Less inhibited and more depressed? The puzzling association between mood, inhibitory control and depressive symptoms.

BACKGROUND: Inhibitory control (IC) deficits have been proposed as a potential risk factor for depression. However, little is known about the intra-individual daily fluctuations in IC, and its relationship to mood and depressive symptoms. Here, we examined the everyday association between IC and mood, in typical adults with various levels of depressive symptoms. METHODS: Participants (N = 106) reported their depressive symptoms and completed a Go-NoGo (GNG) task measuring IC at baseline. Then, they completed a 5-day ecological-momentary-assessment (EMA) protocol, in which they reported their current mood and performed a shortened GNG task twice/day using a mobile app. Depressive symptoms were measured again following the EMA. Hierarchical-linear-modeling (HLM) was applied to examine the association between momentary IC and mood, with post-EMA depressive symptoms as a moderator. RESULTS: Individuals with elevated depressive symptoms demonstrated worse and more variable IC performance over the EMA. In addition, post-EMA depressive symptoms moderated the association between momentary IC and daily mood, such that reduced IC was associated with more negative mood only for those with lower, but not higher, symptoms. LIMITATIONS: Future investigations should examine the validity of these outcomes in clinical samples, including patients with Major Depressive Disorder. CONCLUSIONS: Variable, rather than mere reduced, IC, is related to depressive symptoms. Moreover, the role of IC in modulating mood may differ in non-depressed individuals and individuals with sub-clinical depression. These findings contribute to our understanding of IC and mood in real life and help account for some of the discrepant findings related to cognitive control models of depression.

Modeling beta-sheet peptide-protein interactions: Rosetta FlexPepDock in CAPRI rounds 38-45.

Peptide-protein docking is challenging due to the considerable conformational freedom of the peptide. CAPRI rounds 38-45 included two peptide-protein interactions, both characterized by a peptide forming an additional beta strand of a beta sheet in the receptor. Using the Rosetta FlexPepDock peptide docking protocol we generated top-performing, high-accuracy models for targets 134 and 135, involving an interaction between a peptide derived from L-MAG with DLC8. In addition, we were able to generate the only medium-accuracy models for a particularly challenging target, T121. In contrast to the classical peptide-mediated interaction, in which receptor side chains contact both peptide backbone and side chains, beta-sheet complementation involves a major contribution to binding by hydrogen bonds between main chain atoms. To establish how binding affinity and specificity are established in this special class of peptide-protein interactions, we extracted PeptiDBeta, a benchmark of solved structures of different protein domains that are bound by peptides via beta-sheet complementation, and tested our protocol for global peptide-docking PIPER-FlexPepDock on this dataset. We find that the beta-strand part of the peptide is sufficient to generate approximate and even high resolution models of many interactions, but inclusion of adjacent motif residues often provides additional information necessary to achieve high resolution model quality.

Choosing to avoid the positive? Emotion regulation strategy choice in depression.

Individuals with major depressive disorder (MDD) are more likely than nondepressed individuals to use emotion regulation strategies that decrease pleasant emotions (e.g., distraction from positive stimuli) and increase unpleasant emotions (e.g., negative rumination). If such strategies are actively chosen, these choices may partly reflect weaker motivation for pleasant emotions or stronger motivation for unpleasant emotions. Therefore, this investigation tested, for the first time, whether such strategies are actively chosen, even when alternatives are available. In Study 1, using a behavioral task, MDD participants (N = 38) were more likely than healthy controls (N = 39) to choose to use distraction over positive rumination in response to pleasant stimuli, resulting in reductions in pleasant affect. When instructed to choose the strategy that would make them feel better, however, MDD participants did not differ from controls in their strategy choices. In Study 2, using ecological momentary assessments, MDD participants (N = 58) were more likely than controls (N = 62) to use distraction from pleasant emotions and to use negative rumination in daily life. This pattern of strategy use was predicted by stronger motivation for unpleasant emotions among MDD participants, compared to controls. Stronger motivation for unpleasant emotions in daily life also predicted increases in unpleasant affect and decreases in pleasant affect. Findings suggest that compared to nondepressed individuals, people with MDD are more likely to choose emotion regulation strategies that decrease pleasant emotions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Anti-T lymphocyte globulin (ATG) induces generation of regulatory T cells, at least part of them express activated CD44.

