Kernel-based active subspaces with application to computational fluid dynamics parametric problems using the discontinuous Galerkin method.

Nonlinear extensions to the active subspaces method have brought remarkable results for dimension reduction in the parameter space and response surface design. We further develop a kernel-based nonlinear method. In particular, we introduce it in a broader mathematical framework that contemplates also the reduction in parameter space of multivariate objective functions.

Extracellular vesicles from pristane-treated CD38-deficient mice express an anti-inflammatory neutrophil protein signature, which reflects the mild lupus severity elicited in these mice.

In CD38-deficient ( mice intraperitoneal injection of pristane induces a lupus-like disease, which is milder than that induced in WT mice, showing significant differences in the inflammatory and autoimmune processes triggered by pristane. Extracellular vesicles (EV) are present in all body fluids. Shed by cells, their molecular make-up reflects that of their cell of origin and/or tissue pathological situation.

Pemphigus Vulgaris Localized to the Scalp with Complete Response to Topical Steroids.

Pemphigus vulgaris (PV) is an anti-cadherin autoimmune disease, characterized by the production of anti-desmoglein 3 (and to a lesser extent anti-desmoglein 1) antibodies, producing acanthosis, typically suprabasal, which clinically translates into flaccid blisters and erosions, generally starting on mucous membranes, with subsequent appearance of skin lesions. Only about 25 cases of PV of exclusively cutaneous location have been described in the literature. Treatment with potent topical steroids is usually sufficient to control the symptoms.

Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis.

Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows.

Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior in SAPAP3 knockout mice.

Obsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fast-acting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms.

Real-World Characteristics and Outcome of Patients Treated With Single-Agent Ibrutinib for Chronic Lymphocytic Leukemia in Spain (IBRORS-LLC Study).

Background: Ibrutinib demonstrated remarkable efficacy and favorable tolerability in patients with untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), including those with high-risk genetic alterations. The IBRORS-CLL study assessed the characteristics, clinical management and outcome of CLL patients receiving ibrutinib in routine clinical practice in Spain.

Patients: Observational, retrospective, multicenter study in CLL patients who started single-agent ibrutinib as first-line treatment or at first or second relapse between January 2016 and January 2019.

A kinesin 1-protrudin complex mediates AMPA receptor synaptic removal during long-term depression.

The synaptic removal of AMPA-type glutamate receptors (AMPARs) is a core mechanism for hippocampal long-term depression (LTD). In this study, we address the role of microtubule-dependent transport of AMPARs as a driver for vesicular trafficking and sorting during LTD. Here, we show that the kinesin-1 motor KIF5A/C is strictly required for LTD expression in CA3-to-CA1 hippocampal synapses.

KIF13A drives AMPA receptor synaptic delivery for long-term potentiation via endosomal remodeling.

The regulated trafficking of AMPA-type glutamate receptors (AMPARs) from dendritic compartments to the synaptic membrane in response to neuronal activity is a core mechanism for long-term potentiation (LTP). However, the contribution of the microtubule cytoskeleton to this synaptic transport is still unknown. In this work, using electrophysiological, biochemical, and imaging techniques, we have found that one member of the kinesin-3 family of motor proteins, KIF13A, is specifically required for the delivery of AMPARs to the spine surface during LTP induction.

Bone marrow infiltration by flow cytometry at diffuse large B-cell lymphoma NOS diagnosis implies worse prognosis without considering bone marrow histology.

Background: The significance of discrepant findings between histology (BMB) and flow cytometry (FC) in bone marrow (BM) examination at diffuse large B-cell lymphoma (DLBCL) diagnosis is uncertain.

Methods: We performed a 5-year retrospective single-center study of patients diagnosed by DLBCL not otherwise specified (n = 82), divided into three groups according to BM infiltration at diagnosis: BMB-/FC- (75.6%), BMB+/FC+ (13.

Central Centrifugal Cicatricial Alopecia Following a Patchy Pattern: A New Form of Clinical Presentation and a Challenging Diagnosis for the Dermatologist.

Central centrifugal cicatricial alopecia (CCCA) is included among the primary lymphocytic cicatricial alopecias. The current nomenclature of CCCA suggested by the North American Hair Research Society refers to the traditional clinical presentation pattern of this type of alopecia, which begins in the central area of the scalp and has a progressive and symmetric centrifuge evolution. However, some exceptions should be highlighted, and a new clinical variety of CCCA presenting with patches of hair loss affecting the lateral and posterior scalp has been recently described.

MAP1B Light Chain Modulates Synaptic Transmission via AMPA Receptor Intracellular Trapping.

The regulated transport of AMPA-type glutamate receptors (AMPARs) to the synaptic membrane is a key mechanism to determine the strength of excitatory synaptic transmission in the brain. In this work, we uncovered a new role for the microtubule-associated protein MAP1B in modulating access of AMPARs to the postsynaptic membrane. Using mice and rats of either sex, we show that MAP1B light chain (LC) accumulates in the somatodendritic compartment of hippocampal neurons, where it forms immobile complexes on microtubules that limit vesicular transport.

A multicentric study to evaluate the use of relative retention times in targeted proteomics.

Unlabelled: Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII).

