The stress kinase GCN2 does not mediate suppression of antitumor T cell responses by tryptophan catabolism in experimental melanomas.

Tryptophan metabolism is a key process that shapes the immunosuppressive tumor microenvironment. The two rate-limiting enzymes that mediate tryptophan depletion, indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO), have moved into the focus of research and inhibitors targeting IDO and TDO have entered clinical trials. Local tryptophan depletion is generally viewed as the crucial immunosuppressive mechanism.

An overlooked horticultural crop, Smyrnium olusatrum, as a potential source of compounds effective against African trypanosomiasis.

Among natural products, sesquiterpenes have shown promising inhibitory effects against bloodstream forms of Trypanosoma brucei, the protozoan parasite causing human African trypanosomiasis (HAT). Smyrnium olusatrum (Apiaceae), also known as Alexanders or wild celery, is a neglected horticultural crop characterized by oxygenated sesquiterpenes containing a furan ring. In the present work we explored the potential of its essential oils obtained from different organs and the main oxygenated sesquiterpenes, namely isofuranodiene, germacrone and β-acetoxyfuranoeudesm-4(15)-ene, as inhibitors of Trypanosoma brucei.

Emotional Intelligence and cognitive abilities - associations and sex differences.

In order to expand on previous research, this cross-sectional study investigated the relationship between Emotional Intelligence (EI) and cognitive abilities in healthy adults with a special focus on potential sex differences. EI was assessed by means of the Mayer-Salovey-Caruso-Emotional-Intelligence Test (MSCEIT), whereas cognitive abilities were investigated using the Brief Assessment of Cognition in Schizophrenia (BACS), which measures key aspects of cognitive functioning, i.e.

Estimation of local and external contributions of biomass burning to PM in an industrial zone included in a large urban settlement.

A total of 85 PM samples were collected at a site located in a large industrial zone (Porto Marghera, Venice, Italy) during a 1-year-long sampling campaign. Samples were analyzed to determine water-soluble inorganic ions, elemental and organic carbon, and levoglucosan, and results were processed to investigate the seasonal patterns, the relationship between the analyzed species, and the most probable sources by using a set of tools, including (i) conditional probability function (CPF), (ii) conditional bivariate probability function (CBPF), (iii) concentration weighted trajectory (CWT), and (iv) potential source contribution function (PSCF) analyses. Furthermore, the importance of biomass combustions to PM was also estimated.

Recent advances in understanding the extracellular calcium-sensing receptor.

The extracellular calcium-sensing receptor (CaR), a ubiquitous class C G-protein-coupled receptor (GPCR), is responsible for the control of calcium homeostasis in body fluids. It integrates information about external Ca and a surfeit of other endogenous ligands into multiple intracellular signals, but how is this achieved? This review will focus on some of the exciting concepts in CaR signaling and pharmacology that have emerged in the last few years.

Prescribing Practice in Inpatients Versus Outpatients With Schizophrenia Initiating Treatment With Second-Generation Antipsychotics: A Naturalistic Follow-Up Study.

Objective: The primary objective of this study was to investigate whether the choice and dosage of antipsychotic medication differ between patients with schizophrenia starting treatment in an inpatient or outpatient unit. In addition, we investigated whether the reason for the introduction of new antipsychotic medication had an impact on the treatment setting and whether the use of benzodiazepines differed between inpatients and outpatients.

Method: From October 1997 to September 2010, patients with a schizophrenia spectrum disorder according to the International Classification of Diseases, Tenth Revision aged between 18 and 65 years were allocated to a naturalistic drug-monitoring program when starting treatment with a second-generation antipsychotic drug.

Emotional intelligence and non-social cognition in schizophrenia and bipolar I disorder.

Background: The different patterns of Emotional Intelligence (EI) deficits in schizophrenia and bipolar I disorder are are not yet well understood. This study compares EI levels among these groups and highlights the potential impact of non-social cognition on EI.

Method: Fifty-eight schizophrenia and 60 bipolar outpatients were investigated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Brief Assessment of Cognition in Schizophrenia (BACS).

