Cellular and humoral immunity to SARS-CoV-2 is critical to control primary infection and correlates with severity of disease. The role of SARS-CoV-2-specific T cell immunity, its relationship to ...antibodies, and pre-existing immunity against endemic coronaviruses (huCoV), which has been hypothesized to be protective, were investigated in 82 healthy donors (HDs), 204 recovered (RCs), and 92 active COVID-19 patients (ACs). ACs had high amounts of anti-SARS-CoV-2 nucleocapsid and spike IgG but lymphopenia and overall reduced antiviral T cell responses due to the inflammatory milieu, expression of inhibitory molecules (PD-1, Tim-3) as well as effector caspase-3, -7, and -8 activity in T cells. SARS-CoV-2-specific T cell immunity conferred by polyfunctional, mainly interferon-γ-secreting CD4+ T cells remained stable throughout convalescence, whereas humoral responses declined. Immune responses toward huCoV in RCs with mild disease and strong cellular SARS-CoV-2 T cell reactivity imply a protective role of pre-existing immunity against huCoV.
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•high SARS-CoV-2 IgG but overall reduced T cell immunity in active COVID-19 patients•PD-1, Tim-3, and active caspases in T cells result in impaired T cell function•stable SARS-CoV-2 T cell repertoire yet declining humoral responses during recovery•potentially protective role of pre-existing anti-huCoV CD4+ and CD8+ T cell immunity
COVID-19 varies from asymptomatic infection to multiorgan failure, but data on cellular immunity against SARS-CoV-2 during disease and beyond are lacking. Bonifacius et al. show a beneficial effect of preexisting immunity to endemic coronaviruses during disease and stable cellular immunity with concomitant decrease of humoral responses early during convalescence.
Recent advancements in quantum sensing have sparked transformative detection technologies with high sensitivity, precision, and spatial resolution. Owing to their atomic-level tunability, molecular ...qubits and ensembles thereof are promising candidates for sensing chemical analytes. Here, we show quantum sensing of lithium ions in solution at room temperature with an ensemble of organic radicals integrated in a microporous metal–organic framework (MOF). The organic radicals exhibit electron spin coherence and microwave addressability at room temperature, thus behaving as qubits. The high surface area of the MOF promotes accessibility of the guest analytes to the organic qubits, enabling unambiguous identification of lithium ions and quantitative measurement of their concentration through relaxometric and hyperfine spectroscopic methods based on electron paramagnetic resonance (EPR) spectroscopy. The sensing principle presented in this work is applicable to other metal ions with nonzero nuclear spin.
We reveal here the construction of Ni-based metal–organic frameworks (MOFs) and conjugated coordination polymers (CCPs) with different structural dimensionalities, including closely π-stacked 1D ...chains (Ni-1D), aggregated 2D layers (Ni-2D), and a 3D framework (Ni-3D), based on 2,3,5,6-tetraamino-1,4-hydroquinone (TAHQ) and its various oxidized forms. These materials have the same metal–ligand composition but exhibit distinct electronic properties caused by different dimensionalities and supramolecular interactions between SBUs, ligands, and structural motifs. The electrical conductivity of these materials spans nearly 8 orders of magnitude, approaching 0.3 S/cm.
Protein Numb, first identified as a cell-fate determinant inDrosophila, has been shown to promote the development of neurites in mammals and to be cotransported with endocytic receptors in ...clathrin-coated vesicles in vitro. Nevertheless, its function in mature neurons has not yet been elucidated. Here we show that cerebellar Purkinje cells (PCs) express high levels of Numb during adulthood and that conditional deletion of Numb in PCs is sufficient to impair motor coordination despite maintenance of a normal cerebellar cyto-architecture. Numb proved to be critical for internalization and recycling of metabotropic glutamate 1 receptor (mGlu1) in PCs. A significant decrease of mGlu1 and an inhibition of long-term depression at the parallel fiber–PC synapse were observed in conditional Numb knockout mice. Indeed, the trafficking of mGlu1 induced by agonists was inhibited significantly in these mutants, but the expression of ionotropic glutamate receptor subunits and of mGlu1-associated proteins was not affected by the loss of Numb. Moreover, transient and persistent forms of mGlu1 plasticity were robustly induced in mutant PCs, suggesting that they do not require mGlu1 trafficking. Together, our data demonstrate that Numb is a regulator for constitutive expression and dynamic transport of mGlu1.
Deciphering neuronal circuitry is central to understanding brain function and dysfunction, yet it remains a daunting task. To facilitate the dissection of neuronal circuits, a process requiring ...functional analysis of synaptic connections and morphological identification of interconnected neurons, we present here a method for stable simultaneous octuple patch-clamp recordings. This method allows physiological analysis of synaptic interconnections among 4-8 simultaneously recorded neurons and/or 10-30 sequentially recorded neurons, and it allows anatomical identification of >85% of recorded interneurons and >99% of recorded principal neurons. We describe how to apply the method to rodent tissue slices; however, it can be used on other model organisms. We also describe the latest refinements and optimizations of mechanics, electronics, optics and software programs that are central to the realization of a combined single- and two-photon microscopy-based, optogenetics- and imaging-assisted, stable, simultaneous quadruple-viguple patch-clamp recording system. Setting up the system, from the beginning of instrument assembly and software installation to full operation, can be completed in 3-4 d.
The coronavirus disease 2019 (COVID-19) pandemic may have affected the preventability of 30-day hospital revisits, including readmissions and emergency department (ED) visits without admission. This ...study was conducted to examine the preventability of 30-day revisits for patients admitted with COVID-19 in order to inform the design of interventions that may decrease preventable revisits in the future.
The study team retrospectively reviewed a cohort of adults admitted to an academic medical center with COVID-19 between March 21 and June 29, 2020, and discharged alive. Patients with a 30-day revisit following hospital discharge were identified. Two-physician review was used to determine revisit preventability, identify factors contributing to preventable revisits, assess potential preventive interventions, and establish the influence of pandemic-related conditions on the revisit.
Seventy-six of 576 COVID-19 hospitalizations resulted in a 30-day revisit (13.2%), including 21 ED visits without admission (3.6%) and 55 readmissions (9.5%). Of these 76 revisits, 20 (26.3%) were potentially preventable. The most frequently identified factors contributing to preventable revisits were related to the choice of postdischarge location and to patient/caregiver understanding of the discharge medication regimen, each occurring in 25.0% of cases. The most frequently cited potentially preventive intervention was "improved self-management plan at discharge," occurring in 65.0% of cases. Five of the 20 preventable revisits (25.0%) had contributing factors that were thought to be directly related to the COVID-19 pandemic.
Although only approximately one quarter of 30-day hospital revisits following admission with COVID-19 were potentially preventable, these results highlight opportunities for improvement to reduce revisits going forward.
Background
The association of influenza with meteorological variables in tropical climates remains controversial. Here, we investigate the impact of weather conditions on influenza in the tropics and ...factors that may contribute to this uncertainty.
Methods
We computed the monthly viral positive rate for each of the 3 circulating influenza (sub)types (ie, A/H1N1, A/H3N2, and B) among patients presenting with influenza‐like illness (ILI) or severe acute respiratory infections (SARI) in 2 Ugandan cities (Entebbe and Kampala). Using this measure as a proxy for influenza activity, we applied regression models to examine the impact of temperature, relative humidity, absolute humidity, and precipitation, as well as interactions among the 3 influenza viruses on the epidemic dynamics of each influenza (sub)type. A full analysis including all 4 weather variables was done for Entebbe during 2007‐2015, and a partial analysis including only temperature and precipitation was done for both cities during 2008‐2014.
Results
For Entebbe, the associations with weather variables differed by influenza (sub)type; with adjustment for viral interactions, the models showed that precipitation and temperature were negatively correlated with A/H1N1 activity, but not for A/H3N2 or B. A mutually negative association between A/H3N2 and B activity was identified in both Entebbe and Kampala.
Conclusion
Our findings suggest that key interactions exist among influenza (sub)types at the population level in the tropics and that such interactions can modify the association of influenza activity with weather variables. Studies of the relationship between influenza and weather conditions should therefore determine and account for co‐circulating influenza (sub)types.
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