Cytokine Signalling at the Microglial Penta-Partite Synapse

Microglial cell processes form part of a subset of synaptic contacts that have been dubbed microglial tetra-partite or quad-partite synapses. Since tetrapartite may also refer to the presence of extracellular matrix components, we propose the more precise term microglial penta-partite synapse for synapses that show a microglial cell process in close physical proximity to neuronal and astrocytic synaptic constituents. Microglial cells are now recognised as key players in central nervous system (CNS) synaptic changes. When synaptic plasticity involving microglial penta-partite synapses occurs, microglia may utilise their cytokine arsenal to facilitate the generation of new synapses, eliminate those that are not needed anymore, or modify the molecular and structural properties of the remaining synaptic contacts. In addition, microglia–synapse contacts may develop de novo under pathological conditions. Microglial penta-partite synapses have received comparatively little attention as unique sites in the CNS where microglial cells, cytokines and other factors they release have a direct influence on the connections between neurons and their function. It concerns our understanding of the penta-partite synapse where the confusion created by the term “neuroinflammation” is most counterproductive. The mere presence of activated microglia or the release of their cytokines may occur independent of inflammation, and penta-partite synapses are not usually active in a neuroimmunological sense. Clarification of these details is the main purpose of this review, specifically highlighting the relationship between microglia, synapses, and the cytokines that can be released by microglial cells in health and disease.

Surveying the Bright Stars by Optical Interferometry. III. A Magnitude-limited Multiplicity Survey of Classical Be Stars

We present the results of a multiplicity survey for a magnitude-limited sample of 31 classical Be stars conducted with the Navy Precision Optical Interferometer and the Mark III Stellar Interferometer. The interferometric observations were used to detect companions in 10 previously known binary systems. For two of these sources (66 Oph and β Cep) new orbital solutions were obtained, while for a third source (υ Sgr) our observations provide the first direct, visual detection of the hot companion to the primary star. Combining our interferometric observations with an extensive literature search, we conclude that an additional four sources (o Cas, 15 Mon, β Lyr, and β Cep) also contain wider binary components that are physical companions to the narrow binaries, thus forming hierarchical multiple systems. Among the sources not previously confirmed as spectroscopic or visual binaries, BK Cam was resolved on a number of nights within a close physical proximity of another star with relative motion possibly suggesting a physical binary. Combining our interferometric observations with an extensive literature search, we provide a detailed listing of companions known around each star in the sample, and discuss the multiplicity frequency in the sample. We also discuss the prospects for future multiplicity studies of classical Be stars by long-baseline optical interferometry.

Correlational selection and genetic architecture promote the leaf economics spectrum in a perennial grass

The leaf economics spectrum (LES) is hypothesized to result from a trade-off between resource acquisition and conservation. Yet few studies have examined the evolutionary mechanisms behind the LES, perhaps because most species exhibit relatively specialized leaf economics strategies. In a genetic mapping population of the phenotypically diverse grass Panicum virgatum, we evaluate two interacting mechanisms that may drive LES evolution: 1) genetic architecture, where multiple traits are coded by the same gene (pleiotropy) or by genes in close physical proximity (linkage), and 2) correlational selection, where selection acts non-additively on combinations of multiple traits. We found evidence suggesting that shared genetic architecture (pleiotropy) controls covariation between two pairs of leaf economics traits. Additionally, at five common gardens spanning 17 degrees of latitude, correlational selection favored particular combinations of leaf economics traits. Together, these results demonstrate how the LES can evolve within species.

Analyzing the demographic, spatial, and temporal factors influencing social contact patterns in U.S. and implications for infectious disease spread

