Determination of composition and structure of spongy bone tissue in human head of femur by Raman spectral mapping

Biomechanical properties of bone depend on the composition and organization of collagen fibers. In this study, Raman microspectroscopy was employed to determine the content of mineral and organic constituents and orientation of collagen fibers in spongy bone in the human head of femur at the microstructural level. Changes in composition and structure of trabecula were illustrated using Raman spectral mapping. The polarized Raman spectra permit separate analysis of local variations in orientation and composition. The ratios of ν2PO43−/Amide III, ν4PO43−/Amide III and ν1CO32−/ν2PO43− are used to describe relative amounts of spongy bone components. The ν1PO43−/Amide I ratio is quite susceptible to orientation effect and brings information on collagen fibers orientation. The results presented illustrate the versatility of the Raman method in the study of bone tissue. The study permits better understanding of bone physiology and evaluation of the biomechanical properties of bone

A Novel Xenogeneic Co-Culture System to Examine Neuronal Differentiation Capability of Various Adult Human Stem Cells

Background: Targeted differentiation of stem cells is mainly achieved by the sequential administration of defined growth factors and cytokines, although these approaches are quite artificial, cost-intensive and time-consuming. We now present a simple xenogeneic rat brain co-culture system which supports neuronal differentiation of adult human stem cells under more in vivo-like conditions. Methods and Findings: This system was applied to well-characterized stem cell populations isolated from human skin, parotid gland and pancreas. In addition to general multi-lineage differentiation potential, these cells tend to differentiate spontaneously into neuronal cell types in vitro and are thus ideal candidates for the introduced co-culture system. Consequently, after two days of co-culture up to 12% of the cells showed neuronal morphology and expressed corresponding markers on the mRNA and protein level. Additionally, growth factors with the ability to induce neuronal different iation in stem cells could be found in the media supernatants of the co-cultures. Conclusions: The co-culture system described here is suitable for testing neuronal differentiation capability of numerous types of stem cells. Especially in the case of human cells, it may be of clinical relevance for future cell-based therapeutic applications

Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists

BACKGROUND: Cytokine production is critical in ischemia/reperfusion (IR) injury. Acetylcholine binds to macrophages and inhibits cytokine synthesis, through the cholinergic anti-inflammatory pathway. This study examined the role of the cholinergic pathway in cytokine production and hepatic IR- injury. METHODS: Adult male mice underwent 90-min of partial liver ischemia followed by reperfusion. The AChR agonists (1,1-dimethyl-4-phenyl-L-pioperazinium-iodide [DMPP], and nicotine) or saline-vehicle were administered i.p. before ischemia. Plasma cytokine tumor necrosis factor (TNF)-α, macrophage inflammatory protein-2, and Interleukin-6 were measured. Liver injury was assessed by plasma alanine transaminase (ALT) and liver histopathology. RESULTS: A reperfusion time-dependent hepatocellular injury occurred as was indicated by increased plasma-ALT and histopathology. The injury was associated with marked elevation of plasma cytokines/chemokines. Pre-ischemic treatment of mice with DMPP or nicotine significantly decreased plasma-ALT and cytokines after 3 h of reperfusion. After 6 h of reperfusion, the protective effect of DMPP decreased and reached a negligible level by 24 h of reperfusion, despite significantly low levels of plasma cytokines. Histopathology showed markedly diminished hepatocellular injury in DMPP- and nicotine-pretreated mice during the early-phase of hepatic-IR, which reached a level comparable to saline-treated mice at late-phase of IR. CONCLUSION: Pharmacological modulation of the cholinergic pathway provides a means to modulate cytokine production and to delay IR-induced heaptocellular injury

Sex-specific regulation of chemokine Cxcl5/6 controls neutrophil recruitment and tissue injury in acute inflammatory states

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Barts and The London Trustees Studentship (SM), Marie Curie fellowships (MB, JD), Arthritis Research UK career development fellowship (JW), William Harvey Research Foundation grant (JW/RSS), Kidney Research UK fellowship (NSAP), Barts and The London Vacation Scholarship (ISN), Wellcome Trust senior fellowship (DWG), and a Wellcome Trust career development fellowship (RSS). This work forms part of the research themes contributing to the translational research portfolio of Barts and The London Cardiovascular Biomedical Research Unit, which is supported and funded by National Institute for Health Researc

