Cyclophilin D in Mitochondrial Dysfunction: A Key Player in Neurodegeneration?

Mitochondrial dysfunction plays a pivotal role in numerous complex diseases. Understanding the molecular mechanisms by which the “powerhouse of the cell” turns into the “factory of death” is an exciting yet challenging task that can unveil new therapeutic targets. The mitochondrial matrix protein CyPD is a peptidylprolyl cis-trans isomerase involved in the regulation of the permeability transition pore (mPTP). The mPTP is a multi-conductance channel in the inner mitochondrial membrane whose dysregulated opening can ultimately lead to cell death and whose involvement in pathology has been extensively documented over the past few decades. Moreover, several mPTP-independent CyPD interactions have been identified, indicating that CyPD could be involved in the fine regulation of several biochemical pathways. To further enrich the picture, CyPD undergoes several post-translational modifications that regulate both its activity and interaction with its clients. Here, we will dissect what is currently known about CyPD and critically review the most recent literature about its involvement in neurodegenerative disorders, focusing on Alzheimer’s Disease and Parkinson’s Disease, supporting the notion that CyPD could serve as a promising therapeutic target for the treatment of such conditions. Notably, significant efforts have been made to develop CyPD-specific inhibitors, which hold promise for the treatment of such complex disorders

Universal Behavior of the Coefficients of the Continuous Equation in Competitive Growth Models

The competitive growth models involving only one kind of particles (CGM), are a mixture of two processes one with probability $p$ and the other with probability $1-p$. The $p-$dependance produce crossovers between two different regimes. We demonstrate that the coefficients of the continuous equation, describing their universality classes, are quadratic in $p$ (or $1-p$). We show that the origin of such dependance is the existence of two different average time rates. Thus, the quadratic $p-$dependance is an universal behavior of all the CGM. We derive analytically the continuous equations for two CGM, in 1+1 dimensions, from the microscopic rules using a regularization procedure. We propose generalized scalings that reproduce the scaling behavior in each regime. In order to verify the analytic results and the scalings, we perform numerical integrations of the derived analytical equations. The results are in excellent agreement with those of the microscopic CGM presented here and with the proposed scalings.Comment: 9 pages, 3 figure

Proteomics boosts translational and clinical microbiology

The application of proteomics to translational and clinical microbiology is one of the most advanced frontiers in the management and control of infectious diseases and in the understanding of complex microbial systems within human fluids and districts. This new approach aims at providing, by dedicated bioinformatic pipelines, a thorough description of pathogen proteomes and their interactions within the context of human host ecosystems, revolutionizing the vision of infectious diseases in biomedicine and approaching new viewpoints in both diagnostic and clinical management of the patient.Indeed, in the last few years, many laboratories have matured a series of advanced proteomic applications, aiming at providing individual proteome charts of pathogens, with respect to their morph and/or cell life stages, antimicrobial or antimycotic resistance profiling, epidemiological dispersion. Herein, we aim at reviewing the current state-of-the-art on proteomic protocols designed and set-up for translational and diagnostic microbiological purposes, from axenic pathogens' characterization to microbiota ecosystems' full description. The final goal is to describe applications of the most common MALDI-TOF MS platforms to advanced diagnostic issues related to emerging infections, increasing of fastidious bacteria, and generation of patient-tailored phylotypes. This article is part of a Special Issue entitled: Trends in Microbial Proteomics. © 2013 The Authors

Edge phonons in black phosphorus

Exfoliated black phosphorus has recently emerged as a new two-dimensional crystal that, due to its peculiar and anisotropic crystalline and electronic band structures, may have potentially important applications in electronics, optoelectronics and photonics. Despite the fact that the edges of layered crystals host a range of singular properties whose characterization and exploitation are of utmost importance for device development, the edges of black phosphorus remain poorly characterized. In this work, the atomic structure and the behavior of phonons near different black phosphorus edges are experimentally and theoretically studied using Raman spectroscopy and density functional theory calculations. Polarized Raman results show the appearance of new modes at the edges of the sample, and their spectra depend on the atomic structure of the edges (zigzag or armchair). Theoretical simulations confirm that the new modes are due to edge phonon states that are forbidden in the bulk, and originated from the lattice termination rearrangements.Comment: 15 pages, 4 figure

Color fundus autofluorescence to determine activity of macular neovascularization in age-related macular degeneration

