Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo

Cell divisions that create daughter cells of different sizes are crucial for the generation of cell diversity during animal development. In such asymmetric divisions, the mitotic spindle must be asymmetrically positioned at the end of anaphase. The mechanisms by which cell polarity translates to asymmetric spindle positioning remain unclear. Here we examine the nature of the forces governing asymmetric spindle positioning in the single-cell-stage Caenorhabditis elegans embryo. To reveal the forces that act on each spindle pole, we removed the central spindle in living embryos either physically with an ultraviolet laser microbeam, or genetically by RNA-mediated interference of a kinesin. We show that pulling forces external to the spindle act on the two spindle poles. A stronger net force acts on the posterior pole, thereby explaining the overall posterior displacement seen in wild-type embryos. We also show that the net force acting on each spindle pole is under control of the par genes that are required for cell polarity along the anterior-posterior embryonic axis. Finally, we discuss simple mathematical models that describe the main features of spindle pole behaviour. Our work suggests a mechanism for generating asymmetry in spindle positioning by varying the net pulling force that acts on each spindle pole, thus allowing for the generation of daughter cells with different sizes.     

NO-independent regulatory site on soluble guanylate cyclase

Nitric oxide (NO) is a widespread, potent, biological mediator that has many physiological and pathophysiological roles. Research in the field of NO appears to have followed a straightforward path, and the findings have been progressive: NO and cyclic GMP are involved in vasodilatation; glycerol trinitrate relaxes vascular smooth muscles by bioconversion to NO; mammalian cells synthesize NO; and last, NO mediates vasodilatation by stimulating the soluble guanylate cyclase (sGC), a heterodimeric (alpha/beta) haem protein that converts GTP to cGMP2-4. Here we report the discovery of a regulatory site on sGC. Using photoaffinity labelling, we have identified the cysteine 238 and cysteine 243 region in the alpha1-subunit of sGC as the target for a new type of sGC stimulator. Moreover, we present a pyrazolopyridine, BAY 41-2272, that potently stimulates sGC through this site by a mechanism that is independent of NO. This results in antiplatelet activity, a strong decrease in blood pressure and an increase in survival in a low-NO rat model of hypertension, and as such may offer an approach for treating cardiovascular diseases.     

Earthquake slip on oceanic transform faults

Oceanic transform faults are one of the main types of plate boundary, but the manner in which they slip remains poorly understood. Early studies suggested that relatively slow earthquake rupture might be common; moreover, it has been reported that very slow slip precedes some oceanic transform earthquakes, including the 1994 Romanche earthquake. The presence of such detectable precursors would have obvious implications for earthquake prediction. Here we model broadband seismograms of body waves to obtain well-resolved depths and rupture mechanisms for 14 earthquakes on the Romanche and Chain transform faults in the equatorial Atlantic Ocean. We found that earthquakes on the longer Romanche transform are systematically deeper than those on the neighbouring Chain transform. These depths indicate that the maximum depth of brittle failure is at a temperature of approximately 600 degrees C in oceanic lithosphere. We find that the body waves from the Romanche 1994 earthquake can be well modelled with relatively deep slip on a single fault, and we use the mechanism and depth of this earthquake to recalculate its source spectrum. The previously reported slow precursor can be explained as an artefact of uncertainties in the assumed model parameters.     

A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure

Complex III (CIII; ubiquinol cytochrome c reductase of the mitochondrial respiratory chain) catalyzes electron transfer from succinate and nicotinamide adenine dinucleotide-linked dehydrogenases to cytochrome c. CIII is made up of 11 subunits, of which all but one (cytochrome b) are encoded by nuclear DNA. CIII deficiencies are rare and manifest heterogeneous clinical presentations. Although pathogenic mutations in the gene encoding mitochondrial cytochrome b have been described, mutations in the nuclear-DNA-encoded subunits have not been reported. Involvement of various genes has been indicated in assembly of yeast CIII (refs. 8-11). So far only one such gene, BCS1L, has been identified in human. BCS1L represents, therefore, an obvious candidate gene in CIII deficiency. Here, we report BCS1L mutations in six patients, from four unrelated families and presenting neonatal proximal tubulopathy, hepatic involvement and encephalopathy. Complementation study in yeast confirmed the deleterious effect of these mutations. Mutation of BCS1L would seem to be a frequent cause of CIII deficiency, as one-third of our patients have BCS1L mutations.     

The publication-citation matrix and its derived quantities

We give an overview of the main data of a publication-citation matrix. We show how impact factors are defined, and, in particular, point out the difference between the synchronous and the diachronous impact factor. The advantages and disadvantages of using both as tools in research evaluation are discussed.     

Microbial production of biopoly esters-poly hydroxyalkanoates

Polyhydroxyalkanoate, abbreviated to PHA, is a family of polyesters produced by a variety of microorganisms. Over 90 PHA with various structure variations have been reported and the number is still increasing. Some interesting physical properties of PHA such as piezoelectricity, nonlinear optical activity and biocompatibility, offer promising applications in areas such as tissue engineering and drug delivery. Worldwide there have been many attempts to produce PHA as biodegradable plastics using various microorganisms obtained from screening natural environments, genetic engineering and mutation methods. It has been found that PHA synthesis is a common phenomenon of bacteria inhabiting in various locations, especially oil-contaminated soils. Bacterial strains capable of synthesizing PHA with various monomers have been identified from oil-contaminated soils, and PHA production strains capable of rapid growth and rapid PHA synthesis on molasses substrate have also been found on molasses contaminated soil. It seems that the combination of novel properties and lower cost will allow easier commercialization of PHA.     

Full-glacial shoreline vegetation during the maximum highstand at Owens Lake, California

Owens Valley, California, was markedly different during the Wisconsin glacial stage from what it is today. Alpine glaciers bounded the Sierra Nevada, and pluvial Owens Lake reached highstands and overflowed its natural basin. We analyzed three layers from two packrat middens, dated to ca 23,000-14,500 yr BP, obtained from Haystack Mountain (1155 m) only 10 m above and Juniperus osteosperma ) and single-needle pinyon pine ( Pinus monophylla ) woodland existed at the site. In the layers dated to ca 17,500 and 16,000 yr BP, macrofossils document the presence of Rocky Mountain juniper ( Juniperus scopulorum ), a species that no longer occurs in California. It is suggested that meltwater from the retreating glacial ice inundated the Owens River Lake chain causing pluvial Owens Lake to reach its highstand. This caused an increase in effective moisture, due to high groundwater, allowing the mesophytic Rocky Mountain juniper to exist at the site.     

Survival and sprouting responses of Chihuahua pine after the Rodeo-Chediski fire on the Mogollon Rim, Arizona

Chihuahua pines ( Pinus leiophylla Schiede and Deppe var. chihuahuana Engelmann) were surveyed on 11 study plots on the Mogollon Rim in east central Arizona to compare characteristics of trees that sprouted from the base or root collar after the Rodeo-Chediski fire with those of trees that did not sprout. The differences in trees killed and top-killed by the fire versus those that survived were also assessed. Trees that sprouted were significantly smaller in height and diameter at breast height; they also experienced lower fire intensities than trees that did not sprout. Smaller trees had higher incidences of mortality than larger trees. These results indicate that, even though Chihuahua pine has fire resiliency, sprouting rates after fire are related to size of trees, age of trees, and burn intensity. Since Chihuahua pine is a rare species in the area studied, its ability to recover from and tolerate fire could prove advantageous for sustainability.