1,175 research outputs found
Istruzione terziaria e finanziamenti pubblici: un’opportunità di crescita?
Get PDFLuca Bonacini, Giuseppe Pignataro e Cristina Specchi in relazione alle politiche universitarie, centrali anche per il PNRR, sottolineano l’importanza di un loro orientamento ad accrescere l’attrattività dell’università e, in questa prospettiva, della riduzione del divario tra Nord e Sud, tra centro e periferia
Unfair credit allocations
No full textThis article investigates the impact of credit allocation on heterogeneous wealth entrepre- neurs. We show that with decreasing risk aversion and unobservable wealth, poorer borrowers exert more effort. As a consequence of endogenous adverse selection, they are either excluded from the market or necessarily subsidize richer borrowers in a pooling equilibrium resulting in a paradoxical and inequitable redistribution. Alternatively, a less likely separating equilibrium may occur, in which poor types bear the entire weight of separation in the form of excess risk taking
Emerging Role of microRNAs in Stroke Protection Elicited by Remote Postconditioning
Get PDFRemote ischemic conditioning (RIC) represents an innovative and attractive neuroprotective approach in brain ischemia. The purpose of this intervention is to activate endogenous tolerance mechanisms by inflicting a subliminal ischemia injury to the limbs, or to another “remote” region, leading to a protective systemic response against ischemic brain injury. Among the multiple candidates that have been proposed as putative mediators of the protective effect generated by the subthreshold peripheral ischemic insult, it has been hypothesized that microRNAs may play a vital role in the infarct-sparing effect of RIC. The effect of miRNAs can be exploited at different levels: (1) as transducers of protective messages to the brain or (2) as effectors of brain protection. The purpose of the present review is to summarize the most recent evidence supporting the involvement of microRNAs in brain protection elicited by remote conditioning, highlighting potential and pitfalls in their exploitation as diagnostic and therapeutic tools. The understanding of these processes could help provide light on the molecular pathways involved in brain protection for the future development of miRNA-based theranostic agents in stroke
SALICYLALDEHYDE-TAGGED PEPTIDES FOR THE REVERSIBLE-COVALENT ENGAGEMENT OF PROTEIN LYSINE RESIDUES
Get PDFInserting electrophilic species into small molecule ligands or peptides is a well-established method for enhancing binding affinity to target proteins. The amino acid Lysine (Lys) is highly abundant in the proteome and one of the most frequent residues on the outer structural layers of proteins. For these reasons, the derivatization of synthetic ligands with aldehyde tags capable of imine bond formation with Lys ɛ-amino groups may represent a general strategy for the discovery of potent small-molecule inhibitors.
Ortho-hydroxy aldehydes such as pyridoxal or salicylaldehyde (SA) derivatives have been used to form imines in aqueous media, stabilized by an intramolecular H-bond between the imine N atom and the ortho-phenolic proton. By virtue of this reactivity, SA derivatives are being installed into various classes of protein ligands, aimed at the reversible-covalent engagement of protein Lys residues.1,2
This talk will describe our recent contribution to this field, with focus on the installation of the Lys-engaging SA module into peptide ligands.3,4
Figure 1. Left: Binding mechanism of a reversible-covalent ligand equipped with a salicylaldehyde (SA) tag. Ideally, SA forms a remarkably stable imine bond with a Lys(ε-NH2) residue proximal to the ligand binding site. This covalent ligand-protein connection is stabilized by a H bond between the OH phenolic proton and the imine N atom. As a result, the final ligand-protein complex is stabilized by a combination of non-covalent and covalent interactions. Right: Current options for the SA tag installation at different peptide positions, recently developed by our group.
References
1. A. Dal Corso, M. Catalano, A. Schmid, J. Scheuermann, D. Neri, Angew. Chem. Int. Ed. 2018, 57, 17178.
2. M. Mason, L. Belvisi, L. Pignataro, A. Dal Corso, ChemBioChem 2023, e202300743.
3. G. Sacco, D. Arosio, M. Paolillo, A. Gloger, J. Scheuermann, L. Pignataro, L. Belvisi, A. Dal Corso, C. Gennari, Chem. Eur. J. 2023, e202203768.
4. M. Mason, B. Nava, L. Belvisi, L. Pignataro, A. Dal Corso, Eur. J. Org. Chem. 2024, 27, 202400229
The poor are twice cursed: Wealth inequality and inefficient credit market
No full textThis paper investigates the role of unobservable wealth differences on credit market equilibrium, given there is also asymmetric information concerning effort preferences and choices. In equilibrium, poor but able entrepreneurs may subsidise the rich and incompetent or be excluded. As a result, investment may exceed or fall short of the optimal level. Low inequality may deliver conditions for perfect screening and an efficient level of investment. The equilibrium with cross subsidisation is consistent with otherwise puzzling empirical observations
Equality of Opportunity: Policy and Measurement Paradigms
No full textEquality of opportunity is a widely accepted principle of distributive justice and it is the leading idea of most political platforms in several countries. According to this principle, a society might institute policies that secure an equal distribution of the means to reach a valuable outcome among its members. Once the set of opportunities have been equalized, which particular opportunity, the individual chooses from those open to her, is outside the scope of justice. Ex ante inequalities, and only those inequalities, should be eliminated or compensated for by public intervention. The recent literature on the opportunity egalitarianism often merges these questions introducing two different economic issues. On one side the design of a public policy intended to implement the equality of opportunity view and on the other side the problem of measuring the degree of opportunity inequality in a society. We describe the basic setting and assumptions of some different approaches derived by Roemer’s algorithm for public policy and then we discuss some theoretical and empirical studies to separate and test alternative paradigms on the measurement of inequality of opportunity. Accordingly, an extended critique on the causality issue on policies and measurements is taken into account
Bioanalysis in Femtoliter Scale Printed Artificial Systems
No full textPrinting has fueled the development of a new class of artificial biosystems for the qualitative and
quantitative determination of bioanalytes [1]. In particular, the multiscale organization (from nanometers
to millimeters) and multiplexed molecular composition (DNA, proteins, lipids, polymers) of such platforms
enable the determination of molecular interactions in conditions mimicking/redesigning those of the living
systems. Since the development of microarrays platforms [2], the downsizing of the “analyzable” feature
down to femtoliter (fL) scales has permitted to develop new researches in the field of molecular
condensates/confinement. Herein, two relevant examples of fL-scale systems will be discussed,
highlighting their applications in bioanalysis. The first one includes molecular inks containing DNA
nanoswitches or CYP2E1 catalyzed enzymatic reactions produced by inkjet printing fL-scale compartments
into mineral oil drops [3]. The downscaling triggers the organization of a confined environment at the
water/oil interface, resulting in up-concentration effects and molecular crowding. The employ of
fluorescence lifetime imaging permits to analyze downscaling induced effects, namely up-concentration,
heterogeneity and molecular proximity. The second example consists in fL-scale droplets
produced by microchannel cantilever spotting (μCS) of inks containing single strand DNA (ssDNA) into
porous substrates (nylon), resulting in oligonucleotides microarrays for sensing applications [4]. The
downscaling to fL-scale imbibition into porous substrates highlights an intriguing and complex process
controlled by the interplay of spreading, evaporation and capillary effects, being facilitated by glycerol
additive in the ink. The DNA sequences functionality is demonstrated by hybridization with a fluorolabeled
complementary sequence, producing a double strand sequence (dsDNA). The signal distribution in the spot
is homogeneous and allows for the optical detection of spotted oligonucleotides down to few tents of
zeptomoles
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