Near Ambient Condition Hydrogen Storage in a Synergized Tricomponent Hydride System

Reversible hydrogen storage over hydrides of light elements (HLEs) under ambient condition has been pursued actively for nearly two decades. However, because of unfavorable thermodynamics and/or severe kinetic barrier of HLEs, limited progress has been made. Here, it is demonstrated that the interaction of LiBH₄ with Mg(NH₂)₂ and LiH, three of the most investigated HLEs, can lead to a fully reversible dehydrogenation/rehydrogenation cycle at temperatures below 373 K. More importantly, with the desorption enthalpy of 24 kJ (mol H₂)^?1 the dehydrogenation process at 1.0 bar H₂ is theoretically possible to be as low as 266 K. Characterization of this combination of HLEs shows that LiBH₄ serves as a reagent complexing with intermediates and products of the dehydrogenation of Mg(NH₂)₂‐LiH, and significantly alters the overall thermodynamic and kinetic properties of the system.     

Estimating mating rates in wild Drosophila melanogaster females by decay rates of male reproductive proteins in their reproductive tracts

Female Drosophila melanogaster frequently mate with multiple males in nature as shown through parentage analysis. Although polyandry is well documented, we know little about the timing between mating events in wild Drosophila populations due to the challenge of following behaviours of individual females. In this study, we used the presence of a male reproductive protein that is transferred to the female during mating (Sex Peptide, SP) to determine whether she had recently mated. We sampled females throughout the day, conducted control matings to determine the decay rate of SP within the female reproductive tract and performed computer simulations to fit the observed proportion of mated females to a nonhomogenous Poisson process that defined the expected time between successive matings for a given female. In our control matings, 100% of mated females tested positive for SP 0.5 h after the start of mating (ASM), but only 24% tested positive 24 h ASM. Overall, 35% of wild‐caught females tested positive for the presence of SP. Fitting our observed data to our simple nonhomogenous Poisson model provided the inference that females are mating, on average, approximately every 27 h (with 95% credibility interval 23–31 h). Thus, it appears that females are mating a bit less frequently that once per day in this natural population and that mating events tend to occur either early in the morning or late in the afternoon.     

High‐throughput downstream process development for cell‐based products using aqueous two‐phase systems (ATPS) – A case study

The availability of preparative‐scale downstream processing strategies for cell‐based products presents a critical juncture between fundamental research and clinical development. Aqueous two‐phase systems (ATPS) present a gentle, scalable, label‐free, and cost‐effective method for cell purification, and are thus a promising tool for downstream processing of cell‐based therapeutics. Here, the application of a previously developed robotic screening platform that enables high‐throughput cell partitioning analysis in ATPS is reported. In the present case study a purification strategy for two model cell lines based on high‐throughput screening (HTS)‐data and countercurrent distribution (CCD)‐modeling, and validated the CCD‐model experimentally is designed. The obtained data are shown an excellent congruence between CCD‐model and experimental data, indicating that CCD‐models in combination with HTS‐data are a powerful tool in downstream process development. Finally, the authors are shown that while cell cycle phase significantly influences cell partitioning, cell type specific differences in surface properties are the main driving force in charge‐dependent separation of HL‐60 and L929 cells. In order to design a highly robust purification process it is, however, advisable to maintain constant growth conditions.     

Systems pharmacology and enhanced pharmacodynamic models for understanding antibody-based drug action and toxicity

Pharmacokinetic (PK) and pharmacodynamic (PD) models seek to describe the temporal pattern of drug exposures and their associated pharmacological effects produced at micro- and macro-scales of organization. Antibody-based drugs have been developed for a large variety of diseases, with effects exhibited through a comprehensive range of mechanisms of action. Mechanism-based PK/PD and systems pharmacology models can play a major role in elucidating and integrating complex antibody pharmacological properties, such as nonlinear disposition and dynamical intracellular signaling pathways triggered by ligation to their cognate targets. Such complexities can be addressed through the use of robust computational modeling techniques that have proven powerful tools for pragmatic characterization of experimental data and for theoretical exploration of antibody efficacy and adverse effects. The primary objectives of such multi-scale mathematical models are to generate and test competing hypotheses and to predict clinical outcomes. In this review, relevant systems pharmacology and enhanced PD (ePD) models that are used as predictive tools for antibody-based drug action are reported. Their common conceptual features are highlighted, along with approaches used for modeling preclinical and clinically available data. Key examples illustrate how systems pharmacology and ePD models codify the interplay among complex biology, drug concentrations, and pharmacological effects. New hybrid modeling concepts that bridge cutting-edge systems pharmacology models with established PK/ePD models will be needed to anticipate antibody effects on disease in subpopulations and individual patients.     

