The [1,2,4]Triazolo[4,3-a]pyridine as a New Player in the Field of IDO1 Catalytic Holo-Inhibitors

Inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) are considered a promising strategy in cancer immunotherapy as they are able to boost the immune response and to work in synergy with other immunotherapeutic agents. Despite the fact that no IDO1 inhibitor has been approved so far, recent studies have shed light on the additional roles that IDO1 mediates beyond its catalytic activity, conferring new life to the field. Here we present a novel class of compounds originated from a structure-based virtual screening made on IDO1 active site. The starting hit compound is a novel chemotype based on a [1,2,4]triazolo[4,3-a]pyridine scaffold, so far underexploited among the heme binding moieties. Thanks to the rational and in silico-guided design of analogues, an improvement of the potency to sub-micromolar levels has been achieved, with excellent in vitro metabolic stability and exquisite selectivity with respect to other heme-containing enzymes.     

Dreams and reality monitoring.

Exp I tested the counterintuitive prediction that memories for one's own dreams should not be particularly easy to discriminate from memories for someone else's dreams. 10 pairs of undergraduate and graduate students reported dreams to each other that they had either dreamed, read, or made up the night before. On a test requiring them to discriminate events they had reported from those reported by their partner, Ss had more difficulty with real dreams than with dreams they read or made up. Data from 10 new pairs of Ss in Exp II provide evidence that real dreams do not simply produce overall weaker memories; the deficit for dreams was eliminated with more time to respond and with more detailed cues. In addition, Ss' ratings of various characteristics of their memories (e.g., vividness, personal relevance) indicated that dreams were not generally weaker or impoverished. Results are interpreted within the framework for reality monitoring described by M. K. Johnson and C. L. Raye (1981). A comparison of recognition and recall indicated that dreams may leave persisting memories that are difficult to access via free recall. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

(Z)6, (E)8-Heneicosadien-11-One: Synergistic Sex Pheromone Component of Douglas-Fir Tussock Moth, Orgyia pseudotsugata (McDunnough) (Lepidoptera: Lymantriidae)

Three candidate sex pheromone components, (Z)6,(Z)9-, (Z)6,(E)8-, and (Z)6,(E)9-heneicosadien-11-one (Z6Z9, Z6E8, and Z6E9) were identified in pheromone gland extracts of female Douglas-fir tussock moths (DFTM), Orgyia pseudotsugata (McDunnough). Their occurrence in subnanogram quantities in extracts and structural conversion during analytical procedures and bioassays complicated chemical identifications. Complete identification required comparative analyses of stereoselectively synthesized and female-produced dienones by coupled gas chromatographic–electroantennographic detection (GC-EAD), high-performance liquid chromatography (HPLC) and coupled GC–mass spectrometry (MS). Determination of the pheromone component was contingent upon an experimental design that minimized structural rearrangement of dienones before and during the field test. In a 40-min field experiment, acetonitrile solutions of each of the above dienones were carried on Dry Ice to traps and were syringed onto cotton release devices below trap lids. In combination with the previously known sex pheromone component of DFTM, (Z)6-heneicosen-11-one (Z6), Z6E8 was the only synergistic dienone and the mixture was highly attractive. Because Z6 by itself attracts seven species of tussock moths (two sympatric with DFTM), a blend of Z6 and Z6E8 may impart specificity to DFTM pheromone communication. In commercial lures, this binary blend may facilitate species-specific, sensitive monitoring and efficacious control by mating disruption of this important forest defoliator.     

Therapist complementarity as a function of experience and client stimuli.

Assessed degree of therapist (TP) complementarity (CMP), an interpersonal communication strategy, in 67 TPs' responses to client statements (CSTs) that varied on 3 dimensions (directness, power, and type of affect as it varied over TP experience level). TPs at all experience levels responded similarly to different types of CSTs. CMP was lowest in response to hostile-dominant CSTs and highest in response to hostile-submissive CSTs. Differences in CMP were found across levels of experience toward direct and indirect CSTs. Professional TPs were significantly more likely to respond to indirect client statements with lower CMP than were student TPs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The structure of interests and self-efficiency expectations: An expanded examination of the spherical model of interests.

