• Toxoplasma gondii (/ˈtɒksəˌplæzmə ˈɡɒndi.aɪ, -iː/) is a parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. (wikipedia.org)
  • When a feline is infected with T. gondii (e.g. by consuming an infected mouse carrying the parasite's tissue cysts), the parasite survives passage through the stomach, eventually infecting epithelial cells of the cat's small intestine. (wikipedia.org)
  • We report here the identification of seven putative aspartic proteases, TgASP1 to TgASP7, in the apicomplexan parasite Toxoplasma gondii. (unige.ch)
  • Interleukin (IL)-12 is a proinflammatory cytokine generally regarded as a master regulator of type 1 T cell mediated immunity against intracellular pathogens, including T. gondii and cancers. (aai.org)
  • As expected, IFN-γ + CD4 + T cells decreased from an avg 29% to 9% in WT mice compared to IL-12 -/- mice respectively when infected with T. gondii . (aai.org)
  • Toxoplasma gondii is an obligate intracellular protozoan parasite capable of infecting warm-blooded animals by ingestion. (life-science-alliance.org)
  • We characterized the role of IRG protein Irgb6 in the cell-autonomous response against T. gondii , which involves vacuole ubiquitination and breakdown. (life-science-alliance.org)
  • Toxoplasmosis is a disease caused by an obligate intracellular protozoal parasite, Toxoplasma gondii , whose name was derived from the crescent shape of the parasite ( toxon is Greek for "arc"), as well as the name of the North African rodent in which it was first observed, Ctenodactylus gundi . (medscape.com)
  • Researchers report they have identified a way in which Toxoplasma gondii may modify brain cells. (neurosciencenews.com)
  • Researchers have discovered how the parasite Toxoplasma gondii is able to cross the blood-brain barrier. (neurosciencenews.com)
  • A new study reports people with intermittent explosive disorder are twice as likely to have been exposed to toxoplasma gondii. (neurosciencenews.com)
  • Immune system response to chronic infection may be more directly to blame for health and behavioral changes associated with Toxoplasma gondii infections. (neurosciencenews.com)
  • The entire process is based on the Toxoplasma gondii parasite model. (linksium.fr)
  • TgAP2IX-5 is a key transcriptional regulator of the asexual cell cycle division in Toxoplasma gondii. (pluginlabs-hautsdefrance.fr)
  • We generated a CD8 T-cell receptor (TCR) transnuclear (TN) mouse specific to the Ld -restricted immunodominant epitope of GRA6 from Toxoplasma gondii as a source of cells to facilitate further investigation into the CD8 T-cell-mediated response against this pathogen. (figshare.com)
  • Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection. (edu.au)
  • Our research is mainly focused on T. gondii , which is a relevant model for many features conserved throughout the phylum. (labex-parafrap.fr)
  • 3. Nguyen HM, El Hajj H, El Hajj R, Tawil N, Berry L, Lebrun M , Bordat Y, Besteiro S. Toxoplasma gondii autophagy-related protein ATG9 is crucial for the survival of parasites in their host. (labex-parafrap.fr)
  • 5. Lévêque MF, Berry L, Cipriano MJ, Nguyen HM, Striepen B, Besteiro S . Autophagy- Related Protein ATG8 Has a Noncanonical Function for Apicoplast Inheritance in Toxoplasma gondii . (labex-parafrap.fr)
  • The infection and multiplication of Toxoplasma gondii and Trypanosoma cruzi were compared in primary cultures of white rat, mouse and hamster astrocytes. (ucr.ac.cr)
  • Toxoplasma gondii ist ein obligater intrazellulärer Parasit, der bei Menschen und Nutztieren Toxoplasmose verursacht. (hu-berlin.de)
  • Toxoplasma gondii is an obligate intracellular parasite that causes Toxoplasmosis in human and livestock. (hu-berlin.de)
  • C-reactive protein, TORCH (Toxoplasma discarded as a plate contaminant, but for gondii, other microorganisms, rubella virus, its unusual features. (who.int)
  • Congenital Toxoplasmosis Congenital toxoplasmosis is caused by transplacental acquisition of Toxoplasma gondii . (msdmanuals.com)
  • For Mukherjee, the paper was a revelation: not only did it identify the fastest way yet to target Golgi biology, it suggested that scientists could use intracellular bacteria "as a lens to understand basic processes inside the cell. (the-scientist.com)
  • So-called facultative intracellular bacteria such as Listeria monocytogenes and Legionella pneumophila do not need to be inside a host cell to reproduce. (the-scientist.com)
  • The objectives of our team are to decipher cellular and molecular features related to two essential parasitic functions: host cell invasion and intracellular replication, with the aim of identifying novel therapeutic strategies. (labex-parafrap.fr)
  • Because of the newborn is at the base aortic insufficiency is best documented by anti-toxoplasma igm or culture of the. (elastizell.com)
  • These cells, including macrophages and neutrophils, were found to provide a rapid response to virtually all pathogens and to initiate inflammation at sites of local infection. (aacrjournals.org)
  • The virus destroys CD4+ cells in the replication process and CD4+ cell count can fall rapidly after infection. (pharmaceutical-journal.com)
  • The destruction of CD4+ cells impairs cell-mediated immunity - increasing the risk of opportunistic infection and some cancers. (pharmaceutical-journal.com)
  • This practical feature various aspects of infection biology, including bacteriology, fungal pathogens, virology and immunology. (uni-wuerzburg.de)
  • Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues. (pluginlabs-hautsdefrance.fr)
  • Here, we demonstrate that both viral mRNAs and antigens are detectable in CD4 + T cells despite the absence of productive infection. (prolekarniky.cz)
  • Cell-to-cell fusion of permissive Huh7 cells with non-permissive Jurkat T cells impaired productive EBOV infection suggesting the presence of a cellular restriction factor. (prolekarniky.cz)
  • These data indicate that exposure of T cells to EBOV results in an abortive infection, which likely contributes to the lymphopenia observed during EBOV infections. (prolekarniky.cz)
  • Pathogenesis of Ebola hemorrhagic fever in cynomolgus macaques: evidence that dendritic cells are early and sustained targets of infection. (prolekarniky.cz)
  • Adoptively transferred Gra6 TN CD8 T cells proliferated upon Toxoplasma infection in vivo and exhibited an activated phenotype similar to host CD8 T cells specific to Gra6. (figshare.com)
  • The brain of Toxoplasma-infected mice carried Gra6 TN cells already at day 8 post-infection. (figshare.com)
  • Both Gra6 TN mice as well as adoptively transferred Gra6 TN cells were able to significantly reduce the parasite burden in the acute phase of Toxoplasma infection. (figshare.com)
  • Overall, the Gra6 TN mouse represents a functional tool to study the protective and immunodominant specific CD8 T-cell response to Toxoplasma in both the acute and the chronic phases of infection. (figshare.com)
  • He was featured on the 2019 GRAMMY-nominated album, 'Black Cowboys. (zombiemed.org)
  • Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA-RON2 pair. (labex-parafrap.fr)
  • These microbes all enjoy at least part of their lives shielded from the onslaught of white blood cells, antibodies, and other immune defenses that the body launches against pathogens that live outside of host cells. (the-scientist.com)
  • IL-12 subsequently stimulates the antipathogen type I immune response, wherein naïve CD4 + or CD8 + T cells become antigen-specific Th1 cells and cytotoxic T cells, respectively, with the help of antigen-presenting cells. (life-science-alliance.org)
  • The differential diagnosis for CNS lesions include infiltration of lymphoma cells, metastatic brain tumors, toxoplasmosis, and tuberculosis. (medscape.com)
  • Roy's team had found that "this protein called AnkX, when microinjected into cells-even at picomole levels-could cause the entire Golgi to fragment in, like, five minutes," Mukherjee says. (the-scientist.com)
  • Although it can infect numerous cells, its main targets are lymphocytes that express the protein CD4 (referred to as CD4+ cells). (pharmaceutical-journal.com)
  • A protein phosphatase 1 inhibitor, 1E7-03, and siRNA-mediated suppression of viral antigens were used to demonstrate de novo synthesis of viral RNAs and antigens in CD4 + T cells, respectively. (prolekarniky.cz)
  • We have adopted an interdisciplinary approach to disease research, from cell biology to protein expression and chemical synthesis. (edu.au)
  • 2. Guérin A , Corrales RM, Parker ML, Lamarque MH, Jacot D, El Hajj H, Soldati-Favre D, Boulanger MJ, Lebrun M . Efficient invasion by Toxoplasma depends on the subversion of host protein networks. (labex-parafrap.fr)
  • In addition, mannosebinding-lectin (MBL) is an epithelial-cell associated host protein that binds to Candida mannan, activates complement, and thus inhibits Candida growth. (paperzz.com)
  • As a postdoc in Manoj Duraisingh's lab at Harvard School of Public Health she performed a genetic screen to identify critical host factors for Plasmodium falciparum malaria using red blood cells derived from hematopoietic stem cells. (stanford.edu)
  • Here the lipid profiles of red blood cells infected with the five different sexual stages of Plasmodium falciparum were analysed by mass spectrometry and compared to those from uninfected and asexual trophozoite infected erythrocytes. (biomedcentral.com)
  • The prolonged duration of gametocyte maturation is a unique feature of only a few Plasmodium species infecting higher primates ( P. falciparum and P. reichenowi ) [ 1 , 2 ]. (biomedcentral.com)
  • whilst both may present with similar clinical features, they are best considered as distinct disease entities since the underlying pathophysiology and treatment strategies are very different. (dovepress.com)
  • Data on baseline clinical features, management, and admission outcomes were analyzed. (bvsalud.org)
  • Other clinical features - Although clinical features cannot reliably distinguish between the various etiologies, presence or absence of certain signs and symptoms can increase or decrease the likelihood of certain disease entities. (medilib.ir)
  • Reliable diagnosis of VVC requires a correlation of clinical features with mycological evidence. (paperzz.com)
  • It also includes Toxoplasma , a prominent cause of human congenital infections, and Cryptosporidium , a leading cause of severe diarrhea and mortality in infants. (labex-parafrap.fr)
  • Due to the absence of FDA-cleared/approved evaluations, Toxoplasma and also Bartonella antigen diagnosis is currently carried out by utilizing lab established tests. (search-i.info)
  • The cellular or innate immune system was first described by the pathologist Elie Metchnikoff who recognized the existence of cells in the blood and tissues whose role was to identify, capture, and destroy invading pathogens. (aacrjournals.org)
  • We now understand that adaptive immunity is the purview of a second set of leukocytes, T and B lymphocytes, which are responsible not only for antibody production but also for the generation of T cells that can directly identify and kill host cells infected by pathogens (e.g., viruses). (aacrjournals.org)
  • Scientists studying pathogens such as Chlamydia , Legionella , and Listeria get a master class in how to control the internal workings of mammalian cells. (the-scientist.com)
  • By then it was known that Listeria infects cells such as macrophages-motile human immune cells that engulf pathogens and cellular debris-by being taken up into vacuoles and breaking out of those vacuoles into the cytoplasm. (the-scientist.com)
  • This process is essential for the parasitic lifestyle of these pathogens and relies on an exocytic machinery sharing structural features and molecular components with free-living ciliates. (stanford.edu)
  • 39 Inside these intestinal cells, the parasites undergo sexual development and reproduction, producing millions of thick-walled, zygote-containing cysts known as oocysts. (wikipedia.org)
  • Although the notion that malaria has helped shape the human genome is well- accepted, the lack of a nucleus in human erythrocytes has hindered our ability to study genetic interactions between these unusual host cells and P. falciparum parasites. (stanford.edu)
  • Our part focuses on the cell biology of parasites. (uni-wuerzburg.de)
  • We will cover different aspects of the host/parasite interaction, the complex life cycles of these parasites and motility of parasites on a single cell level. (uni-wuerzburg.de)
  • In contrast to the 48-hour blood stage life cycle of asexual parasites, it takes 9-12 days for P. falciparum gametocytes to fully develop inside human red blood cells (RBCs). (biomedcentral.com)
  • An auxin-inducible conditional repression of TgPIS abrogated the lytic cycle of the parasite in mammalian cells due to defects in the replication, motility and egress. (hu-berlin.de)
  • Infected epithelial cells eventually rupture and release oocysts into the intestinal lumen, whereupon they are shed in the cat's feces. (wikipedia.org)
  • Notably, colonisation of the vagina requires yeast adherence to vaginal epithelial cells. (paperzz.com)
  • The aim of this survey was to introduce a quantitative and objective mathematical method for pinpointing the differences between malignant and non -malignant epithelial cells in urine cytology by the use of software analysis. (iranpath.org)
  • Study had selected a cut-off point to (1.732 ± 0.006) to discriminate malignant and non-malignant epithelial cells in urinary smears. (iranpath.org)
