ß1/ß2/ß3-adrenoceptor knockout mice are obese and cold-sensitive but have normal lipolytic responses to fasting

Catecholamines are viewed as major stimulants of diet- and cold-induced thermogenesis and of fasting-induced lipolysis, through the β-adrenoceptors (β1/β2/β3). To test this hypothesis, we generated β1/β2/β3-adrenoceptor triple knockout (TKO) mice and compared them to wild type animals. TKO mice exhibited normophagic obesity and cold-intolerance. Their brown fat had impaired morphology and lacked responses to cold of uncoupling protein-1 expression. In contrast, TKO mice had higher circulating levels of free fatty acids and glycerol at basal and fasted states, suggesting enhanced lipolysis. Hence, β-adrenergic signalling is essential for the resistance to obesity and cold, but not for the lipolytic response to fasting.

Evolution in a cold climate

A brief appraisal of marine fossils from high latitudes and episodically cold climate especially in east Australia and New Zealand during Late Palaeozoic and Early Mesozoic times shows patterns of evolution and survival that differ from those adduced for the palaeotropics and Northern Hemisphere. Examples taken from amongst phyla Scyphozoa, Bryozoa, Brachiopoda and Classes Bivalvia and Class Cephalopoda suggest these attributes:
1. Evolution and demise of species and genera proceeded at a rate close to that known for palaeotropical and Northern Hemisphere macro-invertebrates, but involved fewer families and orders.
2. Possibly, intraspecific variation was greater amongst southern palaeohemisphere Permian species than in those of the Permian palaeotropics.
3. There was no proven diminution of life at the end of the Guadalupian (Middle Permian) at southern high latitudes, where however the fossil record is meagre for this interval. Younger Wuchiapingian and Changhsingian faunas were moderately diverse.
4. There is no evidence for a high latitude Southern Hemisphere anoxic event in the Early Triassic despite claims of a world-wide anoxic interval. Nor has any substantial volcanic eruption or bolide impact left any marked traces in the sedimentary record.
5. As a consequence, some major groups such as Bryozoa and Conulariida (Staurozoa) survived the end- Permian extinction shock in the Southern Hemisphere.
6. Other major groups appear to have survived better in the south than in the north, notably, mollusc Bivalvia and Cephalopoda. It therefore appears likely that Triassic seas were restocked substantially from the Southern Hemisphere and that the Permian extinction shock was asymmetric with respect to latitudes in its distribution and affect.

PTEX is an essential nexus for protein export in malaria parasites

During the blood stages of malaria, several hundred parasite-encoded proteins are exported beyond the double-membrane barrier that separates the parasite from the host cell cytosol. These proteins have a variety of roles that are essential to virulence or parasite growth. There is keen interest in understanding how proteins are exported and whether common machineries are involved in trafficking the different classes of exported proteins. One potential trafficking machine is a protein complex known as the Plasmodium translocon of exported proteins (PTEX). Although PTEX has been linked to the export of one class of exported proteins, there has been no direct evidence for its role and scope in protein translocation. Here we show, through the generation of two parasite lines defective for essential PTEX components (HSP101 or PTEX150), and analysis of a line lacking the non-essential component TRX2 (ref. 12), greatly reduced trafficking of all classes of exported proteins beyond the double membrane barrier enveloping the parasite. This includes proteins containing the PEXEL motif (RxLxE/Q/D) and PEXEL-negative exported proteins (PNEPs). Moreover, the export of proteins destined for expression on the infected erythrocyte surface, including the major virulence factor PfEMP1 in Plasmodium falciparum, was significantly reduced in PTEX knockdown parasites. PTEX function was also essential for blood-stage growth, because even a modest knockdown of PTEX components had a strong effect on the parasite's capacity to complete the erythrocytic cycle both in vitro and in vivo. Hence, as the only known nexus for protein export in Plasmodium parasites, and an essential enzymic machine, PTEX is a prime drug target.