Multiple Potential Applications Research Articles

The reactivity of endohedral fullerenes. What can be learnt from computational studies?

The last two decades have witnessed major advances in the synthesis and characterization of endohedral fullerenes. These species have interesting physicochemical properties with many potential interesting applications in the fields of magnetism, superconductivity, nonlinear optical properties, radioimmunotherapy, and magnetic resonance imaging contrast agents, among others. In addition to the synthesis and characterization, the chemical functionalization of these species has been a main focus of research for at least four reasons: first, to help characterize endohedral fullerenes that could not be well described structurally otherwise; second, to generate materials with fine-tuned properties leading to enhanced functionality in one of their multiple potential applications; third, to produce water-soluble endohedral fullerenes needed for their use in medicinal sciences; and fourth, to generate electron donor-acceptor conjugates that can be used in solar energy conversion/storage. The functionalization of these species has been achieved through different types of reactions, the most common being the Diels-Alder reactions, 1,3-dipolar cycloadditions, Bingel-Hirsch reactions, and free-radical reactions. It has been found that the performance of these reactions in endohedral fullerenes may be quite different from that of the empty fullerenes. Indeed, encapsulated species have a large influence on the thermodynamics, kinetics, and regiochemistry of these reactions. A detailed understanding of the changes in chemical reactivity due to incarceration of atoms or clusters of atoms is essential to assist the synthesis of new functionalized endohedral fullerenes with specific properties. This Perspective seeks to highlight the key role played by computational chemistry in the analysis of the chemical reactivity of these systems. It is shown that the information obtained through calculations is highly valuable in the process of designing new materials based on endohedral fullerenes.

Millimeter-wave phase resonances in compound reflection gratings with subwavelength grooves

Experimental evidence of phase resonances in a dual-period reflection structure comprising three subwavelength grooves in each period is provided in the millimeter-wave regime. We have analyzed and measured the response of these structures and show that phase resonances are characterized by a minimum in the reflected response, as predicted by numerical calculations. It is also shown that under oblique incidence these structures exhibit additional phase resonances not present for normal illumination because of the potentially permitted odd field distribution. A satisfactory agreement between the experimental and numerical reflectance curves is obtained. These results confirm the recent theoretical predictions of phase resonances in reflection gratings in the millimeter-wave regime, and encourage research in this subject due to the multiple potential applications, such as frequency selective surfaces, backscattering reduction and complex-surface-wave-based sensing. In addition, it is underlined here that the response becomes much more complex than the mere infinite analysis when one considers finite periodic structures as in the real experiment.

A new microtitre plate screening method for evaluating the viability of aerobic respiring bacteria in high surface biofilms

It is difficult to determine the effects of bactericidal compounds against bacteria in a biofilm because classical procedures for determining cell viability require several working days, multiple complicated steps and are frequently only applicable to cells in suspension. We attempt to develop a compact, inexpensive and versatile system to measure directly the extent of biofilm formation from water systems and to determine the viability of respiring bacteria in high surface biofilms. It has been reported that the reduction of tetrazolium sodium salts, such as XTT (sodium 3,3'-[1-[(phenylamino)carbonyl]-3,4-tetrazolium]Bis(4-methoxy)-6-nitro)benzene sulfonic acid hydrate), during active bacterial metabolism can be incorporated into a colorimetric method for quantifying cell viability. XTT is reduced to a soluble formazan compound during bacterial aerobic metabolism such that the amount of formazan generated is proportional to the bacterial biomass. We show here, for the first time, that this colorimetric approach can be used to determine the metabolic activity of adherent aerobic bacteria in a biofilm as a measure of cell viability. This technique has been used to estimate viability and proliferation of bacteria in suspension, but this is the first application to microbial communities in a real undisturbed biofilm. This simple new system can be used to evaluate the complex biofilm community without separating the bacteria from their support. Thus, the results obtained by this practice may be more representative of the circumstances in a natural system, opening the possibility to multiple potential applications.

