Lethal Arg9Cys phospholamban mutation hinders Ca2+-ATPase regulation and phosphorylation by protein kinase A

The regulatory interaction of phospholamban (PLN) with Ca(2+)-ATPase controls the uptake of calcium into the sarcoplasmic reticulum, modulating heart muscle contractility. A missense mutation in PLN cytoplasmic domain (R9C) triggers dilated cardiomyopathy in humans, leading to premature death. Using a combination of biochemical and biophysical techniques both in vitro and in live cells, we show that the R9C mutation increases the stability of the PLN pentameric assembly via disulfide bridge formation, preventing its binding to Ca(2+)-ATPase as well as phosphorylation by protein kinase A. These effects are enhanced under oxidizing conditions, suggesting that oxidative stress may exacerbate the cardiotoxic effects of the PLN(R9C) mutant. These results reveal a regulatory role of the PLN pentamer in calcium homeostasis, going beyond the previously hypothesized role of passive storage for active monomers.     

Benefits of Adherence to Psychotropic Medications on Depressive Symptoms and Antiretroviral Medication Adherence Among Men and Women Living with HIV/AIDS

Background  

Psychotropic medications are commonly used for depressive symptoms among people living with HIV/AIDS.     

Reliability and validity of the PDS and PSS-I among participants with PTSD and alcohol dependence

The prevalence of alcohol use disorder (e.g., alcohol dependence; AD) among individuals with posttraumatic stress disorder (PTSD) is quite high, with estimates of 52% for men and 30% for women (Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995). There are several interviews and self-report measures of PTSD with good published psychometric properties, and they are routinely used with comorbid AD and PTSD. However, none of these instruments was validated with this population. The current study fills this gap by examining the psychometric properties of the PTSD Symptom Scale-Interview (PSS-I) and the self-report PTSD Diagnostic Scale (PDS) in individuals diagnosed with current PTSD and AD. Both scales comprised of 17 items provide diagnostic and symptom severity information according to DSM-IV-TR criteria. Participants were 167 individuals who were diagnosed with AD and chronic PTSD and were enrolled in a randomized controlled treatment study. Results revealed excellent internal consistency of both the PSS-I and the PDS, good test-retest reliability over a 1-month period, and good convergent validity with the SCID. The specificity of the PSS-I diagnosis of PTSD was better than the PDS diagnosis, the latter exhibiting a greater percentage of false positives. In sum, the results showed that the PSS-I and PDS performed well in this population and can be used with confidence to assess PTSD diagnosis and symptom severity.     

Gross motor development in children adopted from orphanage settings

Aim This study sought to examine the effect of environmental enrichment on the motor skills of children adopted from orphanage settings. We investigated balance and bilateral coordination skills in 33 internationally adopted postinstitutionalized children (16 males, 17 females; age range 8y 5mo–15y 10mo; mean age 10y 9mo; SD 2y 2mo) and compared them with 34 non‐institutionalized children (21 males, 13 females; age range 8y 3mo–14y 10mo; mean age 11y 2mo; SD 2y 1mo) being raised in their birth families. Method The children were individually administered the balance and bilateral coordination subtests of the Bruininks–Oseretsky Test of Motor Proficiency in a research laboratory. Parents completed questionnaires about developmental history, family environment, and orphanage care. Results Postinstitutionalized children showed motor system delays compared with the non‐institutionalized comparison children (postinstitutionalized balance mean 9.44, SD 5.92, comparison children balance mean 14.12, SD 4.39; postinstitutionalized bilateral coordination mean 11.97, SD 5.43, comparison children mean 19.97, SD 3.97). The length of time that children remained institutionalized before adoption predicted balance delays (b=?1.57, t=?2.33, p=0.027) and the severity of caregiving deprivation the children experienced correlated with bilateral coordination (r=?0.44, p=0.013). Interpretation These findings suggest that institutionalized settings do not provide the early life experiences needed for the development of age‐level motor skills later in childhood and that simple environmental enrichment following adoption is not enough to remediate skills. Children who have experienced early institutional care may benefit from early identification and targeted intervention.     

Noise overexposure alters long-term somatosensory-auditory processing in the dorsal cochlear nucleus--possible basis for tinnitus-related hyperactivity?

The dorsal cochlear nucleus (DCN) is the first neural site of bimodal auditory-somatosensory integration. Previous studies have shown that stimulation of somatosensory pathways results in immediate suppression or enhancement of subsequent acoustically evoked discharges. In the unimpaired auditory system suppression predominates. However, damage to the auditory input pathway leads to enhancement of excitatory somatosensory inputs to the cochlear nucleus, changing their effects on DCN neurons (Shore et al., 2008; Zeng et al., 2009). Given the well described connection between the somatosensory system and tinnitus in patients we sought to determine whether plastic changes in long-lasting bimodal somatosensory-auditory processing accompany tinnitus. Here we demonstrate for the first time in vivo long-term effects of somatosensory inputs on acoustically evoked discharges of DCN neurons in guinea pigs. The effects of trigeminal nucleus stimulation are compared between normal-hearing animals and animals overexposed with narrow band noise and behaviorally tested for tinnitus. The noise exposure resulted in a temporary threshold shift in auditory brainstem responses but a persistent increase in spontaneous and sound-evoked DCN unit firing rates and increased steepness of rate-level functions. Rate increases were especially prominent in buildup units. The long-term somatosensory enhancement of sound-evoked responses was strengthened while suppressive effects diminished in noise-exposed animals, especially those that developed tinnitus. Damage to the auditory nerve is postulated to trigger compensatory long-term synaptic plasticity of somatosensory inputs that might be an important underlying mechanism for tinnitus generation.