Dynamically Driven Evolution of the Interstellar Medium in M51

We report the highest-fidelity observations of the spiral galaxy M51 in CO emission, revealing the evolution of giant molecular clouds (GMCs) vis-a-vis the large-scale galactic structure and dynamics. The most massive GMCs (so-called GMAs) are first assembled and then broken up as the gas flow through the spiral arms. The GMAs and their H2 molecules are not fully dissociated into atomic gas as predicted in stellar feedback scenarios, but are fragmented into smaller GMCs upon leaving the spiral arms. The remnants of GMAs are detected as the chains of GMCs that emerge from the spiral arms into interarm regions. The kinematic shear within the spiral arms is sufficient to unbind the GMAs against self-gravity. We conclude that the evolution of GMCs is driven by large-scale galactic dynamics --their coagulation into GMAs is due to spiral arm streaming motions upon entering the arms, followed by fragmentation due to shear as they leave the arms on the downstream side. In M51, the majority of the gas remains molecular from arm entry through the inter-arm region and into the next spiral arm passage.Comment: 6 pages, including 3 figures. Accepted, ApJ

Mutation of neuron-specific chromatin remodeling subunit BAF53b:rescue of plasticity and memory by manipulating actin remodeling

Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons. We generated transgenic mice lacking subdomain 2 of Baf53b (BAF53b Delta SB2). Long-term synaptic potentiation (LTP) and long-term memory, both of which are associated with phosphorylation of the actin severing protein cofilin, were assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically delivered into the hippocampus of BAF53b Delta SB2 mice in an effort to rescue LTP and memory. BAF53b Delta SB2 mutant mice show impairments in phosphorylation of synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory deficits are rescued by overexpression of a phosphorylation mimetic of cofilin. Baseline physiology and behavior were not affected by the mutation or the experimental treatment. This study suggests a potential link between nBAF function, actin cytoskeletal remodeling at the dendritic spine, and memory formation. This work shows that a targeted manipulation of synaptic function can rescue adult plasticity and memory deficits caused by manipulations of nBAF, and thereby provides potential novel avenues for therapeutic development for multiple intellectual disability disorders

The CARMA Paired Antenna Calibration System: Atmospheric Phase Correction for Millimeter Wave Interferometry and its Application to Mapping the Ultraluminous Galaxy Arp 193

Phase fluctuations introduced by the atmosphere are the main limiting factor in attaining diffraction limited performance in extended interferometric arrays at millimeter and submillimeter wavelengths. We report the results of C-PACS, the Combined Array for Research in Millimeter-Wave Astronomy Paired Antenna Calibration System. We present a systematic study of several hundred test observations taken during the 2009–2010 winter observing season where we utilize CARMA's eight 3.5 m antennas to monitor an atmospheric calibrator while simultaneously acquiring science observations with 6.1 and 10.4 m antennas on baselines ranging from a few hundred meters to ~2 km. We find that C-PACS is systematically successful at improving coherence on long baselines under a variety of atmospheric conditions. We find that the angular separation between the atmospheric calibrator and target source is the most important consideration, with consistently successful phase correction at CARMA requiring a suitable calibrator located ≾6° away from the science target. We show that cloud cover does not affect the success of C-PACS. We demonstrate C-PACS in typical use by applying it to the observations of the nearby very luminous infrared galaxy Arp 193 in ^(12)CO(2-1) at a linear resolution of ≈70 pc (0".12 × 0".18), 3 times better than previously published molecular maps of this galaxy. We resolve the molecular disk rotation kinematics and the molecular gas distribution and measure the gas surface densities and masses on 90 pc scales. We find that molecular gas constitutes ~30% of the dynamical mass in the inner 700 pc of this object with a surface density ~10^4 M_⊙ pc^(−2); we compare these properties to those of the starburst region of NGC 253

Species-selective killing of bacteria by antimicrobial peptide-PNAs

This is an open-access article distributed under the terms of the Creative Commons Attribution License, CC BY 4.0 which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Broad-spectrum antimicrobials kill indiscriminately, a property that can lead to negative clinical consequences and an increase in the incidence of resistance. Species-specific antimicrobials that could selectively kill pathogenic bacteria without targeting other species in the microbiome could limit these problems. The pathogen genome presents an excellent target for the development of such antimicrobials. In this study we report the design and evaluation of species-selective peptide nucleic acid (PNA) antibacterials. Selective growth inhibition of B. subtilis, E. coli, K. pnuemoniae and S. enterica serovar Typhimurium in axenic or mixed culture could be achieved with PNAs that exploit species differences in the translation initiation region of essential genes. An S. Typhimurium-specific PNA targeting ftsZ resulted in elongated cells that were not observed in E. coli, providing phenotypic evidence of the selectivity of PNA-based antimicrobials. Analysis of the genomes of E. coli and S. Typhimurium gave a conservative estimate of >150 PNA targets that could potentially discriminate between these two closely related species. This work provides a basis for the development of a new class of antimicrobial with a tuneable spectrum of activity.Peer reviewedFinal Published versio