Fine grain pipeline architecture for high performance phase-based optical flow computation

Accurate motion analysis of real life sequences is a very active research field due to its multiple potential applications. Currently, new technologies offer us very fast and accurate sensors that provide a huge quantity of data per second. Processing these data streams is very expensive (in terms of computing power) for general purpose processors and therefore, is beyond processing capabilities of most current embedded devices. In this work, we present a specific hardware architecture that implements a robust optical flow algorithm able to process input video sequences at a high frame rate and high resolution, up to 160 fps for VGA images. We describe a superpipelined datapath of more than 85 stages (some of them configured with superscalar units able to process several data in parallel). Therefore, we have designed an intensive parallel processing engine. System speed (frames per second) produces fine optical flow estimations (by constraining the actual motion ranges between consecutive frames) and the phase-based method confers the system robustness to image noise or illumination changes. In this work, we analyze the architecture of different frame rates and input image noise levels. We compare the results with other approaches in the state of the art and validate our implementation using several hardware platforms.

Celastrol regulates multiple nuclear transcription factors belonging to HSP90's clients in a dose- and cell type-dependent way

Celastrol, a novel HSP90 inhibitor, has recently attracted much attention due to its potential in multiple applications, such as anti-inflammation use, degenerative neuron disease relief, and tumor management. At present, the studies in celastrol's effects on HSP90's clients have focused on the kinase sub-population, while another key sub-population, nuclear transcription factors (TFs), is not being well-explored. In this study, we observe the effects of celastrol on 18 TFs (belonging to HSP90 clients) in three human cell lines: MCF-7 (breast cancer), HepG2 (hepatoma), and THP-1 (monocytic leukemia). The results show that at least half of the detectable TFs were affected by celastrol, though the effect patterns varied with cell type and dosage. Bi-directional regulations of some TFs were identified, a phenomenon not yet seen with other HSP90 inhibitors. Celastrol's capability to affect multiple TFs was consistent with its altering HSP90/TFs interactions and disrupting HSP90/Hop interaction, in addition to the reported damaging HSP90/Cdc37 interaction. This work confirms, for the first time, that celastrol has broad effects on TFs belonging to HSP90's clients, casts new light on understanding these reported actions, and suggests new possible applications for celastrol, such as diabetes management.

Fabrication and characterization of high-density arrays of P3HT nanopillars on ITO/glass substrates

High-density arrays of semiconducting Poly(3-hexylthiophene) nanopillars are fabricated on indium-tin-oxide/glass substrates by replicating from nanoporous anodic alumina via spin-coating and melt-assisted wetting methods. The geometry of the resulting nanostructure, which is analyzed in detail through environmental scanning electron microscopy, presents an average nanopillar height of 300 nm and an average distance between adjacent nanopillars of 50 nm. In order to check if the fabricated nanopillars are entirely solid without any entrapped gas bubbles, cross-sectional transmission electron microscopy is performed. The current density–voltage characteristic of these arrays is characterized by current sensing atomic force microscopy. Results show higher conductivity than thin films of the same polymer. It is demonstrated that there is nanoconfinement of polymer chains into the pores during the template-assisted process by means of μ-X-ray diffraction. This implies a high alignment of such chains into the nanopillars bulk and, thus, an increasing of conductivity. It is expected that this nanostructure will have multiple potential applications such as organic bulk-heterojunction solar cells, sensors, optoelectronic devices, etc.

