Effects of social and inanimate enrichment on the behavior of yearling rhesus monkeys

Certain types of inanimate environmental enrichment have been shown to positively affect the behavior of laboratory primates, as has housing them in appropriate social conditions. While social housing is generally advocated as an important environmental enhancement, few studies have attempted to measure the influence of social conditions on the effects of inanimate enrichment or to compare the relative merits of social and inanimate enhancements. In the present study, inanimate enrichment (predominately physical and feeding enhancements) resulted in increased species-typical behavior for socially restricted subjects. However, social enrichment (living in groups) appeared to be more beneficial for young rhesus monkeys, leading to increased species-typical activities and decreased abnormal activities. The behavior of one cohort of yearling rhesus monkeys (Macaca mulatta) housed in small peer groups was compared with the behavior of four yearling cohorts housed in single cages. Half the animals in each cohort received a three-phase enrichment program and the rest served as controls. Group-housed yearlings spent significantly more time feeding and exploring and significantly less time behaving abnormally, self-grooming, and drinking than did singly housed yearlings. Enriched subjects spent significantly more time playing by themselves, and significantly less time self-grooming and exploring than did controls. Among group-housed subjects only, there were no differences between enriched and control monkeys. Captive primates should be housed socially, whenever appropriate, as the first and most important step in an enrichment program, with the provision of inanimate enhancements being considerably less important. Limited resources for inanimate enrichment programs instead should be focused on those individuals who can not be housed socially. © 1996 Wiley-Liss, Inc.     

Metallohelix vectors for efficient gene delivery via cationic DNA nanoparticles

The design of efficient and safe gene delivery vehicles remains a major challenge for the application of gene therapy. Of the many reported gene delivery systems, metal complexes with high affinity for nucleic acids are emerging as an attractive option. We have discovered that certain metallohelices—optically pure, self-assembling triple-stranded arrays of fully encapsulated Fe—act as nonviral DNA delivery vectors capable of mediating efficient gene transfection. They induce formation of globular DNA particles which protect the DNA from degradation by various restriction endonucleases, are of suitable size and electrostatic potential for efficient membrane transport and are successfully processed by cells. The activity is highly structure-dependent—compact and shorter metallohelix enantiomers are far less efficient than less compact and longer enantiomers.     

A three-dimensional multiscale model for the prediction of thrombus growth under flow with single-platelet resolution

Modeling thrombus growth in pathological flows allows evaluation of risk under patient-specific pharmacological, hematological, and hemodynamical conditions. We have developed a 3D multiscale framework for the prediction of thrombus growth under flow on a spatially resolved surface presenting collagen and tissue factor (TF). The multiscale framework is composed of four coupled modules: a Neural Network (NN) that accounts for platelet signaling, a Lattice Kinetic Monte Carlo (LKMC) simulation for tracking platelet positions, a Finite Volume Method (FVM) simulator for solving convection-diffusion-reaction equations describing agonist release and transport, and a Lattice Boltzmann (LB) flow solver for computing the blood flow field over the growing thrombus. A reduced model of the coagulation cascade was embedded into the framework to account for TF-driven thrombin production. The 3D model was first tested against in vitro microfluidics experiments of whole blood perfusion with various antiplatelet agents targeting COX-1, P₂Y₁, or the IP receptor. The model was able to accurately capture the evolution and morphology of the growing thrombus. Certain problems of 2D models for thrombus growth (artifactual dendritic growth) were naturally avoided with realistic trajectories of platelets in 3D flow. The generalizability of the 3D multiscale solver enabled simulations of important clinical situations, such as cylindrical blood vessels and acute flow narrowing (stenosis). Enhanced platelet-platelet bonding at pathologically high shear rates (e.g., von Willebrand factor unfolding) was required for accurately describing thrombus growth in stenotic flows. Overall, the approach allows consideration of patient-specific platelet signaling and vascular geometry for the prediction of thrombotic episodes.     

