The Vocal Breeding Behaviour of Harbour Seals (Phoca vitulina) in Georgia Strait, Canada: Temporal Patterns and Vocal Repertoire

During the breeding season, male harbour seals (Phoca vitulina) produce underwater calls used in intra-sexual competition and advertisement. One call type, called a roar, has been documented in every population of this species that has been studied. Because calls vary in structure and temporal patterns among populations, it can be inferred that regional vocal dialects may exist, and that the influence of local environmental and biological conditions may affect the timing of calls. Breeding calls have only been studied in relatively few locations worldwide; however, the effect of ambient noise on the underwater vocal behaviour of harbour seals has not been studied. I investigated the temporal patterns, structure and complexity of harbour seal breeding calls at Hornby Island, British Columbia. Underwater recordings were made near the south end of Hornby Island in the summer breeding season of 2014 using a single omnidirectional hydrophone while concurrent visual observations were conducted at a nearby site on shore. I investigated the relationships between roars per hour, tide level, ambient noise and time of day. Logistic regression showed that roars were over eight times more likely to be heard during night-time hours than during the day. When roars were heard, roar number was most influenced by time of day and the progression of the breeding season, with more roars heard later into the breeding season. Roar density was inversely related with ambient noise; however, ambient noise and time of day were highly auto-correlated, and therefore the effects of these two variables could not be assessed independently. Whereas harbour seal call timing in other areas has been attributed to tidally-driven haul-out patterns, the tide level at Hornby Island did not statistically correlate with roar density. I hypothesize that ambient noise may be a cause of the strong diel pattern of call density at Hornby Island, and suggest further study to determine the mechanistic link between ambient noise cycles and calling behaviour. Four breeding call types were identified, one of which was the ‘roar’ call described in every population that has been studied. The structure of the roars at Hornby Island was comparable to those of other populations, but displayed wide variation in several parameters. Each of the three non-roar call types were distinguished from roars qualitatively by aural-visual classification, and quantitatively by trained linear discriminants analysis (LDA). Agreement between these two classification systems was 88%, suggesting that the four call types were distinct. The three non-roar call types contained five call subtypes which were also identified through aural-visual and LDA classification. Agreement was slightly lower at 74%, but more variable, suggesting that some call subtypes were more distinct than others. One non-roar call type, the sweep, was distinct from any call previously described for harbour seals worldwide. I suggest that more than one of these call types are used by each individual, supporting the results of a previous study in California which identified several call types produced by harbour seals. If this is the case, then the vocal breeding repertoire of harbour seals at Hornby Island is more complex than that of most previously studied populations. Further study of this population with the ability to localize calls and identify individuals is required to support or refute the hypothesis that individual harbour seals at Hornby Island produce several call types

FABRIC: A National-Scale Programmable Experimental Network Infrastructure

FABRIC is a unique national research infrastructure to enable cutting-edge and exploratory research at-scale in networking, cybersecurity, distributed computing and storage systems, machine learning, and science applications. It is an everywhere-programmable nationwide instrument comprised of novel extensible network elements equipped with large amounts of compute and storage, interconnected by high speed, dedicated optical links. It will connect a number of specialized testbeds for cloud research (NSF Cloud testbeds CloudLab and Chameleon), for research beyond 5G technologies (Platforms for Advanced Wireless Research or PAWR), as well as production high-performance computing facilities and science instruments to create a rich fabric for a wide variety of experimental activities

Leaders or Followers? A Temporal Analysis of Tweets from IRA Trolls

The Internet Research Agency (IRA) influences online political conversations in the United States, exacerbating existing partisan divides and sowing discord. In this paper we investigate the IRA's communication strategies by analyzing trending terms on Twitter to identify cases in which the IRA leads or follows other users. Our analysis focuses on over 38M tweets posted between 2016 and 2017 from IRA users (n=3,613), journalists (n=976), members of Congress (n=526), and politically engaged users from the general public (n=71,128). We find that the IRA tends to lead on topics related to the 2016 election, race, and entertainment, suggesting that these are areas both of strategic importance as well having the highest potential impact. Furthermore, we identify topics where the IRA has been relatively ineffective, such as tweets on military, political scandals, and violent attacks. Despite many tweets on these topics, the IRA rarely leads the conversation and thus has little opportunity to influence it. We offer our proposed methodology as a way to track the strategic choices of future influence operations in real-time.Comment: ICWSM 202

