Thymic and T-cell intrinsic critical roles associated with Severe Combined Immunodeficiency and Omenn syndrome due to a heterozygous variant (G201R) in PSMB10.

Background: Heterozygous immunoproteasome subunit beta-type 10 (PSMB10) mutations can cause severe combined immunodeficiency (SCID) and Omenn syndrome (OS). Hematopoietic stem cell transplantation in these patients is associated with severe complications and poor immune reconstitution, often resulting in death.

Objective: To perform immunological and molecular characterization of an infant with a PSMB10 heterozygous variant.

Bystander monocytic cells drive infection-independent NLRP3 inflammasome response to SARS-CoV-2.

Unlabelled: The pathogenesis of COVID-19 is associated with a hyperinflammatory immune response. Monocytes and macrophages play a central role in this hyperinflammatory response to SARS-CoV-2. NLRP3 inflammasome activation has been observed in monocytes of patients with COVID-19, but the mechanism and consequences of inflammasome activation require further investigation.

Greenspace exposure and the retinal microvasculature in healthy adults across three European cities.

Background: Emerging evidence points to the beneficial role of greenspace exposure in promoting cardiovascular health. Most studies have evaluated such associations with conventional cardiovascular endpoints such as mortality, morbidity, or macrovascular markers. In comparison, the microvasculature, a crucial compartment of the vascular system where early subclinical signs of cardiovascular problems appear, has not been studied in association with greenspace exposure.

Contributions of white adipose tissue to energy requirements for female reproduction.

Body composition impacts female fertility and there are established relationships between adipose tissue and the reproductive system. Maintaining functional adipose tissue is vital for meeting the energetic demands during the reproductive process, from ovulation to delivery and lactation. White adipose tissue (WAT) shows plastic responses to daily physiology and secretes diverse adipokines that affect the hypothalamic-pituitary-ovarian axis, but many other interorgan interactions remain to be determined.

N-acetylaspartate from fat cells regulates postprandial body temperature.

N-acetylaspartate (NAA), the brain's second most abundant metabolite, provides essential substrates for myelination through its hydrolysis. However, activities and physiological roles of NAA in other tissues remain unknown. Here, we show aspartoacylase (ASPA) expression in white adipose tissue (WAT) governs systemic NAA levels for postprandial body temperature regulation.

Growth media affects susceptibility of air-lifted human nasal epithelial cell cultures to SARS-CoV2, but not Influenza A, virus infection.

Primary differentiated human epithelial cell cultures have been widely used by researchers to study viral fitness and virus-host interactions, especially during the COVID19 pandemic. These cultures recapitulate important characteristics of the respiratory epithelium such as diverse cell type composition, polarization, and innate immune responses. However, standardization and validation of these cultures remains an open issue.

Dectin-1 multimerization and signaling depends on fungal β-glucan structure and exposure.

Dectin-1A is a C-type lectin innate immunoreceptor that recognizes β-(1,3;1,6)-glucan, a structural component of Candida species cell walls. β-Glucans can adopt solution structures ranging from random coil to insoluble fiber due to tertiary (helical) and quaternary structure. Fungal β-glucans of medium and high molecular weight are highly structured, but low molecular weight glucan is much less structured.

The D614G mutation redirects SARS-CoV-2 spike to lysosomes and suppresses deleterious traits of the furin cleavage site insertion mutation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) egress occurs by lysosomal exocytosis. We show that the Spike D614G mutation enhances Spike trafficking to lysosomes, drives Spike-mediated reprogramming of lysosomes, and reduces cell surface Spike expression by ~3-fold. D614G is not a human-specific adaptation.

PCP consensus protein/peptide alphavirus antigens stimulate broad spectrum neutralizing antibodies.

Vaccines based on proteins and peptides may be safer and if calculated based on many sequences, more broad-spectrum than those designed based on single strains. Physicochemical Property Consensus (PCP) alphavirus (AV) antigens from the B-domain of the E2 envelope protein were designed, synthesized recombinantly and shown to be immunogenic (i.e.

L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis.

Macrophage adhesion and stretching have been shown to induce interleukin (IL)-1β production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1β production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome.

Hidden in plain sight: Working class and low-income atheists.

The current study sought to qualitatively examine the role of social class in the development of atheist identity, the experience of atheism-related minority stress, and relationships between atheists. Using a critical phenomenological design, we captured the experiences of 15 working-class and the low-income U.S.

Synthetic proteins for COVID-19 diagnostics.

There is an urgent need for inexpensive, rapid and specific antigen-based assays to test for vaccine efficacy and detect infection with SARS-CoV-2 and its variants. We have identified a small, synthetic protein (JS7), representing a region of maximum variability within the receptor binding domain (RBD), which binds antibodies in sera from nine patients with PCR-verified COVID-19 of varying severity. Antibodies binding to either JS7 or the SARS-CoV-2 recombinant RBD, as well as those that disrupt binding between a fragment of the ACE2 receptor and the RBD, are proportional to disease severity and clinical outcome.

Novel Mouse Model Reveals That Serine Phosphorylation of L-Plastin Is Essential for Effective Splenic Clearance of Pneumococcus.

