Deep infiltrating endometriosis (DIE) is a debilitating subset of endometriosis with an ill-defin... more Deep infiltrating endometriosis (DIE) is a debilitating subset of endometriosis with an ill-defined set of symptoms and lacks specific diagnostic criteria to identify, leading to significant delays in treatment. Endometriosis itself is associated with chronic pain and infertility, leading to significant healthcare costs. A literature has shown that DIE is a non-progressive and curable disease. Currently, diagnosis is based purely on surgical diagnosis, which carriers a higher rate of morbidity, and fear of surgery or reluctance on behalf of provider, may delay diagnosis and thus treatment. Multiple attempts have been made to create an appropriate classification system mainly based on symptoms or imaging, however no one scheme has been successful to appropriately identify DIE. Research has now been geared towards the use of biomarkers, including blood, urine, peritoneal/follicular fluid, or endometrial tissue, to construct a diagnostic tool for DIE. This has the potential to create a less invasive mechanism for earlier identification and treatment of this curable disease.
The more than two hundred species of primates live and reproduce in a large variety of ways. Most... more The more than two hundred species of primates live and reproduce in a large variety of ways. Most species are highly social. Recent studies of primates in nature are revealing new facets of their social and mating systems. Female primates follow their own reproductive strategies, which are less conspicuous than male strategies. The slow development of young primates makes them crucially dependent on intense and prolonged maternal care, exacerbating the imbalance in reproductive effort between the sexes. Primate mating systems seem more flexible than previously thought, as social changes, ecological conditions, and individual character all affect the ways in which primates mate and reproduce. Interactions between males and females range from the molecular, such as interactions between egg and sperm or harmonious expression of paternal and maternal genes in the offspring, to the behavioral, including mating patterns, social affiliation, and parental care. There is increasing evidence for the importance of multiple paternity for females. This evidence includes the need for diverse offspring, for good and compatible genes from the fathers, and for male assistance. Primate mating systems result from a delicate balance between male and female strategies and the constraints exerted by the physical and social environments.
ABSTRACT Efforts to control the global pandemic of human hepatitis B virus (hHBV) infection have ... more ABSTRACT Efforts to control the global pandemic of human hepatitis B virus (hHBV) infection have been hampered by incomplete understanding of viral-host interactions in this disease. This situation has been confounded by the fact that hHBV has a limited host range and cannot be propagated in simple cell culture (1). Reproducible experimental infection with determination of infectivity was demonstrated in chimpanzees (Pan troglodytes), but not other primates (2–4), long before other animal models such as the woodchuck were identified. After successful inoculation of chimpanzees was reported in 1972, multiple institutions, including a multigroup collaboration between the FDA, CDC, and NIH, initiated studies to evaluate them as a model for the study of HBV. For the majority of studies only chimpanzees “with no prior exposure” to virus were used because those with positive serology [either from exposure to hHBV or chimpanzee HBV (chHBV)], with an estimated prevalence of 3–6% in Africa (5), were not reproducibly susceptible to infection (3). It has been widely reported that the effects of HBV infection in chimpanzees are milder than in humans, that is, few have developed fulminant hepatitis, and inoculated chimpanzees exhibit few symptoms or signs of infection. Furthermore, the incidence of chronic infection with HBV (see Table 2) and horizontal and vertical transmission (from mother to offspring) in chimpanzees is lower than in humans (6,7). Chimpanzees have been the cornerstone of all research on infectivity of HBV and safety and efficacy of vaccines.
