A novel culture medium with reduced nutrient concentrations supports the development and viability of mouse embryos

Further refinement of culture media is needed to improve the quality of embryos generated in vitro. Previous results from our laboratory demonstrated that uptake of nutrients by the embryo is significantly less than what is supplied in traditional culture media. Our objective was to determine the impact of reduced nutrient concentrations in culture medium on mouse embryo development, metabolism, and quality as a possible platform for next generation medium formulation. Concentrations of carbohydrates, amino acids, and vitamins could be reduced by 50% with no detrimental effects, but blastocyst development was impaired at 25% of standard nutrient provision (reduced nutrient medium; RN). Addition of pyruvate and L-lactate (+PL) to RN at 50% of standard concentrations restored blastocyst development, hatching, and cell number. In addition, blastocysts produced in RN\u2009+PL contained more ICM cells and ATP than blastocysts cultured in our control (100% nutrient) medium; however, metabolic activity was altered. Similarly, embryos produced in the RN medium with elevated (50% control) concentrations of pyruvate and lactate in the first step medium and EAA and Glu in the second step medium were competent to implant and develop into fetuses at a similar rate as embryos produced in the control medium. This novel approach to culture medium formulation could help define the optimal nutrient requirements of embryos in culture and provide a means of shifting metabolic activity towards the utilization of specific metabolic pathways that may be beneficial for embryo viability

Spectroscopic and photometric periods of six ultracompact accreting binaries

Ultracompact accreting binary systems each consist of a stellar remnant accreting helium-enriched material from a compact donor star. Such binaries include two related sub-classes, AM CVn-type binaries and helium cataclysmic variables, in both of which the central star is a white dwarf. We present a spectroscopic and photometric study of six accreting binaries with orbital periods in the range of 40--70 min, including phase-resolved VLT spectroscopy and high-speed ULTRACAM photometry. Four of these are AM CVn systems and two are helium cataclysmic variables. For four of these binaries we are able to identify orbital periods (of which three are spectroscopic). SDSS J1505+0659 has an orbital period of 67.8 min, significantly longer than previously believed, and longer than any other known AM CVn binary. We identify a WISE infrared excess in SDSS J1505+0659 that we believe to be the first direct detection of an AM CVn donor star in a non-direct impacting binary. The mass ratio of SDSS J1505+0659 is consistent with a white dwarf donor. CRTS J1028-0819 has an orbital period of 52.1 min, the shortest period of any helium cataclysmic variable. MOA 2010-BLG-087 is co-aligned with a K-class star that dominates its spectrum. ASASSN-14ei and ASASSN-14mv both show a remarkable number of echo outbursts following superoutbursts (13 and 10 echo outbursts respectively). ASASSN-14ei shows an increased outburst rate over the years following its superoutburst, perhaps resulting from an increased accretion rate

The delivery of personalised, precision medicines via synthetic proteins

Introduction: The design of advanced drug delivery systems based on synthetic and su-pramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. The Problem: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. The Solution: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein the use of synthetic proteins for drug delivery has been reviewed

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness