Chill out! The impact of stress hormones on cancer cells in vitro

Norepinephrine, the neurotransmitter responsible for stress response, is known to increase the life span ofcancer cells in the human body. By administeringnorepinephrine directly to HeLa cells in vitro, we wereable to track the impact that this neurotransmitter hason the proliferation cancer cells. In our study, we foundthat norepinephrine actually had a negative impact onthe proliferation of HeLa cells in vitro, but our resultsare deemed inconclusive due to possible experimentalerrors

Characterization of large in-frame von Willebrand factor deletions highlights differing pathogenic mechanisms

Copy number variation (CNV) is known to cause all von Willebrand disease (VWD) types, although the associated pathogenic mechanisms involved have not been extensively studied. Notably, in-frame CNV provides a unique opportunity to investigate how specific von Willebrand factor (VWF) domains influence the processing and packaging of the protein. Using multiplex ligation-dependent probe amplification, this study determined the extent to which CNV contributed to VWD in the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease cohort, highlighting in-frame deletions of exons 3, 4-5, 32-34, and 33-34. Heterozygous in vitro recombinant VWF expression demonstrated that, although deletion of exons 3, 32-34, and 33-34 all resulted in significant reductions in total VWF (P < .0001, P < .001, and P < .01, respectively), only deletion of exons 3 and 32-34 had a significant impact on VWF secretion (P < .0001). High-resolution microscopy of heterozygous and homozygous deletions confirmed these observations, indicating that deletion of exons 3 and 32-34 severely impaired pseudo-Weibel-Palade body (WPB) formation, whereas deletion of exons 33-34 did not, with this variant still exhibiting pseudo-WPB formation similar to wild-type VWF. In-frame deletions in VWD, therefore, contribute to pathogenesis via moderate or severe defects in VWF biosynthesis and secretion

Effects of feeding time on markers of muscle metabolic flexibility following acute aerobic exercise in trained mice undergoing time restricted feeding

Time-restricted feeding (TRF) is becoming a popular way of eating in physically active populations, despite a lack of research on metabolic and performance outcomes as they relate to the timing of food consumption in relation to the time of exercise. The purpose of this study was to determine if the timing of feeding/fasting after exercise training differently affects muscle metabolic flexibility and response to an acute bout of exercise. Male C57BL/6 mice were randomized to one of three groups for 8 weeks. The control had ad libitum access to food before and after exercise training. TRF-immediate had immediate access to food for 6 h following exercise training and the TRF-delayed group had access to food 5-h post exercise for 6 h. The timing of fasting did not impact performance in a run to fatigue despite TRF groups having lower hindlimb muscle mass. TRF-delayed had lower levels of muscle HSL mRNA expression and lower levels of PGC-1α expression but displayed no changes in electron transport chain enzymes. These results suggest that in young populations consuming a healthy diet and exercising, the timing of fasting may not substantially impact metabolic flexibility and running performance

Exotic island arc Paleozoic terranes on the eastern margin of Gondwana: Geochemical whole rock and zircon U–Pb–Hf isotope evidence from Barry Station, New South Wales, Australia

Early Paleozoic intra-oceanic terranes crop out along the Peel-Manning Fault System, in the southern New England Orogen, NSW Australia. These are the Cambrian ophiolitic Weraerai terrane and the Siluro-Devonian island arc Gamilaroi terrane. There has been debate whether these terranes formed at the Gondwana margin or if they are intra-oceanic, and were accreted to Gondwana later in the Paleozoic. Major-trace-REE elemental data indicate Weraerai terrane formed in a supra-subduction environment. Rare zircons extracted from Weraerai terrane gabbro-plagiogranite suites at Barry Station yield a U-Pb zircon date of 504.9 ± 3.5 Ma with initial εHf values of + 11.1 indicating a juvenile source. Amphibole-bearing felsic dykes and net-vein complexes are also found within the gabbro with a U-Pb zircon date of 503.2 ± 5.7 Ma and initial εHf values of + 11.6. These are coeval in age with their host rocks and we propose they represent partial melts of the mafic crust during the circulation of seawater. The Gamilaroi trondhjemites of prehnite-pumpellyite-greenschist metamorphic grade terrane yielded very few zircons with an age of 413 ± 8.7 Ma. Zircon initial εHf values range from + 5.0 to + 2.9, indicating an input from an evolved crustal source, unlike the purely oceanic Weraerai terrane. Gamilaroi terrane trondhjemites are enriched in LREE have low K2O and K2O/Na2O ratios and strong negative Nb anomalies consistent with supra-subduction zone environments. Multiple subduction zones may well have existed within the Panthalassa Ocean during the early-mid Paleozoic with the Weraerai-Gamilaroi being accreted onto the Gondwanan margin during the latest Devonian