In Silico Translation of Cellular and Molecular Mechanisms to Clinical Phenomena in Atheroma Development with an Agent Based Model

Introduction: Atherosclerosis is the build-up of fatty deposits, cholesterol, cellular wastes, calcium and other substances as a “plaque” in the inner lining of arteries. These building plaques can rupture to form a blood clot, effectively blocking blood flow. Although the pathogenesis of atheromas as cell-mediated responses to inflammation have been postulated and shown in specific static models, the integration of this information into a model that captures the dynamics of the process is lacking. To develop effective treatment strategies and techniques, it is essential to characterize plaque formation through the integration of inflammatory responses, treatments, and predisposing factors. Agent-based modeling utilizes mechanistic basic science knowledge to develop a computational model that dynamically represents the inflammatory influences on atherosclerosis. Methods: A basic science literature review was conducted to identify the mechanisms of specific cell-cell interactions in inflammation and atheroma formation. This information was organized into influence diagrams of each cell type's behavior. Cells were treated as input-output devices, where the cell's local environment (molecules, mediators and neighboring cells) led to actions within the cells (expressed as mechanistic rules) to produce outputs back into the local environment. These cellular influence diagrams were converted into an abstract agent based model (ABM) using NetLogo. The resulting ABM included the multiple arterial layers: intima, media, and adventitia; and cellular agent classes: endothelial cells, smooth muscles cells, macrophages, foam cells, platelets, monocytes, t-lymphocytes and fibroblasts. Pattern oriented analysis was used to evaluate the model's behavior under differential shear forces associated with bifurcations of the vascular tree, where increased endothelial activation leading to atheroma formation occurs. Results: The arterial wall ABM successfully simulated general vascular wall cell interactions in macro-vessel endothelial activation, clot formation, intra-intimal inflammation and pre-atheroma formation. These behaviors matched those seen in histological examinations of atheroma formation. Furthermore, varying levels of predisposing factors, such as LDL and platelets, corresponded to respective changes in the likelihood and severity of atheroma development. When subjected to different abstract therapies for specified conditions, the ABM demonstrated behaviors similar to those seen in clinical situations. Conclusions: Combining atherosclerotic and generative inflammatory responses within an ABM provides a dynamic representation of the mechanistic hypothesis associated with atheroma formation. This model has multiple potential applications for modeling arterial wall responses to stent placements, angioplasty or surgical intervention. Agent based modeling, used as a means of dynamic knowledge representation, can be integrated into traditional biomedical research environments, where it can be the first step in the evaluation proposed mechanisms and interventions. Future work includes the incorporation of anti-platelet modalities, anti-nitric oxide therapies, anti-inflammatory therapies, and drug-eliciting stents.

Procalcitonin as a Marker of Severe Bacterial Infection in Children in the Emergency Department

Procalcitonin, the prohormone of calcitonin, is a relatively new and innovative marker of bacterial infection that has multiple potential applications in the pediatric emergency department. In healthy individuals, circulating levels of procalcitonin are generally very low (<0.05 ng/mL), but in the setting of severe bacterial infection and sepsis, levels can increase by hundreds to thousands of fold within 4 to 6 hours. Although the exact physiologic function of procalcitonin has not been determined, the consistent response and rapid rise of this protein in the setting of severe bacterial infection make procalcitonin a very useful biomarker for invasive bacterial disease. In Europe, serum procalcitonin measurements are frequently used in the diagnosis and the management of patients in a variety of clinical settings. To date, the use of procalcitonin has been limited in the United States, but this valuable biomarker has many potential applications in both the pediatric emergency department and the intensive care unit. The intent of this article is to review the history of procalcitonin, describe the kinetics of the molecule in response to bacterial infection, describe the laboratory methods available for measuring procalcitonin, examine the main causes of procalcitonin elevation, and evaluate the potential applications of procalcitonin measurements in pediatric patients.

