Hsp-90 and the biology of nematodes

BACKGROUND: Hsp-90 from the free-living nematode Caenorhabditis elegans is unique in that it fails to bind to the specific Hsp-90 inhibitor, geldanamycin (GA). Here we surveyed 24 different free-living or parasitic nematodes with the aim of determining whether C. elegans Hsp-90 was the exception or the norm amongst the nematodes. We combined these data with codon evolution models in an attempt to identify whether hsp-90 from GA-binding and non-binding species has evolved under different evolutionary constraints.<BR/>RESULTS: We show that GA-binding is associated with life history: free-living nematodes and those parasitic species with free-living larval stages failed to bind GA. In contrast, obligate parasites and those worms in which the free-living stage in the environment is enclosed within a resistant egg, possess a GA-binding Hsp-90. We analysed Hsp-90 sequences from fifteen nematode species to determine whether nematode hsp-90s have undergone adaptive evolution that influences GA-binding. Our data provide evidence of rapid diversifying selection in the evolution of the hsp-90 gene along three separate lineages, and identified a number of residues showing significant evidence of adaptive evolution. However, we were unable to prove that the selection observed is correlated with the ability to bind geldanamycin or not.<BR/>CONCLUSION: Hsp-90 is a multi-functional protein and the rapid evolution of the hsp-90 gene presumably correlates with other key cellular functions. Factors other than primary amino acid sequence may influence the ability of Hsp-90 to bind to geldanamycin

Electro-hyperthermia in Oncology

Hyperthermia is a rapidly developing treatment method in oncology. The classical effect is based on well-focused energy absorption targeting the malignant tissue. Unfortunately, the heat-shock protein (HSP) synthesis may considerably suppress the treatment’s efficiency, causing cells to adapt and survive the shock. Electro-hyperthermia heats the targeted tissue by means of electricity, producing less HSP in the cells than classical hyperthermia. The main improvement is keeping the energy absorption within the extracellular matrix (ECM). By heating the ECM, ion-mobility increases, metabolic rates increase, and the heat destroys the cells’ membrane before the heat-shock activates the intra-cellular HSP mechanisms

A Case of Henoch-Schonlein Purpura Associated with Rotavirus Infection in an Elderly Asian Male and Review of the Literature.

BACKGROUND Henoch-Schönlein purpura (HSP), a small vessel vasculitis mediated by deposition of immune-complexes containing IgA in the skin, gut, and glomeruli, often presents with abdominal pain, purpuric rash in the lower extremities and buttocks, joint pain, and hematuria. The disease most commonly targets children but can affect adults who tend to have a worse prognosis. CASE REPORT We discuss a case of HSP in an elderly Chinese male who presented with severe proximal bowel inflammation, vasculitic rash, and proteinuria; he was found to have positive stool rotavirus and giardia. He improved significantly with high dose steroids. We believe rotavirus may have been a triggering event in this patient. A brief review of the literature is also presented. CONCLUSIONS This is the first case report describing a classic presentation of HSP in an adult following a rotavirus infection. HSP can cause significant morbidity and mortality in adult patients predominantly from progressive renal failure; therefore careful management and monitoring is important. GI infections seem to be a common trigger for HSP and this case report suggests that rotavirus may be part of the spectrum

SPG10 is a rare cause of spastic paraplegia in European families

Background: SPG10 is an autosomal dominant form of hereditary spastic paraplegia (HSP), which is caused by mutations in the neural kinesin heavy chain KIF5A gene, the neuronal motor of fast anterograde axonal transport. Only four mutations have been identified to date.Objective: To determine the frequency of SPG10 in European families with HSP and to specify the SPG10 phenotype.Patients and methods: 80 index patients from families with autosomal dominant HSP were investigated for SPG10 mutations by direct sequencing of the KIF5A motor domain. Additionally, the whole gene was sequenced in 20 of these families.Results: Three novel KIF5A mutations were detected in German families, including one missense mutation (c.759G>T, p.K253N), one in frame deletion (c.768_770delCAA, p.N256del) and one splice site mutation (c.217G>A). Onset of gait disturbance varied from infancy to 30 years of age. All patients presented clinically with pure HSP, but a subclinical sensory--motor neuropathy was detected by neurophysiology studies.Conclusions: SPG10 accounts for approximately 3% of European autosomal dominant HSP families. All mutations affect the motor domain of kinesin and thus most likely impair axonal transport. Clinically, SPG10 is characterised by spastic paraplegia with mostly subclinical peripheral neuropathy

Further supporting evidence for REEP1 phenotypic and allelic heterogeneity.

