Cognitive Habits and Memory Distortions in Anxiety and Depression

When anxious or depressed people try to recall emotionally ambiguous events, they produce errors that reflect their habits of interpreting ambiguity in negative ways. These distortions are revealed by experiments that evaluate performance on memory tasks after taking interpretation biases into account—an alternative to the standard memory-bias procedure that examines the accuracy of memory for clearly emotional material. To help establish the causal role of interpretation bias in generating memory bias, these disortions have been simulated by training interpretation biases in nondisordered groups. The practical implications of these findings for therapeutic intervention are discussed; future directions are described

Mechanisms of vascular smooth muscle contraction and the basis for pharmacologic treatment of smooth muscle disorders

The smooth muscle cell directly drives the contraction of the vascular wall and hence regulates the size of the blood vessel lumen. We review here the current understanding of the molecular mechanisms by which agonists, therapeutics, and diseases regulate contractility of the vascular smooth muscle cell and we place this within the context of whole body function. We also discuss the implications for personalized medicine and highlight specific potential target molecules that may provide opportunities for the future development of new therapeutics to regulate vascular function.Accepted manuscrip

Biases in Interpretation and Memory in Generalized Social Phobia

Two experiments examined the link between interpretation and memory in individuals diagnosed with Generalized Social Phobia (GSP). In Experiment 1, GSP and control participants generated continuations for nonsocial and ambiguous social scenarios. GSP participants produced more socially anxious and negative continuations for the social scenarios than did the controls. On the subsequent test of recalling the social scenarios, intrusion errors that shared meaning with the original continuations were made more frequently by the GSP group, producing false recall with emotionally negative features. To examine whether nonanxious individuals would also produce such errors if given emotional interpretations, in Experiment 2 the authors asked university students to read the scenarios plus endings produced by GSP participants in Experiment 1. The students either constructed vivid mental images of themselves as the main characters or thought about whether the endings provided closure. Low-anxious students in the closure condition produced fewer ending-based intrusions in recalling the social scenarios than did students in the other 3 conditions. Results illustrate the importance of examining the nature of source-monitoring errors in investigations of memory biases in social anxiety

Remembering the Good, Forgetting the Bad: Intentional Forgetting of Emotional Material in Depression

The authors examined intentional forgetting of negative material in depression. Participants were instructed to not think about emotional nouns that they had learned to associate with a neutral cue word. The authors provided participants with multiple occasions to suppress the unwanted words. Overall, depressed participants successfully forgot negative words. Moreover, the authors obtained a clear practice effect. However, forgetting came at a cost: Compared with the nondepressed participants and with the depressed participants who were instructed to forget positive words, depressed participants who were instructed to forget negative words showed significantly worse recall of the baseline words. These results indicate that training depressed individuals in intentional forgetting could prove to be an effective strategy to counteract automatic ruminative tendencies and mood-congruent biases

Leukemia induction by Friend virus in normally leukemia virus resistant mice after treatment with methyl methane sulfonate

F1 offspring of virus-resistant C57B1/10 females and virus-sensitive SJL/J males are normally resistant to Friend leukemia virus. However, after treatment of these hybrids with methyl methane sulfonate (MMS), Friend leukemia virus given within 5 hrs of the treatment caused many individuals to succumb to erythroleukemia with characteristic elevated white counts, hepatometaly, splenomegaly, and high hematocrit. Although MMS was found immunosuppressive in these mice when given alone, it was found to enhance humoral immune function measured by a plaque forming assay against sheep red blood cells, when given in combination with the virus. These results suggest that MMS enhances viral leukemogenesis by some mechanism other than immunosuppression

Effect of phosphate and temperature on force exerted by white muscle fibres from dogfish.

Effects of Pi (inorganic phosphate) are relevant to the in vivo function of muscle because Pi is one of the products of ATP hydrolysis by actomyosin and by the sarcoplasmic reticulum Ca pump. We have measured the Pi sensitivity of force produced by permeabilized muscle fibres from dogfish (Scyliorhinus canicula) and rabbit. The activation conditions for dogfish fibres were crucial: fibres activated from the relaxed state at 5, 12, and 20°C were sensitive to Pi, whereas fibres activated from rigor at 12°C were insensitive to Pi in the range 5-25 mmol l. Rabbit fibres activated from rigor were sensitive to Pi. Pi sensitivity of force produced by dogfish fibres activated from the relaxed state was greater below normal body temperature (12°C for dogfish) in agreement with what is known for other species. The force-temperature relationship for dogfish fibres (intact and permeabilized fibres activated from relaxed) showed that at 12°C, normal body temperature, the force was near to its maximum value

