Origin and maintenance of genetic polymorphism

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Presenilin/γ-Secretase and Inflammation

Presenilins (PS) are the catalytic components of γ-secretase, an aspartyl protease that regulates through proteolytic processing the function of multiple signaling proteins. Specially relevant is the γ-secretase-dependent cleavage of the β-amyloid precursor protein (APP) since generates the β-amyloid (Aβ) peptides that aggregate and accumulate in the brain of Alzheimer's disease (AD) patients. Abnormal processing and/or accumulation of Aβ disrupt synaptic and metabolic processes leading to neuron dysfunction and neurodegeneration. Studies in presenilin conditional knockout mice have revealed that presenilin-1 is essential for age-dependent Aβ accumulation and inflammation. By contrast, mutations in the presenilin genes responsible for early onset familial AD cause rapid disease progression and accentuate clinical and pathological features including inflammation. In addition, a number of loss of function mutations in presenilin-1 have been recently associated to non-Alzheimer's dementias including frontotemporal dementia and dementia with Lewy bodies. In agreement, total loss of presenilin function in the brain results in striking neurodegeneration and inflammation, which includes activation of glial cells and induction of proinflammatory genes, besides altered inflammatory responses in the periphery. Interestingly, some non-steroidal anti-inflammatory drugs that slow cognitive decline and reduce the risk of AD, decrease amyloidogenic Aβ42 levels by modulating allosterically PS/γ-secretase. In this review, I present current evidence supporting a role of presenilin/γ-secretase signaling on gliogenesis and gliosis in normal and pathological conditions. Understanding the cellular mechanisms regulated by presenilin/γ-secretase during chronic inflammatory processes may provide new approaches for the development of effective therapeutic strategies for AD

Y-stent-assisted coil embolization of anterior circulation aneurysms using two solitaire AB devices: a single enter experience

Wide-neck intracranial aneurysms remain a challenge to endovascular treatment. We describe our experience in repairing wide-neck aneurysms of the anterior circulation located at arterial branch points using coil embolization assisted by Y-stenting using two Solitaire® stents. Six wide-neck intracranial aneurysms located on the middle cerebral artery bifurcation 3, pericallosal artery 1, and anterior communicating artery 2 were repaired by Y-stent-assisted coil embolization using two Solitaire® stents. Four cases were incidental findings of aneurysm and two cases were previously treated ruptured aneurysms that had undergone recanalization. All the cases were successfully treated without complications. Follow-up by digital subtraction angiography and magnetic resonance angiography at six months showed the stents to be patent with no recanalization of the aneurysm sacs. Repairing wide-neck aneurysms of the anterior circulation by Y-stent-assisted coil embolization using two Solitaire® stents is a simple and safe method of treating complex aneurysms. While the results are promising, larger series with longer term follow-ups are needed to corroborate that this treatment method is superior to other technique

The Mobility of Homomeric Lasso- and Daisy Chain-Like Rotaxanes in Solution and in the Gas Phase as a means to Study Structure and Switching Behaviour

A precise structural determination of supramolecular architectures is a non-trivial challenge. This daunting task can be made even more difficult when interlocked species are to be analysed having macrocycles covalently equipped with a thread as repeating units, such as molecular lassos and daisy chains. When such functionalized macrocycles are included as scaffolds, different products having analogous NMR spectra as well as dynamic libraries can be obtained. Furthermore, if control over the motion of the parts relative to each other is to be achieved, a full understanding of the machinery's operation mechanism requires detailed insight into the structures involved. This understanding also helps designing improved synthetic molecular machines. Diffusion-ordered NMR spectroscopy and ion-mobility MS techniques are ideal tools to study such compounds in depth. This review covers recent examples on the use of the above-mentioned techniques to characterize these interlocked architectures

Conventional and Non-Conventional Roles of Non-Muscle Myosin II-Actin in Neuronal Development and Degeneration

