Refilling Nitrogen to Oxygen Vacancies in Ultrafine Tungsten Oxide Clusters for Superior Lithium Storage

Morphological engineering of nanosized transitional metal oxides shows great promise for performance improvement, yet limited efforts have been attempted to engineer the atomic structure. Oxygen vacancy (V_O) can boost charge transfer leading to enhanced performance; yet excessive V_O may impair the conductivity. Herein, tungsten oxide is atomically tailored by incorporating nitrogen heteroatoms into the oxygen vacancies. The efficient nitrogen‐filling into the oxygen vacancies is evidenced by the electron paramagnetic resonance spectroscopy and X‐ray absorption spectroscopy. The coordinated N atoms play a crucial role in facilitating the charge transfer and maintaining efficient lithium‐ion diffusion. Consequently, the tungsten oxide with N‐filled oxygen vacancies exhibits superior lithium‐ion storage performance.     

Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects

Hepatic and cardiac drug adverse effects are among the leading causes of attrition in drug development programs, in part due to predictive failures of current animal or in vitro models. Hepatocytes and cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) hold promise for predicting clinical drug effects, given their human-specific properties and their ability to harbor genetically determined characteristics that underlie inter-individual variations in drug response. Currently, the fetal-like properties and heterogeneity of hepatocytes and cardiomyocytes differentiated from iPSCs make them physiologically different from their counterparts isolated from primary tissues and limit their use for predicting clinical drug effects. To address this hurdle, there have been ongoing advances in differentiation and maturation protocols to improve the quality and use of iPSC-differentiated lineages. Among these are in vitro hepatic and cardiac cellular microsystems that can further enhance the physiology of cultured cells, can be used to better predict drug adverse effects, and investigate drug metabolism, pharmacokinetics, and pharmacodynamics to facilitate successful drug development. In this article, we discuss how cellular microsystems can establish microenvironments for these applications and propose how they could be used for potentially controlling the differentiation of hepatocytes or cardiomyocytes. The physiological relevance of cells is enhanced in cellular microsystems by simulating properties of tissue microenvironments, such as structural dimensionality, media flow, microfluidic control of media composition, and co-cultures with interacting cell types. Recent studies demonstrated that these properties also affect iPSC differentiations and we further elaborate on how they could control differentiation efficiency in microengineered devices. In summary, we describe recent advances in the field of cellular microsystems that can control the differentiation and maturation of hepatocytes and cardiomyocytes for drug evaluation. We also propose how future research with iPSCs within engineered microenvironments could enable their differentiation for scalable evaluations of drug effects.     

Comparison of the penetrability of the egg vestments in follicular oocytes, unfertilized and fertilized ova of the rabbit

Mixed populations of rabbit ovulated eggs and follicular oocytes, one labelled with a fluorescent marker, were transferred to the same tubal ampulla of an inseminated recipient female and were then recovered 3 hr later. There was no significant difference in the number spermatozoa penetrating to the perivitelline space or within the substance of the zona pellucida of follicular oocytes (immature or atretic) and mature ovulated ova. In contrast to mature ovulated ova, however, none of the spermatozoa reaching the perivitelline space of vesicular (dictyate) oocytes had attached to or penetrated the vitelline surface to enter the ooplasm.The same approach involving transfer of nonpenetrated eggs together with eggs penetrated previously in a donor female, demonstrated that prior entry of spermatozoa does not reduce the penetrability or receptivity of the rabbit zona pellucida to subsequent spermatozoa.These experiments indicate: (a) that the penetrability of the granulosa cell investment and/or zona pellucida of the rabbit follicular oocyte does not change from the time of antrum formation until the point at which follicular atresia ensures; (b) that between the time of initial LH stimulation and ovulation important changes mediating the onset of the fertizability of the dictyate oocyte of the rabbit probably occur at the vitelline surface; and (c) that in neither a qualitative nor quantitative sense has the demonstrably greater resistance of the rabbit zona pellucida to proteolysis following fertilization any physiological significance for sperm penetration.     

Seasonal metabolism of a small, arboreal monitor lizard, Varanus scalaris, in tropical Australia

