A schizophrenia-like psychotic disorder secondary to an arachnoid cyst remitted with neurosurgical treatment of the cyst

We describe a case of delusional psychosis that was terminated by neurosurgical removal of a large arachnoid cyst. The patient was suffering his first psychotic episode and had symptoms typical of schizophrenia. The case underscores the importance of considering that an arachnoid cyst can induce psychopathological symptoms, even those of schizophrenia. Indeed, such symptoms may be the cyst's only clinical manifestation. In addition, the case highlights the importance of doing a structural imaging test when confronted with a first episode of psychosis, especially if the episode is relatively late in appearance. Such imaging may lead to a diagnosis that in turn can enable a definitive neurosurgical resolution of the psychosis

The impact of the Val158Met COMT polymorphism on context processing in patients on the schizophrenia spectrum and their relatives

Introduction: The level of dopamine in the prefrontal cortex (PFC) appears to play a fundamental role in cognitive alterations in schizophrenia. The Val158Met polymorphism of the catechol-O-methyltransferase (COMT) enzyme impacts dopamine availability in the prefrontal cortex and can thus influence cognitive functioning. Among the different cognitive deficits found in schizophrenia patients, context processing deficits have been noted as a specific characteristic of schizophrenia, for which the cerebral substrate appears to be located in the dorsolateral PFC. In this study, we examine the impact of the Val158Met COMT polymorphism on context processing in a sample of patients on the schizophrenia spectrum, their relatives, and healthy control subjects evaluated using the Dot Probe Expectancy Task (DPX). Methods: Forty patients on the schizophrenia spectrum, 26 relatives, and 63 healthy control subjects were genotyped and performed the DPX test. Results: Both patients and their relatives demonstrated deficits in context processing influenced by the Val158Met COMT polymorphism. Compared with the other subjects, the Val/Val subjects showed poorer performance on context processing tasks. Conclusions: Deficits in context processing in schizophrenic patients and their families are influenced by the Val158Met COMT functional polymorphism, likely as a consequence of reduced dopamine availability in the PFC

Imported Human West Nile Virus Lineage 2 Infection in Spain: Neurological and Gastrointestinal Complications

We report the first human case of West Nile virus (WNV) lineage 2 infection imported to Spain by a traveler returning from Romania. Serum, cerebrospinal fluid and urine samples were analyzed and West Nile virus infection was identified by PCR and serological tests. The patient developed fever, diarrhea and neurological symptoms, accompanied by mild pancreatitis, described previously in very few cases as a complication of WNV infection and by alithiasic cholecystitis. Viral RNA was detected in urine until 30 days after the onset of symptoms and neutralizing antibodies were detected at very low titers. The phylogenetic analysis in a fragment of the NS5 gene of the virus showed a homology with sequences from WNV lineage 2 belonging to the monophyletic Central/Southern European group.This work was partially funded by the Instituto de Salud Carlos III Projects “PI14CIII/00014” and “PI19CIII_00014”.S

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

University quality measurement model based on balanced scorecard

A Higher Education Institution (HEI) has the responsibility to track the processes through indicators that guarantee the measurement of the results in almost real time. This article presents the design of a management and quality model of the processes in a university, through the integration of a Balance Scorecard (BSC) and the implementation of an information system. For which it was required: a review of existing tracing and monitoring systems in the academic sector, definition of the requirements of the proposed technological, a diagnosis of the current measurement system of the HEI analyzed, identify measurement indicators and develop a technological tool. The designed model presents a precise and clear methodological guide that can be replicated in any HEI to monitor its processes

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Probing the Mutational Interplay between Primary and Promiscuous Protein Functions: A Computational-Experimental Approach

Protein promiscuity is of considerable interest due its role in adaptive metabolic plasticity, its fundamental connection with molecular evolution and also because of its biotechnological applications. Current views on the relation between primary and promiscuous protein activities stem largely from laboratory evolution experiments aimed at increasing promiscuous activity levels. Here, on the other hand, we attempt to assess the main features of the simultaneous modulation of the primary and promiscuous functions during the course of natural evolution. The computational/experimental approach we propose for this task involves the following steps: a function-targeted, statistical coupling analysis of evolutionary data is used to determine a set of positions likely linked to the recruitment of a promiscuous activity for a new function; a combinatorial library of mutations on this set of positions is prepared and screened for both, the primary and the promiscuous activities; a partial-least-squares reconstruction of the full combinatorial space is carried out; finally, an approximation to the Pareto set of variants with optimal primary/promiscuous activities is derived. Application of the approach to the emergence of folding catalysis in thioredoxin scaffolds reveals an unanticipated scenario: diverse patterns of primary/promiscuous activity modulation are possible, including a moderate (but likely significant in a biological context) simultaneous enhancement of both activities. We show that this scenario can be most simply explained on the basis of the conformational diversity hypothesis, although alternative interpretations cannot be ruled out. Overall, the results reported may help clarify the mechanisms of the evolution of new functions. From a different viewpoint, the partial-least-squares-reconstruction/Pareto-set-prediction approach we have introduced provides the computational basis for an efficient directed-evolution protocol aimed at the simultaneous enhancement of several protein features and should therefore open new possibilities in the engineering of multi-functional enzymes

Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery

To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery

βα-Hairpin Clamps Brace βαβ Modules and Can Make Substantive Contributions to the Stability of TIM Barrel Proteins

Non-local hydrogen bonding interactions between main chain amide hydrogen atoms and polar side chain acceptors that bracket consecutive βα or αβ elements of secondary structure in αTS from E. coli, a TIM barrel protein, have previously been found to contribute 4–6 kcal mol−1 to the stability of the native conformation. Experimental analysis of similar βα-hairpin clamps in a homologous pair of TIM barrel proteins of low sequence identity, IGPS from S. solfataricus and E. coli, reveals that this dramatic enhancement of stability is not unique to αTS. A survey of 71 TIM barrel proteins demonstrates a 4-fold symmetry for the placement of βα-hairpin clamps, bracing the fundamental βαβ building block and defining its register in the (βα)8 motif. The preferred sequences and locations of βα-hairpin clamps will enhance structure prediction algorithms and provide a strategy for engineering stability in TIM barrel proteins