364 research outputs found
A network model to investigate structural and electrical properties of proteins
One of the main trend in to date research and development is the
miniaturization of electronic devices. In this perspective, integrated
nanodevices based on proteins or biomolecules are attracting a major interest.
In fact, it has been shown that proteins like bacteriorhodopsin and azurin,
manifest electrical properties which are promising for the development of
active components in the field of molecular electronics. Here we focus on two
relevant kinds of proteins: The bovine rhodopsin, prototype of GPCR protein,
and the enzyme acetylcholinesterase (AChE), whose inhibition is one of the most
qualified treatments of Alzheimer disease. Both these proteins exert their
functioning starting with a conformational change of their native structure.
Our guess is that such a change should be accompanied with a detectable
variation of their electrical properties. To investigate this conjecture, we
present an impedance network model of proteins, able to estimate the different
electrical response associated with the different configurations. The model
resolution of the electrical response is found able to monitor the structure
and the conformational change of the given protein. In this respect, rhodopsin
exhibits a better differential response than AChE. This result gives room to
different interpretations of the degree of conformational change and in
particular supports a recent hypothesis on the existence of a mixed state
already in the native configuration of the protein.Comment: 25 pages, 12 figure
Deciphering the folding kinetics of transmembrane helical proteins
Nearly a quarter of genomic sequences and almost half of all receptors that
are likely to be targets for drug design are integral membrane proteins.
Understanding the detailed mechanisms of the folding of membrane proteins is a
largely unsolved, key problem in structural biology. Here, we introduce a
general model and use computer simulations to study the equilibrium properties
and the folding kinetics of a -based two helix bundle fragment
(comprised of 66 amino-acids) of Bacteriorhodopsin. Various intermediates are
identified and their free energy are calculated toghether with the free energy
barrier between them. In 40% of folding trajectories, the folding rate is
considerably increased by the presence of non-obligatory intermediates acting
as traps. In all cases, a substantial portion of the helices is rapidly formed.
This initial stage is followed by a long period of consolidation of the helices
accompanied by their correct packing within the membrane. Our results provide
the framework for understanding the variety of folding pathways of helical
transmembrane proteins
A K-Nearest Neighbours Based Inverse Sensor Model for Occupancy Mapping
OctoMap is a popular 3D mapping framework which can model the data consistently and keep the 3D models compact with the octree. However, the occupancy map derived by OctoMap can be incorrect when the input point clouds are with noisy measurements. Point cloud filters can reduce the noisy data, but it is unreasonable to apply filters in a sparse point cloud. In this paper, we present a k-nearest neighbours (k-NN) based inverse sensor model for occupancy mapping. This method represents the occupancy information of one point with the average distance from the point to its k-NN in the point cloud. The average distances derived by all the points and their corresponding k-NN are assumed to be normally distributed. Our inverse sensor model is presented based on this normal distribution. The proposed approach is able to deal with sparse and noisy point clouds. We implement the model in the OctoMap to carry out experiments in the real environment. The experimental results show that the 3D occupancy map generated by our approach is more reliable than that generated by the inverse sensor model in OctoMap
Folding of small proteins: A matter of geometry?
