scholarly journals Uncovering Membrane-Bound Models of Coagulation Factors by Combined Experimental and Computational Approaches

2021 ◽  
Author(s):  
Y. Zenmei Ohkubo ◽  
Jesper J. Madsen
Keyword(s):  
Coagulation Factors ◽  
The Body ◽  
Computational Studies ◽  
Biological Processes ◽  
Membrane Surfaces ◽  
Health And Disease ◽  
Membrane Bound ◽  
High Space ◽  
Underlying Mechanisms ◽  
Work Done

AbstractIn the life sciences, including hemostasis and thrombosis, methods of structural biology have become indispensable tools for shedding light on underlying mechanisms that govern complex biological processes. Advancements of the relatively young field of computational biology have matured to a point where it is increasingly recognized as trustworthy and useful, in part due to their high space–time resolution that is unparalleled by most experimental techniques to date. In concert with biochemical and biophysical approaches, computational studies have therefore proven time and again in recent years to be key assets in building or suggesting structural models for membrane-bound forms of coagulation factors and their supramolecular complexes on membrane surfaces where they are activated. Such endeavors and the proposed models arising from them are of fundamental importance in describing and understanding the molecular basis of hemostasis under both health and disease conditions. We summarize the body of work done in this important area of research to drive forward both experimental and computational studies toward new discoveries and potential future therapeutic strategies.

scholarly journals A Novel Murine Anti-Lactoferrin Monoclonal Antibody Activates Human Polymorphonuclear Leukocytes through Membrane-Bound Lactoferrin and TLR4

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Xiao-Min Hu ◽  
Yan-Rui Xu ◽  
Ru Yan ◽  
Shu-Liang Sun ◽  
Hong-Liang Dong ◽  
...  
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Iron Homeostasis ◽  
Prognostic Biomarker ◽  
Conformational Epitope ◽  
Health And Disease ◽  
Membrane Bound ◽  
Underlying Mechanisms ◽  
And Function ◽  
Human Polymorphonuclear Leukocytes ◽  
Murine Igg1

Soluble lactoferrin (LTF) is a versatile molecule that not only regulates the iron homeostasis, but also harbors direct microbicidal and immunomodulating abilities in mammalian body fluids. In contrast, little is known about the function of membrane-bound LTF (mbLTF), although its expression on human polymorphonuclear leukocytes (huPMNs) has been reported for decades. Given that LTF/anti-LTF antibodies represent a potential diagnostic/prognostic biomarker and a therapeutic target in patients with immune disorders, we wished, in the present study, to generate a novel human LTF- (huLTF-) specific mAb suitable for detailed analyses on the expression and function of mbLTF as well as for deciphering the underlying mechanisms. By using the traditional hybridoma cell fusion technology, we obtained a murine IgG1 (kappa) mAb, M-860, against huLTF. M-860 recognizes a conformational epitope of huLTF as it binds to natural, but not denatured, huLTF in ELISA. Moreover, M-860 detects mbLTF by FACS and captures endogenous huLTF in total cell lysates of huPMNs. Functionally, M-860 induces the activation of huPMNs partially through TLR4 but independently of phagocytosis. M-860 is thus a powerful tool to analyze the expression and function of human mbLTF, which will further our understanding of the roles of LTF in health and disease.

Analysis of the Anterior Secretory Cells of Onchidohs Muricata (Nudibranchia)

1981 ◽  
Vol 39 ◽  
pp. 614-615
Author(s):  
Roy Skidmore
Keyword(s):  
Endoplasmic Reticulum ◽  
Secretory Granules ◽  
Golgi Body ◽  
The Body ◽  
Secretory Cells ◽  
Secretory Vesicles ◽  
High Magnification ◽  
Large Numbers ◽  
Membrane Bound ◽  
Sole Of The Foot

