The Cloning and Characterization of a Three-Finger Toxin Homolog (NXH8) from the Coralsnake Micrurus corallinus That Interacts with Skeletal Muscle Nicotinic Acetylcholine Receptors.

Coralsnakes (Micrurus spp.) are the only elapids found throughout the Americas. They are recognized for their highly neurotoxic venom, which is comprised of a wide variety of toxins, including the stable, low-mass toxins known as three-finger toxins (3FTx). Due to difficulties in venom extraction and availability, research on coralsnake venoms is still very limited when compared to that of other Elapidae snakes like cobras, kraits, and mambas. In this study, two previously described 3FTx from the venom of M. corallinus, NXH1 (3SOC1_MICCO), and NXH8 (3NO48_MICCO) were characterized. Using in silico, in vitro, and ex vivo experiments, the biological activities of these toxins were predicted and evaluated. The results showed that only NXH8 was capable of binding to skeletal muscle cells and modulating the activity of nAChRs in nerve-diaphragm preparations. These effects were antagonized by anti-rNXH8 or antielapidic sera. Sequence analysis revealed that the NXH1 toxin possesses eight cysteine residues and four disulfide bonds, while the NXH8 toxin has a primary structure similar to that of non-conventional 3FTx, with an additional disulfide bond on the first loop. These findings add more information related to the structural diversity present within the 3FTx class, while expanding our understanding of the mechanisms of the toxicity of this coralsnake venom and opening new perspectives for developing more effective therapeutic interventions.

Cognitive Control Deficits in Depression: A Novel Target to Improve Suboptimal Outcomes in Childhood.

Cognitive control deficits are one of three primary endophenotypes in depression, and the enhanced targeting of these deficits in clinical and research work is expected to lead to improved depression outcomes. Cognitive control is a set of self-regulatory processes responsible for goal-oriented behavior that predicts clinical/functional outcomes across the spectrum of brain-based disorders. In depression, cognitive control deficits emerge by the first depressive episode, persist during symptom remission, and worsen over the course of depression. In addition, the presence of these deficits predicts a poor response to evidence-based depression treatments, including psychotherapy and antidepressant medication. This is particularly relevant to childhood depression, as 1%-2% of children are diagnosed with depression, yet there are very limited evidence-based treatment options. Cognitive control deficits may be a previously underaddressed factor contributing to poor outcomes, although there remains a dearth of research examining the topic. The investigators describe the prior literature on cognitive control in depression to argue for the need for increased focus on this endophenotype. They then describe cognitive control-focused clinical and research avenues that would likely lead to improved treatments and outcomes for this historically undertreated aspect of childhood depression.

Assessing performance validity with the TOMM and automatized sequences task in a pediatric psychiatric inpatient setting.

This study examined the performance of children consecutively admitted to an inpatient psychiatric unit on the Test of Memory Malingering (TOMM) (aged 5-12; n = 96) and Automatized Sequences Task (aged 8-12; n = 67). Eighty-three percent of children passed the TOMM Trial 2 (M raw score = 47.7, SD = 4.7) and 76% of children passed the Automatized Sequences Task total time (M = 23.1 seconds; SD = 8.2). The concordance rate between the TOMM and the total time on the Automatized Sequences Task was 73.1%. Receiver operating characteristic curves indicated that of the Automatized Sequences Task subtests, only Counting 1-20 significantly differentiated children who passed Trial 2 of the TOMM from those who did not pass Trial 2 of the TOMM (area under the curve = .756, p = .006). Performance on both PVTs was unrelated to demographic characteristics and measures of psychological and neuropsychological functioning on both the TOMM and Automatized Sequences Task. Further research is needed to determine whether the nearly 1 in 4 children (23.9%) who performed below recommended cutoffs on Automatized Sequences Task reflects genuine suboptimal effort, cognitive difficulties among these children, and/or other factors.