Likelihood of changes in forest species suitability,distribution, and diversity under future climate: The case of Southern Europe

Forest conservation strategies and plans can be unsuccessful if the new habitat conditions determined by climate change are not considered. Our work aims at investigating the likelihood of future suitability, distribution and diversity for some common European forest species under the projected changes in climate, focusing on Southern Europe. We combine an Ensemble Platform for Species Distribution Models (SDMs) to five Global Circulation Models (GCMs) driven by two Representative Concentration Pathways (RCPs), to produce maps of future climate‐driven habitat suitability for ten categories of forest species and two time horizons. For each forest category and time horizon, ten maps of future distribution (5 GCMs by 2 RCPs) are thus combined in a single suitability map supplied with information about the “likelihood” adopting the IPCC terminology based on consensus among projections. Then, the statistical significance of spatially aggregated changes in forest composition at local and regional level is analyzed. Finally, we discuss the importance, among SDMs, that environmental predictors seem to have in influencing forest distribution. Future impacts of climate change appear to be diversified across forest categories. A strong change in forest regional distribution and local diversity is projected to take place, as some forest categories will find more suitable conditions in previously unsuitable locations, while for other categories the same new conditions will become less suited. A decrease in species diversity is projected in most of the area, with Alpine region showing the potentiality to become a refuge for species migration.     

Sex‐biased oviposition by a nursery pollinator on a gynodioecious host plant: Implications for breeding system evolution and evolution of mutualism

Dioecy, a breeding system where individual plants are exclusively male or female, has evolved repeatedly. Extensive theory describes when dioecy should arise from hermaphroditism, frequently through gynodioecy, where females and hermaphrodites coexist, and when gynodioecy should be stable. Both pollinators and herbivores often prefer the pollen‐bearing sex, with sex‐specific fitness effects that can affect breeding system evolution. Nursery pollination, where adult insects pollinate flowers but their larvae feed on plant reproductive tissues, is a model for understanding mutualism evolution but could also yield insights into plant breeding system evolution. We studied a recently established nursery pollination interaction between native Hadena ectypa moths and introduced gynodioecious Silene vulgaris plants in North America to assess whether oviposition was biased toward females or hermaphrodites, which traits were associated with oviposition, and the effect of oviposition on host plant fitness. Oviposition was hermaphrodite‐biased and associated with deeper flowers and more stems. Sexual dimorphism in flower depth, a trait also associated with oviposition on the native host plant (Silene stellata), explained the hermaphrodite bias. Egg‐receiving plants experienced more fruit predation than plants that received no eggs, but relatively few fruits were lost, and egg receipt did not significantly alter total fruit production at the plant level. Oviposition did not enhance pollination; egg‐receiving flowers usually failed to expand and produce seeds. Together, our results suggest that H. ectypa oviposition does not exert a large fitness cost on host plants, sex‐biased interactions can emerge from preferences developed on a hermaphroditic host species, and new nursery pollination interactions can arise as negative or neutral rather than as mutualistic for the plant.     

Who's My Daddy? Considerations for the influence of sexual selection on multiple paternity in elasmobranch mating systems

Polyandry resulting in multiply‐sired litters has been documented in the majority of elasmobranch species examined to date. Although commonly observed, reasons for this mating system remain relatively obscure, especially in batoids. The round stingray (Urobatis halleri) is an abundant, well‐studied elasmobranch distributed throughout the northeastern Pacific that we used to explore hypotheses regarding multiple paternity in elasmobranchs. Twenty mid‐ to late‐term pregnant females were sampled off the coast of southern California and their litters analyzed for the occurrence of multiple paternity using five nuclear microsatellite loci. In addition, embryo sizes and their position within the female reproductive system (i.e., right or left uterus) were recorded and used to make inferences for patterns of ovulation. Multiple paternity was observed in 90% of litters and male reproductive success within litters was relatively even among sires. High variability in testes mass was observed suggesting that sperm competition is high in this species, although male reproductive success per litter appeared to be relatively even. Using embryo size as a proxy for fertilization, females were found to exhibit a variety of ovulation patterns that could function to limit a male's access to eggs and possibly promote high rates of multiple paternity. Our study highlights that elasmobranch mating systems may be more varied and complex than presumed and further investigation is warranted.     

