RB1CC1 duplication and aberrant overexpression in a patient with schizophrenia: further phenotype delineation and proposal of a pathogenetic mechanism

Background: Copy number variants in coding and noncoding genomic regions have been implicated as risk factor for schizophrenia (SCZ). Rare duplications of the RB1CC1 gene were found enriched in SCZ patients. Considering that the effect of such duplications on RB1CC1 expression has never been evaluated and partial gene duplications of RB1CC1 have also been reported in SCZ patients, it is unclear whether the pathogenesis is mediated by haploinsufficiency rather than genuine overexpression of the gene. Methods and results: We studied a patient with schizophrenia, suicidality, and obesity, who carried a de novo RB1CC1 complete duplication, as assessed by high-resolution array-CGH. Molecular breakpoint cloning allowed to identify nonhomologous end joining (NHEJ) as driving mechanism in this rearrangement. On the contrary, trio-based whole-exome sequencing excluded other potential causative variants related to the phenotype. Functional assays showed significant overexpression of RB1CC1 in the peripheral blood lymphocytes of the proband compared to control subjects, suggesting overdosage as leading mechanism in SCZ pathophysiology. Conclusion: We hypothesized a pathogenetic model that might explain the correlation between RB1CC1 overexpression and schizophrenia by altering different cell signaling pathways, including autophagy, a promising therapeutic target for schizophrenic patients

Case report: Ponatinib as a bridge to CAR-T cells and subsequent maintenance in a patient with relapsed/refractory Philadelphia-like acute lymphoblastic leukemia

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) constitutes a heterogeneous subset of ALL with a uniformly unfavorable prognosis. The identification of mutations amenable to treatment with tyrosine kinase-inhibitors (TKIs) represents a promising field of investigation. We report the case of a young patient affected by relapsed/refractory Ph-like ALL treated with chimeric antigen receptor T (CAR-T) cells after successful bridging with compassionate-use ponatinib and low-dose prednisone. We restarted low-dose ponatinib maintenance three months later. Twenty months later, measurable residual disease negativity and B-cell aplasia persist. To the best of our knowledge, this is the first case reporting the use of ponatinib in Ph-like ALL as a bridge to and maintenance after CAR-T cell therapy

DisProt in 2022: improved quality and accessibility of protein intrinsic disorder annotation

The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure.Fil: Quaglia, Federica. Università di Padova; Italia. Consiglio Nazionale delle Ricerche; ItaliaFil: Mészáros, Bálint. European Molecular Biology Laboratory; AlemaniaFil: Salladini, Edoardo. Università di Padova; ItaliaFil: Hatos, András. Università di Padova; ItaliaFil: Pancsa, Rita. Research Centre for Natural Sciences; HungríaFil: Chemes, Lucia Beatriz. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Pajkos, Mátyás. Eötvös Loránd University; HungríaFil: Lazar, Tamas. Vlaams Instituut voor Biotechnology; Hungría. Vrije Unviversiteit Brussel; BélgicaFil: Peña Díaz, Samuel. Universitat Autònoma de Barcelona; EspañaFil: Santos, Jaime. Universitat Autònoma de Barcelona; EspañaFil: Ács, Veronika. Research Centre for Natural Sciences; HungríaFil: Farahi, Nazanin. Vlaams Instituut voor Biotechnology; Bélgica. Vrije Unviversiteit Brussel; BélgicaFil: Fichó, Erzsébet. Research Centre for Natural Sciences; HungríaFil: Aspromonte, Maria Cristina. Università di Padova; Italia. Città della Speranza Pediatric Research Institute; ItaliaFil: Bassot, Claudio. Stockholms Universitet; SueciaFil: Chasapi, Anastasia. Centre for Research & Technology Hellas; GreciaFil: Davey, Norman E.. Chester Beatty Laboratories; Reino UnidoFil: Davidović, Radoslav. University of Belgrade; SerbiaFil: Laszlo Holland, Alicia Verónica. European Molecular Biology Laboratory; Alemania. Research Centre for Natural Sciences; HungríaFil: Elofsson, Arne. Stockholms Universitet; SueciaFil: Erdős, Gábor. Eötvös Loránd University; HungríaFil: Gaudet, Pascale. Swiss Institute of Bioinformatics; SuizaFil: Giglio, Michelle. University of Maryland School of Medicine; Estados UnidosFil: Glavina, Juliana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Iserte, Javier Alonso. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Iglesias, Valentín. Universitat Autònoma de Barcelona; EspañaFil: Kálmán, Zsófia. Pázmány Péter Catholic University; HungríaFil: Lambrughi, Matteo. Danish Cancer Society Research Center; DinamarcaFil: Leonardi, Emanuela. Università di Padova; Italia. Pediatric Research Institute Città della Speranza; ItaliaFil: Rodriguez Sawicki, Luciana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Association between preoperative evaluation with lung ultrasound and outcome in frail elderly patients undergoing orthopedic surgery for hip fractures: study protocol for an Italian multicenter observational prospective study (LUSHIP)

Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of "indirect" and "direct" cardiac and pulmonary lung ultrasound signs

Determination of the molecular packing in diketopiperazine crystal by means of Van der Waals and hydrogen bonding energy calculations

The crystal packing of diketopiperazine may be predicted from the approximate molecular geometry and space group symmetry. The van der Waals and hydrogen bonding energies were computed as a function of three rotational degrees of freedom (space group P21/a and Z = 2). The Eulerian angles, relative to the deepest minimum, correspond to a good approximation to the real structure. The calculations were carried out using potential functions tested in some crystals and in the conformational analysis of synthetic and biological macromolecules. A potential function proposed by Stockmayer was chosen to describe the hydrogen bond formation. The rigid-body translations of the molecules in the crystal, known from an analysis of the anisotropic atomic thermal parameters, were qualitatively checked. For this purpose the van der Waals potential energy was computed by moving one chain of molecules and leaving the surrounding chains fixed. The good results obtained again confirm the validity of this method for the solution of the phase problem. It is hoped that this approach may be useful in crystal structure determinations of organic molecules of biological interest

Calculation of the van der Waals potential energy for polyethylene and polytetrafluoroethylene as two-atom and three-atom chains: rotational freedom in the crystals

The van der Waals potential energy of polyethylene [9002-88-4] and polytetrafluoroethylene [9002-84-0], computed as a function of both 2 and 3 angles of rotation around the bonds of the backbone chain, showed more minima than predicted by the equivalence principle. The van der Waals potential energy in PTFE crystals, rotating the polymer chains around their helical axes in phase, indicated that the macromols. were free-rotating

Van der Waals and electrostatic interactions in crystals

Some potentials describing electrostatic interactions between oxygen and sodium, potassium, rubidium and caesium ions are tested in known organic crystal structures. The atomic and ionic coordinates may be predicted satisfactorily by locating the deepest minimum of the potential energy which depends on rotational and translational degrees of freedom

Comment on "Two-Dimensional NMR study on the structures of micelles of sodium taurocholate"

A polemic. The paper "Two-Dimensional NMR Study on the Structures of Micelles of Sodium Taurocholate" by N. Funasaki et al. (2004) demands some remarks that, in the authors opinion, throw doubts on the conclusions of this article. The authors do not want to pursue this polemic, even because they believe that these remarks are sufficient to promote a reinterpretation of the NMR and GFC data, at least. On the other hand, the conclusions are unwarranted and the optimistic sentence (see the Abstr. and also p 442) "Thus, a novel NMR method in surfactant chem. has provided the first step to resolve the 20-years debate about the structures of dimers and micelles of TC." is unfounded in their opinion

Potential energy calculations about the chain folding of a(-)poly(L-alanine).

Van der Waals energy calcns. on .alpha.-poly(L-alanine) [25191-17-7] were consistent with a chain structure of 2 parallel helical left- and right-handed segments joined by a tight fold