  • There is enormous demand for lipids due to parasite growth inside the host cell [developing organelles (e.g. nucleus, mitochondria, food vacuoles and apicoplast) surrounded by membranes and accumulating lipids in lipid bodies] and subsequent replication. (biomedcentral.com)
  • Dendritic cells (DC) are responsible for initiating all antigen-specific immune responses. (aacrjournals.org)
  • Upon completion of this activity, the participant should understand the critical roles of dendritic cells in guiding host immune responses, and the details of how they mature, process, and present antigens. (aacrjournals.org)
  • Understanding the paradoxical importance of dendritic cells in immunity and tolerance will inform the development of successful cancer immunotherapies. (aacrjournals.org)
  • It has long been appreciated that the innate and adaptive arms of the immune system must be coordinated, but it was not until the discovery of dendritic cells (DC) by Ralph Steinman at The Rockefeller University in the early 1980s that we truly understood conceptually how the immune system functions as a coherent unit. (aacrjournals.org)
  • The innate immune response first induces IL-12 production by antigen-presenting cells, such as macrophages and dendritic cells. (life-science-alliance.org)
  • Dendritic cells in host response to biologic scaffolds. (leiferlab.com)
  • Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever. (prolekarniky.cz)
  • The section Cell Biology mainly regards the eukaryotic cell and intends to elucidate the vast diversity in structure and function of molecules, organelles and cells in addition to basic principles of modern molecular cell biology. (uni-wuerzburg.de)
  • Key aspects include the organization of the bacterial genome, the transcription and translation machinery, mechanisms of regulation of gene expression, transport of small molecules and macromolecules, cell division and differentiation, bacterial motility and chemotaxis, signal transduction and bacterial communication mechanisms. (uni-wuerzburg.de)
  • Upon induction of gametocytes the infected red blood cell undergoes remarkable modifications: initially the cell morphology is indistinguishable from asexual infected RBC, but in later stages the gametocyte-infected RBC elongate before rounding up again. (biomedcentral.com)
  • They are exceptionally efficient at antigen presentation and also adept at generating just the right type of T cells in response to a given pathogen. (aacrjournals.org)
  • We evaluated pathologic changes in the marmosets, localized virus and antigen, and assessed epidemiologic features. (cdc.gov)
  • None of the samples of small cell carcinoma had a false negative diagnosis on cytology, while only one case of squamous cell carcinoma was diagnosed as negative. (cytojournal.com)
  • Symptomatic and severe combined immunodeficiency disorders, later, as affected by hemophilia a with the down syndrome are the essentials of diagnosis & typical features firm, freely movable, called a positive or present, decreased, increased n, normal or only minimally elevated. (elastizell.com)
  • Conclusion: Based on diagnostic accuracy measures (sensitivity and specificity), probability of disease measures (predictive value of a positive and negative test results), and likelihood ratio of positive and negative tests, it seems fractal dimension of nuclear cell boundaries for urinary smears can be used as a feature extraction in the field of automated cancer diagnosis. (iranpath.org)
  • The immunosuppression caused by HIV results in decreased antiparasitic T-cell response, allowing reactivation of Toxoplasma . (medscape.com)
  • Infectious agents can cause acute or chronic changes through: (1) direct infiltration of inflammatory cells, (2) action of released toxins or (3) the delayed type immune response. (biomedcentral.com)
  • In the subacute stage, infiltration of mononuclear cells becomes more prominent, while in the acute stage, polymorphonuclear neutrophils infiltrate all layers of the vessel wall. (medscape.com)
  • Transmission electron microscopy revealed intranuclear herpetic inclusions, and immunostaining revealed HuAHV1 and herpesvirus particles in neurons, glial cells, tongue mucosal epithelium, and hepatocytes. (cdc.gov)
  • Great Moments in Science The 2016 Nobel Prize in Medicine or Physiology was awarded for research into autophagy - the process where your cells eat and recycle themselves. (abc.net.au)
  • One of the IFN-γ-induced cell-autonomous programs is associated with IFN-inducible GTPases, such as p47 immunity-related GTPases (IRGs) and p65 guanylate-binding proteins (GBPs) ( Kim et al, 2012 ). (life-science-alliance.org)
  • As such, they are the master regulators of the immune response and serve this function by linking the microbial sensing features of the innate immune system to the exquisite specificity of the adaptive response. (aacrjournals.org)
  • Given their central role in controlling the immune response in patients with cancer, DCs are emerging as a critical cell type that must be considered as we come to understand basic cancer immunobiology. (aacrjournals.org)
  • As a trade-off, they have had to come up with ways to bypass a cell's internal immune system, navigate the complicated, busy environment of the cell cytoplasm, and ultimately escape that environment to infect other cells-becoming tiny maestros of manipulation in the process. (the-scientist.com)
  • Animal models of viral myocarditis predict a post-viral immune-mediated immunological response that is maladaptive and eventually results in reduced contractility and dysfunction of myocardial cells. (ontariohomeopath.ca)
  • TgASP1 shows a novel punctate localization associated with the secretory system in non-dividing cells, and relocalizes dramatically and unambiguously to the nascent inner membrane complex of daughter cells at replication, before coalescing again at the end of division. (unige.ch)
  • Subsequently, the presence and intensity of changes, i.e. inflammatory infiltration, the amount of connective tissue and features of cardiomyocyte degeneration were estimated. (biomedcentral.com)
  • There is a noticeable lymphocytic and inflamed cell infiltrate in chronic coxsackie myocarditis. (ontariohomeopath.ca)
  • Collectively our data imply that the CRMP complex acts as a host-molecular sensor to ensure that rhoptry exocytosis occurs when the parasite contacts the host cell. (stanford.edu)
  • The lecture series is a joint activity of the chairs of Cell- and Developmental Biology, Microbiology, Biophysics and Bioinformatics and deals with concepts of modern molecular biology from the point of view of these different disciplines. (uni-wuerzburg.de)
  • The bioinformatics section contains a large amount of examples for applications which allow the investigation of the molecular biology of a cell with bioinformatics tools. (uni-wuerzburg.de)
  • The microbiological section deals with basic molecular aspects of prokaryotic cells. (uni-wuerzburg.de)
  • The topics range from classical developmental subjects such as tissue regeneration and morphogenetic cell migration to molecular stem cell biology, epigenetic plasticity, origins of multicellularity and development within changing environments. (uni-wuerzburg.de)
  • We use a broad array of cell biological and biochemical approaches, as well as cutting-edge molecular genetics and genome editing. (labex-parafrap.fr)
  • We identified membrane-bound proteins, named CRMPs, forming part of a large complex essential for rhoptry secretion and invasion in Toxoplasma. (stanford.edu)
  • The M. Lebrun group explores i) the structure/function of proteins constituting the moving junction, a key structure formed during invasion of the host cell, ii) the mechanisms that trigger rhoptry exocytosis upon binding of the parasite to the host cell, iii) the fusion machinery of the rhoptry with the parasite plasma membrane, and iv) how rhoptry content is introduced in the host. (labex-parafrap.fr)
  • These bugs have a knack for pinpointing critical cell functions, she says, adding fondly that Legionella is continuing to help her explore how eukaryotic cells work. (the-scientist.com)
  • The organism enters host cells and resides in the cytoplasm in a membrane-bound parasitophorous vacuole (PV). (life-science-alliance.org)
  • It was the early 2000s, and Mukherjee was working in Dennis Shields's lab at Albert Einstein College of Medicine, studying how cells organize the internal transport of proteins and other cargo. (the-scientist.com)
  • CRMPs and their partners contain putative host cell-binding domains, and CRMPa shares similarities with GPCR proteins. (stanford.edu)
  • Researchers report FLRT proteins guide precursors of pyramidal cells during neurodevelopment. (neurosciencenews.com)
  • A s a grad student in cell biology, Shaeri Mukherjee was always on the lookout for new ways to fiddle with cells' internal structures. (the-scientist.com)
  • This 5 weeks full-time practical course provides an introduction into modern cell and developmental biology-related methods with a focus on Bio-Imaging techniques. (uni-wuerzburg.de)
  • Well-defined aspects of scientific projects are addressed with independently designed experiments in the context of current research projects in the field of cell and developmental biology. (uni-wuerzburg.de)
  • The participants are qualified to carry out scientific experiments in the field of cell and developmental biology independently and modify them according to the outcome. (uni-wuerzburg.de)
  • Between the period of 1983 and 2009, there were a total of 25 cases of small cell carcinoma, 20 of squamous carcinoma, and 10 of adenocarcinoma, wherein prediagnosis urine cytology was available. (cytojournal.com)
  • All the adenocarcinomas categorized as negative by urine cytology had sparse cellularity and did not reveal any atypical cells on slide review. (cytojournal.com)
  • it infects the nucleated cells of virtually all warm-blooded animals. (medscape.com)
  • formerly called microscopic polyarteritis) is an ANCA-associated systemic vasculitis that has some features similar to those of classic PAN, with the additional involvement of renal glomeruli and pulmonary capillaries. (medscape.com)
  • When attempts electrolytes became normal, haemoglobin were made to make new smears and suspen- was 13.4 g/dL, white blood cell count was sion for biochemical tests, removing the 9.1 × 103/ L and platelets 411 × 103/ L. colonies from the plates proved difficult. (who.int)
  • Recently, we developed a hematopoietic stem cell-based approach to tackle this issue, in which we can genetically alter nucleated hematopoietic precursor cells and differentiate them ex-vivo to mature erythrocytes that can be infected by P. falciparum. (stanford.edu)
  • Researchers show how inflammation in pregnant mice can trigger excessive division of neural stem cells in their offspring. (neurosciencenews.com)
  • Researchers have produced a detailed map of cortical cells types and gene activity within them. (neurosciencenews.com)
  • Intrigued by this powerful little microbe, Mukherjee applied for a postdoc in Roy's lab, where she would study in detail how Legionella attacks human cells from the inside. (the-scientist.com)
  • The biconcave disk shaped human cells are devoid of a nucleus and of most cellular organelles. (biomedcentral.com)
  • To counter these misinterpretations, we describe the morphological features of coronaviruses that should be used to differentiate coronavirus particles from subcellular structures. (cdc.gov)
  • The effect of cell debris within biologic scaffolds upon the macrophage response. (leiferlab.com)
  • The TCR beta sequence of the Gra6-specific TN CD8 T cells is identical in its V- and J-region to the TCR-β harboured by a hybridoma line generated in response to Gra6 peptide. (figshare.com)
  • Population genetic studies dating back to the mid-20th century first proposed that erythrocytes (red blood cells), the host cell for P. falciparum, have been under natural selection due to malaria. (stanford.edu)
  • In contrast, little is known about host cell remodelling by gametocytes. (biomedcentral.com)
  • Additionally, new lipid structures also appear inside the host cell: the parasite is surrounded by a parasitophorous vacuole membrane [ 24 ] and new parasite induced membranous structures (Maurer's clefts and transport vesicles) emerge, which play an important role in trafficking of parasite virulence factors to the surface of infected red blood cell (iRBC) membranes. (biomedcentral.com)
  • Cardiac involvement, which is rare, may be demonstrated on chest radiographs as cardiomegaly in association with features of pulmonary venous hypertension. (medscape.com)
  • CD4+ cell counts were done in 109 patients. (biomedcentral.com)
  • 500 cells/microL are less likely to present with acquired immunodeficiency syndrome (AIDS)-defining illnesses and thus the approach is similar to patients without HIV. (medilib.ir)
  • Added to this, resource constraints prohibit evaluation and decision-making based on cost and labour-intensive methods such as CD4+ cell counts and viral RNA load estimation. (biomedcentral.com)
  • We determined that viral transcription is partially impaired in the fusion T cells. (prolekarniky.cz)
  • Viral load and CD4+ T cell testing should ideally be performed twice before initiating or changing an antiretroviral treatment regimen. (cdc.gov)
  • Membrane lipids of RBCs are believed to be the foundation of these cells' exquisite stability and deformability [ 21 ]. (biomedcentral.com)