Transcriptional Response to Acute Thermal Exposure in Juvenile Chinook Salmon Determined by RNAseq.

Thermal exposure is a serious and growing challenge facing fish species worldwide. Chinook salmon (Oncorhynchus tshawytscha) living in the southern portion of their native range are particularly likely to encounter warmer water due to a confluence of factors. River alterations have increased the likelihood that juveniles will be exposed to warm water temperatures during their freshwater life stage, which can negatively impact survival, growth, and development and pose a threat to dwindling salmon populations. To better understand how acute thermal exposure affects the biology of salmon, we performed a transcriptional analysis of gill tissue from Chinook salmon juveniles reared at 12° and exposed acutely to water temperatures ranging from ideal to potentially lethal (12° to 25°). Reverse-transcribed RNA libraries were sequenced on the Illumina HiSeq2000 platform and a de novo reference transcriptome was created. Differentially expressed transcripts were annotated using Blast2GO and relevant gene clusters were identified. In addition to a high degree of downregulation of a wide range of genes, we found upregulation of genes involved in protein folding/rescue, protein degradation, cell death, oxidative stress, metabolism, inflammation/immunity, transcription/translation, ion transport, cell cycle/growth, cell signaling, cellular trafficking, and structure/cytoskeleton. These results demonstrate the complex multi-modal cellular response to thermal stress in juvenile salmon

Barotrauma is a significant cause of bat fatalities at wind turbines

SummaryBird fatalities at some wind energy facilities around the world have been documented for decades, but the issue of bat fatalities at such facilities — primarily involving migratory species during autumn migration — has been raised relatively recently [1,2]. Given that echolocating bats detect moving objects better than stationary ones [3], their relatively high fatality rate is perplexing, and numerous explanations have been proposed [1]. The decompression hypothesis proposes that bats are killed by barotrauma caused by rapid air-pressure reduction near moving turbine blades [1,4,5]. Barotrauma involves tissue damage to air-containing structures caused by rapid or excessive pressure change; pulmonary barotrauma is lung damage due to expansion of air in the lungs that is not accommodated by exhalation. We report here the first evidence that barotrauma is the cause of death in a high proportion of bats found at wind energy facilities. We found that 90% of bat fatalities involved internal haemorrhaging consistent with barotrauma, and that direct contact with turbine blades only accounted for about half of the fatalities. Air pressure change at turbine blades is an undetectable hazard and helps explain high bat fatality rates. We suggest that one reason why there are fewer bird than bat fatalities is that the unique respiratory anatomy of birds is less susceptible to barotrauma than that of mammals

Failure of catecholamines to shift T-cell cytokine responses toward a Th2 profile in patients with rheumatoid arthritis

To further understand the role of neuro-immunological interactions in the pathogenesis of rheumatoid arthritis (RA), we studied the influence of sympathetic neurotransmitters on cytokine production of T cells in patients with RA. T cells were isolated from peripheral blood of RA patients or healthy donors (HDs), and stimulated via CD3 and CD28. Co-incubation was carried out with epinephrine or norepinephrine in concentrations ranging from 10(-5 )M to 10(-11 )M. Interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-4, and IL-10 were determined in the culture supernatant with enzyme-linked immunosorbent assay. In addition, IFN-γ and IL-10 were evaluated with intracellular cytokine staining. Furthermore, basal and agonist-induced cAMP levels and catecholamine-induced apoptosis of T cells were measured. Catecholamines inhibited the synthesis of IFN-γ, TNF-α, and IL-10 at a concentration of 10(-5 )M. In addition, IFN-γ release was suppressed by 10(-7 )M epinephrine. Lower catecholamine concentrations exerted no significant effect. A reduced IL-4 production upon co-incubation with 10(-5 )M epinephrine was observed in RA patients only. The inhibitory effect of catecholamines on IFN-γ production was lower in RA patients as compared with HDs. In RA patients, a catecholamine-induced shift toward a Th2 (type 2) polarised cytokine profile was abrogated. Evaluation of intracellular cytokines revealed that CD8-positive T cells were accountable for the impaired catecholaminergic control of IFN-γ production. The highly significant negative correlation between age and catecholamine effects in HDs was not found in RA patients. Basal and stimulated cAMP levels in T-cell subsets and catecholamine-induced apoptosis did not differ between RA patients and HDs. RA patients demonstrate an impaired inhibitory effect of catecholamines on IFN-γ production together with a failure to induce a shift of T-cell cytokine responses toward a Th2-like profile. Such an unfavorable situation is a perpetuating factor for inflammation

Neutrino Decays over Cosmological Distances and the Implications for Neutrino Telescopes

We discuss decays of ultra-relativistic neutrinos over cosmological distances by solving the decay equation in terms of its redshift dependence. We demonstrate that there are significant conceptual differences compared to more simplified treatments of neutrino decay. For instance, the maximum distance the neutrinos have traveled is limited by the Hubble length, which means that the common belief that longer neutrino lifetimes can be probed by longer distances does not apply. As a consequence, the neutrino lifetime limit from supernova 1987A cannot be exceeded by high-energy astrophysical neutrinos. We discuss the implications for neutrino spectra and flavor ratios from gamma-ray bursts as one example of extragalactic sources, using up-to-date neutrino flux predictions. If the observation of SN 1987A implies that \nu_1 is stable and the other mass eigenstates decay with rates much smaller than their current bounds, the muon track rate can be substantially suppressed compared to the cascade rate in the region IceCube is most sensitive to. In this scenario, no gamma-ray burst neutrinos may be found using muon tracks even with the full scale experiment, whereas reliable information on high-energy astrophysical sources can only be obtained from cascade measurements. As another consequence, the recently observed two cascade event candidates at PeV energies will not be accompanied by corresponding muon tracks.Comment: 20 pages, 6 figures, 1 table. Matches published versio