Polyelectrolyte and carbon nanotube multilayers made from ionic liquid solutions

The inevitable contact of substrates with water during the traditional practice of layer-by-layer assembly (LBL) creates problems for multiple potential applications of LBL films in electronics. To resolve this issue, we demonstrate here the possibility of a LBL process using ionic liquids (ILs), which potentially eliminates corrosion and hydration processes related to aqueous media and opens additional possibilities in structural control of LBL films. ILs are also considered to be one of the best "green" processing solvents, and hence, are advantageous in respect to traditional organic solvents. Poly(ethyleneimine) (PEI) and poly(sodium styrenesulfonate) (PSS) were dispersed in a hydrophilic IL and successfully deposited in the LBL fashion. To produce electroactive thin films with significance to electronics, a similar process was realized for PSS-modified single-walled carbon nanotubes (SWNT-PSS) and poly(vinyl alcohol) (PVA). Characterization of the coating using standard spectroscopy and microscopy techniques typical of the multilayer field indicated that there are both similarities and differences in the structure and properties of LBL films build from ILs and aqueous solutions. The films exhibited electrical conductivity of 10(2) S m(-1) with transparency as high as 98% for visible light, which is comparable to similar parameters for many carbon nanotube and graphene films prepared by both aqueous LBL and other methods.

Hormona de crecimiento: acciones y aplicaciones preventivas y terapéuticas

Growth hormone (GH) is a pleiotropic hormone, expressed at pituitary and peripheral level, which plays a number of different roles far beyond of those classically described. Among these effects it is remarkable the neurotropic role of GH: the hormone increases the proliferation and survival of neural precursors in response to neurological injuries. At the cardiovascular level, GH improves the lipidic profile and decreases the factors of cardiac risk; the hormone recovers the endothelial function, improves the cardiac function and potentiates revascularisation in ischemic territories. Differently to that occurring with autocrine GH, exogenous GH administration does not seem to be related to oncogenesis. According to its effects, there are multiple potential clinical applications of GH: acute treatment of brain injury, due to its antiapoptotic effect; central or peripheral neural regeneration; acute treatment of perinatal anoxia, prevention cerebral palsy; revascularisation of ischemic areas; decrease of the time of bone consolidation after a bone fracture; and torpid ulcer healing.

Diagnostic Ultrasound at MACH 20: Retroperitoneal and Pelvic Imaging in Space

An operationally available diagnostic imaging capability augments spaceflight medical support by facilitating the diagnosis, monitoring and treatment of medical or surgical conditions, by improving medical outcomes and, thereby, by lowering medical mission impacts and the probability of crew evacuation due to medical causes. Microgravity-related physiological changes occurring during spaceflight can affect the genitourinary system and potentially cause conditions such as urinary retention or nephrolithiasis for which ultrasonography (U/S) would be a useful diagnostic tool. This study describes the first genitourinary ultrasound examination conducted in space, and evaluates image quality, frame rate, resolution requirements, real-time remote guidance of nonphysician crew medical officers and evaluation of on-orbit tools that can augment image acquisition. A nonphysician crew medical officer (CMO) astronaut, with minimal training in U/S, performed a self-examination of the genitourinary system onboard the International Space Station, using a Philips/ATL Model HDI-5000 ultrasound imaging unit located in the International Space Station Human Research Facility. The CMO was remotely guided by voice commands from experienced, earth-based sonographers stationed in Mission Control Center in Houston. The crewmember, with guidance, was able to acquire all of the target images. Real-time and still U/S images received at Mission Control Center in Houston were of sufficient quality for the images to be diagnostic for multiple potential genitourinary applications. Microgravity-based ultrasound imaging can provide diagnostic quality images of the retroperitoneum and pelvis, offering improved diagnosis and treatment for onboard medical contingencies. Successful completion of complex sonographic examinations can be obtained even with minimally trained nonphysician ultrasound operators, with the assistance of ground-based real-time guidance. (E-mail: jeffrey.a.jones@nasa.gov)

EUS-Guided In Vivo Microdialysis of Pancreas: A Novel Technique of Potential Diagnostic and Therapeutic Application

Background: Microdialysis has been used as an in vivo research and clinical diagnostic tool in diverse organs to to measure dynamic temporal variations in the extracellular or interstitial concentration of non-protein-bound substance which is undetectable or unstable in the systemic circulation. Thus, we undertook a pre-clinical study to test the technical feasibility of in vivo pancreatic microdialysis with a specially developed microdialysis probe to be inserted into the pancreatic parenchyma through a EUS-guided FNA needle. Methods: Eight beagle dogs were used. Echoendoscope was inserted into the dog stomach under anesthesia. With the scanning plane displaying the pancreas, a 19-gauge needle was punctured into the pancreatic parenchyma. The microdialysis probe (membrane length, 3mm; whole length, 2m; outer diameter, 0.22mm, Fig.) was threaded through the lumen of the 19-gauge puncture needle and probe tip was protruded about 5mm that had been set in advance. The probe was constantly perfused with saline at a flow rate of 1.0 μl/min via the inlet tube and the dialysate in the outlet tube was allowed to drain into 1ml polypropylene vials before and after a single bouls intravenous infusion (20mg/kg) of 5-fluorouracil (5-FU). 5-FU concentration in microdialysates were measured serially every 10 minutes. Results. Microdialysis was unsuccessful in two dogs because the probe tips were broken while insertion into pancreatic parenchyma. In the other six dogs, the concentration of 5-FU in all samples after infusion of 5-FU could be measured as more than 100 folds of the cut-off value. The concentration of 5-FU in the microdialysate increased rapidly and peaked within 10 min (13.9 μg/ml). The peak was followed by a gradual decline. No local bleeding or abnormal fluid collections were observed around the pancreas. Conclusion. EUS-guided pancreatic microdialysis is feasible and has multiple potential clinical applications such as focal pharmocokinetics and detecting new biomarkers of pancreatic carcinomas.

Experimental demonstration of phase resonances in metallic compound gratings with subwavelength slits in the millimeter wave regime

We provide experimental evidence of phase resonances in metallic periodic structures in which each period comprises several subwavelength slits of the same width. We have analyzed and measured the response of these structures in the millimeter wave regime and show that phase resonances are characterized by a remarkable minimum in the transmission response, as predicted by numerical calculations. We compare experimental with numerical results, obtaining a very good agreement between them. This experimental confirmation encourages research in compound structures and their multiple potential applications, such as frequency selective surfaces.

Assessment of the sources of error affecting the quantitative accuracy of SPECT imaging in small animals

Small animal SPECT imaging systems have multiple potential applications in biomedical research. Whereas SPECT data are commonly interpreted qualitatively in a clinical setting, the ability to accurately quantify measurements will increase the utility of the SPECT data for laboratory measurements involving small animals. In this work, we assess the effect of photon attenuation, scatter and partial volume errors on the quantitative accuracy of small animal SPECT measurements, first with Monte Carlo simulation and then confirmed with experimental measurements. The simulations modeled the imaging geometry of a commercially available small animal SPECT system. We simulated the imaging of a radioactive source within a cylinder of water, and reconstructed the projection data using iterative reconstruction algorithms. The size of the source and the size of the surrounding cylinder were varied to evaluate the effects of photon attenuation and scatter on quantitative accuracy. We found that photon attenuation can reduce the measured concentration of radioactivity in a volume of interest in the center of a rat-sized cylinder of water by up to 50% when imaging with iodine-125, and up to 25% when imaging with technetium-99m. When imaging with iodine-125, the scatter-to-primary ratio can reach up to approximately 30%, and can cause overestimation of the radioactivity concentration when reconstructing data with attenuation correction. We varied the size of the source to evaluate partial volume errors, which we found to be a strong function of the size of the volume of interest and the spatial resolution. These errors can result in large (>50%) changes in the measured amount of radioactivity. The simulation results were compared with and found to agree with experimental measurements. The inclusion of attenuation correction in the reconstruction algorithm improved quantitative accuracy. We also found that an improvement of the spatial resolution through the use of resolution recovery techniques (i.e. modeling the finite collimator spatial resolution in iterative reconstruction algorithms) can significantly reduce the partial volume errors.