Proceedings of the National Academy of Sciences of the United States of America, Sep 28, 2021
Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving... more Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving as nonproductive decoys that capture infectious agents and clear them from the cell surface and by erecting a physical barrier that restricts their access to target receptors on host cells. However, the mechanisms through which mucins function are still poorly defined because of a limited repertoire of tools available for tailoring their structure and composition in living cells with molecular precision. Using synthetic glycopolymer mimetics of mucins, we modeled the mucosal glycocalyx on red blood cells (RBCs) and evaluated its influence on lectin (SNA) and virus (H1N1) adhesion to endogenous sialic acid receptors. The glycocalyx inhibited the rate of SNA and H1N1 adhesion in a size- and density-dependent manner, consistent with the current view of mucins as providing a protective shield against pathogens. Counterintuitively, increasing the density of the mucin mimetics enhanced the retention of bound lectins and viruses. Careful characterization of SNA behavior at the RBC surface using a range of biophysical and imaging techniques revealed lectin-induced crowding and reorganization of the glycocalyx with concomitant enhancement in lectin clustering, presumably through the formation of a more extensive glycan receptor patch at the cell membrane. Our findings indicate that glycan-targeting pathogens may exploit the biophysical and biomechanical properties of mucins to overcome the mucosal glycocalyx barrier.
Anthropogeny is a classic term encompassing transdisciplinary investigations of the origins of th... more Anthropogeny is a classic term encompassing transdisciplinary investigations of the origins of the human species. Comparative anthropogeny is a systematic comparison of humans and other living nonhuman hominids (so-called “great apes”), aiming to identify distinctly human features in health and disease, with the overall goal of explaining human origins. We begin with a historical perspective, briefly describing how the field progressed from the earliest evolutionary insights to the current emphasis on in-depth molecular and genomic investigations of “human-specific” biology and an increased appreciation for cultural impacts on human biology. While many such genetic differences between humans and other hominids have been revealed over the last two decades, this information remains insufficient to explain the most distinctive phenotypic traits distinguishing humans from other living hominids. Here we undertake a complementary approach of “comparative physiological anthropogeny,” along the lines of the preclinical medical curriculum, i.e., beginning with anatomy and considering each physiological system and in each case considering genetic and molecular components that are relevant. What is ultimately needed is a systematic comparative approach at all levels from molecular to physiological to sociocultural, building networks of related information, drawing inferences, and generating testable hypotheses. The concluding section will touch on distinctive considerations in the study of human evolution, including the importance of gene-culture interactions.
Deep infiltrating endometriosis (DIE) is a debilitating subset of endometriosis with an ill-defin... more Deep infiltrating endometriosis (DIE) is a debilitating subset of endometriosis with an ill-defined set of symptoms and lacks specific diagnostic criteria to identify, leading to significant delays in treatment. Endometriosis itself is associated with chronic pain and infertility, leading to significant healthcare costs. A literature has shown that DIE is a non-progressive and curable disease. Currently, diagnosis is based purely on surgical diagnosis, which carriers a higher rate of morbidity, and fear of surgery or reluctance on behalf of provider, may delay diagnosis and thus treatment. Multiple attempts have been made to create an appropriate classification system mainly based on symptoms or imaging, however no one scheme has been successful to appropriately identify DIE. Research has now been geared towards the use of biomarkers, including blood, urine, peritoneal/follicular fluid, or endometrial tissue, to construct a diagnostic tool for DIE. This has the potential to create a less invasive mechanism for earlier identification and treatment of this curable disease.
The more than two hundred species of primates live and reproduce in a large variety of ways. Most... more The more than two hundred species of primates live and reproduce in a large variety of ways. Most species are highly social. Recent studies of primates in nature are revealing new facets of their social and mating systems. Female primates follow their own reproductive strategies, which are less conspicuous than male strategies. The slow development of young primates makes them crucially dependent on intense and prolonged maternal care, exacerbating the imbalance in reproductive effort between the sexes. Primate mating systems seem more flexible than previously thought, as social changes, ecological conditions, and individual character all affect the ways in which primates mate and reproduce. Interactions between males and females range from the molecular, such as interactions between egg and sperm or harmonious expression of paternal and maternal genes in the offspring, to the behavioral, including mating patterns, social affiliation, and parental care. There is increasing evidence for the importance of multiple paternity for females. This evidence includes the need for diverse offspring, for good and compatible genes from the fathers, and for male assistance. Primate mating systems result from a delicate balance between male and female strategies and the constraints exerted by the physical and social environments.
