Dynamical Criticality: Overview and Open Questions

Systems that exhibit complex behaviours are often found in a particular dynamical condition, poised between order and disorder. This observation is at the core of the so-called criticality hypothesis, which states that systems in a dynamical regime between order and disorder attain the highest level of computational capabilities and achieve an optimal trade-off between robustness and flexibility. Recent results in cellular and evolutionary biology, neuroscience and computer science have revitalised the interest in the criticality hypothesis, emphasising its role as a viable candidate general law in adaptive complex systems. This paper provides an overview of the works on dynamical criticality that are — To the best of our knowledge — Particularly relevant for the criticality hypothesis. The authors review the main contributions concerning dynamics and information processing at the edge of chaos, and illustrate the main achievements in the study of critical dynamics in biological systems.Finally, the authors discuss open questions and propose an agenda for future work.     

SHARP1 suppresses breast cancer metastasis by promoting degradation of hypoxia-inducible factors

The molecular determinants of malignant cell behaviours in breast cancer remain only partially understood. Here we show that SHARP1 (also known as BHLHE41 or DEC2) is a crucial regulator of the invasive and metastatic phenotype in triple-negative breast cancer (TNBC), one of the most aggressive types of breast cancer. SHARP1 is regulated by the p63 metastasis suppressor and inhibits TNBC aggressiveness through inhibition of hypoxia-inducible factor 1α (HIF-1α) and HIF-2α (HIFs). SHARP1 opposes HIF-dependent TNBC cell migration in vitro, and invasive or metastatic behaviours in vivo. SHARP1 is required, and sufficient, to limit expression of HIF-target genes. In primary TNBC, endogenous SHARP1 levels are inversely correlated with those of HIF targets. Mechanistically, SHARP1 binds to HIFs and promotes HIF proteasomal degradation by serving as the HIF-presenting factor to the proteasome. This process is independent of pVHL (von Hippel-Lindau tumour suppressor), hypoxia and the ubiquitination machinery. SHARP1 therefore determines the intrinsic instability of HIF proteins to act in parallel to, and cooperate with, oxygen levels. This work sheds light on the mechanisms and pathways by which TNBC acquires invasiveness and metastatic propensity.     

Late survival of Neanderthals at the southernmost extreme of Europe

The late survival of archaic hominin populations and their long contemporaneity with modern humans is now clear for southeast Asia. In Europe the extinction of the Neanderthals, firmly associated with Mousterian technology, has received much attention, and evidence of their survival after 35 kyr bp has recently been put in doubt. Here we present data, based on a high-resolution record of human occupation from Gorham's Cave, Gibraltar, that establish the survival of a population of Neanderthals to 28 kyr bp. These Neanderthals survived in the southernmost point of Europe, within a particular physiographic context, and are the last currently recorded anywhere. Our results show that the Neanderthals survived in isolated refuges well after the arrival of modern humans in Europe.     

Charon's size and an upper limit on its atmosphere from a stellar occultation

Pluto and its satellite, Charon (discovered in 1978; ref. 1), appear to form a double planet, rather than a hierarchical planet/satellite couple. Charon is about half Pluto's size and about one-eighth its mass. The precise radii of Pluto and Charon have remained uncertain, leading to large uncertainties on their densities. Although stellar occultations by Charon are in principle a powerful way of measuring its size, they are rare, as the satellite subtends less than 0.3 microradians (0.06 arcsec) on the sky. One occultation (in 1980) yielded a lower limit of 600 km for the satellite's radius, which was later refined to 601.5 km (ref. 4). Here we report observations from a multi-station stellar occultation by Charon, which we use to derive a radius, R(C) = 603.6 +/- 1.4 km (1sigma), and a density of rho = 1.71 +/- 0.08 g cm(-3). This occultation also provides upper limits of 110 and 15 (3sigma) nanobar for an atmosphere around Charon, assuming respectively a pure nitrogen or pure methane atmosphere.     

Interneuronal barrages and ripple superposed on inhibitory postsynaptic potentials

Résumé L'activité électrique des neurones du noyau thalamique ventro-latéral est étudiée ici chez des chats anesthésiés au nembutal et immobilisés avec du flaxedil au moyen d'un enregistrement intracellulaire. Nous avons observé que l'enregistrement de certains neurones montre que le potentiel nommé inhibiteur postsynaptique (IPSP) est accompagné de la décharge en barrage d'un autre neurone probablement semblable à la cellule deRenshaw.

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We thank Mr.G. Bilanow for invaluable technical help.     

Selective inhibition of the multiplication of phage T1 inE. coli K12

Riassunto Un nuovo antibiotico, la Distamicina, inibisce selettivamente lo sviluppo del batteriofago T1 inE. coli K12 pur non esercitando alcuna azione sullo sviluppo del microorganismo ospite. L'antibiotico può inibire sia la penetrazione del batteriofago nelle cellule batteriche sia la sua liberazione.     

Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion

Peripheral infection is the natural route of transmission in most prion diseases. Peripheral prion infection is followed by rapid prion replication in lymphoid organs, neuroinvasion and progressive neurological disease. Both immune cells and nerves are involved in pathogenesis, but the mechanisms of prion transfer from the immune to the nervous system are unknown. Here we show that ablation of the chemokine receptor CXCR5 juxtaposes follicular dendritic cells (FDCs) to major splenic nerves, and accelerates the transfer of intraperitoneally administered prions into the spinal cord. Neuroinvasion velocity correlated exclusively with the relative locations of FDCs and nerves: transfer of CXCR5-/- bone marrow to wild-type mice induced perineural FDCs and enhanced neuroinvasion, whereas reciprocal transfer to CXCR5-/- mice abolished them and restored normal efficiency of neuroinvasion. Suppression of lymphotoxin signalling depleted FDCs, abolished splenic infectivity, and suppressed acceleration of pathogenesis in CXCR5-/- mice. This suggests that prion neuroimmune transition occurs between FDCs and sympathetic nerves, and relative positioning of FDCs and nerves controls the efficiency of peripheral prion infection.