Consumer input into research: the Australian Cancer Trials website

<p>Abstract</p> <p>Background</p> <p>The Australian Cancer Trials website (ACTO) was publicly launched in 2010 to help people search for cancer clinical trials recruiting in Australia, provide information about clinical trials and assist with doctor-patient communication about trials. We describe consumer involvement in the design and development of ACTO and report our preliminary patient evaluation of the website.</p> <p>Methods</p> <p>Consumers, led by Cancer Voices NSW, provided the impetus to develop the website. Consumer representative groups were consulted by the research team during the design and development of ACTO which combines a search engine, trial details, general information about trial participation and question prompt lists. Website use was analysed. A patient evaluation questionnaire was completed at one hospital, one week after exposure to the website.</p> <p>Results</p> <p>ACTO's main features and content reflect consumer input. In February 2011, it covered 1, 042 cancer trials. Since ACTO's public launch in November 2010, until the end of February 2011, the website has had 2, 549 new visits and generated 17, 833 page views. In a sub-study of 47 patient users, 89% found the website helpful for learning about clinical trials and all respondents thought patients should have access to ACTO.</p> <p>Conclusions</p> <p>The development of ACTO is an example of consumers working with doctors, researchers and policy makers to improve the information available to people whose lives are affected by cancer and to help them participate in their treatment decisions, including consideration of clinical trial enrolment. Consumer input has ensured that the website is informative, targets consumer priorities and is user-friendly. ACTO serves as a model for other health conditions.</p

Characterization of Granulations of Calcium and Apatite in Serum as Pleomorphic Mineralo-Protein Complexes and as Precursors of Putative Nanobacteria

Calcium and apatite granulations are demonstrated here to form in both human and fetal bovine serum in response to the simple addition of either calcium or phosphate, or a combination of both. These granulations are shown to represent precipitating complexes of protein and hydroxyapatite (HAP) that display marked pleomorphism, appearing as round, laminated particles, spindles, and films. These same complexes can be found in normal untreated serum, albeit at much lower amounts, and appear to result from the progressive binding of serum proteins with apatite until reaching saturation, upon which the mineralo-protein complexes precipitate. Chemically and morphologically, these complexes are virtually identical to the so-called nanobacteria (NB) implicated in numerous diseases and considered unusual for their small size, pleomorphism, and the presence of HAP. Like NB, serum granulations can seed particles upon transfer to serum-free medium, and their main protein constituents include albumin, complement components 3 and 4A, fetuin-A, and apolipoproteins A1 and B100, as well as other calcium and apatite binding proteins found in the serum. However, these serum mineralo-protein complexes are formed from the direct chemical binding of inorganic and organic phases, bypassing the need for any biological processes, including the long cultivation in cell culture conditions deemed necessary for the demonstration of NB. Thus, these serum granulations may result from physiologically inherent processes that become amplified with calcium phosphate loading or when subjected to culturing in medium. They may be viewed as simple mineralo-protein complexes formed from the deployment of calcification-inhibitory pathways used by the body to cope with excess calcium phosphate so as to prevent unwarranted calcification. Rather than representing novel pathophysiological mechanisms or exotic lifeforms, these results indicate that the entities described earlier as NB most likely originate from calcium and apatite binding factors in the serum, presumably calcification inhibitors, that upon saturation, form seeds for HAP deposition and growth. These calcium granulations are similar to those found in organisms throughout nature and may represent the products of more general calcium regulation pathways involved in the control of calcium storage, retrieval, tissue deposition, and disposal

Fungal microbiomes are determined by host phylogeny and exhibit widespread associations with the bacterial microbiome

Interactions between hosts and their resident microbial communities are a fundamental component of fitness for both agents. Though recent research has highlighted the importance of interactions between animals and their bacterial communities, comparative evidence for fungi is lacking, especially in natural populations. Using data from 49 species, we present novel evidence of strong covariation between fungal and bacterial communities across the host phylogeny, indicative of recruitment by hosts for specific suites of microbes. Using co-occurrence networks, we demonstrate that fungi form critical components of putative microbial interaction networks, where the strength and frequency of interactions varies with host taxonomy. Host phylogeny drives differences in overall richness of bacterial and fungal communities, but the effect of diet on richness was only evident in mammals and for the bacterial microbiome. Collectively these data indicate fungal microbiomes may play a key role in host fitness and suggest an urgent need to study multiple agents of the animal microbiome to accurately determine the strength and ecological significance of host-microbe interactions. SIGNIFICANCE STATEMENT Microbes perform vital metabolic functions that shape the physiology of their hosts. However, almost all research to date in wild animals has focused exclusively on the bacterial microbiota, to the exclusion of other microbial groups. Although likely to be critical components of the host microbiome, we have limited knowledge of the drivers of fungal composition across host species. Here we show that fungal community composition is determined by host species identity and phylogeny, and that fungi form extensive interaction networks with bacteria in the microbiome of a diverse range of animal species. This highlights the importance of microbial interactions as mediators of microbiome-health relationships in the wild