Identification of active edge sites for electrochemical H2 evolution from MoS2 nanocatalysts

The identification of the active sites in heterogeneous catalysis requires a combination of surface sensitive methods and reactivity studies. We determined the active site for hydrogen evolution, a reaction catalyzed by precious metals, on nanoparticulate molybdenum disulfide (MoS2) by atomically resolving the surface of this catalyst before measuring electrochemical activity in solution. By preparing MoS2 nanoparticles of different sizes, we systematically varied the distribution of surface sites on MoS2 nanoparticles on Au(111), which we quantified with scanning tunneling microscopy. Electrocatalytic activity measurements for hydrogen evolution correlate linearly with the number of edge sites on the MoS2 catalyst.     

Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion

Replicated chromosomes are held together by the chromosomal cohesin complex from the time of their synthesis in S phase onward. This requires the replication fork-associated acetyl transferase Eco1, but Eco1's mechanism of action is not known. We identified spontaneous suppressors of the thermosensitive eco1-1 allele in budding yeast. An acetylation-mimicking mutation of a conserved lysine in cohesin's Smc3 subunit makes Eco1 dispensable for cell growth, and we show that Smc3 is acetylated in an Eco1-dependent manner during DNA replication to promote sister chromatid cohesion. A second set of eco1-1 suppressors inactivate the budding yeast ortholog of the cohesin destabilizer Wapl. Our results indicate that Eco1 modifies cohesin to stabilize sister chromatid cohesion in parallel with a cohesion establishment reaction that is in principle Eco1-independent.     

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.     

Electric field-induced modification of magnetism in thin-film ferromagnets

A large electric field at the surface of a ferromagnetic metal is expected to appreciably change its electron density. In particular, the metal's intrinsic magnetic properties, which are commonly regarded as fixed material constants, will be affected. This requires, however, that the surface has a strong influence on the material's properties, as is the case with ultrathin films. We demonstrated that the magnetocrystalline anisotropy of ordered iron-platinum (FePt) and iron-palladium (FePd) intermetallic compounds can be reversibly modified by an applied electric field when immersed in an electrolyte. A voltage change of -0.6 volts on 2-nanometer-thick films altered the coercivity by -4.5 and +1% in FePt and FePd, respectively. The modification of the magnetic parameters was attributed to a change in the number of unpaired d electrons in response to the applied electric field. Our device structure is general and should be applicable for characterization of other thin-film magnetic systems.     

Patches with links: a unified system for processing faces in the macaque temporal lobe

The brain processes objects through a series of regions along the ventral visual pathway, but the circuitry subserving the analysis of specific complex forms remains unknown. One complex form category, faces, selectively activates six patches of cortex in the macaque ventral pathway. To identify the connectivity of these face patches, we used electrical microstimulation combined with simultaneous functional magnetic resonance imaging. Stimulation of each of four targeted face patches produced strong activation, specifically within a subset of the other face patches. Stimulation outside the face patches produced an activation pattern that spared the face patches. These results suggest that the face patches form a strongly and specifically interconnected hierarchical network.     

Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis

The mechanisms involved in prion neurotoxicity are unclear, and therapies preventing accumulation of PrPSc, the disease-associated form of prion protein (PrP), do not significantly prolong survival in mice with central nervous system prion infection. We found that depleting endogenous neuronal PrPc in mice with established neuroinvasive prion infection reversed early spongiform change and prevented neuronal loss and progression to clinical disease. This occurred despite the accumulation of extraneuronal PrPSc to levels seen in terminally ill wild-type animals. Thus, the propagation of nonneuronal PrPSc is not pathogenic, but arresting the continued conversion of PrPc to PrPSc within neurons during scrapie infection prevents prion neurotoxicity.     

Cross-linking cellular prion protein triggers neuronal apoptosis in vivo

Neuronal death is a prominent, but poorly understood, pathological hallmark of prion disease. Notably, in the absence of the cellular prion protein (PrPC), the disease-associated isoform, PrPSc, appears not to be intrinsically neurotoxic, suggesting that PrPC itself may participate directly in the prion neurodegenerative cascade. Here, cross-linking PrPC in vivo with specific monoclonal antibodies was found to trigger rapid and extensive apoptosis in hippocampal and cerebellar neurons. These findings suggest that PrPC functions in the control of neuronal survival and provides a model to explore whether cross-linking of PrPC by oligomeric PrPSc can promote neuronal loss during prion infection.     

Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast

Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.