The long-necked secretory cells in Onchidoris muricata are distributed in the anterior sole of the foot. These cells are interspersed among ciliated columnar and conical cells as well as short-necked secretory gland cells. The long-necked cells contribute a significant amount of mucoid materials to the slime on which the nudibranch travels. The body of these cells is found in the subepidermal tissues. A long process extends across the basal lamina and in between cells of the epidermis to the surface of the foot. The secretory granules travel along the process and their contents are expelled by exocytosis at the foot surface.The contents of the cell body include the nucleus, some endoplasmic reticulum, and an extensive Golgi body with large numbers of secretory vesicles (Fig. 1). The secretory vesicles are membrane bound and contain a fibrillar matrix. At high magnification the similarity of the contents in the Golgi saccules and the secretory vesicles becomes apparent (Fig. 2).

scholarly journals Gut Microbiota and Host Metabolism: From Proof of Concept to Therapeutic Intervention

2021 ◽  
Vol 9 (6) ◽  
pp. 1302
Author(s):  
Patrice D. Cani ◽  
Emilie Moens de Hase ◽  
Matthias Van Hul
Keyword(s):  
Gut Microbiota ◽  
Research Field ◽  
Proof Of Concept ◽  
Clinical Implementation ◽  
Science Area ◽  
Microbiome Research ◽  
Fast Pace ◽  
Health And Disease ◽  
Underlying Mechanisms ◽  
Host Metabolism

The field of the gut microbiota is still a relatively young science area, yet many studies have already highlighted the translational potential of microbiome research in the context of human health and disease. However, like in many new fields, discoveries are occurring at a fast pace and have provided new hope for the development of novel clinical applications in many different medical conditions, not in the least in metabolic disorders. This rapid progress has left the field vulnerable to premature claims, misconceptions and criticism, both from within and outside the sector. Tackling these issues requires a broad collaborative effort within the research field and is only possible by acknowledging the difficulties and challenges that are faced and that are currently hindering clinical implementation. These issues include: the primarily descriptive nature of evidence, methodological concerns, disagreements in analysis techniques, lack of causality, and a rather limited molecular-based understanding of underlying mechanisms. In this review, we discuss various studies and models that helped identifying the microbiota as an attractive tool or target for developing various translational applications. We also discuss some of the limitations and try to clarify some common misconceptions that are still prevalent in the field.

scholarly journals Insights into how environment shapes post-mortem RNA transcription in mouse brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raphael Severino Bonadio ◽  
Larissa Barbosa Nunes ◽  
Patricia Natália S. Moretti ◽  
Juliana Forte Mazzeu ◽  
Stefano Cagnin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mouse Brain ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Rna Degradation ◽  
The Body ◽  
Biological Processes ◽  
Post Mortem ◽  
Gene Expression Alterations ◽  
Upregulated Genes

AbstractMost biological features that occur on the body after death were already deciphered by traditional medicine. However, the molecular mechanisms triggered in the cellular microenvironment are not fully comprehended yet. Previous studies reported gene expression alterations in the post-mortem condition, but little is known about how the environment could influence RNA degradation and transcriptional regulation. In this work, we analysed the transcriptome of mouse brain after death under three concealment simulations (air exposed, buried, and submerged). Our analyses identified 2,103 genes differentially expressed in all tested groups 48 h after death. Moreover, we identified 111 commonly upregulated and 497 commonly downregulated genes in mice from the concealment simulations. The gene functions shared by the individuals from the tested environments were associated with RNA homeostasis, inflammation, developmental processes, cell communication, cell proliferation, and lipid metabolism. Regarding the altered biological processes, we identified that the macroautophagy process was enriched in the upregulated genes and lipid metabolism was enriched in the downregulated genes. On the other hand, we also described a list of biomarkers associated with the submerged and buried groups, indicating that these environments can influence the post-mortem RNA abundance in its particular way.

scholarly journals Mitochondrial Protein Network: From Biogenesis to Bioenergetics in Health and Disease

2020 ◽  
Vol 22 (1) ◽  
pp. 1
Author(s):  
Alessandra Ferramosca
Keyword(s):  
Crucial Role ◽  
Mitochondrial Protein ◽  
Protein Network ◽  
Eukaryotic Cells ◽  
Double Membrane ◽  
Health And Disease ◽  
Membrane Bound

