In vivo and in vitro excystation of Zygocotyle lunata (Trematoda) metacercariae and histochemical observations on the cyst.

Encysted metacercariae of Zygocotyle lunata (Trematoda) excyst within 2 hr postexposure in the lower ileum of the domestic chick. Optimal in vitro excystation of this species occurs following pretreatment of the cyst for 15 min in 1% acidified pepsin, treatment in 0.02 M sodium dithionite (a reductant) for 1 to 2 min and then 2 hr treatment in an excystation medium containing 1% sodium glycocholate plus 1% trypsin in Earle's BSS adjusted to pH 8.8 with tris and maintained at 41 C. The cyst of this species is a dome-shaped hemisphere containing an inner and outer wall. The outer wall contains mainly acid mucopolysaccharides, whereas the inner wall is mainly proteinaceous. The cyst contains a ventral lid which only was visualized during excystation.     

Nonlinear effects of intrinsic dynamics on temporal encoding in a model of avian auditory cortex

Neurons exhibit diverse intrinsic dynamics, which govern how they integrate synaptic inputs to produce spikes. Intrinsic dynamics are often plastic during development and learning, but the effects of these changes on stimulus encoding properties are not well known. To examine this relationship, we simulated auditory responses to zebra finch song using a linear-dynamical cascade model, which combines a linear spectrotemporal receptive field with a dynamical, conductance-based neuron model, then used generalized linear models to estimate encoding properties from the resulting spike trains. We focused on the effects of a low-threshold potassium current (K_LT) that is present in a subset of cells in the zebra finch caudal mesopallium and is affected by early auditory experience. We found that K_LT affects both spike adaptation and the temporal filtering properties of the receptive field. The direction of the effects depended on the temporal modulation tuning of the linear (input) stage of the cascade model, indicating a strongly nonlinear relationship. These results suggest that small changes in intrinsic dynamics in tandem with differences in synaptic connectivity can have dramatic effects on the tuning of auditory neurons.     

The influence of whole body vibration on the plantarflexors during heel raise exercise

Whole body vibration (WBV) during exercise offers potential to augment the effects of basic exercises. However, to date there is limited information on the basic physiological and biomechanical effects of WBV on skeletal muscles. The aim of this study was to determine the effects of WBV (40 Hz, 1.9 mm synchronous vertical displacement) on the myoelectrical activity of selected plantarflexors during heel raise exercise. 3D motion capture of the ankle, synchronised with sEMG of the lateral gastrocnemius and soleus, was obtained during repetitive heel raises carried out at 0.5 Hz on 10 healthy male subjects (age 27 ± 5 years, height 1.78 ± 0.04 m, weight 75.75 ± 11.9 kg). During both vibration and non vibration the soleus activation peaked earlier than that of the lateral gastrocnemius. The results indicate that WBV has no effect on the timing of exercise completion or the amplitude of the lateral gastrocnemius activity, however significant increases in amplitudes of the soleus muscle activity (77.5–90.4% MVC P < 0.05). WBV had no significant effect on median frequencies of either muscle. The results indicate that the greatest effect of WBV during heel raise activity is in the soleus muscles during the early phases of heel raise.     

Placental Syncytium Forms a Biophysical Barrier against Pathogen Invasion

Fetal syncytiotrophoblasts form a unique fused multinuclear surface that is bathed in maternal blood, and constitutes the main interface between fetus and mother. Syncytiotrophoblasts are exposed to pathogens circulating in maternal blood, and appear to have unique resistance mechanisms against microbial invasion. These are due in part to the lack of intercellular junctions and their receptors, the Achilles heel of polarized mononuclear epithelia. However, the syncytium is immune to receptor-independent invasion as well, suggesting additional general defense mechanisms against infection. The difficulty of maintaining and manipulating primary human syncytiotrophoblasts in culture makes it challenging to investigate the cellular and molecular basis of host defenses in this unique tissue. Here we present a novel system to study placental pathogenesis using murine trophoblast stem cells (mTSC) that can be differentiated into syncytiotrophoblasts and recapitulate human placental syncytium. Consistent with previous results in primary human organ cultures, murine syncytiotrophoblasts were found to be resistant to infection with Listeria monocytogenes via direct invasion and cell-to-cell spread. Atomic force microscopy of murine syncytiotrophoblasts demonstrated that these cells have a greater elastic modulus than mononuclear trophoblasts. Disruption of the unusually dense actin structure – a diffuse meshwork of microfilaments - with Cytochalasin D led to a decrease in its elastic modulus by 25%. This correlated with a small but significant increase in invasion of L. monocytogenes into murine and human syncytium. These results suggest that the syncytial actin cytoskeleton may form a general barrier against pathogen entry in humans and mice. Moreover, murine TSCs are a genetically tractable model system for the investigation of specific pathways in syncytial host defenses.     

Natural killer cells promote early CD8 T cell responses against cytomegalovirus

Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK) cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV) by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-alpha/beta production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs) for cytokine production, preserves the conventional dendritic cell (cDC) compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-alpha administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate cytokine shock and to the promotion of adaptive immunity.