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A diagnosis of the plasma waves responsible for the explosive energy release of substorm onset
During geomagnetic substorms, stored magnetic and plasma thermal energies are explosively converted into plasma kinetic energy. This rapid reconfiguration of Earth’s nightside magnetosphere is manifest in the ionosphere as an auroral display that fills the sky. Progress in understanding of how substorms are initiated is hindered by a lack of quantitative analysis of the single consistent feature of onset; the rapid brightening and structuring of the most equatorward arc in the ionosphere. Here, we exploit state-of-the-art auroral measurements to construct an observational dispersion relation of waves during substorm onset. Further, we use kinetic theory of high-beta plasma to demonstrate that the shear Alfven wave dispersion relation bears remarkable similarity to the auroral dispersion relation. In contrast to prevailing theories of substorm initiation, we demonstrate that auroral beads seen during the majority of substorm onsets are likely the signature of kinetic Alfven waves driven unstable in the high-beta magnetotail
Gene Flow and Hybridization between Numerically Imbalanced Populations of Two Duck Species in the Falkland Islands
Interspecific hybridization is common in plants and animals, particularly in waterfowl (Anatidae). One factor shown to contribute to hybridization is restricted mate choice, which can occur when two species occur in sympatry but one is rare. The Hubbs principle, or “desperation hypothesis,” states that under such circumstances the rarer species is more likely to mate with heterospecifics. Here we report interspecific hybridization between two waterfowl species that coexist in broad sympatry and mixed flocks throughout southern South America. Speckled teal (Anas flavirostris) and yellow-billed pintails (Anas georgica) are abundant in continental South America, but in the Falkland Islands speckled teal outnumber yellow-billed pintails approximately ten to one. Using eight genetic loci (mtDNA and 7 nuclear introns) coupled with Bayesian assignment tests and relatedness analysis, we identified a speckled teal x yellow-billed pintail F1 hybrid female and her duckling sired by a male speckled teal. Although our sample in the Falkland Islands was small, we failed to identify unequivocal evidence of hybridization or introgression in a much larger sample from Argentina using a three-population “isolation with migration” coalescent analysis. While additional data are needed to determine if this event in the Falkland Islands was a rare singular occurrence, our results provide further support for the “desperation hypothesis,” which states that scarcity in one population and abundance of another will often lead to hybridization
Respiration and substrate transport rates as well as reactive oxygen species production distinguish mitochondria from brain and liver
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Mitochondrial damage-associated molecular patterns (DAMPs) in inflammatory bowel disease
Background
The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s
disease (CD) are chronic relapsing inflammatory disorders which have a rising
incidence and cause significant morbidity. There are currently several
treatment options with many more in the drug pipeline, but there are a lack of
accurate biomarkers for decisions on treatment choice, assessment of disease
activity and prognostication. There is a growing interest and desire for
personalised or ‘precision’ medicine in IBD where novel biomarkers may help
individualise IBD care in terms of diagnosis, choice of therapy, monitoring of
response and detection of relapse. One class of functionally active biomarkers
which have yet to be thoroughly investigated in IBD is damage-associated
molecular patterns (DAMPs) including mitochondrial DNA (mtDNA). It has
been recently shown that gut mitochondrial dysfunction can result in loss of
epithelial barrier function and the development of colitis. Mitochondrial DAMPs
have recently been described as elevated in several inflammatory diseases.
Hypothesis
The primary hypothesis of this thesis is that circulating levels of mtDNA is
elevated in IBD. Secondary hypotheses are: (a) levels of other mitochondrial
DAMPs are elevated in IBD, (b) circulating mtDNA can be used as a novel
biomarker in IBD and (c) mtDNA is released locally at sites of inflammation in
IBD.
Methods
Plasma and serum were collected prospectively from recruited IBD patients
and non-IBD controls. Faeces and colonic tissue were collected from a subset
of these patients. mtDNA in serum, plasma and faeces was measured using
qPCR (amplifying COXIII/ND2 genes). Mass spectrometry was used to detect
mitochondrial formylated peptides in the plasma of a subset of patients. IBD
tissue was assessed for (a) mitochondrial damage using transmission electron
microscopy (TEM) and (b) TLR9 expression, the target for mtDNA.
Results
97 patients with IBD (67 UC and 30 CD), and 40 non-IBD controls were
recruited. Plasma mtDNA levels were increased in UC and CD (both p<0.0001)
compared to non-IBD controls; with significant correlations with blood (CRP,
albumin, white cell count), clinical and endoscopic markers of severity; and
disease activity. In active UC, we detected significantly higher circulating
mitochondrial formylated peptides and faecal mtDNA levels (vs. non-IBD
controls [p<0.01 and <0.0001 respectively]) with demonstrable TEM evidence
of intestinal mucosal mitochondrial damage. In active IBD, TLR9+ lamina
propria inflammatory cells were significantly higher in UC/CD compared to
controls (both p<0.05).
Conclusions
Taken together, the findings suggest mtDNA is released during active
inflammation in inflammatory bowel disease and is a potential novel
mechanistic biomarker