The Panchromatic Hubble Andromeda Treasury: Triangulum Extended Region (PHATTER). III. The Mass Function of Young Star Clusters in M33

We measure the star cluster mass function for the Local Group galaxy M33. We use the catalog of stellar clusters selected from the Panchromatic Hubble Andromeda Treasury: Triangulum Extended Region (PHATTER) survey. We analyze 711 clusters in M33 with $\rm 7.0$ 3.0 as determined from color-magnitude diagram fits to individual stars. The M33 cluster mass function is best described by a Schechter function with power law slope $\alpha = -2.06^{+0.14}_{-0.13}$, and truncation mass log($M_c/M_{\odot}$) $= 4.24^{+0.16}_{-0.13}$. The data show strong evidence for a high-mass truncation, thus strongly favoring a Schechter function fit over a pure power law. M33's truncation mass is consistent with the previously identified linear trend between $M_c$, and star formation rate surface density, \SigSFR. We also explore the effect that individual cluster mass uncertainties have on derived mass function parameters, and find evidence to suggest that large cluster mass uncertainties have the potential to bias the truncation mass of fitted mass functions on the one sigma level.Comment: 18 pages, 15 figures, 1 table, Accepted to ApJ (February 2, 2022

Antigenic Variation of the Dengue Virus 2 Genotypes Impacts the Neutralization Activity of Human Antibodies in Vaccinees

Martinez et al. demonstrate that dengue virus serotype 2 (DENV2) genetic variation modulates neutralizing antibody activity from infection and vaccination. This observation underlines that genotypic variation impacts dengue virus 2 evasion from humoral immunity, suggesting that intraserotype genotypic variation should be considered in designing dengue vaccines. © 2020 The Author(s); Dengue virus (DENV) infects an estimated 390 million people each year worldwide. As tetravalent DENV vaccines have variable efficacy against DENV serotype 2 (DENV2), we evaluated the role of genetic diversity within the pre-membrane (prM) and envelope (E) proteins of DENV2 on vaccine performance. We generated a recombinant DENV2 genotype variant panel with contemporary prM and E isolates that are representative of global genetic diversity. The DENV2 genotype variants differ in growth kinetics, morphology, and virion stability. Importantly, the DENV2 genotypic variants are differentially neutralized by monoclonal antibodies, polyclonal serum neutralizing antibodies from DENV2-infected human subjects, and vaccine-elicited antibody responses from the TV003 NIH DENV2 monovalent and DENV tetravalent vaccines. We conclude that DENV2 prM and E genetic diversity significantly modulates antibody neutralization activity. These findings have important implications for dengue vaccines, which are being developed under the assumption that intraserotype variation has minimal impact on neutralizing antibodies

A tetravalent live attenuated dengue virus vaccine stimulates balanced immunity to multiple serotypes in humans

The four-dengue virus (DENV) serotypes infect several hundred million people annually. For the greatest safety and efficacy, tetravalent DENV vaccines are designed to stimulate balanced protective immunity to all four serotypes. However, this has been difficult to achieve. Clinical trials with a leading vaccine demonstrated that unbalanced replication and immunodominance of one vaccine component over others can lead to low efficacy and vaccine enhanced severe disease. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a live attenuated tetravalent DENV vaccine (TV003), which is currently being tested in phase 3 clinical trials. Here we report, our study to determine if TV003 stimulate balanced and serotype-specific (TS) neutralizing antibody (nAb) responses to each serotype. Serum samples from twenty-one dengue-naive individuals participated under study protocol CIR287 (ClinicalTrials.gov NCT02021968) are analyzed 6 months after vaccination. Most subjects (76%) develop TS nAbs to 3 or 4 DENV serotypes, indicating immunity is induced by each vaccine component. Vaccine-induced TS nAbs map to epitopes known to be targets of nAbs in people infected with wild type DENVs. Following challenge with a partially attenuated strain of DENV2, all 21 subjects are protected from the efficacy endpoints. However, some vaccinated individuals develop post challenge nAb boost, while others mount post-challenge antibody responses that are consistent with sterilizing immunity. TV003 vaccine induced DENV2 TS nAbs are associated with sterilizing immunity. Our results indicate that nAbs to TS epitopes on each serotype may be a better correlate than total levels of nAbs currently used for guiding DENV vaccine development

