Peroxisome division in the yeast Yarrowia lipolytica is regulated by a signal from inside the peroxisome

We describe an unusual mechanism for organelle division. In the yeast Yarrowia lipolytica, only mature peroxisomes contain the complete set of matrix proteins. These mature peroxisomes assemble from several immature peroxisomal vesicles in a multistep pathway. The stepwise import of distinct subsets of matrix proteins into different immature intermediates along the pathway causes the redistribution of a peroxisomal protein, acyl-CoA oxidase (Aox), from the matrix to the membrane. A significant redistribution of Aox occurs only in mature peroxisomes. Inside mature peroxisomes, the membrane-bound pool of Aox interacts with Pex16p, a membrane-associated protein that negatively regulates the division of early intermediates in the pathway. This interaction inhibits the negative action of Pex16p, thereby allowing mature peroxisomes to divide

Infrared spectroscopic studies of hydrogenated silicon clusters - guiding the search for Si₂H_x species in the Circumstellar Envelope of IRC+10216

Silicon-bearing species Si2Hx (x = 1-6) are probable candidates in the circumstellar envelope of IRC+ 10216. We have observed several fundamentals of new silicon-containing radicals Si2H3 and Si2H5 in addition to the well-known Si2H4 and Si2H6 species from infrared spectroscopy in low temperature silane matrices at 10 K. Several infrared bands identify the Si2Hx species and can be used to search for these molecules in the circumstellar envelope of IRC+ 10216. These infrared bands are confirmed by ab initio quantum chemical calculation as well as via corresponding infrared spectra detected for the deuterated species Si2Dx

Back to the Future: Studying Cholera Pathogenesis Using Infant Rabbits

Cholera is a severe diarrheal disease, caused by Vibrio cholerae, for which there has been no reproducible, nonsurgical animal model. Here, we report that orogastric inoculation of V. cholerae into 3-day-old rabbits pretreated with cimetidine led to lethal, watery diarrhea in virtually all rabbits. The appearance and chemical composition of the rabbit diarrheal fluid were comparable to those of the “rice-water stool” produced by cholera patients. As in humans, V. cholerae mutants that do not produce cholera toxin (CT) and toxin-coregulated pilus (TCP) did not induce cholera-like disease in rabbits. CT induced extensive exocytosis of mucin from intestinal goblet cells, and wild-type V. cholerae was predominantly found in close association with mucin. Large aggregates of mucin-embedded V. cholerae were observed, both attached to the epithelium and floating within the diarrheal fluid. These findings suggest that CT-dependent mucin secretion significantly influences V. cholerae’s association with the host intestine and its exit from the intestinal tract. Our model should facilitate identification and analyses of factors that may govern V. cholerae infection, survival, and transmission, such as mucin. In addition, our results using nontoxigenic V. cholerae suggest that infant rabbits will be useful for study of the reactogenicity of live attenuated-V. cholerae vaccines

Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia

The leukemogenic effects of Myc drive recurrent trisomy in a mouse model of acute myeloid leukemia

Plasticity of the Mycobacterium tuberculosis respiratory chain and its impact on tuberculosis drug development.

The viability of Mycobacterium tuberculosis (Mtb) depends on energy generated by its respiratory chain. Cytochrome bc1-aa3 oxidase and type-2 NADH dehydrogenase (NDH-2) are respiratory chain components predicted to be essential, and are currently targeted for drug development. Here we demonstrate that an Mtb cytochrome bc1-aa3 oxidase deletion mutant is viable and only partially attenuated in mice. Moreover, treatment of Mtb-infected marmosets with a cytochrome bc1-aa3 oxidase inhibitor controls disease progression and reduces lesion-associated inflammation, but most lesions become cavitary. Deletion of both NDH-2 encoding genes (Δndh-2 mutant) reveals that the essentiality of NDH-2 as shown in standard growth media is due to the presence of fatty acids. The Δndh-2 mutant is only mildly attenuated in mice and not differently susceptible to clofazimine, a drug in clinical use proposed to engage NDH-2. These results demonstrate the intrinsic plasticity of Mtb's respiratory chain, and highlight the challenges associated with targeting the pathogen's respiratory enzymes for tuberculosis drug development

Relationships between Specific Airway Resistance and Forced Expiratory Flows in Asthmatic Children

. The first aim was to assess the relationships between forced expiratory flows and sRaw in a large group of asthmatic children in a transversal study. We then performed a longitudinal study in order to determine whether sRaw of preschool children could predict subsequent impairment of forced expiratory flows at school age.Pulmonary function tests (sRaw and forced expiratory flows) of 2193 asthmatic children were selected for a transversal analysis, while 365 children were retrospectively selected for longitudinal assessment from preschool to school age. (% predicted) (−0.09, 95% CI, −0.20 to 0). and could be used in preschool children to predict subsequent mild airflow limitation

New Ar-Ar ages of southern Indian kimberlites and a lamproite and their geochemical evolution

The kimberlites and lamproites of southern India are thought to have formed in the most prolific known period of Precambrian ultramafic/ultrapotassic magmatism at around 1100 Ma. This study reports new age data for southern Indian ultrapotassic rocks (kimberlites and lamproites), a controversial topic due to the wide range of published age data and disagreements over the reliability of previously published ages. In this study we obtained new high-precision Ar–Ar data that better constrain the ages of southern Indian ultrapotassic rocks. Dates from three samples are presented, including two kimberlites from Wajrakarur kimberlite field and one lamproite from the Krishna lamproite field. These age data are then combined with bulk-rock geochemical and Nd isotopic data to provide further constraints on the source region and primary magma composition of southern Indian kimberlites and lamproites. Previously, the Chelima lamproite (ca. 1400 Ma) was considered to be one of the oldest lamproites in the world. However, our age data suggest that at least one lamproite (Pochampalle) was generated in the same region 100 Ma before the Chelima event. The Pochampalle lamproite was emplaced around ~1500 Ma as shown by the Ar–Ar data in this study, roughly 250 Ma before the other Krishna lamproites. It would seem that the Pochampalle lamproite was also derived from an isotopically distinct source region with a lower 143Nd/144Nd ratio than other lamproites in the Krishna field. These findings not only have implications for regional ultramafic/ultrapotassic magmatism, but also demonstrate that the mantle processes for producing lamproitic melts existed earlier than previously thought