bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural Stem/Progenitor Cells of the Spinal Cord are Activated in Response to Tail Loss in the Leopard Gecko
Authors: Gilbert Emily , Vickaryous Matthew 
Published: June 2021

As for many lizards, the leopard gecko (Eublepharis macularius) is able to self‐detach its tail as an anti‐predation strategy and subsequently regenerate a replacement. The replacement tail includes a regenerated spinal cord. We hypothesize that endogenous neural stem progenitor cells (NSPCs) are present in the original spinal cord and that these cells are activated during regeneration. As many stem cells are slow cycling, we used a Bromodeoxyuridine (BrdU) pulse‐chase experiment to identify label‐retaining populations in the original spinal cord. We also conducted a spatiotemporal characterization of spinal cord cells before and during regeneration using a panel of common NSPC markers (including Sox2, Sox9, Vimentin, βIII‐Tubulin and Musashi‐1, and the proliferation marker PCNA). BrdU retaining cells were still present after a 20‐week chase. Prior to injury, expression of NSPC markers is limited, but co‐localization of BrdU and Sox2 in ependymal cells was observed. Following tail loss, ependymal cells in the original stump of the tail become highly proliferative and express our panel of NSPC markers. Outgrowth of the new tail is matched by proliferating, NSPC marker‐positive ependymal cells. These cells appear to contribute to regenerating spinal cord. We conclude that ependymal cells are a likely source of endogenous NSPCs in the gecko and that they are activated following tail loss.NSERC Grant: 400358
The Role of the Eda Pathway in the Morphogenesis of Molar Roots
Authors: Star Haza , Tucker Abigail 
Published: June 2021

The role of the Eda gene during the formation of ectodermal appendages such as nail, hair, teeth, and sweat glands have been unveiled through many studies. Mutation in the Eda pathway (Eda, Edar, Edaradd) results in Hypohydrotic Ectodermal Dysplasia (HED) with patients showing hypodontia and abnormally shaped teeth. The role of the Eda pathway in tooth crown development has been widely studied using the mouse as a model but the role of the Eda pathway during root formation is not well known. I have used computerised tomography (CT) and histological sections of Eda ‐/‐ (tabby) and Edar ‐/‐ (downless) mice to investigate possible root defects in these mice.My analysis shows a clear variation in the size, shape, and number of roots in mutants (tabby and downless) compared to wild type littermates. In particular the mutant teeth showed late or no bifurcation of roots (Taurodontism), indicating disruption in the development of the cells that create the roots (Hertwig epithelial root sheath, HERS). In situ analysis also indicated that Shh expression was reduced in these cells. The results show that the Eda pathway has a role in root morphogenesis and we are now further investigating the mechanisms by which loss of the Eda pathway affects root formation.
Skeletal kinematics reveal the complex interactions of degrees of freedom at joints
Authors: Kambic Robert 
Published: June 2021

Measuring range of motion (ROM) is a common technique for investigating the relationship between morphology and function at joints in both extant and extinct taxa. ROM studies often present results as tables or graphs of minimum and maximum joint angles; however, joint motion is a complex three‐dimensional interaction among multiple degrees of freedom. Using X‐ray Reconstruction of Moving Morphology, I present results from experiments that directly measure three rotational degree of freedom kinematics in birds. Every pose achieved at a joint is plotted in angle‐angle‐angle space for the three possible degrees of freedom, producing a ROM envelope. The results demonstrate that degrees of freedom interact in complex ways that cannot be summarized as mere minima and maxima. Two and three degree of freedom joints produce irregular two‐dimensional surfaces and three‐dimensional volumes. Plotting in vivo poses within these ROM envelopes demonstrates that the ROM of certain degrees of freedom may be overestimated, but that living animals were willing to push joints farther than the researchers in other cases. These results demonstrate that soft tissues and bone interact in complex ways to guide joint motion.The NSF, the W.M. Keck Foundation, and the Bushnell Research and Education Fund supported this work.
Prebiotics Impact Fecal Microbiota and Gut Physiology in Diet‐Induced Obese Mice
Authors: Liu Tzu‐Wen , Holscher Hannah , Cephas Kimberly , Kerr Katherine , Mangian Heather , Tappenden Kelly , Swanson Kelly 
Published: June 2021