Balancing end-to-end budgets of the Georges Bank ecosystem

Author Posting. © Elsevier, 2007. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Progress In Oceanography 74 (2007): 423-448, doi:10.1016/j.pocean.2007.05.003.Oceanographic regimes on the continental shelf display a great range in the time scales of physical exchange, biochemical processes and trophic transfers. The close surface-to-seabed physical coupling at intermediate scales of weeks to months means that the open ocean simplification to a purely pelagic food web is inadequate. Top-down trophic depictions, starting from the fish populations, are insufficient to constrain a system involving extensive nutrient recycling at lower trophic levels and subject to physical forcing as well as fishing. These pelagic-benthic interactions are found on all continental shelves but are particularly important on the relatively shallow Georges Bank in the northwest Atlantic. We have generated budgets for the lower food web for three physical regimes (well mixed, transitional and stratified) and for three seasons (spring, summer and fall/winter). The calculations show that vertical mixing and lateral exchange between the three regimes are important for zooplankton production as well as for nutrient input. Benthic suspension feeders are an additional critical pathway for transfers to higher trophic levels. Estimates of production by mesozooplankton, benthic suspension feeders and deposit feeders, derived primarily from data collected during the GLOBEC years of 1995-1999, provide input to an upper food web. Diets of commercial fish populations are used to calculate food requirements in three fish categories, planktivores, benthivores and piscivores, for four decades, 1963-2002, between which there were major changes in the fish communities. Comparisons of inputs from the lower web with fish energetic requirements for plankton and benthos indicate that we obtained reasonable agreement for the last three decades, 1973 to 2002. However, for the first decade, the fish food requirements were significantly less than the inputs. This decade, 1963-1972, corresponds to a period characterized by a strong Labrador Current and lower nitrate levels at the shelf edge, demonstrating how strong bottom-up physical forcing may determine overall fish yields.The research was done under the aegis of the U.S.-GLOBEC Northwest Atlantic Georges Bank Study, a program sponsored jointly by the U.S. National Science Foundation and the U.S. National Oceanic and Atmospheric Administration. We acknowledge NOAA-CICOR award NA17RJ1233 (J.H. Steele), NSF awards OCE0217399 (D.J. Gifford), OCE0217122 (J.J. Bisagni) and OCE0217257 (M.E. Sieracki). W.T. Stockhausen was supported by the NOAA Sponsored Coastal Ocean Research Program

Prior dengue virus exposure shapes T Cell immunity to Zika Virus in humans

While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether pre-existing dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with Tetravalent Dengue Attenuated Vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors, but declines in DENV pre-exposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells form DENV pre-exposed donors selectively up-regulated granzyme B and PD1, as compared to DENV-naïve donors. Finally, we discovered that ZIKV structural proteins (E, prM and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins

Cutting Edge:Transcriptional profiling reveals multifunctional and cytotoxic antiviral responses of zika virus-specific CD8 + T cells

Zika virus (ZIKV) constitutes an increasing public health problem. Previous studies have shown that CD8 + T cells play an important role in ZIKV-specific protective immunity. We have previously defined antigenic targets of the ZIKV-specific CD8 + T cell response in humans. In this study, we characterized the quality and phenotypes of these responses by a combined use of flow cytometry and transcriptomic methods, using PBMCs from donors deriving from different geographical locations collected in the convalescent phase of infection. We show that ZIKVspecific CD8 + T cells are characterized by a polyfunctional IFN-g signature with upregulation of TNF-a, TNF receptors, and related activation markers, such as CD69, as well as a cytotoxic signature characterized by strong upregulation of GZMB and CRTAM. The signature is stable and not influenced by previous dengue virus exposure, geographical location, or time of sample collection postinfection. To our knowledge, this work elucidates the first in-depth characterization of human CD8 + T cells responding to ZIKV infection

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Empirical 2MASS-WFC3/IR Filter Transformations Across the H-R Diagram from Synthetic Photometry

Near-infrared bandpasses on spaceborne observatories diverge from their ground-based counterparts as they are free of atmospheric telluric absorption. Available transformations between respective filter systems in the literature rely on theoretical stellar atmospheres, which are known to have difficulties reproducing the observed spectral energy distributions of cool giants. We present new transformations between the Two Micron All Sky Survey JHKS and Hubble Space Telescope WFC3/IR F110W, F125W, and F160W photometric systems based on synthetic photometry of empirical stellar spectra from four spectral libraries. This sample comprises over 1000 individual stars, which together span nearly the full H-R diagram and sample stellar populations from the solar neighborhood out to the Magellanic Clouds, covering a broad range of ages, metallicities, and other relevant stellar properties. In addition to global color-dependent transformations, we examine band-to-band differences for cool, luminous giant stars in particular, including multiple types of primary distance indicators. © 2023. The Author(s). Published by the American Astronomical Society.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]