Digital Commons Network^™

The Association Of Plasma Biomarkers With Computed Tomography-Assessed Emphysema Phenotypes, Brendan J. Carolan, Grant Hughes, Jarrett Morrow, Craig P. Hersh, Wanda K. O'Neal, Stephen I. Rennard, Sreekumar G. Pillai, Paula Belloni, Debra A. Cockayne, Alejandro P. Comellas, Meilan Han, Rachel L. Zemans, Katerina Kechris, Russell P. Bowler

Journal Articles: Pulmonary & Critical Care Med

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a phenotypically heterogeneous disease. In COPD, the presence of emphysema is associated with increased mortality and risk of lung cancer. High resolution computed tomography (HRCT) scans are useful in quantifying emphysema but are associated with radiation exposure and high incidence of false positive findings (i.e., nodules). Using a comprehensive biomarker panel, we sought to determine if there was a peripheral blood biomarker signature of emphysema.

METHODS: 114 plasma biomarkers were measured using a custom assay in 588 individuals enrolled in the COPDGene study. Quantitative emphysema measurements included percent low lung attenuation (%LAA) ≤ …

Broad And Direct Interaction Between Tlr And Siglec Families Of Pattern Recognition Receptors And Its Regulation By Neu1., Guo-Yun Chen, Nicholas K. Brown, Wei Wu, Zahra Khedri, Hai Yu, Xi Chen, Diantha Van De Vlekkert, Alessandra D'Azzo, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Both pathogen- and tissue damage-associated molecular patterns induce inflammation through toll-like receptors (TLRs), while sialic acid-binding immunoglobulin superfamily lectin receptors (Siglecs) provide negative regulation. Here we report extensive and direct interactions between these pattern recognition receptors. The promiscuous TLR binders were human SIGLEC-5/9 and mouse Siglec-3/E/F. Mouse Siglec-G did not show appreciable binding to any TLRs tested. Correspondingly, Siglece deletion enhanced dendritic cell responses to all microbial TLR ligands tested, while Siglecg deletion did not affect the responses to these ligands. TLR4 activation triggers Neu1 translocation to cell surface to disrupt TLR4:Siglec-E interaction. Conversely, sialidase inhibitor Neu5Gc2en prevented TLR4 ligand-induced …

Influence Of Diet And Obesity On Copd Development And Outcomes, Corrine K. Hanson, Erica P. Rutten, Emiel F.M. Wouters, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

The global increase in the prevalence and incidence of obesity has called serious attention to this issue as a major public health concern. Obesity is associated with many chronic diseases, including cardiovascular disease and diabetes, and recently the role of overweight and obesity in lung disease has received new interest. Independently of obesity, diet also plays a role as a risk factor for many chronic diseases, and evidence is accumulating to support a role for diet in the prevention and management of several lung diseases. Chronic obstructive lung disease is the third-leading cause of death globally, and both obesity and …

Brain Metastases From Breast Cancer: Lessons From Experimental Magnetic Resonance Imaging Studies And Clinical Implications., Donna Murrell, Paula J Foster, Ann F Chambers

Medical Biophysics Publications

Breast cancer that has metastasized to the brain presents difficult clinical challenges. This diagnosis comes with high mortality rates, largely due to complexities in early detection and ineffective therapies associated with both dormancy and impermeability of the blood-brain barrier (BBB). Magnetic resonance imaging (MRI) is the current gold standard for diagnosis and assessment of brain tumors. It has been used clinically to investigate metastatic development as well as monitor response to therapy. Here, we describe preclinical imaging strategies that we have used to study the development of brain metastases due to breast cancer. Using this approach, we have identified three …

There Are Laterality Effects In Memory Functioning In Children/Adolescents With Focal Epilepsy., Michelle Y Kibby, Morris J Cohen, Sylvia E Lee, Lisa Stanford, Yong D Park, Suzanne M Strickland

Publications

In a sample of individuals with childhood focal epilepsy, children/adolescents with left hemisphere foci outperformed those with right foci on both measures of nonverbal learning. Participants with left foci performed worse than controls on paired associate delayed recall and semantic memory, and they had greater laterality effects in IQ. Participants with right foci performed worse than controls on delayed facial recognition. Both groups displayed reduced focused attention and poor passage retention over time. Although participants with bilateral foci displayed poor learning and lower IQ than controls, they did not have worse impairment than those with a unilateral focus.

