Effects of SAPK/JNK inhibitors on preimplantation mouse embryo development are influenced greatly by the amount of stress induced by the media

Stress-activated protein kinase/c-Jun kinase (SAPK/JNK) is thought to be necessary for preimplantation embryonic development (Maekawa et al., 2005). However, media increases SAPK/JNK phosphorylation and these levels negatively correlate with embryonic development (Wang et al., 2005). Culture-induced stress could confuse analysis of the role of SAPK in development. In this study, we tested how SAPK/JNK inhibitors influence embryonic development in optimal and non-optimal media and define the contribution of cell survival and proliferation to the embryonic response to these media. SAPK/JNK inhibitors retard embryonic development in suboptimal Ham’s F10, but improve development in optimal potassium (K+) simplex optimized media (KSOM) +AA. In KSOM + amino acids (KSOM+AA), two SAPK/JNK inhibitors increase the rate of cavitation and hatching. These data suggest that (i) SAPK/JNK mediates the response to culture stress, not normal preimplantation embryonic development and (ii) SAPK/JNK inhibitors may be useful in ameliorating embryo stress caused by culture. To define the effects of media, we assayed the contribution of cell survival and proliferation and the differences in total cell number of cultured embryos. Embryos cultured from E3.5+24 h in the suboptimal medium (Ham’s F10) induced significant but small increases in TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling (TUNEL) positive cells. Bromodeoxyuridine (BrdU) incorporation in suboptimal Ham’s F10 was significantly lower than in optimal KSOM+AA, suggesting that cell cycle arrest also contributes to slower increase in cell number in stressful media. This is the first report where TUNEL and BrdU were both assayed to define the relative contribution of cell cycle/S phase commitment and apoptosis to lessened cell number increase during embryo culture

Enhanced photoproduction of hydrogen on Pd/TiO2 prepared by mechanochemistry

Supported metal clusters are considered as promising cocatalysts in heterogeneous photocatalysis due to their singular geometric structures and unique reactivity. Nevertheless, to explore efficient synthetic routes that result in stable supported clusters with tailored active sites is an urgent yet challenging task. Here, a photocatalyst with highly dispersed Pd clusters onto TiO2 is synthesized through only one-step ball milling procedure. The obtained Pd clusters form a particular metal-support interface, which has the ability to rearrange the small clusters evolving into Pd nanoparticles during the photocatalytic H2 production process, and maintain a stable photocatalytic performance up to 100 h of continuous operation. Moreover, the unique interaction between Pd clusters and titania support was only observed in the ball-milled sample, and it disappeared after a calcination treatment. The mechanochemical strategy paves the way to stabilize supported metal clusters onto semiconductors without any organic compounds involved.Postprint (published version

Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency

Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC), elevated O2 and mitochondrial function are necessary to placental lineages at the maternal–placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. In an implantation site O2 is normally ~ 2%. In culture, exposure to 2% O2 and fibroblast growth factor 4 (FGF4) enabled the highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% O2) initiated the most TSC differentiation after 24 h despite exposure to FGF4. However, hypoxic stress supported differentiation poorly after 4–7 days, despite FGF4 removal. At all tested O2 levels, FGF4 maintained Warburg metabolism; mitochondrial inactivity and aerobic glycolysis. However, hypoxic stress suppressed mitochondrial membrane potential and maintained low mitochondrial cytochrome c oxidase (oxidative phosphorylation/OxPhos), and high pyruvate kinase M2 (glycolysis) despite FGF4 removal. Inhibiting OxPhos inhibited optimum differentiation at 20% O2. Moreover, adding differentiation-inducing hyperosmolar stress failed to induce differentiation during hypoxia. Thus, differentiation depended on OxPhos at 20% O2; hypoxic and hyperosmolar stresses did not induce differentiation at 0.5% O2. Hypoxia-limited differentiation and mitochondrial inhibition and activation suggest that differentiation into two lineages of the labyrinthine placenta requires O2 \u3e 0.5–2% and mitochondrial function. Stress-activated protein kinase increases an early lineage and suppresses later lineages in proportion to the deviation from optimal O2 for multipotency, thus it is the first enzyme reported to prioritize differentiation

Stabilization of anti-aromatic and strained five-membered rings with a transition metal

1981年诺贝尔化学奖获得者、美国康奈尔大学RoaldHoffmann教授评价该项工作说：'The　paper is an excellent one--it's　quite a mazing that the parent Os　system,molecule 1,chooses to give the osmapentalyne'。德国化学家Uwe Rosenthal教授等在同期《自然—化学》杂志的《News and Views》栏目以《Breaking the rules》为题撰文评述了这一研究成果。全文地址：http://www.nature.com/nchem/journal/vaop/ncurrent/pdf/nchem.1702.pdfAnti-aromatic compounds, as well as small cyclic alkynes or carbynes, are particularly challenging synthetic goals. The combination of their destabilizing features hinders attempts to prepare molecules such as pentalyne, an 8π-electron anti-aromatic bicycle with extremely high ring strain. Here we describe the facile synthesis of osmapentalyne derivatives that are thermally viable, despite containing the smallest angles observed so far at a carbyne carbon. The compounds are characterized using X-ray crystallography, and their computed energies and magnetic properties reveal aromatic character. Hence, the incorporation of the osmium centre not only reduces the ring strain of the parent pentalyne, but also converts its Hückel anti-aromaticity into Craig-type Möbius aromaticity in the metallapentalynes. The concept of aromaticity is thus extended to five-membered rings containing a metal–carbon triple bond. Moreover, these metal–aromatic compounds exhibit unusual optical effects such as near-infrared photoluminescence with particularly large Stokes shifts, long lifetimes and aggregation enhancement

