Life and death of a BiP substrate

BiP is the mammalian endoplasmic reticulum (ER) Hsp70 orthologue that plays a major role in all functions of this organelle including the seemingly opposing functions of aiding the maturation of unfolded nascent proteins and identifying and targeting chronically unfolded proteins for degradation. The recent identification of mammalian BiP co-factors combined with delineation of the ER degradation machinery and data suggesting that the ER is subdivided into unique regions helps explain how these different functions can occur in the same organelle and raises some unresolved issues.     

Two‐state conformational equilibrium in the Par‐4 leucine zipper domain

Prostate apoptosis response factor‐4 (Par‐4) is a pro‐apoptotic and tumor‐suppressive protein. A highly conserved heptad repeat sequence at the Par‐4 C‐terminus suggests the presence of a leucine zipper (LZ). This C‐terminal region is essential for Par‐4 self‐association and interaction with various effector proteins. We have used nuclear magnetic resonance (NMR) spectroscopy to fully assign the chemical shift resonances of a peptide comprising the LZ domain of Par‐4 at neutral pH. Further, we have investigated the properties of the Par‐4 LZ domain and two point mutants under a variety of conditions using NMR, circular dichroism (CD), light scattering, and bioinformatics. Results indicate an environment‐dependent conformational equilibrium between a partially ordered monomer (POM) and a predominantly coiled coil dimer (CCD). The combination of techniques used allows the time scales of the equilibrium to be probed and also helps to identify features of the amino acid sequence that may influence the equilibrium. Proteins 2010. © 2010 Wiley‐Liss, Inc.     

Expressive Aphasia as a Presentation of Encephalitis with Bartonella henselae Infection in an Immunocompetent Adult

Objective: To show the first clinically reported case of Cat Scratch Disease (CSD) presenting as a focal neurologic deficit in an immunocompetent adult.Patient: 59-year-old male with a history of a previous stroke.Results: Examination showed an expressive aphasia, word substitution errors, and impaired repetition. A head CT and MRI showed no acute changes. The EEG findings were non-focal and did not show any epileptiform activity. The patient had a history of contact with stray kittens and previous axillary lymphadenopathy. Bartonella henselae serology titers were IgG positive 1:1024 (< 64) and IgM positive 1:20 (< 16). After antibiotic administration, the patient’s symptoms and aphasia resolved.Conclusions: Focal presentations concerning for stroke or partial seizure activity may have underlying infectious etiology. We recommend consideration of CSD in the differential diagnosis of any adult with a history of lymphadenopathy, fever, and recent contact with a cat who presents with neurologic complications.     

Population Genetics of Two Key Mosquito Vectors of Rift Valley Fever Virus Reveals New Insights into the Changing Disease Outbreak Patterns in Kenya

Rift Valley fever (RVF) outbreaks in Kenya have increased in frequency and range to include northeastern Kenya where viruses are increasingly being isolated from known (Aedes mcintoshi) and newly-associated (Ae. ochraceus) vectors. The factors contributing to these changing outbreak patterns are unclear and the population genetic structure of key vectors and/or specific virus-vector associations, in particular, are under-studied. By conducting mitochondrial and nuclear DNA analyses on >220 Kenyan specimens of Ae. mcintoshi and Ae. ochraceus, we uncovered high levels of vector complexity which may partly explain the disease outbreak pattern. Results indicate that Ae. mcintoshi consists of a species complex with one of the member species being unique to the newly-established RVF outbreak-prone northeastern region of Kenya, whereas Ae. ochraceus is a homogeneous population that appears to be undergoing expansion. Characterization of specimens from a RVF-prone site in Senegal, where Ae. ochraceus is a primary vector, revealed direct genetic links between the two Ae. ochraceus populations from both countries. Our data strongly suggest that unlike Ae. mcintoshi, Ae. ochraceus appears to be a relatively recent, single ''introduction'' into Kenya. These results, together with increasing isolations from this vector, indicate that Ae. ochraceus will likely be of greater epidemiological importance in future RVF outbreaks in Kenya. Furthermore, the overall vector complexity calls into question the feasibility of mosquito population control approaches reliant on genetic modification.     

Effect of prolonged prostaglandin exposure on prostaglandin synthesis by human lung fibroblasts

Pretreatment of human lung fibroblasts with PGE₂ but not PGF_2α enhanced synthesis of prostaglandins (PGs). The effect of the pretreatment on PG synthesis was related to the concentration of PGE₂ that was added to the culture medium. Pretreatment with PGE₂ at 5 × 10⁻¹²M did not enhance PG synthesis whereas pretreatment with PGE₂ at 5 × 10⁻⁶M induced a maximal effect. Production of PGs was increased following 1 day of pretreatment with PGE₂ and was increased further following 3 days of pretreatment. The PGE₂ treated cells showed only a slight increase in the bradykinin-induced release of radioactivity from cells prelabeled with [³H]arachidonic acid but showed a dramatic increase in the bradykinin-induced synthesis of radio-labeled PGs. The conversion of free arachidonate to PGs in both intact cells and in a cell-free preparation was increased by PGE₂ pretreatment. The presence of cyclohexamide during the pretreatment did not inhibit the PGE₂-induced activation of PG synthesis. Taken together, the results indicate that pretreatment of cells with PGE₂ increased PG synthesis by augmenting the conversion of arachidonate to PGs.     

Why do imagery and perception look and feel so different?

Despite the past few decades of research providing convincing evidence of the similarities in function and neural mechanisms between imagery and perception, for most of us, the experience of the two are undeniably different, why? Here, we review and discuss the differences between imagery and perception and the possible underlying causes of these differences, from function to neural mechanisms. Specifically, we discuss the directional flow of information (top-down versus bottom-up), the differences in targeted cortical layers in primary visual cortex and possible different neural mechanisms of modulation versus excitation. For the first time in history, neuroscience is beginning to shed light on this long-held mystery of why imagery and perception look and feel so different.This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation''.