Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by pre-existing immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

Co-evolution patterns of university patenting and technological specialization in European regions

This paper provides novel evidence on co-evolution patterns of the technological specialization of innovation activities of firms and academic institutions located in the same European region during the years from 2003 to 2014. We exploit a novel and unique dataset merging data on EU-funded R&D projects, universities, patents, and economic region-level data for a large sample of universities and firms co-located in geographical areas at the third level of the Nomenclature of Territorial Units for Statistics (NUTS3), which correspond to a sub-regional scale of analysis. Our results indicate the presence of substantial heterogeneity across the analyzed EU regions with respect to the co-evolution of industry and academia specializations. In particular, we find that the specialization into a new technological domain is led by the local academic research system only in a few cases. We also document that a number of factors, at both the university and region levels, are associated with convergent or divergent processes in the relative specialization of the innovation activities carried out by firms and universities co-located in the same region.

Magnitude and breadth of neutralizing antibody responses elicited by SARS-CoV-2 infection or vaccination

Multiple SARS-CoV-2 variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. While the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.529) spike appear to diminish the efficacy of pre-existing immunity. Using pseudoparticles expressing the spike of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in naturally infected and in mRNA-vaccinated individuals. We observed that while boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta and Omicron variants, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses while responses were relatively reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

Activity and Coupling to Hippocampal Oscillations of Median Raphe GABAergic Cells in Awake Mice

Ascending serotonergic/glutamatergic projection from the median raphe region (MRR) to the hippocampal formation regulates both encoding and consolidation of memory and the oscillations associated with them. The firing of various types of MRR neurons exhibits rhythmic modulation coupled to hippocampal oscillatory activity. A possible intermediary between rhythm-generating forebrain regions and entrained ascending modulation may be the GABAergic circuit in the MRR, known to be targeted by a diverse array of top-down inputs. However, the activity of inhibitory MRR neurons in an awake animal is still largely unexplored. In this study, we utilized whole cell patch-clamp, single cell, and multichannel extracellular recordings of GABAergic and non-GABAergic MRR neurons in awake, head-fixed mice. First, we have demonstrated that glutamatergic and serotonergic neurons receive both transient, phasic, and sustained tonic inhibition. Then, we observed substantial heterogeneity of GABAergic firing patterns but a marked modulation of activity by brain states and fine timescale coupling of spiking to theta and ripple oscillations. We also uncovered a correlation between the preferred theta phase and the direction of activity change during ripples, suggesting the segregation of inhibitory neurons into functional groups. Finally, we could detect complementary alteration of non-GABAergic neurons’ ripple-coupled activity. Our findings support the assumption that the local inhibitory circuit in the MRR may synchronize ascending serotonergic/glutamatergic modulation with hippocampal activity on a subsecond timescale.

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

Breast cancer (BC) is the leading cause of death among female patients with cancer. Patients with triple-negative breast cancer (TNBC) have the lowest survival rate. TNBC has substantial heterogeneity within the BC population. This study utilized our novel patient stratification and drug repositioning method to find subgroups of BC patients that share common genetic profiles and that may respond similarly to the recommended drugs. After further examination of the discovered patient subgroups, we identified five homogeneous druggable TNBC subgroups. A drug repositioning algorithm was then applied to find the drugs with a high potential for each subgroup. Most of the top drugs for these subgroups were chemotherapy used for various types of cancer, including BC. After analyzing the biological mechanisms targeted by these drugs, ferroptosis was the common cell death mechanism induced by the top drugs in the subgroups with neoplasm subdivision and race as clinical variables. In contrast, the antioxidative effect on cancer cells was the common targeted mechanism in the subgroup of patients with an age less than 50. Literature reviews were used to validate our findings, which could provide invaluable insights to streamline the drug repositioning process and could be further studied in a wet lab setting and in clinical trials.

Face Specific vs. Expertise Hypotheses: Insights into the Underlying Mechanisms of Face Processing in Prosopagnosia

<p>A prominent debate in visual perception centers on the nature of mechanisms underlying face processing. One side of this debate argues that faces are processed by specialised mechanisms that are not involved in any form of object processing. By contrast, the other side argues that faces are processed by generic mechanisms common to all objects for which we are experts. To distinguish between these two hypotheses, I investigated whether participants with impaired face processing (developmental prosopagnosia) can acquire expertise with novel objects called greebles. To do so, I recruited 10 developmental prosopagnosics and 10 neurotypical control participants. All participants completed a standard training program for developing expertise with greebles, as well as two similar training programs with upright faces and inverted faces. Prosopagnosics were able to acquire expertise with greebles to the same extent as controls but were impaired when learning upright faces. These results demonstrate that deficits for face processing in individuals with prosopagnosia are dissociated from their ability to gain expertise with objects. Overall, the results support the hypothesis that face processing relies on specialised mechanisms, rather than generic expertise mechanisms. Despite their deficits, though, prosopagnosics still showed some evidence of learning with upright faces and showed better learning with upright faces than inverted faces. These findings suggest that prosopagnosics have face-specific mechanisms that are somewhat functional, and that training could be a useful rehabilitation tool in developmental prosopagnosia. Finally, I found substantial heterogeneity among the patterns of performance of the prosopagnosics, suggesting that further investigations into the subtypes of prosopagnosia are warranted.</p>

Face Specific vs. Expertise Hypotheses: Insights into the Underlying Mechanisms of Face Processing in Prosopagnosia

<p>A prominent debate in visual perception centers on the nature of mechanisms underlying face processing. One side of this debate argues that faces are processed by specialised mechanisms that are not involved in any form of object processing. By contrast, the other side argues that faces are processed by generic mechanisms common to all objects for which we are experts. To distinguish between these two hypotheses, I investigated whether participants with impaired face processing (developmental prosopagnosia) can acquire expertise with novel objects called greebles. To do so, I recruited 10 developmental prosopagnosics and 10 neurotypical control participants. All participants completed a standard training program for developing expertise with greebles, as well as two similar training programs with upright faces and inverted faces. Prosopagnosics were able to acquire expertise with greebles to the same extent as controls but were impaired when learning upright faces. These results demonstrate that deficits for face processing in individuals with prosopagnosia are dissociated from their ability to gain expertise with objects. Overall, the results support the hypothesis that face processing relies on specialised mechanisms, rather than generic expertise mechanisms. Despite their deficits, though, prosopagnosics still showed some evidence of learning with upright faces and showed better learning with upright faces than inverted faces. These findings suggest that prosopagnosics have face-specific mechanisms that are somewhat functional, and that training could be a useful rehabilitation tool in developmental prosopagnosia. Finally, I found substantial heterogeneity among the patterns of performance of the prosopagnosics, suggesting that further investigations into the subtypes of prosopagnosia are warranted.</p>

Estimating the strength of selection for new SARS-CoV-2 variants

Controlling the SARS-CoV-2 pandemic becomes increasingly challenging as the virus adapts to human hosts through the continual emergence of more transmissible variants. Simply observing that a variant is increasing in frequency is relatively straightforward, but more sophisticated methodology is needed to determine whether a new variant is a global threat and the magnitude of its selective advantage. We present two models for quantifying the strength of selection for new and emerging variants of SARS-CoV-2 relative to the background of contemporaneous variants. These methods range from a detailed model of dynamics within one country to a broad analysis across all countries, and they include alternative explanations such as migration and drift. We find evidence for strong selection favoring the D614G spike mutation and B.1.1.7 (Alpha), weaker selection favoring B.1.351 (Beta), and no advantage of R.1 after it spreads beyond Japan. Cutting back data to earlier time horizons reveals that uncertainty is large very soon after emergence, but that estimates of selection stabilize after several weeks. Our results also show substantial heterogeneity among countries, demonstrating the need for a truly global perspective on the molecular epidemiology of SARS-CoV-2.

A Public Health Analysis of the Relationship Between Loneliness, Isolation, and Dementia

Loneliness and isolation are now characterised as major public health problems largely because of reported associations with negative health outcomes including dementia. We adopt a public health perspective and review the relationship between loneliness/isolation and dementia focussing on how these concepts are defined, measured, and reported. We identified community based longitudinal studies which measured loneliness/isolation at baseline and dementia at follow up (minimum 12 months) published up to February 2021. We identified 12 papers for loneliness and 15 for isolation which demonstrated substantial heterogeneity in how exposure (loneliness/ isolation) and outcome (dementia) were measured and reported. For example, dementia was measured in 5 different ways: death, hospitalisation, clinical diagnosis, dementia screening tools or cognitive function. Evidence to support a relationship between loneliness/isolation and dementia is inconclusive largely because of this methodological heterogeneity. Using consistent exposure and outcome measures is a prerequisite for determining the health consequences of loneliness and isolation.