Age related decline in aluminum-activated human platelet adenylate cyclase: post-receptor changes in cyclic AMP second messenger signal amplification in normal aging and dementia of the Alzheimer type

Low, micromolar concentrations of aluminum (in the presence of NaF) were shown to strongly activate human platelet adenylate cyclase and provided a useful probe for evaluating cyclic AMP second messenger function distal to the receptor: The effect of normal aging and disease state on second messenger activity in man was studied by measurements of the aluminum-activated enzyme. A significant decline in aluminum-stimulated platelet adenylate cyclase activity in older, healthy subjects was observed. An age-associated decline in NaF-stimulated cyclic AMP synthesis was also demonstrated for normal, non-demented subjects. These findings suggest an age-associated lesion at the level of the guanine nucleotide regulatory protein/catalytic subunit of the adenylate cyclase complex. However, for patients with Alzheimer's disease no such decline in platelet adenylate cyclase activity was detected, and increased sensitivity to both aluminum and NaF was demonstrated.     

Alloy Anode Materials for Rechargeable Mg Ion Batteries

Rechargeable magnesium ion batteries are interesting as one of the alternative metal ion battery systems to lithium ion batteries due to the wide availability and accessibility of magnesium in the earth's crust. On the one hand, electrolyte solutions in which Mg metal anodes are fully reversible are not suitable for the use of high voltage/high capacity transition metal oxide cathodes due to complex surface phenomena. On the other hand, Mg metal anodes cannot work reversibly in conventional electrolyte solutions in which high voltage/high capacity Mg insertion cathodes can work because of passivation phenomena that fully block them. Replacing Mg metal with alternative anodes that can work reversibly in conventional electrolyte solutions could provide a promising route to elaborate high voltage and high capacity rechargeable Mg battery systems. Herein, the recent progress in alloy anodes based on group IIIA, IVA, VA elements is summarized. The theoretical evaluations, achievable capacities, synthetic strategies, battery test configurations, electrochemical properties, and underlying reaction mechanisms are systematically summarized and discussed. The key issues and challenges impeding their current use are identified and some valuable suggestions for their future development as practical reversible anodes for Mg batteries are provided.     

A Unique haplotype found in apple accessions exhibiting early bud-break could serve as a marker for breeding apples with low chilling requirements

Most commercial apple cultivars have high to medium chilling requirements and consequently are not grown in regions with warm winters. Furthermore, global climate changes raise the concern that some regions where apples are currently being produced will become unsuitable in the future. Therefore, mapping and understanding the factors governing chilling requirements are important goals towards the breeding of new apple varieties. In this study, we characterized 73 apple accessions: old local accessions, modern cultivars, and selected hybrids, all grown in the Newe Ya’ar germplasm collection in Israel under moderate winter conditions. We measured the time of vegetative bud-break as an indicator of chilling requirements and genotyped the accessions for known genetic markers and for markers we developed by re-sequencing the genome of ‘Anna’, a cultivar with very low chilling requirements. Our results show that while most of the accessions that were characterized as having early bud-break are genetically different from each other, they all share a unique haplotype in a region of ～190 kb, within a previously identified QTL for bud-break time, on chromosome 9. The alleles in the early bud-break-associated haplotype were not found in any of the late accessions tested, suggesting that the causative difference leading to the variation in bud-break time lays within or near this region, and that there is a common ancestor carrying early bud-break trait of the early accessions tested. Moreover, the markers of the unique haplotype can serve as genetic markers to accelerate the breeding of apple cultivars better adapted to warm climates.     

Biphasic Activation of WNT Signaling Facilitates the Derivation of Midbrain Dopamine Neurons from hESCs for Translational Use

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Localized Sampling Enables Monitoring of Cell State via Inline Electrospray Ionization Mass Spectrometry

Nascent advanced therapies, including regenerative medicine and cell and gene therapies, rely on the production of cells in bioreactors that are highly heterogeneous in both space and time. Unfortunately, advanced therapies have failed to reach a wide patient population due to unreliable manufacturing processes that result in batch variability and cost prohibitive production. This can be attributed largely to a void in existing process analytical technologies (PATs) capable of characterizing the secreted critical quality attribute (CQA) biomolecules that correlate with the final product quality. The Dynamic Sampling Platform (DSP) is a PAT for cell bioreactor monitoring that can be coupled to a suite of sensor techniques to provide real-time feedback on spatial and temporal CQA content in situ. In this study, DSP is coupled with electrospray ionization mass spectrometry and direct-from-culture sampling to obtain measures of CQA content in bulk media and the cell microenvironment throughout the entire cell culture process (≈3 weeks). Post hoc analysis of this real-time data reveals that sampling from the microenvironment enables cell state monitoring (e.g., confluence, differentiation). These results demonstrate that an effective PAT should incorporate both spatial and temporal resolution to serve as an effective input for feedback control in biomanufacturing.