bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stellar X-rays and magnetic activity in 3D MHD coronal models
Authors: Zhuleku J. , Warnecke J. , Peter H. 
Published: June 2021

Context. Observations suggest a power-law relation between the coronal emission in X-rays, LX, and the total (unsigned) magnetic flux at the stellar surface, Φ. The physics basis for this relation is poorly understood.
Aims. We use three-dimensional (3D) magnetohydrodynamics (MHD) numerical models of the coronae above active regions, that is, strong concentrations of magnetic field, to investigate the LX versus Φ relation and illustrate this relation with an analytical model based on simple well-established scaling relations.
Methods. In the 3D MHD model horizontal (convective) motions near the surface induce currents in the coronal magnetic field that are dissipated and heat the plasma. This self-consistently creates a corona with a temperature of 1 MK. We run a series of models that differ in terms of the (unsigned) magnetic flux at the surface by changing the (peak) magnetic field strength while keeping all other parameters fixed.
Results. In the 3D MHD models we find that the energy input into the corona, characterized by either the Poynting flux or the total volumetric heating, scales roughly quadratically with the unsigned surface flux Φ. This is expected from heating through field-line braiding. Our central result is the nonlinear scaling of the X-ray emission as LX ∝ Φ3.44. This scaling is slightly steeper than found in recent observations that give power-law indices of up to only 2 or 3. Assuming that on a real star, not only the peak magnetic field strength in the active regions changes but also their number (or surface filling factor), our results are consistent with observations.
Conclusions. Our model provides indications of what causes the steep increase in X-ray luminosity by four orders of magnitude from solar-type activity to fast rotating active stars.
Thrombin: A Pivotal Player in Hemostasis and Beyond
Authors: Larsen Julie Brogaard , Hvas Anne-Mette 
Published: June 2021

AbstractThe serine protease thrombin, a naturally derived enzyme, plays a key role in hemostasis by converting fibrinogen to fibrin and activating coagulation factor XIII whereby the fibrin clot is stabilized. Furthermore, thrombin activates platelets through protease-activated receptors on the platelet surface. Conversely, thrombin also exerts anticoagulant effects, enhancing the protein C activity while complexed with thrombomodulin. During recent years, it has become evident that thrombin has significant effects beyond hemostasis, as it contributes also to modulation of the endothelium, promotes inflammation and angiogenesis, and plays a role in tumor progression. Yet, due to the very short half-life and almost immediate inhibition in fluid phase by antithrombin, thrombin itself remains elusive, and only indirect measurement of thrombin generation is possible. This review provides a description of structure and mechanisms of action of thrombin both in physiological and pathological processes. Furthermore, it summarizes laboratory tests that measure in vivo or ex vivo thrombin generation, and presents knowledge on the value of these biomarkers in bleeding disorders, cardiopulmonary bypass surgery, and thromboembolic risk assessment in different patient populations. Finally, this review outlines further perspectives on using thrombin generation biomarkers for research purposes and in clinical practice.
Test structure in some pioneer multichambered Paleozoic foraminifera
Authors: Dubicka Zofia , Gajewska Maria , Kozłowski Wojciech , Mikhalevich Valeria 
Published: June 2021

SignificanceMost calcareous Paleozoic foraminifera have been traditionally assigned to one high-level taxonomic rank, Fusulinata, based on one common feature, a microgranular test texture. Unfortunately, this inorganic trait has not been sufficiently documented. These results show that Paleozoic foraminifera are taxonomically diverse as observed in recent foraminifera with varied test characteristics, suggesting that different biomineralization mechanisms occurred in Paleozoic foraminifera.
Environmental drivers of annual population fluctuations in a trans-Saharan insect migrant
Authors: Hu Gao , Stefanescu Constanti , Oliver Tom H. , Roy David B. , Brereton Tom , Van Swaay Chris , Reynolds Don R. , Chapman Jason W. 
Published: June 2021