Effective Control of Chronic γ-Herpesvirus Infection by Unconventional MHC Class Ia–Independent CD8 T Cells

Control of virus infection is mediated in part by major histocompatibility complex (MHC) Class Ia presentation of viral peptides to conventional CD8 T cells. Although important, the absolute requirement for MHC Class Ia–dependent CD8 T cells for control of chronic virus infection has not been formally demonstrated. We show here that mice lacking MHC Class Ia molecules (K(b−/−)xD(b−/−) mice) effectively control chronic γ-herpesvirus 68 (γHV68) infection via a robust expansion of β(2)-microglobulin (β(2)-m)-dependent, but CD1d-independent, unconventional CD8 T cells. These unconventional CD8 T cells expressed: (1) CD8αβ and CD3, (2) cell surface molecules associated with conventional effector/memory CD8 T cells, (3) TCRαβ with a significant Vβ4, Vβ3, and Vβ10 bias, and (4) the key effector cytokine interferon-γ (IFNγ). Unconventional CD8 T cells utilized a diverse TCR repertoire, and CDR3 analysis suggests that some of that repertoire may be utilized even in the presence of conventional CD8 T cells. This is the first demonstration to our knowledge that β(2)-m–dependent, but Class Ia–independent, unconventional CD8 T cells can efficiently control chronic virus infection, implicating a role for β(2)-n–dependent non-classical MHC molecules in control of chronic viral infection. We speculate that similar unconventional CD8 T cells may be able to control of other chronic viral infections, especially when viruses evade immunity by inhibiting generation of Class Ia–restricted T cells

IRF-3, IRF-5, and IRF-7 Coordinately Regulate the Type I IFN Response in Myeloid Dendritic Cells Downstream of MAVS Signaling

Although the transcription factors IRF-3 and IRF-7 are considered master regulators of type I interferon (IFN) induction and IFN stimulated gene (ISG) expression, Irf3-/-×Irf7-/- double knockout (DKO) myeloid dendritic cells (mDC) produce relatively normal levels of IFN-β after viral infection. We generated Irf3-/-×Irf5-/-×Irf7-/- triple knockout (TKO) mice to test whether IRF-5 was the source of the residual induction of IFN-β and ISGs in mDCs. In pathogenesis studies with two unrelated positive-sense RNA viruses (West Nile virus (WNV) and murine norovirus), TKO mice succumbed at rates greater than DKO mice and equal to or approaching those of mice lacking the type I IFN receptor (Ifnar-/-). In ex vivo studies, after WNV infection or exposure to Toll-like receptor agonists, TKO mDCs failed to produce IFN-β or express ISGs. In contrast, this response was sustained in TKO macrophages following WNV infection. To define IRF-regulated gene signatures, we performed microarray analysis on WNV-infected mDC from wild type (WT), DKO, TKO, or Ifnar-/- mice, as well as from mice lacking the RIG-I like receptor adaptor protein MAVS. Whereas the gene induction pattern in DKO mDC was similar to WT cells, remarkably, almost no ISG induction was detected in TKO or Mavs-/- mDC. The relative equivalence of TKO and Mavs-/- responses suggested that MAVS dominantly regulates ISG induction in mDC. Moreover, we showed that MAVS-dependent induction of ISGs can occur through an IRF-5-dependent yet IRF-3 and IRF-7-independent pathway. Our results establish IRF-3, -5, and -7 as the key transcription factors responsible for mediating the type I IFN and ISG response in mDC during WNV infection and suggest a novel signaling link between MAVS and IRF-5

