Ultraviolet Irradiation Induces the Accumulation of Chondroitin Sulfate, but Not Other Glycosaminoglycans, in Human Skin

Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV

Mast cell glycosaminoglycans

Mast cells contain granules packed with a mixture of proteins that are released on degranulation. The proteoglycan serglycin carries an array of glycosaminoglycan (GAG) side chains, sometimes heparin, sometimes chondroitin or dermatan sulphate. Tight packing of granule proteins is dependent on the presence of serglycin carrying these GAGs. The GAGs of mast cells were most intensively studied in the 1970s and 1980s, and though something is known about the fine structure of chondroitin sulphate and dermatan sulphate in mast cells, little is understood about the composition of the heparin/heparan sulphate chains. Recent emphasis on the analysis of mast cell heparin from different species and tissues, arising from the use of this GAG in medicine, lead to the question of whether variations within heparin structures between mast cell populations are as significant as variations in the mix of chondroitins and heparins

Offline 2, ISOLDE’s target, laser and beams development facility

Offline 2 is an entirely new research and development mass separator laboratory for the ISOLDE facility located on the Meyrin site of CERN. It closely resembles beam production (for non-radioactive beams) of the on-line (radioactive) systems at ISOLDE with machine versatility and flexibility at the core of its design. The beam optics and down stream beam preparation can deliver bunched beams or continuous beams of negative or positive ions with kinetic energies up to 60 keV. The mass resolving power of the separator operating with a typical ISOLDE ion source is $R$∼500 . All of this is housed within a highly accessible 125 m $^{2}$ work area with multiple beam optics instruments to determine the beam quality, quantify modifications, develop new technologies and create alternate beam tunes, with the purpose of improving the beams and targets used during on-line operations

A new fast time of flight detector for single ion counting to high flux radioactive beams at ISOLDE

Beam diagnostics at the Isotope Separator On-Line DEvice (ISOLDE) consists mainly of wire SCanners and Faraday Cups (FC) coupled to charge sensitive picoammeters. Presented here is the design, simulations, and results of a new FC combined Secondary Electron Emission (SEE) multiplication detector for the beam energies found at ISOLDE (up to 60 keV). It expands the region of sensitivity from the current noise limit (≃0.25 pA) to individual ion counting. The detector is capable of counting rates of 105 ion ms−1 (≃10 pA) for DC or bunched beams with a high sensitivity timing resolution of σt = 0.10 ± 0.03 ns for individual ions. The device also operates as a conventional FC with integrated current measurements on the SEE plate for non-time sensitive operation with efficiency ε = 94% ± 1%. The detector was tested both at the ISOLDE Offline 2 facility and the high resolution separator beam line at the ISOLDE on-line facility where bunched and DC beams from ISCOOL were used

Adapting forest health assessments to changing perspectives on threats – a case example from Sweden

A revised Swedish forest health assessment system is presented. The assessment system is composed of several interacting components which target information needs for strategic and operational decision making and accommodate a continuously expanding knowledge base. The main motivation for separating information for strategic and operational decision making is that major damage outbreaks are often scattered throughout the landscape. Generally, large-scale inventories (such as national forest inventories) cannot provide adequate information for mitigation measures. In addition to broad monitoring programs that provide time-series information on known damaging agents and their effects, there is also a need for local and regional inventories adapted to specific damage events. While information for decision making is the major focus of the health assessment system, the system also contributes to expanding the knowledge base of forest conditions. For example, the integrated monitoring programs provide a better understanding of ecological processes linked to forest health. The new health assessment system should be able to respond to the need for quick and reliable information and thus will be an important part of the future monitoring of Swedish forests

Identification of potent biodegradable adjuvants that efficiently break self-tolerance--a key issue in the development of therapeutic vaccines

Monoclonal antibodies are used successfully in the treatment of many human disorders. However, these antibodies are expensive and have in many countries put a major strain on the health care economy. Therapeutic vaccines, directed against the same target molecules, may offer a solution to this problem. Vaccines usually involve lower amount of recombinant protein, approximately 10,000-20,000 times less, which is significantly more cost effective. Attempts to develop such therapeutic vaccines have also been made. However, their efficacy has been limited by the lack of potent immunostimulatory compounds, adjuvants, for human use. To address this problem we have conducted a broad screening for adjuvants that can enhance the efficacy of therapeutic vaccines, whilst at the same time being non-toxic and biodegradable. We have now identified adjuvants that show these desired characteristics. A combination of Montanide ISA720 and phosphorothioate stabilized CpG stimulatory DNA, induced similar or even higher anti-self-antibody titers compared to Freund's adjuvant, currently the most potent, but also toxic, adjuvant available. This finding removes one of the major limiting factors in the field and facilitates the development of a broad range of novel therapeutic vaccines