Pieter Borger

W+W Research Association

The performance of diagnostic tests crucially depends on the disease prevalence, test sensitivity, and test specificity. However, these quantities are often not well known when tests are performed outside defined routine lab procedures which make the rating of the test results somewhat problematic. A current example is the mass testing taking place...

The performance of diagnostic tests crucially depends on the disease prevalence, test sensitivity, and test specificity. However, these quantities are often not well known when tests are performed outside defined routine lab procedures which make the rating of the test results somewhat problematic. A current example is the mass testing taking place...

The performance of diagnostic tests crucially depends on the disease prevalence, test sensitivity, and test specificity. However, these quantities are often not well known when tests are performed outside clinical practice which makes the rating of the test results somewhat problematic. A current example is the mass testing taking place within the...

Background:: After submitting our review report on Corman et al. (referred hereinafter as CD-report) and republishing it on a scientific preprint server (http://doi.org/10.5281/zenodo.4298004) and Researchgate.net we offered the report for public discussion at cormandrostenreview.com on 27th November 2020. The scientific community provided addition...

The genetic code as we find it in nature—the canonical code—has been shown to be highly optimal according to various criteria. It is commonly believed the genetic code was optimised during the course of an evolutionary process (for various purposes). We evaluate this claim and find it wanting. We identify difficulties related to the three families...

In 1970, Susumo Ohno proposed gene and genome duplications as the principal forces that drove the increasing complexity during the evolution from microbes to microbiologists.1 Today, evolutionists assume duplication followed by neo-functionalization is the major source of new genes. Since life is claimed to have started simple and evolved new funct...

In the standard genetic code, 64 codons map to 20 amino acids and a stop signal. The particular assignments show clear evidence that the coding convention used protects against the deleterious effects of mutations. Evolutionists believe the standard code went through multiple refining stages preceding the Last Universal Common Ancestor (LUCA). Vari...

This extensive review report has been officially submitted to Eurosurveillance editorial board on 27th November 2020 via their submission-portal, enclosed to this review report is a retraction request letter, signed by all the main & co-authors. First and last listed names are the first and second main authors. All names in between are co-authors....

Background: bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other prognostic biomarkers, such as expr...

Heterostyly is a fascinating feature of the flowers of a variety of plant families. It both helps to promote sexual reproduction and prevents inbreeding. In the most common form of heterostyly, plants develop either flowers with a short style and long stamens or with a long style and short stamens. The fact that in nature only plants with either of...

Despite numerous studies addressing normal liver regeneration, we still lack comprehensive understanding of the biological processes underlying failed liver regeneration. Therefore, we analyzed the activity of 271 intracellular signaling pathways (ISPs) by genome wide profiling of differentially expressed RNAs in murine liver tissue biopsies after...

It was common knowledge that some strain of coronavirus-sooner or later-was going to cause a pandemic. It was known since the SARS-CoV-outbreak in 2003. In 2013 and 2015, the world was informed that a variant of SARS-CoV in bats was emerging as a threat for humans. Why was no action taken by our governments and the World Health Organization (WHO)?...

Transposable and Transposed Elements are an integral part of all higher genomes and were long regarded junk DNA. It was--and still is--believed they were they are remnants of ancient virus invasions. In the light of current knowledge this vision is untenable. In this perspective a few recent insight on the functions of Lines and ERVs are reported....

Science and dogmatic ideology don’t go very well together. Two biological concepts, "Junk DNA" "pseudogenes" were derived from the darwinian philosophy and have been taught as dogmas for over 40 years. A recent article in Nature argued that the old darwinian idea that pseudogenes are functionless is clearly false. There is now ample evidence--and m...

Background and Aims: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy), a novel 2-staged hepatectomy, dramatically accelerates liver regeneration and thus enables extensive liver tumor resection. The signaling networks underlying the ALPPS-induced accelerated regeneration process are largely unknown. Methods: We pe...

Background: Retroelements (REs) are transposable elements occupying ~40% of the human genome that can regulate genes by providing transcription factor binding sites (TFBS). RE-linked TFBS profile can serve as a marker of gene transcriptional regulation evolution. This approach allows for interrogating the regulatory evolution of organisms with RE-...

Despite the significant achievements in chemotherapy, cancer remains one of the leading causes of death. Target therapy revolutionized this field, but efficiencies of target drugs show dramatic variation among individual patients. Personalization of target therapies remains, therefore, a challenge in oncology. Here, we proposed molecular pathway-ba...

Citation: Miglino N, Tamm M, Borger (2018) Fast Up-regulation of The LINE-1 ORF2 Proteins in Pulmonary Cells after Exposure to Cigarette Smoke. J Pulm Respir Med 8: 454.