Key role of T cell defects in age-related vulnerability to West Nile virus

West Nile virus (WNV) infection causes a life-threatening meningoencephalitis that becomes increasingly more prevalent over the age of 50 and is 40–50× more prevalent in people over the age of 70, compared with adults under the age of 40. In a mouse model of age-related vulnerability to WNV, we demonstrate that death correlates with increased viral titers in the brain and that this loss of virus control with age was the result of defects in the CD4 and CD8 T cell response against WNV. Specific age-related defects in T cell responses against dominant WNV epitopes were detected at the level of cytokine and lytic granule production, each of which are essential for resistance against WNV, and in the ability to generate multifunctional anti-WNV effector T cells, which are believed to be critical for robust antiviral immunity. In contrast, at the peak of the response, old and adult T cells exhibited superimposable peptide sensitivity. Most importantly, although the adult CD4 or CD8 T cells readily protected immunodeficient mice upon adoptive transfer, old T cells of either subset were unable to provide WNV-specific protection. Consistent with a profound qualitative and quantitative defect in T cell immunity, old brains contained at least 12× fewer total effector CD8 T cells compared with adult mice at the peak of brain infection. These findings identify potential targets for immunomodulation and treatment to combat lethal WNV infection in the elderly

Immune Response to the West Nile Virus in Aged Non-Human Primates

Background: Risk of encephalitis from West Nile virus (WNV) infection increases dramatically with age. Understanding the basis of this susceptibility requires development of suitable animal models. Here, we investigated the immune response to WNV in old non-human primates. Methodology/Principal Findings: We investigated clinical, immunological and virological correlates of WNV infection in aging non-human primates. Aged (17-30yrs) and adult (6-9yrs) Rhesus macaques (RM) were challenged with WNV in the presence or the absence of the mosquito salivary gland extract (SGE) to approximate natural infection. None of the 26 animals exhibited clinical signs of the disease. Quantitative PCR suggested discrete and short-lived viremia, but infectious virus was never isolated. There was markedly increased, age-independent, proliferation of CD3- non-B cells, followed by Bcell proliferation, which correlated to the loss of detectable WNV genomes. Moreover, animals primed with mosquito salivary gland extract exhibited reduced circulating WNV RNA. While we found the expected age-associated reduction in T cell proliferation, adaptive immunity did not correlate with infection outcome. That was further confirmed in a cohort of thymectomized and/or CD8 T-cell depleted Cynomolgus macaques (CM; N = 15), who also failed to develop WNV disease. Conclusions/significance: Results are consistent with strong and age-independent innate resistance of macaques against WNV challenge. This animal model is therefore not suitable for vaccine and therapeutic testing against WNV. However, understanding the basis of their innate resistance against WNV in macaques could provide helpful clues to improve anti- WNV protection of older adults. © 2010 Wertheimer et al

Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors

Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections

Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults

Background: Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells. Methodology/Principal Findings: To test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi-infected children and compared with long-term T. cruzi-infected adults with no evidence of heart failure. The phenotype of CD4+ T cells was also assessed in T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was prevalent among T. cruzi-infected children. Flow cytometric analysis of co-expression profiles of CD4+ T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to T. cruzi showed polyfunctional T cell responses in most T. cruzi-infected children. Monofunctional T cell responses and an absence of CD4+TNF-α+-secreting T cells were observed in T. cruzi-infected adults. A relatively high degree of activation and differentiation of CD4+ T cells was evident in T. cruzi-infected children. Conclusions/Significance: Our observations are compatible with our initial hypothesis that persistent T. cruzi infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.Fil: Albareda, María Cecilia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: de Rissio, Ana María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Tomas, Gonzalo. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Serjan, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Alvarez, María Gabriela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Viotti, Rodolfo Jorge. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Fichera, Laura Edith. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Esteva, Mónica Inés. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Potente, Daniel Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Armenti, Alejandro. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Tarleton, Rick L.. University of Georgia; Estados UnidosFil: Laucella, Susana Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin