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Frontiers in Immunology 2018Many parasitic worms possess complex and intriguing life cycles, and schistosomes are no exception. To exit the human body and progress to their successive snail host,... (Review)
Review
Many parasitic worms possess complex and intriguing life cycles, and schistosomes are no exception. To exit the human body and progress to their successive snail host, eggs must migrate from the mesenteric vessels, across the intestinal wall and into the feces. This process is complex and not always successful. A vast proportion of eggs fail to leave their definite host, instead becoming lodged within intestinal or hepatic tissue, where they can evoke potentially life-threatening pathology. Thus, to maximize the likelihood of successful egg passage whilst minimizing host pathology, intriguing egg exit strategies have evolved. Notably, schistosomes actively exert counter-inflammatory influences on the host immune system, discreetly compromise endothelial and epithelial barriers, and modulate granuloma formation around transiting eggs, which is instrumental to their migration. In this review, we discuss new developments in our understanding of schistosome egg migration, with an emphasis on and the intestine, and outline the host-parasite interactions that are thought to make this process possible. In addition, we explore the potential immune implications of egg penetration and discuss the long-term consequences for the host of unsuccessful egg transit, such as fibrosis, co-infection and cancer development.
Topics: Animals; Antigens, Helminth; Disease Models, Animal; Endothelium, Vascular; Feces; Host-Parasite Interactions; Humans; Intestinal Mucosa; Mesenteric Arteries; Mesenteric Veins; Ovum; Peyer's Patches; Schistosoma mansoni
PubMed: 30619372
DOI: 10.3389/fimmu.2018.03042 -
Molecular Microbiology Dec 2018Bacteriophage-encoded endolysins can recognize and bind specific bacteria, and act to cleave the glycosidic and/or amide bonds in the peptidoglycan (PG) bacterial cell... (Review)
Review
Bacteriophage-encoded endolysins can recognize and bind specific bacteria, and act to cleave the glycosidic and/or amide bonds in the peptidoglycan (PG) bacterial cell wall. Cleavage of the cell wall generally results in the death of the bacteria. Their utility as bacteriolytic agents could be exploited for human and veterinary medicines as well as various biotechnological applications. As interest grows in the commercial uses of these proteins, there has been much effort to successfully employ rational design and engineering to produce endolysins with bespoke properties. In this review, we interrogate the current structural data and identify structural features that would be of benefit to engineering the activity and specificity of phage endolysins. We show that the growing body of structural data can be used to predict catalytic residues and mechanism of action from sequences of hypothetical endolysins, and probe the importance of secondary structure repeats in bacterial cell wall-binding domains.
Topics: Anti-Bacterial Agents; Bacteriolysis; Bacteriophages; Biocatalysis; Cell Wall; Computer Simulation; Kinetics; N-Acetylmuramoyl-L-alanine Amidase; Protein Binding; Protein Domains; Protein Structure, Quaternary; Substrate Specificity; Viral Proteins
PubMed: 30230642
DOI: 10.1111/mmi.14134 -
Journal of Dental Research May 2019Bacteria from the Saccharibacteria phylum (formerly known as TM7) are ubiquitous members of the human oral microbiome and are part of the Candidate Phyla Radiation.... (Review)
Review
Bacteria from the Saccharibacteria phylum (formerly known as TM7) are ubiquitous members of the human oral microbiome and are part of the Candidate Phyla Radiation. Recent studies have revealed remarkable 16S rRNA diversity in environmental and mammalian host-associated members across this phylum, and their association with oral mucosal infectious diseases has been reported. However, due to their recalcitrance to conventional cultivation, TM7's physiology, lifestyle, and role in health and diseases remain elusive. The recent cultivation and characterization of Nanosynbacter lyticus type strain TM7x (HMT_952)-the first Saccharibacteria strain coisolated as an ultrasmall obligate parasite with its bacterial host from the human oral cavity-provide a rare glimpse into the novel symbiotic lifestyle of these enigmatic human-associated bacteria. TM7x is unique among all bacteria: it has an ultrasmall size and lives on the surface of its host bacterium. With a highly reduced genome, it lacks the ability to synthesize any of its own amino acids, vitamins, or cell wall precursors and must parasitize other oral bacteria. TM7x displays a highly dynamic interaction with its bacterial hosts, as reflected by the reciprocal morphologic and physiologic changes in both partners. Furthermore, depending on environmental conditions, TM7x can exhibit virulent killing of its host bacterium. Thus, Saccharibacteria potentially affect oral microbial ecology by modulating the oral microbiome structure hierarchy and functionality through affecting the bacterial host's physiology, inhibiting the host's growth dynamics, or affecting the relative abundance of the host via direct killing. At this time, several other uncharacterized members of this phylum have been detected in various human body sites at high prevalence. In the oral cavity alone, at least 6 distinct groups vary widely in relative abundance across anatomic sites. Here, we review the current knowledge on the diversity and unique biology of this recently uncovered group of ultrasmall bacteria.