SignificanceThe painted lady butterfly is an annual migrant to northern regions, but the size of the immigration varies by more than 100-fold in successive years. Unlike the monarch, the painted lady breeds year round, and it has long been suspected that plant-growing conditions in winter-breeding locations drive this high annual variability. However, the regions where caterpillars develop over winter remained unclear. Here, we show for the European summer population that winter plant greenness in the savanna of sub-Saharan Africa is the key driver of the size of the spring immigration. Our results show that painted ladies regularly cross the Sahara Desert and elucidate the climatic drivers of the annual population dynamics.
Combination inhibition of triple-negative breast cancer cell growth with CD36 siRNA-loaded DNA nanoprism and genistein
Authors: Wang Beinuo , Yan Ni , Wu Di , Dou Yin , Liu Zhenyu , Hu Xiaojuan , Chen Cancan 
Published: June 2021

Abstract
Currently, a single treatment is less effective for triple-negative breast cancer (TNBC) therapy. Additionally, there are some limitations to the use of siRNA alone as a new method to treat breast cancer, such as its effective delivery into cells. In this study, we proposed a strategy that combines a siRNA-loaded DNA nanostructure and genistein for TNBC therapy. Both CD36 siRNA-loaded self-assembled DNA nanoprisms (NP-siCD36) and genistein knocked down CD36, resulting in enhanced anticancer efficacy through phosphorylation of the p38 MAPK pathway. In vitro studies showed that combination therapy could effectively enhance cell apoptosis and reduce cell proliferation, achieving an antitumor effect in TNBC cells. The current study suggests that NP-siCD36 combined with genistein might be a promising strategy for breast cancer and treatment.
Huntington’s disease: nearly four decades of human molecular genetics
Authors: Gusella James F , Lee Jong-Min , MacDonald Marcy E 
Published: June 2021

AbstractHuntington’s disease (HD) is a devastating neurogenetic disorder whose familial nature and progressive course were first described in the 19th century but for which no disease-modifying treatment is yet available. Through the active participation of HD families, this disorder has acted as a flagship for the application of human molecular genetic strategies to identify disease genes, understand pathogenesis and identify rational targets for development of therapies.
Citrullination Inhibits SERPIN Activity
Authors: Thompson Paul R. 
Published: June 2021

The Protein Arginine Deiminases (PADs) hydrolyze arginine residues to form citrulline. This post‐translational modification, termed citrullination, is upregulated in numerous cancers and autoimmune disorders including Rheumatoid Arthritis (RA), lupus, and Alzheimer's disease. While these enzymes are important regulators of gene transcription, the full spectrum of biological activities is relatively underexplored. Recently, the Thompson group reported the development of a suite of probes to detect and isolate citrullinated proteins. These probes are premised on the chemo‐selective reaction of citrulline with phenylglyoxals under acidic conditions. Herein, I will discuss our development of these probes and their use to uncover the RA citrullinome. Specifically, these probes were used to identify the citrullinated proteins present in RA serum, RA synovial fluid, and RA synovial tissue. The proteins identified from these analyses include >150 proteins that were previously not known to be citrullinated. Moreover, these proteins include numerous metabolic enzymes and serine protease inhibitors (SERPINs). Citrullination inactivates the activity of a subset of these proteins, including nicotinamide N‐methyltransferase and numerous P1‐arginine containing SERPINs (e.g., C1 inhibitor, anti‐thrombin, and anti‐plasmin). The ability to inhibit SERPIN activity is highly significant because it suggests PAD release within the RA synovium leads to SERPIN citrullination with a consequent increase in protease activity, thereby activating multiple processes including tissue remodeling, altered blood coagulation, and the activation of the complement cascade.Support or Funding InformationThis work was supported in part by NIH grant GM109767 to P.R.T.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Loss of mitochondrial phosphate carrier in skeletal muscle: dissociation of muscle dysfunction from lower ADP phosphorylating potential
Authors: Seifert Erin L. , Anderson‐Pullinger Lauren , Sharpadskaya Yana 
Published: June 2021

