Rewarding properties of social interactions in adolescent and adult male and female rats: impact of social versus isolate housing of subjects and partners

Social interactions have been shown to be rewarding for adolescent and adult rats; however, there has been little emphasis on comparing the strength of the rewarding value of social stimuli across ontogeny. Since age differences in social interactions may vary with sex or housing circumstances, the present study assessed social conditioned place preference (CPP) in adolescent and adult male and female Sprague-Dawley rats housed either socially or in isolation and conditioned with either group-housed or isolate-housed partners. Isolated animals of both sexes and ages demonstrated social CPP, with the strongest preference emerging in adolescent males. Social CPP was not evident in group-housed adults whereas group-housed adolescents developed a preference for the compartment previously paired with similarly housed partners; however, when socially housed adolescents were conditioned with isolated partners, social CPP did not emerge. Age differences in social CPP may reflect age-related neural alterations in brain systems implicated in regulation of social behavior.     

Latency of adaptive vergence eye movements induced by vergence-vestibular interaction training in monkeys

Clear vision of objects that move in depth toward or away from an observer requires vergence eye movements. The vergence system must interact with the vestibular system to maintain the object images on the foveae of both eyes during head movement. Previous studies have shown that training with sinusoidal vergence-vestibular interaction improves the frequency response of vergence eye movements during pitch rotation: vergence eye velocity gains increase and phase-lags decrease. To further understand the changes in eye movement responses in this adaptation, we examined latencies of vergence eye movements before and after vergence-vestibular training. Two head-stabilized Japanese monkeys were rewarded for tracking a target spot moving in depth that required vergence eye movements of 10°/s. This target motion was synchronized with pitch rotation at 20°/s. Both target and chair moved in a trapezoidal waveform interspersed with random inter-trial intervals. Before training, pitch rotation in complete darkness without a target did not induce vergence eye movements. Mean latencies of convergence and divergence eye movements induced by vergence target motion alone were 182 and 169 ms, respectively. After training, mean latencies of convergence and divergence eye movements to a target synchronized with pitch rotation shortened to 65 and 53 ms, and vergence eye velocity gains (relative to vergence target velocity) at the normal latencies were 0.68 and 1.53, respectively. Pitch rotation alone without a target induced vergence eye movements with similar latencies after training. These results indicate that vestibular information can be used effectively to initiate vergence eye movements following vergence-vestibular training.     

A non-classical monocyte-derived macrophage subset provides a splenic replication niche for intracellular Salmonella

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The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours

In a previous study of phyllodes tumours, it has been shown that both the stroma and the epithelium can exhibit distinct molecular changes, suggesting that both are part of the neoplastic process. In view of this finding, it was decided to study stromal-epithelial interactions in these tumours by examining the Wnt-APC-beta-catenin pathway. Beta-catenin and cyclin D1 immunohistochemistry was performed on 119 phyllodes tumours. Eighty-six (72%) showed stromal nuclear beta-catenin localization and in 57% the staining was moderate or strong; however, of the eight malignant tumours in the series, seven showed absent or weak nuclear staining (p<0.025). In no tumour was nuclear beta-catenin staining seen in the epithelial component. Moderate or strong stromal cyclin D1 staining correlated with nuclear stromal beta-catenin staining (p<0.05). Forty-five of the tumours, including two malignant lesions, were screened for beta-catenin exon 3 mutations using SSCP and sequencing, but none was found. Loss of heterozygosity (LOH) of the marker D5S346 was used to infer APC mutation, but only one (benign) tumour showed LOH. Wnt2 and Wnt5a mRNA was localized by in situ hybridization in 13 cases (three malignant) chosen to reflect the different beta-catenin staining patterns. There was an association between strong nuclear beta-catenin staining of stromal cells and epithelial Wnt5a expression (p<0.0015). These data suggest that stromal proliferation in benign phyllodes tumours relies on abnormalities in the Wnt pathway which result not from mutation, but from Wnt5a expression in the epithelium. In the progression to malignancy, the stromal proliferation appears to become independent of the Wnt pathway and, presumably, of the epithelial component of these tumours.     

