Cellular effects ofβ-adrenergic and of cAMP stimulation on potassium transport in rat alveolar epithelium

Alveolar fluid absorption is greatly enhanced by cAMP and by -adrenergic agonists via an increase in Na⁺ transport. Little is known about K⁺ homeostasis under these circumstances. We studied K⁺ transport across alveolar epithelium in isolated perfused rat lungs stimulated either by dibutyryl-cAMP or isoproterenol. K⁺ fluxes and the apparent permeability of⁸⁶Rb across the epithelium (alveoli to plasma) were interpreted according to a model involving two types of cells, B and L, distinguished by the location of Na⁺–K⁺-ATPases (basal and luminal). Water is considered to be absorbed by B cells in a solute-coupled process energized by a basolateral Na⁺–K⁺-ATPase that is stimulated by isoproterenol and cAMP. K⁺ transport out of the alveoli is due to the activity of a Na⁺–K⁺-ATPase located in the apical membrane of L cells. In the present study net transport rate of K⁺ was –0.5±0.15 nmol/s,n=20 (out of alveoli) in control conditions. When the epithelium was stimulated by dibutyryl-cAMP (10^–4 mol/l) net absorption of K⁺ reversed to net secretion into alveoli (3.2±0.31 nmol/s), fluid absorption was not stimulated. K⁺ secretion was abolished by apical Ba²⁺, indicating it was due to opening of apical K⁺ channels. Basolateral ouabain reversed net K⁺ secretion to net absorption indicating that K⁺ entry into alveoli was dependent on activity of B cell basolateral Na⁺–K⁺-ATPase (masking simultaneous K⁺ removal by apical L cell Na⁺–K⁺-pump). When larger concentrations of dibutyryl-cAMP (10^–3 mol/l) or when isoproterenol were used to stimulate the epithelium there was a tripling of fluid absorption. In this situation a biphasic response of K⁺ transport was observed. Initially, net K⁺ influx similar to that observed in 10^–4 mol/l dibutyryl-cAMP experiments occurred, followed by a large K⁺ efflux from alveolar spaces. This may reflect stimulation of apical Na⁺–K⁺-ATPase in L cells, combined with partial closure of apical K⁺ channels in B cells. The variations of the apparent permeability of⁸⁶Rb, measured from alveoli to plasma, reinforce this interpretation of the mechanisms of K⁺ transport. Our results suggest that K⁺ transport across alveolar epithelium is modulated by isoproterenol and cAMP, by stimulation of Na⁺–K⁺-ATPase in B and L cells supplemented by control of K⁺ channels.     

Colorectal cancer,comorbidity, and risk of venous thromboembolism: assessment of biological interactions in a Danish nationwide cohort

Background:

Venous thromboembolism (VTE) is a major source of morbidity and mortality in cancer patients. Incident colorectal cancer (CRC) and comorbidity both predict VTE, but potential synergy between these factors has not been explored.

Methods:

Danish nationwide cohort study of CRC cases diagnosed in 1995–2010 and a matched general population reference cohort of subjects without CRC who matched cases on age, sex, and comorbidities. We calculated the Charlson Comorbidity Index using diagnoses recorded in the Danish National Patient Registry. We calculated standardised incidence rates (SIRs) and interaction contrasts (IC) to measure additive interaction between comorbidity and CRC status with respect to 5-year VTE incidence.

Results:

Among 56 189 CRC patients, 1372 VTE cases were diagnosed over 145 211 person-years (SIR=9.5 cases per 1000 person-years). Among 271 670 reference subjects, 2867 VTE cases were diagnosed over 1 068  860 person-years (SIR=2.8 cases per 1000 person-years). CRC and comorbidity were positively and independently associated with VTE, but there was no evidence for biological interaction between these factors (e.g., comparing the ‘severe comorbidity'' stratum with the ‘no comorbidity'' stratum, IC=0.8, 95% CI: −3.3, 4.8).

Conclusions:

There is neither a deficit nor a surplus of VTE cases among patients with both comorbidity and CRC, compared with rates expected from these risk factors in isolation.     

Amplitude of the maximum motor response (Mmax) in human muscles typically decreases during the course of an experiment

 It was shown that the amplitude of the soleus M _max and H _max responses decreases in the course of long-lasting H-reflex studies. The peak-to-peak amplitudes of the M _max and H _max responses in the soleus muscle (and the M _max in the tibialis anterior muscle and small hand muscles) were measured repeatedly for 1–3 h in 20 subjects. 3–5 M _max responses and 5–10 H _max responses were elicited about every 3 min while the subject was at rest. Decreases in the soleus M _max response of up to 50.5% (mean 20.5% SEM 2.2) and of the soleus H _max of up to 49.7% (mean 19.1% SEM 3.7) in relation to the amplitudes measured at the beginning of the experiment were seen in 17 subjects. In 3 subjects no M _max amplitude decrease was seen. The maximum decrease was reached between 10 and 100 min (mean 44.2 min SEM 4.3). An M_max amplitude decrease was also seen in the tibialis anterior muscle and in two small hand muscles. In some subjects the decrease of the M _max response seemed to be initiated by the infrequent supramaximal stimulations. The possible causes for this amplitude reduction, as well as the methodological consequences of these findings for H-reflex studies and fatigue studies, are briefly discussed. Received: 1 July 1998 / Accepted: 9 October 1998     