Myosins are motor proteins that use chemical energy to produce mechanical forces driving actin cytoskeletal dynamics. In the brain, the conventional non-muscle myosin II (NMII) regulates actin filament cytoskeletal assembly and contractile forces during structural remodeling of axons and dendrites, contributing to morphology, polarization, and migration of neurons during brain development. NMII isoforms also participate in neurotransmission and synaptic plasticity by driving actin cytoskeletal dynamics during synaptic vesicle release and retrieval, and formation, maturation, and remodeling of dendritic spines. NMIIs are expressed differentially in cerebral non-neuronal cells, such as microglia, astrocytes, and endothelial cells, wherein they play key functions in inflammation, myelination, and repair. Besides major efforts to understand the physiological functions and regulatory mechanisms of NMIIs in the nervous system, their contributions to brain pathologies are still largely unclear. Nonetheless, genetic mutations or deregulation of NMII and its regulatory effectors are linked to autism, schizophrenia, intellectual disability, and neurodegeneration, indicating non-conventional roles of NMIIs in cellular mechanisms underlying neurodevelopmental and neurodegenerative disorders. Here, we summarize the emerging biological roles of NMIIs in the brain, and discuss how actomyosin signaling contributes to dysfunction of neurons and glial cells in the context ofneurological disorders. This knowledge is relevant for a deep understanding of NMIIs on the pathogenesis and therapeutics of neuropsychiatric and neurodegenerative diseases

The Mobility of Homomeric Lasso- and Daisy Chain-Like Rotaxanes in Solution and in the Gas Phase as a Means to Study Structure and Switching Behaviour

©2023 The Authors. This manuscript version is made available under the CC-BY-NC 4.0 license https://creativecommons.org/licenses/by-nc/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in Israel Journal of Chemistry. To access the final edited and published work see https://doi.org/10.1002/ijch.202300022A precise structural determination of supramolecular architectures is a non-trivial challenge. This daunting task can be made even more difficult when interlocked species are to be analysed having macrocycles covalently equipped with a thread as repeating units, such as molecular lassos and daisy chains. When such functionalized macrocycles are included as scaffolds, different products having analogous NMR spectra as well as dynamic libraries can be obtained. Furthermore, if control over the motion of the parts relative to each other is to be achieved, a full understanding of the machinery's operation mechanism requires detailed insight into the structures involved. This understanding also helps designing improved synthetic molecular machines. Diffusion-ordered NMR spectroscopy and ion-mobility MS techniques are ideal tools to study such compounds in depth. This review covers recent examples on the use of the above-mentioned techniques to characterize these interlocked architectures

Scratch-Resistant Hydrophobic Coating with Supramolecular-Polymer Co-Assembly

Supramolecular assembly for superhydrophobic coatings is known for its efficiency and efficacy. However, the mechanical fragility of the coatings limits their use as coating materials. Herein, the combination of (±)-N,N'-(trans-cyclohexane-1,2-diyl)-bis(perfluorooctanamide) CF7, a cyclohexyl diamide-based low molecular weight gelator, with acrylate polymers for the generation of semi-transparent omniphobic coatings with significantly enhanced scratch proofness is presented. CF7 has shown the ability to self-assemble in common solvents into highly entangled fibrous networks with extreme water repellency. The incorporation of covalent polymers, specifically poly(methyl methacrylate) (PMMA) and poly(trifluoroethyl methacrylate) (PTFEMA), helps to fixate the supramolecular CF7 fibers without interfering with the self-assembled structures. The resulting coatings, namely CF7/PMMA and CF7/PTFEMA, show significantly improved mechanical resistance as well as optical transparency while maintaining excellent water and oil repellency. Furthermore, the homogeneity of the coating in bulk is confirmed by depth profiling of the 3D distribution of the components using time-of-flight secondary ion mass spectrometry imaging, which turns out to be an essential technique in order to characterize such materials

Rising and falling diapirs, shifting depocenters, and flap overturning in the Cretaceous Sopeira and Sant Gervàs subbasins (Ribagorça Basin, southern Pyrenees)