Purpose: To evaluate with color fundus autofluorescence (FAF) different lesion components of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) and to assess its activity. Methods: In total, 137 eyes (102 patients) with MNV underwent a complete eye exami-nation, including color fundus photography, optical coherence tomography (OCT), OCT angiography, and confocal color FAF, with an excitation wavelength at 450 nm. Each image was imported into a custom-image analysis software for quantitative estimation of emission wavelength and green and red emission fluorescence (GEFC/REFC) inten-sity, considering both single components of neovascular AMD and different MNV types (type 1 and type 2 MNV, active and inactive MNV). Results: Subretinal fluid (SRF) had significantly higher values of GEFC (P = 0.008 and P = 0.0004) and REFC intensity (P = 0.005 and P = 0.0003) versus fibrosis and atrophy. The emission wavelength from SRF was lower compared to atrophy (P = 0.024) but not to fibrosis (P = 0.46). No significant differences were detected between type 1 and 2 MNV. Considering active versus inactive MNVs, a difference was detected for all evaluated parameters (P < 0.001). Mean FAF wavelength of both MNV with SRF and intrareti-nal fluid (IRF) was lower versus inactive MNV (P < 0.001 and P = 0.005). MNV with SRF (P < 0.001) had higher values of GEFC and REFC versus inactive MNV (P < 0.001). MNV with IRF had higher values of GEFC versus inactive MNV (P = 0.05). Conclusions: Quantitative color FAF can differentiate active versus inactive MNV, whereas no differences were found between type 1 and type 2 MNV. If these data can be further confirmed, color FAF may be useful for automatic detection of active MNV in AMD and as a guide for treatment. Translational Relevance: Automatic quantitative evaluation of green and red emission components of FAF in AMD can help determine the activity of MNV and guide the treatment

Green Tattoo Pre-Operative Renal Embolization for Robotic-Assisted and Laparoscopic Partial Nephrectomy: A Practical Proof of a New Technique

Background: Our aim is to describe a new mixed indocyanine-non-adhesive liquid embolic agent (Onyx-18) pre-operative renal embolization technique for assisted-robotic and laparoscopic partial nephrectomy with near-infra-red fluorescence imaging. (2) Methods: Thirteen patients with biopsy-proven renal tumors underwent pre-operative mixed indocyanine–ethylene vinyl alcohol (EVOH) embolization (Green-embo) between June 2021 and August 2022. All pre-operative embolizations were performed with a super selective stop-flow technique using a balloon microcatheter to deliver an indocyanine-EVOH mixture into tertiary order arterial branch feeders and the intra-lesional vascular supply. Efficacy (evaluated as complete embolization, correct tumor mapping on infra-red fluorescence imaging and clamp-off surgery) and safety (evaluated as complication rate and functional outcomes) were primary goals. Clinical and pathological data were also collected. (3) Results: Two male and eleven female patients (mean age 72 years) received pre-operative Green-embo. The median tumor size was 29 mm (range 15–50 mm). Histopathology identified renal cell carcinoma (RCC) in 9 of the 13 (69%) patients, oncocytoma in 3 of the 13 (23%) patients and sarcomatoid RCC in 1 of the 13 (8%) patients. Lesions were equally distributed between polar, meso-renal, endo- and exophytic locations. Complete embolization was achieved in all the procedures. A correct green mapping was identified during all infra-red fluorescence imaging. All patients were discharged on the second day after the surgery. The median blood loss was 145 cc (10–300 cc). No significant differences were observed in serum creatinine levels before and after the embolization procedures. (4) Conclusions: The Green-tattoo technique based on a mixed indocyanine-non-adhesive liquid embolic agent (Onyx-18) is a safe and effective pre-operative embolization technique. The main advantages are the excellent lesion mapping for fluorescence imaging, reduction in surgical time, and definitive, complete and immediate tumor devascularization based on the deep Onyx-18 penetration, leading to a very low intra-operative blood loss

Early Detection of Microvascular Changes in Patients with Diabetes Mellitus without and with Diabetic Retinopathy: Comparison between Different Swept-Source OCT-A Instruments

Optical coherence tomography angiography (OCT-A) has recently improved the ability to detect subclinical and early clinically visible microvascular changes occurring in patients with diabetes mellitus (DM). The aim of the present study is to evaluate and compare early quantitative changes of macular perfusion parameters in patients with DM without DR and with mild nonproliferative DR (NPDR) evaluated by two different swept-source (SS) OCT-A instruments using two scan protocols (3 73 mm and 6 76 mm). One hundred eleven subjects/eyes were prospectively evaluated: 18 healthy controls (control group), 73 eyes with DM but no DR (no-DR group), and 20 eyes with mild NPDR (DR group). All quantitative analyses were performed using ImageJ and included vessel and perfusion density, area and circularity index of the FAZ, and vascular complexity parameters. The agreement between methods was assessed according to the method of Bland-Altman. A significant decrease in the majority of the considered parameters was found in the DR group versus the controls with both instruments. The results of Bland-Altman analysis showed the presence of a systemic bias between the two instruments with PLEX Elite providing higher values for the majority of the tested parameters when considering 6 76 mm angiocubes and a less definite difference in 3 73 mm angiocubes. In conclusion, this study documents early microvascular changes occurring in the macular region of patients at initial stages of DR, confirmed with both SS OCT-A instruments. The fact that early microvascular alterations could not be detected with one instrument does not necessarily mean that these alterations are not actually present, but this could be an intrinsic limitation of the device itself. Further, larger longitudinal studies are needed to better understand microvascular damage at very early stages of diabetic retinal disease and to define the strengths and weaknesses of different OCT-A devices