Non-invasive assessment of coronary flow and coronary flow reserve by transthoracic Doppler echocardiography: a magic tool for the real world

Transthoracic Doppler echocardiography, introduced in the echo-lab in recent last years, to measure coronary flow and coronary flow reserve, is a very attractive tool, totally non-invasive, and easily available at bedside. This review summarizes the actual possibilities of this tool, its multiple potential clinical applications and diagnostic insights, and its arising prognosis value, in coronary artery disease as in various settings affecting the coronary microcirculation.

Minimal invasive reconstruction of posttraumatic hemi facial atrophy by 3-D computer-assisted lipofilling

Facial hemi atrophy is seen after trauma, Parry-Romberg syndrome and on other rare occasions. Since the aesthetic deficit is very obvious and irritating, facial reconstruction is often requested by these patients. In most cases the only option for sufficient reconstruction is free flap reconstruction, which represents the standard treatment. Recently in plastic surgery, various new techniques have been developed with the potential for multiple applications. Lipofilling has been presented primarily for the correction of cosmetic lesions or the reconstruction of minor soft tissue defects, but even reconstruction of larger soft tissue deficits is possible. The concept of using 3-D technology in facial reconstruction has multiple advantages. Primarily, the ideal final aesthetic outcome can be simulated by virtual reconstruction. Mathematic calculations deliver exact numbers in volume deficits, enabling precise planning of soft tissue substitution especially in lipofilling, ideally avoiding unnecessary corrections. Since autologous soft tissue reconstruction represents a dynamic process with periods of swelling as well as atrophy, quality control is required for achieving optimal results. Use of 3-D scanning has the advantage of reliable visualisation in soft tissue reconstruction without the limitations of harmful side effects. We present the history of a female suffering from the posttraumatic consequences of head injuries related to a car accident and the successful correction of her hemi facial atrophy by autologous lipofilling. Technical details and the potential of 3-D scanning in plastic surgery are discussed.

Monoclonal antibodies capable of discriminating the human inhibitory Fcγ‐receptor IIB (CD32B) from the activating Fcγ‐receptor IIA (CD32A): biochemical, biological and functional characterization

Human CD32B (FcgammaRIIB), the low-affinity inhibitory Fcgamma receptor (FcgammaR), is highly homologous in its extracellular domain to CD32A (FcgammaRIIA), an activating FcgammaR. Available monoclonal antibodies (mAb) against the extracellular region of CD32B recognize both receptors. Through immunization of mice transgenic for human CD32A, we generated a set of antibodies specific for the extracellular region of CD32B with no cross-reactivity with CD32A, as determined by enzyme-linked immunosorbent assay and surface plasmon resonance with recombinant CD32A and CD32B, and by fluorescence-activated cell sorting analysis of CD32 transfectants. A high-affinity mAb, 2B6, was used to explore the expression of CD32B by human peripheral blood leucocytes. While all B lymphocytes expressed CD32B, only a fraction of monocytes and almost no polymorphonuclear cells stained with 2B6. Likewise, natural killer cells, which express CD32C, a third CD32 variant, did not react with 2B6. Immune complexes co-engage the inhibitory receptor with activating Fcgamma receptors, a mechanism that limits cell responses. 2B6 competed for immune complex binding to CD32B as a monomeric Fab, suggesting that it directly recognizes the Fc-binding region of the receptor. Furthermore, when co-ligated with an activating receptor, 2B6 triggered CD32B-mediated inhibitory signalling, resulting in diminished release of inflammatory mediators by FcepsilonRI in an in vitro allergy model or decreased proliferation of human B cells induced by B-cell receptor stimulation. These antibodies form the basis for the development of investigational tools and therapeutics with multiple potential applications, ranging from adjuvants in FcgammaR-mediated responses to the treatment of allergy and autoimmunity.

