Has SARS-CoV-2 reached peak fitness?

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Heterogeneous Mean Field for neural networks with short term plasticity

We report about the main dynamical features of a model of leaky-integrate-and fire excitatory neurons with short term plasticity defined on random massive networks. We investigate the dynamics by a Heterogeneous Mean-Field formulation of the model, that is able to reproduce dynamical phases characterized by the presence of quasi-synchronous events. This formulation allows one to solve also the inverse problem of reconstructing the in-degree distribution for different network topologies from the knowledge of the global activity field. We study the robustness of this inversion procedure, by providing numerical evidence that the in-degree distribution can be recovered also in the presence of noise and disorder in the external currents. Finally, we discuss the validity of the heterogeneous mean-field approach for sparse networks, with a sufficiently large average in-degree

Average synaptic activity and neural networks topology: a global inverse problem

The dynamics of neural networks is often characterized by collective behavior and quasi-synchronous events, where a large fraction of neurons fire in short time intervals, separated by uncorrelated firing activity. These global temporal signals are crucial for brain functioning. They strongly depend on the topology of the network and on the fluctuations of the connectivity. We propose a heterogeneous mean--field approach to neural dynamics on random networks, that explicitly preserves the disorder in the topology at growing network sizes, and leads to a set of self-consistent equations. Within this approach, we provide an effective description of microscopic and large scale temporal signals in a leaky integrate-and-fire model with short term plasticity, where quasi-synchronous events arise. Our equations provide a clear analytical picture of the dynamics, evidencing the contributions of both periodic (locked) and aperiodic (unlocked) neurons to the measurable average signal. In particular, we formulate and solve a global inverse problem of reconstructing the in-degree distribution from the knowledge of the average activity field. Our method is very general and applies to a large class of dynamical models on dense random networks

Molecular signatures of hepatitis C virus (HCV)-induced type II mixed cryoglobulinemia (MCII)

The role of hepatitis C virus (HCV) infection in the induction of type II mixed cryoglobulinemia (MCII) and the possible establishment of related lymphoproliferative disorders, such as B-cell non-Hodgkin lymphoma (B-NHL), is well ascertained. However, the molecular pathways involved and the factors predisposing to the development of these HCV-related extrahepatic complications deserve further consideration and clarification. To date, several host- and virus-related factors have been implicated in the progression to MCII, such as the virus-induced expansion of selected subsets of B-cell clones expressing discrete immunoglobulin variable (IgV) gene subfamilies, the involvement of complement factors and the specific role of some HCV proteins. In this review, we will analyze the host and viral factors taking part in the development of MCII in order to give a general outlook of the molecular mechanisms implicated

A closer look at prion strains: characterization and important implications

Prions are infectious proteins that are responsible for transmissible spongiform encephalopathies (TSEs) and consist primarily of scrapie prion protein (PrPSc), a pathogenic isoform of the host-encoded cellular prion protein (PrPC). The absence of nucleic acids as essential components of the infectious prions is the most striking feature associated to these diseases. Additionally, different prion strains have been isolated from animal diseases despite the lack of DNA or RNA molecules. Mounting evidence suggests that prion-strain-specific features segregate with different PrPSc conformational and aggregation states. Strains are of practical relevance in prion diseases as they can drastically differ in many aspects, such as incubation period, PrPSc biochemical profile (e.g., electrophoretic mobility and glycoform ratio) and distribution of brain lesions. Importantly, such different features are maintained after inoculation of a prion strain into genetically identical hosts and are relatively stable across serial passages. This review focuses on the characterization of prion strains and on the wide range of important implications that the study of prion strains involves

Possible future monoclonal antibody (mAb)-based therapy against arbovirus infections

More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminary in vitro and in vivo models of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy

HCV Proteins and Immunoglobulin Variable Gene (IgV) Subfamilies in HCV-Induced Type II Mixed Cryoglobulinemia: A Concurrent Pathogenetic Role

The association between hepatitis C virus (HCV) infection and type II mixed cryoglobulinemia (MCII) is well established, but the role played by distinct HCV proteins and by specific components of the anti-HCV humoral immune response remains to be clearly defined. It is widely accepted that HCV drives the expansion of few B-cell clones expressing a restricted pool of selected immunoglobulin variable (IgV) gene subfamilies frequently endowed with rheumatoid factor (RF) activity. Moreover, the same IgV subfamilies are frequently observed in HCV-transformed malignant B-cell clones occasionally complicating MCII. In this paper, we analyze both the humoral and viral counterparts at the basis of cryoglobulins production in HCV-induced MCII, with particular attention reserved to the single IgV subfamilies most frequently involved

Influenza B-cells protective epitope characterization: a passkey for the rational design of new broad-range anti-influenza vaccines

The emergence of new influenza strains causing pandemics represents a serious threat to human health. From 1918, four influenza pandemics occurred, caused by H1N1, H2N2 and H3N2 subtypes. Moreover, in 1997 a novel influenza avian strain belonging to the H5N1 subtype infected humans. Nowadays, even if its transmission is still circumscribed to avian species, the capability of the virus to infect humans directly from avian reservoirs can result in fatalities. Moreover, the risk that this or novel avian strains could adapt to inter-human transmission, the development of resistance to anti-viral drugs and the lack of an effective prevention are all incumbent problems for the world population. In this scenario, the identification of broadly neutralizing monoclonal antibodies (mAbs) directed against conserved regions shared among influenza isolates has raised hopes for the development of monoclonal antibody-based immunotherapy and “universal” anti-influenza vaccines