Obesity is associated with compromised intestinal barrier function and shifts in microbiota that may contribute to inflammation. Previous research suggests benefits of supplemental fiber, but the impacts of fermentable vs. non‐fermentable fibers are not well understood.OBJECTIVETo determine the impact of cellulose vs. fructan (short‐chain fructooligosaccharides [scFOS] or inulin) supplementation on fecal microbiota and gut physiology in obese mice.METHODS18‐wk old C57BL/6J mice (n=6/group) were fed high‐fat diets (45% kcal fat) containing 5% cellulose, 10% cellulose, 10% scFOS or 10% inulin for 4‐wk. Cecum and distal colon were collected to assess barrier function, histomorphology and gene expression. Fecal DNA was extracted, followed by 16S rRNA amplicon Illumina MiSeq sequencing and analysis with QIIME 1.8.0.RESULTSBoth fructans increased (p<0.05) intestinal transmural resistance and crypt depth but reduced (p<0.05) mRNA abundance of ZO‐1 and occludin. Principal coordinates analysis (PCoA) of weighted and unweighted UniFrac distances of fecal microbiota revealed a sharp separation (p<0.05) between fructan and cellulose groups. Alpha diversity measures revealed lower (p<0.05) species richness with fructan supplementation. Fructans reduced (p<0.05) the relative abundance of Firmicutes and increased (p<0.05) Actinobacteria and Verrucomicrobia (Akkermansia).CONCLUSIONFructan supplementation may modulate gut microbiota and physiological responses via multiple mechanisms.
A Plasma Proteome Associated with Inflammation in Nepalese School‐aged Children
Authors: Lee Sun Eun , West Keith , Cole Robert , Schulze Kerry , Yager James , Groopman John , Christian Parul 
Published: June 2021

Micronutrient status may be influenced by inflammation, however, it is typically characterized by only C‐reactive protein (CRP) or alpha‐1‐acid glycoprotein (AGP) in nutrition studies. We applied quantitative proteomics to explore plasma proteins that co‐vary with inflammation, reflected by AGP in 500 children 6‐8 yr of age in rural Nepal where elevated AGP was common. Among 982 proteins, 41 and 58 proteins were positively and negatively associated with AGP, respectively, passing a false discovery rate threshold of 0.001%. Positively associated proteins included major positive acute phase proteins including CRP, complement components, protease inhibitors, transport proteins with anti‐oxidative activity, and intracellular signaling molecules. Negatively associated proteins showed a distinct pattern in the abundance profile, characterized by tissue origin: proteins of hepatic origin included plasma transporters for lipids, micronutrients (vitamin A and calcium), growth factors and sex hormones, while extra‐hepatic proteins included structural components of extracellular matrix (ECM) or regulators of ECM metabolism. Our findings reveal a vast number of plasma proteins associated with AGP that reflect active homeostasis of the host defense systems, metabolism of nutrients and other biomolecules, and tissue repair processes. Using population data, we provide evidence of a “plasma inflammasome”, reflecting proteomic dynamics of inflammation, as an extended list of potential candidates for inflammation biomarkers.This study was funded by Bill and Melinda Gates Foundation (OPP5241 and GH614).
Prospective Study of Vitamin B2 Intake and Colorectal Cancer
Authors: Cho Eunyoung , Yoon Yeongsook , Jung Seungyoun , Zhang Xuehong , Giovannucci Edward 
Published: June 2021

