Where Cosmic Dawn Breaks First: Mapping the Primordial Overdensity Powering a z 9 Ionized Bubble

Models of cosmic reionization predict that the earliest star-forming systems develop in primordial overdensities which, in turn, create ionized bubbles. With time, these bubbles grow and coalesce until the intergalactic medium is fully ionized. Since Lyman-alpha photons originating in these protoclusters can propagate freely through ionized gas, the highest redshift Lyman Alpha emitters (LAEs) act as valuable tracers of early ionized bubbles. We present evidence that the highest redshift LAE, EGSz8p7 (z=8.68), is likely embedded in such an overdensity. Collectively, in all of HST's deep fields, blank fields and gravitationally-lensed fields spanning >1000 arcmin^2 there are ~30 photometric candidates at z~9, yet a third lie within 3.75' (10 cMpc) of EGSz8p7. To confirm and exploit this extraordinary early overdensity we seek systemic redshifts and diagnostic features only JWST can provide. We propose blind, grism spectroscopy to map the ionized bubble around EGSz8p7 using the [OIII] doublet. A blind survey is optimal for determining a complete census of EGSz8p7's physical neighbors. Spitzer/IRAC color excesses at z>8 imply extreme [OIII] EWs (~6000 A) ensuring efficient use of JWST. Stellar population modeling of the sources around EGSz8p7 may give us the strongest constraints yet on when star-formation first commenced after the Big Bang (i.e., cosmic dawn). Our spectra will likewise constrain the ionizing photon production efficiency, a key unknown in reionization calculations. Our observing strategy is designed for maximum legacy value with a footprint overlapping the CEERS ERS survey and use of the wide F444W grism that will guarantee additional

Genotyping Performance Assessment of Whole Genome Amplified DNA with Respect to Multiplexing Level of Assay and Its Period of Storage

Whole genome amplification can faithfully amplify genomic DNA (gDNA) with minimal bias and substantial genome coverage. Whole genome amplified DNA (wgaDNA) has been tested to be workable for high-throughput genotyping arrays. However, issues about whether wgaDNA would decrease genotyping performance at increasing multiplexing levels and whether the storage period of wgaDNA would reduce genotyping performance have not been examined. Using the Sequenom MassARRAY iPLEX Gold assays, we investigated 174 single nucleotide polymorphisms for 3 groups of matched samples: group 1 of 20 gDNA samples, group 2 of 20 freshly prepared wgaDNA samples, and group 3 of 20 stored wgaDNA samples that had been kept frozen at −70°C for 18 months. MassARRAY is a medium-throughput genotyping platform with reaction chemistry different from those of high-throughput genotyping arrays. The results showed that genotyping performance (efficiency and accuracy) of freshly prepared wgaDNA was similar to that of gDNA at various multiplexing levels (17-plex, 21-plex, 28-plex and 36-plex) of the MassARRAY assays. However, compared with gDNA or freshly prepared wgaDNA, stored wgaDNA was found to give diminished genotyping performance (efficiency and accuracy) due to potentially inferior quality. Consequently, no matter whether gDNA or wgaDNA was used, better genotyping efficiency would tend to have better genotyping accuracy

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Calmodulin Activation by Calcium Transients in the Postsynaptic Density of Dendritic Spines

The entry of calcium into dendritic spines can trigger a sequence of biochemical reactions that begins with the activation of calmodulin (CaM) and ends with long-term changes to synaptic strengths. The degree of activation of CaM can depend on highly local elevations in the concentration of calcium and the duration of transient increases in calcium concentration. Accurate measurement of these local changes in calcium is difficult because the spaces are so small and the numbers of molecules are so low. We have therefore developed a Monte Carlo model of intracellular calcium dynamics within the spine that included calcium binding proteins, calcium transporters and ion channels activated by voltage and glutamate binding. The model reproduced optical recordings using calcium indicator dyes and showed that without the dye the free intracellular calcium concentration transient was much higher than predicted from the fluorescent signal. Excitatory postsynaptic potentials induced large, long-lasting calcium gradients across the postsynaptic density, which activated CaM. When glutamate was released at the synapse 10 ms before an action potential occurred, simulating activity patterns that strengthen hippocampal synapses, the calcium gradient and activation of CaM in the postsynaptic density were much greater than when the order was reversed, a condition that decreases synaptic strengths, suggesting a possible mechanism underlying the induction of long-term changes in synaptic strength. The spatial and temporal mechanisms for selectivity in CaM activation demonstrated here could be used in other signaling pathways

Low-latency gravitational wave alert products and their performance in anticipation of the fourth LIGO-Virgo-KAGRA observing run

Multi-messenger searches for binary neutron star (BNS) and neutron star-black hole (NSBH) mergers are currently one of the most exciting areas of astronomy. The search for joint electromagnetic and neutrino counterparts to gravitational wave (GW)s has resumed with Advanced LIGO (aLIGO)'s, Advanced Virgo (AdVirgo)'s and KAGRA's fourth observing run (O4). To support this effort, public semi-automated data products are sent in near real-time and include localization and source properties to guide complementary observations. Subsequent refinements, as and when available, are also relayed as updates. In preparation for O4, we have conducted a study using a simulated population of compact binaries and a Mock Data Challenge (MDC) in the form of a real-time replay to optimize and profile the software infrastructure and scientific deliverables. End-to-end performance was tested, including data ingestion, running online search pipelines, performing annotations, and issuing alerts to the astrophysics community. In this paper, we present an overview of the low-latency infrastructure as well as an overview of the performance of the data products to be released during O4 based on a MDC. We report on expected median latencies for the preliminary alert of full bandwidth searches (29.5 s) and for the creation of early warning triggers (-3.1 s), and show consistency and accuracy of released data products using the MDC. This paper provides a performance overview for LVK low-latency alert structure and data products using the MDC in anticipation of O4

Lack of Galectin-3 Drives Response to Paracoccidioides brasiliensis toward a Th2-Biased Immunity

There is recent evidence that galectin-3 participates in immunity to infections, mostly by tuning cytokine production. We studied the balance of Th1/Th2 responses to P. brasiliensis experimental infection in the absence of galectin-3. The intermediate resistance to the fungal infection presented by C57BL/6 mice, associated with the development of a mixed type of immunity, was replaced with susceptibility to infection and a Th2-polarized immune response, in galectin-3-deficient (gal3−/−) mice. Such a response was associated with defective inflammatory and delayed type hypersensitivity (DTH) reactions, high IL-4 and GATA-3 expression and low nitric oxide production in the organs of infected animals. Gal3−/− macrophages exhibited higher TLR2 transcript levels and IL-10 production compared to wild-type macrophages after stimulation with P. brasiliensis antigens. We hypothesize that, during an in vivo P. brasiliensis infection, galectin-3 exerts its tuning role on immunity by interfering with the generation of regulatory macrophages, thus hindering the consequent Th2-polarized type of response