Characterization of the photocurrents generated by the laser of atomic force microscopes.

The conductive atomic force microscope (CAFM) has become an essential tool for the nanoscale electronic characterization of many materials and devices. When studying photoactive samples, the laser used by the CAFM to detect the deflection of the cantilever can generate photocurrents that perturb the current signals collected, leading to unreliable characterization. In metal-coated semiconductor samples, this problem is further aggravated, and large currents above the nanometer range can be observed even without the application of any bias.

[Antipsychotic-induced tardive syndromes].

Tardive dyskinesia (TD) remains a relevant clinical problem despite the increasing use of new-generation antipsychotics. Antipsychotic-induced tardive syndromes are difficult to treat and have a low tendency of remission. Therefore, prophylaxis is of utmost importance, with the responsible use of antipsychotics as a prime desideratum.

Biological Activities of the Essential Oil from Erigeron floribundus.

Erigeron floribundus (Asteraceae) is an herbaceous plant widely used in Cameroonian traditional medicine to treat various diseases of microbial and non-microbial origin. In the present study, we evaluated the in vitro biological activities displayed by the essential oil obtained from the aerial parts of E. floribundus, namely the antioxidant, antimicrobial and antiproliferative activities.

A ribonucleotide reductase inhibitor with deoxyribonucleoside-reversible cytotoxicity.

Ribonucleotide Reductase (RNR) is the sole enzyme that catalyzes the reduction of ribonucleotides into deoxyribonucleotides. Even though RNR is a recognized target for antiproliferative molecules, and the main target of the approved drug hydroxyurea, few new leads targeted to this enzyme have been developed. We have evaluated a recently identified set of RNR inhibitors with respect to inhibition of the human enzyme and cellular toxicity.

A German e-learning-training in the context of early preventive intervention and child protection: preliminary findings of a pre-post evaluation.

Background: In recent years, a number of government-sponsored initiatives have been implemented in Germany that are focused on early preventive intervention in child protection. In response to the need for interdisciplinary training in this area, the internet-based e-learning program "Early Preventive Intervention and Child Protection" was developed for professionals in the child welfare and health care systems working with families with infants and toddlers. The program is currently undergoing evaluation for effectiveness and user satisfaction.

Quality of life in stabilized patients with schizophrenia is mainly associated with resilience and self-esteem.

Objective: Improving quality of life (QoL) is an important objective in the treatment of schizophrenia. The aim of the current study was to examine to what extent resilience, self-esteem, hopelessness, and psychopathology are correlated with QoL.

Method: We recruited 52 out-patients diagnosed with schizophrenia according to DSM-IV criteria and 77 healthy control subjects from the general community.

Therapeutic Alliance in Patients With Schizophrenia: Introduction of a New Rating Instrument.

Objective: The quality of the patient-psychiatrist relationship can be seen as a cornerstone of adherence to medications in patients with chronic psychiatric disorders. Although therapeutic alliance in psychotherapy has been investigated broadly, it has received little attention in the context of medication adherence. The goal of this study was to develop and validate a user-friendly questionnaire for the assessment of therapeutic alliance in clinically stable outpatients with schizophrenia.

Identifying Kinase Substrates via a Heavy ATP Kinase Assay and Quantitative Mass Spectrometry.

Mass spectrometry-based in vitro kinase screens play an essential role in the discovery of kinase substrates, however, many suffer from biological and technical noise or necessitate genetically-altered enzyme-cofactor systems. We describe a method that combines stable γ-[(18)O2]-ATP with classical in vitro kinase assays within a contemporary quantitative proteomic workflow. Our approach improved detection of known substrates of the non-receptor tyrosine kinase ABL1; and identified potential, new in vitro substrates.

VP3 is crucial for the stability of Nora virus virions.

Nora virus is an enteric virus that causes persistent, non-pathological infection in Drosophila melanogaster. It replicates in the fly gut and is transmitted via the fecal-oral route. Nora virus has a single-stranded positive-sense RNA genome, which is translated in four open reading frames.

Chemoselective Dimerization of Phosphates.

A methodology for the synthesis of oligophosphate conjugates using phosphordiamidites is described. This strategy facilitates the straightforward preparation of C2-symmetric dinucleoside tri-, penta-, and heptaphosphates. Moreover, unsymmetric compounds such as thiamine adenosine triphosphate and thiamine cytidine triphosphate can be prepared.

Differences Between Psoriasis Patients and Skin-healthy Controls Concerning Appraisal of Touching, Shame and Disgust.

Psoriasis is a chronic skin disease associated with high levels of psychological distress and considerable life impact. Feelings of shame and stigmatization can lead to avoidance of social activity and intimacy. In this study, the questionnaire TSD-Q was used to evaluate pleasure in touching oneself and in a partnership, parental touching during childhood and (skin-related) shame and disgust.

Clinical and biological correlates of resilience in patients with schizophrenia and bipolar disorder: A cross-sectional study.

Objective: The concept of resilience is relevant in understanding the heterogeneous outcomes noted in schizophrenia and bipolar disorder. However, clinical and biological correlates of resilience in these populations have rarely been investigated. We aimed to identify key correlates of subjective resilience in such patients using comprehensive assessments and to explore associations between resilience levels and peripheral biomarkers.

Structural Mechanism of Allosteric Activity Regulation in a Ribonucleotide Reductase with Double ATP Cones.

Ribonucleotide reductases (RNRs) reduce ribonucleotides to deoxyribonucleotides. Their overall activity is stimulated by ATP and downregulated by dATP via a genetically mobile ATP cone domain mediating the formation of oligomeric complexes with varying quaternary structures. The crystal structure and solution X-ray scattering data of a novel dATP-induced homotetramer of the Pseudomonas aeruginosa class I RNR reveal the structural bases for its unique properties, namely one ATP cone that binds two dATP molecules and a second one that is non-functional, binding no nucleotides.

Trypanosoma brucei Methylthioadenosine Phosphorylase Protects the Parasite from the Antitrypanosomal Effect of Deoxyadenosine: IMPLICATIONS FOR THE PHARMACOLOGY OF ADENOSINE ANTIMETABOLITES.

Trypanosoma brucei causes African sleeping sickness for which no vaccine exists and available treatments are of limited use due to their high toxicity or lack of efficacy. T. brucei cultivated in the presence of deoxyadenosine accumulates high levels of dATP in an adenosine kinase-dependent process and dies within a few hours.

Bilirubin concentration correlates with positive symptoms in patients with schizophrenia.

Objective: Besides its toxic effects, bilirubin has been demonstrated to have antioxidant properties to counteract oxidative stress, which has been suggested to play a role in the pathophysiology of schizophrenia.

Methods: This study investigated the potential association between changes in psychopathology measured by the Lindenmayer model of the Positive and Negative Syndrome Scale (PANSS) and changes in total plasma bilirubin concentrations. Data of patients with schizophrenia (ICD-10) starting monotherapy with a new-generation antipsychotic were analyzed at baseline (N = 52) and 2 (n = 40), 4 (n = 46), and 12 weeks (n = 30) after the initiation of treatment.

Economic analysis of two-stage septic revision after total hip arthroplasty: What are the relevant costs for the hospital's orthopedic department?

Background: The number of septic total hip arthroplasty (THA) revisions is increasing continuously, placing a growing financial burden on hospitals. Orthopedic departments performing septic THA revisions have no basis for decision making regarding resource allocation as the costs of this procedure for the departments are unknown. It is widely assumed that septic THA procedures can only be performed at a loss for the department.

Emotional Intelligence deficits in schizophrenia: The impact of non-social cognition.

Background: Previous studies using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) revealed significant performance deficits across all areas of Emotional Intelligence (EI) in schizophrenia patients compared to healthy controls. However, none of these studies has investigated a potential influence of non-social cognition on these findings.

Methods: 56 schizophrenia outpatients and 84 control subjects were investigated using the MSCEIT and the Brief Assessment of Cognition in Schizophrenia (BACS).