Motor neuron degeneration, severe myopathy and TDP-43 increase in a transgenic pig model of SOD1-linked familiar ALS

Amyotrophic Lateral Sclerosis (ALS) is a neural disorder gradually leading to paralysis of the whole body. Alterations in superoxide dismutase SOD1 gene have been linked with several variants of familial ALS. Here, we investigated a transgenic (Tg) cloned swine model expressing the human pathological hSOD1G93A allele. As in patients, these Tg pigs transmitted the disease to the progeny with an autosomal dominant trait and showed ALS onset from about 27 months of age. Post mortem analysis revealed motor neuron (MN) degeneration, gliosis and hSOD1 protein aggregates in brainstem and spinal cord. Severe skeletal muscle pathology including necrosis and inflammation was observed at the end stage, as well. Remarkably, as in human patients, these Tg pigs showed a quite long presymptomatic phase in which gradually increasing amounts of TDP-43 were detected in peripheral blood mononuclear cells. Thus, this transgenic swine model opens the unique opportunity to investigate ALS biomarkers even before disease onset other than testing novel drugs and possible medical devices

A bibliometric analysis of family firm internationalization research: current themes, theoretical roots, and ways forward

This paper presents a bibliometric analysis and a systematic literature review of 161 core contributions concerning family firm internationalization. A bibliographic coupling analysis and a co-citation analysis reveal the richness of family firm internationalization research and help to organize this large body of work into five thematic clusters and seven theoretical roots. By examining the linkages between research themes and theoretical roots, we advance an integrative framework, clarifying the variety of research paths available regarding the internationalization of family firms, and identifying new and important research avenues for further developing the field