A Bistable Model of Cell Polarity

Ultrasensitivity, as described by Goldbeter and Koshland, has been considered for a long time as a way to realize bistable switches in biological systems. It is not as well recognized that when ultrasensitivity and reinforcing feedback loops are present in a spatially distributed system such as the cell plasmamembrane, they may induce bistability and spatial separation of the system into distinct signaling phases. Here we suggest that bistability of ultrasensitive signaling pathways in a diffusive environment provides a basic mechanism to realize cell membrane polarity. Cell membrane polarization is a fundamental process implicated in several basic biological phenomena, such as differentiation, proliferation, migration and morphogenesis of unicellular and multicellular organisms. We describe a simple, solvable model of cell membrane polarization based on the coupling of membrane diffusion with bistable enzymatic dynamics. The model can reproduce a broad range of symmetry-breaking events, such as those observed in eukaryotic directional sensing, the apico-basal polarization of epithelium cells, the polarization of budding and mating yeast, and the formation of Ras nanoclusters in several cell types

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Posterior reversible encephalopathy syndrome: role of transorbital ultrasound

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Automatic segmentation of the optic nerve in transorbital ultrasound images using a deep learning approach

Transorbital sonography is able to provide reliable information about (a) intra-cranial pressure estimation through the optic nerve sheath diameter (ONSD) measurement, and (b) optic nerve atrophy in patients with multiple sclerosis through the optic nerve diameter (OND). In this study, we present the first method for the automatic measurement of the OND and ONSD using a deep learning technique (UNet with ResNet50 encoder) for the optic nerve segmentation. The dataset included 201 images from 50 patients. The automated measurements were compared with manual ones obtained by one operator. The mean error was equal to 0.07 ± 0.34 mm and -0.07 ± 0.67 mm, for the OND and ONSD, respectively. The developed system should aid in standardizing OND and ONSD measurements and reduce manual evaluation variability

FPGA applications for single dish activity at Medicina radio telescopes

FPGA technologies are gaining major attention in the recent years in the field of radio astronomy. At Medicina radio telescopes, FPGAs have been used in the last ten years for a number of purposes and in this article we will take into exam the applications developed and installed for the Medicina Single Dish 32m Antenna: these range from high performance digital signal processing to instrument control developed on top of smaller FPGAs

Mass Vaccine Administration under Supply Uncertainty

The insurgence of COVID-19 requires fast mass vaccination, hampered by scarce availability and uncertain supply of vaccine doses and a tight schedule for boosters. In this paper, we analyze planning strategies for the vaccination campaign to vaccinate as many people as possible while meeting the booster schedule. We compare a conservative strategy and q-days-ahead strategies against the clairvoyant strategy. The conservative strategy achieves the best trade-off between utilization and compliance with the booster schedule. Q-days-ahead strategies with q < 7 provide a larger utilization but run out of stock in over 30% of days

Investigating in vitro amyloid peptide 1-42 aggregation: impact of higher molecular weight stable adducts

The self-assembly of amyloid peptides (Aβ), in particular Aβ1–42, into oligomers and fibrils is one of the main pathological events related to Alzheimer’s Disease (AD). Recent studies have demonstrated the ability of carbon monoxide releasing molecules (CORMs) to protect neurons and astrocytes from Aβ1-42 toxicity. In fact, CORMs are able to carry and release controlled levels of CO and are known to exert a wide range of anti-inflammatory and anti-apoptotic activities at physiologically relevant concentrations. In order to investigate the direct effects of CORMs on Aβ1–42, we studied the reactivity of CORM-2 and CORM-3 with Aβ1–42 in vitro and the potential inhibition of its aggregation by mass spectrometry (MS), as well as fluorescence and circular dichroism (CD) spectroscopies. The application of an electrospray ionisation-mass spectrometry (ESI-MS) method allowed the detection of stable Aβ1–42/CORMs adducts, involving the addition of the Ru(CO)2 portion of CORMs at histidine residues on the Aβ1-42 skeleton. Moreover, CORMs showed anti-aggregating properties through formation of stable adducts with Aβ1–42 as demonstrated by a thioflavin T (ThT) fluorescence assay and MS analysis. As a further proof, comparison of the CD spectra of Aβ1–42 recorded in the absence and in the presence of CORM-3 at 1:1 molar ratio showed the ability of CORM-3 to stabilize the peptide in its soluble, unordered conformation, thereby preventing its misfolding and aggregation. This multi-methodological investigation revealed novel interactions between Aβ1–42 and CORMs, contributing new insights into the proposed neuroprotective mechanisms mediated by CORMs and disclosing a new strategy to divert amyloid aggregation and toxicity

Feasibility and usefulness of ultrasonography in idiopathic intracranial hypertension or secondary intracranial hypertension

Transorbital sonography (TOS) has been proven to be able to non-invasively detect elevated intracranial pressure. In this condition TOS shows an increase in optic nerve sheath diameter (ONSD). It has been suggested that internal jugular vein valve insufficiency (IJVVI) may represent a factor contributing to the pathogenesis of idiopathic intracranial hypertension (IIH). The aim of this study was to investigate whether patients with IIH or secondary IH have higher ONSD values and higher frequency of IJVVI compared to subjects without IH

Longitudinal Assessment of Transorbital Sonography, Visual Acuity, and Biomarkers for Inflammation and Axonal Injury in Optic Neuritis

Background and Objective. To investigate the relationship between optic nerve sheath diameter, optic nerve diameter, visual acuity and osteopontin, and neurofilament heavy chain in patients with acute optic neuritis. Patients and Methods. Sonographic and visual acuity assessment and biomarker measurements were executed in 23 patients with unilateral optic neuritis and in 19 sex- and age-matched healthy controls. Results. ONSD was thicker on the affected side at symptom onset (median 6.3 mm; interquartile range 6.0–6.5) than after 12 months (5.3 mm; 4.9–5.6; p<0.001) or than in controls (5.2 mm; 4.8–5.5; p<0.001). OND was significantly increased in the affected side (3.4 mm; 2.9–3.8) compared to healthy controls (2.7 mm; 2.5–2.9; p<0.001) and was thicker at baseline than after 12 months (2.8 mm; 2.7–3.0; p<0.01). Visual acuity improved significantly after 12 months (1.00; 0.90–1.00) compared to onset of symptoms (0.80; 0.40–1.00; p<0.001). OPN levels were significantly higher in patients at presentation (median 6.44 ng/ml; 2.05–10.06) compared to healthy controls (3.21 ng/ml, 1.34–4.34; p<0.03). Concentrations of NfH were significantly higher in patients than in controls. Conclusion. ONSD and OND are increased in the affected eye. OPN and NfH are elevated in patients, confirming the presence of any underlying inflammation and axonal injury