Microfluidic large-scale integration

We developed high-density microfluidic chips that contain plumbing networks with thousands of micromechanical valves and hundreds of individually addressable chambers. These fluidic devices are analogous to electronic integrated circuits fabricated using large-scale integration. A key component of these networks is the fluidic multiplexor, which is a combinatorial array of binary valve patterns that exponentially increases the processing power of a network by allowing complex fluid manipulations with a minimal number of inputs. We used these integrated microfluidic networks to construct the microfluidic analog of a comparator array and a microfluidic memory storage device whose behavior resembles random-access memory.     

Chemical communication in social behavior of a fish, the yellow bullhead (Ictalurus natalis)

Studies of behavior in yellow bullheads showed that they recognized individuals of their own species by means of pheromones. After training by reward and punishment, blinded bullheads were able to discriminate between the odors of two donor fish, but they lost this ability when deprived of their sense of smell. The main source of the intraspecific chemical stimuli involved in recognition is the mucus. A change in status after fighting was chemically communicated to other bullheads.     

Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor

Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.     

Discovery of olivine in the Nili Fssae region of Mars

We have detected a 30,000-square-kilometer area rich in olivine in the Nili Fossae region of Mars. Nili Fossae has been interpreted as a complex of grabens and fractures related to the formation of the Isidis impact basin. We propose that post-impact faulting of this area has exposed subsurface layers rich in olivine. Linear mixture analysis of Thermal Emission Spectrometer spectra shows surface exposures of 30% olivine, where the composition of the olivine ranges from Fo30 to Fo70.     

Comparative genomics of trypanosomatid parasitic protozoa

A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.     

Capillary wrinkling of floating thin polymer films

A freely floating polymer film, tens of nanometers in thickness, wrinkles under the capillary force exerted by a drop of water placed on its surface. The wrinkling pattern is characterized by the number and length of the wrinkles. The dependence of the number of wrinkles on the elastic properties of the film and on the capillary force exerted by the drop confirms recent theoretical predictions on the selection of a pattern with a well-defined length scale in the wrinkling instability. We combined scaling relations that were developed for the length of the wrinkles with those for the number of wrinkles to construct a metrology for measuring the elasticity and thickness of ultrathin films that relies on no more than a dish of fluid and a low-magnification microscope. We validated this method on polymer films modified by plasticizer. The relaxation of the wrinkles affords a simple method to study the viscoelastic response of ultrathin films.     

Mutational inactivation of STAG2 causes aneuploidy in human cancer

Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins of aneuploidy through integrative genomic analyses of human tumors. A diverse range of tumor types were found to harbor deletions or inactivating mutations of STAG2, a gene encoding a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Because STAG2 is on the X chromosome, its inactivation requires only a single mutational event. Studying a near-diploid human cell line with a stable karyotype, we found that targeted inactivation of STAG2 led to chromatid cohesion defects and aneuploidy, whereas in two aneuploid human glioblastoma cell lines, targeted correction of the endogenous mutant alleles of STAG2 led to enhanced chromosomal stability. Thus, genetic disruption of cohesin is a cause of aneuploidy in human cancer.     

Extracting 3D from motion: differences in human and monkey intraparietal cortex

We compared three-dimensional structure-from-motion (3D-SFM) processing in awake monkeys and humans using functional magnetic resonance imaging. Occipital and midlevel extrastriate visual areas showed similar activation by 3D-SFM stimuli in both species. In contrast, intraparietal areas showed significant 3D-SFM activation in humans but not in monkeys. This suggests that human intraparietal cortex contains visuospatial processing areas that are not present in monkeys.     

The ecoresponsive genome of Daphnia pulex

We describe the draft genome of the microcrustacean Daphnia pulex, which is only 200 megabases and contains at least 30,907 genes. The high gene count is a consequence of an elevated rate of gene duplication resulting in tandem gene clusters. More than a third of Daphnia's genes have no detectable homologs in any other available proteome, and the most amplified gene families are specific to the Daphnia lineage. The coexpansion of gene families interacting within metabolic pathways suggests that the maintenance of duplicated genes is not random, and the analysis of gene expression under different environmental conditions reveals that numerous paralogs acquire divergent expression patterns soon after duplication. Daphnia-specific genes, including many additional loci within sequenced regions that are otherwise devoid of annotations, are the most responsive genes to ecological challenges.