Viral-induced encephalitis initiates distinct and functional CD103+ CD11b+ brain dendritic cell populations within the olfactory bulb.

Dendritic cells (DC) are antigen-presenting cells found in both lymphoid and nonlymphoid organs, including the brain (bDC) of Cd11c/eyfp transgenic C57BL/6 mice. Using an intranasal vesicular stomatitis virus infection, we demonstrated that EYFP(+) cells amass in areas associated with viral antigens, take on an activated morphology, and project their processes into infected neuronal tissue within the olfactory bulb. These bDC separated into three EYFP(+) CD45(+) CD11b(+) populations, all but one being able to functionally promote both T lymphocyte proliferation and T(H)1 cytokine production. One population was shown to emanate from the brain and a second population was peripherally derived. The third population was of indeterminate origin, being both radiosensitive and not replenished by donor bone marrow. Finally, each EYFP(+) population contained CD11b(+) CD103(+) subpopulations and could be distinguished in terms of CD115, Gr-1, and Ly-6C expression, highlighting mucosal and monocyte-derived DC lineages.

Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects.

OBJECTIVES: One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects. DESIGN: Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later. RESULTS: Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure. CONCLUSIONS: These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in future TTS studies, including protective agent evaluations, that some noise exposures have resulted in neural degeneration in animal models, even when both audiometric thresholds and DPOAE levels returned to pre-exposure values.

Evolutionary disruption of S&P 500 trading concentration: An intriguing tale of a financial innovation.

The novel finding of Balakrishnan, Miller & Shankar (2008) that investors, overwhelmed by the plethora of stock investment offerings, limit their analysis and daily choices to only a small subset of stocks (i.e., herding behavior) now seems to be common wisdom (Iosebashvili, 2019). We investigate whether the introduction of an innovation in financial products designed to allow investors to trade the entire product bundle of S&P 500 stocks, namely S&P 500 index funds, altered "herding behavior" by creating a new class of index investors. We model the distribution of daily trading concentration as a power law function and examine changes over the last six decades. Intriguingly, we discover a unique pattern in the trading concentration distribution that exhibits two distinct trends. For the period 1960-75, the trading concentration of the S&P 500 stocks tracks the increasing trend for the entire market, i.e., the unevenness in trading has steadily increased. However, after the introduction of S&P 500 index funds in 1975, concentration of trading in the S&P 500 stocks has steadily decreased, i.e., trading distribution has become more even across all 500 stocks, contrary to the current belief of equity analysts. This is also in sharp contrast to the case of U.S. stocks that are not in the S&P 500 index where trading concentration has steadily increased. We further corroborate the uniqueness of the inverted V-shape by a counterfactual investigation of the trading concentration patterns for other sets of 500 stock portfolios. This uniquely distinctive trading concentration pattern for S&P 500 stocks appears to be driven by the increasing dominance of bundle trading by index investors.

Draft Genome Sequence of a Novel Luteimonas sp. Strain from Coral Mucus, Hawai'i.

Luteimonas sp. strain JM171 was cultivated from mucus collected around the coral Porites lobata The JM171 draft genome of 2,992,353 bp contains 2,672 protein-coding open reading frames, 45 tRNA coding regions, and encodes a putative globin-coupled diguanylate cyclase, JmGReg.

Vesicular stomatitis virus modified with single chain IL-23 exhibits oncolytic activity against tumor cells in vitro and in vivo.

Viruses are potentially attractive agents for development as novel oncolytic agents. Reverse genetic approaches allow for the attenuation of candidate viruses and can enhance their ability to exploit inherent cellular and molecular properties of tumors, including deficiencies in interferon (IFN) signaling. Vesicular stomatitis virus (VSV) is a promising oncolytic agent for exactly these reasons. VSV infection of immunocompetent mice is usually rapidly cleared due to the virus' sensitivity to type I IFN responses. However, in tumors that are unable to activate the IFN response, VSV is able to replicate without inhibition, resulting in cell destruction. Unfortunately, when VSV is introduced into mice intranasally or systemically via therapeutic doses into tumor-bearing rodents, hosts may develop fatal encephalitis. We have previously found that a recombinant VSV expressing the pro-inflammatory cytokine interleukin-23 (IL-23) is significantly attenuated in the central nervous system (CNS). As a result of this, we hypothesized that attenuation in the CNS is partially a result of enhanced NO response as a result of IL-23 signaling. Infection of the CNS with this virus (designated VSV23) is characterized by decreased viral replication, morbidity, and mortality. We have now extended those studies which reveal that VSV23 maintains oncolytic capacity in vitro in multiple cell lines including NB41A3 neuroblastomas, L929 adipose-derived cells, immortalized BHK-21 cells, and the murine mammary derived JC cells. Additionally, in vivo VSV23 infection results in JC tumor destruction and induces enhanced memory responses against tumor cells.