Loss of T-bet, But Not STAT1, Prevents the Development of Experimental Autoimmune Encephalomyelitis

The transcription factors signal transducer and activator of transcription (STAT)1 and T-bet control the differentiation of interferon (IFN)-γ–producing T helper type (Th)1 cells. Here we compare the role of T-bet and STAT1 in the initiation and regulation of experimental autoimmune encephalomyelitis (EAE), a disease initiated by Th1 cells. T-bet–deficient mice immunized with myelin oligodendrocyte glycoprotein (MOG) were resistant to the development of EAE. This protection was also observed when T-bet−/− mice were crossed to the MOG-specific 2D2 T cell receptor transgenic strain. In contrast, although T-bet is downstream of STAT1, STAT1−/− mice were highly susceptible to EAE and developed more severe and accelerated disease with atypical neuropathologic features. The function of T-bet was dominant as mice deficient in both T-bet and STAT1 were also protected from EAE. CD4+ CD25+ regulatory T cells from these two mice strains were fully competent and do not explain the difference in disease susceptibility. However, enhanced EAE in STAT1−/− mice was associated with continued generation of IFN-γ–producing Th1 cells and up-regulation of selective chemokines responsible for the increased recruitment of macrophages and neutrophils in the central nervous system. Although the two transcription factors, STAT1 and T-bet, both induce IFN-γ gene transcription, our results demonstrate marked differences in their function in regulating pathogenic Th1 cell responses

Langmuir Turbulence under Hurricane Gustav (2008)

Extreme winds and complex wave fields drive upper-ocean turbulence in tropical cyclone conditions. Motivated by Lagrangian float observations of bulk vertical velocity variance (VVV) under Hurricane Gustav (2008), upper-ocean turbulence is investigated based on large-eddy simulation (LES) of the wave-averaged Navier–Stokes equations. To realistically capture wind- and wave-driven Langmuir turbulence (LT), the LES model imposes the Stokes drift vector from spectral wave simulations; both the LES and wave model are forced by the NOAA Hurricane Research Division (HRD) surface wind analysis product. Results strongly suggest that without LT effects simulated VVV underestimates the observed VVV. LT increases the VVV, indicating that it plays a significant role in upper-ocean turbulence dynamics. Consistent with observations, the LES predicts a suppression of VVV near the hurricane eye due to wind-wave misalignment. However, this decrease is weaker and of shorter duration than that observed, potentially due to large-scale horizontal advection not present in the LES. Both observations and simulations are consistent with a highly variable upper ocean turbulence field beneath tropical cyclone cores. Bulk VVV, a TKE budget analysis, and anisotropy coefficient (ratio of horizontal to vertical velocity variances) profiles all indicate that LT is suppressed to levels closer to that of shear turbulence (ST) due to misaligned wind and wave fields. VVV approximately scales with the directional surface layer Langmuir number. Such a scaling provides guidance for the development of an upper-ocean boundary layer parameterization that explicitly depends on sea state

Preparing aquatic research for an extreme future: call for improved definitions and responsive, multidisciplinary approaches

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Aoki, L. R., Brisbin, M. M., Hounshell, A. G., Kincaid, D. W., Larson, E., Sansom, B. J., Shogren, A. J., Smith, R. S., & Sullivan-Stack, J. Preparing aquatic research for an extreme future: call for improved definitions and responsive, multidisciplinary approaches. Bioscience, 72(6), (2022): 508-520, https://doi.org/10.1093/biosci/biac020.Extreme events have increased in frequency globally, with a simultaneous surge in scientific interest about their ecological responses, particularly in sensitive freshwater, coastal, and marine ecosystems. We synthesized observational studies of extreme events in these aquatic ecosystems, finding that many studies do not use consistent definitions of extreme events. Furthermore, many studies do not capture ecological responses across the full spatial scale of the events. In contrast, sampling often extends across longer temporal scales than the event itself, highlighting the usefulness of long-term monitoring. Many ecological studies of extreme events measure biological responses but exclude chemical and physical responses, underscoring the need for integrative and multidisciplinary approaches. To advance extreme event research, we suggest prioritizing pre- and postevent data collection, including leveraging long-term monitoring; making intersite and cross-scale comparisons; adopting novel empirical and statistical approaches; and developing funding streams to support flexible and responsive data collection