Barnase–barstar high affinity interaction phenomenon as the base for the heterogenous bioluminescence pseudorabies virus' immunoassay

The effective new variant of “sandwich” bioluminescent enzyme immunoassay (BEIA) for the sensitive detection of glycoprotein B (gB) of pseudorabies virus (PrV) was presently developed. The high affinity interaction of barnase–barstar protein pair and photoprotein obelin as bioluminescent marker were for the first time successfully applied to BEIA development. Preliminary the two monoclonal antibodies, 11/5 and 34/2, were raised against gB for ELISA PrV detection. Presently we used the same immuno-“sandwich” principle for BEIA. To do this the two different bioconjugates were elaborated. Recombinant barnase was chemically conjugated with monoclonal anti-PrV's gB IgG, and also barstar was fused in frame to obelin. The characteristics of BEIA method have been compared to ELISA PrV detection. We have shown the proposed here gB-BEIA was 40-fold more sensitive as opposed to gB-ELISA test. The construction might have a broad promise in multiple potential immunological applications.

Adaptive extent and seed yield predictions for Microula sikkimensis grown in the Qinghai-Tibet Plateau, China

Microula sikkimensis (Family Boraginaceae) is a species with multiple potential applications in medicine, food and fodder. From 1994 to 2004, field surveys and transplanting trials were conducted in eleven counties of three provinces in China in order to collect information about the habitat of this species. Extending Hutchinson's concept of a niche as an n-dimensional super-volume, the habitat niche-fitness (HNF) of M. sikkimensis is defined as the degree of similarity between the supply of an actual habitat and the requirement for the habitat to be optimum, in which the supply of the actual habitat and the requirement for the optimum habitat represent realistic habitat conditions and species attributes, respectively. A new model of HNF is constructed to evaluate the adaptive extent of M. sikkimensi with the main habitat factors as independent variables and factor weights as parameters. The calculation results show that the model of HNF notably outperforms the proportional similarity index and the geometric parallelism formula both in mathematical justification and biological principle testing. With HNF as a surrogate for composite environmental factors, a seed yield prediction model was selected from all probable regression models by cross validation method. The apparent prediction error and 45° line test showed that there was no significant difference between the observed seed yield from the test set and the corresponding expected seed yield values from the selected model, confirming the validity of the selected model in predicting seed yield across a wide-spread area. The seed yield prediction model and its uses are recommended within the limitations of the data used in the study area. Beyond this range, validation of the seed yield prediction model will be necessary.

Molecular chaperones: Multiple functions, pathologies, and potential applications

Cell stressors are ubiquitous and frequent, challenging cells often, which leads to the stress response with activation of anti-stress mechanisms. These mechanisms involve a variety of molecules, including molecular chaperones also known as heat-shock proteins (Hsp). The chaperones treated in this article are proteins that assist other proteins to fold, refold, travel to their place of residence (cytosol, organelle, membrane, extracellular space), and translocate across membranes. Molecular chaperones participate in a variety of physiological processes and are widespread in organisms, tissues, and cells. It follows that chaperone failure will have an impact, possibly serious, on one or more cellular function, which may lead to disease. Chaperones must recognize and interact with proteins in need of assistance or client polypeptides (e.g., nascent at the ribosome, or partially denatured by stressors), and have to interact with other chaperones because the chaperoning mechanism involves teams of chaperone molecules, i.e., multimolecular assemblies or chaperone machines. Consequently, chaperone molecules have structural domains with distinctive functions: bind the client polypeptide, interact with other chaperone molecules to build a machine, and interact with other complexes that integrate the chaperoning network. Also, various chaperones have ATP-binding and ATPase sites because the chaperoning process requires as, a rule, energy from ATP hydrolysis. Alterations in any one of these domains due to a mutation or an aberrant post-translational modification can disrupt the chaperoning process and cause diseases termed chaperonopathies. This article presents the pathologic concept of chaperonopathy with examples, and discusses the potential of using chaperones (genes or proteins) in treatment (chaperonotherapy). In addition, emerging topics within the field of study of chaperones (chaperonology) are highlighted, e.g., genomics (chaperonomics), systems biology, extracellular chaperones, and anti-chaperone antibodies.