Hsp70/Hsp90 Organising Protein (Hop): Coordinating Much More than Chaperones.

The Hsp70/Hsp90 organising protein (Hop, also known as stress-inducible protein 1/STI1/STIP1) has received considerable attention for diverse cellular functions in both healthy and diseased states. There is extensive evidence that intracellular Hop is a co-chaperone of the major chaperones Hsp70 and Hsp90, playing an important role in the productive folding of Hsp90 client proteins, although recent evidence suggests that eukaryotic Hop is regulatory within chaperone complexes rather than essential. Consequently, Hop is implicated in many key signalling pathways, including aberrant pathways leading to cancer. Hop is also secreted, and it is now well established that Hop interacts with the prion protein, PrPC, to mediate multiple signalling events. The intracellular and extracellular forms of Hop most likely represent two different isoforms, although the molecular determinants of these divergent functions are yet to be identified. There is also a growing body of research that reports the involvement of Hop in cellular activities that appear independent of either chaperones or PrPC. While the various cellular functions of Hop have been described, its biological function remains elusive. However, recent knockout studies in mammals suggest that Hop has an important role in embryonic development. This review provides a critical overview of the latest molecular, cellular and biological research on Hop, critically evaluating its function in healthy systems and how this function is adapted in diseased states.

Hsp70/Hsp90 organising protein (hop): beyond interactions with chaperones and prion proteins.

The Hsp70/Hsp90 organising protein (Hop), also known as stress-inducible protein 1 (STI1), has received considerable attention for diverse cellular functions in both healthy and diseased states. There is extensive evidence that intracellular Hop is a co-chaperone of the major chaperones Hsp70 and Hsp90, playing an important role in the productive folding of Hsp90 client proteins. Consequently, Hop is implicated in a number of key signalling pathways, including aberrant pathways leading to cancer. However, Hop is also secreted and it is now well established that Hop also serves as a receptor for the prion protein, PrP(C). The intracellular and extracellular forms of Hop most likely represent two different isoforms, although the molecular determinants of these divergent functions are yet to be identified. There is also a growing body of research that reports the involvement of Hop in cellular activities that appear independent of either chaperones or PrP(C). While Hop has been shown to have various cellular functions, its biological function remains elusive. However, recent knockout studies in mammals suggest that Hop has an important role in embryonic development. This review provides a critical overview of the latest molecular, cellular and biological research on Hop, critically evaluating its function in healthy systems and how this function is adapted in diseases states.

The emerging role of PEDF in stem cell biology.

Encoded by a single gene, PEDF is a 50 kDa glycoprotein that is highly conserved and is widely expressed among many tissues. Most secreted PEDF deposits within the extracellular matrix, with cell-type-specific functions. While traditionally PEDF is known as a strong antiangiogenic factor, more recently, as this paper highlights, PEDF has been linked with stem cell biology, and there is now accumulating evidence demonstrating the effects of PEDF in a variety of stem cells, mainly in supporting stem cell survival and maintaining multipotency.

A comparison of macroscopic and microscopic hair color measurements and a quantification of the relationship between hair color and thickness.

Microscopic images of hair from 36 individuals were evaluated for color (using the CIE L*a*b* color space), hair thickness, and the pattern of pigmentation. These measurements were compared to each other and to reflective spectrophotometric measurements of macroscopic hair color. Three areas on three strands of hair were examined for each individual. Despite a large Delta E* value, there is a strong relationship between macroscopic and microscopic L* values that would be useful if one was trying to predict the color of a head of hair (macroscopic) from a strand (microscopic). A relationship between hair lightness (L*) and thickness is also found at both the macroscopic and microscopic levels. The information acquired in this study may be useful to those conducting a microscopic examination of hair, especially in forensic science, as well as those researchers investigating macroscopic hair color and hair morphology for the purposes of forensic science, anthropology, and medical science. Further investigation into objectively measuring and quantifying the microscopic color and properties of hair will assist in increasing its validity as evidence in forensic casework.

Hair color measurement and variation.

Pigmentation of hair in humans has been investigated by medical scientists, anthropologists and, more recently, by forensic scientists. In every investigation, hair color must first be defined by the researchers. Subjective color assessment inhibits the reproducibility of experiments and the direct comparison of results. The aim of this study was to objectively measure human hair color and examine the variation found in a population with European ancestry, using the CIE L*a*b* color space. Observer-perceived hair colors were compared with self-reported hair colors and the color as measured by reflective spectrophotometry of 132 subjects of European ancestry. The presented data show that self-reported hair colors and observer-reported colors are similar; however, these categories are not necessarily the best way to categorize hair color for quantitative research. Using a two-step cluster analysis, hair color can be divided into categories or clusters based on spectrophotometric measurements in the CIE L*a*b* color space and these clusters can be well discriminated from each other. This separation is primarily based on the b* (yellow) color component and the clusters show agreement to observer-reported colors. This study illustrates the possibilities for and necessity of objectively defining the hair color phenotype for various downstream applications.

Alginate Bead-Encapsulated PEDF Induces Ectopic Bone Formation In Vivo in the Absence of Co-Administered Mesenchymal Stem Cells.