Neutrophil histamine contributes to inflammation in mycoplasma pneumonia

Mycoplasmas cause chronic inflammation and are implicated in asthma. Mast cells defend against mycoplasma infection and worsen allergic inflammation, which is mediated partly by histamine. To address the hypothesis that mycoplasma provokes histamine release, we exposed mice to Mycoplasma pulmonis, comparing responses in wild-type and mast cell–deficient KitW-sh/KitW-sh (W-sh) mice. Low histamine levels in uninfected W-sh mice confirmed the conventional wisdom that mast cells are principal sources of airway and serum histamine. Although mycoplasma did not release histamine acutely in wild-type airways, levels rose up to 50-fold above baseline 1 week after infection in mice heavily burdened with neutrophils. Surprisingly, histamine levels also rose profoundly in infected W-sh lungs, increasing in parallel with neutrophils and declining with neutrophil depletion. Furthermore, neutrophils from infected airway were highly enriched in histamine compared with naive neutrophils. In vitro, mycoplasma directly stimulated histamine production by naive neutrophils and strongly upregulated mRNA encoding histidine decarboxylase, the rate-limiting enzyme in histamine synthesis. In vivo, treatment with antihistamines pyrilamine or cimetidine decreased lung weight and severity of pneumonia and tracheobronchitis in infected W-sh mice. These findings suggest that neutrophils, provoked by mycoplasma, greatly expand their capacity to synthesize histamine, thereby contributing to lung and airway inflammation

Improved Standardization of Type II-P Supernovae: Application to an Expanded Sample

In the epoch of precise and accurate cosmology, cross-confirmation using a variety of cosmographic methods is paramount to circumvent systematic uncertainties. Owing to progenitor histories and explosion physics differing from those of Type Ia SNe (SNe Ia), Type II-plateau supernovae (SNe II-P) are unlikely to be affected by evolution in the same way. Based on a new analysis of 17 SNe II-P, and on an improved methodology, we find that SNe II-P are good standardizable candles, almost comparable to SNe Ia. We derive a tight Hubble diagram with a dispersion of 10% in distance, using the simple correlation between luminosity and photospheric velocity introduced by Hamuy & Pinto 2002. We show that the descendent method of Nugent et al. 2006 can be further simplified and that the correction for dust extinction has low statistical impact. We find that our SN sample favors, on average, a very steep dust law with total to selective extinction R_V<2. Such an extinction law has been recently inferred for many SNe Ia. Our results indicate that a distance measurement can be obtained with a single spectrum of a SN II-P during the plateau phase combined with sparse photometric measurements.Comment: ApJ accepted version. Minor change

Constraints on the Progenitor System of the Type Ia Supernova SN 2011fe/PTF11kly

Type Ia supernovae (SNe) serve as a fundamental pillar of modern cosmology, owing to their large luminosity and a well-defined relationship between light-curve shape and peak brightness. The precision distance measurements enabled by SNe Ia first revealed the accelerating expansion of the universe, now widely believed (though hardly understood) to require the presence of a mysterious "dark" energy. General consensus holds that Type Ia SNe result from thermonuclear explosions of a white dwarf (WD) in a binary system; however, little is known of the precise nature of the companion star and the physical properties of the progenitor system. Here we make use of extensive historical imaging obtained at the location of SN 2011fe/PTF11kly, the closest SN Ia discovered in the digital imaging era, to constrain the visible-light luminosity of the progenitor to be 10-100 times fainter than previous limits on other SN Ia progenitors. This directly rules out luminous red giants and the vast majority of helium stars as the mass-donating companion to the exploding white dwarf. Any evolved red companion must have been born with mass less than 3.5 times the mass of the Sun. These observations favour a scenario where the exploding WD of SN 2011fe/PTF11kly, accreted matter either from another WD, or by Roche-lobe overflow from a subgiant or main-sequence companion star.Comment: 22 pages, 6 figures, submitte