Non-Invasive Mri And Spectroscopy Of Mdx Mice Reveal Temporal Changes In Dystrophic Muscle Imaging And In Energy Deficits., Christopher R. Heier, Alfredo D. Guerron, Alexandru Korotcov, Stephen Lin, Heather Gordish-Dressman, Stanley Fricke, Raymond W. Sze, Eric P. Hoffman, Paul Wang, Kanneboyina Nagaraju

Genomics and Precision Medicine Faculty Publications

In Duchenne muscular dystrophy (DMD), a genetic disruption of dystrophin protein expression results in repeated muscle injury and chronic inflammation. Magnetic resonance imaging shows promise as a surrogate outcome measure in both DMD and rehabilitation medicine that is capable of predicting clinical benefit years in advance of functional outcome measures. The mdx mouse reproduces the dystrophin deficiency that causes DMD and is routinely used for preclinical drug testing. There is a need to develop sensitive, non-invasive outcome measures in the mdx model that can be readily translatable to human clinical trials. Here we report the use of magnetic resonance imaging …

Primary Microrna Processing Assay Reconstituted Using Recombinant Drosha And Dgcr8., Ian Barr, Feng Guo

Natural Sciences and Mathematics | Faculty Scholarship

In animals, the Microprocessor complex cleaves primary transcripts of microRNAs (pri-miRNAs) to produce precursor microRNAs in the nucleus. The core components of Microprocessor include the Drosha ribonuclease and its RNA-binding partner protein DiGeorge critical region 8 (DGCR8). DGCR8 has been shown to tightly bind an Fe(III) heme cofactor, which activates its pri-miRNA processing activity. Here we describe how to reconstitute pri-miRNA processing using recombinant human Drosha and DGCR8 proteins. In particular, we present the procedures for expressing and purifying DGCR8 as an Fe(III) heme-bound dimer, the most active form of this protein, and for estimating its heme content.

Novel Roles For Actin In Mitochondrial Fission, Anna L. Hatch, Pinar S. Gurel, Henry N. Higgs

Dartmouth Scholarship

Mitochondrial dynamics, including fusion, fission and translocation, are crucial to cellular homeostasis, with roles in cellular polarity, stress response and apoptosis. Mitochondrial fission has received particular attention, owing to links with several neurodegenerative diseases. A central player in fission is the cytoplasmic dynamin-related GTPase Drp1, which oligomerizes at the fission site and hydrolyzes GTP to drive membrane ingression. Drp1 recruitment to the outer mitochondrial membrane (OMM) is a key regulatory event, which appears to require a pre-constriction step in which the endoplasmic reticulum (ER) and mitochondrion interact extensively, a process termed ERMD (ER-associated mitochondrial division). It is unclear how ER-mitochondrial …

The Forkhead Transcription Factor, Foxp3: A Critical Role In Male Fertility In Mice., Jake S Jasurda, Deborah O Jung, Erin D Froeter, David B Schwartz, Torin D Hopkins, Corrie L Farris, Stacey Mcgee, Prema Narayan, Buffy S Ellsworth

Articles

Fertility is dependent on the hypothalamic-pituitary-gonadal axis. Each component of this axis is essential for normal reproductive function. Mice with a mutation in the forkhead transcription factor gene, Foxp3, exhibit autoimmunity and infertility. We have previously shown that Foxp3 mutant mice have significantly reduced expression of pituitary gonadotropins. To address the role of Foxp3 in gonadal function, we examined the gonadal phenotype of these mice. Foxp3 mutant mice have significantly reduced seminal vesicle and testis weights compared with Foxp3(+/Y) littermates. Spermatogenesis in Foxp3 mutant males is arrested prior to spermatid elongation. Activation of luteinizing hormone signaling in Foxp3 mutant mice …

Overexpression Of Dcf1 Inhibits Glioma Through Destruction Of Mitochondria And Activation Of Apoptosis Pathway, Yuqiong Xie, Qang Li, Qingbo Yang

Electrical and Computer Engineering Faculty Research & Creative Works

Gliomas are the most common brain tumors affecting the central nervous system and are associated with a high mortality rate. DCF1 is a membrane protein that was previously found to play a role in neural stem cell differentiation. In the present study, we found that overexpression of dcf1 significantly inhibited cell proliferation, migration, and invasion and dramatically promoted apoptosis in the glioblastoma U251 cell line. DCF1 deletion mutations in the functional region showed that the complete structure of DCF1 was necessary for apoptosis. Furthermore, significantly lower tumorigenicity was observed in athymic nude mice by transplanting U251 cells overexpressing dcf1. To …

Benthic And Pelagic Pathways Of Methylmercury Bioaccumulation In Estuarine Food Webs Of The Northeast United States, Celia Y. Chen, Mark E. Borsuk, Deenie M. Bugge, Terill Hollweg