Topics: Animals; Bacteria; Bacterial Physiological Phenomena; Humans; Microbiota; Mouth; RNA, Ribosomal, 16S
PubMed: 30894042
DOI: 10.1177/0022034519831671 -
Anaesthesiology Intensive Therapy 2019Intra-abdominal hypertension and the abdominal compartment syndrome are well-known, serious, life-threatening clinical entities in acute care surgery. A common... (Review)
Review
Intra-abdominal hypertension and the abdominal compartment syndrome are well-known, serious, life-threatening clinical entities in acute care surgery. A common characteristic of these syndromes is the permanent and irreversible damage that may affect the organs which can be found inside the given compartment if quick intervention cannot be provided. All factors which may and can lead to a sudden increase in the intra-abdominal pressure can be found among the triggering factors of abdominal compartment syndrome. Despite the modern and quick diagnostics, and the adequate surgical interventions performed in time, the mortality of this syndrome is extremely high (38-71%). It affects practically all vital organ systems: cardiovascular, respiratory, urinary and central nervous system. There are four major compartments in the human body: the head, the chest, the abdomen and the extremities. When two or more compartments have elevated pressures the name of the clinical entity is polycompartment syndrome, first described in 2007. The only possible way of establishing the diagnosis is to measure the intra-abdominal pressure, a widespread manner of which is the measurement through the bladder. Treatment of abdominal and polycompartment syndrome is nearly always surgical decompression with temporary abdominal wall closure or open abdominal treatment. Clinicians need to be aware of the real existence of polycompartment syndrome and the complex and constant interplay of raised pressure between compartments. This highlights the importance of research and development of new intra-abdominal pressure measurement techniques.
Topics: Compartment Syndromes; Decompression, Surgical; Humans; Intra-Abdominal Hypertension; Severity of Illness Index
PubMed: 31517472
DOI: 10.5114/ait.2019.87474 -
Development (Cambridge, England) May 2012Tissue fusion events during embryonic development are crucial for the correct formation and function of many organs and tissues, including the heart, neural tube, eyes,... (Review)
Review
Tissue fusion events during embryonic development are crucial for the correct formation and function of many organs and tissues, including the heart, neural tube, eyes, face and body wall. During tissue fusion, two opposing tissue components approach one another and integrate to form a continuous tissue; disruption of this process leads to a variety of human birth defects. Genetic studies, together with recent advances in the ability to culture developing tissues, have greatly enriched our knowledge of the mechanisms involved in tissue fusion. This review aims to bring together what is currently known about tissue fusion in several developing mammalian organs and highlights some of the questions that remain to be addressed.
Topics: Animals; Embryonic Development; Heart; Humans; Neural Tube; Palate
PubMed: 22510983
DOI: 10.1242/dev.068338 -
The European Respiratory Journal Dec 2019Epidemiological studies report that overweight or obese asthmatic subjects have more severe disease than those of a healthy weight. We postulated that accumulation of...