BackgroundDespite the involvement of vitamin B2 to regulate the one‐carbon metabolism and the immune system, only few prospective cohort studies have examined the association between vitamin B2 intake and colorectal cancer (CRC) reporting inconsistent results.ObjectiveTo examine the association between vitamin B2 intake and risk of CRC and to evaluate if the association varies by alcohol consumption and folate intake.DesignAmong 105,628 women and 44,527 men followed up to 2010 in the Nurses' Health Study and Health Professionals Follow‐Up Study, 3,285 cases of incident CRC were identified (2,359 women and 926 men). Vitamin B2 intake was measured by a validated food frequency questionnaire administered every 4 years during follow‐up. To estimate the association between vitamin B2 intake and CRC, Cox proportional hazard models were used to calculate the relative risks (RRs) and its 95% confidence intervals (CIs).ResultsVitamin B2 intake was associated with a borderline reduced risk of CRC among women (Ptrend = 0.03), but not among men (>Ptrend = 0.73). The multivariate RRs (95% CI) for individuals in the highest quintile of total vitamin B2 intake (from food and supplements) compared to those in the lowest quintile were 0.89 (0.77‐1.03) in women and 0.98 (0.77‐1.23) in men. The associations were similar when stratified by alcohol consumption and folate intake.ConclusionsOur results suggest no strong association between high vitamin B2 intake and the risk of CRC.Source of research support : This work was supported by research grants CA136950, CA87969, and CA167552 from the National Institutes of Health.
Ambient fine particulate matter induces endothelial progenitor cells apoptosis via reactive oxygen species formation
Authors: Cui Yuqi , Xie Xiaoyun , Jia Fengpeng , He Jianfeng , Li Zhihong , Fu Minghuan , Hao Hong , Liu Ying , Liu Jason , Cowan Peter , Zhu Hua , Sun Qinghua , Liu Zhenguo 
Published: June 2021

Background/AimsBone marrow (BM)‐derived endothelial progenitor cells (EPCs) play a critical role in the angiogenesis. Some environmental insults, like fine particulate matter (PM) exposure, significantly inhibit EPCs‐mediated functions. However, the mechanisms remain largely unknown. The present research was to study the detrimental effects of PMon EPCs and explore the potential mechanisms.MethodsPMwas intranasal‐distilled into male C57BL/6 mice for one month. Flow cytometry was used to measure the total number, apoptosis of circulating EPCs and intracellular reactive oxygen species (ROS) formation. Serum TNF‐ α and IL‐1β were measured using ELISA. To determine the role of PM‐induced ROS in EPC apoptosis, PMwas co‐administrated with the antioxidant N‐acetylcysteine (NAC) in wild type mice or used in a triple transgenic mouse line (TG) with overexpression of antioxidant enzyme network (AON) composed of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase (Gpx‐1) with decreased in vivo ROS production.ResultsPM treatment significantly decreased circulating EPC population, promoted apoptosis of EPCs in association with increased ROS production and serum TNF‐α and IL‐1β levels, which could be effectively reversed by either NAC treatment or overexpression of AON.ConclusionPM exposure significantly decreased circulating EPCs population due to increased apoptosis via ROS formation in mice.Funding sources: NIH R01 HL094650; AHA 12SDG12070174
Evaluating anti‐β‐Catenin monoclonal antibodies for cancer diagnosis and prognosis
Authors: Lu Hsiangmin Emily , Fu Wei , Yuan Kehu , Chu Boyang , Wang Guangli , Shu Youmin , He Weiwu , Ma Donghui 
Published: June 2021

