Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban

Molecular etiologies of heart failure, an emerging cardiovascular epidemic affecting 4.7 million Americans and costing 17.8 billion health-care dollars annually, remain poorly understood. Here we report that an inherited human dilated cardiomyopathy with refractory congestive heart failure is caused by a dominant Arg --> Cys missense mutation at residue 9 (R9C) in phospholamban (PLN), a transmembrane phosphoprotein that inhibits the cardiac sarcoplasmic reticular Ca2+-adenosine triphosphatase (SERCA2a) pump. Transgenic PLN(R9C) mice recapitulated human heart failure with premature death. Cellular and biochemical studies revealed that, unlike wild-type PLN, PLN(R9C) did not directly inhibit SERCA2a. Rather, PLN(R9C) trapped protein kinase A (PKA), which blocked PKA-mediated phosphorylation of wild-type PLN and in turn delayed decay of calcium transients in myocytes. These results indicate that myocellular calcium dysregulation can initiate human heart failure-a finding that may lead to therapeutic opportunities.     

Ciliary photoreceptors with a vertebrate-type opsin in an invertebrate brain

For vision, insect and vertebrate eyes use rhabdomeric and ciliary photoreceptor cells, respectively. These cells show distinct architecture and transduce the light signal by different phototransductory cascades. In the marine rag-worm Platynereis, we find both cell types: rhabdomeric photoreceptor cells in the eyes and ciliary photoreceptor cells in the brain. The latter use a photopigment closely related to vertebrate rod and cone opsins. Comparative analysis indicates that both types of photoreceptors, with distinct opsins, coexisted in Urbilateria, the last common ancestor of insects and vertebrates, and sheds new light on vertebrate eye evolution.     

Lipopeptide Antibiotics Produced by the Engineered Strain Bacillus subtilis GEB3 and Detection of Its Bioactivity

MALDI-TOF-MS technology was used for identification of lipopeptide antibiotics produced by GEB3 strain,a derivative of Bacillus subtilis 168 which was transformed by lpaB3gene.The result showed GEB3 only produced lipopeptide antibiotic surfactin.The analysis by LC-MS demonstrated that GEB3 produced standard surfactin isoforms with side chain lengths of 13,14 and 15 carbon atoms.The bioactivity detection of surfactin indicated that the surfactin produced by GEB3 had inhibition effect on plant pathogens Rhizoctonia solani and Pyricularia oryzae.     

High-probability uniquantal transmission at excitatory synapses in barrel cortex

The number of vesicles released at excitatory synapses and the number of release sites per synaptic connection are key determinants of information processing in the cortex, yet they remain uncertain. Here we show that the number of functional release sites and the number of anatomically identified synaptic contacts are equal at connections between spiny stellate and pyramidal cells in rat barrel cortex. Moreover, our results indicate that the amount of transmitter released per synaptic contact is independent of release probability and the intrinsic release probability is high. These properties suggest that connections between layer 4 and layer 2/3 are tuned for reliable transmission of spatially distributed, timing-based signals.     

The calicheamicin gene cluster and its iterative type I enediyne PKS

The enediynes exemplify nature's ingenuity. We have cloned and characterized the biosynthetic locus coding for perhaps the most notorious member of the nonchromoprotein enediyne family, calicheamicin. This gene cluster contains an unusual polyketide synthase (PKS) that is demonstrated to be essential for enediyne biosynthesis. Comparison of the calicheamicin locus with the locus encoding the chromoprotein enediyne C-1027 reveals that the enediyne PKS is highly conserved among these distinct enediyne families. Contrary to previous hypotheses, this suggests that the chromoprotein and nonchromoprotein enediynes are generated by similar biosynthetic pathways.     

Slow fertilization of stickleback eggs: the result of sexual conflict?

Background  

The fertilization success in sperm competition in externally fertilizing fish depends on number and quality of sperm. The time delay between sequential ejaculations may further influence the outcome of sperm competition. Such a time interval can load the raffle over fertilization if fertilization takes place very fast. Short fertilization times are generally assumed for externally fertilizing fish such as the three-spined stickleback (Gasterosteus aculeatus). In this pair-spawning fish, territorial males often try to steal fertilizations in nests of neighbouring males. This sneaking behaviour causes sperm competition. Sneakers will only get a share of paternity when eggs are not fertilized immediately after sperm release. Contrary to males, females may be interested in multiple paternity of their clutch of eggs. There thus may be a sexual conflict over the speed of fertilization.     

Contagious bovine pleuropneumonia (CBPP) caused by vaccine strain T1/44 of Mycoplasma mycoides subsp. mycoides SC

A study was carried out on four adult cattle to assess the pathogenicity of Mycoplasma mycoides subsp. mycoides SC strain T1/44, currently used as a vaccine for the control of contagious bovine pleuropneumonia (CBPP) in Namibia. Post mortem examination 9 weeks after endobronchial inoculation of the vaccine strain to three of the four animals revealed unilateral pleuropneumonic lesions, pleuritis and well-developed sequesters in two of the three inoculated animals and several small sequesters surrounded by pleuropneumonic lesions in the diaphragmatic and apical lobes in one animal. The fourth animal, which was not directly inoculated but was in close contact with the inoculated animals, revealed only an adhesion area of the lung to the ribcage. Serological examination carried out using the complement fixation test (CFT) detected positive titres in all three intubated animals and the indirect CBPP-LppQ-ELISA was positive for two of the three inoculated animals. The contact animal showed no seroconversion. M. mycoides subsp. mycoides SC was isolated from the sequesters of two of the inoculated animals. Isolation of mycoplasmas was not possible from the third inoculated animal due to heavy contamination of the samples by other bacteria, but the presence of M. mycoides subsp. mycoides SC could be evidenced by PCR from clinical samples. The identity of the T1/44 vaccine strain isolated from the sequesters of two animals was confirmed by T1/44-specific PCR analysis and by IS1296 typing using Southern blot. These results clearly show that inoculation of T1/44 vaccine via the endobronchial route can lead to CBPP.