Kinematic Analysis of a Protostellar Multiple System: Measuring the Protostar Masses and Assessing Gravitational Instability in the Disks of L1448 IRS3B and L1448 IRS3A

We present new Atacama Large Millimeter/submillimeter Array (ALMA) observations towards a compact (230~au separation) triple protostar system, L1448 IRS3B, at 879~\micron with \contbeam~resolution. Spiral arm structure within the circum-multiple disk is well resolved in dust continuum toward IRS3B, and we detect the known wide (2300~au) companion, IRS3A, also resolving possible spiral substructure. Using dense gas tracers, C17O, H13CO$+$, and H13CN, we resolve the Keplerian rotation for both the circum-triple disk in IRS3B and the disk around IRS3A. Furthermore, we use the molecular line kinematic data and radiative transfer modeling of the molecular line emission to confirm that the disks are in Keplerian rotation with fitted masses of $1.19^{+0.13}_{-0.07}$ for IRS3B-ab, $1.51^{+0.06}_{-0.07}$~Msun for IRS3A, and place an upper limit on the central protostar mass for the tertiary IRS3B-c of 0.2~Msun. We measure the mass of the fragmenting disk of IRS3B to be 0.29~Msun from the dust continuum emission of the circum-multiple disk and estimate the mass of the clump surrounding IRS3B-c to be 0.07~Msun. We also find that the disk around IRS3A has a mass of 0.04~Msun. By analyzing the Toomre~Q parameter, we find the IRS3A circumstellar disk is gravitationally stable (Q$>$5), while the IRS3B disk is consistent with a gravitationally unstable disk (Q$<$1) between the radii 200-500~au. This coincides with the location of the spiral arms and the tertiary companion IRS3B-c, supporting the hypothesis that IRS3B-c was formed in situ via fragmentation of a gravitationally unstable disk

Bridging the Gap Between Stars and Planets: The Formation and Early Evolution of Brown Dwarfs

This White Paper, submitted to the National Academy of Sciences' Astro2010 Decadal Review Committee, focuses on 2 central themes in the study of young brown dwarfs -- their formation mechanism and disk characteristics -- which are of direct relevance to fundamental questions of stellar and planetary origins and properties.Comment: 8 pages, 3 figures, Astro2010 Science White Paper (v2 has 2 references corrected/updated, and 3 repeated references in the v1 reference list removed

A structural biology community assessment of AlphaFold2 applications

Most proteins fold into 3D structures that determine how they function and orchestrate the biological processes of the cell. Recent developments in computational methods for protein structure predictions have reached the accuracy of experimentally determined models. Although this has been independently verified, the implementation of these methods across structural-biology applications remains to be tested. Here, we evaluate the use of AlphaFold2 (AF2) predictions in the study of characteristic structural elements; the impact of missense variants; function and ligand binding site predictions; modeling of interactions; and modeling of experimental structural data. For 11 proteomes, an average of 25% additional residues can be confidently modeled when compared with homology modeling, identifying structural features rarely seen in the Protein Data Bank. AF2-based predictions of protein disorder and complexes surpass dedicated tools, and AF2 models can be used across diverse applications equally well compared with experimentally determined structures, when the confidence metrics are critically considered. In summary, we find that these advances are likely to have a transformative impact in structural biology and broader life-science research

The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars. I. Identifying and Characterizing the Protostellar Content of the OMC-2 FIR4 and OMC-2 FIR3 Regions