The nature of the self: Neural analyses and heritability estimates of self‐evaluations in middle childhood

How neural correlates of self‐concept are influenced by environmental versus genetic factors is currently not fully understood. We investigated heritability estimates of behavioral and neural correlates of self‐concept in middle childhood since this phase is an important time window for taking on new social roles in academic and social contexts. To do so, a validated self‐concept fMRI task was applied in a twin sample of 345 participants aged between 7 and 9 years. In the self‐concept condition, participants were asked to indicate whether academic and social traits applied to them whereas the control condition required trait categorization. The self‐processing activation analyses (n = 234) revealed stronger medial prefrontal cortex (mPFC) activation for self than for control conditions. This effect was more pronounced for social‐self than academic self‐traits, whereas stronger dorsolateral prefrontal cortex (DLPFC) activation was observed for academic versus social self‐evaluations. Behavioral genetic modeling (166 complete twin pairs) revealed that 25–52% of the variation in academic self‐evaluations was explained by genetic factors, whereas 16–49% of the variation in social self‐evaluations was explained by shared environmental factors. Neural genetic modeling (91 complete twin pairs) for variation in mPFC and anterior prefrontal cortex (PFC) activation for academic self‐evaluations confirmed genetic and unique environmental influences, whereas anterior PFC activation for social self‐evaluations was additionally influenced by shared environmental influences. This indicates that environmental context possibly has a larger impact on the behavioral and neural correlates of social self‐concept at a young age. This is the first study demonstrating in a young twin sample that self‐concept depends on both genetic and environmental factors, depending on the specific domain.     

Pregnancy and adolescence entail similar neuroanatomical adaptations: A comparative analysis of cerebral morphometric changes

Mapping the impact of pregnancy on the human brain is essential for understanding the neurobiology of maternal caregiving. Recently, we found that pregnancy leads to a long‐lasting reduction in cerebral gray matter volume. However, the morphometric features behind the volumetric reductions remain unexplored. Furthermore, the similarity between these reductions and those occurring during adolescence, another hormonally similar transitional period of life, still needs to be investigated. Here, we used surface‐based methods to analyze the longitudinal magnetic resonance imaging data of a group of 25 first‐time mothers (before and after pregnancy) and compare them to those of a group of 25 female adolescents (during 2 years of pubertal development). For both first‐time mothers and adolescent girls, a monthly rate of volumetric reductions of 0.09 mm³ was observed. In both cases, these reductions were accompanied by decreases in cortical thickness, surface area, local gyrification index, sulcal depth, and sulcal length, as well as increases in sulcal width. In fact, the changes associated with pregnancy did not differ from those that characterize the transition during adolescence in any of these measures. Our findings are consistent with the notion that the brain morphometric changes associated with pregnancy and adolescence reflect similar hormonally primed biological processes.     

A three‐wave longitudinal study of subcortical–cortical resting‐state connectivity in adolescence: Testing age‐ and puberty‐related changes

Adolescence is the transitional period between childhood and adulthood, characterized by substantial changes in reward‐driven behavior. Although reward‐driven behavior is supported by subcortical‐medial prefrontal cortex (PFC) connectivity, the development of these circuits is not well understood. Particularly, while puberty has been hypothesized to accelerate organization and activation of functional neural circuits, the relationship between age, sex, pubertal change, and functional connectivity has hardly been studied. Here, we present an analysis of resting‐state functional connectivity between subcortical structures and the medial PFC, in 661 scans of 273 participants between 8 and 29 years, using a three‐wave longitudinal design. Generalized additive mixed model procedures were used to assess the effects of age, sex, and self‐reported pubertal status on connectivity between subcortical structures (nucleus accumbens, caudate, putamen, hippocampus, and amygdala) and cortical medial structures (dorsal anterior cingulate, ventral anterior cingulate, subcallosal cortex, frontal medial cortex). We observed an age‐related strengthening of subcortico‐subcortical and cortico‐cortical connectivity. Subcortical–cortical connectivity, such as, between the nucleus accumbens—frontal medial cortex, and the caudate—dorsal anterior cingulate cortex, however, weakened across age. Model‐based comparisons revealed that for specific connections pubertal development described developmental change better than chronological age. This was particularly the case for changes in subcortical–cortical connectivity and distinctively for boys and girls. Together, these findings indicate changes in functional network strengthening with pubertal development. These changes in functional connectivity may maximize the neural efficiency of interregional communication and set the stage for further inquiry of biological factors driving adolescent functional connectivity changes.     

Brain network dynamics in the human articulatory loop

Objective

The articulatory loop is a fundamental component of language function, involved in the short-term buffer of auditory information followed by its vocal reproduction. We characterized the network dynamics of the human articulatory loop, using invasive recording and stimulation.