In functional genomics studies, research is dedicated to unveiling the function of genes using gene-knockouts, model organisms in which a gene is artificially inactivated. The idea is that, by knocking out the gene, the provoked phenotype would inform us about the function of the gene. Still, the function of many genes cannot be elucidated, because...

Background: Temporary portal vein embolization may be a safe alternative to permanent portal vein embolization. Such a new approach could be applied in living-related liver transplantation to increase graft volume before procurement. The impact of temporary portal vein embolization on occluded liver after recanalization, however, has never been as...

Background & Aims ALPPS, a novel two-staged approach for the surgical removal of large/multiple liver tumors, combines portal vein ligation (PVL) with parenchymal transection. This causes acceleration of compensatory liver growth, enabling faster and more extensive tumor removal. We sought to identify the plasma factors thought to mediate the regen...

Background: Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive ("primed") phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This "primed" phenotype helps to understand pathogenesis of asthma, as changes in BSM func...

Aberrant expression of small noncoding RNAs (sncRNAs), microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) in particular, define several pathologic processes. Asthma is characterized by airway hyperreactivity, chronic inflammation, and airway wall remodeling. Asthma-specific miRNA profiles were reported for bronchial epithelial cells, whereas snc...

Asthma affects more than 300 million people worldwide and its prevalence is still rising. Acute asthma attacks are characterized by severe symptoms such as breathlessness, wheezing, tightness of the chest, and coughing, which may lead to hospitalization or death. Besides the acute symptoms, asthma is characterized by persistent airway inflammation...

Background. Bronchial smooth muscle cells (BSMC) are a major source of proinflammatory and proangiogenic cytokines and chemokines, including VEGF and CXC-chemokines. CXC-chemokines act primarily on neutrophils, mediating their recruitment to and activation at the site of inflammation. In humans, house-dust mite (HDM) allergens can cause asthmatic e...

For oxygen supply, airway wall cells depend on diffusion though the basement membrane, as well as on delivery by micro-vessels. In the asthmatic lung, local hypoxic conditions may occur due to increased thickness and altered composition of the basement membrane, as well as due to edema of the inflamed airway wall. In our study we investigated the e...

Airway wall remodelling is a key pathology of asthma. It includes thickening of the airway wall, hypertrophy and hyperplasia of bronchial smooth muscle cells (BSMC), as well as an increased vascularity of the sub-epithelial cell layer. BSMC are known to be the effector cells of bronchoconstriction, but they are increasingly recognized as an importa...

Background Interpretation of gene expression microarray data in the light of external information on both columns and rows (experimental variables and gene annotations) facilitates the extraction of pertinent information hidden in these complex data. Biologists classically interpret genes of interest after retrieving functional information from a s...

Transforming growth factor β (TGF-β), a key mediator of fibrotic responses, is increased in asthma and drives airway remodeling by inducing expression of extracellular matrix (ECM) proteins. We investigated the molecular mechanisms underlying TGF-β-induced ECM expression by airway smooth muscle cells and demonstrate a novel link between TGF-β and W...

Background Airway wall remodelling is a key pathology of asthma. It includes thickening of the airway wall, hypertrophy and hyperplasia of bronchial smooth muscle cells (BSMC), as well as an increased vascularity of the sub-epithelial cell layer. BSMC are known to be the effector cells of bronchoconstriction, but they are increasingly recognized as...

Asthma is a complex disease characterised by inflammation and remodelling of the airways. Over the past few decades enormous progress has been made to understand which genes are associated with asthma development and several interactions between genes and environmental factors have been elucidated. Investigations into genetic and gene expression pr...

Asthma is a highly complex disease, involving both environmental factors and genetics. The origin and aetiology of asthma remain elusive. Dr Pieter Borger hypothesises that variation in transposable elements that act as genetic switches (promoter/enhancers) present in asthma susceptibility genes may be the genetic component of asthma.

Asthma and chronic obstructive pulmonary disease (COPD) are the two most prominent chronic inflammatory lung diseases with increasing prevalence. Both diseases are associated with mild or severe remodeling of the airways. In this review, we postulate that the pathologies of asthma and COPD may result from inadequate responses and/or a deregulated b...

Background. Calreticulin controls the C/EBPαp42/p30 at the translational level trough a cis-regulatory CNG rich loop in the CEBPA mRNA. We determined the effects of steroids and long-acting beta-agonists on the p42/p30 ratio and on calreticulin expression in primary human bronchial smooth muscle (BSM) cells. Methods. The effects of budesonide (10(-...

Cigarette smoke is a major cause of chronic obstructive pulmonary disease (COPD) and emphysema. Although cigarette smoke represses cellular proliferation, the molecular mechanisms underlying this phenomenon are unknown. CCAAT/enhancer-binding proteins (C/EBPs) are key regulators of cell cycle progression, differentiation and pro-inflammatory gene e...

