Elevated Fibroblast growth factor 21 (FGF21) in obese, insulin resistant states is normalised by the synthetic retinoid Fenretinide in mice

The authors would like to thank undergraduate student Aleksandra Kowalczuk (University of Aberdeen) for assisting in experiments and Dr. Emma K. Lees (School of Health Sciences, Liverpool Hope University, Liverpool, UK) for invaluable discussions concerning the regulation of FGF21. We thank Dr. Calum Sutherland and Dr. Amy Cameron (both Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK) for technical support and expertise in performing hepatocyte studies. Fenretinide was a generous gift of T. Martin (Johnson & Johnson, New Brunswick, NJ) and U. Thumeer (Cilag AG, Schaffhausen, Switzerland), for use completely without restriction or obligation. Quantitative-PCR was carried out using the qPCR Core Facility (Institute of Medical Sciences, University of Aberdeen). RNA-sequencing was carried out at the University of Aberdeen Centre for Genome Enabled Biology and Medicine. Pancreas histology was performed by Dr Linda Davidson (Department of Histology, Aberdeen Royal Infirmary, NHS Grampian, Foresterhill Health Campus, Aberdeen, UK). This study was supported by the British Heart Foundation Intermediate Basic Research Fellowship FS/09/026 to N. Mody, RCUK fellowship to MD, EFSD/Lilly Programme Grant to MD and N. Mody, Tenovus Scotland grants G10/04 and G14/14 to N. Mody, University of Aberdeen Centre for Genome Enabled Biology and Medicine (CGEBM) PhD studentship to N. Morrice and Biotechnology and Biological Sciences Research Council studentship to GDM.Peer reviewedPublisher PD

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Do Aging and Dual-Tasking Impair the Capacity to Store and Retrieve Visuospatial Information Needed to Guide Perturbation-Evoked Reach-To-Grasp Reactions?

A recent study involving young adults showed that rapid perturbation-evoked reach-to-grasp balance-recovery reactions can be guided successfully with visuospatial-information (VSI) retained in memory despite: 1) a reduction in endpoint accuracy due to recall-delay (time between visual occlusion and perturbation-onset, PO) and 2) slowing of the reaction when performing a concurrent cognitive task during the recall-delay interval. The present study aimed to determine whether this capacity is compromised by effects of aging. Ten healthy older adults were tested with the previous protocol and compared with the previously-tested young adults. Reactions to recover balance by grasping a small handhold were evoked by unpredictable antero-posterior platform-translation (barriers deterred stepping reactions), while using liquid-crystal goggles to occlude vision post-PO and for varying recall-delay times (0-10s) prior to PO (the handhold was moved unpredictably to one of four locations 2s prior to vision-occlusion). Subjects also performed a spatial- or non-spatial-memory cognitive task during the delay-time in a subset of trials. Results showed that older adults had slower reactions than the young across all experimental conditions. Both age groups showed similar reduction in medio-lateral end-point accuracy when recall-delay was longest (10s), but differed in the effect of recall delay on vertical hand elevation. For both age groups, engaging in either the non-spatial or spatial-memory task had similar (slowing) effects on the arm reactions; however, the older adults also showed a dual-task interference effect (poorer cognitive-task performance) that was specific to the spatial-memory task. This provides new evidence that spatial working memory plays a role in the control of perturbation-evoked balance-recovery reactions. The delays in completing the reaction that occurred when performing either cognitive task suggest that such dual-task situations in daily life could increase risk of falling in seniors, particularly when combined with the general age-related slowing that was observed across all experimental conditions