Background Diseases such as COVID-19 are spread through social contact. Reducing social contacts is required to stop disease spread in pandemics for which vaccines have not yet been developed. However, existing data on social contact patterns in the United States (U.S.) is limited. Method We use American Time Use Survey data from 2003–2018 to describe and quantify the age-pattern of disease-relevant social contacts. For within-household contacts, we construct age-structured contact duration matrices (who spends time with whom, by age). For both within-household and non-household contacts, we also estimate the mean number and duration of contact by location. We estimate and test for differences in the age-pattern of social contacts based on demographic, temporal, and spatial characteristics. Results The mean number and duration of social contacts vary by age. The biggest gender differences in the age-pattern of social contacts are at home and at work; the former appears to be driven by caretaking responsibilities. Non-Hispanic Blacks have a shorter duration of contact and fewer social contacts than non-Hispanic Whites. This difference is largely driven by fewer and shorter contacts at home. Pre-pandemic, non-Hispanic Blacks have shorter durations of work contacts. Their jobs are more likely to require close physical proximity, so their contacts are riskier than those of non-Hispanic Whites. Hispanics have the highest number of household contacts and are also more likely to work in jobs requiring close physical proximity than non-Hispanic Whites. With the exceptions of work and school contacts, the duration of social contact is higher on weekends than on weekdays. Seasonal differences in the total duration of social contacts are driven by school-aged respondents who have significantly shorter contacts during the summer months. Contact patterns did not differ by metro status. Age patterns of social contacts were similar across regions. Conclusion Social contact patterns differ by age, race and ethnicity, and gender. Other factors besides contact patterns may be driving seasonal variation in disease incidence if school-aged individuals are not an important source of transmission. Pre-pandemic, there were no spatial differences in social contacts, but this finding has likely changed during the pandemic.

Prevalent uses of exons as regulatory sequences are possible and inevitable

ABSTRACTIt has long been known that exons can encode transcriptional enhancers. However, the prevalence of such dual-use exons and related questions remain elusive. Our recently predicted highly accurate, large sets of cis-regulatory module candidates (CRMCs) and non-CRMCs in the human genome provide us an opportunity to address these questions. We find that exonic transcription factor binding sites(eTFBSs) occupy at least a third of the total exon lengths, suggesting exonic enhancers(eEHs) are more prevalent than originally thought. Moreover, active eTFBSs significantly overlap experimentally determined active eEHs, and enhance the transcription of nearby genes. Furthermore, both A/T and C/G in eTFBSs are more likely under evolutionary selection than those in non-CRMC exons, indicating the eTFBSs might be in dual-use. Interestingly, eTFBSs in codons tend to encode loops rather than more critical helices and strands in protein structures, while eTFBSs in untranslated regions (UTRs) tend to avoid positions where known UTR-related functions were located. Intriguingly, active eTFBSs are found to be in close physical proximity to distal promoters and involved in the activation of target genes. The close physical proximity between exons and promoters in topologically associating domains might render less critical exons to opt for parts of enhancers when non-exonic sequences are unavailable due to space constraints. It appears that nature avoids the dilemma of evolving a sequence for two unrelated functions by using less-critical, physically available exons for eTFBSs. Therefore, the prevalent dual-use of exons is not only possible but also inevitable.

Notes on the natural history of Stillingia aquatica (Euphorbiaceae): with special attention to reproductive biology

Stillingia aquatica, a wetland shrub in the Southeastern U.S., was profiled in Southeast Florida from a natural history standpoint. The stem has exceptionally lightweight wood in common with other periodically root-inundated woody plants. Pseudowhorled tufts of conspicuous yellow leaves subtend the similarly colored spikelike thyrsoid inflorescences. The plants are monoecious, self-compatible, protogynous with respect to inflorescences, and with a mixed mating system. After a pistillate-only phase, pistillate and staminate phases overlap in time, and are positioned in close physical proximity within inflorescences. Then follows a prolonged phase of only staminate flowers plus maturing fruits. The inflorescences attract ants, bees, and especially abundant wasps, switching from mixed bees and wasps in the dry season to essentially just wasps in the wet season. Wind-pollination is minimal to none. Ants are often abundant in the inflorescences and believed to contribute to geitonogamy but are not necessary for fruitset. Agamospermy is none to negligible. The seeds often fail, with the failure rates varying between populations and between individual plants.

Genetic architecture underlying the expression of eight α-amylase trypsin inhibitors

Key message Wheat cultivars largely differ in the content and composition of ATI proteins, but heritability was quite low for six out of eight ATIs. The genetic architecture of ATI proteins is built up of few major and numerous small effect QTL. Abstract Amylase trypsin inhibitors (ATIs) are important allergens in baker’s asthma and suspected triggers of non-celiac wheat sensitivity (NCWS) inducing intestinal and extra-intestinal inflammation. As studies on the expression and genetic architecture of ATI proteins in wheat are lacking, we evaluated 149 European old and modern bread wheat cultivars grown at three different field locations for their content of eight ATI proteins. Large differences in the content and composition of ATIs in the different cultivars were identified ranging from 3.76 pmol for ATI CM2 to 80.4 pmol for ATI 0.19, with up to 2.5-fold variation in CM-type and up to sixfold variation in mono/dimeric ATIs. Generally, heritability estimates were low except for ATI 0.28 and ATI CM2. ATI protein content showed a low correlation with quality traits commonly analyzed in wheat breeding. Similarly, no trends were found regarding ATI content in wheat cultivars originating from numerous countries and decades of breeding history. Genome-wide association mapping revealed a complex genetic architecture built of many small, few medium and two major quantitative trait loci (QTL). The major QTL were located on chromosomes 3B for ATI 0.19-like and 6B for ATI 0.28, explaining 70.6 and 68.7% of the genotypic variance, respectively. Within close physical proximity to the medium and major QTL, we identified eight potential candidate genes on the wheat reference genome encoding structurally related lipid transfer proteins. Consequently, selection and breeding of wheat cultivars with low ATI protein amounts appear difficult requiring other strategies to reduce ATI content in wheat products.

Proximity to the Promoter and Terminator Regions Regulates the Transcription Enhancement Potential of an Intron

An evolutionarily conserved feature of introns is their ability to enhance expression of genes that harbor them. Introns have been shown to regulate gene expression at the transcription and post-transcription level. The general perception is that a promoter-proximal intron is most efficient in enhancing gene expression and the effect diminishes with the increase in distance from the promoter. Here we show that the intron regains its positive influence on gene expression when in proximity to the terminator. We inserted ACT1 intron into different positions within IMD4 and INO1 genes. Transcription Run-On (TRO) analysis revealed that the transcription of both IMD4 and INO1 was maximal in constructs with a promoter-proximal intron and decreased with the increase in distance of the intron from the promoter. However, activation was partially restored when the intron was placed close to the terminator. We previously demonstrated that the promoter-proximal intron stimulates transcription by affecting promoter directionality through gene looping-mediated recruitment of termination factors in the vicinity of the promoter region. Here we show that the terminator-proximal intron also enhances promoter directionality and results in compact gene architecture with the promoter and terminator regions in close physical proximity. Furthermore, we show that both the promoter and terminator-proximal introns facilitate assembly or stabilization of the preinitiation complex (PIC) on the promoter. On the basis of these findings, we propose that proximity to both the promoter and the terminator regions affects the transcription regulatory potential of an intron, and the terminator-proximal intron enhances transcription by affecting both the assembly of preinitiation complex and promoter directionality.

Impacts of Jobs Requiring Close Physical Proximity and High Interaction with the Public on U.S. Industry Employment Change During the Early Stages of the COVID-19 Pandemic

This paper examines the factors affecting U.S. industry employment change in the early months of the COVID-19 pandemic. Results show that the percentage of industry employment in occupations that require close physical proximity has a negative effect on year-over-year employment change in the six months of April through September of 2020. On the other hand, the percentage of industry employment in jobs that involve high interaction with the public has a negative effect on year-over-year employment change in April and May, but not in the months of June to September. These different results related to physical proximity and interaction with the public are driven, in part, by the uneven impacts of COVID-19 on hospitality and retail businesses.

Use of robotic assistance to reduce proximity and air-sharing during percutaneous cardiovascular intervention

Aim: Traditional percutaneous cardiovascular interventions require close physical proximity between the patients and the healthcare team, posing occupational hazards that range from radiation exposure to interpersonal air contamination. Materials & methods: Prospective single-arm pilot study (n = 10) to investigate robotic-assisted intervention as a strategy to reduce proximity during the procedure. Primary end point: composite of angiographic success, intervention performed with the team positioned >2 meters from the patient for ≥50% procedure duration, and absence of in-hospital death or acute target lesion occlusion. Results: The composite primary end point was achieved in 100% of cases. Conclusion: Robotic-assisted percutaneous intervention provided successful invasive treatment while reducing proximity and shared air space between the care-delivery team and the patient during the procedure. Trial registration number: NCT04379453 ( Clinicaltrials.gov ).