Traveling waves in the prefrontal cortex during working memory

Neural oscillations are evident across cortex but their spatial structure is not well- explored. Are oscillations stationary or do they form “traveling waves”, i.e., spatially organized patterns whose peaks and troughs move sequentially across cortex? Here, we show that oscillations in the prefrontal cortex (PFC) organized as traveling waves in the theta (4-8Hz), alpha (8-12Hz) and beta (12-30Hz) bands. Some traveling waves were planar but most rotated. The waves were modulated during performance of a working memory task. During baseline conditions, waves flowed bidirectionally along a specific axis of orientation. Waves in different frequency bands could travel in different directions. During task performance, there was an increase in waves in one direction over the other, especially in the beta band.     

Levels of androgen conjugates and oestrone sulphate in patients with breast cysts

Plasma and cyst fluid were obtained from patients with palpable breast cysts and analysed for androgen conjugates and oestrone sulphate content by radioimmunoassay. Concentrations of androgen conjugates in cyst fluids varied from 15.6 to 475.5 mumols/l. These levels were much greater than those in plasma (1.3-5.2 mumols/l) and there was no association between values in cyst aspirates and plasmas obtained from the same individuals. Levels of oestrone sulphate in breast cyst fluids (1.5-744.0 nmol/l) were also generally in excess of those in plasma (2.0-59.9 nmol/l) and again no relationship was evident between concentrations in cyst fluid and the circulation. Neither was there a relationship between levels of androgen conjugate and oestrone sulphate in plasma. In contrast, a highly significant correlation (P less than 0.001) was identified between the androgen conjugate and oestrone sulphate content of cyst fluids. Levels of both androgen conjugates and oestrone sulphate were also significantly different in groups of cysts subdivided according to electrolyte classification, cysts with low Na+:K+ ratios having higher steroid concentrations than those with high Na+:K+ ratios. The biological significance of the relationship between the two conjugates in cyst fluids remains unclear but it is suggested that the accumulation of these steroids involves a common mechanism.     

Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system

Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV since in vivo animal models are limited and in vitro cancer cell models often show dysregulated immune and proliferative responses. Here, we developed a CD8⁺ T cell and adult stem cell liver organoid system using a microfluidic chip to coculture 3D human liver organoids embedded in extracellular matrix with HLA-matched primary human T cells in suspension. We then employed automated phase contrast and immunofluorescence imaging to monitor T cell invasion and morphological changes in the liver organoids. This microfluidic coculture system supports targeted killing of liver organoids when pulsed with a peptide specific for HCV non-structural protein 3 (NS3) (KLVALGINAV) in the presence of patient-derived CD8⁺ T cells specific for KLVALGINAV. This demonstrates the novel potential of the coculture system to molecularly study adaptive immune responses to HCV in an in vitro setting using primary human cells.     

Effects of Rhododendron removal and prescribed fire on bees and plants in the southern Appalachians

Rhododendron maximum is an evergreen shrub native to the Appalachian Mountains of North America that has expanded in recent decades due to past disturbances and land management. The purpose of this study was to explore how bees and plants were affected by the experimental removal of R. maximum followed by a prescribed fire in one watershed compared to a neighboring reference watershed. Bees and plants were sampled for three years in both watersheds. Comparisons were based on the rarefaction and extrapolation sampling curves of Hill numbers as well as multivariate methods to assess effects on community composition. Bee richness, Shannon''s diversity, and Simpson''s diversity did not differ between watersheds in the year after removal but were all significantly higher in the removal watershed in year two, following the prescribed fire. Bee Shannon''s diversity and Simpson''s diversity, but not richness, remained significantly higher in the removal watershed in the third year. Similar but weaker patterns were observed for plants. Comparisons of community composition found significant differences for bees in the second and third year and significant differences for plants in all three years. For both groups, significant indicator taxa were mostly associated with the removal watershed. Because bees appeared to respond more strongly to the prescribed fire than to the removal of R. maximum and these benefits weakened considerably one year after the fire, clearing R. maximum does not appear to dramatically improve pollinator habitat in the southern Appalachians. This conclusion is underscored by the fact that about one quarter of the bee species in our study area were observed visiting R. maximum flowers. The creation of open areas with wildflowers may be a better way to benefit bees in this region judging from the high diversity of bees captured in the small roadside clearings in this study.