Downregulation of heat shock protein 70 protects rheumatoid arthritis fibroblast-like synoviocytes from nitric oxide-induced apoptosis

Introduction  

Heat shock protein 70 (Hsp70) is a well-known anti-apoptotic protein that blocks multiple steps in the stress-induced apoptotic pathway. Enhanced Hsp70 expression has previously been demonstrated in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs). The authors investigated the role of Hsp70 in the survival of RA FLSs in a sodium nitroprusside (SNP)-treated environment.     

Geldanamycin induces production of heat shock protein 70 and partially attenuates ototoxicity caused by gentamicin in the organ of Corti explants

Background  

Heat shock protein 70 (HSP70) protects inner ear cells from damage and death induced by e.g. heat or toxins. Benzoquinone ansamycin antibiotic geldanamycin (GA) was demonstrated to induce the expression of HSP70 in various animal cell types. The aim of our study was to investigate whether GA induces HSP70 in the organ of Corti (OC), which contains the auditory sensory cells, and whether GA can protect these cells from toxicity caused by a common aminoglycoside antibiotic gentamicin.     

Phospholipse c inhibitor,u73122, stimulates release of hsp-70 stress protein from A431 human carcinoma cells

Background  

Accumulating evidences suggest that Hsp 70, the inducible component of Hsp70 family, might release from a living cell. Here we show that a pharmacological inhibitor of phospholipase C activity U73122 caused a 2–4 fold reduction of an intracellular level of Hsp70 in A431 human carcinoma cells.     

Inducible and constitutive heat shock gene expression responds to modification of Hsp70 copy number in Drosophila melanogaster but does not compensate for loss of thermotolerance in Hsp70 null flies

Background  

The heat shock protein Hsp70 promotes inducible thermotolerance in nearly every organism examined to date. Hsp70 interacts with a network of other stress-response proteins, and dissecting the relative roles of these interactions in causing thermotolerance remains difficult. Here we examine the effect of Hsp70 gene copy number modification on thermotolerance and the expression of multiple stress-response genes in Drosophila melanogaster, to determine which genes may represent mechanisms of stress tolerance independent of Hsp70.     

Enhanced inhibition of Aspergillus niger on sedge (Lepironia articulata) treated with heat‐cured lime oil

Aims

This study aimed to examine heat curing effect (30–100°C) on antifungal activities of lime oil and its components (limonene, p‐cymene, β‐pinene and α‐pinene) at concentrations ranging from 100 to 300 μl ml^?1 against Aspergillus niger in microbiological medium and to optimize heat curing of lime oil for efficient mould control on sedge (Lepironia articulata).

Methods and Results

Broth dilution method was employed to determine lime oil minimum inhibitory concentration, which was at 90 μl ml^?1 with heat curing at 70°C. Limonene, a main component of lime oil, was an agent responsible for temperature dependencies of lime oil activities observed. Response surface methodology was used to construct the mathematical model describing a time period of zero mould growth on sedge as functions of heat curing temperature and lime oil concentration. Heat curing of 90 μl ml^?1 lime oil at 70°C extended a period of zero mould growth on sedge to 18 weeks under moist conditions.

Conclusions

Heat curing at 70°C best enhanced antifungal activity of lime oil against A. niger both in medium and on sedge.

Significance and Impact of the Study

Heat curing of lime oil has potential to be used to enhance the antifungal safety of sedge products.     

The crystal structure of the putative peptide-binding fragment from the human Hsp40 protein Hdj1

Background  

The mechanism by which Hsp40 and other molecular chaperones recognize and interact with non-native polypeptides is a fundamental question. How Hsp40 co-operates with Hsp70 to facilitate protein folding is not well understood. To investigate the mechanisms, we determined the crystal structure of the putative peptide-binding fragment of Hdj1, a human member of the type II Hsp40 family.     

Thermophilic enrichment of microbial communities in the presence of the ionic liquid 1‐ethyl‐3‐methylimidazolium acetate

Aims

The aim of the study was to develop an approach to enrich ionic liquid tolerant micro‐organisms that efficiently decompose lignocellulose in a thermophilic and high‐solids environment.

