X-ray Small and Wide Scattering scanning microscopies have been adopted to inspect morphological and structural properties of collagen-based tissues at the atomic and nano scale1. Examples will be discussed on specific pathologies:
- osteoarthritis of the hip, also named osteoarthrosis of the hip or coxarthrosis, which is a chronic degenerative disorder of the hip joint, causing...
Drug-induced blockade of the human ether-à-go-go-related gene (hERG) channel is today considered the main cause of cardiotoxicity in post-marketing surveillance. Hence, several ligand-based approaches were developed in the last years and are currently employed in the early stages of a drug discovery process for in silico cardiac safety assessment of drug candidates. The first structure-based...
The four member family of “Cyclin and Cystathionine-synthase (CBS) domain divalent metal cation transport mediators”, CNNMs, are the least-studied mammalian magnesium transport mediators. CNNM4 is abundant in the brain and the intestinal tract, and its abnormal activity causes Jalili Syndrome. Recent findings show that suppression of CNNM4 in mice promotes malignant progression of intestinal...
Alzheimer’s disease (AD) is the most common cause of senile dementia affecting more than 50 million people worldwide. AD is a disorder of the central nervous system, clinically characterized by progressive loss of memory and other cognitive skills. Unfortunately, there is no cure for AD.
The major pathophysiological hallmark is the formation of amyloid deposits with a common β-sheet...
MiRNAs, small, highly conserved non coding RNAs, directly regulate more than 60% of the entire human mRNAs.1 They are involved in the regulation of many biological processes as well as their dysregulation can lead to various human diseases.2 As a result, miRNAs represent an attractive class of molecules in drug development and diagnostic. Peptide Nucleic Acid...
Nanostructured materials exhibit outstanding size/shape dependent properties that make them extremely promising in several application fields. Fundamental features that include (but are not limited to) their optical response, thermodynamic behaviour, plasmonic, magnetic and catalytic properties can be modulated by varying nanocrystal size and shape, without altering their chemical...
Neurodegenerative disorders (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and prion diseases are some of the most common forms of age-related diseases. Even if pathogenesis of these neurodegenerative diseases remains unclear, increasing evidences point out a common critical molecular process involving the assembly of various aggregated protein with a β-sheet conformation,...
WHY FORESIGHT?
The Science and Technology Foresight Project has carried out initiatives of great relevance, in order to define research strategies able to address crucial social problems related to energy, food, health, water, as well as the cross-sectoral topic of breakthrough innovative materials, complexity of systems and data science. Both, the holistic approach applied to the...
More than 1000km from the coast and at 3200m of altitude, the Concordia base is one of the 3 bases in the middle of the Antarctic plateau.
Temperatures that go down to -80 degrees have a great effect on activities.
During the long 4-month winter night a small group of people maintain the base and carry out measures and observers.
the National Research Program in Antarctica, PNRA, and the...
Type I collagen is the main fibril-forming protein of the extracellular matrix (ECM), that provides mechanical support to tissues and organs. The protein distribution and organization is tissue-specific, depending on the bio-mechanical function of the tissue itself. From the molecular order, up to supramolecular scale, type I collagen is organized in triple helices assembled in fibrils and...
Over the years, there has been a growing interest in the development of nanofibrous structures with natural (collagen, silk fibroin, elastin, chitosan, alginate) and synthetic (polylactic acid - PLA, poly-lactic-co-glycolic acid – PLGA, polycaprolactone – PCL) polymers as fibrous structures. Thanks to tunable specific features linked to their nanostructure, the application of nanofibers in...
Molecular Replacement is the most used technique to solve macromolecules; an original algorithm called REMO09 (Caliandro et al., 2009) has been developed and implemented in the software produced by Institute of Crystallography. In order to get a final model as complete and refined as possible, we have developed a pipeline based on the synergy between our phase refinement algorithms (Burla et...
The advent of new-generation X-ray sources as well as more sensitive and fast detectors discloses the possibility of deeper static and dynamic structural investigations. X-ray powder diffraction (XPD) and pair distribution function (PDF) measurements are sensitive to long and short-range order, which can be modelled by fitting procedures. Subtle structural changes induced in situ by varying...
Nerve growth factor (NGF) is an important neurotrophic factor involved in the regulation of cell differentiation and survival of target neurons. Expressed as a proNGF precursor, NGF is matured by furin-mediated protease cleavage.
Increasing evidence suggests that NGF and proNGF have distinct functional roles. While the structure of mature NGF is available, little is known about that of the...