Variation in the benefits of multiple mating on female fertility in wild stalk‐eyed flies

Polyandry, female mating with multiple males, is widespread across many taxa and almost ubiquitous in insects. This conflicts with the traditional idea that females are constrained by their comparatively large investment in each offspring, and so should only need to mate once or a few times. Females may need to mate multiply to gain sufficient sperm supplies to maintain their fertility, especially in species in which male promiscuity results in division of their ejaculate among many females. Here, we take a novel approach, utilizing wild‐caught individuals to explore how natural variation among females and males influences fertility gains for females. We studied this in the Malaysian stalk‐eyed fly species Teleopsis dalmanni. After an additional mating, females benefit from greatly increased fertility (proportion fertile eggs). Gains from multiple mating are not uniform across females; they are greatest when females have high fecundity or low fertility. Fertility gains also vary spatially, as we find an additional strong effect of the stream from which females were collected. Responses were unaffected by male mating history (males kept with females or in male‐only groups). Recent male mating may be of lesser importance because males in many species, including T. dalmanni, partition their ejaculate to maintain their fertility over many matings. This study highlights the importance of complementing laboratory studies with data on wild‐caught populations, where there is considerable heterogeneity between individuals. Future research should focus on environmental, demographic and genetic factors that are likely to significantly influence variation in individual female fecundity and fertility.     

Methionine sulfoximine supplementation enhances productivity in GS–CHOK1SV cell lines through glutathione biosynthesis

In Lonza Biologics' GS Gene Expression System?, recombinant protein‐producing GS–CHOK1SV cell lines are generated by transfection with an expression vector encoding both GS and the protein product genes followed by selection in MSX and glutamine‐free medium. MSX is required to inhibit endogenous CHOK1SV GS, and in effect create a glutamine auxotrophy in the host that can be complemented by the expression vector encoded GS in selected cell lines. However, MSX is not a specific inhibitor of GS as it also inhibits the activity of GCL (a key enzyme in the glutathione biosynthesis pathway) to a similar extent. Glutathione species (GSH and GSSG) have been shown to provide both oxidizing and reducing equivalents to ER‐resident oxidoreductases, raising the possibility that selection for transfectants with increased GCL expression could result in the isolation of GS–CHOKISV cell lines with improved capacity for recombinant protein production. In this study we have begun to address the relationship between MSX supplementation, the amount of intracellular GCL subunit and mAb production from a panel of GS–CHOK1SV cell lines. We then evaluated the influence of reduced GCL activity on batch culture of an industrially relevant mAb‐producing GS–CHOK1SV cell line. To the best of our knowledge, this paper describes for the first time the change in expression of GCL subunits and recombinant mAb production in these cell lines with the degree of MSX supplementation in routine subculture. Our data also shows that partial inhibition of GCL activity in medium containing 75 µM MSX increases mAb productivity, and its more specific inhibitor BSO used at a concentration of 80 µM in medium increases the specific rate of mAb production eight‐fold and the concentration in harvest medium by two‐fold. These findings support a link between the inhibition of glutathione biosynthesis and recombinant protein production in industrially relevant systems and provide a process‐driven method for increasing mAb productivity from GS–CHOK1SV cell lines. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:17–25, 2017     

雄性根田鼠的同胞竞争及其对同性个体的气味识别

采用两两互作实验并以尿标记来确定共居至成年的2雄性根田鼠同胞在行为竞争上的差异,之后在行为选择箱中分别观察它们对来自熟悉和陌生同性个体的新鲜尿气味的行为反应,以确定气味识别差异。结果表明：①雄性根田鼠两两互作时,尿标记的多少可以作为判断其社会等级的标准;②从属鼠对熟悉气味存在明显偏好,其对熟悉气味的访问时间、接近频次和自我修饰频次都显著高于陌生气味;③优势鼠则优先访问陌生气味,其对陌生气味的访问时间、嗅舔频次、嗅舔时间、自我修饰及反标记均显著高于熟悉气味;④对于陌生气味,优势鼠和从属鼠之间存在明显不同的行为反应模式。本实验结果提示,雄性根田鼠对同性尿气味识别的差异以及对陌生气味的行为反应,可能暗含着其领域防卫的信息。