Losartan Decreases p42/44 MAPK Signaling and Preserves LZ+ MYPT1 Expression

Heart failure is associated with impairment in nitric oxide (NO) mediated vasodilatation, which has been demonstrated to result from a reduction in the relative expression of the leucine zipper positive (LZ+) isoform of the myosin targeting subunit (MYPT1) of myosin light chain phosphatase. Further, captopril preserves normal LZ+ MYPT1 expression, the sensitivity to cGMP-mediated vasodilatation and modulates the expression of genes in the p42/44 MAPK and p38 MAPK signaling cascades. This study tests whether angiotensin receptor blockade (ARB) with losartan decreases p42/44 MAPK or p38 MAPK signaling and preserves LZ+ MYPT1 expression in a rat infarct model of heart failure. In aortic smooth muscle, p42/44 MAPK activation increases and LZ+ MYPT1 expression falls after LAD ligation. Losartan treatment decreases the activation of p42/44 MAPK to the uninfarcted control level and preserves normal LZ+ MYPT1 expression. The expression and activation of p38 MAPK, however, is low and does not change following LAD ligation or with losartan therapy. These data suggest that either reducing or blocking the effects of circulating angiotensin II, both decreases the activation of the p42/44 MAPK signaling cascade and preserves LZ+ MYPT1 expression. Thus, the ability of ACE-inhibitors and ARBs to modulate the vascular phenotype, to preserve normal flow mediated vasodilatation may explain the beneficial effects of these drugs compared to other forms of afterload reduction in the treatment of heart failure

The frequency response of smooth muscle stiffness during Ca2+-activated contraction.

To investigate the mechanism of smooth muscle contraction, the frequency response of the muscle stiffness of single beta-escin permeabilized smooth muscle cells in the relaxed state was studied. Also, the response was continuously monitored for 3 min from the beginning of the exchange of relaxing solution to activating solution, and then at 5-min intervals for up to 20 min. The frequency response (30 Hz bandwidth, 0.33 Hz (or 0.2 Hz) resolution) was calculated from the Fourier-transformed force and length sampled during a 3-s (or 5-s) constant-amplitude length perturbation of increasing-frequency (1-32 Hz) sine waves. In the relaxed state, a large negative phase angle was observed, which suggests the existence of attached energy generating cross-bridges. As the activation progressed, the muscle stiffness and phase angle steadily increased; these increases gradually extended to higher frequencies, and reached a steady state by 100 s after activation or approximately 40 s after stiffness began to increase. The results suggest that a fixed distribution of cross-bridge states was reached after 40 s of Ca2+ activation and the cross-bridge cycling rate did not change during the period of force maintenance

The smooth muscle cross-bridge cycle studied using sinusoidal length perturbations.

The mechanical characteristics of smooth muscle can be broadly defined as either phasic, or fast contracting, and tonic, or slow contracting (, Pharmacol. Rev. 20:197-272). To determine if differences in the cross-bridge cycle and/or distribution of the cross-bridge states could contribute to differences in the mechanical properties of smooth muscle, we determined force and stiffness as a function of frequency in Triton-permeabilized strips of rabbit portal vein (phasic) and aorta (tonic). Permeabilized muscle strips were mounted between a piezoelectric length driver and a piezoresistive force transducer. Muscle length was oscillated from 1 to 100 Hz, and the stiffness was determined as a function of frequency from the resulting force response. During calcium activation (pCa 4, 5 mM MgATP), force and stiffness increased to steady-state levels consistent with the attachment of actively cycling cross-bridges. In smooth muscle, because the cross-bridge states involved in force production have yet to be elucidated, the effects of elevation of inorganic phosphate (P(i)) and MgADP on steady-state force and stiffness were examined. When portal vein strips were transferred from activating solution (pCa 4, 5 mM MgATP) to activating solution with 12 mM P(i), force and stiffness decreased proportionally, suggesting that cross-bridge attachment is associated with P(i) release. For the aorta, elevating P(i) decreased force more than stiffness, suggesting the existence of an attached, low-force actin-myosin-ADP- P(i) state. When portal vein strips were transferred from activating solution (pCa 4, 5 mM MgATP) to activating solution with 5 mM MgADP, force remained relatively constant, while stiffness decreased approximately 50%. For the aorta, elevating MgADP decreased force and stiffness proportionally, suggesting for tonic smooth muscle that a significant portion of force production is associated with ADP release. These data suggest that in the portal vein, force is produced either concurrently with or after P(i) release but before MgADP release, whereas in aorta, MgADP release is associated with a portion of the cross-bridge powerstroke. These differences in cross-bridge properties could contribute to the mechanical differences in properties of phasic and tonic smooth muscle

Muscle contraction generates discrete sound bursts.

Isolated frog sartorius muscles were stimulated to shorten under lightly loaded conditions. A piezoelectric transducer was placed alongside the muscle to record sounds generated during contraction. Shortening was accompanied by the generation of a series of discrete sound bursts. The bursts were found to be moderately repeatable among successive contractions; 44% repeated from contraction to contraction. The duration of each sound burst was on the order of 400 mus, and the temperature dependence of the interval between successive bursts had a Q10 of approximately 2. Sound intensity was variable: average acoustic power ranged from 0.05-0.4 mW/g, or approximately 1% of the heat generated during contraction. The generation of discrete bursts of sound during contraction, rather than continuous sound, implies that contractile behavior may be discontinuous