Stress-induced elevation of glucocorticoids increases microglia proliferation through NMDA receptor activation.

The immunosuppressive nature of glucocorticoids has been well documented both in vitro and in vivo. This glucocorticoid-mediated immunosuppression has also been observed in immune cells within the central nervous system (CNS). For example, microglia have previously been shown to exhibit decreased proliferation, cytokine production, and antigen presentation upon treatment with glucocorticoids in vitro.

Corticosterone impairs MHC class I antigen presentation by dendritic cells via reduction of peptide generation.

The presentation of viral peptide-MHC class I complexes by antigen presenting cells, such as dendritic cells (DCs), is obligatory for the generation of antiviral effector and memory CD8(+) cytotoxic T lymphocyte (CTL) responses. Prolonged psychological stress is immunosuppressive and undermines primary and memory CTL-mediated antiviral immunity; however, the mechanisms involved are unknown. Using a panel of novel reagents and techniques, we quantitatively measured the effect of the stress-induced hormone corticosterone (CORT) on the efficiency of DCs to process and present virally expressed antigen, characterized the conditions for this CORT-mediated effect, and delineated the components of the MHC class I pathway that were affected.

THUMP: an immersive haptic console for surgical simulation and training.

Telerobotic systems are revolutionizing minimally invasive surgery (MIS), giving the surgeon complete control over precise dexterous movements of tiny robotic instruments. Such 'surgery-by-wire' approaches also create unique opportunities for simulation and training, as the surgeon operates at a computer-mediated haptic console. Possible extensions include offline training in simulated environments and advanced guidance and mentoring during actual operations.

Genome sequence of Haloarcula marismortui: a halophilic archaeon from the Dead Sea.

We report the complete sequence of the 4,274,642-bp genome of Haloarcula marismortui, a halophilic archaeal isolate from the Dead Sea. The genome is organized into nine circular replicons of varying G+C compositions ranging from 54% to 62%. Comparison of the genome architectures of Halobacterium sp.

Impact of maternal stress on the transmammary transfer and protective capacity of herpes simplex virus-specific immunity.

In adults, psychological stress regulates immune responsiveness in part via the increased levels of corticosterone that are produced as a result of hypothalamic-pituitary-adrenal (HPA) axis activation. However, there is a lack of knowledge as to the role such regulation may play in the neonate. Neonates are severely compromised in their ability to generate an immune response to pathogens encountered after birth and therefore rely heavily on maternally derived antibody acquired postnatally through the milk.

Comprehensive de novo structure prediction in a systems-biology context for the archaea Halobacterium sp. NRC-1.

Background: Large fractions of all fully sequenced genomes code for proteins of unknown function. Annotating these proteins of unknown function remains a critical bottleneck for systems biology and is crucial to understanding the biological relevance of genome-wide changes in mRNA and protein expression, protein-protein and protein-DNA interactions. The work reported here demonstrates that de novo structure prediction is now a viable option for providing general function information for many proteins of unknown function.

Capsaicin-mediated denervation of sensory neurons promotes mammary tumor metastasis to lung and heart.

Capsaicin specifically activates or destroys small diameter nociceptive sensory neurons that contain the capsaicin receptor, also called vanilloid receptor 1. Neurons sensitive to capsaicin mediate inflammatory pain and are important targets for management of chronic pain. These neurons also regulate local tissue homeostasis, inflammation, healing and development, especially under conditions of psychological stress.

Systems level insights into the stress response to UV radiation in the halophilic archaeon Halobacterium NRC-1.

We report a remarkably high UV-radiation resistance in the extremely halophilic archaeon Halobacterium NRC-1 withstanding up to 110 J/m2 with no loss of viability. Gene knockout analysis in two putative photolyase-like genes (phr1 and phr2) implicated only phr2 in photoreactivation. The UV-response was further characterized by analyzing simultaneously, along with gene function and protein interactions inferred through comparative genomics approaches, mRNA changes for all 2400 genes during light and dark repair.

Postpartum maternal corticosterone decreases maternal and neonatal antibody levels and increases the susceptibility of newborn mice to herpes simplex virus-associated mortality.

The effects of corticosterone on the transmammary transfer of herpes simplex virus (HSV)-specific antibody and the ability of the neonate to survive HSV-2 infection were assessed. Increased postpartum maternal corticosterone reduced the levels of total and HSV-specific IgG in the serum and milk of mothers. Neonates nursed by these mothers received increased levels of corticosterone and decreased levels of total and HSV-specific IgG.

Neutralizing antibody against interleukin-6 attenuates posthemorrhagic vasospasm in the rat femoral artery model.

Objective: The degree to which inflammation contributes to the development of posthemorrhagic vasospasm is controversial. In the present study, we investigated the relationship between various inflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-1alpha, IL-1beta, and IL-6) and the development of experimental vasospasm.

Methods: Posthemorrhagic vasospasm was produced in the rat femoral artery model.

Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in normoglycemic but not diabetic female mice.

Diabetic hyperglycemia increases ischemic brain damage in experimental animals and humans. The mechanisms are unclear but may involve enhanced apoptosis in penumbral regions. Estrogen is an established neuroprotectant in experimental stroke.

Prenatal transfer of low amounts of herpes simplex virus (HSV)-specific antibody protects newborn mice against HSV infection during acute maternal stress.

Given their immunocompromised status, neonates rely heavily upon maternally derived, herpes simplex virus (HSV)-specific antibody for resistance to HSV infection. Interestingly, previous studies have documented a decreased transfer of maternal IgG antibody and immunocompetence of the offspring following perinatal exposure to stress-induced corticosterone. However, we recently demonstrated that the transplacental transfer of relatively high amounts of HSV-specific antibody is resilient to acute maternal stress and protects neonatal mice against HSV-2-associated mortality.

Low-dose remifentanil infusion does not impair natural killer cell function in healthy volunteers.

Background: Mu opioid agonists suppress natural killer (NK) cell activity in animal models. Studies in human volunteers, however, have yielded conflicting results, with morphine suppressing and fentanyl increasing NK cell activity. This study evaluated the effect of a constant 8-h infusion of remifentanil on NK cell number and function in human volunteers.

Automated prediction of CASP-5 structures using the Robetta server.

Robetta is a fully automated protein structure prediction server that uses the Rosetta fragment-insertion method. It combines template-based and de novo structure prediction methods in an attempt to produce high quality models that cover every residue of a submitted sequence. The first step in the procedure is the automatic detection of the locations of domains and selection of the appropriate modeling protocol for each domain.

An improved protein decoy set for testing energy functions for protein structure prediction.

We have improved the original Rosetta centroid/backbone decoy set by increasing the number of proteins and frequency of near native models and by building on sidechains and minimizing clashes. The new set consists of 1,400 model structures for 78 different and diverse protein targets and provides a challenging set for the testing and evaluation of scoring functions. We evaluated the extent to which a variety of all-atom energy functions could identify the native and close-to-native structures in the new decoy sets.

The dual role of CD8+ T lymphocytes in the development of stress-induced herpes simplex encephalitis.

Despite the generally restrictive nature of the blood-brain barrier (BBB), circulating lymphocytes can infiltrate into the central nervous system (CNS) during a variety of disease states. Although the contributions of these lymphocytes to CNS-associated disease have been identified in some viral models, the factors which govern this infiltration following herpes simplex virus (HSV) infection remain to be elucidated. We have developed a murine model of HSV encephalitis (HSE) to define the relationship among psychological stress, the recruitment of HSV-specific T cells into the CNS, and the development of HSE.

Transplacental transfer and subsequent neonate utilization of herpes simplex virus-specific immunity are resilient to acute maternal stress.

Neonates are severely compromised in the ability to generate an immune response to pathogens and thus rely heavily on maternally derived immunity that is acquired by transplacental and transmammary means. The passive transfer of maternal herpes simplex virus (HSV)-specific antibody is critical in determining the outcome of neonatal HSV infection. In adults, psychological stress alters immune responsiveness via the increased level of corticosterone that is produced as a result of hypothalamic-pituitary-adrenal axis activation.

Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia.

This study challenges the concept that herpes simplex virus type 1 (HSV-1) latency represents a silent infection that is ignored by the host immune system, and suggests antigen-directed retention of memory CD8(+) T cells. CD8(+) T cells specific for the immunodominant gB(498-505) HSV-1 epitope are selectively retained in the ophthalmic branch of the latently infected trigeminal ganglion, where they acquire and maintain an activation phenotype and the capacity to produce IFN-gamma. Some CD8(+) T cells showed TCR polarization to junctions with neurons.

Photoprotodesilylation of 9-trimethylsilylanthracene in alcohols.

It was found that the anomalous fluorescence quenching in methanol (as compared to other solvents) of 9-trimethylsilylanthracene (2) is accompanied by a chemical reaction leading to anthracene. This ipso substitution is due to a hydrogen bonding formation in the excited singlet state preceding the carbon-silicon bond cleavage. The mechanism was studied using stationary and dynamic fluorescence, laser flash photolysis and reactivity kinetics as a function of temperature.

De novo prediction of three-dimensional structures for major protein families.

We use the Rosetta de novo structure prediction method to produce three-dimensional structure models for all Pfam-A sequence families with average length under 150 residues and no link to any protein of known structure. To estimate the reliability of the predictions, the method was calibrated on 131 proteins of known structure. For approximately 60% of the proteins one of the top five models was correctly predicted for 50 or more residues, and for approximately 35%, the correct SCOP superfamily was identified in a structure-based search of the Protein Data Bank using one of the models.

Contact order and ab initio protein structure prediction.

Although much of the motivation for experimental studies of protein folding is to obtain insights for improving protein structure prediction, there has been relatively little connection between experimental protein folding studies and computational structural prediction work in recent years. In the present study, we show that the relationship between protein folding rates and the contact order (CO) of the native structure has implications for ab initio protein structure prediction. Rosetta ab initio folding simulations produce a dearth of high CO structures and an excess of low CO structures, as expected if the computer simulations mimic to some extent the actual folding process.

Distributions of beta sheets in proteins with application to structure prediction.

We recently developed the Rosetta algorithm for ab initio protein structure prediction, which generates protein structures from fragment libraries using simulated annealing. The scoring function in this algorithm favors the assembly of strands into sheets. However, it does not discriminate between different sheet motifs.