Dartmouth Scholarship

Methylmercury (MeHg) is a contaminant of global concern that bioaccumulates and bioamagnifies in marine food webs. Lower trophic level fauna are important conduits of MeHg from sediment and water to estuarine and coastal fish harvested for human consumption. However, the sources and pathways of MeHg to these coastal fisheries are poorly known particularly the potential for transfer of MeHg from the sediment to biotic compartments. Across a broad gradient of human land impacts, we analyzed MeHg concentrations in food webs at ten estuarine sites in the Northeast US (from the Hackensack Meadowlands, NJ to the Gulf of Maine). MeHg concentrations …

Differential Responding By Rhesus Monkeys (Macaca Mulatta) And Humans (Homo Sapiens) To Variable Outcomes In The Assurance Game, Audrey E. Parrish, Sarah F. Brosnan, Bart J. Wilson, Michael J. Beran

Economics Faculty Articles and Research

Behavioral flexibility in how one responds to variable partner play can be examined using economic coordination games in which subjects play against a variety of partners and therefore may need to alter their behavior to produce the highest payoff. But how do we study this behavioral flexibility once players have settled on a response? Here, we investigated how responding by rhesus monkeys (Macaca mulatta) and humans (Homo sapiens) playing a computerized single-player version of a coordination game, the Assurance game, changed as a function of the variable responses (Stag/Hare) generated by multiple simulations (SIMs). We were interested in whether individuals …

Effect Of Bdnf Val66met On Memory Decline And Hippocampal Atrophy In Prodromal Alzheimer's Disease: A Preliminary Study, Yen Y. Lim, Victor L. Villemagne, Simon M. Laws, David Ames, Robert H. Pietrzak, Kathryn A. Ellis, Karra Harrington, Pierrick Bourgeat, Ashley I. Bush, Ralph N. Martins, Colin L. Masters, Christopher C. Rowe, Paul Maruff

Research outputs 2014 to 2021

Objective: Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer's disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ. Methods: Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, …

The Effects Of Sex-Steroids And Menstrual Cycle/Oestrous Phases On Knee Ligament Laxity In Humans And Rodents / Firouzeh Dehghan, Firouzeh Dehghan

Student Works (2010-2019)

The incidence of non-contact knee injury was reported higher in female than male. In female, the occurrence of this injury was related to different phases of the menstrual cycle. In view of this, we investigated the followings: (i) changes in knee laxity in rodent model under different sex-steroid influence; (ii) mechanisms underlying changes in knee laxity, which involves differential expression of relaxin receptors and (iii) correlation between knee laxity and serum levels of sex-steroids and relaxin at different phases of the menstrual cycle. In first part of the study, ovariectomized WKY rats were divided into different treatment groups (n=6 per …

Pax Genes: Regulators Of Lineage Specification And Progenitor Cell Maintenance, Judith A. Blake, Mel R. Ziman

Research outputs 2014 to 2021

Pax genes encode a family of transcription factors that orchestrate complex processes of lineage determination in the developing embryo. Their key role is to specify and maintain progenitor cells through use of complex molecular mechanisms such as alternate RNA splice forms and gene activation or inhibition in conjunction with protein co-factors. The significance of Pax genes in development is highlighted by abnormalities that arise from the expression of mutant Pax genes. Here, we review the molecular functions of Pax genes during development and detail the regulatory mechanisms by which they specify and maintain progenitor cells across various tissue lineages. We …

Predictors Of Grandparental Investment Decisions In Contemporary Europe: Biological Relatedness And Beyond, David A. Coall, Sonja Hilbrand, Ralph Hertwig

Research outputs 2014 to 2021

Across human cultures, grandparents make a valued contribution to the health of their families and communities. Moreover, evidence is gathering that grandparents have a positive impact on the development of grandchildren in contemporary industrialized societies. A broad range of factors that influence the likelihood grandparents will invest in their grandchildren has been explored by disciplines as diverse as sociology, economics, psychology and evolutionary biology. To progress toward an encompassing framework, this study will include biological relatedness between grandparents and grandchildren, a factor central to some discipline's theoretical frameworks (e.g., evolutionary biology), next to a wide range of other factors in …

The Reliability Of An Adolescent Dietary Pattern Identified Using Reduced-Rank Regression: Comparison Of A Ffq And 3 D Food Record, Geeta Appannah, Gerda K. Pot, Therese A. O'Sullivan, Wendy H. Oddy, Susan A. Jebb, Gina L. Ambrosini