[New mutation in a young woman diagnosed with Niemann-Pick disease type C].

Background And Objetive: To describe a new molecular variant of Niemann-Pick disease type C (NPC) in a 27 year-old patient with splenomegaly and abolition of osteotendinous reflexes.

Material And Methods: NPC1 is the main gene with described mutation in NPC disease. Here we report a case with a new mutation, p.

Supporting data for the MS identification of distinct transferrin glycopeptide glycoforms and citrullinated peptides associated with inflammation or autoimmunity.

This data article presents the results of all the statistical analyses applied to the relative intensities of the detected 2D-DiGE protein spots for each of the 3 performed DiGE experiments. The data reveals specific subsets of protein spots with significant differences between WT and CD38-deficient mice with either Collagen-induced arthritis (CIA), or with chronic inflammation induced by CFA, or under steady-state conditions. This article also shows the MS data analyses that allowed the identification of the protein species which serve to discriminate the different experimental groups used in this study.

Eculizumab Treatment in a Patient with Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy and Steroid-Refractory Acute Graft Versus Host Disease.

A 30-year-old man with acquired aplastic anemia underwent an HLA-identical bone marrow transplant. He developed a grade III acute graft versus host disease (GVHD) refractory to various lines of treatment. On post-transplant day 196, he was diagnosed with stem cell transplantation-associated thrombotic micro-angiopathy (HSCT-TMA) and he received treatment with eculizumab 900 mg iv weekly for 4 doses followed by a single dose of 1200 mg 2 weeks later.

Identification of multiple transferrin species in the spleen and serum from mice with collagen-induced arthritis which may reflect changes in transferrin glycosylation associated with disease activity: The role of CD38.

Unlabelled: Collagen type II-induced arthritis (CIA) is an inflammatory and autoimmune disease. Spleen protein extracts were subjected to 2D-DiGE and MS-MALDI-TOF/TOF analysis to identify protein species that differ in abundance in CD38-KO versus B6 WT mice either with arthritis or with inflammation. Using multivariate analyses, in Col-II-immunized mice, 23 distinct spleen protein species were able to discriminate between WT and CD38-KO mice.

Distinct serum proteome profiles associated with collagen-induced arthritis and complete Freund's adjuvant-induced inflammation in CD38⁻/⁻ mice: The discriminative power of protein species or proteoforms.

Collagen-type-II-induced arthritis (CIA) is an autoimmune disease, which involves a complex host systemic response including inflammatory and autoimmune reactions. CIA is milder in CD38(-/-) than in wild-type (WT) mice. ProteoMiner-equalized serum samples were subjected to 2D-DiGE and MS-MALDI-TOF/TOF analyses to identify proteins that changed in their relative abundances in CD38(-/-) versus WT mice either with arthritis (CIA(+) ), with no arthritis (CIA(-) ), or with inflammation (complete Freund's adjuvant (CFA)-treated mice).

Von Willebrand Factor Deficiency Corrected by Lung Transplantation.

Background: In experimental models with von Willebrand disease pigs, plasma von Willebrand factor (vWF) was significantly increased after lung transplantation because lung endothelial cells strongly express vWF. However, these findings have not been confirmed in human beings.

Methods: A 26-year-old man with mild vWF deficiency (FvW:antigen 39 IU/dL; FvW:ristocetin cofactor activity 44 IU/dL; factor VIII 99%; normal multimeric plasma vWF pattern) was referred to our institution and underwent bilateral lung transplantation for cystic fibrosis.

Cluster-based comparison of the peptide mass fingerprint obtained by MALDI-TOF mass spectrometry. A case study: long-term stability of rituximab.

We evaluated the use of the peptide mass fingerprint (PMF) obtained by matrix assisted laser desorption and ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) to track changes in the structure of a protein. The first problem we had to overcome was the inherent complexity of the PMF, which makes it difficult to compare. We dealt with this problem by developing a cluster-based comparison algorithm which takes into account the proportional error made by the mass spectrometer.

PTEN counteracts PIP3 upregulation in spines during NMDA-receptor-dependent long-term depression.

Phosphoinositide 3-kinase (PI3K) and PTEN have been shown to participate in synaptic plasticity during long-term potentiation (LTP) and long-term depression (LTD), respectively. Nevertheless, the dynamics of phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) and the regulation of its synthesis and degradation at synaptic compartments is far from clear. Here, we have used fluorescence resonance energy transfer (FRET) imaging to monitor changes in PIP3 levels in dendritic spines from CA1 hippocampal neurons under basal conditions and upon induction of NMDA receptor (NMDAR)-dependent LTD and LTP.

Increased expression and phosphorylation of the two S100A9 isoforms in mononuclear cells from patients with systemic lupus erythematosus: a proteomic signature for circulating low-density granulocytes.

Proteins differentially expressed in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) patients versus Normal controls were identified by 2-DE and MALDI-MS. Thus, S100A9 expression was significantly increased in SLE PBMCs relative to Normal PBMCs at both mRNA and protein levels. Increased S100A9 levels in SLE PBMCs correlated positively with the abnormal presence of low-density granulocytes (LDGs) detected by flow-cytometry in the mononuclear cell fractions.