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Three Dimensional Model of Technology Innovation System Centered on Enterprises

Although there is a high level of practitioner, policymaker, and scholar interest in social entrepreneurship, most research is based on case studies and success stories of successful social entrepreneurs in a single country. We develop a methodology to measure population-based social entrepreneurship activity (SEA) prevalence rates and test it in 49 countries. Our results provide insights into institutional and individual drivers of SEA. Using the Global Entrepreneurship Monitor (GEM) methodology of Total Entrepreneurial Activity (TEA), we find that countries with higher rates of traditional entrepreneurial activity also tend to have higher rates of social entrepreneurial activity. We develop a broad definition of social entrepreneurship and then explore types based on social mission, revenue model, and innovativeness

New Technology Innovation Model Centered on Enterprises

As the elderly care sector is characterized by several challenges, rethought and restructured organizations and institutions and thus innovation are necessary. This study investigated (1) what innovation in the elderly care sector means and (2) which factors determine the innovativeness of elderly care organizations. Our goal was to develop a framework to catch innovation and explain the capacity for innovation in the elderly care sector. Via case studies within five Flemish elderly care organizations, the applicability of the complex adaptive system (CAS) theory was examined. The results showed that organizations partially acted as CASs, but totally acting as CASs was restrained by top-down forces, procedures, and regulations

Adaptive and Pathogenic Responses to Stress by Stem Cells during Development

Cellular stress is the basis of a dose-dependent continuum of responses leading to adaptive health or pathogenesis. For all cells, stress leads to reduction in macromolecular synthesis by shared pathways and tissue and stress-specific homeostatic mechanisms. For stem cells during embryonic, fetal, and placental development, higher exposures of stress lead to decreased anabolism, macromolecular synthesis and cell proliferation. Coupled with diminished stem cell proliferation is a stress-induced differentiation which generates minimal necessary function by producing more differentiated product/cell. This compensatory differentiation is accompanied by a second strategy to insure organismal survival as multipotent and pluripotent stem cells differentiate into the lineages in their repertoire. During stressed differentiation, the first lineage in the repertoire is increased and later lineages are suppressed, thus prioritized differentiation occurs. Compensatory and prioritized differentiation is regulated by at least two types of stress enzymes. AMP-activated protein kinase (AMPK) which mediates loss of nuclear potency factors and stress-activated protein kinase (SAPK) that does not. SAPK mediates an increase in the first essential lineage and decreases in later lineages in placental stem cells. The clinical significance of compensatory and prioritized differentiation is that stem cell pools are depleted and imbalanced differentiation leads to gestational diseases and long term postnatal pathologies

Nonlinear Transient Dynamics of Graphene Nanoplatelets Reinforced Pipes Conveying Fluid under Blast Loads and Thermal Environment

This work aims at investigating the nonlinear transient response of fluid-conveying pipes made of graphene nanoplatelet (GPL)-reinforced composite (GPLRC) under blast loads and in a thermal environment. A modified Halpin–Tsai model is used to approximate the effective Young’s modulus of the GPLRC pipes conveying fluid; the mass density and Poisson’s ratio are determined by using the Voigt model. A slender Euler–Bernoulli beam is considered for modeling the pipes conveying fluid. The vibration control equation of the GPLRC pipes conveying fluid under blast loads is obtained by using Hamilton’s principle. A set of second-order ordinary differential equations are obtained by using the second-order Galerkin discrete method and are solved by using the adaptive Runge–Kutta method. Numerical experiments show that GPL distribution and temperature; GPL weight fraction; pipe length-to-thickness ratio; flow velocity; and blast load parameters have important effects on the nonlinear transient response of the GPLRC pipes conveying fluid. The numerical results also show that due to the fluid–structure interaction, the vibration amplitudes of the GPLRC pipes conveying fluid decay after the impact of blast loads

COPPER (I) IODIDE-CATALYZED SOLVENT-FREE SYNTHESIS OF alpha-AMINOPHOSPHONATES

National Natural Science Foundation of China [40806032]; Natural Science Foundation of Fujian Province of China [2009J05099, 2011J05101, 2010NZ0001-2]A method for the synthesis of alpha-aminophosphonates through the three-component coupling reaction of aldehydes, amines, and diisopropyl phosphite using copper (I) iodide salt catalyst is demonstrated, The reaction is highly efficient, economic, and also environment friendly. [Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental resource: Table S1, Figures S1-S9.