Functional Crosstalk between Type I and II Interferon through the Regulated Expression of STAT1

Small "priming" quantities of type I interferon enhance cellular responses to type II interferon by maintaining basal levels of STAT1, explaining the observed crosstalk between these two cytokines

Engineered Protein Nano-Compartments for Targeted Enzyme Localization

Compartmentalized co-localization of enzymes and their substrates represents an attractive approach for multi-enzymatic synthesis in engineered cells and biocatalysis. Sequestration of enzymes and substrates would greatly increase reaction efficiency while also protecting engineered host cells from potentially toxic reaction intermediates. Several bacteria form protein-based polyhedral microcompartments which sequester functionally related enzymes and regulate their access to substrates and other small metabolites. Such bacterial microcompartments may be engineered into protein-based nano-bioreactors, provided that they can be assembled in a non-native host cell, and that heterologous enzymes and substrates can be targeted into the engineered compartments. Here, we report that recombinant expression of Salmonella enterica ethanolamine utilization (eut) bacterial microcompartment shell proteins in E. coli results in the formation of polyhedral protein shells. Purified recombinant shells are morphologically similar to the native Eut microcompartments purified from S. enterica. Surprisingly, recombinant expression of only one of the shell proteins (EutS) is sufficient and necessary for creating properly delimited compartments. Co-expression with EutS also facilitates the encapsulation of EGFP fused with a putative Eut shell-targeting signal sequence. We also demonstrate the functional localization of a heterologous enzyme (β-galactosidase) targeted to the recombinant shells. Together our results provide proof-of-concept for the engineering of protein nano-compartments for biosynthesis and biocatalysis

PHANGS-JWST First Results: A Global and Moderately Resolved View of Mid-Infrared and CO Line Emission from Galaxies at the Start of the JWST Era

We explore the relationship between mid-infrared (mid-IR) and CO rotational line emission from massive star-forming galaxies, which is one of the tightest scalings in the local universe. We assemble a large set of unresolved and moderately ($\sim 1$ kpc) spatially resolved measurements of CO (1-0) and CO (2-1) intensity, $I_{\rm CO}$, and mid-IR intensity, $I_{\rm MIR}$, at 8, 12, 22, and 24$\mu$m. The $I_{\rm CO}$ vs. $I_{\rm MIR}$ relationship is reasonably described by a power law with slopes $0.7{-}1.2$ and normalization $I_{\rm CO} \sim 1$ K km s$^{-1}$ at $I_{\rm MIR} \sim 1$ MJy sr$^{-1}$. Both the slopes and intercepts vary systematically with choice of line and band. The comparison between the relations measured for CO~(1-0) and CO (2-1) allow us to infer that $R_{21} \propto I_{\rm MIR}^{0.2}$, in good agreement with other work. The $8\mu$m and $12\mu$m bands, with strong PAH features, show steeper CO vs. mid-IR slopes than the $22\mu$m and $24\mu$m, consistent with PAH emission arising not just from CO-bright gas but also from atomic or CO-dark gas. The CO-to-mid-IR ratio correlates with global galaxy stellar mass ($M_\star$) and anti-correlates with SFR/$M_\star$. At $\sim 1$ kpc resolution, the first four PHANGS-JWST targets show CO to mid-IR relationships that are quantitatively similar to our larger literature sample, including showing the steep CO-to-mid-IR slopes for the JWST PAH-tracing bands, although we caution that these initial data have a small sample size and span a limited range of intensities.Comment: 29 pages, 13 figures, key quantitative results in Table 3, Accepted as part of a PHANGS-JWST Focus Issue to appear in Ap

Earliest evidence for the ivory trade in southern Africa : isotopic and ZooMS analysis of seventh-tenth century AD ivory from KwaZulu-Natal

KwaGandaganda, Ndondondwane and Wosi were major Early Farming Community settlements in what is today the KwaZulu-Natal province of South Africa. These sites have yielded, among other remains, abundant evidence of ivory and ivory working dating to the seventh–tenth centuries ad, pre-dating by approximately 200 years the better-known ivory artefacts from sites in the Limpopo River Valley and surrounding regions. We report the results of carbon, nitrogen and strontium isotope analysis to explore the origins and procurement of this ivory, in combination with Zooarchaeology by Mass Spectrometry (ZooMS) to identify the species of animals from which it was derived. All of the ivory studied using ZooMS was elephant, despite the presence of hippopotamus remains on all three sites. Some ivory was probably obtained from elephant herds that lived close to the sites, in the densely wooded river valleys favoured by both elephants and early farmers. Other material came from savannah environments further afield. Ivory found at these three sites was drawn from different catchments, implying a degree of landscape/resource partitioning even at this early stage. These communities clearly invested substantial effort in obtaining ivory from across the region, which speaks to the importance of this commodity in the economy of the time. We suggest that some ivory items were for local use, but that some may have been intended for more distant markets via Indian Ocean trade

A Genome-Wide Association Study of Total Bilirubin and Cholelithiasis Risk in Sickle Cell Anemia

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10−8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10−25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10−4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities