by Keyword: Association

Andreu, I, Granero-Moya, I, Garcia-Manyes, S, Roca-Cusachs, P, (2022). Understanding the role of mechanics in nucleocytoplasmic transport Apl Bioengineering 6, 020901

Cell nuclei are submitted to mechanical forces, which in turn affect nuclear and cell functions. Recent evidence shows that a crucial mechanically regulated nuclear function is nucleocytoplasmic transport, mediated by nuclear pore complexes (NPCs). Mechanical regulation occurs at two levels: first, by force application to the nucleus, which increases NPC permeability likely through NPC stretch. Second, by the mechanical properties of the transported proteins themselves, as mechanically labile proteins translocate through NPCs faster than mechanically stiff ones. In this perspective, we discuss this evidence and the associated mechanisms by which mechanics can regulate the nucleo-cytoplasmic partitioning of proteins. Finally, we analyze how mechanical regulation of nucleocytoplasmic transport can provide a systematic approach to the study of mechanobiology and open new avenues both in fundamental and applied research. (C) 2022 Author(s).

JTD Keywords: Architecture, Association, Force, Nuclear-pore complex, Pathways, Protein import, Sun1

Ferrer I, Andrés-Benito P, Ausín K, Pamplona R, del Rio JA, Fernández-Irigoyen J, Santamaría E, (2021). Dysregulated protein phosphorylation: A determining condition in the continuum of brain aging and Alzheimer's disease Brain Pathology 31,

Tau hyperphosphorylation is the first step of neurofibrillary tangle (NFT) formation. In the present study, samples of the entorhinal cortex (EC) and frontal cortex area 8 (FC) of cases with NFT pathology classified as stages I–II, III–IV, and V–VI without comorbidities, and of middle-aged (MA) individuals with no NFT pathology, were analyzed by conventional label-free and SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) to assess the (phospho)proteomes. The total number of identified dysregulated phosphoproteins was 214 in the EC, 65 of which were dysregulated at the first stages (I–II) of NFT pathology; 167 phosphoproteins were dysregulated in the FC, 81 of them at stages I–II of NFT pathology. A large percentage of dysregulated phosphoproteins were identified in the two regions and at different stages of NFT progression. The main group of dysregulated phosphoproteins was made up of components of the membranes, cytoskeleton, synapses, proteins linked to membrane transport and ion channels, and kinases. The present results show abnormal phosphorylation of proteins at the first stages of NFT pathology in the elderly (in individuals clinically considered representative of normal aging) and sporadic Alzheimer's disease (sAD). Dysregulated protein phosphorylation in the FC precedes the formation of NFTs and SPs. The most active period of dysregulated phosphorylation is at stages III–IV when a subpopulation of individuals might be clinically categorized as suffering from mild cognitive impairment which is a preceding determinant stage in the progression to dementia. Altered phosphorylation of selected proteins, carried out by activation of several kinases, may alter membrane and cytoskeletal functions, among them synaptic transmission and membrane/cytoskeleton signaling. Besides their implications in sAD, the present observations suggest a molecular substrate for “benign” cognitive deterioration in “normal” brain aging.

JTD Keywords: (phospho)proteomics, alzheimer's disease, amyloid-beta, association guidelines, brain aging, cytoskeleton, frontal-cortex, kinases, lipid rafts, membranes, national institute, neuropathologic assessment, pathological process, protein phosphorylation, synapse pathology, synapses, tau, tau pathology, (phospho)proteomics, Age-related tauopathy, Alzheimer's disease, Brain aging, Cytoskeleton, Kinases, Membranes, Protein phosphorylation, Synapses, Tau

Grob, M, Anselmetti, D, Fernandez-Busquets, X, (2021). In memory of Max Burger Journal Of Cellular Biochemistry 122, 1259-1261

Ferrer-Lluis I, Castillo-Escario Y, Montserrat JM, Jané R, (2021). SleepPos app: An automated smartphone application for angle based high resolution sleep position monitoring and treatment Sensors 21,