The field metabolic rates (FMR) and water fluxes of Varanus scalaris were measured during the wet and dry seasons by the doubly-labelled water technique. Seasonal measurements of standard (night-time) metabolism (SMR) and resting (daytime) metabolism (RMR) were made in the laboratory at 18, 24, 30 and 36°C, and maximal oxygen consumption was measured at 36°C on a motorized treadmill. This population was active throughout the year. In the wet season, the mean FMR was 7.8 kJ day⁻¹ (128.0 kJkg⁻¹ day⁻¹; mean mass = 66.4 g, n = 13), and during the dry season the mean was 5.0 kJ day⁻¹ (67.6 kJ kg⁻¹ day⁻¹; mean mass = 77.4 g, n = 17). The mean water flux rates for these animals were 3.6 and 1.2 ml day⁻¹, respectively (60.4 and 16.6 ml kg⁻¹ day⁻¹). The seasonal means of FMR and water flux were significantly different by ANCOVA ( P < 0.0001). Measurements of SMR and RMR were significantly higher in the wet season (ANCOVA: P < 0.0001), but we found no difference in the maximal oxygen consumption between seasons (ANCOVA: P = 0.6). The maximal oxygen consumption of the lizards on the treadmill (2.9 ml min⁻¹= 1.8 ml g⁻¹ h⁻¹), mean mass = 97.4 g, n = 16) was 20 times that of the SMR at the same temperature during the dry season, and 11 times that of the SMR during the wet season. The seasonal differences in FMR were attributable to: changes in SMR (12.2%) and RMR (16.4%); differences in night-time body temperatures (11.3) and daytime body temperatures (16.4%); and activity (broadly defined to include locomotion, digestion, and reproductive costs (43.7%).     

The Roles of Competition and Mutation in Shaping Antigenic and Genetic Diversity in Influenza

Influenza A (H3N2) offers a well-studied, yet not fully understood, disease in terms of the interactions between pathogen population dynamics, epidemiology and genetics. A major open question is why the virus population is globally dominated by a single and very recently diverged (2–8 years) lineage. Classically, this has been modeled by limiting the generation of new successful antigenic variants, such that only a small subset of progeny acquire the necessary mutations to evade host immunity. An alternative approach was recently suggested by Recker et al. in which a limited number of antigenic variants are continuously generated, but most of these are suppressed by pre-existing host population immunity. Here we develop a framework spanning the regimes described above to explore the impact of rates of mutation and levels of competition on phylodynamic patterns. We find that the evolutionary dynamics of the subtype H3N2 influenza is most easily generated within this framework when it is mutation limited as well as being under strong immune selection at a number of epitope regions of limited diversity.     

Tyrosine Phosphorylation of the Rho Guanine Nucleotide Exchange Factor Trio Regulates Netrin-1/DCC-Mediated Cortical Axon Outgrowth

The chemotropic guidance cue netrin-1 mediates attraction of migrating axons during central nervous system development through the receptor Deleted in Colorectal Cancer (DCC). Downstream of netrin-1, activated Rho GTPases Rac1 and Cdc42 induce cytoskeletal rearrangements within the growth cone. The Rho guanine nucleotide exchange factor (GEF) Trio is essential for Rac1 activation downstream of netrin-1/DCC, but the molecular mechanisms governing Trio activity remain elusive. Here, we demonstrate that Trio is phosphorylated by Src family kinases in the embryonic rat cortex in response to netrin-1. In vitro, Trio was predominantly phosphorylated at Tyr²⁶²² by the Src kinase Fyn. Though the phospho-null mutant Trio^Y2622F retained GEF activity toward Rac1, its expression impaired netrin-1-induced Rac1 activation and DCC-mediated neurite outgrowth in N1E-115 neuroblastoma cells. Trio^Y2622F impaired netrin-1-induced axonal extension in cultured cortical neurons and was unable to colocalize with DCC in growth cones, in contrast to wild-type Trio. Furthermore, depletion of Trio in cortical neurons reduced the level of cell surface DCC in growth cones, which could be restored by expression of wild-type Trio but not Trio^Y2622F. Together, these findings demonstrate that Trio^Y2622 phosphorylation is essential for the regulation of the DCC/Trio signaling complex in cortical neurons during netrin-1-mediated axon outgrowth.     

Formation and Longevity of Chimeric and Duplicate Genes in Drosophila melanogaster

Historically, duplicate genes have been regarded as a major source of novel genetic material. However, recent work suggests that chimeric genes formed through the fusion of pieces of different genes may also contribute to the evolution of novel functions. To compare the contribution of chimeric and duplicate genes to genome evolution, we measured their prevalence and persistence within Drosophila melanogaster. We find that ~80.4 duplicates form per million years, but most are rapidly eliminated from the genome, leaving only 4.1% to be preserved by natural selection. Chimeras form at a comparatively modest rate of ~11.4 per million years but follow a similar pattern of decay, with ultimately only 1.4% of chimeras preserved. We propose two mechanisms of chimeric gene formation, which rely entirely on local, DNA-based mutations to explain the structure and placement of the youngest chimeric genes observed. One involves imprecise excision of an unpaired duplication during large-loop mismatch repair, while the other invokes a process akin to replication slippage to form a chimeric gene in a single event. Our results paint a dynamic picture of both chimeras and duplicate genes within the genome and suggest that chimeric genes contribute substantially to genomic novelty.