We present ALMA (0.87~mm) and VLA (9~mm) observations toward OMC2-FIR4 and OMC2-FIR3 within the Orion integral-shaped filament that are thought to be the nearest regions of intermediate mass star formation. We characterize the continuum sources within these regions on $\sim$40~AU (0\farcs1) scales and associated molecular line emission at a factor of $\sim$30 better resolution than previous observations at similar wavelengths. We identify six compact continuum sources within OMC2-FIR4, four in OMC2-FIR3, and one additional source just outside OMC2-FIR4. This continuum emission is tracing the inner envelope and/or disk emission on less than 100~AU scales. HOPS-108 is the only protostar in OMC2-FIR4 that exhibits emission from high-excitation transitions of complex organic molecules (e.g., methanol and other lines) coincident with the continuum emission. HOPS-370 in OMC2-FIR3 with L~$\sim$~360~\lsun, also exhibits emission from high-excitation methanol and other lines. The methanol emission toward these two protostars is indicative of temperatures high enough to thermally evaporate methanol from icy dust grains; overall these protostars have characteristics similar to hot corinos. We do not identify a clear outflow from HOPS-108 in \twco, but find evidence of interaction between the outflow/jet from HOPS-370 and the OMC2-FIR4 region. The multitude of observational constraints indicate that HOPS-108 is likely a low to intermediate-mass protostar in its main mass accretion phase and it is the most luminous protostar in OMC2-FIR4. The high resolution data presented here are essential for disentangling the embedded protostars from their surrounding dusty environments and characterizing them

Towards a structurally resolved human protein interaction network

Cellular functions are governed by molecular machines that assemble through protein-protein interactions. Their atomic details are critical to studying their molecular mechanisms. However, fewer than 5% of hundreds of thousands of human protein interactions have been structurally characterized. Here we test the potential and limitations of recent progress in deep-learning methods using AlphaFold2 to predict structures for 65,484 human protein interactions. We show that experiments can orthogonally confirm higher-confidence models. We identify 3,137 high-confidence models, of which 1,371 have no homology to a known structure. We identify interface residues harboring disease mutations, suggesting potential mechanisms for pathogenic variants. Groups of interface phosphorylation sites show patterns of co-regulation across conditions, suggestive of coordinated tuning of multiple protein interactions as signaling responses. Finally, we provide examples of how the predicted binary complexes can be used to build larger assemblies helping to expand our understanding of human cell biology

Themis2/ICB1 Is a Signaling Scaffold That Selectively Regulates Macrophage Toll-Like Receptor Signaling and Cytokine Production

BACKGROUND: Thymocyte expressed molecule involved in selection 1 (Themis1, SwissProt accession number Q8BGW0) is the recently characterised founder member of a novel family of proteins. A second member of this family, Themis2 (Q91YX0), also known as ICB1 (Induced on contact with basement membrane 1), remains unreported at the protein level despite microarray and EST databases reporting Themis2 mRNA expression in B cells and macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Here we characterise Themis2 protein for the first time and show that it acts as a macrophage signalling scaffold, exerting a receptor-, mediator- and signalling pathway-specific effect on TLR responses in RAW 264.7 macrophages. Themis2 over-expression enhanced the LPS-induced production of TNF but not IL-6 or Cox-2, nor TNF production induced by ligands for TLR2 (PAM3) or TLR3 (poly IratioC). Moreover, LPS-induced activation of the MAP kinases ERK and p38 was enhanced in cells over-expressing Themis2 whereas the activation of JNK, IRF3 or NF-kappaB p65, was unaffected. Depletion of Themis2 protein by RNA inteference inhibited LPS-induced TNF production in primary human macrophages demonstrating a requirement for Themis2 in this event. Themis2 was inducibly tyrosine phosphorylated upon LPS challenge and interacted with Lyn kinase (P25911), the Rho guanine nucleotide exchange factor, Vav (P27870), and the adaptor protein Grb2 (Q60631). Mutation of either tyrosine 660 or a proline-rich sequence (PPPRPPK) simultaneously interrupted this complex and reduced by approximately 50% the capacity of Themis2 to promote LPS-induced TNF production. Finally, Themis2 protein expression was induced during macrophage development from murine bone marrow precursors and was regulated by inflammatory stimuli both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: We hypothesise that Themis2 may constitute a novel, physiological control point in macrophage inflammatory responses