A bipartite structural organization defines the SERINC family of HIV-1 restriction factors

The human integral membrane protein SERINC5 potently restricts HIV-1 infectivity and sensitizes the virus to antibody-mediated neutralization. Here, using cryo-EM, we determine the structures of human SERINC5 and its orthologue from Drosophila melanogaster at subnanometer and near-atomic resolution, respectively. The structures reveal a novel fold comprised of ten transmembrane helices organized into two subdomains and bisected by a long diagonal helix. A lipid binding groove and clusters of conserved residues highlight potential functional sites. A structure-based mutagenesis scan identified surface-exposed regions and the interface between the subdomains of SERINC5 as critical for HIV-1-restriction activity. The same regions are also important for viral sensitization to neutralizing antibodies, directly linking the antiviral activity of SERINC5 with remodeling of the HIV-1 envelope glycoprotein

Severe acute respiratory syndrome coronavirus 2 serosurveillance in a patient population reveals differences in virus exposure and antibody-mediated immunity according to host demography and healthcare setting

Identifying drivers of SARS-CoV-2 exposure and quantifying population immunity is crucial to prepare for future epidemics. We performed a serial cross-sectional serosurvey throughout the first pandemic wave among patients from the largest health board in Scotland. Screening of 7480 patient sera showed a weekly seroprevalence ranging from 0.10% to 8.23% in primary and 0.21% to 17.44% in secondary care, respectively. Neutralisation assays showed that around half of individuals who tested positive by ELISA assay, developed highly neutralising antibodies, mainly among secondary care patients. We estimated the individual probability of SARS-CoV-2 exposure and quantified associated risk factors. We show that secondary care patients, males and 45-64-year-olds exhibit a higher probability of being seropositive. The identification of risk factors and the differences in virus neutralisation activity between patient populations provided insights into the patterns of virus exposure during the first pandemic wave and shed light on what to expect in future waves

Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which ∼20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants

Author Correction: Scalable and robust SARS-CoV-2 testing in an academic center.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

The cellular and molecular basis of the Nef requirement for HIV-1 infectivity

Nef is an HIV -1 accessory protein with a fundamental role for virus replication in vivo and for the development of AIDS. Among its several activities, Nef is essential for full HIV-1 infectivity, a function highly prominent in lymphoid cells. So far, the mechanism by which Nef promotes HIV-1 infectivity has remained elusive. Over the course of 3 years, my PhD research activity has led to the identification of the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as potent inhibitors of HIV-1 infectivity counteracted by the viral protein Nef [Rosa et al., 2015]. SERINC5 is predominantly localized on the plasma membrane where it is efficiently incorporated into budding HIV-1 virions and impairs subsequent virion penetration of susceptible target cells. Nef relocalizes SERINC5 to an endosomal compartment preventing its incorporation into HIV-1 particles. The ability to counteract SERINC5 is conserved in Nef proteins encoded by different primate immunodeficiency viruses, as well as in the structurally unrelated glycosylated Gag from murine leukaemia virus (MLV). These examples of functional conservation and convergent evolution emphasize the fundamental importance of SERINC5 in the interaction of the host with retroviral pathogens. Remarkably, SERINC5 potently inhibits HIV-1 even in the presence of Nef in a dose-dependent manner, suggesting that this cellular factor might be exploited as an anti-HIV-1 therapeutic gene

Perception of the Ebbinghaus illusion in four-day-old domestic chicks (Gallus gallus)

In the Ebbinghaus size illusion, a central circle surrounded by small circles (inducers) appears bigger than an identical one surrounded by large inducers. Previous studies have failed to demonstrate sensitivity to this illusion in pigeons and baboons, leading to the conclusion that avian species (possibly also nonhuman primates) might lack the neural substrate necessary to perceive the Ebbinghaus illusion in a human-like fashion. Such a substrate may have been only recently evolved in the primate lineage. Here, we show that this illusion is perceived by 4-day-old domestic chicks. During rearing, chicks learnt, according to an observational-learning paradigm, to find food in proximity either of a big or of a small circle. Subjects were then tested with Ebbinghaus stimuli: two identical circles, one surrounded by larger and the other by smaller inducers. The percentage of approaches to the perceptually bigger target in animals reinforced on the bigger circle (and vice versa for the other group) was computed. Over four experiments, we demonstrated that chicks are reliably affected by the illusory display. Subjects reinforced on the small target choose the configuration with big inducers, in which the central target appears perceptually smaller; the opposite is true for subjects reinforced on the big target. This result has important implications for the evolutionary history of the neural substrate involved in the perception of the Ebbinghaus illusion

Global processing of visual configurations in domestic chicks.

Perceptual organization refers to the process by which several visual elements are grouped in a coherent scene by the relationship among them. It is plausible that the general principles of perceptual organization are common between species because of environmental regularities, which are relatively independent from the specific niche of each species. The most relevant case is the segmentation of a visual scene in biologically relevant units, the objects which are composed by elements that can be analysed separately (local processing), but also integrated in a unitary percept by extracting the overall configuration (global processing). There are two important examples which demonstrate the advantage of global over local processing configuration. The first one concerns the Ebbinghaus illusion in which an object surrounded by small inducers appears larger than another surrounded by large inducers. In this case, to perceive the illusion it is essential to process the global configuration. This illusion has been extensively studied in humans. In animals, up to the present moment, it has been studied only in adult subjects of one primate species (baboons, Parron e Fagot, 2007) and in pigeons (Nakamura et al. 2008). We devised a procedure to test the Ebbinghaus illusion in domestic chicks: this species, which has been already employed for testing sensitivity to other visual illusions (e.g. Regolin & Vallortigara, 1995; Zanforlin, 1981) offers the advantage of allowing to test very young animals (being a precocial species), of controlling for the role of previous visual experience and allowing comparisons with data obtained in human infants and children. We reinforced chicks for choosing either a small or a large orange circle (for half of the chicks food was associated with the large circle, and vice versa for the other half). Subjects were then tested with Ebbinghaus-stimuli: two identical orange circles were presented one surrounded by large and the other by small gray inducer circles. Results suggest that the Ebbinghaus-illusion may be perceived at least by part of the chicks. Another important example which demonstrates the advantage of global over local processing configuration concerns the impossible objects in which several local cues need to be integrated to detect global inconsistencies in structural information, allowing discrimination between possible and impossible objects. Here we show that, after exposure to objects in which junctions providing cues to global structure were occluded, day-old chicks selectively approach the two-dimensional image that depicted the possible rather than impossible version of a three-dimensional object, after restoration of the junctions. Even more impressively, completely naive newly hatched chicks showed spontaneous preferences towards approaching two-dimensional depictions of structurally possible rather than impossible objects. These results show that natural selection can produce organisms perfectly able to deal with the problem of global coherence in three-dimensional objects as recovered from two-dimensional images in the absence of any specific experience of real three-dimensional objects

Holistic perception of visual configurations in young domestic chicks.

Perceptual organization involves the grouping of visual elements in a coherent scene. The most relevant case is the segmentation of a visual scene in biologically relevant units, which are composed by elements that can be analysed separately (local processing), but also integrated in a unitary percept by extracting the overall configuration (global processing). A peculiar example of global processing is the perception of artificially figures (the \u201cimpossible objects\u201d). These are represented by 2D drawings giving the impression of 3D objects; each part of the figure is acceptable as a correct representation of a 3D object, nevertheless the whole figure results \u201cimpossible\u201d due to false connections between parts. The identification of an impossible figure requires the integration of local and global processing, providing a unique possibility to study implicit knowledge about objects\u2019 properties. The general principles of perceptual organization are shared by different species. Indeed domestic chicks, similarly to human infants, proved able to discriminate between possible and impossible figures and also showed spontaneous preferences for two-dimensional depictions of possible rather than impossible objects, suggesting an innate ability to recognize global coherence in two-dimensional representations of three-dimensional objects. We also investigated another example of the predominance of global-configural processing. In the Ebbinghaus illusion, a stimulus surrounded by smaller stimuli appears larger than an identical stimulus surrounded by larger inducers. The global configuration of the stimulus is essential to perceive the illusion. This illusion has been extensively investigated in human adults, for whom it seems to be modulated by cultural factors, though data on pre-verbal infants or children are either scanty or contradictory. In animal species, the Ebbinghaus illusion has been studied only in adult baboons and pigeons. We devised a procedure to test the Ebbinghaus illusion in 3-day old domestic chicks. This species offers the advantage of allowing to test very young animals and of controlling previous visual experience, providing fruitful comparisons with data obtained in human infants and children. In the main experiment, during the first two days of life chicks were food reinforced in their home cages for approaching either a small orange circle (half of the sample, N=8) or a bigger circle (N=8). Subjects were then tested with Ebbinghaus-stimuli: two identical orange target circles were presented, one surrounded by larger and the other by smaller gray inducer circles. The percentage of correct choices (e.g. approach of the perceptually bigger target in chicks reinforced on the bigger circle) performed by each animal was computed. Results suggest that the Ebbinghaus-illusion may be perceived at least by part of the chicks (those reinforced on the smaller target, t(7) =2.646, p=0.033). Our data call for more in depth investigations concerning the role of cultural/experiential factors in the perception of the Ebbinghaus Illusion, since they support the possibility that global processing of visual configurations can be performed by animals, early in life, and in conditions of controlled visual experience

One, two, three, four, or is there something more? Numerical discrimination in day-old domestic chicks

Human adults master sophisticated, abstract numerical calculations that are mostly based on symbolic language and thus inimitably human. Humans may nonetheless share a subset of non-verbal numerical skills, available soon after birth and considered the evolutionary foundation of more complex numerical reasoning, with other animals. These skills are thought to be based on the two systems: the object file system which processes small values ( 4). Infants' ability to discriminate 1 vs. 2, 1 vs. 3, 2 vs. 3, but not 1 vs. 4, seems to indicate that the two systems are independent, implying that the conception of a continuous number processing system is based on precursors that appear to be interrupted at or about the number four. The findings from the study being presented here indicating that chicks are able to make a series of discriminations regarding that borderline number (1 vs. 4, 1 vs. 5, 2 vs. 4) support the hypothesis that there is continuity in the number system which processes both small and large numerousnes

Atmospheric gas plasma treatment of fresh-cut apples

In this study we pioneered the use of gas plasma for the treatment of fresh-cut apples and its potential application in the agri-food precesses. Treatments were conducted on fresh-cut Pink Lady\uae apples using a Dielectric Barrier Discharge (DBD) generator and considering three different times: 10, 20 and 30 min. Main quality (soluble solid content, titrable acidy, colour by computer vision system and texture) and metabolic parameters (polyphenol oxidase PPO activity, respiration and heat production) were assessed immediately after the treatment and during a storage of 24 h (10 \ub0C, 90% RH). In terms of browned areas, a significant decrease was observed in treated samples compared to the control ones (up to about 65% for 30 min and after 4 h of storage). PPO residual activity decreased linearly by increasing the treatment time (up to about 42%). In general the treatment appeared to slow down the metabolic activity of the tissue. Other qualitative parameters were only slightly affected by the treatment