SUNBIM (supramolecular and submolecular nano- and biomaterials X-ray imaging) [1] is a suite of integrated programs which, through a user-friendly graphical interface, are optimized to perform a number of functions, such as: centering, q-scale calibration, two-dimensional to one-dimensional folding of small- and wide-angle X-ray scattering (SAXS/WAXS) data, also in grazing-incidence...
Molecules in crystal form represent nowadays one of the preferred formulation for bio-therapeutics. In addition, protein crystallization ensures high stability and a high purity level of the active ingredients and it is potentially able to reduce downstream manufacturing costs by improving the efficiency of the biomolecule purification step with respect to conventional chromatographic methods...
Anthracene derivative compounds have recently known an increasing scientific interest thanks to their unique physical properties (i.e., bright luminescence and large charge mobility)[1], making them ideal candidates for applications in new optoelectronic devices.
A structural study of new anthracene derivative compounds was carried out by single-crystal synchrotron X-ray diffraction to have...
Label-free Multiscale X-ray Imaging can be performed by Table-Top equipment, exploiting both Absorption (usually referred to as X-ray Transmission Microscopy “XTM”) and Scattering contrast. X-ray scattering techniques can provide a large amount of structural and morphological information, both at the atomic and nano-scale, and are thus particularly suited to study composite/nanostructured...
Proteins involved in copper transport and regulation, such as the human Antioxidant 1 copper chaperone (Atox1), are able to mediate the cellular uptake, sequestration, and efflux from cell of platinum-based drugs, affecting their anticancer activity.1 X-ray crystallographic investigations have disclosed the Pt binding sites of Atox1, and shown that the metal binding site of the Atox1 dimer is...
Modern environmental and food monitoring practices require reliable, facile, and on-site detection of hazardous compounds potentially affecting human health. By satisfying these requirements, sensors represent complementary screening tools with a lower impact on the environment compared to conventional chromatographic-based methods. Specifically, biosensor technology offers the possibility to...
Fundamental aspects and an overview of applications of cutting-edge nanocrystallography tools grounded on Wide Angle X-ray Total Scattering (WAXTS) techniques (mainly synchrotron-based) and the use of the Debye Scattering Equation (DSE) for data modeling in reciprocal space will be presented. [1,2]
The approach overcome the limits of conventional diffraction-based methods for characterizing...
The Italian synchrotron Elettra was one of the first 3rd generation accumulation rings designed and built with the aim of producing photon beams to be used in radiation-matter interaction experiments, in which photons constitute a probe to investigate electronic, magnetic and structural properties of matter in solid, liquid and gaseous state. Elettra houses four beamlines dedicated to...
Structural and electronic disorder at nano and mesoscale plays an important role in the functionality of complex materials. Here local heterogeneity and weak interactions developing between structural units cause dynamical spatio-temporal configurations with dynamical correlated disorder. Visualizing these configurations is fundamental for understanding the physical properties of complex...
Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin 3 and Neurotrophin 4 play a range of crucial functions in the developing and adult peripheral and central nervous systems. Initially synthesized as precursors, named proneurotrophins (proNTs), that are cleaved to release C-terminal mature forms, they act through two types of receptors, the specific Trk receptors and the...
Although the crystal structure solution from powder diffraction data is limited respect to the single crystal case, its interest has surprisingly increased in the last twenty-five years. The difficult chance to get a correct interpretation of the experimental powder diffraction pattern, due to peak overlap, background estimation, and preferred orientation, is addressed with improvement in...
The self-assembling of the amyloid β (Aβ) is considered an hallmark in the pathogenesis of Alzheimer’s disease (AD). Many efforts have been devoted in designing molecules able to halt disease progression by inhibiting Aβ self-assembly. We combine biophysical, biochemical and computational techniques to investigate the capacity of four optically pure components of the natural product...
Calcium phosphates (CaP) materials, employed in different biomedical applications because of their density very close to those of CaP mineralized phases of human bones, are largely investigated in many scientific fields [1]. The most known CaP are tricalcium phosphate Ca3(PO4)2 (TCP) and hydroxyapatite Ca5(PO4)3OH (HAp). In the present work, we investigated two sets of substituted β-TCP...
Cultural heritage, whatever their composition and location (indoor or outdoor), are susceptible to deterioration triggered by several factors, such as thermo-hygrometric conditions, mechanical stress, electromagnetic radiation and biodeterioration. One of the main challenges in this sector is the promotion of innovative products for the restoration/protection of artistic value surfaces.