ABSTRACT Efforts to control the global pandemic of human hepatitis B virus (hHBV) infection have ... more ABSTRACT Efforts to control the global pandemic of human hepatitis B virus (hHBV) infection have been hampered by incomplete understanding of viral-host interactions in this disease. This situation has been confounded by the fact that hHBV has a limited host range and cannot be propagated in simple cell culture (1). Reproducible experimental infection with determination of infectivity was demonstrated in chimpanzees (Pan troglodytes), but not other primates (2–4), long before other animal models such as the woodchuck were identified. After successful inoculation of chimpanzees was reported in 1972, multiple institutions, including a multigroup collaboration between the FDA, CDC, and NIH, initiated studies to evaluate them as a model for the study of HBV. For the majority of studies only chimpanzees “with no prior exposure” to virus were used because those with positive serology [either from exposure to hHBV or chimpanzee HBV (chHBV)], with an estimated prevalence of 3–6% in Africa (5), were not reproducibly susceptible to infection (3). It has been widely reported that the effects of HBV infection in chimpanzees are milder than in humans, that is, few have developed fulminant hepatitis, and inoculated chimpanzees exhibit few symptoms or signs of infection. Furthermore, the incidence of chronic infection with HBV (see Table 2) and horizontal and vertical transmission (from mother to offspring) in chimpanzees is lower than in humans (6,7). Chimpanzees have been the cornerstone of all research on infectivity of HBV and safety and efficacy of vaccines.
Proceedings of the National Academy of Sciences of the United States of America, Sep 28, 2021
Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving... more Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving as nonproductive decoys that capture infectious agents and clear them from the cell surface and by erecting a physical barrier that restricts their access to target receptors on host cells. However, the mechanisms through which mucins function are still poorly defined because of a limited repertoire of tools available for tailoring their structure and composition in living cells with molecular precision. Using synthetic glycopolymer mimetics of mucins, we modeled the mucosal glycocalyx on red blood cells (RBCs) and evaluated its influence on lectin (SNA) and virus (H1N1) adhesion to endogenous sialic acid receptors. The glycocalyx inhibited the rate of SNA and H1N1 adhesion in a size- and density-dependent manner, consistent with the current view of mucins as providing a protective shield against pathogens. Counterintuitively, increasing the density of the mucin mimetics enhanced the retention of bound lectins and viruses. Careful characterization of SNA behavior at the RBC surface using a range of biophysical and imaging techniques revealed lectin-induced crowding and reorganization of the glycocalyx with concomitant enhancement in lectin clustering, presumably through the formation of a more extensive glycan receptor patch at the cell membrane. Our findings indicate that glycan-targeting pathogens may exploit the biophysical and biomechanical properties of mucins to overcome the mucosal glycocalyx barrier.
Anthropogeny is a classic term encompassing transdisciplinary investigations of the origins of th... more Anthropogeny is a classic term encompassing transdisciplinary investigations of the origins of the human species. Comparative anthropogeny is a systematic comparison of humans and other living nonhuman hominids (so-called “great apes”), aiming to identify distinctly human features in health and disease, with the overall goal of explaining human origins. We begin with a historical perspective, briefly describing how the field progressed from the earliest evolutionary insights to the current emphasis on in-depth molecular and genomic investigations of “human-specific” biology and an increased appreciation for cultural impacts on human biology. While many such genetic differences between humans and other hominids have been revealed over the last two decades, this information remains insufficient to explain the most distinctive phenotypic traits distinguishing humans from other living hominids. Here we undertake a complementary approach of “comparative physiological anthropogeny,” along the lines of the preclinical medical curriculum, i.e., beginning with anatomy and considering each physiological system and in each case considering genetic and molecular components that are relevant. What is ultimately needed is a systematic comparative approach at all levels from molecular to physiological to sociocultural, building networks of related information, drawing inferences, and generating testable hypotheses. The concluding section will touch on distinctive considerations in the study of human evolution, including the importance of gene-culture interactions.
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Papers by Pascal Gagneux