Rapid Fishery Assessment by Market Survey (RFAMS) – An Improved Rapid-Assessment Approach to Characterising Fish Landings in Developing Countries

The complex multi-gear, multi-species tropical fisheries in developing countries are poorly understood and characterising the landings from these fisheries is often impossible using conventional approaches. A rapid assessment method for characterising landings at fish markets, using an index of abundance and estimated weight within taxonomic groups, is described. This approach was developed for contexts where there are no detailed data collection protocols, and where consistent data collection across a wide range of fisheries types and geographic areas is required, regardless of the size of the site and scale of the landings. This methodology, which was demonstrated at seven fish landing sites/fish markets in southern Indonesia between July 2008 and January 2011, provides a rapid assessment of the abundance and diversity in the wild catch over a wide variety of taxonomic groups. The approach has wider application for species-rich fisheries in developing countries where there is an urgent need for better data collection protocols, monitoring future changes in market demographics, and evaluating health of fisheries.     

Probing the Tumor Suppressor Function of BAP1 in CRISPR-Engineered Human Liver Organoids

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Design and visualization of second‐generation cyanoisoindole‐based fluorescent strigolactone analogs

Strigolactones (SLs) are a family of terpenoid allelochemicals that were recognized as plant hormones only a decade ago. They influence a myriad of both above‐ and below‐ground developmental processes, and are an important survival strategy for plants in nutrient‐deprived soils. A rapidly emerging approach to gain knowledge on hormone signaling is the use of traceable analogs. A unique class of labeled SL analogs was constructed, in which the original tricyclic lactone moiety of natural SLs is replaced by a fluorescent cyanoisoindole ring system. Biological evaluation as parasitic seed germination stimulant and hypocotyl elongation repressor proved the potency of the cyanoisoindole strigolactone analogs (CISAs) to be comparable to the commonly accepted standard GR24. Additionally, via a SMXL6 protein degradation assay, we provided molecular evidence that the compounds elicit SL‐like responses through the natural signaling cascade. All CISAs were shown to exhibit fluorescent properties, and the high quantum yield and Stokes shift of the pyrroloindole derivative CISA‐7 also enabled in vivo visualization in plants. In contrast to the previously reported fluorescent analogs, CISA‐7 displays a large similarity in shape and structure with natural SLs, which renders the analog a promising tracer to investigate the spatiotemporal distribution of SLs in plants and fungi.     

Targets,models and challenges in osteoarthritis research

Osteoarthritis is a chronic degenerative disorder of the joint and represents one of the most common diseases worldwide. Its prevalence and severity are increasing owing to aging of the population, but treatment options remain largely limited to painkillers and anti-inflammatory drugs, which only provide symptomatic relief. In the late stages of the disease, surgical interventions are often necessary to partially restore joint function. Although the focus of osteoarthritis research has been originally on the articular cartilage, novel findings are now pointing to osteoarthritis as a disease of the whole joint, in which failure of different joint components can occur. In this Review, we summarize recent progress in the field, including data from novel ‘omics’ technologies and from a number of preclinical and clinical trials. We describe different in vitro and in vivo systems that can be used to study molecules, pathways and cells that are involved in osteoarthritis. We illustrate that a comprehensive and multisystem approach is necessary to understand the complexity and heterogeneity of the disease and to better guide the development of novel therapeutic strategies for osteoarthritis.KEY WORDS: Osteoarthritis, Cartilage, Bone, Animal models     

Progress in spondylarthritis. Mechanisms of new bone formation in spondyloarthritis

Targeted therapies that neutralize tumour necrosis factor are often able to control the signs and symptoms of spondyloarthritis. However, recent animal model data and clinical observations indicate that control of inflammation may not be sufficient to impede disease progression toward ankylosis in these patients. Bone morphogenetic proteins and WNTs (wingless-type like) are likely to play an important role in ankylosis and could be therapeutic targets. The relationship between inflammation and new bone formation is still unclear. This review summarizes progress made in our understanding of ankylosis and offers an alternative view of the relationship between inflammation and ankylosis.     

Synthesis and biological evaluation of 11C-labeled β-galactosyl triazoles as potential PET tracers for in vivo LacZ reporter gene imaging

In our aim to develop LacZ reporter probes with a good retention in LacZ expressing cells, we report the synthesis and preliminary evaluation of two carbon-11 labeled β-galactosyl triazoles 1-(β-d-galactopyranosyl)-4-(p-[¹¹C]methoxyphenyl)-1,2,3-triazole ([¹¹C]-6) and 1-(β-d-galactopyranosyl)-4-(6-[¹¹C]methoxynaphthyl)-1,2,3-triazole ([¹¹C]-13). The precursors for the radiolabeling and the non-radioactive analogues (6 and 13) were synthesized using straightforward ‘click’ chemistry. In vitro incubation experiments of 6 with β-galactosidase in the presence of o-nitrophenyl β-d-galactopyranoside (ONPG) showed that the triazolic compound was an inhibitor of β-galactosidase activity. Radiolabeling of both precursors was performed using [¹¹C]methyl iodide as alkylating agent at 70 °C in DMF in the presence of a small amount of base. The log P values were ?0.1 and 1.4, respectively, for [¹¹C]-6 and [¹¹C]-13, the latter therefore being a good candidate for increased cellular uptake via passive diffusion. Biodistribution studies in normal mice showed a good clearance from blood for both tracers. [¹¹C]-6 was mainly cleared via the renal pathway, while the more lipophilic [¹¹C]-13 was excreted almost exclusively via the hepatobiliary system. Despite the lipophilicity of [¹¹C]-13, no brain uptake was observed. Reversed phase HPLC analysis of murine plasma and urine revealed high in vivo stability for both tracers. In vitro evaluation in HEK-293T cells showed an increased cell uptake for the more lipophilic [¹¹C]-13, however, there was no statistically higher uptake in LacZ expressing cells compared to control cells.