweenS. maltophiliaand the zebrafish host. Colonisation by live, or exposure to heat-killed,Enterococcus faecalisaccelerates hyperlipidaemia via host Myd88 signalling. The hyperlipidaemic effect is replicated by exposure to the Gram positive Toll-like receptor agonists peptidoglycan and lipoteichoic acid in a MyD88-dependent manner. In this work, we demonstrate the applicability of zebrafish as a tractable host for the identification of gut microbes that can induce conditional host phenotypes via microbiota transplantation and subsequent challenge with a high fat diet.
Customer loyalty and value anticipation: does perceived competition matter?
Authors: Christian Ishmael Ofoli , Anning-Dorson Thomas , Tackie Nii Nookwei 
Published: April 2021

PurposeDrawing on customer value theory and the demanding nature of today's customers, this paper examines the moderating effects of competition, as perceived by customers, on the nexus between customer value anticipation (CVA), satisfaction and loyalty.Design/methodology/approachUtilizing data from the Ghanaian banking sector, which has been going through some reforms that are changing the banking landscape, the study analyzes data from 587 customers. Respondents were drawn from a cluster of banks within an enclave with different types of customers and epitomize the competitive nature of Ghana's banking sector.FindingsCVA drives customer satisfaction, attitudinal loyalty and behavioral loyalty among bank customers. However, between attitudinal and behavioral loyalty, customers will be more behaviorally loyal to banks that successfully anticipate their needs than they would be in attitude. The relationships between CVA and satisfaction and loyalty are such that the level of competition among sector players does not alter the effect; thus, when a bank is able to anticipate customer value, customers are going to stay loyal to such a bank irrespective of the competitive offers.Originality/valueAlthough the impact CVA has on satisfaction and loyalty is justified in the existing literature, extant research has not systematically examined the influence of external boundary and situational effects on the potency of anticipating customer value in detail. The current study shows the effect of competition on CVA and customer behavioral outcome. The study further concludes that irrespective of competition, banks that are perceived to be high on CVA will have their customers being loyal. This is very important in the development of bank marketing and product innovation strategies.