MicroRNA Implications across Neurodevelopment and Neuropathology

MicroRNAs (miRNAs) have rapidly emerged as biologically important mediators of posttranscriptional and epigenetic regulation in both plants and animals. miRNAs function through a variety of mechanisms including mRNA degradation and translational repression; additionally, miRNAs may guide gene expression by serving as transcription factors. miRNAs are highly expressed in human brain. Tissue and cell type-specific enrichments of certain miRNAs within the nervous system argue for a biological significance during neurodevelopmental stages. On the other hand, a large number of studies have reported links between alterations of miRNA homeostasis and pathologic conditions such as cancer, heart diseases, and neurodegeneration. Thus, profiles of distinct or aberrant miRNA signatures have most recently surged as one of the most fascinating interests in current biology. Here, the most recent insights into the involvement of miRNAs in the biology of the nervous system and the occurrence of neuropathological disorders are reviewed and discussed

Clickable polymer ligand-functionalized iron oxide nanocubes: A promising nanoplatform for 'local hot spots' magnetically triggered drug release

Exploiting the local heat on the surface of magnetic nanoparticles (MNPs) upon exposure to an alternating magnetic field (AMF) to cleave thermal labile bonds represents an interesting approach in the context of remotely triggered drug delivery. Here, taking advantages of a simple and scalable two-step ligand exchange reaction, we have prepared iron oxide nanocubes (IONCs) functionalized with a novel multifunctional polymer ligand having multiple catechol moieties, furfuryl pendants, and polyethylene glycol (PEG) side chains. Catechol groups ensure a strong binding of the polymer ligands to the IONCs surface, while the PEG chains provide good colloidal stability to the polymer-coated IONCs. More importantly, furfuryl pendants on the polymer enable to click the molecules of interest (either maleimide–fluorescein or maleimide–doxorubicin) via a thermal labile Diels–Alder adduct. The resulting IONCs functionalized with a fluorescein/doxorubicin-conjugated polymer ligand exhibit good colloidal stability in buffer saline and serum solution along with outstanding heating performance in aqueous solution or even in viscous media (81% glycerol/water) when exposed to the AMF of clinical use. The release of conjugated bioactive molecules such as fluorescein and doxorubicin could be boosted by applying AMF conditions of clinical use (16 kAm–1 and 110 kHz). It is remarkable that the magnetic hyperthermia-mediated release of the dye/drug falls in the concentration range 1.0–5.0 μM at an IONCs dose as low as 0.5 gFe/L and at no macroscopical temperature change. This local release effect makes this magnetic nanoplatform a potential tool for drug delivery with remote magnetic hyperthermia actuation and with a dose-independent action of MNPs.This work was partially supported by the Marie Sklodowska-Curie Innovative training network MSCA-ITN-ETN (HeatNMof project, GA 860942), partially by the AIRC Foundation (AIRC IG-14527 to T.P.), partially by the European Research Council (starting grant ICARO, Contract No. 678109), and partially by ERC proof of concept Hypercube, Contract No. 899661)

A MALDI-TOF MS approach for mammalian, human, and formula milks’ profiling

Human milk composition is dynamic, and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), followed by multivariate data analyses as a tool to analyze the peptide profiles of mammalian, human, and formula milks. Breast milk samples from women at different lactation stages (2 (n = 5), 30 (n = 6), 60 (n = 5), and 90 (n = 4) days postpartum), and milk from donkeys (n = 4), cows (n = 4), buffaloes (n = 7), goats (n = 4), ewes (n = 5), and camels (n = 2) were collected. Different brands (n = 4) of infant formulae were also analyzed. Protein content (<30 kDa) was analyzed by MS, and data were exported for statistical elaborations. The mass spectra for each milk closely clustered together, whereas different milk samples resulted in well-separated mass spectra. Human samples formed a cluster in which colostrum constituted a well-defined subcluster. None of the milk formulae correlated with animal or human milk, although they were specifically characterized and correlated well with each other. These findings propose MALDI-TOF MS milk profiling as an analytical tool to discriminate, in a blinded way, different milk types. As each formula has a distinct specificity, shifting a baby from one to another formula implies a specific proteomic exposure. These profiles may assist in milk proteomics for easiness of use and minimization of costs, suggesting that the MALDI-TOF MS pipelines may be useful for not only milk adulteration assessments but also for the characterization of banked milk specimens in pediatric clinical settings

Numerical Modelling of Landslide-Generated Tsunamis with OpenFOAM®: a New Approach

In this paper we present a new method for numerically modelling landslide-generated tsunamis in OpenFOAM® by using a new approach based on the Overset mesh technique. This technique, which is based on the use of two (or more) numerical domains, is new in the coastal engineering field and appears to be extremely powerful to model the interaction between a moving body and one or more fluids. Indeed, the accurate resolution around the moving body (i.e. body-fitted approach), guaranteed by this method, offers a great advantage to study the momentum exchange between the body and the water. Furthermore, in order to overcome a drawback of the Overset mesh implementation we modelled the solid boundaries, along which the landslide body moves, as a porous media with a very low permeability. The new approach has been preliminarily, and successfully, validated through the numerical reproduction of past experiments for landslide-generated tsunamis triggered by a solid and impermeable wedge at a sloping coast

Cr(III) Complexes Bearing a β-Ketoimine Ligand for Olefin Polymerization: Are There Differences between Coordinative and Covalent Bonding?

β-ketoimines are extensively applied for the synthesis of organometallic complexes intended as (pre)catalysts for a variety of chemical transformations. We were interested in the synthesis of two Cr complexes bearing a simple bidentate β-ketoimine (L), with different ligand binding modes, as well as their application as a precatalyst in the polymerization of olefins. Complex 1 (L2CrCl3) was obtained by direct reaction of L with CrCl3(THF)3, while, for the synthesis of complex 2 (LCrCl2), the ligand was first deprotonated with nBuLi, giving the β-ketoiminato ligand L─Li+, and then reacted with CrCl3(THF)3. Characterization of the complexes proved that the Cr(III) ion is coordinatively bonded to L in 1, while it is covalently bonded to L in 2. The complexes were then used as precatalysts for the polymerization of ethylene and various cyclic olefins. Upon activation with methylaluminoxane, both the complexes exhibited poor activity in the polymerization of ethylene, whilst they exhibit good productivity in the polymerization of cyclic olefins, affording semicrystalline oligomers, without a significant difference between 1 and 2. To gain more insight, we investigated the reaction of the complexes with the Al-cocatalyst by IR and UV-Vis spectroscopies. The results proved that, in case of 1, the Al-activator deprotonates the ligand, bringing to the formation of an active species analogous to that of 2

OSMOSIS: Enabling Multi-Tenancy in Datacenter SmartNICs

Multi-tenancy is essential for unleashing SmartNIC's potential in datacenters. Our systematic analysis in this work shows that existing on-path SmartNICs have resource multiplexing limitations. For example, existing solutions lack multi-tenancy capabilities such as performance isolation and QoS provisioning for compute and IO resources. Compared to standard NIC data paths with a well-defined set of offloaded functions, unpredictable execution times of SmartNIC kernels make conventional approaches for multi-tenancy and QoS insufficient. We fill this gap with OSMOSIS, a SmartNICs resource manager co-design. OSMOSIS extends existing OS mechanisms to enable dynamic hardware resource multiplexing on top of the on-path packet processing data plane. We implement OSMOSIS within an open-source RISC-V-based 400Gbit/s SmartNIC. Our performance results demonstrate that OSMOSIS fully supports multi-tenancy and enables broader adoption of SmartNICs in datacenters with low overhead.Comment: 12 pages, 14 figures, 103 reference