scholarly journals Molecular Basis of the Functional Differences between Soluble Human Versus Murine MD-2: Role of Val135 in Transfer of Lipopolysaccharide from CD14 to MD-2

2016 ◽  
Vol 196 (5) ◽  
pp. 2309-2318 ◽  
Author(s):  
Jožica Vašl ◽  
Alja Oblak ◽  
Tina T. Peternelj ◽  
Javier Klett ◽  
Sonsoles Martín-Santamaría ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Functional Differences

scholarly journals Does the Interaction between Local and Systemic Inflammation Provide a Link from Psychology and Lifestyle to Tissue Health in Musculoskeletal Conditions?

2021 ◽  
Vol 22 (14) ◽  
pp. 7299
Author(s):  
David M. Klyne ◽  
Mary F. Barbe ◽  
Greg James ◽  
Paul W. Hodges
Keyword(s):  
Connective Tissue ◽  
Systemic Inflammation ◽  
Molecular Basis ◽  
Tissue Level ◽  
Lifestyle Factors ◽  
Local Inflammation ◽  
Musculoskeletal Conditions ◽  
Tissue Biology ◽  
Mind And Body

Musculoskeletal conditions are known to involve biological, psychological, social and, often, lifestyle elements. However, these domains are generally considered in isolation from each other. This siloed approach is unlikely to be adequate to understand the complexity of these conditions and likely explains a major component of the disappointing effects of treatment. This paper presents a hypothesis that aims to provide a foundation to understand the interaction and integration between these domains. We propose a hypothesis that provides a plausible link between psychology and lifestyle factors with tissue level effects (such as connective tissue dysregulation/accumulation) in musculoskeletal conditions that is founded on understanding the molecular basis for interaction between systemic and local inflammation. The hypothesis provides plausible and testable links between mind and body, for which empirical evidence can be found for many aspects. We present this hypothesis from the perspective of connective tissue biology and pathology (fibrosis), the role of inflammation locally (tissue level), and how this inflammation is shaped by systemic inflammation through bidirectional pathways, and various psychological and lifestyle factors via their influence on systemic inflammation. This hypothesis provides a foundation for new consideration of the development and refinement of personalized multidimensional treatments for individuals with musculoskeletal conditions.

scholarly journals From Capsids to Complexes: Expanding the Role of TRIM5α in the Restriction of Divergent RNA Viruses and Elements

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 446
Author(s):  
Kevin M. Rose ◽  
Stephanie J. Spada ◽  
Rebecca Broeckel ◽  
Kristin L. McNally ◽  
Vanessa M. Hirsch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Molecular Basis ◽  
Human Population ◽  
Rna Viruses ◽  
Arms Race ◽  
Innate Immune ◽  
Immunodeficiency Virus ◽  
Underlying Mechanisms ◽  
Hiv 1

An evolutionary arms race has been ongoing between retroviruses and their primate hosts for millions of years. Within the last century, a zoonotic transmission introduced the Human Immunodeficiency Virus (HIV-1), a retrovirus, to the human population that has claimed the lives of millions of individuals and is still infecting over a million people every year. To counteract retroviruses such as this, primates including humans have evolved an innate immune sensor for the retroviral capsid lattice known as TRIM5α. Although the molecular basis for its ability to restrict retroviruses is debated, it is currently accepted that TRIM5α forms higher-order assemblies around the incoming retroviral capsid that are not only disruptive for the virus lifecycle, but also trigger the activation of an antiviral state. More recently, it was discovered that TRIM5α restriction is broader than previously thought because it restricts not only the human retroelement LINE-1, but also the tick-borne flaviviruses, an emergent group of RNA viruses that have vastly different strategies for replication compared to retroviruses. This review focuses on the underlying mechanisms of TRIM5α-mediated restriction of retroelements and flaviviruses and how they differ from the more widely known ability of TRIM5α to restrict retroviruses.

On the molecular basis of pyruvate kinase deficiency II. Role of thiol groups in pyruvate kinase from pyruvate kinase-deficient patients

1974 ◽  
Vol 334 (2) ◽  
pp. 361-367 ◽  
Author(s):  
Th.J.C. Van Berkel ◽  
G.E.J. Staal ◽  
J.F. Koster ◽  
J.G. Nyessen ◽  
L. van Milligen-Boersma
Keyword(s):  
Pyruvate Kinase ◽  
Molecular Basis ◽  
Thiol Groups ◽  
Pyruvate Kinase Deficiency

Molecular Basis for Nucleotide-binding Specificity: Role of the Exocyclic Amino Group “N2” in Recognition by a Guanylyl-ribonuclease

2006 ◽  
Vol 355 (1) ◽  
pp. 72-84 ◽  
Author(s):  
Greta L. Schrift ◽  
Travis T. Waldron ◽  
Mitchell A. Timmons ◽  
S. Ramaswamy ◽  
William R. Kearney ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Binding Specificity ◽  
Nucleotide Binding ◽  
Amino Group

scholarly journals Molecular Basis of Passive Stress Relaxation in Human Soleus Fibers: Assessment of the Role of Immunoglobulin-Like Domain Unfolding

2003 ◽  
Vol 85 (5) ◽  
pp. 3142-3153 ◽  
Author(s):  
K. Trombitás ◽  
Y. Wu ◽  
M. McNabb ◽  
M. Greaser ◽  
M.S.Z. Kellermayer ◽  
...  
Keyword(s):  
Stress Relaxation ◽  
Molecular Basis ◽  
Passive Stress

scholarly journals Haptoglobin and Its Related Protein, Zonulin—What Is Their Role in Spondyloarthropathy?

2021 ◽  
Vol 10 (5) ◽  
pp. 1131
Author(s):  
Magdalena Chmielińska ◽  
Marzena Olesińska ◽  
Katarzyna Romanowska-Próchnicka ◽  
Dariusz Szukiewicz
Keyword(s):  
Immune Response ◽  
Free Radicals ◽  
Immune System ◽  
Potential Role ◽  
Acute Phase Protein ◽  
Related Protein ◽  
Functional Differences ◽  
Phase Protein ◽  
Its Polymorphism

Haptoglobin (Hp) is an acute phase protein which supports the immune response and protects tissues from free radicals. Its concentration correlates with disease activity in spondyloarthropathies (SpAs). The Hp polymorphism determines the functional differences between Hp1 and Hp2 protein products. The role of the Hp polymorphism has been demonstrated in many diseases. In particular, the Hp 2-2 phenotype has been associated with the unfavorable course of some inflammatory and autoimmune disorders. Its potential role in modulating the immune system in SpA is still unknown. This article contains pathophysiological considerations on the potential relationship between Hp, its polymorphism and SpA.

Molecular Basis for Functional Differences of AMPA-Subtype Glutamate Receptors

Physiology ◽  
1996 ◽  
Vol 11 (2) ◽  
pp. 77-82 ◽  
Author(s):  
S Ozawa ◽  
J Rossier
Keyword(s):  
Polymerase Chain Reaction ◽  
Ampa Receptors ◽  
Molecular Basis ◽  
Hippocampal Neurons ◽  
Polymerase Chain Reaction Amplification ◽  
Inward Rectification ◽  
Chain Reaction ◽  
Functional Differences ◽  
Reaction Amplification ◽  
Polymerase Chain

To trace the molecular basis of functional properties of native a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors, we have coupled patch-clamp recordings and reverse transcription followed by polymerase chain reaction amplification. AMPA receptors lacking the GluR2 subunit in a population of hippocampal neurons exhibited a strong inward rectification and were highly permeable to Ca2+.

Assessment of Cereal Quality by Micro-Raman Analysis of the Grain Molecular Composition

2002 ◽  
Vol 56 (9) ◽  
pp. 1132-1138 ◽  
Author(s):  
Olivier Piot ◽  
Jean Claude Autran ◽  
Michel Manfait
Keyword(s):  
Molecular Basis ◽  
High Spatial Resolution ◽  
Microscopic Structure ◽  
Grain Texture ◽  
Wheat Grain ◽  
Raman Analysis ◽  
Cereal Grain ◽  
Confocal Raman Microspectroscopy ◽  
Confocal Raman

The development of confocal Raman microspectroscopy for cereal grain studies has led to breakthroughs in the understanding of the molecular basis of grain texture. The high spatial resolution and the nondestructive nature of the technique are its main assets, enabling more detailed analysis of the microscopic structure of wheat grain and investigation of the role of specific components involved in hardness. Hardness is the most relevant criterion in determining the suitability of wheat grain to be processed into flour. Our findings indicate that the α-helical secondary structure of protein could be associated with hardness.

scholarly journals Molecular basis of the dual role of the Mlh1-Mlh3 endonuclease in MMR and in meiotic crossover formation

2021 ◽  
Vol 118 (23) ◽  
pp. e2022704118
Author(s):  
Jingqi Dai ◽  
Aurore Sanchez ◽  
Céline Adam ◽  
Lepakshi Ranjha ◽  
Giordano Reginato ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Molecular Basis ◽  
Crystal Packing ◽  
Critical Role ◽  
Holliday Junctions ◽  
Dual Roles ◽  
Terminal Domain ◽  
C Terminus ◽  
Meiotic Crossover

In budding yeast, the MutL homolog heterodimer Mlh1-Mlh3 (MutLγ) plays a central role in the formation of meiotic crossovers. It is also involved in the repair of a subset of mismatches besides the main mismatch repair (MMR) endonuclease Mlh1-Pms1 (MutLα). The heterodimer interface and endonuclease sites of MutLγ and MutLα are located in their C-terminal domain (CTD). The molecular basis of MutLγ’s dual roles in MMR and meiosis is not known. To better understand the specificity of MutLγ, we characterized the crystal structure of Saccharomyces cerevisiae MutLγ(CTD). Although MutLγ(CTD) presents overall similarities with MutLα(CTD), it harbors some rearrangement of the surface surrounding the active site, which indicates altered substrate preference. The last amino acids of Mlh1 participate in the Mlh3 endonuclease site as previously reported for Pms1. We characterized mlh1 alleles and showed a critical role of this Mlh1 extreme C terminus both in MMR and in meiotic recombination. We showed that the MutLγ(CTD) preferentially binds Holliday junctions, contrary to MutLα(CTD). We characterized Mlh3 positions on the N-terminal domain (NTD) and CTD that could contribute to the positioning of the NTD close to the CTD in the context of the full-length MutLγ. Finally, crystal packing revealed an assembly of MutLγ(CTD) molecules in filament structures. Mutation at the corresponding interfaces reduced crossover formation, suggesting that these superstructures may contribute to the oligomer formation proposed for MutLγ. This study defines clear divergent features between the MutL homologs and identifies, at the molecular level, their specialization toward MMR or meiotic recombination functions.

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