Defective ribosomal products challenge nuclear function by impairing nuclear condensate dynamics and immobilizing ubiquitin

Nuclear protein aggregation has been linked to genome instability and disease. The main source of aggregation-prone proteins in cells is defective ribosomal products (DRiPs), which are generated by translating ribosomes in the cytoplasm. Here, we report that DRiPs rapidly diffuse into the nucleus and accumulate in nucleoli and PML bodies, two membraneless organelles formed by liquid\u2013liquid phase separation. We show that nucleoli and PML bodies act as dynamic overflow compartments that recruit protein quality control factors and store DRiPs for later clearance. Whereas nucleoli serve as constitutive overflow compartments, PML bodies are stress-inducible overflow compartments for DRiPs. If DRiPs are not properly cleared by chaperones and proteasomes due to proteostasis impairment, nucleoli undergo amyloidogenesis and PML bodies solidify. Solid PML bodies immobilize 20S proteasomes and limit the recycling of free ubiquitin. Ubiquitin depletion, in turn, compromises the formation of DNA repair compartments at fragile chromosomal sites, ultimately threatening cell survival

Sum rules for X-ray magnetic circular dichroism spectra in strongly correlated ferromagnets

It is proven that the sum rules for X-ray magnetic dichroism (XMCD) spectra that are used to separate spin and orbital contributions to the magnetic moment are formally correct for an arbitrary strength of electron-electron interactions. However, their practical application for strongly correlated systems can become complicated due to the spectral density weight spreading over a broad energy interval. Relevance of incoherent spectral density for the XMCD sum rules is illustrated by a simple model of a ferromagnet with orbital degrees of freedom.Comment: 4 pages, final versio

P316Expression and functional role of Ccdc80 in developing heart and in cardiomyopathies.

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Autochthonous cases of mucosal leishmaniasis in Northeastern Italy: clinical management and novel treatment approaches

Mucosal leishmaniasis (ML) is a rare clinical variant of tegumentary leishmaniasis in Mediterranean Europe. Here we report on three autochthonous cases of head and neck ML in patients living in Northeastern Italy. Patients presented with non-specific, long-standing symptoms of upper respiratory tract involvement, mimicking other diseases. Parasitological diagnosis was reached by histopathology, immunohistochemistry and molecular biology on tissue specimens. Leishmania infantum was identified by molecular typing in all three cases. All patients reached a complete remission with protracted multivalent antileishmanial drugs; in one case, a novel approach of combined medical and endoscopic surgical treatment was carried out. High clinical suspicion led to a prompt diagnosis and deployment of a multivalent treatment. ML should be considered in the differential diagnosis of nasal, oral, and pharyngolaryngeal lesions in endemic areas. A prompt diagnosis is mandatory to establish a correct management; different antileishmanial medications as well as endoscopic surgical options may be required to reach a complete remission

Design and Vertical Tests of SPS-series Double-Quarter Wave (DQW) Cavity Prototypes for the HL-LHC Crab Cavity System

Crab crossing is essential for high-luminosity colliders. The High Luminosity Large Hadron Collider (HL-LHC) will equip one of its Interaction Points (IP1) with Double-Quarter Wave (DQW) crab cavities. A DQW cavity is a new generation of deflecting RF cavities that stands out for its compactness and broad frequency separation between fundamental and first high-order modes. The deflecting kick is provided by its fundamental mode. Each HL-LHC DQW cavity shall provide a nominal deflecting voltage of 3.4 MV, although up to 5.0 MV may be required. A Proof-of-Principle (PoP) DQW cavity was limited by quench at 4.6 MV. This paper describes a new, highly optimized cavity, designated DQW SPS-series, which satisfies dimensional, cryogenic, manufacturing and impedance requirements for beam tests at SPS and operation in LHC. Two prototypes of this DQW SPS-series were fabricated by US industry and cold tested after following conventional SRF surface treatment. Both units outperformed the PoP cavity, reaching a deflecting voltage of 5.3-5.9 MV. This voltage - the highest reached by a DQW cavity - is well beyond the nominal voltage of 3.4 MV and may even operate at the ultimate voltage of 5.0MVwith sufficient margin. This paper covers fabrication, surface preparation and cryogenic RF test results and implications

Rare earth contributions to the X-ray magnetic circular dichroism at the Co K edge in rare earth-cobalt compounds investigated by multiple-scattering calculations

The X-ray magnetic circular dichroism (XMCD) has been measured at the Co K edge in Co-hcp and R-Co compounds (R=La, Tb, Dy). The structure of the experimental XMCD spectra in the near-edge region has been observed to be highly sensitive to the magnetic environment of the absorbing site. Calculations of the XMCD have been carried out at the Co K edge in Co metal, LaCo$_5$ and TbCo$_5$ within the multiple-scattering framework including the spin-orbit coupling. In the three systems, the XMCD spectra in the near-edge region are well reproduced. The possibility to separate and quantitatively estimate the local effects from those due to the neighboring atoms in the XMCD cross section makes possible a more physical understanding of the spectra. The present results emphasize the major role played by the $d$ states of the Tb ions in the XMCD spectrum at the Co K edge in the TbCo$_5$ compound.Comment: 34 pages, revtex, 10 eps figures included with epsf, after referee revie

Electronic and Magnetic Structures of Sr2FeMoO6

We have investigated the electronic and magnetic structures of Sr2FeMoO6 employing site-specific direct probes, namely x-ray absorption spectroscopy with linearly and circularly polarized photons. In contrast to some previous suggestions, the results clearly establish that Fe is in the formal trivalent state in this compound. With the help of circularly polarized light, it is unambiguously shown that the moment at the Mo sites is below the limit of detection (< 0.25mu_B), resolving a previous controversy. We also show that the decrease of the observed moment in magnetization measurements from the theoretically expected value is driven by the presence of mis-site disorder between Fe and Mo sites.Comment: To appear in Physical Review Letter

A Systematic Review of Non-pharmacological Strategies to Reduce the Risk of Violence in Patients With Schizophrenia Spectrum Disorders in Forensic Settings

Background: The purpose of this systematic review is to systematically investigate which non-pharmacological interventions are effective in reducing violence risk among patients with schizophrenia spectrum disorders (SSD) in forensic settings. Methods: Six electronic data bases were searched. Two researchers independently screened 6,003 abstracts resulting in 143 potential papers. These were analyzed in detail by two independent researchers yielding 10 articles that could be used. Results: Of the 10 articles, four were non-randomized controlled trials, three were pre-post studies without controls, and one was observational. Only two studies applied a randomized controlled trial design. Cognitive behavioral treatment programs were investigated in three studies. A broad range of other interventions were studied. Often outcome measures were specific to each study and sample sizes were small. Frequently, important methodological information was missing from the papers. It was not possible to carry out a meta-analysis due to the heterogeneity of the study designs and outcome measures. Conclusion: Because of methodological limitations it is difficult to draw firm conclusions about the effectiveness of non-pharmacological interventions to reduce the risk of violence in patents with SSD in forensic psychiatry settings. Studies applying better methods in terms of study design, sample sizes and outcome measures are urgently needed

Robotic multiquadrant colorectal procedures: A single-center experience and a systematic review of the literature

Purpose: Robotic surgery has been progressively implemented for colorectal procedures but is still limited for multiquadrant abdominal resections. The present study aims to describe our experience in robotic multiquadrant colorectal surgeries and provide a systematic review and meta-analysis of the literature investigating the outcomes of robotic total proctocolectomy (TPC), total colectomy (TC), subtotal colectomy (STC), or completion proctectomy (CP) compared to laparoscopy. Methods: At our institution 16 consecutive patients underwent a 2- or 3-stage totally robotic total proctocolectomy (TPC) with ileal pouch-anal anastomosis. A systematic review of the literature was performed to select studies on robotic and laparoscopic multiquadrant colorectal procedures. Meta-analyses were used to compare the two approaches. Results: In our case series, 14/16 patients underwent a 2-stage robotic TPC for ulcerative colitis with a mean operative time of 271.42 (SD:37.95) minutes. No conversion occurred. Two patients developed postoperative complications. The mean hospital stay was 8.28 (SD:1.47) days with no readmissions. Mortality was nil. All patients underwent loop-ileostomy closure, and functional outcomes were satisfactory. The literature appraisal was based on 23 retrospective studies, including 736 robotic and 9,904 laparoscopic multiquadrant surgeries. In the robotic group, 36 patients underwent STC, 371 TC, 166 TPC, and 163 CP. Pooled data analysis showed that robotic TC and STC had a lower conversion rate (OR = 0.17;95% CI, 0.04–0.82; p = 0.03) than laparoscopic TC and STC. The robotic approach was associated with longer operative time for TC and STC (MD = 104.64;95% CI, 18.42–190.87; p = 0.02) and TPC and CP (MD = 38.8;95% CI, 18.7–59.06; p = 0.0002), with no differences for postoperative complications and hospital stay. Reports on urological outcomes, sexual dysfunction, and quality of life were missing. Conclusions: Our experience and the literature suggest that robotic multiquadrant colorectal surgery is safe and effective, with low morbidity and mortality rates. Nevertheless, the overall level of evidence is low, and functional outcomes of robotic approach remain largely unknown. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022303016

X-Ray Magnetic Circular Dichroism at the K edge of Mn3GaC

We theoretically investigate the origin of the x-ray magnetic circular dichroism (XMCD) spectra at the K edges of Mn and Ga in the ferromagnetic phase of Mn3GaC on the basis of an ab initio calculation. Taking account of the spin-orbit interaction in the LDA scheme, we obtain the XMCD spectra in excellent agreement with the recent experiment. We have analyzed the origin of each structure, and thus elucidated the mechanism of inducing the orbital polarization in the p symmetric states. We also discuss a simple sum rule connecting the XMCD spectra with the orbital moment in the p symmetric states.Comment: 5 pages, 5 figures, accepted for publication in Physical Review