35,936 research outputs found
Extracting physical chemistry from mechanics: a new approach to investigate DNA interactions with drugs and proteins in single molecule experiments
In this review we focus on the idea of establishing connections between the
mechanical properties of DNAligand complexes and the physical chemistry of
DNA-ligand interactions. This type of connection is interesting because it
opens the possibility of performing a robust characterization of such
interactions by using only one experimental technique: single molecule
stretching. Furthermore, it also opens new possibilities in comparing results
obtained by very different approaches, in special when comparing single
molecule techniques to ensemble-averaging techniques. We start the manuscript
reviewing important concepts of the DNA mechanics, from the basic mechanical
properties to the Worm-Like Chain model. Next we review the basic concepts of
the physical chemistry of DNA-ligand interactions, revisiting the most
important models used to analyze the binding data and discussing their binding
isotherms. Then, we discuss the basic features of the single molecule
techniques most used to stretch the DNA-ligand complexes and to obtain force x
extension data, from which the mechanical properties of the complexes can be
determined. We also discuss the characteristics of the main types of
interactions that can occur between DNA and ligands, from covalent binding to
simple electrostatic driven interactions. Finally, we present a historical
survey on the attempts to connect mechanics to physical chemistry for
DNA-ligand systems, emphasizing a recently developed fitting approach useful to
connect the persistence length of the DNA-ligand complexes to the
physicochemical properties of the interaction. Such approach in principle can
be used for any type of ligand, from drugs to proteins, even if multiple
binding modes are present
On C1-robust transitivity of volume-preserving flows
We prove that a divergence-free and C1-robustly transitive vector field has
no singularities. Moreover, if the vector field is C4 then the linear Poincare
flow associated to it admits a dominated splitting over M
Antimicrobial peptides and complement in neonatal hypoxia-ischemia induced brain damage
Hypoxic-ischemic encephalopathy (HIE) is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1-5/1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy, and cognitive disabilities. Even though the brain is considered as an immune-privileged site, it has innate and adaptive immune response and can produce complement (C) components and antimicrobial peptides (AMPs). Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain. Brain ischemia triggers a prolonged inflammatory response affecting the progression of injury and secondary energy failure and involves both innate and adaptive immune systems, including immune-competent and non-competent cells. Following injury to the central nervous system (CNS), including neonatal hypoxia-ischemia (HI), resident microglia, and astroglia are the main cells providing immune defense to the brain in a stimulus-dependent manner. They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation, resulting in neurodegeneration. Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system. Complement activation following neonatal HI injury has been reported to contribute to neurodegeneration. Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs. Astrocytes express β-defensins, which can chemoattract and promote maturation of dendritic cells (DC), and can also limit inflammation by controlling the viability of these same DC. This review will focus on the balance of complement components and AMPs within the CNS following neonatal HI injury and the effect of that balance on the subsequent brain damage
Non-Associativity in the Clifford Bundle on the Parallelizable Torsion 7-Sphere
In this paper we discuss generalized properties of non-associativity in
Clifford bundles on the 7-sphere S7. Novel and prominent properties inherited
from the non-associative structure of the Clifford bundle on S7 are
demonstrated. They naturally lead to general transformations of the spinor
fields on S7 and have dramatic consequences for the associated Kac-Moody
current algebras. All additional properties concerning the non-associative
structure in the Clifford bundle on S7 are considered. We further discuss and
explore their applications.Comment: 16 page
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