BACKGROUND: Bone defects can be severely debilitating and reduce quality of life. Osteoregeneration can alleviate some of the complications in bony defects. For therapeutic use in future, a single factor that can cause potent bone regeneration is highly preferred as it will be more costeffective, any off-target effects will be more easily monitored and potentially managed, and for ease of administration which would lead to better patient compliance and satisfaction. OBJECTIVE: We demonstrate that pigment epithelium-derived factor (PEDF), one such factor that is known to be potent against angiogenesis, promotes osteoblastogenesis in mesenchymal stem cells in vitro, but does not need co-encapsulation of cells in alginate bead scaffolds for osteogeneration in vivo. RESULTS: Osteogenic differentiation by PEDF in vitro was confirmed with immunoblotting and immunocytochemical staining for bone markers (alkaline phosphatase, osteocalcin, osteopontin, collagen I), calcified mineral deposition, and assay for alkaline phosphatase activity. PEDF-mediated bone formation in a muscle pocket in vivo model was confirmed by microcomputed tomography (microCT), histology (haematoxylin and eosin, Alcian blue staining), immunostaining for bone markers and for collagen I-processing proteins (heat shock protein 47 and membrane type I matrix metalloproteinase). CONCLUSION: PEDF therefore presents itself as a promising biological for osteogeneration.

Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: comparison with osteosarcoma cells.

OBJECTIVE: Doxorubicin (Dox) is a frontline chemotherapeutic against osteosarcoma (OS) that is plagued by side effects, particularly in the heart. The specific objective of this article is to investigate whether low-dose Dox treatment had pro-autophagic effects in cardiomyocytes as well as osteosarcoma cells. METHODS: This study characterises apoptotic (Bax) and autophagic (Beclin-1) biomarker levels in human OS and cardiomyocyte cell lines as well as in various tissues when mice are exposed to low (1 mg/kg, thrice weekly) and high (3 mg/kg thrice weekly) dose Dox for a month. KEY FINDINGS: There was a decrease in Bax and increase in Beclin-1 in cardiac tissue in the high-dose group. Dox decreased Beclin-1 in the skin and liver, with no clear indication in the stomach, small intestine and testis. At low Dox doses of 10 and 100 nm in cardiomyocytes and OS cells, there is a pro-apoptotic effect, with a quicker response in the 100-nm condition, and a slower but steady increase of a pro-apoptotic response at the lower 10-nm dose. However, electron microscopy images revealed changes to human OS cells that resembled autophagy. Human prostate, breast and colorectal cells treated with 10-nm Dox showed ∼ 40% reduction in cell viability after 24 h. CONCLUSION: In culture, cells of both cardiomyocytes and OS revealed a predominant pro-apoptotic response at the expense of autophagy, although both seemed to be occurring in vivo.

Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy.

Pigment epithelium-derived factor (PEDF) is a pluripotent glycoprotein belonging to the serpin family. PEDF can stimulate several physiological processes such as angiogenesis, cell proliferation, and survival. Oxidative stress plays an important role in the occurrence of diabetic retinopathy (DR), which is the major cause of blindness in young diabetic adults. PEDF plays a protective role in DR and there is accumulating evidence of the neuroprotective effect of PEDF. In this paper, we review the role of PEDF and the mechanisms involved in its antioxidative, anti-inflammatory, and neuroprotective properties.

A comparison of hair colour measurement by digital image analysis with reflective spectrophotometry.

While reflective spectrophotometry is an established method for measuring macroscopic hair colour, it can be cumbersome to use on a large number of individuals and not all reflective spectrophotometry instruments are easily portable. This study investigates the use of digital photographs to measure hair colour and compares its use to reflective spectrophotometry. An understanding of the accuracy of colour determination by these methods is of relevance when undertaking specific investigations, such as those on the genetics of hair colour. Measurements of hair colour may also be of assistance in cases where a photograph is the only evidence of hair colour available (e.g. surveillance). Using the CIE L(*)a(*)b(*) colour space, the hair colour of 134 individuals of European ancestry was measured by both reflective spectrophotometry and by digital image analysis (in V++). A moderate correlation was found along all three colour axes, with Pearson correlation coefficients of 0.625, 0.593 and 0.513 for L(*), a(*) and b(*) respectively (p-values=0.000), with means being significantly overestimated by digital image analysis for all three colour components (by an average of 33.42, 3.38 and 8.00 for L(*), a(*) and b(*) respectively). When using digital image data to group individuals into clusters previously determined by reflective spectrophotometric analysis using a discriminant analysis, individuals were classified into the correct clusters 85.8% of the time when there were two clusters. The percentage of cases correctly classified decreases as the number of clusters increases. It is concluded that, although more convenient, hair colour measurement from digital images has limited use in situations requiring accurate and consistent measurements.

Investigation of telomere lengths measurement by quantitative real-time PCR to predict age.

Currently DNA profiling methods only compare a suspect's DNA with DNA left at the crime scene. When there is no suspect, it would be useful for the police to be able to predict what the person of interest looks like by analysing the DNA left behind in a crime scene. Determination of the age of the suspect is an important factor in creating an identikit. Human somatic cells gradually lose telomeric repeats with age. This study investigated if one could use a correlation between telomere length and age, to predict the age of an individual from their DNA. Telomere length, in buccal cells, of 167 individuals aged between 1 and 96 years old was measured using real-time quantitative PCR. Telomere length decreased with age (r=-0.185, P<0.05) and the age of an individual could be roughly determined by the following formula: (age=relative telomere length -1.5/-0.005). The regression (R(2)) value between telomere length and age was approximately 0.04, which is too low to be use for forensics. The causes for the presence of large variation in telomere lengths in the population were further investigated. The age prediction accuracies were low even after dividing samples into non-related Caucasians, males and females (5%, 9% and 1%, respectively). Mean telomere lengths of eight age groups representing each decade of life showed non-linear decrease in telomere length with age. There were variations in telomere lengths even among similarly aged individuals aged 26 years old (n=10) and age 54 years old (n=9). Therefore, telomere length measurement by real-time quantitative PCR cannot be used to predict age of a person, due to the presence of large inter-individual variations in telomere lengths.