Comparing ocean surface boundary vertical mixing schemes including langmuir turbulence

Six recent Langmuir turbulence parameterization schemes and five traditional schemes are implemented in a common single‐column modeling framework and consistently compared. These schemes are tested in scenarios versus matched large eddy simulations, across the globe with realistic forcing (JRA55‐do, WAVEWATCH‐III simulated waves) and initial conditions (Argo), and under realistic conditions as observed at ocean moorings. Traditional non‐Langmuir schemes systematically underpredict large eddy simulation vertical mixing under weak convective forcing, while Langmuir schemes vary in accuracy. Under global, realistic forcing Langmuir schemes produce 6% (−1% to 14% for 90% confidence) or 5.2 m (−0.2 m to 17.4 m for 90% confidence) deeper monthly mean mixed layer depths than their non‐Langmuir counterparts, with the greatest differences in extratropical regions, especially the Southern Ocean in austral summer. Discrepancies among Langmuir schemes are large (15% in mixed layer depth standard deviation over the mean): largest under wave‐driven turbulence with stabilizing buoyancy forcing, next largest under strongly wave‐driven conditions with weak buoyancy forcing, and agreeing during strong convective forcing. Non‐Langmuir schemes disagree with each other to a lesser extent, with a similar ordering. Langmuir discrepancies obscure a cross‐scheme estimate of the Langmuir effect magnitude under realistic forcing, highlighting limited understanding and numerical deficiencies. Maps of the regions and seasons where the greatest discrepancies occur are provided to guide further studies and observations

Drosophila histone locus bodies form by hierarchical recruitment of components

An assembly process involving sequential recruitment of components and hierarchical dependency drives formation of the nuclear structures known as histone locus bodies

Meta-analysis indicates that common variants at the DISC1 locus are not associated with schizophrenia

Several polymorphisms in the Disrupted-in-Schizophrenia-1 (DISC1) gene are reported to be associated with schizophrenia. However, to date, there has been little effort to evaluate the evidence for association systematically. We carried out an imputation-driven meta-analysis, the most comprehensive to date, using data collected from 10 candidate gene studies and three genome-wide association studies containing a total of 11 626 cases and 15 237 controls. We tested 1241 single-nucleotide polymorphisms in total, and estimated that our power to detect an effect from a variant with minor allele frequency >5% was 99% for an odds ratio of 1.5 and 51% for an odds ratio of 1.1. We find no evidence that common variants at the DISC1 locus are associated with schizophrenia

708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects:analysis for association with psychiatric disorder and cognitive traits

A balanced t(1;11) translocation that transects the Disrupted in schizophrenia 1 (DISC1) gene shows genome-wide significant linkage for schizophrenia and recurrent major depressive disorder (rMDD) in a single large Scottish family, but genome-wide and exome sequencing-based association studies have not supported a role for DISC1 in psychiatric illness. To explore DISC1 in more detail, we sequenced 528 kb of the DISC1 locus in 653 cases and 889 controls. We report 2718 validated single-nucleotide polymorphisms (SNPs) of which 2010 have a minor allele frequency of &lt;1%. Only 38% of these variants are reported in the 1000 Genomes Project European subset. This suggests that many DISC1 SNPs remain undiscovered and are essentially private. Rare coding variants identified exclusively in patients were found in likely functional protein domains. Significant region-wide association was observed between rs16856199 and rMDD (P=0.026, unadjusted P=6.3 × 10-5, OR=3.48). This was not replicated in additional recurrent major depression samples (replication P=0.11). Combined analysis of both the original and replication set supported the original association (P=0.0058, OR=1.46). Evidence for segregation of this variant with disease in families was limited to those of rMDD individuals referred from primary care. Burden analysis for coding and non-coding variants gave nominal associations with diagnosis and measures of mood and cognition. Together, these observations are likely to generalise to other candidate genes for major mental illness and may thus provide guidelines for the design of future studies. © 2014 Macmillan Publishers Limited