Social Media Message Designs to Educate Adolescents About E-Cigarettes

PurposeE-cigarette use is increasing among adolescents, despite potential harms. Social media messages are a promising way to educate youth about e-cigarettes, yet little is known about what message topics and formats will have beneficial impacts for message reception, reach, e-cigarette knowledge, and beliefs about harms.MethodsA national convenience sample of adolescents (n = 928, aged 15–18 years) in high school was recruited for an online experiment. In October 2019, participants were randomized to view one of three social media formats (visual based, quiz, and text only) or a no-message control. Participants in format conditions viewed six unique topics in a random order. Outcomes were e-cigarette knowledge and beliefs. Message reactions and sharing preferences were also assessed among youth who saw social media messages.ResultsSocial media messages led to greater knowledge (Cohen's f = .19; p < .001) and beliefs (f = .16; p < .001) about harms of e-cigarettes compared with the control, regardless of format. Almost four in five adolescents (79%) reported they would share the social media messages, most likely in person (49%) and with friends (52%). Message topics for missing out because of lung damage, having uncontrolled moods, and ingesting specific harmful chemicals elicited higher intended message reactions.ConclusionsSocial media messages can educate about e-cigarette harms. Social media campaigns are a promising e-cigarette education strategy to reach youth, directly and potentially through peer-to-peer sharing.     

A Theoretical Model for the Margination of Particles within Blood Vessels

The margination of a particle circulating in the blood stream has been analyzed. The contribution of buoyancy, hemodynamic forces, van der Waals, electrostatic and steric interactions between the circulating particle and the endothelium lining the vasculature has been considered. For practical applications, the contribution of buoyancy, hemodynamic forces and van der Waals interactions should be only taken into account, whilst the effect of electrostatic and steric repulsion becomes important only at very short distances from the endothelium (1–10 nm). The margination speed and the time for margination t_s have been estimated as a function of the density of the particle relative to blood , the Hamaker constant A and radius R of the particle. A critical radius R_c exists for which the margination time t_s has a maximum, which is influenced by both and A: the critical radius decreases as the relative density increases and the Hamaker constant decreases. Therefore, particles used for drug delivery should have a radius smaller than the critical value (in the range of 100 nm) to facilitate margination and interaction with the endothelium. While particles used as nanoharvesting agents in proteomics or genomics analysis should have a radius close to the critical value to minimize margination and increase their circulation time.     

A defasciculating dose of d-tubocurarine causes resistance to succinylcholine

Forty-four patients, ASA physical status I or II, undergoing thiamylal, fentanyl, N2O/O2 anaesthesia were studied to determine the dose-response to succinylcholine (Sch) without prior defasciculation (24 pt - Group 1), or three minutes following d-tubocurarine (dTC), 0.043 mg.kg-1 (20 pt - Group 2). The individual log dose-logit response curve for each patient was determined using a cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle. The mean (+/- SEM) ED50, ED90 and ED95 values for Sch in Group 1 were 0.13 +/- 0.01, 0.19 +/- 0.01 and 0.22 +- 0.01 mg.kg-1, and in Group 2 were 0.16 +/- 0.01, 0.25 +/- 0.01 and 0.29 +/- 0.02 mg.kg-1, respectively. The mean ED values in Group 2 were significantly greater than the equivalent values in Group 1 (P less than 0.05). Compared with values in Group 1, ED values in Group 2 represented mean increases of 23, 32, and 32 per cent, respectively. These pharmacodynamic data indicate that the dose of Sch needs to be increased by 32 per cent following a defasciculating dose of dTC 3 mg.70 kg-1 (0.043 mg.kg-1).     

Organ-preference of metastasis

Summary The initial, site-specific colonization of secondary organs by blood-borne cancer cells appears to be mediated by endothelial cell adhesion molecules. These molecules are part of the organ-specific microvascular phenotype and are regulated through complex interactions of the endothelium with the extracellular matrix (e.g., distinct matrix macromolecules and growth factors). They are inducedin vitro by growing unspecific (large vessel) endothelial cells on extracts of organ-specific biomatrices. In many respects, these molecules are similar to the various classes of chemically different adhesion molecules that regulate lymphocyte traffic, but are believed to be distinct from the inducible adhesion molecules that govern leukocyte adhesion during acute episodes of inflammation. Biochemical and biophysical data indicate that preference of tumor cell adhesion to organ-specific microvascular endothelium may not require qualitative differences of such homing receptors between endothelia, but may be explained on the basis of quantitative receptor differences as well as differences of receptor avidity. Following adhesion, the metastatic cascade proceeds by the establishment of metabolic conduits between the endothelium and adherent tumor cells. This heterotypic coupling represents an early step in the extravasation of cancer cells from the microvasculature, initiating endothelial cell retraction from its basement membrane and recanalization around the arrested tumor cell. These events, together with local growth promoting effects exerted by the metastasized organ, are believed to provide the basis for Paget's seed and soil hypothesis of metastasis.