Effect and fate of intravenously administered porphobilin in rats

Summary It rats after i.v. prophobilin, blood pressure and pulse rate remained stable, the animals were calm and moved freely with no symptoms or signs of nervous effect. Prophobilin was rapidly excreted in the urine.     

Apparent arylsulfatase A activity in excretory fluids

Summary Arylsulfatase activity has been demonstrated in rat and human parotid and submandibular saliva indicating that oral bacteria are not the only source of salivary sulfatase activity. Activity was also observed in human sweat, tears and in snake venom.Acknowledgments. We extent appreciation to Drs.C. Dawes andK. Abe for assistance in saliva collection, to Dr.K. W. Stewart who provided fresh snake venoms and to Dr.E. T. Pritchard in whose laboratory this study was conducted. Supported by grant Nr. MT 3536 from MRC of Canada.     

Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system

In the continuing search for effective treatments for cancer, the emerging model is the combination of traditional chemotherapy with anti-angiogenesis agents that inhibit blood vessel growth. However, the implementation of this strategy has faced two major obstacles. First, the long-term shutdown of tumour blood vessels by the anti-angiogenesis agent can prevent the tumour from receiving a therapeutic concentration of the chemotherapy agent. Second, inhibiting blood supply drives the intra-tumoural accumulation of hypoxia-inducible factor-1alpha (HIF1-alpha); overexpression of HIF1-alpha is correlated with increased tumour invasiveness and resistance to chemotherapy. Here we report the disease-driven engineering of a drug delivery system, a 'nanocell', which overcomes these barriers unique to solid tumours. The nanocell comprises a nuclear nanoparticle within an extranuclear pegylated-lipid envelope, and is preferentially taken up by the tumour. The nanocell enables a temporal release of two drugs: the outer envelope first releases an anti-angiogenesis agent, causing a vascular shutdown; the inner nanoparticle, which is trapped inside the tumour, then releases a chemotherapy agent. This focal release within a tumour results in improved therapeutic index with reduced toxicity. The technology can be extended to additional agents, so as to target multiple signalling pathways or distinct tumour compartments, enabling the model of an 'integrative' approach in cancer therapy.     

The optical afterglow of the short gamma-ray burst GRB 050709

It has long been known that there are two classes of gamma-ray bursts (GRBs), mainly distinguished by their durations. The breakthrough in our understanding of long-duration GRBs (those lasting more than approximately 2 s), which ultimately linked them with energetic type Ic supernovae, came from the discovery of their long-lived X-ray and optical 'afterglows', when precise and rapid localizations of the sources could finally be obtained. X-ray localizations have recently become available for short (duration <2 s) GRBs, which have evaded optical detection for more than 30 years. Here we report the first discovery of transient optical emission (R-band magnitude approximately 23) associated with a short burst: GRB 050709. The optical afterglow was localized with subarcsecond accuracy, and lies in the outskirts of a blue dwarf galaxy. The optical and X-ray afterglow properties 34 h after the GRB are reminiscent of the afterglows of long GRBs, which are attributable to synchrotron emission from ultrarelativistic ejecta. We did not, however, detect a supernova, as found in most nearby long GRB afterglows, which suggests a different origin for the short GRBs.     

A tiling resolution DNA microarray with complete coverage of the human genome

We constructed a tiling resolution array consisting of 32,433 overlapping BAC clones covering the entire human genome. This increases our ability to identify genetic alterations and their boundaries throughout the genome in a single comparative genomic hybridization (CGH) experiment. At this tiling resolution, we identified minute DNA alterations not previously reported. These alterations include microamplifications and deletions containing oncogenes, tumor-suppressor genes and new genes that may be associated with multiple tumor types. Our findings show the need to move beyond conventional marker-based genome comparison approaches, that rely on inference of continuity between interval markers. Our submegabase resolution tiling set for array CGH (SMRT array) allows comprehensive assessment of genomic integrity and thereby the identification of new genes associated with disease.     

Systematic distortions in world fisheries catch trends.

Over 75% of the world marine fisheries catch (over 80 million tonnes per year) is sold on international markets, in contrast to other food commodities (such as rice). At present, only one institution, the Food and Agriculture Organization of the United Nations (FAO) maintains global fisheries statistics. As an intergovernmental organization, however, FAO must generally rely on the statistics provided by member countries, even if it is doubtful that these correspond to reality. Here we show that misreporting by countries with large fisheries, combined with the large and widely fluctuating catch of species such as the Peruvian anchoveta, can cause globally spurious trends. Such trends influence unwise investment decisions by firms in the fishing sector and by banks, and prevent the effective management of international fisheries.