A new synthetic sulfur-containing amino acid: S-aminoethylcysteine

Riassunto L'aminoetilcisteina, composto intermedio ipotetico di transulfurazione tra cisteina e etanolamina, è stata preparata cristallina sotto forma di monocloridrato, trattando la cisteina con bromoetilamina in ambiente alcalino.     

Sulfur exchange between thiotaurine and hypotaurine

Résumé Les auteurs ont préparé avec une enzyme de la thiotaurine et de l'hypotaurine marquées par le et S³⁵ ont démontré que ces deux composés peuvent échanger spontanément un atome de soufre en se transformant l'un dans l'autre.     

The transulfuration of sulfinates by polysulfides

Riassunto È stato dimostrato che la transulfurazione che consegue alla incubazione dei solfinati con zolfo ed un composto tiolico è dovuta in parte alla produzione di un polisolfuro organico, formato dal tiolo e zolfo, ed in parte al polisolfuro inorganico, formato dalla decomposizione di quello organico. L'entità della transulfurazione prodotta direttamente dal polisolfuro organico varia con il tipo di polisolfuro e dipende dalla sua stabilità nelle condizioni usate.     

Synthesis and antitumour activity of new daunorubicin and adriamycin analogues

Summary A new synthetic procedure for the preparation of daunorubicin and adriamycin analogues bearing different substituents on ring D, has been developed. The new compounds display outstanding efficacy against experimental tumours of mice.     

Overreaction in Survey Exchange Rate Forecasts

We use survey data on five bilateral exchange rates to provide empirical evidence of the fact that professional forecasters of foreign exchange rates behave irrationally, in the specific sense that they respond inaccurately to available information in the market when forming their predictions. In particular, we find systematic biases in the forecasts resulting in the overreaction of analysts to past information contained in the exchange rate dynamics: forecasters change their prediction more than it would be rational on the basis of past realized changes. In addition, forecasters are heterogeneous in their irrationality: low performers in previous periods show a more pronounced overreaction effect. This can be read as an indication of perpetration of past errors and continued inability to learn from the past. In the second part of the paper, we exploit the novel structure of our dataset, which consists of survey data extracted from the Bloomberg platform and readily available to anyone. This feature allows us to consider their own and others' past forecasts as part of the information set that analysts use in making their predictions. By using past forecasts as proxies for relevant macroeconomic variables, we find evidence that analysts fail to correctly process not only the information contained in the spot rate past dynamics but also the information in this broader set. We see this as confirmation of the existence of inefficiency and heterogeneity between low and high performers also when full information is available. Copyright © 2014 John Wiley & Sons, Ltd.     

Control of cerebral size and thickness

The mammalian neocortex is a sheet of cells covering the cerebrum that provides the structural basis for the perception of sensory inputs, motor output responses, cognitive function, and mental capacity of primates. Recent discoveries promote the concept that increased cortical surface size and thickness in phylogenetically advanced species is a result of an increased generation of neurons, a process that underlies higher cognitive and intellectual performance in higher primates and humans. Here, we review some of the advances in the field, focusing on the diversity of neocortical progenitors in different species and the cellular mechanisms of neurogenesis. We discuss recent views on intrinsic and extrinsic molecular determinants, including the role of epigenetic chromatin modifiers and microRNA, in the control of neuronal output in developing cortex and in the establishment of normal cortical architecture.     

Do we need pharmacogenetics to personalize antidepressant therapy?

This review examines the role of drug metabolism and drug target polymorphism in determining the clinical response to antidepressants. Even though antidepressants are the most effective available treatment for depressive disorders, there is still substantial need for improvement due to the slow onset of appreciable clinical improvement and the association with side effects. Moreover, a substantial group of patients receiving antidepressant therapy does not achieve remission or fails to respond entirely. Even if the large variation in antidepressant treatment outcome across individuals remains poorly understood, one possible source of this variation in treatment outcome are genetic differences. The review focuses on a few polymorphisms which have been extensively studied, while reporting a more comprehensive reference to the existing literature in table format. It is relatively easy to predict the effect of polymorphisms in drug metabolizing enzymes, such as cytochromes P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19), which may be determined in the clinical context in order to explain or prevent serious adverse effects. The role of target polymorphism, however, is much more difficult to establish and may be more relevant for disease susceptibility and presentation rather than for response to therapy.     

The unconventional secretion of stress-inducible protein 1 by a heterogeneous population of extracellular vesicles

The co-chaperone stress-inducible protein 1 (STI1) is released by astrocytes, and has important neurotrophic properties upon binding to prion protein (PrP^C). However, STI1 lacks a signal peptide and pharmacological approaches pointed that it does not follow a classical secretion mechanism. Ultracentrifugation, size exclusion chromatography, electron microscopy, vesicle labeling, and particle tracking analysis were used to identify three major types of extracellular vesicles (EVs) released from astrocytes with sizes ranging from 20–50, 100–200, and 300–400 nm. These EVs carry STI1 and present many exosomal markers, even though only a subpopulation had the typical exosomal morphology. The only protein, from those evaluated here, present exclusively in vesicles that have exosomal morphology was PrP^C. STI1 partially co-localized with Rab5 and Rab7 in endosomal compartments, and a dominant-negative for vacuolar protein sorting 4A (VPS4A), required for formation of multivesicular bodies (MVBs), impaired EV and STI1 release. Flow cytometry and PK digestion demonstrated that STI1 localized to the outer leaflet of EVs, and its association with EVs greatly increased STI1 activity upon PrP^C-dependent neuronal signaling. These results indicate that astrocytes secrete a diverse population of EVs derived from MVBs that contain STI1 and suggest that the interaction between EVs and neuronal surface components enhances STI1–PrP^C signaling.     

Metabolic syndrome as a risk factor for neurological disorders

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic ‘bodyweight/appetite/satiety set point,’ resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer’s disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer’s disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer’s disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders.     

Weights and robustness of model-based seasonal adjustment

Model-based seasonal adjustment implicitly defines a set of weights at the ends of series as well as in the middle. Until now, with the exception of very simple models, the weights have been obtained numerically. In this paper we give the analytical expressions for the weights for both the structural and the ARIMA framework for a model which contains trend, seasonal and irregular component. In the final part of the paper we address the question of robustness of model-based seasonal adjustment. We analyse practically, using real time series, and theoretically, through the analysis of the shape of the weights, how the fitting of different specifications for the non-seasonal part affects the extraction of the seasonal component. © 1998 John Wiley & Sons, Ltd.