We review some of our recent results obtained within the scope of simple
lattice models and Monte Carlo simulations that illustrate the role of native
geometry in the folding kinetics of two state folders.Comment: To appear in Molecular Physic
Entropic Barriers, Frustration and Order: Basic Ingredients in Protein Folding
We solve a model that takes into account entropic barriers, frustration, and
the organization of a protein-like molecule. For a chain of size , there is
an effective folding transition to an ordered structure. Without frustration,
this state is reached in a time that scales as , with
. This scaling is limited by the amount of frustration which
leads to the dynamical selectivity of proteins: foldable proteins are limited
to monomers; and they are stable in {\it one} range of temperatures,
independent of size and structure. These predictions explain generic properties
of {\it in vivo} proteins.Comment: 4 pages, 4 Figures appended as postscript fil
Serum and Salivary IgE, IgA, and IgG4 Antibodies to Dermatophagoides pteronyssinus and Its Major Allergens, Der p1 and Der p2, in Allergic and Nonallergic Children
Allergic rhinitis (AR) is a public health problem with high prevalence worldwide. We evaluated levels of specific IgE, IgA, and IgG4 antibodies to the Dermatophagoides pteronyssinus (Dpt) house dust mite and to its major allergens (Der p1 and Der p2) in serum and saliva samples from allergic and nonallergic children. A total of 86 children were analyzed, from which 72 had AR and 14 were nonallergic healthy children. Serum IgE and serum/salivary IgG4 levels to Dpt, Der p1, and Der p2 were higher in allergic children whereas serum/salivary IgA levels to all allergens were higher in nonallergic children. IgE levels positively correlated with IgG4 and IgA to all allergens in allergic children, while IgA levels negatively correlated with IgG4 to Dpt and Der p1 in nonallergic children. In conclusion, mite-specific IgA antibodies predominate in the serum and saliva of nonallergic children whereas mite-specific IgE and IgG4 are prevalent in allergic children. The presence of specific IgA appears to have a key role for the healthy immune response to mucosal allergens. Also, specific IgA measurements in serum and/or saliva may be useful for monitoring activation of tolerance-inducing mechanisms during allergen specific immunotherapeutic procedures, especially sublingual immunotherapy
Glucosylsphingosine Is a Highly Sensitive and Specific Biomarker for Primary Diagnostic and Follow-Up Monitoring in Gaucher Disease in a Non-Jewish, Caucasian Cohort of Gaucher Disease Patients
Gaucher disease (GD) is the most common lysosomal storage disorder (LSD). Based on a deficient β-glucocerebrosidase it leads to an accumulation of glucosylceramide. Standard diagnostic procedures include measurement of enzyme activity, genetic testing as well as analysis of chitotriosidase and CCL18/PARC as biomarkers. Even though chitotriosidase is the most well-established biomarker in GD, it is not specific for GD. Furthermore, it may be false negative in a significant percentage of GD patients due to mutation. Additionally, chitotriosidase reflects the changes in the course of the disease belatedly. This further enhances the need for a reliable biomarker, especially for the monitoring of the disease and the impact of potential treatments.Here, we evaluated the sensitivity and specificity of the previously reported biomarker Glucosylsphingosine with regard to different control groups (healthy control vs. GD carriers vs. other LSDs).Only GD patients displayed elevated levels of Glucosylsphingosine higher than 12 ng/ml whereas the comparison controls groups revealed concentrations below the pathological cut-off, verifying the specificity of Glucosylsphingosine as a biomarker for GD. In addition, we evaluated the biomarker before and during enzyme replacement therapy (ERT) in 19 patients, demonstrating a decrease in Glucosylsphingosine over time with the most pronounced reduction within the first 6 months of ERT. Furthermore, our data reveals a correlation between the medical consequence of specific mutations and Glucosylsphingosine.In summary, Glucosylsphingosine is a very promising, reliable and specific biomarker for GD
The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts
The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al
Successful Treatment for Hepatic Encephalopathy Aggravated by Portal Vein Thrombosis with Balloon-Occluded Retrograde Transvenous Obliteration
This report presents the case of a 78-year-old female with hepatic encephalopathy due to an inferior mesenteric venous-inferior vena cava shunt. She developed hepatocellular carcinoma affected by hepatitis C virus-related cirrhosis and underwent posterior sectionectomy. Portal vein thrombosis developed and the portal trunk was narrowed after hepatectomy. Portal vein thrombosis resulted in high portal pressure and increased blood flow in an inferior mesenteric venous-inferior vena cava shunt, and hepatic encephalopathy with hyperammonemia was aggravated. The hepatic encephalopathy aggravated by portal vein thrombosis was successfully treated by balloon-occluded retrograde transvenous obliteration via a right transjugular venous approach without the development of other collateral vessels
- …