Research outputs 2014 to 2021

Despite the increasing use of dietary patterns (DP) to study diet and health outcomes, relatively few studies have examined the reliability of DP using different dietary assessment methods. Reduced-rank regression (RRR) is an emerging statistical method that incorporates a priori information to characterise DP related to specific outcomes of interest. The aim of the present study was to compare DP identified using the RRR method in a FFQ with those in a 3 d food record (FR). Participants were 783 adolescents from the Western Australian Pregnancy (Raine) Cohort Study who completed both a FFQ and FR at 14 years of …

A Proto-Architecture For Innate Directionally Selective Visual Maps., Sv Adams, Cm Harris

School of Psychology

Self-organizing artificial neural networks are a popular tool for studying visual system development, in particular the cortical feature maps present in real systems that represent properties such as ocular dominance (OD), orientation-selectivity (OR) and direction selectivity (DS). They are also potentially useful in artificial systems, for example robotics, where the ability to extract and learn features from the environment in an unsupervised way is important. In this computational study we explore a DS map that is already latent in a simple artificial network. This latent selectivity arises purely from the cortical architecture without any explicit coding for DS and prior …

Potential Role Of Orexin And Sleep Modulation In The Pathogenesis Of Alzheimer's Disease, Jee Hoon Roh, Hong Jiang, Mary Beth Finn, Floy R. Stewart, Thomas E. Mahan, John R. Cirrito, Ashish Heda, B. Joy Snider, Mingjie Li, Masashi Yanagisawa, Luis De Lecea, David M. Holtzman

Open Access Publications

Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer's disease (AD) pathogenesis, and it disrupts the sleep-wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. …

Implicit Meaning In 18-Month-Old Toddlers., Luche C Delle, Samantha Durrant, Caroline Floccia, Kim Plunkett

School of Psychology

A substantial body of evidence demonstrates that infants understand the meaning of spoken words from as early as 6 months. Yet little is known about their ability to do so in the absence of any visual referent, which would offer diagnostic evidence for an adult-like, symbolic interpretation of words and their use in language mediated thought. We used the head-turn preference procedure to examine whether infants can generate implicit meanings from word forms alone as early as 18 months of age, and whether they are sensitive to meaningful relationships between words. In one condition, toddlers were presented with lists of …

Development Of A Prototype Lateral Flow Immunoassay (Lfi) For The Rapid Diagnosis Of Melioidosis., Raymond L. Houghton, Dana E. Reed, Mark A. Hubbard, Michael J. Dillon, Hongjing Chen, Bart J. Currie, Mark Mayo, Derek S. Sarovich, Vanessa Theobald, Direk Limmathurotsakul, Gumphol Wongsuvan, Narisara Chantratita, Sharon J. Peacock, Alex R. Hoffmaster, Brea Duval, Paul J. Brett, Mary N. Burtnick, David P. Aucoin

Peninsula Medical School

Burkholderia pseudomallei is a soil-dwelling bacterium and the causative agent of melioidosis. Isolation of B. pseudomallei from clinical samples is the "gold standard" for the diagnosis of melioidosis; results can take 3-7 days to produce. Alternatively, antibody-based tests have low specificity due to a high percentage of seropositive individuals in endemic areas. There is a clear need to develop a rapid point-of-care antigen detection assay for the diagnosis of melioidosis. Previously, we employed In vivo Microbial Antigen Discovery (InMAD) to identify potential B. pseudomallei diagnostic biomarkers. The B. pseudomallei capsular polysaccharide (CPS) and numerous protein antigens were identified as potential …

Insulin Acutely Improves Mitochondrial Function Of Rat And Human Skeletal Muscle By Increasing Coupling Efficiency Of Oxidative Phosphorylation., Raid B. Nisr, Charles Affourtit

School of Biomedical Sciences

Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the …

Self-Regulating Smoking And Snacking Through Physical Activity., Hwajung Oh, Adrian H. Taylor

Peninsula Medical School

OBJECTIVE: Emotional snacking contributes to weight gain after smoking cessation. Exercise acutely reduces cravings for cigarettes and snack food. This study examined if different exercise intensities acutely reduces snack and cigarette cravings and attentional bias (AB) to video clips of snacks and cigarettes among abstinent smokers. METHODS: Abstinent smokers (and snackers; N = 23) randomly did 15 mins of moderate and vigorous cycling and a passive control in a cross-over design. Visual initial AB (IAB) and maintained AB (MAB) were assessed pre- and after treatment while watching paired snacking/neutral or smoking/neutral video clips. Desire to snack and smoke were assessed …

Using Forced Choice To Test Belief Bias In Syllogistic Reasoning., Dries Trippas, Michael F. Verde, Simon J. Handley