The metric and strong coupling limit of the M5-brane

We find the analogue of the Boillat metric of Born-Infeld theory for the M5-brane. We show that it provides the propagation cone of {\sl all} 5-brane degrees. In an arbitrary background field, this cone never lies outside the Einstein cone. An energy momentum tensor for the three-form is defined and shown to satisfy the Dominant Energy Condition. The theory is shown to be well defined for all values of the magnetic field but there is a limiting electric field strength. We consider the strong coupling limit of the M5-brane and show that the corresponding theory is conformally invariant and admits infinitely many conservation laws. On reduction to the Born-Infeld case this agrees with the work of Bia{\l}nicki-Birula.Comment: Version to be published in special issue of JMP, July 2001. Sections 8 and 9 have been remove

G-Structures, Fluxes and Calibrations in M-Theory

We study the most general supersymmetric warped M-theory backgrounds with non-trivial G-flux of the type R^{1,2} x M_8 and AdS_3 x M_8. We give a set of necessary and sufficient conditions for preservation of supersymmetry which are phrased in terms of G-structures and their intrinsic torsion. These equations may be interpreted as calibration conditions for a static ``dyonic'' M-brane, that is, an M5-brane with self-dual three-form turned on. When the electric flux is turned off we obtain the supersymmetry conditions and non-linear PDEs describing M5-branes wrapped on associative and special Lagrangian three-cycles in manifolds with G_2 and SU(3) structures, respectively. As an illustration of our formalism, we recover the 1/2-BPS dyonic M-brane, and also construct some new examples.Comment: 40 pages; v2: one reference added, typos correcte

Is Cortisol Excretion Independent of Menstrual Cycle Day? A Longitudinal Evaluation of First Morning Urinary Specimens

Background Cortisol is frequently used as a marker of physiologic stress levels. Using cortisol for that purpose, however, requires a thorough understanding of its normal longitudinal variability. The current understanding of longitudinal variability of basal cortisol secretion in women is very limited. It is often assumed, for example, that basal cortisol profiles do not vary across the menstrual cycle. This is a critical assumption: if cortisol were to follow a time dependent pattern during the menstrual cycle, then ignoring this cyclic variation could lead to erroneous imputation of physiologic stress. Yet, the assumption that basal cortisol levels are stable across the menstrual cycle rests on partial and contradictory evidence. Here we conduct a thorough test of that assumption using data collected for up to a year from 25 women living in rural Guatemala. Methodology We apply a linear mixed model to describe longitudinal first morning urinary cortisol profiles, accounting for differences in both mean and standard deviation of cortisol among women. To that aim we evaluate the fit of two alternative models. The first model assumes that cortisol does not vary with menstrual cycle day. The second assumes that cortisol mean varies across the menstrual cycle. Menstrual cycles are aligned on ovulation day (day 0). Follicular days are assigned negative numbers and luteal days positive numbers. When we compared Models 1 and 2 restricting our analysis to days between −14 (follicular) and day 14 (luteal) then day of the menstrual cycle did not emerge as a predictor of urinary cortisol levels (p-value >0.05). Yet, when we extended our analyses beyond that central 28-day-period then day of the menstrual cycle become a statistically significant predictor of cortisol levels. Significance The observed trend suggests that studies including cycling women should account for day dependent variation in cortisol in cycles with long follicular and luteal phases

Supersymmetric string model with 30 kappa--symmetries in an extended D=11 superspace and 30/ 32 BPS states

A supersymmetric string model in the D=11 superspace maximally extended by antisymmetric tensor bosonic coordinates, $\Sigma^{(528|32)}$, is proposed. It possesses 30 $\kappa$-symmetries and 32 target space supersymmetries. The usual preserved supersymmetry-$\kappa$-symmetry correspondence suggests that it describes the excitations of a BPS state preserving all but two supersymmetries. The model can also be formulated in any $\Sigma^{({n(n+1)\over 2}|n)}$ superspace, n=32 corresponding to D=11. It may also be treated as a `higher--spin generalization' of the usual Green--Schwarz superstring. Although the global symmetry of the model is a generalization of the super--Poincar\'e group, ${\Sigma}^{({n(n+1)\over 2}|n)}\times\supset Sp(n)$, it may be formulated in terms of constrained OSp(2n|1) orthosymplectic supertwistors. We work out this supertwistor realization and its Hamiltonian dynamics. We also give the supersymmetric p-brane generalization of the model. In particular, the $\Sigma^{(528|32)}$ supersymmetric membrane model describes excitations of a 30/32 BPS state, as the $\Sigma^{(528|32)}$ supersymmetric string does, while the supersymmetric 3-brane and 5-brane correspond, respectively, to 28/32 and 24/32 BPS states.Comment: 23 pages, RevTex4. V2: minor corrections in title and terminology, some references and comments adde

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches