Intercontinental antenna arraying by symbol stream combining at ICE Giacobini-Zinner encounter

Deep space tracking stations on different continents were arrayed during the encounter of the International Cometary Explorer (ICE) spacecraft with the comet Giacobini-Zinner during September 9 through 12, 1985. This is the first time that telemetry signals received on different continents have been combined to enhance signal to noise ratio. The arraying was done in non-real time using the method of symbol stream combining. The improvement in signal to noise ratio was typically 2 dB over the stronger of the two stations in each array

Assessing the Impact of Sample Heterogeneity on Transcriptome Analysis of Human Diseases Using MDP Webtool

Transcriptome analyses have increased our understanding of the molecular mechanisms underlying human diseases. Most approaches aim to identify significant genes by comparing their expression values between healthy subjects and a group of patients with a certain disease. Given that studies normally contain few samples, the heterogeneity among individuals caused by environmental factors or undetected illnesses can impact gene expression analyses. We present a systematic analysis of sample heterogeneity in a variety of gene expression studies relating to inflammatory and infectious diseases and show that novel immunological insights may arise once heterogeneity is addressed. The perturbation score of samples is quantified using nonperturbed subjects (i.e., healthy subjects) as a reference group. Such a score allows us to detect outlying samples and subgroups of diseased patients and even assess the molecular perturbation of single cells infected with viruses. We also show how removal of outlying samples can improve the “signal” of the disease and impact detection of differentially expressed genes. The method is made available via the mdp Bioconductor R package and as a user-friendly webtool, webMDP, available at http://mdp.sysbio.tools

Characterizing the culturable surface microbiomes of diverse marine animals

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Keller, A. G., Apprill, A., Lebaron, P., Robbins, J., Romano, T. A., Overton, E., Rong, Y., Yuan, R., Pollara, S., & Whalen, K. E. Characterizing the culturable surface microbiomes of diverse marine animals. FEMS Microbiology Ecology, 97(4), (2021): fiab040, https://doi.org/10.1093/femsec/fiab040.Biofilm-forming bacteria have the potential to contribute to the health, physiology, behavior and ecology of the host and serve as its first line of defense against adverse conditions in the environment. While metabarcoding and metagenomic information furthers our understanding of microbiome composition, fewer studies use cultured samples to study the diverse interactions among the host and its microbiome, as cultured representatives are often lacking. This study examines the surface microbiomes cultured from three shallow-water coral species and two whale species. These unique marine animals place strong selective pressures on their microbial symbionts and contain members under similar environmental and anthropogenic stress. We developed an intense cultivation procedure, utilizing a suite of culture conditions targeting a rich assortment of biofilm-forming microorganisms. We identified 592 microbial isolates contained within 15 bacterial orders representing 50 bacterial genera, and two fungal species. Culturable bacteria from coral and whale samples paralleled taxonomic groups identified in culture-independent surveys, including 29% of all bacterial genera identified in the Megaptera novaeangliae skin microbiome through culture-independent methods. This microbial repository provides raw material and biological input for more nuanced studies which can explore how members of the microbiome both shape their micro-niche and impact host fitness.Funding was provided by the National Science Foundation (Biological Oceanography) award #1657808 and National Institutes of Health grants 1R21-AI119311–01 to K. E. Whalen, as well as funding from the Koshland Integrated Natural Science Center and Green Fund at Haverford College. This constitutes scientific manuscript #298 from the Sea Research Foundation

Persistent T Cell Repertoire Perturbation and T Cell Activation in HIV After Long Term Treatment

Objective: In people living with HIV (PLHIV), we sought to test the hypothesis that long term anti-retroviral therapy restores the normal T cell repertoire, and investigate the functional relationship of residual repertoire abnormalities to persistent immune system dysregulation. Methods: We conducted a case-control study in PLHIV and HIV-negative volunteers, of circulating T cell receptor repertoires and whole blood transcriptomes by RNA sequencing, complemented by metadata from routinely collected health care records. Results: T cell receptor sequencing revealed persistent abnormalities in the clonal T cell repertoire of PLHIV, characterized by reduced repertoire diversity and oligoclonal T cell expansion correlated with elevated CD8 T cell counts. We found no evidence that these expansions were driven by cytomegalovirus or another common antigen. Increased frequency of long CDR3 sequences and reduced frequency of public sequences among the expanded clones implicated abnormal thymic selection as a contributing factor. These abnormalities in the repertoire correlated with systems level evidence of persistent T cell activation in genome-wide blood transcriptomes. Conclusions: The diversity of T cell receptor repertoires in PLHIV on long term anti-retroviral therapy remains significantly depleted, and skewed by idiosyncratic clones, partly attributable to altered thymic output and associated with T cell mediated chronic immune activation. Further investigation of thymic function and the antigenic drivers of T cell clonal selection in PLHIV are critical to efforts to fully re-establish normal immune function

Bacterial quorum-sensing signal arrests phytoplankton cell division and impacts virus-induced mortality

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Pollara, S. B., Becker, J. W., Nunn, B. L., Boiteau, R., Repeta, D., Mudge, M. C., Downing, G., Chase, D., Harvey, E. L., & Whalen, K. E. Bacterial quorum-sensing signal arrests phytoplankton cell division and impacts virus-induced mortality. Msphere, 6(3), (2021): e00009-21, https://doi.org/10.1128/mSphere.00009-21.Interactions between phytoplankton and heterotrophic bacteria fundamentally shape marine ecosystems by controlling primary production, structuring marine food webs, mediating carbon export, and influencing global climate. Phytoplankton-bacterium interactions are facilitated by secreted compounds; however, linking these chemical signals, their mechanisms of action, and their resultant ecological consequences remains a fundamental challenge. The bacterial quorum-sensing signal 2-heptyl-4-quinolone (HHQ) induces immediate, yet reversible, cellular stasis (no cell division or mortality) in the coccolithophore Emiliania huxleyi; however, the mechanism responsible remains unknown. Using transcriptomic and proteomic approaches in combination with diagnostic biochemical and fluorescent cell-based assays, we show that HHQ exposure leads to prolonged S-phase arrest in phytoplankton coincident with the accumulation of DNA damage and a lack of repair despite the induction of the DNA damage response (DDR). While this effect is reversible, HHQ-exposed phytoplankton were also protected from viral mortality, ascribing a new role of quorum-sensing signals in regulating multitrophic interactions. Furthermore, our data demonstrate that in situ measurements of HHQ coincide with areas of enhanced micro- and nanoplankton biomass. Our results suggest bacterial communication signals as emerging players that may be one of the contributing factors that help structure complex microbial communities throughout the ocean.Funding for this work was supported by an NSF grant (OCE-1657808) awarded to K.E.W. and E.L.H. K.E.W. was also supported by a faculty research grant from Haverford College as well as funding from the Koshland Integrated Natural Science Center and Green Fund at Haverford College. E.L.H. was also supported by a Sloan Foundation research fellowship. B.L.N. was supported by an NSF grant (OCE-1633939). M.C.M. was supported by an NIH training grant (T32 HG000035). Mass spectrometry was partially supported by the University of Washington Proteomics Resource (UWPR95794). D.R. was supported by funding through the Gordon and Betty Moore Foundation (grant 6000), a Simons Collaboration for Ocean Processes and Ecology grant (329108), and an NSF grant (OCE-1736280). R.B. was supported by an NSF graduate research fellowship and an NSF grant (OCE-1829761)

Experiences that \u201creach the heart\u201d. Taking part in a whole body dissection course at the University of Malta