Epidemiological studies report that overweight or obese asthmatic subjects have more severe disease than those of a healthy weight. We postulated that accumulation of adipose tissue within the airway wall may occur in overweight patients and contribute to airway pathology. Our aim was to determine the relationship between adipose tissue within the airway wall and body mass index (BMI) in individuals with and without asthma.Transverse airway sections were sampled in a stratified manner from lungs of control subjects (n=15) and cases of nonfatal (n=21) and fatal (n=16) asthma. The relationship between airway adipose tissue, remodelling and inflammation was assessed. The areas of the airway wall and adipose tissue were estimated by point count and expressed as area per mm of basement membrane perimeter (Pbm). The number of eosinophils and neutrophils were expressed as area densities.BMI ranged from 15 to 45 kg·m and was greater in nonfatal asthma cases (p<0.05). Adipose tissue was identified in the outer wall of large airways (Pbm >6 mm), but was rarely seen in small airways (Pbm <6 mm). Adipose tissue area correlated positively with eosinophils and neutrophils in fatal asthma (Pbm >12 mm, p<0.01), and with neutrophils in control subjects (Pbm >6 mm, p=0.04).These data show that adipose tissue is present within the airway wall and is related to BMI, wall thickness and the number of inflammatory cells. Therefore, the accumulation of airway adipose tissue in overweight individuals may contribute to airway pathophysiology.
Topics: Adipose Tissue; Adult; Asthma; Basement Membrane; Body Mass Index; Bronchi; Case-Control Studies; Eosinophils; Female; Humans; Inflammation; Leukocyte Count; Linear Models; Male; Middle Aged; Neutrophils; Obesity; Overweight; Young Adult
PubMed: 31624112
DOI: 10.1183/13993003.00857-2019 -
Platelets Dec 2023Currently, point-of-care assays for human platelet function and coagulation are used to assess bleeding risks and drug testing, but they lack intact endothelium, a... (Review)
Review
Currently, point-of-care assays for human platelet function and coagulation are used to assess bleeding risks and drug testing, but they lack intact endothelium, a critical component of the human vascular system. Within these assays, the assessment of bleeding risk is typically indicated by the lack of or reduced platelet function and coagulation without true evaluation of hemostasis. Hemostasis is defined as the cessation of bleeding. Additionally, animal models of hemostasis also, by definition, lack human endothelium, which may limit their clinical relevance. This review discusses the current state-of-the-art of hemostasis-on-a-chip, specifically, human cell-based microfluidic models that incorporate endothelial cells, which function as physiologically relevant models of bleeding. These assays recapitulate the entire process of vascular injury, bleeding, and hemostasis, and provide real-time, direct observation, thereby serving as research-enabling tools that enhance our understanding of hemostasis and also as novel drug discovery platforms.
Topics: Animals; Humans; Endothelial Cells; Microfluidics; Hemorrhage; Blood Coagulation; Endothelium; Lab-On-A-Chip Devices
PubMed: 36872890
DOI: 10.1080/09537104.2023.2185453 -
NeuroImage Nov 2020Sensory information is processed in the visual cortex in distinct streams of different anatomical and functional properties. A comparable organizational principle has...
Sensory information is processed in the visual cortex in distinct streams of different anatomical and functional properties. A comparable organizational principle has also been proposed to underlie auditory processing. This raises the question of whether a similar principle characterize the somatosensory domain. One property of a cortical stream is a hierarchical organization of the neuronal response properties along an anatomically distinct pathway. Indeed, several hierarchies between specific somatosensory cortical regions have been identified, primarily using electrophysiology, in non-human primates. However, it has been unclear how these local hierarchies are organized throughout the cortex. Here we used phase-encoded bilateral full-body light touch stimulation in healthy humans under functional MRI to study the large-scale organization of hierarchies in the somatosensory domain. We quantified two measures of hierarchy of BOLD responses, selectivity and laterality. We measured how selectivity and laterality change as we move away from the central sulcus within four gross anatomically-distinct regions. We found that both selectivity and laterality decrease in three directions: parietal, posteriorly along the parietal lobe, frontal, anteriorly along the frontal lobe and medial, inferiorly-anteriorly along the medial wall. The decline of selectivity and laterality along these directions provides evidence for hierarchical gradients. In view of the anatomical segregation of these three directions, the multiplicity of body representations in each region and the hierarchical gradients in our findings, we propose that as in the visual and auditory domains, these directions are streams of somatosensory information processing.
Topics: Adult; Auditory Perception; Brain Mapping; Cerebral Cortex; Female; Frontal Lobe; Functional Laterality; Humans; Male; Parietal Lobe; Somatosensory Cortex; Touch Perception; Visual Cortex; Visual Perception
PubMed: 32822812
DOI: 10.1016/j.neuroimage.2020.117257 -
Clinical Cardiology Jun 2012Marijuana is the most abused recreational drug in the United States. Cannabinoids, the active ingredients of marijuana, affect multiple organ systems in the human body.... (Review)
Review
Marijuana is the most abused recreational drug in the United States. Cannabinoids, the active ingredients of marijuana, affect multiple organ systems in the human body. The pharmacologic effects of marijuana, based on stimulation of cannabinoid receptors CB1 and CB2, which are widely distributed in the cardiovascular system, have been well described. Activation of these receptors modulates the function of various cellular elements of the vessel wall, and may contribute to the pathogenesis of atherosclerosis. Clinically, there are reports linking marijuana smoking to the precipitation of angina and acute coronary syndromes. Recently, large published clinical trials with CB1 antagonist rimonabant did not show any significant benefit of this agent in preventing progression of atherosclerosis. In light of these findings and emerging data on multiple pathways linking cannabinoids to atherosclerosis, we discuss the literature on the role of cannabinoids in the pathophysiology of atherosclerosis. We also propose a marijuana paradox, which implies that inhalation of marijuana may be linked to precipitation of acute coronary syndromes, but modulation of the endocannabinoid system by a noninhalation route may have a salutary effect on the development of atherosclerosis.
Topics: Cannabinoids; Cannabis; Coronary Artery Disease; Coronary Vessels; Endothelium, Vascular; Humans; Inflammation; Lipid Metabolism; United States
PubMed: 22278660
DOI: 10.1002/clc.21962 -
Temperature (Austin, Tex.) 2015Hairless skin acts as a heat exchanger between body and environment, and thus greatly contributes to body temperature regulation by changing blood flow to the skin... (Review)
Review
Hairless skin acts as a heat exchanger between body and environment, and thus greatly contributes to body temperature regulation by changing blood flow to the skin (cutaneous) vascular bed during physiological responses such as cold- or warm-defense and fever. Cutaneous blood flow is also affected by alerting state; we 'go pale with fright'. The rabbit ear pinna and the rat tail have hairless skin, and thus provide animal models for investigating central pathway regulating blood flow to cutaneous vascular beds. Cutaneous blood flow is controlled by the centrally regulated sympathetic nervous system. Sympathetic premotor neurons in the medullary raphé in the lower brain stem are labeled at early stage after injection of trans-synaptic viral tracer into skin wall of the rat tail. Inactivation of these neurons abolishes cutaneous vasomotor changes evoked as part of thermoregulatory, febrile or psychological responses, indicating that the medullary raphé is a common final pathway to cutaneous sympathetic outflow, receiving neural inputs from upstream nuclei such as the preoptic area, hypothalamic nuclei and the midbrain. Summarizing evidences from rats and rabbits studies in the last 2 decades, we will review our current understanding of the central pathways mediating cutaneous vasomotor control.
PubMed: 27227053
DOI: 10.1080/23328940.2015.1069437