Colorectal cancer is one of the most common cancers and ranks second in mortality in the US. Wnt/β‐Catenin signaling pathway plays an important role in colorectal cancer, and the mutation events have been studied the most for colorectal carcinogenesis. However, other studies have shown the nuclear translocation of β‐Catenin could be an additional factor for clinical diagnosis of colorectal cancer. Therefore, it is essential to develop the monoclonal antibody with the highest sensitivity and specificity. Even though there are many monoclonal antibodies being used for β‐Catenin studies, they have not been carefully examined for potential cross‐reactivity which could cause false diagnosis.To develop the most suitable monoclonal antibody for β‐Catenin studies, we used different immunoassays to validate the specificity and sensitivity of the commercially available antibodies. By the high density protein microarray chip technology and other assays, we identified that β‐Catenin UltraMAB antibody can be used for different applications in basic research. Furthermore, we used immunohistochemistry with tissues from colorectal cancer patients and showed that β‐CateninUltraMAB antibody is a great tool for potential cancer diagnosis and prognosis.
Functional Role of MicroRNA‐200 Family in Human Gall Bladder Cancer Stem Cells
Authors: Meng Fanyin , Francis Heather , Han Yuyan , Glaser Shannon , Alpini Gianfranco 
Published: June 2021

BACKGROUND & AIMSMicroRNAs (miRNAs) are highly conserved 19‐25 nucleotide noncoding small RNAs which are primarily involved in gene silencing. Our aim was to characterize the functional roles of epigenetic regulated microRNAs in human gall bladder cancer stem cells.METHODSmiRNA expression in human gall bladder cancer tissues, human gall bladder cancer stem cells (GB‐CSCs), Mz‐ChA‐1 gall bladder cancer cells and H69 non‐malignant cholangiocytes was assessed using a hybridization based microarray and was further evaluated by Taqman real‐time PCR analysis. Promoter methylation, matrix metalloproteinase (MMP) 1, 2, 3 and 9 mRNA expression was quantitated by real‐time PCR analysis.RESULTSWe identified miR‐200 family including miR‐200a, miR‐200b and miR‐200c that are differentially expressed in doxorubicin‐enriched cell fractions in a mouse xenograft tumor model of gall bladder cancer. Expression of miR‐200 family microRNAs was substantially enhanced concomitant with GBCs differentiation and loss of self‐renewal. Methylation‐specific PCR detected that miR‐200b and miR‐200c promoter was hypermethylated in GB‐CSCs, GBCs as well as Mz‐ChA‐1 cells. Cell migration and invasion were significantly decreased by miR‐200 precursor introduction in GB‐CSCs and Mz‐ChA‐1 cells. Bioinformatics and dual‐luciferase reporter assays identified ZEB1 and ZEB2 as the direct targets of miR‐200 family.CONCLUSIONOur results define a novel epigenetic regulatory mechanism of specific microRNA group and suggesting that miR‐200 cluster may be the molecular targets for eradication of human gall bladder cancer.
T Cells Control Cardiac Remodeling in Pressure Overload Induced Heart Failure
Authors: Nevers Tania , Salvador Ane , Grodecki‐Pena Anna , Knapp Andrew , Velazquez Francisco , Aronovitz Mark , Kershaw Tanya , Blanton Robert , Kapur Navin , Karas Richard , Alcaide Pilar 
Published: June 2021

Patients with heart failure (HF) have increased activation of pro‐inflammatory cytokines in their circulation, and the mechanisms associated with this increase are still unknown. Recent studies have suggested T cells as an important cellular source for this observed systemic inflammation and immune activation in chronic HF. Thus, we hypothesize that T cells are major players influencing cardiac remodeling and contributing to the pathogenesis of pressure overload induced HF. We observe by immunohistochemistry analysis that T cells infiltrated the left ventricle (LV) of the heart in patients with end stage HF compared with subjects without HF. Additionally, systemic T cells from patients with advanced HF adhered to activated human umbilical vein endothelial cells (HUVECs) in higher numbers than T cells from healthy donors under flow conditions. To study this phenomenon further, we utilized the mouse model of thoracic aortic constriction (TAC) in wild type (WT) and T cell deficient (TCRα‐/‐) mice to mimic pressure overload induced HF. We found that in WT mice, T cells can also infiltrate into the left ventricle (LV) and this was associated with worsening cardiac function. Conversely, TCRα‐/‐ mice subjected to TAC had improved cardiac functions as determined by echocardiographic and hemodynamic evaluations, reduced fibrosis and LV hypertrophy, and improved survival compared to WT TAC mice. Thus, our studies indicate that T cell mediated immune responses and their recruitment into the heartinfluence cardiac remodeling and inhibiting T cell activation may be a potential therapeutic strategy to improve the deficits of the failing heart.
Inhibitors of the Renin‐Angiotensin System (RAS) Completely Prevents Cardiac Hypertrophy (CH) Induced by Ischemic Renal Injury (IRI) via Angiotensin II (AngII)/Toll‐Like Receptors (TLR) Cross‐Talk
Authors: Abrahão Mariana , Monnerat‐Cahli Gustavo , Medei Emiliano , Carneiro‐Ramos Marcela 
Published: June 2021