The halokinetic structure of inverted salt-related continental margins is frequently obliterated by compressional overprinting. The Cretaceous Sopeira and Sant Gervàs subbasins of the Ribagorça Basin (south central Pyrenees) show evidence of salt-related extensional tectonics and diapiric growth along the Iberian Margin of the Mesozoic Pyrenean rift. We present an integrated field-based tectonic-sedimentary study to reconstruct the evolution of the Ribagorça Basin system previous to, and in the early stages of, the Pyrenean orogeny. The ~4km thick Albian-Cenomanian Sopeira minibasin infill thins toward the basin borders, especially toward the eastern, N-S trending, Llastarri salt weld. The 90° tilt to the south of the Sopeira basin bottom records the growth of the buried north dipping Sopeira listric fault from Albian to Santonian times, when it evolved as an extensional rollover associated with the Aulet salt roller. The ~3km thick Cenomanian-Campanian succession filling the Sant Gervàs flap displays 130° bed fanning attitude from overturned Cenomanian carbonate platform strata to upright Campanian turbidite beds. The Sant Gervàs flap development since Cenomanian times was related to the fall of a large salt pillow after the main Soperia minibasin stage. Jurassic-Campanian diachronous subsidence is also observed in the adjacent Montiberri, Faiada, and Tamurcia depocenters. Correlation with the Pedraforca, Cotiella, and Basque-Cantabrian Basins along the southern Pyrenees suggests that a significant segment of the Iberian side of the Pyrenean rift experienced a gravity-driven extension from Albian to late Santonian. The Ribagorça Basin provides an excellent field analogue for presently buried salt-related structures of extended passive margins.This research was carried out with the aid of grants by CSIC-ESF 2007–2013 JAE-Doc postdoctoral research contract (E.S.) and with funding from the Spanish Research Agency through projects CGL2009-1355, CGL2011-26670, and CGL2010-15416. Additional funding was provided by Atlas Project and Statoil Research CenterPeer reviewe

Scratch-Resistant Hydrophobic Coating with Supramolecular-Polymer Co-Assembly

Está pagada la tasa. Se trata de un artículo de open access. La información que debe recogerse en Digitum es la siguiente: ©2023 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH. This manuscript version is made available under the CC-BY-NC 4.0 license https://creativecommons.org/licenses/by-nc/4.0/ This document is the Published Manuscript version of a Published Work that appeared in final form in Advanced Functional Materials. To access the final edited and published work see https://doi.org/10.1002/adfm.202309140Supramolecular assembly for superhydrophobic coatings is known for its efficiency and efficacy. However, the mechanical fragility of the coatings limits their use as coating materials. Herein, the combination of (±)-N,N'-(trans-cyclohexane-1,2-diyl)-bis(perfluorooctanamide) CF7, a cyclohexyl diamide-based low molecular weight gelator, with acrylate polymers for the generation of semi-transparent omniphobic coatings with significantly enhanced scratch proofness is presented. CF7 has shown the ability to self-assemble in common solvents into highly entangled fibrous networks with extreme water repellency. The incorporation of covalent polymers, specifically poly(methyl methacrylate) (PMMA) and poly(trifluoroethyl methacrylate) (PTFEMA), helps to fixate the supramolecular CF7 fibers without interfering with the self-assembled structures. The resulting coatings, namely CF7/PMMA and CF7/PTFEMA, show significantly improved mechanical resistance as well as optical transparency while maintaining excellent water and oil repellency. Furthermore, the homogeneity of the coating in bulk is confirmed by depth profiling of the 3D distribution of the components using time-of-flight secondary ion mass spectrometry imaging, which turns out to be an essential technique in order to characterize such materials

GENETIC DIFFERENTIATION IN SYMPATRIC BUT TEMPORALLY ISOLATED PINE BARK BUGS, ARADUS-CINNAMOMEUS (HETEROPTERA)

Peer reviewe