Asplenia imparts susceptibility to life-threatening sepsis with encapsulated bacteria, such as the pneumococcus. However, the cellular components within the splenic environment that guard against pneumococcal bacteremia have not been defined. The actin-bundling protein L-plastin (LPL) is essential for the generation of marginal zone B cells and for anti-pneumococcal host defense, as revealed by a mouse model of genetic LPL deficiency.

Cyclist Injury Severity in Spain: A Bayesian Analysis of Police Road Injury Data Focusing on Involved Vehicles and Route Environment.

This study analyses factors associated with cyclist injury severity, focusing on vehicle type, route environment, and interactions between them. Data analysed was collected by Spanish police during 2016 and includes records relating to 12,318 drivers and cyclist involving in collisions with at least one injured cyclist, of whom 7230 were injured cyclists. Bayesian methods were used to model relationships between cyclist injury severity and circumstances related to the crash, with the outcome variable being whether a cyclist was killed or seriously injured (KSI) rather than slightly injured.

"Isn't atheism a White thing?": Centering the voices of atheists of color.

Despite a general shift toward secularity, very few people of color in the United States identify as atheist. Further, atheists of color are underrepresented in studies of atheists, and the experiences of atheists of color specifically have, to date, not been captured in the extant scholarship. Addressing this gap in the literature, we interviewed 17 self-identified adult atheists of color, predominantly from Christian backgrounds, residing in the United States using a critical feminist phenomenological approach.

Short-term effects of physical activity, air pollution and their interaction on the cardiovascular and respiratory system.

Physical activity (PA) in urban environments may lead to increased inhalation of air pollutants. As PA and air pollution (AP) have respectively beneficial and detrimental effects on the cardiorespiratory system, the responses to these exposures can interact. Therefore, we assessed the short-term effects of PA, AP and their interaction on a set of subclinical cardiovascular and respiratory outcomes in a panel of healthy adults: heart rate variability (HRV), retinal vessel diameters, lung function and fractional exhaled nitric oxide (FeNO).

Production and Purification of Filovirus Glycoproteins in Insect and Mammalian Cell Lines.

Filoviruses are highly virulent pathogens capable of causing severe disease. The glycoproteins of filoviruses are the only virally expressed proteins on the virion surface and are required for receptor binding. As such, they are the main candidate vaccine antigen.

Physical activity and sedentary behaviour in daily life: A comparative analysis of the Global Physical Activity Questionnaire (GPAQ) and the SenseWear armband.

Reduction of sedentary time and an increase in physical activity offer potential to improve public health. However, quantifying physical activity behaviour under real world conditions is a major challenge and no standard of good practice is available. Our aim was to compare the results of physical activity and sedentary behaviour obtained with a self-reported instrument (Global Physical Activity Questionnaire (GPAQ)) and a wearable sensor (SenseWear) in a repeated measures study design.

Visual-spatial sequence learning and memory in trained musicians.

Previous research has shown that musicians have enhanced visual-spatial abilities and sensorymotor skills. As a result of their long-term musical training and their experience-dependent activities, musicians may learn to associate sensory information with fine motor movements. Playing a musical instrument requires musicians to rapidly translate musical symbols into specific sensory-motor actions while also simultaneously monitoring the auditory signals produced by their instrument.

Long-term musical experience and auditory and visual perceptual abilities under adverse conditions.

Musicians have been shown to have enhanced speech perception in noise skills. It is unclear whether these improvements are limited to the auditory modality, as no research has examined musicians' visual perceptual abilities under degraded conditions. The current study examined associations between long-term musical experience and visual perception under noisy or degraded conditions.

Private and public modes of bicycle commuting: a perspective on attitude and perception.

Background: Public bicycle-sharing initiatives can act as health enhancement strategies among urban populations. The aim of the study was to determine which attitudes and perceptions of behavioural control toward cycling and a bicycle-sharing system distinguish commuters with a different adherence to bicycle commuting.

Methods: The recruitment process was conducted in 40 random points in Barcelona from 2011 to 2012.

Physical Activity through Sustainable Transport Approaches (PASTA): a study protocol for a multicentre project.

Introduction: Only one-third of the European population meets the minimum recommended levels of physical activity (PA). Physical inactivity is a major risk factor for non-communicable diseases. Walking and cycling for transport (active mobility, AM) are well suited to provide regular PA.

Optimizing sgRNA structure to improve CRISPR-Cas9 knockout efficiency.

Background: Single-guide RNA (sgRNA) is one of the two key components of the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 genome-editing system. The current commonly used sgRNA structure has a shortened duplex compared with the native bacterial CRISPR RNA (crRNA)-transactivating crRNA (tracrRNA) duplex and contains a continuous sequence of thymines, which is the pause signal for RNA polymerase III and thus could potentially reduce transcription efficiency.

Results: Here, we systematically investigate the effect of these two elements on knockout efficiency and showed that modifying the sgRNA structure by extending the duplex length and mutating the fourth thymine of the continuous sequence of thymines to cytosine or guanine significantly, and sometimes dramatically, improves knockout efficiency in cells.