ObjectivesThe cardio‐renal syndrome comprises a set of pathophysiological kidney‐heart interactions. Renal injury promotes release of inflammatory cytokines (CTK), which may act through cardiac TLR and lead to CH, as well as AngII. This study aims to investigate a possible interaction between TLR and RAS in CH model induced by IRI.MethodsC57BL/6 male mice (n=84) treated with Losartan (Los‐10 mg/kg) or Enalapril (Ena‐40 mg/kg) were subjected to surgical occlusion of left renal pedicle and kept under observation for 20d. IRI, CH and systolic blood pressure (SBP) were assessed by morphologic, molecular and functional parameters, as well as tail‐cuff plethysmography and electrocardiography (ECG) before and after surgery. Serum/cardiac RAS components, TLR2/TLR4 and inflammatory CTK were evaluated by Real‐Time PCR, protein expression and ELISA.ResultsThe successfully‐performed IRI induced an enhancement of serum IL‐6, TNF‐a and IFN‐y (p<0.001) and did not promote SBP alteration. CH was observed after 12d of reperfusion, when cardiac AT1, ACE2, TLR2/TLR4 levels were increased (p<0.001). Los/Ena prevented CH (p<0.001) without changing SBP and modulated serum AngII and CTK levels (p<0.05). Also, ECG showed an improvement in cardiac function.ConclusionThe presented data shows that RAS inhibition is able to completely prevent CH via regulation of cardiac TLR and serum AngII/CTK levels, suggesting the existence of a key cross‐talk between TLR and RAS in CH induced by IRI. Financial Support: FAPESP; CNPq.
Structural Mechanisms of PI3K and PTEN Regulation
Authors: Williams Roger , Masson G. , Vadas O. , Burke J. , Perisic O. 
Published: June 2021

The products of the phosphoinositide 3‐kianses (PI3Ks) have essential roles in intracellular signalling and sorting. Using X‐ray crystallography and hydrogen/deuterium exchange mass spectrometry (HDX‐MS) have enabled us to understand mechanisms whereby the PI3Ks and the lipid phosphatase PTEN are activated. HDX‐MS has allowed us characterise protein/protein and protein/membrane interactions for states inaccessible to X‐ray crystallography, and it has provided information about the dynamics of structures.Two sites in the intrinsically disordered tail of PTEN have the ability to to switch its substrate specificity from lipid membranes to soluble substrates. The structural mechanism that regulates the enzyme involves the interaction of both the C2 domain and the lipid phosphatase domain with the C‐terminal tail in phosphorylation‐dependent manner.The p110γ/p101 heterodimeric PI3K is activated downstream of GPCRs by association with Gβγ heterodimers, and HDX‐MS has shown that the p110 helical domain is central to this and other PI3K regulatory influences. The p101 regulatory subunit protects the helical domain, while lipid membrane association exposes it. Membrane binding enables the p110γ/p101 heterodimer to engage Gβγ heterodimers on membranes, using both p110 and p101 subunits.The combination of these methods has enabled us to explore regulation of the broad family of enzymes related to PI3Ks.
Constitutive and Antigen‐Induced Secretion of Cytokines by Peripheral Blood Mononuclear Cells of Tuberculosis Patients
Authors: Mustafa AbuSalim 
Published: June 2021

