Brain imaging factors associated with progression of subcortical hyperintensities in CADASIL over two year follow up

Background: Mutations in the NOTCH3 gene cause CADASIL, a cerebral small vessel disease manifesting with stroke, migraine and dementia in adults. The disease displays significant phenotypic variability which is incompletely explained. Early abnormalities in vascular function have been shown in animal models. We postulated that studying changes in vascular function may offer insights into disease progression. Methods: Twenty two subjects with CADASIL (50% female, 50 (±11) years) from 19 pedigrees were included in a longitudinal multimodality study using brain MRI, clinical measures, neuropsychology, and measures of peripheral vascular function. MRI studies included measurement of structural brain changes, cerebral blood flow (CBF) and cerebrovascular reactivity by arterial spin labelling and a CO2 respiratory challenge. Results: Over two years, new stroke or TIA occurred in 5 (23%) subjects and new significant disability in 1 (5%). There were significant increases in number of lacunes, subcortical hyperintensity volume and microbleeds, and a decrease in brain volume. CBF declined by 3.2 (±4.5) ml/100g/min over two years. CBF and carotid‐femoral pulse wave velocity at baseline predicted change in subcortical hyperintensity volume at follow up. Carotid‐intima‐media thickness and age predicted brain atrophy. Baseline CBF was lower in subjects who showed a decline in attention and working memory. Conclusion: CBF predicts radiological progression of hyperintensities and thus is a potential biomarker of disease progression in CADASIL. Over two years, there were changes in several relevant imaging biomarkers (CBF, brain volume, lacunes, microbleeds, and hyperintensity volume). Future studies in CADASIL should consider assessment of CBF as prognostic factor

A research agenda for seed-trait functional ecology

Trait-based approaches have improved our understanding of plant evolution, community assembly and ecosystem functioning. A major challenge for the upcoming decades is to understand the functions and evolution of early life-history traits, across levels of organization and ecological strategies. Although a variety of seed traits are critical for dispersal, persistence, germination timing and seedling establishment, only seed mass has been considered systematically. Here we suggest broadening the range of morphological, physiological and biochemical seed traits to add new understanding on plant niches, population dynamics and community assembly. The diversity of seed traits and functions provides an important challenge that will require international collaboration in three areas of research. First, we present a conceptual framework for a seed ecological spectrum that builds upon current understanding of plant niches. We then lay the foundation for a seed-trait functional network, the establishment of which will underpin and facilitate trait-based inferences. Finally, we anticipate novel insights and challenges associated with incorporating diverse seed traits into predictive evolutionary ecology, community ecology and applied ecology. If the community invests in standardized seed-trait collection and the implementation of rigorous databases, major strides can be made at this exciting frontier of functional ecology

The evolution of the Australian ‘ndrangheta. An historical perspective

This paper explores the phenomenon of the ‘ndrangheta – a criminal organisation from Calabria, South of Italy and allegedly the most powerful among the Italian mafias – through its migrating routes. In particular, by focusing on the peculiar case of Australia, the paper aims to show the overlapping of migrating flows with criminal colonisation, which has proven to be a strategy of this particular mafia. The paper uses the very thin literature on the subject alongside official reports and newspaper articles on migration and crime, mainly from Italian sources, to trace an historical journey on the migration of people from Calabria to Australia in various moments of the last century. The aim is to present the evolution and growth of Calabrian clans in Australia. The topic is largely unexplored and is still underreported among Australian institutions and scholars, which is why the paper chooses an historical approach to describe the principal paths in this very new field of research

Sport, War and Democracy in Classical Athens

This article concerns the paradox of athletics in classical Athens. Democracy may have opened up politics to every class of Athenian but it had little impact on sporting participation. The city’s athletes continued to drawn predominantly from the upper class. It comes as a surprise then that lower-class Athenians actually esteemed athletes above every other group in the public eye, honoured them very generously when they won, and directed a great deal of public and private money to sporting competitions and facilities. In addition athletics escaped the otherwise persistent criticism of upper-class activities in the popular culture of the democracy. The research of social scientists on sport and aggression suggests this paradox may have been due to the cultural overlap between athletics and war under the Athenian democracy. The article concludes that the practical and ideological democratization of war by classical Athens legitimized and supported upper-class sport

Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons

The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch, and skin temperature. Despite its importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here, we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters of ALS neurons (ALS1-5) and document their laminar distribution in the spinal cord using in situ hybridization. We identify three clusters of neurons located predominantly in laminae I–III of the dorsal horn (ALS1-3) and two clusters with cell bodies located in deeper laminae (ALS4 and ALS5). Our findings reveal the transcriptional logic that underlies ALS neuronal diversity in the adult mouse and uncover the molecular identity of two previously identified classes of projection neurons. We also show that these molecular signatures can be used to target groups of ALS neurons using retrograde viral tracing. Overall, our findings provide a valuable resource for studying somatosensory biology and targeting subclasses of ALS neurons