Many mutations in the mitochondrial genome and in nuclear genes that encode mitochondrial proteins hamper oxidative phosphorylation (oxphos) and lead to tissue dysfunction. Yet, whether an energy deficit is necessarily a direct cause of tissue dysfunction is not clear. We addressed this question in mice in which the mitochondrial phosphate carrier, PiC, was depleted from skeletal muscle (skm) by tamoxifen‐induced excision of nuclear gene SLC25A3 encoding PiC (Cre+). Three weeks after tamoxifen injections, PiC protein in skm was <5% of levels found in control (Ctrl) wild‐type mice (tamoxifen‐treated). Oxphos, measured in mitochondria isolated from skm, was greatly suppressed to <2%, 35% or 50% of Ctrl, depending on substrate, with essentially no oxphos when succinate (+rotenone) was supplied and the highest residual oxphos when fatty acid substrate and malate were supplied; the residual oxphos may be driven by alternate Pi uptake on the dicarboxylate carrier. Residual oxphos was similar at 3 and 9 wks of PiC depletion, suggesting that the oxphos defect was stable for this interval. Furthermore, subunits of the oxphos machinery were robustly upregulated (50–70% rise) at both time points. Nonetheless, treadmill running capacity worsened during this time. Time‐to‐exhaustion was ~50 mins in Cre+ mice with PiC absent for 3 wks, but ~25 mins when PiC was absent for 9 wks, whereas Ctrl mice ran for the scheduled 80 mins. Thus, deteriorating treadmill running in Cre+ mice seems unrelated to suppressed oxphos per se. Stress signaling via transcription factor ATF4 as well as elevated mTORC1 signaling have been associated with oxphos defects caused by mitochondrial DNA depletion in cell models and in mouse skm. These models have also suggested a causal relationship between persistent mTORC1 activation/stress signaling and cell dysfunction. Yet we found little evidence for stress signaling via ATF4 (or ATF2, ATF3, or ATF5) after 3 or 9 wks of PiC depletion, and evidence for only mild mTORC1 activation after 9 wks of PiC loss. Overall, these observations suggest that skm dysfunction is not related to an oxphos deficit in a simple way. Rather, the oxphos deficit may drive adaptive mechanisms that either become exhausted or turn maladaptive when ongoing over a longer term, or trigger additional processes that are deleterious for muscle function. Furthermore, the model presented here suggests that a mechanism other than stress signaling through ATFs is responsible for tissue dysfunction in the context of a severe oxphos defect.Support or Funding InformationFunding: R01 GM123771 to ELSThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Glycocalyx engineering with tunable synthetic glycopolypeptides
Authors: Kramer Jessica 
Published: June 2021

All cells are coated with an array of glycoproteins, glycolipids, and polysaccharides that collectively form the glycocalyx. In bulk, the glycocalyx functions to hydrate, lubricate, and shield the cell from injury and infection. The glycocalyx also has biochemical functions and plays roles in essential process from adhesion and fertilization to infection and immunity. Glycoproteins are challenging to study at the molecular levels due to complex and heterogeneous glycosylation patterns that dynamically vary. These patterns are metabolically controlled and resist manipulation by traditional biochemical and genetic methods. Synthetic glycopolymers have emerged as useful tools to probe glycan based biological interactions. Glycosylated polypeptides are particularly attractive polymers since they can display glycans in their native form, take on natural secondary structures that are important for function, and are biodegradable.We have developed a chemical route to synthesize glycopolypeptides via polymerization of amino acid N‐carboxyanhydrides. These glycopolypeptide are readily tunable in terms of molecular weight, composition, and glycan density and pattern. Our glycopolypeptides are also dual end‐functionalized with chemical handles that allow for conjugation to probes and biological targets. We have focused on preparing synthetic versions of cell‐surface human mucins and pathogenic glycopolypeptides associated with fungi and bacteria. Our results indicate that glycan pattern and protein‐linkage type have profound effects on conformation. We have also devised methods to engineer the glycocalyx by display these synthetic glycopolypeptides on the cell‐surface to probe and modulate biological outcomes. Overall, these are exciting new materials to systematically examine the role of glycosylation in protein conformation and bioactivity.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Predictors of success on the MCAT for post‐baccalaureate pre‐medicine students
Authors: Dobrydneva Yuliya , Schwartz Lisa 
Published: June 2021