School of Psychology

In deductive reasoning, believable conclusions are more likely to be accepted regardless of their validity. Although many theories argue that this belief bias reflects a change in the quality of reasoning, distinguishing qualitative changes from simple response biases can be difficult (Dube, Rotello, & Heit, 2010). We introduced a novel procedure that controls for response bias. In Experiments 1 and 2, the task required judging which of two simultaneously presented syllogisms was valid. Surprisingly, there was no evidence for belief bias with this forced choice procedure. In Experiment 3, the procedure was modified so that only one set of premises …

Thinking In Circuits: Toward Neurobiological Explanation In Cognitive Neuroscience., Friedemann Pulvermüller, Max Garagnani, Thomas Wennekers

School of Engineering, Computing and Mathematics

Cognitive theory has decomposed human mental abilities into cognitive (sub) systems, and cognitive neuroscience succeeded in disclosing a host of relationships between cognitive systems and specific structures of the human brain. However, an explanation of why specific functions are located in specific brain loci had still been missing, along with a neurobiological model that makes concrete the neuronal circuits that carry thoughts and meaning. Brain theory, in particular the Hebb-inspired neurocybernetic proposals by Braitenberg, now offers an avenue toward explaining brain-mind relationships and to spell out cognition in terms of neuron circuits in a neuromechanistic sense. Central to this endeavor …

English-Learning One- To Two-Year-Olds Do Not Show A Consonant Bias In Word Learning., Caroline Floccia, Thierry Nazzi, Luche C Delle, Silvana Poltrock, Jeremy Goslin

School of Psychology

Following the proposal that consonants are more involved than vowels in coding the lexicon (Nespor, Peña & Mehler, 2003), an early lexical consonant bias was found from age 1;2 in French but an equal sensitivity to consonants and vowels from 1;0 to 2;0 in English. As different tasks were used in French and English, we sought to clarify this ambiguity by using an interactive word-learning study similar to that used in French, with British-English-learning toddlers aged 1;4 and 1;11. Children were taught two CVC labels differing on either a consonant or vowel and tested on their pairing of a third …

Mediofrontal Event-Related Potentials In Response To Positive, Negative And Unsigned Prediction Errors., Thomas D. Sambrook, Jeremy Goslin

School of Psychology

Reinforcement learning models make use of reward prediction errors (RPEs), the difference between an expected and obtained reward. There is evidence that the brain computes RPEs, but an outstanding question is whether positive RPEs ("better than expected") and negative RPEs ("worse than expected") are represented in a single integrated system. An electrophysiological component, feedback related negativity, has been claimed to encode an RPE but its relative sensitivity to the utility of positive and negative RPEs remains unclear. This study explored the question by varying the utility of positive and negative RPEs in a design that controlled for other closely related …

Implementation Of Fourier Transform Infrared Spectroscopy For The Rapid Typing Of Uropathogenic Escherichia Coli., S. E. Dawson, T. Gibreel, N. Nicolaou, H. Alrabiah, Y. Xu, R. Goodacre, M. Upton

School of Biomedical Sciences

In this paper, we demonstrate that Fourier transform infrared (FT-IR) spectroscopy is able to discriminate rapidly between uropathogenic Escherichia coli (UPEC) of key lineages with only relatively simple sample preparation. A total of 95 bacteria from six different epidemiologically important multilocus sequence types (ST10, ST69, ST95, ST73, ST127 and ST131) were used in this project and principal component-discriminant function analysis (PC-DFA) of these samples produced clear separate clustering of isolates, based on the ST. Analysis of data using partial least squares-discriminant analysis (PLS-DA), incorporating cross-validation, indicated a high prediction accuracy of 91.19% for ST131. These results suggest that FT-IR spectroscopy …

Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton

School of Biomedical Sciences

Galleria mellonella larvae are an alternative in vivo model for investigating bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from five leading uropathogenic E. coli (UPEC) lineages using G. mellonella larvae. Larvae were challenged with a range of inoculum doses to determine the 50% lethal dose (LD50) and for analysis of survival outcome using Kaplan-Meier plots. Virulence was correlated with carriage of a panel of 29 virulence factors (VF). Larvae inoculated with ST69 and ST127 isolates (10(4) colony-forming units/larvae) showed significantly higher mortality rates than those infected with ST73, ST95 and ST131 isolates, killing 50% of the larvae …

Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation Of Sdf-1-Cxcr4 Retention Signaling In Bone Marrow, Kasia Mierzejewska, Yuri M. Klyachkin, Janina Ratajczak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak

Saha Cardiovascular Research Center Faculty Publications

Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, one might assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would induce mobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ). We observed that doubling the S1P level in PB from damaged erythrocytes induced only a marginally increased level of mobilization. However, if mice were exposed to PHZ together with the …