A questionnaire packet assessing occupational preferences, activity preferences, and career self-efficacy expectations was administered to 2 samples of college students. The structural invariance of each data set (activity, self-efficacy, and occupation items) was examined for the 1st sample via principal-components analysis and they correlated. The structure was found to be highly similar across data types. The items were then aggregated into 18 scales representing the spherical model of interests proposed by T. J. G. Tracey and J. Rounds (1996b). The 18 scales were found to fit the spherical model for both the original and validation samples. No gender differences in the structure of the scales were found, but there were gender mean differences found in the scale scores similar to results of past research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disability and coping as predictors of psychological adjustment to rheumatoid arthritis.

Rheumatoid arthritis (RA) patients have been identified as a medical population at risk for psychological disorder, largely because of the pain and functional disability that are the hallmarks of the disease. This study examined the degree to which self-reported functional disability and coping efforts contribute to psychological adjustment among adult RA patients over a 6-month period. Adaptive outcomes included maintaining a sense of worth, mastery, and positive affect despite the illness. Hierarchical multiple regression analyses indicated that increases in disability were related to decreased acceptance of illness and increased negative affect. Coping efforts were related to increases in positive affect. The findings provide modest support for the role individual coping efforts play in shaping illness-related outcomes. Although disability is not easily reversed, knowledge about coping strategies that moderate its psychological impact may provide a useful basis for designing psychological interventions to promote adjustment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Empirical evaluation of DSM-IV generalized anxiety disorder criteria in children and adolescents

Evaluated the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV], American Psychiatric Association, 1994) generalized anxiety disorder (GAD) criteria in children and adolescents. Clinic-referred children meeting criteria for DSM-IV GAD, those meeting criteria for another DSM-IV anxiety disorder, and normal children participated in a structured interview and completed self-report questionnaires. Groups were compared in terms of interview and self-report measures to examine convergent and discriminant validity. In addition, developmental differences, cross-informant symptom and syndrome agreement, and validity of parent and child report were determined. Finally, the symptoms comprising the GAD associated symptom criterion (Criterion C) were examined in terms of rate of endorsement and predictive power. Results showed that parameters of worry differentiated children with GAD from those with other anxiety disorders and controls. Developmental differences in the sample did not appear to necessitate a separate criteria set for the classification of generalized anxiety in children of this age. Symptoms from GAD Criterion C evidenced moderately high rates of endorsement and acceptable predictive power. Overall, the DSM-IV GAD criteria for children and adolescents are supported, but further evaluation is necessary before firm conclusions can be drawn.     

Help seeking and problem perception among Asian Americans.

Compared the presenting concerns of 3,050 counseling center clients (undergraduate and graduate students) as those concerns varied by ethnicity, gender, and previous counseling experience. Asian-American clients were much more likely to perceive themselves as having educational or vocational concerns, whereas White clients were disproportionately more likely to admit to personal or emotional concerns. The comparison among 7 different Asian-American groups revealed that Filipino-American and Asian-American/White mixed clients were more likely to endorse personal or emotional concerns than other Asian-American groups. Gender and previous counseling experience were found to be related to the presenting concern, but the effects were the same in each ethnic comparison. Results are interpreted with respect to (1) what counselors should be aware of in interacting with Asian-American clients and (2) how they differ both from White clients and among themselves. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Towards a generalized model for the primary and secondary contamination of lakes by Chernobyl-derived radiocesium

As part of the UK Ministry of Agriculture Fisheries and Food Directorate of Fisheries Research (MAFF/DFR) post-Chernobyl monitoring program, a detailed study was carried out of the change over time in dissolved-phase 137Cs concentrations in a number of lakes in Cumbria, UK. These measurements have been combined with published data on 137Cs in Cumbrian and other European lakes in order to develop and test a "double exponential" model for changes in lakewater concentrations: A exp(-k1t) + B exp(-k2t) where the exponential terms correspond, respectively, to the initial fast flush of activity through the system followed by longer-term transfers (timescale, years) from the catchment. Parameter values have been determined for this model by curve-fitting to the set of measurements of post-Chernobyl 137Cs activities in lakes. Values of fitted parameters are shown to be related, in a simple manner, to the physical characteristics of the system, in particular water residence time and mean lake depth. These parameters are generalized to give a simple empirical model for the full set of study lakes. The model is shown to give estimates of 137Cs activity to within a factor of 5 of field data for a period of several years after the fallout. Initial fractional losses of activity from catchment to lake were determined to be within the range 0.44-8.7% per year, declining exponentially with a mean rate constant 0.98 x 10(-3) d(-1).