Mitochondria are double membrane-bound organelles which are essential for the viability of eukaryotic cells, because they play a crucial role in bioenergetics, metabolism and signaling [...]

scholarly journals Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

2014 ◽  
Vol 94 (4) ◽  
pp. 1027-1076 ◽  
Author(s):  
M. A. Hanson ◽  
P. D. Gluckman
Keyword(s):  
Animal Studies ◽  
Developmental Plasticity ◽  
Current Knowledge ◽  
Evolutionary Developmental Biology ◽  
Noncommunicable Disease ◽  
Normal Range ◽  
Physiological Processes ◽  
New Concepts ◽  
Health And Disease ◽  
Underlying Mechanisms

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention.

scholarly journals The thymus and the science of self

2021 ◽  
Author(s):  
Vincent Geenen
Keyword(s):  
T Cells ◽  
Adaptive Immune System ◽  
Lymphoid Organ ◽  
The Body ◽  
Effector Cells ◽  
Major Organ ◽  
Organ Specific ◽  
Health And Disease ◽  
Essential State ◽  
The 1960S

AbstractThe conventional perception asserts that immunology is the science of ‘discrimination’ between self and non-self. This concept is however no longer tenable as effector cells of the adaptive immune system are first conditioned to be tolerant to the body’s own antigens, collectively known as self until now. Only then attain these effectors the responsiveness to non-self. The acquisition of this essential state of tolerance to self occurs for T cells in the thymus, the last major organ of our body that revealed its intricate function in health and disease. The ‘thymus’ as an anatomical notion was first notably documented in Ancient Greece although our present understanding of the organ’s functions was only deciphered commencing in the 1960s. In the late 1980s, the thymus was identified as the site where clones of cells reactive to self, termed ‘forbidden’ thymocytes, are physically depleted as the result of a process now known as negative selection. The recognition of this mechanism further contributed to the belief that the central rationale of immunology as a science lies in the distinction between self and non-self. This review will discuss the evidence that the thymus serves as a unique lymphoid organ able to instruct T cells to recognize and be tolerant to harmless self before adopting the capacity to defend the body against potentially injurious non-self-antigens presented in the context of different challenges from infections to exposure to malignant cells. The emerging insight into the thymus’ cardinal functions now also provides an opportunity to exploit this knowledge to develop novel strategies that specifically prevent or even treat organ-specific autoimmune diseases.

Exercise Physiology From 1980 to 2020: Application of the Natural Sciences

2021 ◽  
pp. 1-10
Author(s):  
Jane A. Kent ◽  
Kate L. Hayes
Keyword(s):  
Human Performance ◽  
Exercise Physiology ◽  
Natural Sciences ◽  
The Past ◽  
Interdisciplinary Field ◽  
Advanced Technologies ◽  
Health And Disease ◽  
Fundamental Research ◽  
Research Questions ◽  
Underlying Mechanisms

The field of exercise physiology has enjoyed tremendous growth in the past 40 years. With its foundations in the natural sciences, it is an interdisciplinary field that is highly relevant to human performance and health. The focus of this review is on highlighting new approaches, knowledge, and opportunities that have emerged in exercise physiology over the last four decades. Key among these is the adoption of advanced technologies by exercise physiologists to address fundamental research questions, and the expansion of research topics to range from molecular to organismal, and population scales in order to clarify the underlying mechanisms and impact of physiological responses to exercise in health and disease. Collectively, these advances have ensured the position of the field as a partner in generating new knowledge across many scientific and health disciplines.

Illustrations of the Influence of the Mind upon the Body in Health and Disease, with especial reference to the Imagination

1871 ◽  
Vol 16 (76) ◽  
pp. 538-563
Author(s):  
Daniel H. Tuke
Keyword(s):  
The Body ◽  
Especial Reference ◽  
Health And Disease ◽  
The Mind ◽  
Present Section

Under the present section it remains to consider the influence of the emotions in inducing hydrophobia, tetanus, and catalepsy.

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