Methods and Results

High‐solids incubations were conducted, using compost as an inoculum source, to enrich for thermophilic communities that decompose switchgrass in the presence of the ionic liquid 1‐ethyl‐3‐methylimidazolium acetate ([C2mim][OAc]). Ionic liquid levels were increased from 0 to 6% on a total weight basis incrementally. Successful enrichment of a community that decomposed lignocellulose at 55°C in the presence of 6% [C2mim][OAc] was achieved, when the [C2mim][OAc] level was increased stepwise from 2% to 4% to 5% to 6%. Pyrosequencing results revealed a shift in the community and a sharp decrease in richness, when thermophilic conditions were applied.

Conclusions

A community tolerant to a thermophilic, high‐solids environment containing 6% [C2mim][OAc] was enriched from compost. Gradually increasing [C2mim][OAc] concentrations allowed the community to adapt to [C2mim][OAc].

Significance and Impact of the Study

A successful approach to enrich communities that decompose lignocellulose under thermophilic high‐solids conditions in the presence of elevated levels of [C2mim][OAc] has been developed. Communities yielded from this approach will provide resources for the discovery of enzymes and metabolic pathways relevant to biomass pretreatment and fuel production.     

RFX1 regulates CD70 and CD11a expression in lupus T cells by recruiting the histone methyltransferase SUV39H1

Introduction  

Regulatory factor X-box 1 (RFX1) can interact with DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1), and RFX1 down-regulation contributes to DNA hypomethylation and histone H3 hyperacetylation at the cluster of differentiation (CD) 11a and CD70 promoters in CD4⁺ T cells of patients with systemic lupus erythematosus (SLE). This leads to CD11a and CD70 overexpression, thereby triggering autoimmune responses. In order to provide more insight into the epigenetic mechanisms leading to the deregulation of autoimmune-related genes in SLE, we asked whether RFX1 is involved in regulating histone 3 lysine 9 (H3K9) tri-methylation at the CD11a and CD70 promoters in SLE CD4⁺ T cells.     

Elevated autoantibody content in rheumatoid arthritis synovia with lymphoid aggregates and the effect of rituximab

Introduction  

The purpose of this study was to quantitatively evaluate the contribution of synovial lymphoid aggregates to autoantibody (rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP]) and total immunoglobulin (IgG and IgM) production in rheumatoid arthritis (RA) patients and the effect thereon of the B-cell-depleting antibody, rituximab, in the ARISE (Assessment of Rituximab's Immunomodulatory Synovial Effects) trial.     

Investigation of Mannheimia haemolytica bacteriophages relative to host diversity

Aims

This study aimed to characterize the impact of lytic and temperate bacteriophages on the genetic and phenotypic diversity of Mannheimia haemolytica from feedlot cattle.

Methods and Results

Strictly lytic phages were not detected from bovine nasopharyngeal (n = 689) or water trough (n = 30) samples, but Myoviridae‐ or Siphoviridae‐like phages were induced from 54 of 72 M. haemolytica strains by mitomycin C, occasionally from the same strain. Phages with similar restriction fragment length polymorphism profiles (RFLP ≥70% relatedness) shared common host serotypes 1 or 2 (P < 0·000 1). Likewise, phages with similar RFLP tended to occur in genetically related host bacteria (70–79% similarity). Host range assays showed that seven phages from host serotypes 1, 2 and 6 lysed representative strains of serotypes 1, 2 or 8. The genome of vB_MhM_1152AP from serotype 6 was found to be collinear with P2‐like phage φMhaA1‐PHL101.

Conclusions

Prophages are a significant component of the genome of M. haemolytica and contribute significantly to host diversity. Further characterization of the role of prophage in virulence and persistence of M. haemolytica in cattle could provide insight into approaches to control this potential respiratory pathogen.

Significance and Impact of the Study

This study demonstrated that prophages are widespread within the genome of M. haemolytica isolates and emphasized the challenge of isolating lytic phage as a therapeutic against this pathogen.     

Function of SSA Subfamily of Hsp70 Within and Across Species Varies Widely in Complementing Saccharomyces cerevisiae Cell Growth and Prion Propagation

Background

The cytosol of most eukaryotic cells contains multiple highly conserved Hsp70 orthologs that differ mainly by their spatio-temporal expression patterns. Hsp70s play essential roles in protein folding, transport or degradation, and are major players of cellular quality control processes. However, while several reports suggest that specialized functions of Hsp70 orthologs were selected through evolution, few studies addressed systematically this issue.

Methodology/Principal Findings

We compared the ability of Ssa1p-Ssa4p from Saccharomyces cerevisiae and Ssa5p-Ssa8p from the evolutionary distant yeast Yarrowia lipolytica to perform Hsp70-dependent tasks when expressed as the sole Hsp70 for S. cerevisiae in vivo. We show that Hsp70 isoforms (i) supported yeast viability yet with markedly different growth rates, (ii) influenced the propagation and stability of the [PSI⁺] and [URE3] prions, but iii) did not significantly affect the proteasomal degradation rate of CFTR. Additionally, we show that individual Hsp70 orthologs did not induce the formation of different prion strains, but rather influenced the aggregation properties of Sup35 in vivo. Finally, we show that [URE3] curing by the overexpression of Ydj1p is Hsp70-isoform dependent.

Conclusion/Significance

Despite very high homology and overlapping functions, the different Hsp70 orthologs have evolved to possess distinct activities that are required to cope with different types of substrates or stress situations. Yeast prions provide a very sensitive model to uncover this functional specialization and to explore the intricate network of chaperone/co-chaperone/substrates interactions.     

Genomic actions of 1,25-dihydroxyvitamin D<Subscript>3</Subscript> on insulin receptor gene expression,insulin receptor number and insulin activity in the kidney,liver and adipose tissue of streptozotocin-induced diabetic rats

Background  

this study set out to examine the effects of the treatment with 1,25-dihydroxyvitamin D₃ (1,25D ₃) [150 IU/Kg (3.75 μg/Kg) one a day, for 15 days] to non-diabetic rats and in rats rendered diabetic by a single injection of streptozotocin [65 mg/kg].     

Subcutaneously administered Menopur(R), a new highly purified human menopausal gonadotropin,causes significantly fewer injection site reactions than Repronex(R) in subjects undergoing in vitro fertilization

Background  

The safety and tolerability of a new highly purified, urine-derived human menopausal gonadotropin (hMG) preparation [Menopur(R)] was compared with a currently available hMG [Repronex (R)] in women undergoing in vitro fertilization (IVF).     

Conservation prioritisation through genomic reconstruction of demographic histories applied to two endangered suids in the Malay Archipelago

Aim

The biodiversity of the Malay Archipelago is the product of the region's rich biogeographical history with periods of island connectivity and isolation during the Pleistocene glacial cycles. Here, the case of two endemic suid species, the Javan (Sus verrucosus) and Bawean (S. blouchi) warty pigs, was used to illustrate how biogeographic processes and recent anthropogenic pressures can shape demographic histories with significant implications for species conservation.

Location

Malay Archipelago, with focus on Bawean and Java.

Methods

We employed genome-wide single nucleotide polymorphisms from the Porcine SNP60 v2 BeadChip to assess interspecific genetic differentiation, to estimate divergence times and to perform demographic model selection.

Results

In contrast to the hypothesis of recent divergence during the last glacial maximum, S. blouchi was found to have diverged from S. verrucosus at least 166 k years ago following a founder event. The contemporary S. blouchi population was characterised by a recent bottleneck that reduced the effective population size to less than 20. The genomic assessment supports the single species status of S. blouchi, as was previously proposed based on morphometrics. The demographic history of S. verrucosus showed evidence of secondary contact with the sympatric banded pig (S. scrofa vittatus) that colonised Java 70 k years ago.

Main Conclusions

While the Javan and Bawean warty pigs have persisted throughout the Pleistocene climatic oscillations, contemporary pressures from human activities threaten their survival and immediate action should be taken to grant legal protection to both S. verrucosus and S. blouchi. This study highlighted the use of demographic history modelling using genomic data to identify evolutionary significant units and inform conservation.     

A recent duplication revisited: phylogenetic analysis reveals an ancestral duplication highly-conserved throughout the Oryza genus and beyond

Background  

The role of gene duplication in the structural and functional evolution of genomes has been well documented. Analysis of complete rice (Oryza sativa) genome sequences suggested an ancient whole genome duplication, common to all the grasses, some 50-70 million years ago and a more conserved segmental duplication between the distal regions of the short arms of chromosomes 11 and 12, whose evolutionary history is controversial.     

Single cell oils of the cold-adapted oleaginous yeast <Emphasis Type="Italic">Rhodotorula glacialis</Emphasis> DBVPG 4785

Background  

The production of microbial lipids has attracted considerable interest during the past decade since they can be successfully used to produce biodiesel by catalyzed transesterification with short chain alcohols. Certain yeast species, including several psychrophilic isolates, are oleaginous and accumulate lipids from 20 to 70% of biomass under appropriate cultivation conditions. Among them, Rhodotorula glacialis is a psychrophilic basidiomycetous species capable to accumulate intracellular lipids.     

Extracellular heat shock protein 70 inhibits tumour necrosis factor-α induced proinflammatory mediator production in fibroblast-like synoviocytes

Introduction  

It was recently suggested that heat shock protein (HSP)70, an intracellular protein, is a potential mediator of inflammatory disease when it is released into the extracellular compartment. Although elevated HSP70 levels have been identified in rheumatoid arthritis (RA) synovial tissues and RA synovial fluid compared with patients with osteoarthritis and healthy individuals, it remains unclear what role extracellular HSP70 plays in the pathogenesis of RA. This study was conducted to investigate the effects of extracellular HSP70 on the production of RA-associated cytokines in fibroblast-like synoviocytes from patients with RA and to elucidate the mechanisms involved.     

Effect of Cu supplementation on genomic instability in chemically-induced mammary carcinogenesis in the rat

Backround  

The aim of the present study was to assess the effect of dietary supplementation (copper or copper and resveratrol) on the intensity of carcinogenesis and the frequency of microsatellite instability in a widely used model of mammary carcinogenesis induced in the rat by treatment with 7,12-dimethylbenz[a]anthracene (DMBA).     

Increased Plasma Levels of Heat Shock Protein 70 Associated with Subsequent Clinical Conversion to Mild Cognitive Impairment in Cognitively Healthy Elderly

Background and Aims

Heat shock proteins (HSPs) have been regarded as cytoprotectants that protect brain cells during the progression of neurodegenerative diseases and from damage resulting from cerebral ischemia. In this study, we assessed the association between plasma HSP 70/27 levels and cognitive decline.

Methods

Among participants in the community-based cohort study of dementia called the Gwangju Dementia and Mild Cognitive Impairment Study, subjects without cognitive impairment at baseline, who then either remained without impairment (non-conversion group), or suffered mild cognitive impairment (MCI) (conversion group) (non-conversion group, N = 36; conversion group, N = 30) were analyzed.

Results

After a five to six year follow-up period, comparison of the plasma HSP 70 and HSP 27 levels of the two groups revealed that only the plasma HSP 70 level was associated with a conversion to MCI after adjustments for age, gender, years of education, follow-up duration, APOE e4, hypertension, and diabetes (repeated measure analysis of variance: F = 7.59, p = 0.008). Furthermore, an increase in plasma HSP 70 level was associated with cognitive decline in language and executive function (linear mixed model: Korean Boston Naming Test, -0.426 [-0.781, -0.071], p = 0.019; Controlled Oral Word Association Test, -0.176 [-0.328, -0.023], p = 0.024; Stroop Test, -0.304 [-0.458, -0.150], p<0.001).

Conclusions

These findings suggest that the plasma HSP 70 level may be related to cognitive decline in the elderly.