IRCCS San Raffaele Scientific Institute Showcase

The file contains source data on HMGB1-CXCL12 interaction. Data contain: Data contain: Figure 2: data generating bar graphs displayed in b-k Figure 3: data generating bar graphs displayed in c-g Figure 4: data generating bar graphs displayed in c-f Figure 5: ITC sequential pulses displayed in Figure 5a-c, normalized MST signals displayed in Figure d,e Figure 6: SV-AUC data displayed in a-c, MS-SV analysis displayed in f Figure 7:SAXS data displayed in a-d Figure 8:Quantification of PLA signals displayed in a-c Supplementary S3: data generating bar graphs displayed in b-k Supplementary Figure S4:data generating bar graphs displayed in b-d; normalized M ST signals displayed in e Supplementary Figure S6: ITC sequential pulses displayed in c,d Supplementary Figure S7:SV-AUC data displayed in a-j, MS-SV analysis displayed in k. Supplementary Figure S8: SAXS data displayed in Figure a,b Supplementary Figure S9: HMGB1 SAXS dilution series displayed in a-c Supplementary Figure S10: CXCL12 SAXS dilution series displayed in a-c Supplementary Figure S11 SAXS data and EOM analysis displayed in a and b Figure S12: SAXS concnetration series of frHMGB1 titrated with CXCL12 a-b Figure S13: Supplementary Figure S12: Fits to SAXS data of the a) SASREF and b)F oXSDock model of frHMGB1-CXCL12 complex Figure S14: Quantification of PLA displayed in b Figure S15:FAXS analysis displayed in c In SourceDATA/excel all sourcedata in excel format

The composition of the secretome depends on the combined action of cargo receptors that facilitate protein transport and sequential checkpoints that restrict it to native conformers. Acting after endoplasmic reticulum (ER)-resident chaperones, ERp44 retrieves its clients from downstream compartments. To guarantee efficient quality control, ERp44 should exit the ER as rapidly as its clients, or more. Here, we show that appending ERp44 to different cargo proteins increases their secretion rates. ERp44 binds the cargo receptor ER-Golgi intermediate compartment (ERGIC)-53 in the ER to negotiate preferential loading into COPII vesicles. Silencing ERGIC-53, or competing for its COPII binding with 4-phenylbutyrate, causes secretion of Prdx4, an enzyme that relies on ERp44 for intracellular localization. In more acidic, zinc-rich downstream compartments, ERGIC-53 releases its clients and ERp44, which can bind and retrieve non-native conformers via KDEL receptors. By coupling the transport of cargoes and inspector proteins, cells ensure efficiency and fidelity of secretion.

eIF4B silencing (siRNA) experiment and assessment of the protein levels of CDKL5, XIAP and alpha-tubulin

Identifying reproducible brain-based stratifications across independent cohorts is critical for parsing heterogeneity in Major Depressive Disorder (MDD), yet robust profiles spanning micro- and macroscales remain poorly defined. We applied stability-based clustering to cortical thickness (CT) data from 1531 MDD individuals in UK Biobank (UKB), with replication in 144 inpatients from IRCCS San Raffaele Hospital (HSR). Two stable clusters emerged (normalized stability = 0.125) that generalized to a hold-out UKB sample with 96.5% accuracy (majority-cluster baseline = 59.5%). The clusters differed in widespread CT, largely reflected in global CT, with one showing cortical thinning, childhood trauma, and diabetes comorbidity. A two-cluster structure was independently replicated in HSR (normalized stability = 0.29), with a broadly similar cortical topography, although systematic CT differences between cohorts limited direct cross-cohort comparability. The clinical correlates identified in UKB did not replicate after correction for multiple comparisons. In UKB, mapping the CT differences between strata onto Neurosynth meta-analytic activation patterns revealed a ventral-dorsal gradient linked with emotion regulation, interoceptive, and motivational processes. Spatial correlations with 19 neurotransmitter receptors and transporters obtained from positron emission tomography identified the dopamine transporter as the dominant contributor in UKB, and the histamine H3 receptor in HSR. These findings provide a reproducible framework linking CT-based clusters in MDD to multiscale biological organization, although their clinical relevance warrants further investigation.

In this study we determined the effect of glucose concentration and beta-hydroxybutyrate (BHB) on T cell phenotype, metabolism and function. The purpose was to determine potential effect on the systemic inflammatory response (T2D) and autoimmunity (T1D).

These files include the raw data that have generated the figures of the paper

Supplementary Table I. Demographic, clinical, laboratory and histopathologic results in the univariate and multivariate analysis. Supplementary Table II. Demographic, clinical, laboratory and histopathologic findings in overlap cases.

Auditory cueing modulates brain activity associated with improved motor performance in pwPD, thus reduces bradykinesia. The following file is provided to increase trasparency. It contains processed kinematic variables.

Supplementary Fig 1. Workflow illustrating tumors distribution according to dermoscopic, confocal and histologic diagnoses. Supplementary Fig 2. A) Dermoscopy showing brown pseudonetwork with defined borders, interpreted as solar lentigo. B-C) Reflectance confocal microscopy (RCM) revealing LM features, specifically: B) RCM at epidermal layer showing perifollicular and interfollicular dendritic cells. C) RCM at dermal-epidermal layer showing medusa-head like structure. Supplementary Fig 3. Double negative LM case: A) Dermoscopy showing multiple grey dots. B) RCM at epidermal layer showing honeycombed pattern with focal mottled pigmentation. C) RCM at dermal-epidermal layer showing abundant melanophages. Supplementary Fig 4. Double negative BCC case: A) Dermoscopy showing brown-red background. B) RCM at epidermal layer showing honeycombed pattern with focal mottled pigmentation. C) RCM at dermal-epidermal layer showing aspecific structures.

BACKGROUND: Major noncardiac surgery is associated with high rates of postoperative myocardial injury and other complications. Remote ischemic preconditioning (RIPC) was reported to decrease these complication rates. However, such supportive evidence lacks robustness. METHODS: In a multinational, double-blind trial, we randomly assigned adult high-risk patients undergoing noncardiac surgical procedures to receive RIPC or sham RIPC after the induction of general anesthesia and before surgery. RIPC involved three 5-minute ischemic cycles, each followed by 5 minutes of reperfusion, using a blood pressure cuff inflated to 200 mm Hg. The primary end point was the rate of myocardial injury, defined by an increase in postoperative troponin levels above the highest 99th percentile of reference values. Secondary outcomes included myocardial infarction, stroke, acute kidney injury, need for intensive care unit, length of hospital stay, and 30-day all-cause mortality. RESULTS: We recruited 1213 patients in 25 hospitals and 8 countries. We randomly assigned 599 patients to RIPC and 614 to sham RIPC. The most frequent surgical procedures were abdominal or intrathoracic surgeries (406 patients [33.6%]). RIPC was applied to the upper limb in 1014 patients (84.8%) and to the lower limb in 182 patients (15.2%). Postoperative myocardial injury occurred in 215 of 566 patients (38.0%) in the RIPC group and in 223 of 596 patients (37.4%) in the sham RIPC group (relative risk, 1.02 [95% CI, 0.88–1.18; P=0.84). There were no significant differences in the rate of any secondary outcomes. We observed 11 episodes of limb petechiae (10 [1.7%] in the RIPC group versus one [0.2%] in the sham RIPC group) and 34 (6.0%) hospital readmissions in the RIPC group versus 20 (3.5%) in the sham RIPC group. CONCLUSIONS: Among adult patients undergoing noncardiac surgery, RIPC did not reduce myocardial injury or other postoperative complications. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02427867.