Reduced translation of CEBPA mRNA has been associated with increased proliferation of bronchial smooth muscle (BSM) cells of asthma patients. Here, we assessed the effect of house dust mite (HDM) extracts on the cell proliferation ([(3)H]-thymidine incorporation), inflammation (interleukin (IL)-6 release) and upstream translation regulatory protein...

Mutations are a fact of life. Darwin gave mutations, which he called natural variation between individuals, a key role to explain the origin of species. The origin and nature of mutations is one of the most fundamental questions of biology, and are a hot topic in origin debates. If mutations are merely a matter of chance, then the alignment of muta...

In 2001, molecular biologist Dr. Peter Borger left for a study trip to Australia. The journey that followed was unexpected. Not only did it change his life, but it also fundamentally changed his view of biology. He discovered that living systems are very differently from what he was taught in the academia. Biology is very different from what Darwin...

Rationale: Inflammation, increased fibroblast proliferation, and increased deposition of extracellular matrix (ECM) are hallmarks of early lung fibrosis and asthma. Transforming growth factor-(TGF-) has been suggested as a key regulator of lung tissue homeostasis with several and often opposite effects on fibroblast proliferation and ECM production...

Bronchial smooth muscle (BSM) cells of asthmatic patients have an impaired expression of CCAAT/enhancer binding protein (C/EBP) alpha, which is associated with increased proliferation. We sought to assess the translational regulation of CEBPA mRNA in cultured BSM cells of healthy control subjects (n = 11) and asthmatic patients (n = 12). Translatio...

The major difference between the evolution and creation paradigms is that the evolutionist believes that the natural variation found in populations can explain microbe-to-man evolution via natural selection (Darwinism), while the creationist believes it cannot. This is because the evolutionary, naturalistic framework requires something creationists...

Knockout strategies have demonstrated that the function of many genes cannot be studied by disrupting them in model organisms because the inactivation of these genes does not lead to a phenotypic effect. For living systems, this peculiar phenomenon of genetic redundancy seems to be the rule rather than the exception. Genetic redundancy is now defin...

In the healthy lung, airway epithelial cells (AEC) regulate fibroblast proliferation through release of soluble factors, such as prostaglandins and proteins. Fibroproliferative diseases and airway remodelling may result from an inadequate generation of suppressive factors by AEC or the inability of fibroblasts to respond to them appropriately. The...

The glucocorticoid receptor (GR) is a major control factor for proliferation, differentiation, and inflammation. Our knowledge about the GR is focused on its function as a transcription regulator. However, cells do not always respond to steroids in the same way or develop resistance. The mechanism underlying such a modified steroid response is not...

Gene duplication and lateral gene transfer are observed biological phenomena. Their purpose is still a matter of deliberation among creationist and Intelligent Design researchers, but both may serve functions in a process leading to rapid acquisition of adaptive phenotypes in novel environments. Evolutionists claim that copies of duplicate genes ar...

CCAAT/enhancer-binding proteins (C/EBPs) control cell proliferation; lack of C/EBPalpha correlates with increased proliferation of bronchial smooth muscle cells (BSMCs) of asthmatic patients. We sought to assess disease-specific expression of C/EBPalpha, beta, delta, and epsilon and the effects of budesonide (10(-8) mol/L) and formoterol (10(-8) mo...

Asthma is an airway disease highly prevalent in westernized countries and of unknown etiology. Often, asthma is associated with atopy, but not all atopic individuals have asthma. Some patients with asthma outgrow symptoms, whereas many others acquire asthma later in life. Still other patients suffer from asthma their entire life. How can we explain...

House dust mite major allergens Der p 1 and Der p 5 activate human airway-derived epithelial cells by protease-dependent and protease-independent mechanisms. Kauffman HF1, Tamm M, Timmerman JA, Borger P. Author information 1Department of Allergology, University Medical Centre Groningen, Hanzeplein 1, Groningen, The Netherlands. h.f.kauffman@lc.u...

House dust mite allergens (HDM) cause bronchoconstriction in asthma patients and induce an inflammatory response in the lungs due to the release of cytokines, chemokines and additional mediators. The mechanism how HDM components achieve this is largely unknown. The objective of this study was to assess whether HDM components of Dermatophagoides pte...

Increased proliferation of bronchial smooth-muscle cells may lead to increased muscle mass in the airways of patients with asthma. The antiproliferative effect of glucocorticoids in bronchial smooth-muscle cells in subjects without asthma is mediated by a complex of the glucocorticoid receptor and the CCAAT/enhancer binding protein alpha (C/EBPalph...

Obliterative bronchiolitis (OB) is the major cause of morbidity and mortality after lung transplantation. The potential role of immunosuppressive drugs in the development of OB is uncertain, but there are limited data indicating that cyclosporine A (CsA) may have a direct fibrogenic effect on various human cell types. Epithelium-fibroblast interact...

The adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP) system is known to negatively regulate transcriptional activity of T cells, thereby possibly modulating T-cell-mediated responses at the sites of inflammation. Effects of cAMP have been widely studied in freshly isolated T cells and T-cell clones; yet, effects in differentiated Th1 and...

Asthma is an airway disease with increasing prevalence characterized by intermittent reversible airway obstruction, airway inflammation, and airway wall remodeling. The disease is generally triggered by inhalation of allergens, but nonallergic asthma triggers are quite common. The pathogenesis of asthma is well documented, and a great deal of resea...

T helper 2 (Th2) cytokines [interleukin (IL)-4 and IL-5] play a central role in the development of allergic immune responses. After allergen provocation, the expression of Th2 cytokines is rapidly up-regulated in atopy and asthma. IL-6 is a multifunctional cytokine that is able to direct Th2 immune responses and is secreted by multiple tissue cell...

The adhesion of lymphocytes to the epithelium and the release of proinflammatory cytokines are important features observed during acute and chronic allograft rejection. Development of chronic rejection in lung-transplantation patients is preceded by high levels of interleukin (IL)-6 and IL-8 protein in the bronchoalveolar lavage. Therefore, we stud...

Proteases in extracts of Aspergillus fumigatus cause epithelial cell desquamation and release of proinflammatory cytokines. We sought to assess protease activity in Alternaria alternata, Cladosporium herbarum, and Aspergillus fumigatus extracts and study the ability of these extracts to cause desquamation and release of proinflammatory cytokines fr...

The immunosuppressive effects of cyclosporine (CsA), tacrolimus (FK506), mycophenolate mofetil (MMF), and prednisolone in cells from the immunological compartment are well documented. In contrast, limited information is available with respect to the effects of these immunosuppressive drugs on airway-epithelial cells, although these cells may contri...

Proteases secreted by Aspergillus fumigatus induce the production of cytokines by epithelial cells, including interleukin (IL)-6 and IL-8. In the present study, we focused on the mechanism(s) by which A. fumigatus-derived proteases elicit cytokine production in epithelial cells. In the epithelial cell line A549, IL-6 and IL-8 mRNA levels were enhan...

In previous studies, we have found a dysfunctional adenylyl cyclase (AC) system in patients with asthma after allergen provocation, which resulted in a 40-50% decreased generation of intracellular cAMP. In addition, in activated T helper lymphocyte clones, it has been demonstrated that IFN-gamma (TH1-like cytokine) and IL-5 (TH2-like cytokine) are...

The TH2-like cytokines interleukin (IL)-4 and IL-5 play a pivotal role in airway wall inflammation in asthma and these cytokines are increased in peripheral blood and bronchoalveolar lavage fluid from asthmatic patients. It is unclear why specifically TH2-like cytokines are increased in asthmatic patients. A possible explanation may be an impaired...

In this study interleukin (IL)-15 was examined for its ability to modulate the expression of interferon-gamma (IFN-gamma) and IL-4 in activated human T lymphocytes. The effect of IL-15 was compared with IL-2 and IL-7, cytokines all known to use the IL-2 receptor gammaC chain. The results demonstrate that the extent of upregulation of IFN-gamma and...

Cytokine gene expression in T lymphocytes is a strictly regulated process, involving both stimulatory and inhibitory signals. beta-Adrenoceptor (betaAR) agonists are widely used in the treatment of asthma and are able to induce an inhibitory signal on immunological responses after binding to their specific receptors. In this study, the characteriza...

Protein kinase A (PKA) activation is documented to be inhibitory for T helper cell (T[H1])-like cytokines (IL-2, IFN-gamma), whereas T(H2)-like cytokines (IL-4, IL-5) are not affected or upregulated. We have recently shown that IL-4 gene expression can be inhibited by PKA activation but depends on the mode of T-cell activation. For IL-5 gene expres...

In the present report, we studied the role of the stromal-derived cytokine interleukin-7 (IL-7) in the IL-2-gene regulation in activated T lymphocytes. Production of IL-2 requires the formation of transcription factors involved in the IL-2-gene regulation. T-cell receptor (TCR)/CD3 engagement results in the activation of nuclear factor of activated...

In the present report, we studied the role of the stromal-derived cytokine interleukin-7 (IL-7) in the IL-2–gene regulation in activated T lymphocytes. Production of IL-2 requires the formation of transcription factors involved in the IL-2 –gene regulation. T-cell receptor (TCR)/CD3 engagement results in the activation of nuclear factor of activate...

Expression of cytokines by T lymphocytes is a highly balanced process, involving stimulatory and inhibitory intracellular signaling pathways. We have examined the modulating effects of the cAMP-dependent signaling pathway on the expression of interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in activated human T lym...