Cytokines play a major role in protection against and pathogenesis of tuberculosis. Generally, T‐helper (Th)1 and pro‐inflammatory cytokines are considered protective, and anti‐inflammatory and Th2 cytokines are responsible for pathogenesis of tuberculosis. In order to study the release of various cytokines in response to a variety of antigenic stimuli, the in vitro secretion of cytokines was assessed using peripheral blood mononuclear cells from tuberculosis patients (diabetic and non‐diabetic) and healthy subjects in response to various mycobacterial antigens, including whole cells, culture filtrate, cell walls and pools of synthetic peptides corresponding to M. tuberculosis‐specific genomic regions, i.e. the regions of differences (RDs). The results showed that the concentrations of antigen‐induced Th2 cytokines were low/undetected and the pro‐inflammatory cytokines were non‐discriminatory. However, with regard to the Th1 and anti‐inflammatory cytokines, the antigens could be divided into two groups; the first group showed Th1‐bias (culture filtrate, RD1, RD5, RD7, RD9, RD10 and RD15), and the second group had anti‐inflammatory‐bias (whole bacilli and cell walls of M. tuberculosis, RD12 and RD13). Interestingly, the RD1 peptide pool induced the strongest Th1‐bias, and the addition of RD12 and RD13 peptides to the cultures suppressed the secretion of RD1‐induced Th1‐cytokines. Furthermore, when data were compared between diabetic and non‐diabetic TB patients, there was a shift towards pathologic (Th2/anti‐inflammatory) cytokines in diabetic TB patients, which may explain, at least in part, a faster deterioration in clinical condition of diabetic TB patients.Supported by Kuwait University Research Sector grants MI01/10 and SRUL02/13.
Alcohol Exacerbates Liver Injury and Fibrosis in Mice With Liver‐Specific Deficiency of Augmenter of Liver Regeneration
Authors: Kumar Sudhir , Dangi Anil , Gandhi Chandrashekhar 
Published: June 2021

Augmenter of liver regeneration (ALR) protein is expressed predominantly by hepatocytes in the liver, and is essential for their mitochondrial function. Liver‐specific ALR knockout (ALR‐L‐KO) mice develop accelerated steatohepatitis. Our aim was to investigate alcohol‐induced pathology in KO mice. WT or KO mice were fed isocaloric or 4% ethanol diet for 4 weeks. Ethanol‐fed KO mice showed retarded growth, excessive liver injury, increased serum ALT, but lower hepatic triglycerides as compared with WT ethanol‐fed mice. Whereas ethanol increased expressions of acetyl‐CoA carboxylase, fatty acid synthase and sterol regulatory element‐binding transcription factor 1 in WT mice, they were dramatically reduced in KO mice. Additionally, while expressions of alcohol dehydrogenase 1, acetaldehyde dehydrogenase 1 and Cyp2E1 increased in ethanol‐fed WT mice, they decreased in KO mice. These pathologies in KO mice were accompanied by increased oxidative stress, TNFα and TGFβ, and excessive fibrosis; WT mice increased TNFα but did not develop fibrosis. Hepatic ALR was also lower in humans with advanced alcoholic liver disease (ALD) and frequency of several single nucleotide polymorphisms was increased in ALD subjects compared to normal population. Our findings indicate that ALR protein deficiency causes exacerbation of alcohol‐induced liver injury and excessive fibrosis, and abnormality in ALR protein or deficiency may be an important mechanism of advanced ALD in humans, which occurs in about 30% of the populationGrant support: Supported by a VA Merit Review Award (1IO1BX001174) and NIH (PO1AIO81678 and R21AA020846).