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ABSTRACT Widespread usage of high-throughput sequencing (HTS) in the LIFE SCIENCES has produced a demand for undergraduate and graduate institutions to offer classes exposing students to all aspects of HTS (sample acquisition, laboratory work, sequencing technologies, bioinformatics, and statistical analyses). Despite the increase in demand, many challenges exist for these types of classes. We advocate for the usage of the sourdough starter microbiome for implementing meta-amplicon sequencing. The relatively small community, dominated by a few taxa, enables potential contaminants to be easily identified, while between-sample differences can be quickly statistically assessed. Finally, bioinformatic pipelines and statistical analyses can be carried out on personal student laptops or in a teaching computer lab. In two semesters adopting this system, 12 of 14 students were able to effectively capture the sourdough starter microbiome, using the instructor’s paired sample as reference. 

Emerging RNA viruses that target the central nervous system (CNS) lead to cognitive sequelae in survivors. Studies in humans and mice infected with West Nile virus (WNV), a re-emerging RNA virus associated with learning and memory deficits, revealed microglial-mediated synapse elimination within the hippocampus. Moreover, CNS-resident memory T (T_RM) cells activate microglia, limiting synapse recovery and inducing spatial learning defects in WNV-recovered mice. The signals involved in T cell-microglia interactions are unknown.

Here, we examined immune cells within the murine WNV-recovered forebrain using single-cell RNA sequencing to identify putative ligand-receptor pairs involved in intercellular communication between T cells and microglia. Clustering and differential gene analyses were followed by protein validation and genetic and antibody-based approaches utilizing an established murine model of WNV recovery in which microglia and complement promote ongoing hippocampal synaptic loss.

Profiling of host transcriptome immune cells at 25 days post-infection in mice revealed a shift in forebrain homeostatic microglia to activated subpopulations with transcriptional signatures that have previously been observed in studies of neurodegenerative diseases. Importantly, CXCL16/CXCR6, a chemokine signaling pathway involved in T_RM cell biology, was identified as critically regulating CXCR6 expressing CD8⁺T_RM cell numbers within the WNV-recovered forebrain. We demonstrate that CXCL16 is highly expressed by all myeloid cells, and its unique receptor, CXCR6, is highly expressed on all CD8⁺T cells. Using genetic and pharmacological approaches, we demonstrate that CXCL16/CXCR6 not only is required for the maintenance of WNV-specific CD8 T_RM cells in the post-infectious CNS, but also contributes to their expression of T_RM cell markers. Moreover, CXCR6⁺CD8⁺T cells are required for glial activation and ongoing synapse elimination.

We provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD8⁺T cells that maintains forebrain T_RM cells, microglial and astrocyte activation, and ongoing synapse elimination in virally recovered animals. We also show that therapeutic targeting of CXCL16 in mice during recovery may reduce CNS CD8⁺T_RM cells.

 

In recent years, the field of neuroscience has gone through rapid experimental advances and a significant increase in the use of quantitative and computational methods. This growth has created a need for clearer analyses of the theory and modeling approaches used in the field. This issue is particularly complex in neuroscience because the field studies phenomena that cross a wide range of scales and often require consideration at varying degrees of abstraction, from precise biophysical interactions to the computations they implement. We argue that a pragmatic perspective of science, in which descriptive, mechanistic, and normative models and theories each play a distinct role in defining and bridging levels of abstraction, will facilitate neuroscientific practice. This analysis leads to methodological suggestions, including selecting a level of abstraction that is appropriate for a given problem, identifying transfer functions to connect models and data, and the use of models themselves as a form of experiment. 

The pre-merging system of galaxy clusters Abell 3391-Abell 3395 located at a mean redshift of 0.053 has been observed at 1 GHz in an ASKAP/EMU Early Science observation as well as in X-rays with eROSITA. The projected separation of the X-ray peaks of the two clusters is ~50′ or ~3.1 Mpc. Here we present an inventory of interesting radio sources in this field around this cluster merger. While the eROSITA observations provide clear indications of a bridge of thermal gas between the clusters, neither ASKAP nor MWA observations show any diffuse radio emission coinciding with the X-ray bridge. We derive an upper limit on the radio emissivity in the bridge region of 〈 J 〉 1 GHz < 1.2 × 10 −44 W Hz −1 m −3 . A non-detection of diffuse radio emission in the X-ray bridge between these two clusters has implications for particle-acceleration mechanisms in cosmological large-scale structure. We also report extended or otherwise noteworthy radio sources in the 30 deg 2 field around Abell 3391-Abell 3395. We identified 20 Giant Radio Galaxies, plus 7 candidates, with linear projected sizes greater than 1 Mpc. The sky density of field radio galaxies with largest linear sizes of >0.7 Mpc is ≈1.7 deg −2 , three times higher than previously reported. We find no evidence for a cosmological evolution of the population of Giant Radio Galaxies. Moreover, we find seven candidates for cluster radio relics and radio halos. 

Context. Inferences about dark matter, dark energy, and the missing baryons all depend on the accuracy of our model of large-scale structure evolution. In particular, with cosmological simulations in our model of the Universe, we trace the growth of structure, and visualize the build-up of bigger structures from smaller ones and of gaseous filaments connecting galaxy clusters. Aims. Here we aim to reveal the complexity of the large-scale structure assembly process in great detail and on scales from tens of kiloparsecs up to more than 10 Mpc with new sensitive large-scale observations from the latest generation of instruments. We also aim to compare our findings with expectations from our cosmological model. Methods. We used dedicated SRG/eROSITA performance verification (PV) X-ray, ASKAP/EMU Early Science radio, and DECam optical observations of a ~15 deg 2 region around the nearby interacting galaxy cluster system A3391/95 to study the warm-hot gas in cluster outskirts and filaments, the surrounding large-scale structure and its formation process, the morphological complexity in the inner parts of the clusters, and the (re-)acceleration of plasma. We also used complementary Sunyaev-Zeldovich (SZ) effect data from the Planck survey and custom-made Galactic total (neutral plus molecular) hydrogen column density maps based on the HI4PI and IRAS surveys. We relate the observations to expectations from cosmological hydrodynamic simulations from the Magneticum suite. Results. We trace the irregular morphology of warm and hot gas of the main clusters from their centers out to well beyond their characteristic radii, r 200 . Between the two main cluster systems, we observe an emission bridge on large scale and with good spatial resolution. This bridge includes a known galaxy group but this can only partially explain the emission. Most gas in the bridge appears hot, but thanks to eROSITA’s unique soft response and large field of view, we discover some tantalizing hints for warm, truly primordial filamentary gas connecting the clusters. Several matter clumps physically surrounding the system are detected. For the “Northern Clump,” we provide evidence that it is falling towards A3391 from the X-ray hot gas morphology and radio lobe structure of its central AGN. Moreover, the shapes of these X-ray and radio structures appear to be formed by gas well beyond the virial radius, r 100 , of A3391, thereby providing an indirect way of probing the gas in this elusive environment. Many of the extended sources in the field detected by eROSITA are also known clusters or new clusters in the background, including a known SZ cluster at redshift z = 1. We find roughly an order of magnitude more cluster candidates than the SPT and ACT surveys together in the same area. We discover an emission filament north of the virial radius of A3391 connecting to the Northern Clump. Furthermore, the absorption-corrected eROSITA surface brightness map shows that this emission filament extends south of A3395 and beyond an extended X-ray-emitting object (the “Little Southern Clump”) towards another galaxy cluster, all at the same redshift. The total projected length of this continuous warm-hot emission filament is 15 Mpc, running almost 4 degrees across the entire eROSITA PV observation field. The Northern and Southern Filament are each detected at >4 σ . The Planck SZ map additionally appears to support the presence of both new filaments. Furthermore, the DECam galaxy density map shows galaxy overdensities in the same regions. Overall, the new datasets provide impressive confirmation of the theoretically expected structure formation processes on the individual system level, including the surrounding warm-hot intergalactic medium distribution; the similarities of features found in a similar system in the Magneticum simulation are striking. Our spatially resolved findings show that baryons indeed reside in large-scale warm-hot gas filaments with a clumpy structure. 

Genetic and environmental influences on cortical thickness (CT) and surface area (SA) are thought to vary in a complex and dynamic way across the lifespan. It has been established that CT and SA are genetically distinct in older children, adolescents, and adults, and that heritability varies across cortical regions. Very little, however, is known about how genetic and environmental factors influence infant CT and SA. Using structural MRI, we performed the first assessment of genetic and environmental influences on normal variation of SA and CT in 360 twin neonates. We observed strong and significant additive genetic influences on total SA (a² = 0.78) and small and nonsignificant genetic influences on average CT (a² = 0.29). Moreover, we found significant genetic overlap (genetic correlation = 0.65) between these global cortical measures. Regionally, there were minimal genetic influences across the cortex for both CT and SA measures and no distinct patterns of genetic regionalization. Overall, outcomes from this study suggest a dynamic relationship between CT and SA during the neonatal period and provide novel insights into how genetic influences shape cortical structure during early development.