Ni‐Metalloid (B,Si, P,As, and Te) Alloys as Water Oxidation Electrocatalysts

Breakthroughs toward effective water‐splitting electrocatalysts for mass hydrogen production will necessitate material design strategies based on unexplored material chemistries. Herein, Ni‐metalloid (B, Si, P, As, Te) alloys are reported as an emergent class of highly promising electrocatalysts for the oxygen evolution reaction (OER) and insight is offered into the origin of activity enhancement on the premise of the surface electronic structure, the OER activation energy, influence of the guest metalloid elements on the lattice structure of the host metal (Ni), and surface‐oxidized metalloid oxoanions. The metalloids modify the lattice structure of Ni, causing changes in the nearest Ni–Ni interatomic distance (d_Ni–Ni). The activation energy E_a scales with d_Ni–Ni indicating an apparent dependence of the OER activity on lattice properties. During the OER, surface Ni atoms are oxidized to nickel oxyhydroxide, which is the active state of the catalyst, meanwhile, the surface metalloids are oxidized to the corresponding oxoanions that affect the interfacial electrode/electrolyte properties and hence the adsorption/desorption interaction energies of the reacting species.     

A genetic screen for modifiers of the delta1-dependent notch signaling function in the mouse

The Notch signaling pathway is an evolutionarily conserved transduction pathway involved in embryonic patterning and regulation of cell fates during development. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, which are also involved in distinct human diseases. Delta1 is one of the known ligands of the Notch receptors. Mice homozygous for a loss-of-function allele of the Delta1 gene Dll1(lacZ/lacZ) die during embryonic development. Here, we present the results of two phenotype-driven modifier screens. Heterozygous Dll1(lacZ) knockout animals were crossed with ENU-mutagenized mice and screened for dysmorphological, clinical chemical, and immunological variants that are dependent on the Delta1 loss-of-function allele. First, we show that mutagenized heterozygous Dll1(lacZ) offspring have reduced body weight and altered specific clinical chemical parameters, including changes in metabolites and electrolytes relevant for kidney function. In our mutagenesis screen we have successfully generated 35 new mutant lines. Of major interest are 7 mutant lines that exhibit a Dll1(lacZ/+)-dependent phenotype. These mutant mouse lines provide excellent in vivo tools for studying the role of Notch signaling in kidney and liver function, cholesterol and iron metabolism, cell-fate decisions, and during maturation of T cells in the immune system.     

The beta-propensity of Tau determines aggregation and synaptic loss in inducible mouse models of tauopathy

Neurofibrillary lesions are characteristic for a group of human diseases, named tauopathies, which are characterized by prominent intracellular accumulations of abnormal filaments formed by the microtubule-associated protein Tau. The tauopathies are accompanied by abnormal changes in Tau protein, including pathological conformation, somatodendritic mislocalization, hyperphosphorylation, and aggregation, whose interdependence is not well understood. To address these issues we have created transgenic mouse lines in which different variants of full-length Tau are expressed in a regulatable fashion, allowing one to switch the expression on and off at defined time points. The Tau variants differ by small mutations in the hexapeptide motifs that control the ability of Tau to adopt a beta-structure conformation and hence to aggregate. The "pro-aggregation" mutant DeltaK280, derived from one of the mutations observed in frontotemporal dementias, aggregates avidly in vitro, whereas the "anti-aggregation" mutant DeltaK280/PP cannot aggregate because of two beta-breaking prolines. In the transgenic mice, the pro-aggregation Tau induces a pathological conformation and pre-tangle aggregation, even at low expression levels, the anti-aggregation mutant does not. This illustrates that abnormal aggregation is primarily controlled by the molecular structure of Tau in vitro and in the organism. Both variants of Tau become mislocalized and hyperphosphorylated independently of aggregation, suggesting that localization and phosphorylation are mainly a consequence of increased concentration. These pathological changes are reversible when the expression of Tau is switched off. The pro-aggregation Tau causes a strong reduction in spine synapses.     

Reactions of wild tamarins,Saguinus mystax andSaguinus fuscicollis to avian predators

During a field study in northeastern Peru, the reactions of a group ofSaguinus mystax on Padre Isla and of a mixed-species troop ofS. mystax andSaguinus fuscicollis at the Río Blanco to raptorial and other birds were observed. Alarms that are specific to flying stimuli were elicited by birds of prey, but other birds that do not represent a threat to the tamarins also caused alarm calls. Alarm events (i.e., instances when one or more alarm calls were given) were observed at rates of 0.3/hr (Padre Isla) and 0.5/hr (Río Blanco). Rates of alarm events significantly increased after the birth of an infant in the Padre Isla group and after the attack of an ornate hawk-eagle (Spizaetus ornatus) on the Río Blanco group. Reactions to alarming stimuli/alarm calls ranged from looking up to falling down from trees. The modification of the tamarins' behavior by the potential presence of aerial predators indicates that raptors represent an important predatory threat to tamarins.     

Seasonal Variation in Seed Dispersal by Tamarins Alters Seed Rain in a Secondary Rain Forest

Reduced dispersal of large seeds into degraded areas is one of the major factors limiting rain forest regeneration, as many seed dispersers capable of transporting large seeds avoid these sites with a limited forest cover. However, the small size of tamarins allows them to use small trees, and hence to disperse seeds into young secondary forests. Seasonal variations in diet and home range use might modify their contribution to forest regeneration through an impact on the seed rain. For a 2-yr period, we followed a mixed-species group of tamarins in Peru to determine how their role as seed dispersers in a 9-yr-old secondary-growth forest varied across seasons. These tamarins dispersed small to large seeds of 166 tree species, 63 of which were into a degraded area. Tamarins’ efficiency in dispersing seeds from primary to secondary forest varied across seasons. During the late wet season, high dietary diversity and long forays in secondary forest allowed them to disperse large seeds involved in later stages of regeneration. This occurred precisely when tamarins spent a more equal amount of time eating a high diversity of fruit species in primary forest and pioneer species in secondary forest. We hypothesized that well-balanced fruit availability induced the movement of seed dispersers between these 2 habitats. The noteworthy number of large-seeded plant species dispersed by such small primates suggests that tamarins play an important, but previously neglected, role in the regeneration and maintenance of forest structure.     

Activities of the matrix metalloproteinase stromelysin-2 (MMP-10) in matrix degradation and keratinocyte organization in wounded skin

The matrix metalloproteinase stromelysin-2 is expressed in keratinocytes of the epithelial tongue of skin wounds, suggesting a role in keratinocyte migration. Here, we show that stromelysin-2 enhances migration of cultured keratinocytes. To gain insight into the in vivo activities of stromelysin-2 in epithelial repair, we generated transgenic mice expressing a constitutively active stromelysin-2 mutant in keratinocytes. These animals had no alterations in skin architecture, and the healing rate of skin wounds was normal. Histologically, however, we found abnormalities in the organization of the wound epithelium. Keratinocytes at the migrating epidermal tip were scattered in most sections of mice with high expression level, and there was a reduced deposition of new matrix. In particular, the staining pattern of laminin-5 at the wound site was altered. This may be due to proteolytic processing of laminin-5 by stromelysin-2, because degradation of laminin-5 by this enzyme was observed in vitro. The inappropriate matrix contact of keratinocytes was accompanied by aberrant localization of beta1-integrins and phosphorylated focal adhesion kinase, as well as by increased apoptosis of wound keratinocytes. These results suggest that a tightly regulated expression level of stromelysin-2 is required for limited matrix degradation at the wound site, thereby controlling keratinocyte migration.     

B lymphocyte inhibition of anti-tumor response depends on expansion of Treg but is independent of B-cell IL-10 secretion

The mechanisms by which B lymphocytes inhibit anti-tumor immunity remain poorly understood. Murine EMT-6 mammary tumors grow readily in immune competent mice (BALB/c), but poorly in B-cell-deficient μ^?/? BALB/c mice (BCDM). T regulatory cell (Treg) expansion and function were impaired in BCDM compared with BALB/c. In this study, we compared tumor growth, Treg cell proliferation, tumor lymphocyte infiltration and cytolytic T cell activity in BALB/c, BCDM and BCDM partially reconstituted with B cells by adoptive transfer (BCDM+B). Partial reconstitution of BCDM with adoptively transferred B cells restored EMT-6 tumor growth, which was independent of IL-10 secretion by B cells. Instead, high frequencies of intratumoral B cells were associated with increased recruitment and proliferation of Treg cells within the tumor microenvironment. The B-cell-dependent accumulation of Treg within the tumor microenvironment was associated with reduced tumor infiltration by CD49+ NK and CD8+ T cells and reduced cytotoxic T cell activity against EMT-6 targets. Our studies indicate that tumor-dependent immunosuppression of T-cell-mediated anti-tumor immunity is coordinated within the tumor microenvironment by B-cell-dependent cross talk with Treg cells, which does not require production of IL-10 by B cells.     

Switching the mode of metabolism in the yeast Saccharomyces cerevisiae

The biochemistry of most metabolic pathways is conserved from bacteria to humans, although the control mechanisms are adapted to the needs of each cell type. Oxygen depletion commonly controls the switch from respiration to fermentation. However, Saccharomyces cerevisiae also controls that switch in response to the external glucose level. We have generated an S. cerevisiae strain in which glucose uptake is dependent on a chimeric hexose transporter mediating reduced sugar uptake. This strain shows a fully respiratory metabolism also at high glucose levels as seen for aerobic organisms, and switches to fermentation only when oxygen is lacking. These observations illustrate that manipulating a single step can alter the mode of metabolism. The novel yeast strain is an excellent tool to study the mechanisms underlying glucose-induced signal transduction.     

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