Poor sleep quality or disturbed sleep is associated with multiple health conditions. Sleep position affects the severity and occurrence of these complications, and positional therapy is one of the less invasive treatments to deal with them. Sleep positions can be self-reported, which is unreliable, or determined by using specific devices, such as polysomnography, polygraphy or cameras, that can be expensive and difficult to employ at home. The aim of this study is to determine how smartphones could be used to monitor and treat sleep position at home. We divided our research into three tasks: (1) develop an Android smartphone application (‘SleepPos’ app) which monitors angle-based high-resolution sleep position and allows to simultaneously apply positional treatment; (2) test the smartphone application at home coupled with a pulse oximeter; and (3) explore the potential of this tool to detect the positional occurrence of desaturation events. The results show how the ‘SleepPos’ app successfully determined the sleep position and revealed positional patterns of occurrence of desaturation events. The ‘SleepPos’ app also succeeded in applying positional therapy and preventing the subjects from sleeping in the supine sleep position. This study demonstrates how smartphones are capable of reliably monitoring high-resolution sleep position and provide useful clinical information about the positional occurrence of desaturation events.

JTD Keywords: accelerometry, android, apnea patients, app, association, biomedical signal processing, management, mhealth, monitoring, pathophysiology, pilot mhealth, questionnaire, sleep position, smartphone, supine position, time, Accelerometry, Android, App, Biomedical signal processing, Mhealth, Monitoring, Sleep position, Smart-phone, Smartphone, Tennis ball technique

Ferrer-Lluis I, Castillo-Escario Y, Montserrat JM, Jané R, (2021). Enhanced monitoring of sleep position in sleep apnea patients: Smartphone triaxial accelerometry compared with video-validated position from polysomnography Sensors 21,

Poor sleep quality is a risk factor for multiple mental, cardiovascular, and cerebrovascular diseases. Certain sleep positions or excessive position changes can be related to some diseases and poor sleep quality. Nevertheless, sleep position is usually classified into four discrete values: supine, prone, left and right. An increase in sleep position resolution is necessary to better assess sleep position dynamics and to interpret more accurately intermediate sleep positions. This research aims to study the feasibility of smartphones as sleep position monitors by (1) developing algorithms to retrieve the sleep position angle from smartphone accelerometry; (2) monitoring the sleep position angle in patients with obstructive sleep apnea (OSA); (3) comparing the discretized sleep angle versus the four classic sleep positions obtained by the video-validated polysomnography (PSG); and (4) analyzing the presence of positional OSA (pOSA) related to its sleep angle of occurrence. Results from 19 OSA patients reveal that a higher resolution sleep position would help to better diagnose and treat patients with position-dependent diseases such as pOSA. They also show that smartphones are promising mHealth tools for enhanced position monitoring at hospitals and home, as they can provide sleep position with higher resolution than the gold-standard video-validated PSG.

JTD Keywords: accelerometry, actigraphy, association, biomedical signal processing, index, latency, mhealth, monitoring, pathophysiology, quality, questionnaire, score, sleep apnea, sleep position, smartphone, time, Accelerometry, Biomedical signal processing, Mhealth, Monitoring, Sleep apnea, Sleep position, Smartphone, Supine position

Arimon, M., Sanz, F., Giralt, E., Carulla, N., (2012). Template-assisted lateral growth of amyloid-β42 fibrils studied by differential labeling with gold nanoparticles Bioconjugate Chemistry , 23, (1), 27-32

Amyloid-β protein (Aβ) aggregation into amyloid fibrils is central to the origin and development of Alzheimer’s disease (AD), yet this highly complex process is poorly understood at the molecular level. Extensive studies have shown that Aβ fibril growth occurs through fibril elongation, whereby soluble molecules add to the fibril ends. Nevertheless, fibril morphology strongly depends on aggregation conditions. For example, at high ionic strength, Aβ fibrils laterally associate into bundles. To further study the mechanisms leading to fibril growth, we developed a single-fibril growth assay based on differential labeling of two Aβ42 variants with gold nanoparticles. We used this assay to study Aβ42 fibril growth under different conditions and observed that bundle formation is preceded by lateral interaction of soluble Aβ42 molecules with pre-existing fibrils. Based on this data, we propose template-assisted lateral fibril growth as an additional mechanism to elongation for Aβ42 fibril growth.

JTD Keywords: AFM, Beta-Amyloid Fibrils, Polymorphism, Association, Elongation, Dynamics, State