In...
Wound healing is a complex, efficient and highly regulated biological process that consists of four phases: hemostasis, inflammation, proliferation and migration of cells [1]. Copper-dependent stimulation of vessel formation during the wound healing has been mainly attributed to its regulation of vascular endothelial growth factor (VEGF) and angiogenin [2]. The human copper-binding peptide GHK...
Angiogenesis plays a crucial role in numerous physiological and pathological phenomena and consists in a multi-regulated process in which many factors are involved, including growth factors and metals. In particular, Copper stimulation of growth factors, such as vascular endothelial growth factor (VEGF), is involved in the formation of new blood vessels from pre-existing ones1. Although the...
The role of proteasome in the regulation of all cellular functions, is so relevant that its modulation became a useful therapeutic strategy for a large variety of diseases (1). Besides the potential clinical usefulness, proteasome regulators provide interesting and important tools for cell and molecular studies. Some years ago we have proposed cationic porphyrins as a new class of proteasome...
Hyaluronic acid (Hy) is a glycosaminoglycan widely distributed in humans and it is the main component of the extracellular matrix1. The wide range of physiological functions includes hydration and turgidity maintenance of tissue, extracellular matrix structure, regulation of innate immunity, and protection and lubrication of joints. The molecular and mechanical properties make this...
Intrinsically disordered proteins (IDPs) do not have rigid 3D structures, showing changes in their folding depending on the environment or ligands. Intrinsically disordered proteins are widely spread in eukaryotic genomes, and these proteins participate in many cell regulatory metabolism processes. Some IDPs, when aberrantly folded, can be the cause of some diseases such as Alzheimer′s,...
Hyaluronic acid (Hy), is a polyanionic linear nonsulfated glycosaminoglycan (GAG)1. It is widely distributed throughout mammalian cells and tissues and its biomechanical and biochemical properties support its involvement in myriad physiological functions, including hydration and turgidity maintenance of tissue, extracellular matrix structure, regulation of innate immunity, and protection and...
Quorum sensing (QS) is a bacterial cell-to-cell communication mechanism based on the production and detection of chemical signals called autoinducers (AIs) to regulate gene expression in response to changes in population density. QS allows bacteria to behave as a cohesive group under differing environments by means of microbe–microbe and host–microbe interactions1. Interestingly, bacteria...
Neurodegenerative disorders are mainly protein aggregation diseases widespread in the elderly, yet onsets in youngsters are not unheard of. The complexity also arises from their association with each other. For example, a linkage was established between Alzheimer’s disease (AD) and Diabetes mellitus type 2 (T2DM). Studies have shown the increased prevalence of dementia in diabetic vs. non...
Copper (Cu) is an essential micronutrient for most organisms and serves mainly as a redox-active catalytic centre in enzyme cycling between Cu+ and Cu2+. In mammalian cells the membrane transporter Ctr1 regulates the import of Cu into the cytosol (Fig.1). Even though the Cu is imported by Ctr1 as Cu+ , it may be transferred as Cu2+ to the high-affinity N-terminal Cu2+ binding site of the...
The neurotrophins (NTs) are a structurally and functionally related family of growth factors that regulate cell survival, differentiation, neurite outgrowth and regeneration, and synaptic plasticity in both the central and the peripheral nervous system. NTs include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5, -6, -7 [1]. A few...
Many apparently unrelated diseases, including Alzheimer`s Disease (AD), Parkinson Disease (PD) and type II diabetes mellitus (T2DM), result from protein misfolding and abnormal accumulation of toxic amyloid deposits in affected tissues. According to the “Amyloid Hypothesis”, targeting protein misfolding and self-assembly into toxic amyloid aggregates would prevent the diseases. However, the...
Alzheimer's disease (AD), the most common form of dementia worldwide, is an age-related, fatal neurodegenerative disorder. A hallmark of AD is the presence of extracellular proteinaceous deposits (senile plaques) in the brain of affected people.[1] The prevalent component of senile plaques are β-amyloid (Aβ) peptides but it has been underlined the presence of ubiquitin. A reduced Ubiquitin...
Innovative methodologies have been developed and implemented in computer programs aiming at providing efficient computational tools for a wide range of applications in the field of the characterization of polycrystalline materials. The software, based on sound theoretical principles, developed according to the most recent and advanced programming languages and supported by a high level of...