We show here that the anti-T lymphocyte immunoglobulin (ATG) can induce Treg cells following 24-h incubation in human peripheral blood mononuclear cells (PBMCs). The ATG-induced Treg cells express known cell surface markers (e.g., CD25, FoxP3) and suppress the proliferation of autologous responder PBMCs, stimulated with allogeneic PBMCs, when added into the mixed lymphocyte culture (MLC) at zero time point or 48 h later. We expanded the characteristics of the ATG-induced human Treg cells by showing that they express a novel biomarker designated "activated CD44". ATG-induced Treg cells retain their suppressor function after freezing and thawing or irradiation. Suppression of MLC by ATG-induced Treg cells is consistently seen when the Treg cells and the responder cells were derived from the same donor, but not when they derived from different donors. Finally, patients undergoing stem cell transplantation and conditioned with ATG generate in vivo Treg cells that suppress MLC.

Understanding the factors affecting teachers' burnout during the COVID-19 pandemic: A cross-sectional study.

BACKGROUND: During the COVID-19 pandemic, which enforced social distancing and isolation, teachers were required to handle multiple challenges related to their work, including dealing with remote teaching, in addition to personal, medical and financial challenges. The goal of the current research was to examine factors that contributed to professional burnout and commitment to work among teachers during the first and second waves of the COVID-19 pandemic. METHODS: A total of 344 elementary school teachers in Israel completed online self-report questionnaires, including assessments of stressors, anxiety, resilience, self-efficacy beliefs, and coping strategies. Structured Equation Modeling [SEM] was used to examine the contribution of these factors to professional burnout and commitment. RESULTS: The gaps between needed and received support had a direct effect on teachers' burnout and commitment, and an indirect effect through anxiety and self-efficacy beliefs. Stress relating to remote teaching and support-gaps regarding remote teaching were the most significant of all the stressors and sources of support. CONCLUSIONS: Collectively, these findings highlight the significance of remote teaching as the main cause of stress and professional burnout and suggest that proper preparation of teachers-before and during times of crisis, may have a significant impact on their mental and professional well-being.

The association between implicit and explicit affective inhibitory control, rumination and depressive symptoms.

Inhibitory control underlies one's ability to maintain goal-directed behavior by inhibiting prepotent responses or ignoring irrelevant information. Recent models suggest that impaired inhibition of negative information may contribute to depressive symptoms, and that this association is mediated by rumination. However, the exact nature of this association, particularly in non-clinical samples, is unclear. The current study assessed the relationship between inhibitory control over emotional vs. non-emotional information, rumination and depressive symptoms. A non-clinical sample of 119 participants (mean age: 36.44 ± 11.74) with various levels of depressive symptoms completed three variations of a Go/No-Go task online; two of the task variations required either explicit or implicit processing of emotional expressions, and a third variation contained no emotional expressions (i.e., neutral condition). We found reductions in inhibitory control for participants reporting elevated symptoms of depression on all three task variations, relative to less depressed participants. However, for the task variation that required implicit emotion processing, depressive symptoms were associated with inhibitory deficits for sad and neutral, but not for happy expressions. An exploratory analysis showed that the relationship between inhibition and depressive symptoms occurs in part through trait rumination for all three tasks, regardless of emotional content. Collectively, these results indicate that elevated depressive symptoms are associated with both a general inhibitory control deficit, as well as affective interference from negative emotions, with implications for the assessment and treatment of mood disorders.

2-(3-aryl-3-oxopropen-1-yl)-9-tert-butyl-paullones: a new antileishmanial chemotype.

A screening program directed to find new agents against Leishmania donovani, the parasite causing visceral leishmaniasis, revealed that paullones attenuate the proliferation of axenic amastigotes. Because these structures were not active in a test system involving infected macrophages, a structure optimization campaign was carried out. Concomitant introduction of an unsaturated side chain into the 2-position and a tert-butyl substituent into the 9-position of the parent scaffold led to compounds inhibiting also parasites dwelling in macrophages. By inclusion of the so elaborated scaffold into a chalcone substructure, the toxicity against uninfected host cells was significantly reduced. For the synthesis of this new compound class, a novel modification of the Heck-type palladium-catalyzed C,C-cross coupling strategy was used, employing a ketone Mannich base as precursor for the alkene reactant. The so-prepared compounds exhibited improved antileishmanial activity both on axenic amastigotes (GI50 < 1 microM) as well as on parasites in infected macrophages.

Rapid fluorescent assay for screening drugs on Leishmania amastigotes.

A rapid fluorescent viability assay employing alamarBlue was optimized for use with Leishmania axenic amastigotes, the stage of the parasite responsible for disease pathology. The activity of two protein kinase inhibitors, Staurosporine and H-89, as well as Amphotericin B, on promastigotes and amastigotes of Leishmania donovani and Leishmania tropica was compared. Both protein kinase inhibitors inhibited promastigote growth at lower concentrations than amastigotes, while the GI(50) for Amphotericin B on both stages was similar. This assay only requires a limited number of axenic amastigotes (50,000 cells/well) and can be used to rapidly screen large chemical or natural product libraries for activity against amastigotes.

A new Heck reaction modification using ketone Mannich bases as enone precursors: parallel synthesis of anti-leishmanial chalcones.

A new Heck-type reaction for the synthesis of chalcones has been established using Mannich bases as enone precursors. The novel reaction proceeds rapidly in air atmosphere under ligandless conditions and can be adapted for library synthesis in a parallel reactor station. Screening of the synthesized chalcones revealed N-{4-[(1E)-3-oxo-3-(3-pyridinyl)-1-propenyl]phenyl}benzamide (3f) to be a potent anti-leishmanial agent.

Regulatory T-cells in Graves' orbitopathy: baseline findings and immunomodulation by anti-T lymphocyte globulin.

BACKGROUND AND AIM: Graves' orbitopathy (GO) is characterized by orbital T cell infiltration and local release of proinflammatory cytokines. We aimed to evaluate the involvement of baseline regulatory T (Treg) cells and rabbit anti-T lymphocyte globulin (rATG)-induced Treg cells in GO. DESIGN: Peripheral blood mononuclear cells (PBMCs) from seven patients with Graves' disease (GD) without eye manifestations, 29 patients with GO, and 15 healthy controls were incubated with rATG, washed, and analyzed for expression of Treg cell markers and for ability to suppress mixed lymphocyte reaction. RESULTS: Elevation of CD4 to CD8 ratio and enhanced secretion of IL-6, IL-10, and TNFα were detected in PBMCs of GO patients compared with controls (both P < 0.01). Despite this abnormality, the frequencies of CD4(+)CD25(+)FoxP3(+) of GO and control PBMCs were similar and remained unchanged after 24 h incubation with control rabbit IgG (rIgG). Incubation with polyclonal rATG increased the frequency of PBMCs of GO patients, expressing Treg cell markers (CD25, FoxP3, and the IL-7 receptor CD127(low/-)) by 2.5-8 fold over corresponding rIgG-incubated cells (P < 0.05). FoxP3/CD4 rATG-induced Treg cell marker expressed more intensively on GO peripheral blood leukocytes (PBLs) than on GD (P < 0.01) or normal (P < 0.05) PBLs, yet its expression on normal PBLs was stronger than on GD PBLs (P < 0.05). GO rATG-incubated PBMCs, but not rIgG-incubated PBMCs, suppressed (P < 0.05) proliferation of autologous responder cells stimulated with allogeneic irradiated cells in mixed lymphocyte reaction. Such rATG-induced suppressive activity was not detected in GD. CONCLUSION: This study is the first to show that PBMCs of patients with GO substantially increase Treg cells in both frequency and potency after in vitro incubation with rATG.