Mechanisms Regulating Neuromuscular Junction Development and Function and Causes of Muscle Wasting

The neuromuscular junction is the chemical synapse between motor neurons and skeletal muscle fibers. It is designed to reliably convert the action potential from the presynaptic motor neuron into the contraction of the postsynaptic muscle fiber. Diseases that affect the neuromuscular junction may cause failure of this conversion and result in loss of ambulation and respiration. The loss of motor input also causes muscle wasting as muscle mass is constantly adapted to contractile needs by the balancing of protein synthesis and protein degradation. Finally, neuromuscular activity and muscle mass have a major impact on metabolic properties of the organisms. This review discusses the mechanisms involved in the development and maintenance of the neuromuscular junction, the consequences of and the mechanisms involved in its dysfunction, and its role in maintaining muscle mass during aging. As life expectancy is increasing, loss of muscle mass during aging, called sarcopenia, has emerged as a field of high medical need. Interestingly, aging is also accompanied by structural changes at the neuromuscular junction, suggesting that the mechanisms involved in neuromuscular junction maintenance might be disturbed during aging. In addition, there is now evidence that behavioral paradigms and signaling pathways that are involved in longevity also affect neuromuscular junction stability and sarcopenia

The Twannberg iron meteorite strewn field in the Swiss Jura mountains: insights for Quaternary environmental conditions

The ~ 10 km 2 strewn field of the Twannberg type IIG iron meteorite is located in the Swiss Jura Mountains, 30 km northwest of Bern. The strewn field has been mapped by a group of citizen scientists since 2006, yielding more than 2000 meteorite fragments with a total mass of 152.7 kg until the end of 2022. With a terrestrial age of 176 ± 19 ka and a minimum pre-atmospheric mass of ~ 250 t, the Twannberg meteorite is a local time marker in an area with a poorly-known paleoenvironmental history. The Twannberg strewn field is located just outside of the maximum extent of ice during the Last Glacial Maximum (LGM). On the Mont Sujet, meteorites are size-sorted in a 6-km long section of the primary strewn field (altitude 945-1370 m a.s.l.), indicating a fall direction from east-northeast to west-southwest (azimuth approximately 250°). On the Twannberg plateau and in the Twannbach gorge, meteorites are not size-sorted and occur in a ~ 5.7-km long area associated with till and recent stream sediments (altitude 430-1075 m a.s.l.). The mass distribution of meteorites on the Twannberg plateau demonstrate that these meteorites were not found where they fell but that they must have been transported up to several km by glacier ice flow after the fall. The distribution of meteorites and of glacially transported Alpine clasts on the Mont Sujet and on the Chasseral chain indicates the presence of local ice caps and of an approximately 200-m higher Alpine ice surface with respect to the LGM at the time of fall. This high ice level during MIS 6 (Marine Isotopic Stage 6, 191-130 ka) indicated by the meteorite distribution is consistent with surface exposure ages of 50-144 ka from nearby resting erratic boulders at altitudes of up to 1290 m a.s.l., including the newly dated Jobert boulder (63 ka). These boulders indicate an ice level ~ 400 m higher than during LGM at a time not later than MIS 6. Post-LGM luminescence ages of loesscontaining meteorites on the Mont Sujet and 14 C ages of materials associated with meteorite finds indicate relatively young pedoturbation and increased oxidation of meteorites since ~ 7300 cal BP, possibly correlated with deforestation and enhanced erosion resulting from increased human activities since the Neolithic. This study shows that Twannberg meteorites in their palaeoenvironmental context provide valuable information about ice levels and transport directions during MIS 6 and about their interaction with the post-LGM environmental conditions. The unique Twannberg strewn field has the potential to reveal more valuable information