Parkinson’s disease (PD) and α-synucleinopathies are characterized by the progressive loss of neuronal cells and the decline of cognitive and motor functions. Biochemical and neuropathological evidence supports the role of oxidative stress, metal dyshomeostasis and α-synuclein (αSyn, a presynaptic and intrinsically disordered protein), in the development of these disorders. Mounting evidence...
The increase of resistance to antibiotics [1] , also due to a systematic and widespread misuse and abuse of these drugs, is a tremendous problem of healthcare systems and society. Multiple resistance to antibiotics is a global threat aggravated by the lack of novel alternative and effective therapeutic agents [2] . The most worrying multidrug-resistant pathogens are listed by the World Health...
DNA damage caused by free-radicals includes a large variety of base and sugar lesions leading to DNA breaks
and DNA-protein cross-links. Among free radicals, the diffusible hydroxyl radicals (HO · ) are key oxidant species
responsible for reacting with DNA either by hydrogen abstraction from 2-deoxyribose units or by addition to the base
moieties. The purine 5’,8-cyclo-2’-deoxynucleosides...
Carnosine (β-alanyl-L-histidine) is a natural dipeptide widely distributed in mammalian tissues and presented at high concentrations (0.7–2.0mM) in the brain1. As reported previously, carnosine augmented the secretion and expression of various neurotrophic factors (for example, BDNF), leading to the induction of neurite growth in SY-SY5Y cells2. Moreover, carnosine glial release and neuronal...
Peroxisome proliferator-activated receptor gamma Ligand Binding Domain (PPARγ-LBD) represents a key
target for the treatment of type II diabetes and metabolic syndrome. This receptor is the target of
thiazolidinediones, a class of antidiabetic drugs, which improve insulin sensitization and regulate glycemia in
type 2 diabetes. Unfortunately, despite the beneficial effects of synthetic...
Peptides may represent an opportunity for therapeutic intervention that closely mimics natural pathways.1 As a unique class of pharmaceutical compounds peptides are endowed with biochemically and therapeutically distinct properties with respect to small molecules or proteins. Peptides’ favourable pharmaceutical properties include high specificity and potency for their target, minimal potential...
Introduction
This contribution aims to present the design and implementation of an innovative image treatment and 3D printing lab for the production of customized medical devices within a hospital facility.
Methods and Materials
In 2016 a charity from Bank of Italy to Fondazione Santobono Pausilipon (active in assistance, research, training and improvement of the quality of life of...
Con la entrata in vigore del Regolamento generale sulla protezione dei dati UE 2016/679 (RGPD), il CNR ha delineato il proprio assetto organizzativo per la gestione degli adempimenti da questo previsti e posto in essere le attività da svolgere, con il fine di assicurare l’applicazione delle disposizioni in materia di protezione dei dati personali.
Si daranno i principali riferimenti normativi...
It is known since 40’s that the rate of killing by antibiotic is in strict correlation with the bacterial growth rate, and that for non growing bacteria antibiotics result ineffective. The ability of some bacteria to enter and endure in a highly depressed non-replicating metabolic state has been recognize as a frequent cause of failure in the treatment of chronic infections, and the need for...
Understanding of how radiation emitted by a particular radiotracer distributed in various organs, deposits energy in different tissues through various mechanisms of radiation interaction with matter, relies on the correct description of the chemical composition of the scattering medium and the involved radiation transport processes. Monte-Carlo (MC) methods allow the simulation of the...
Introduction. An actual challenge of health systems is the practical implementation of ICT. It is useful to introduce new organizational models and guide decision makers towards an appropriate use of resources. Thanks to a strictly cooperation with healthcare units using ICT techniques and technologies, innovative applications have been studied, designed and implemented.
Telemedicine....
A great challenge in cancer therapy is the selective delivery of anti cancer agents or radiotherapeutic to tumour cells reducing the side effects on normal cells. To further improve delivery efficiency and cancer specificity, great efforts have been dedicated to the development of effective systems that can actively target tumours through the molecular recognition of unique cancer-specific...
Deep Eutectic Solvents (DESs) are mixtures of Lewis or Brønsted acids and bases whose melting point is much lower than that of the individual components.1 Several applications are known in the literature for such neoteric solvents which include the usage of DESs in extraction processes, in biodiesel production and purification, as proton conductors for fuel cells, in metal-, organo- and...
Selection of promising, well characterized hits and leads is essential for success in the drug discovery process. Furthermore, information on the interaction of potential drug candidates with the targeted biomolecule is important as a basis for the understanding of more complex schemes. Binding assays are the type of assays that provide such information on affinity, kinetics and thermodynamics...
One of the institutional tasks of public research bodies is to promote the dissemination of knowledge through editorial initiatives and training courses. Technological progress, in the field of communication, and the diffusion of the Internet makes it possible for the scientific community to produce and distribute academic publishing products on its own. The self-publication of scientific...
Semax is the active component of a drugs developed in Russia in the1982 and originally used as a treatment for brain hypoxia and ischemia, brain traumas, and to facilitate adaptive processes to extreme situations. Semax is now used as a nootropic for mental enhancement in healthy people and for treating many cognitive disorders. N-terminal fragments of the adrenocorticotropic hormone (ACTH),...
Alzheimer’s disease (AD) is a progressive brain disorder that slowly leads to memory loss and cognitive decline. It is considered the most common cause of dementia in the elderly population, with an incidence and related cost of medical care that are expected to increase in the next future. However, none of the pharmacologic treatments available today for AD dementia is able to stop the...
Alzheimer’s disease (AD) is one of the most common form of dementia in the elderly, characterized by a progressive neurodegeneration associated with synaptic dysfunction, pathological accumulation of ß-amyloid (Aß) in plaques, and neuronal loss. The self-association of Aß monomers into soluble oligomers seems to be crucial for the development of neurotoxicity (Walsh and Selkoe, 2007).
Some...
Elettra, the Italian third generation synchrotron source, has been in operation since 1994 and is currently planning a major upgrade of both the storage ring and the beamlines in the framework of a project named Elettra 2.0. A new machine is foresaw, which the current beam parameters1 are very much improved, and planned to be completed in 2026, making Elettra competitive with the most...
Biosensors are interesting devices arising from a synergistic combination of well-established scientific knowledge and cutting-edge technologies, including nanotechnology, biotechnology, and materials science. This cross-disciplinary approach actively contributes to the customization of algae-based biosensors with improved analytical performance (e.g. sensitivity, reproducibility, and fast...
Cockayne syndrome (CS) is a rare genetic progeroid disorder characterized by growth and development defects, severe cutaneous photosensitivity, cachectic dwarfism, progressive neurological dysfunction, and precocious aging. CS is due to mutations in two genes, CSA and CSB. Both gene products are involved in transcription-coupled repair, subpathway of nucleotide excision repair (NER). Although...
The promising, fascinating, and unique optoelectronic properties of lead-halide and lead-chalcogenide nanocrystals motivated, during the last decade, an always increasing scientific interest. The excellent performances of CsPbX3 (X = Cl,Br,I) and PbE (E=S,Se) as nanocrystalline semiconductors naturally raised the attention about the potential advantages of lead-chalcohalides, namely compounds...
Enzyme kinetics relies on a bulky corpus of knowledge which has been consolidated along with more than 100 years of biochemical research. The studies on sucrose hydrolysis by invertase made by Leonor Michaelis and Maud Menten led to the publication in 1913 of their homonymous equation, regarded as the fundamental equation of biochemistry. Since then, enzymologists have devised many different...
Italy holds a huge concentration of historical and cultural heritage. Just in Rome area are present 47 archaeological sites, 180 museums and galleries, 13 villas and palaces (www.beniculturali.it). This amount of artworks needs to be studied and preserved. For more than 6 years, in the Montelibretti IC-CNR secondary location, we are working together with archaeologists, art historians and...
Dall'introduzione nell'ordinamento scolastico della Alternanza Scuola-Lavoro (ASL), con la Legge 107/2015,l’Istituto di Cristallografia (del Consiglio Nazionale delle Ricerche) ha progettato e svolto diversi corsi di formazione presso i suoi laboratori di ricerca a favore degli studenti dell'ultimo triennio delle scuole superiori. I percorsi sono stati progettati con l’intento di accrescere...
Copper is involved in several biological processes. A complex machinery of transporters, storage proteins, chaperones, transcription factors and small molecules as glutathione (GSH which contributes to the cell reducing environment) controls the static and labile copper pools. To follow the fate of intracellular copper labile pool, a variant of human apocarbonic anhydrase has been proposed as...
The abnormal deposition of proteinaceous material is the central pathogenic event of Protein Conformational Diseases (PCDs), which include several incurable disorders such as Alzheimer’s Disease (AD) and Type II Diabetes Mellitus (T2DM). Neuronal damage in AD is closely connected with the presence of abnormal protein aggregates of amyloid-β (Aβ) peptide and protein tau in neurons. T2DM is...