Students who aspire to enter medical school have to take the MCAT (Medical College Admission Test). In 2015, the MCAT was redesigned, covering a new set of foundational concepts. Also in 2015, a 12‐month post‐baccalaureate pre‐medicine certificate program at the GWU School of Medicine and Health Sciences was launched to address the changes to the new MCAT. The program prepares students for medical school coursework, such as biochemistry, histology, physiology and pharmacology. The objectives of post‐bac courses are closely aligned with MCAT objectives. The GW post‐bac pre‐med program is intended for career changers who typically majored in the social sciences or humanities, and thus have little or no science background (“scientifically naïve”). Therefore, in our admissions process, we need to identify predictors of future success in heavily scientific courses for students who have minimal prior exposure to sciences. We have analyzed data of the first and second cohorts of students to determine what predictors appeared to be positively or negatively associated with MCAT performance. Variables include past standardizes test scores (ACT, SAT), undergraduate GPA, performance in post‐bac courses (physics, chemistry, biology, organic chemistry and biochemistry) and demographics data correlated with MCAT overall and sub‐sections performance. The analysis will be expanded in the future to include non‐parametric statistics measures to more precisely define predictors of success.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Regulation of oxidative liver injury by the probiotic Lactobacillus rhamnosus GG
Authors: Saeedi Bejan Jon , Robinson Brian , Owens Joshua , Liu Ken , Luo Liping , Darby Trevor , Jones Dean , Jones Rheinallt , Neish Andrew 
Published: June 2021

The gut microbiome is composed of a diverse and dynamic community of microorganisms colonizing the intestinal lumen and mucosa. Using germ‐free model organisms, recent research has established the importance of these communities in influencing key metabolic, endocrine, and immunologic processes in the host. The majority of this research has focused on its effects on the intestine, the tissue with which the microbiome is in the most intimate contact. Recent studies, however, have revealed that these physiologic effects are significantly more far‐reaching, with roles in hepatic, cardiovascular, and even neurological health. As the primary metabolic and detoxification hub, the liver is a critical checkpoint between the digestive functions of the gut and the rest of the body. Therefore, it is likely that liver health and homeostasis may be affected through alterations in the gut microbiota. This possibility presents an opportunity for therapeutic intervention in hepatic disease by modulating the bacterial communities in the lumen of the intestine. This can be accomplished through the oral administration of probiotics, a group of beneficial bacteria that can influence the health of the host. Previous work by our group demonstrated a key role for the widely‐studied probiotic Lactobacillus rhamnosus GG (LGG) in protection against oxidative liver injury to the intestinal epithelium. It accomplishes this through activation of Nrf2, a basic leucine zipper transcription factor and master regulator of cellular antioxidant and xenobiotic responses. Here, we extend these findings by investigating the ability of LGG to augment this pathway in the liver. We performed daily administration of LGG by oral gavage to conventional mice. In these mice we observe increased hepatic Nrf2 activity relative to vehicle control as determined by increased Nrf2 stabilization, nuclear localization, and target transcription. Induction of the Nrf2 pathway has been shown to protect the liver from xenobiotic and oxidative stress. Indeed, LGG fed animals were protected against a challenge with acetaminophen, a potent inducer of hepatic oxidative stress. These data provide important mechanistic insights into the role of the microbiome and probiotics in regulating systemic host homeostasis.Support or Funding InformationNIH RO1AI64462This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Biological Scaffolds that Mimic Function and Structure of Basement Membranes
Authors: Ogle Roy Clinton 
Published: June 2021