This article summarizes the activities of the four-week whole body dissection course the main authors participated in in August 2016 at the dissection hall of the University of Malta (UoM). Our team comprised 10 second-year medicine students from University of Palermo chosen among who had passed the Human Anatomy exam brilliantly. The need to move to the UoM to take part in such activity derives from the lack of practice approach in Italian schools of medicine, focused mostly on the theoretical studies, neglecting practical experience. The heart dissection reveal itself as a huge opportunity to finally apply our anatomical knowledge, improving it and enabling us to compare images took from books to the actual organ. We had the chance to handle a real heart, to appreciate its weight and consistence. We took part in coronary artery courses focusing on their functions within the heart machinery.This article summarizes the activities of the four-week whole body dissection course the main authors partecipated in August 2016 at the dissection hall of the University of Malta (UoM). Our team comprised 10 second-year medicine students from University of Palermo chosen among who had passed the Human Anatomy exam brilliantly. The need to molve to the UoM to take part in such activity derives from the lack of practice approach in Italian schools of medicine, focused mostly on the theoretical studies, neglecting practical experience. The heart dissection reveal itself as a huge opportunity to finally apply our anatomical knowledge, improving it and enabling us to compare image took from books to the actual organ. We had the chance to handle a real heart, to appreciate its weight and consistence. We took part in coronary artery courses focusing on their functions within the heart machinery

Vitamin D3 replacement enhances antigen-specific immunity in older adults

This article has been accepted for publication in Immunotherapy Advances Published by Oxford University Press

Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor

The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylation, and functional pathway analyses on serial biopsies of vincristine-treated CTVTs and found that regression occurs in sequential steps; activation of the innate immune system and host epithelial tissue remodeling followed by immune infiltration of the tumor, arrest in the cell cycle, and repair of tissue damage. We identified CCL5 as a possible driver of CTVT regression. Changes in gene expression are associated with methylation changes at specific intragenic sites. Our results underscore the critical role of host innate immunity in triggering cancer regression. By analyzing serial biopsies of vincristine-treated canine transmissible venereal tumors, Frampton et al. show that tumor regression occurs in sequential steps involving the activation of the innate immune system and immune infiltration of the tumor, and they identify CCL5 as a possible driver of regression

Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk

ABSTRACT Maternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a modified vaccinia Ankara (MVA) prime/intramuscular (i.m.) protein boost regimen induced functional IgG responses in milk, while MVA prime/intranasal (i.n.) boost induced robust milk Env-specific IgA responses. Yet, recent studies have suggested that prevention of postnatal MTCT may require both Env-specific IgA and functional IgG responses in milk. Thus, to investigate whether both responses could be elicited by a combined systemic/mucosal immunization strategy, animals previously immunized with the MVA prime/i.n. boost regimen received an i.n./i.m. combined C.1086 gp120 boost. Remarkably, high-magnitude Env-specific IgA responses were observed in milk, surpassing those in plasma. Furthermore, 29% of vaccine-elicited Env-specific B cells isolated from breast milk were IgA isotype, in stark contrast to the overwhelming predominance of IgG isotype Env-specific B cells in breast milk of chronically HIV-infected women. A clonal relationship was identified between Env-specific blood and breast milk B cells, suggesting trafficking of that cell population between the two compartments. Furthermore, IgA and IgG monoclonal antibodies isolated from Env-specific breast milk B cells demonstrated diverse Env epitope specificities and multiple effector functions, including tier 1 neutralization, antibody-dependent cellular cytotoxicity (ADCC), infected cell binding, and inhibition of viral attachment to epithelial cells. Thus, maternal i.n./i.m. combined immunization is a novel strategy to enhance protective Env-specific IgA in milk, which is subsequently transferred to the infant via breastfeeding. IMPORTANCE Efforts to increase the availability of antiretroviral therapy to pregnant and breastfeeding women in resource-limited areas have proven remarkably successful at reducing HIV vertical transmission rates. However, more than 200,000 children are infected annually due to failures in therapy implementation, monitoring, and adherence, nearly half by postnatal HIV exposure via maternal breast milk. Intriguingly, in the absence of antiretroviral therapy, only 10% of breastfed infants born to HIV-infected mothers acquire the virus, suggesting the existence of naturally protective immune factors in milk. Enhancement of these protective immune factors through maternal vaccination will be a critical strategy to reduce the global pediatric AIDS epidemic. We have previously demonstrated that a high magnitude of HIV Env-specific IgA in milk correlates with reduced risk of infant HIV acquisition. In this study, we describe a novel HIV vaccine regimen that induces potent IgA responses in milk and therefore could potentially protect against breast milk HIV MTCT