Heterozygous mutations in REEP1 (MIM #609139) encoding the receptor expression-enhancing protein 1 (REEP1) are a well-recognized and relatively frequent cause of autosomal dominant hereditary spastic paraplegia (HSP), SPG31.1 REEP1 localizes in the mitochondria and endoplasmic reticulum (ER) and facilitates ER-mitochondria interactions.2 In addition to the HSP phenotype, REEP1 has been associated with an autosomal dominant spinal type of Charcot-Marie-Tooth disease in 2 families.3 More recently, a patient with homozygous REEP1 mutation with a much more severe phenotype akin to spinal muscular atrophy with respiratory distress type 1 (SMARD1) was reported.4 In this report, we present a patient with a homozygous mutation in REEP1 manifesting a severe congenital distal spinal muscular atrophy (SMA) with diaphragmatic paralysis, expanding the phenotype from mild autosomal dominant HSP through to severe recessive distal SMA pattern

Comparison between TeV and non-TeV BL Lac Objects

BL Lacertae objects (BL Lacs) is the dominant population of TeV emitting blazars. In this work, we investigate whether there is any special observational properties for TeV sources. To do so, we will compare the observational properties of TeV detected BL Lacs (TeV BLs) and non-TeV detected BL Lac objects (non-TeV BLs). From the 3rd $Fermi$/LAT catalog (3FGL), we can get 662 BL Lacs, out of which, 47 are TeV BLs and 615 are non-TeV BLs. Their multi-wavelength flux densities ($F_{\rm R}$, $F_{\rm O}$, $F_{\rm X}$, $F_{\gamma}$), photon spectral indexes ($\alpha_{\rm X}^{\rm ph}$, $\alpha_{\gamma}^{\rm ph}$), and effective spectral indexes ($\alpha_{\rm RO}$ and $\alpha_{\rm OX}$) are compiled from the available literatures. Then the luminosities ($\log\,{\nu}L_{\rm R}$, $\log\,{\nu}L_{\rm O}$, $\log\,{\nu}L_{\rm X}$, $\log\,{\nu}L_{\gamma}$) are calculated. From comparisons, we found that TeV BLs are different from low-synchrotron-peaked BLs (LSP) and intermediate-synchrotron-peaked BLs (ISP), but TeV BLs show similar properties as high-synchrotron-peaked BLs (HSP). Therefore, we concentrated on comparison between TeV HSP BLs and non-TeV HSP BLs. Analysis results suggest that TeV HSP BLs and non-TeV HSP BLs show some differences in their $\alpha_{\rm RO}$ and $\alpha_{\gamma}^{\rm ph}$, while their other properties are quite similar

Multiscale nature of hysteretic phenomena: Application to CoPt-type magnets

We suggest a workable approach for the description of multiscale magnetization reversal phenomena in nanoscale magnets and apply it to CoPt-type alloys. We show that their hysteretic properties are governed by two effects originating at different length scales: a peculiar splitting of domain walls and their strong pinning at antiphase boundaries. We emphasize that such multiscale nature of hysteretic phenomena is a generic feature of nanoscale magnetic materials.Comment: 4 pages (revtex 4), 2 color EPS figure

The cranking formula and the spurious behaviour of the mass parameters

We discuss some aspects of the approach of the mass parameters by means of the simple cranking model. In particular, it is well known that the numerical application of this formula is often subject to ambiguities or contradictions. It is found that these problems are induced by the presence of two derivatives in the formula. To overcome these problems, we state a useful ansatz and we develop a number of simple arguments which tend to justify the removal of these terms. As soon as this is done, the formula becomes simpler and easier to interpret. In this respect, it is shown how the shell effects affect the mass parameters. A number of numerical tests help us in our conclusions.Comment: version 3 corrigendum of the ansatz of section V, corrigendum of the legend of Fig3. Submission = text file + 5 figure