Biological scaffolds mimicking basement membranes are valuable tools to study biological processes like cellular differentiation and phenotypic maintenance in vitro. Such artificial basement membranes also hold great promise for engineering tissues and organs and promoting regenerative processes. Basement membrane‐like sheets were fabricated by electrospinning of nanofibers with fiber size, geometry, and the porosity of authentic basement membranes. Nanofibers were electrospun from pure murine laminin 111, murine reconstituted basement membrane (containing laminin, type IV collagen and perlecan) and human cardiac muscle basement membrane enriched in laminins 411 and 511). These proteins and complex extracts were blended with polymers such as polycaprolactone to create hybrid nanofibers with mechanical properties determined by the degradable polymer and biological properties derived from laminin. Importantly, the protein and hybrid nanofibers, unlike others reported, required no chemical crosslinking, which often disrupts biological activity, to maintain structure. These biological scaffolds were compared to films of pure laminin 111 and the mouse and human basement membrane extracts for their ability to maintain the pluripotent state of induced pluripotent stem cells and embryonic stem cells in defined media. All cell lines examined attached more rapidly and to a greater extent on the nanofibrous basement membrane scaffolds, and antibody and enzymatic staining for a variety of markers of pluripotency showed they resisted the tendency to differentiate in vitro for weeks when maintained on these substrates. Next we examined the ability of the scaffolds to promote attachment and differentiation of mesenchymal stem and PC12 cells to a neuron‐like phenotype. The basement membrane like scaffolds promoted neuronal precursor attachment and differentiation to neuron‐like cells in serum free media without the addition of cAMP or nerve growth factor, suggesting a possible biomimetic effect on differentiation from the scaffold. Together these initial studies illustrate methods to create substrates that mimic native basement membranes in structure and function‐‐these scaffolds may take our in vitro models a bit closer to the in vivo situation.Support or Funding InformationResearch generously supported by: Virginia Biosciences Health Research Corporation Grant, Nanofabrication of Tissue ScaffoldsThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Porcine Lung in Biomedical Research
Authors: Meyerholz David 
Published: June 2021

In biomedical research, animal models are frequently necessary for the study of human diseases. Choosing an animal model requires knowledge of several factors that may influence the relevance of the model compared to humans. In particular, anatomy is a relevant feature when choosing animal models. The lungs are essential for survival, but human lungs are not identical to animal lungs and these variations in anatomy can have significance for the study of diseases. In the lungs, large airways are divided into trachea and bronchi that extend into small airways (i.e. bronchioles) and then the respiratory acini (composed of respiratory bronchioles, alveolar ducts and alveoli). The pig lung is similar in overall size and development to humans. In humans, the tracheal cartilage is “C”‐shaped with the open side of the “C” along the posterior border, but in pigs the edges of the cartilage are longer and extend in overlapping fashion along the posterior (or “dorsal”) border. In both species, bronchi begin at the extrapulmonary tracheal bifurcation and extend into the lungs; however, pig bronchi may extend deeper into the lungs (i.e. to approach the pleural border) than humans, thus causing bronchioles of pigs to be less extensive than in humans. Additionally, human bronchi exhibit dichotomous branching (relatively synchronous) whereas pig bronchi exhibit monopodial branching (asynchronous with one main airway and smaller off‐branches). The respiratory acinus has similar organization between species, but humans have a slightly more prominent respiratory bronchiole. How can anatomical differences in lung affect disease? As one example, cystic fibrosis (CF) is a condition caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Shortly after the discovery of the gene in 1989, CFTR‐deficient mice were generated, but they failed to develop spontaneous CF lung disease. Possible factors for a failure of mice to develop disease included anatomic differences such as lack of intrapulmonary bronchi (i.e. with airway glands and cartilage) and intrapulmonary airways that were equivalent to bronchioles in humans. In 2008, CF pigs were generated and these developed spontaneous CF lung disease like humans. To address the phenotypic differences between these three species, airways were studied and ATP12A, an apical transporter prominent in large but not small airways, was identified as a possible reason for CF disease pigs and human lungs. The presence of ATP12A in bronchi is important for acidification of airways surface liquid in CF and these acidic secretions promote sticky mucus, reduced efficacy of host defenses, and defective mucociliary clearance leading to recurrent/chronic infection and inflammation. In summary, anatomic factors should be considered when developing and trouble‐shooting animal models of human disease.Support or Funding InformationNIH and CFF.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.