Heptad stereotypy, S/Q layering, and remote origin of the SARS-CoV-2 fusion core

The fusion of the SARS-CoV-2 virus with cells, a key event in the pathogenesis of Covid-19, depends on the assembly of a six-helix fusion core (FC) formed by portions of the spike protein heptad repeats (HRs) 1 and 2. Despite the critical role in regulating infectivity, its distinctive features, origin, and evolution are scarcely understood. Thus, we undertook a structure-guided positional and compositional analysis of the SARS-CoV-2 FC, in comparison with FCs of related viruses, tracing its origin and ongoing evolution. We found that clustered amino acid substitutions within HR1, distinguishing SARS-CoV-2 from SARS-CoV-1, enhance local heptad stereotypy and increase sharply the FC serine-to-glutamine (S/Q) ratio, determining a neat alternate layering of S-rich and Q-rich subdomains along the post-fusion structure. Strikingly, SARS-CoV-2 ranks among viruses with the highest FC S/Q ratio, together with highly syncytiogenic respiratory pathogens (RSV, NDV), whereas MERS-Cov, HIV, and Ebola viruses display low ratios, and this feature reflects onto S/Q segregation and H-bonding patterns. Our evolutionary analyses revealed that the SARS-CoV-2 FC occurs in other SARS-CoV-1-like Sarbecoviruses identified since 2005 in Hong Kong and adjacent regions, tracing its origin to >50 years ago with a recombination-driven spread. Finally, current mutational trends show that the FC is varying especially in the FC1 evolutionary hotspot. These findings establish a novel analytical framework illuminating the sequence/structure evolution of the SARS-CoV-2 FC, tracing its long history within Sarbecoviruses, and may help rationalize the evolution of the fusion machinery in emerging pathogens and the design of novel therapeutic fusion inhibitors

A Categorical Framework for Quantum Theory

Underlying any theory of physics is a layer of conceptual frames. They connect the mathematical structures used in theoretical models with physical phenomena, but they also constitute our fundamental assumptions about reality. Many of the discrepancies between quantum physics and classical physics (including Maxwell's electrodynamics and relativity) can be traced back to these categorical foundations. We argue that classical physics corresponds to the factual aspects of reality and requires a categorical framework which consists of four interdependent components: boolean logic, the linear-sequential notion of time, the principle of sufficient reason, and the dichotomy between observer and observed. None of these can be dropped without affecting the others. However, in quantum theory the reduction postulate also addresses the "status nascendi" of facts, i.e., their coming into being. Therefore, quantum phyics requires a different conceptual framework which will be elaborated in this article. It is shown that many of its components are already present in the standard formalisms of quantum physics, but in most cases they are highlighted not so much from a conceptual perspective but more from their mathematical structures. The categorical frame underlying quantum physics includes a profoundly different notion of time which encompasses a crucial role for the present.Comment: 35 pages, 1 figur

Coupling ultracold atoms to mechanical oscillators

In this article we discuss and compare different ways to engineer an interface between ultracold atoms and micro- and nanomechanical oscillators. We start by analyzing a direct mechanical coupling of a single atom or ion to a mechanical oscillator and show that the very different masses of the two systems place a limit on the achievable coupling constant in this scheme. We then discuss several promising strategies for enhancing the coupling: collective enhancement by using a large number of atoms in an optical lattice in free space, coupling schemes based on high-finesse optical cavities, and coupling to atomic internal states. Throughout the manuscript we discuss both theoretical proposals and first experimental implementations.Comment: 19 pages, 9 figure

Diabetic Striatopathy: Case Report and Possible New Actors

Diabetic striatopathy is a very rare neurological complication of diabetes. We report the case of an 86-year-old woman with poorly controlled type 2 diabetes admitted to the internal medicine ward for sudden onset of altered sensorium and severe bilateral choreiform and ballistic movements. The precise pathophysiology of this condition is not well understood. Our communication aims to remind clinicians to consider the possibility of diabetic striatopathy when poor-controlled diabetic patients have sudden-onset choreiform and ballistic movements. Moreover, this case suggests the possibility that oxidative and endoplasmic reticulum stress may be involved in this process