We report dissipative magnon-photon coupling caused by the cavity Lenz effect, where the magnons in a magnet induce a rf current in the cavity, leading to a cavity backaction that impedes the ...magnetization dynamics. This effect is revealed in our experiment as level attraction with a coalescence of hybridized magnon-photon modes, which is distinctly different from level repulsion with mode anticrossing caused by coherent magnon-photon coupling. We develop a method to control the interpolation of coherent and dissipative magnon-photon coupling, and observe a matching condition where the two effects cancel. Our work sheds light on the so-far hidden side of magnon-photon coupling, opening a new avenue for controlling and utilizing light-matter interactions.
Since allozymes were first used to assess genetic diversity in the 1960s and 1970s, biologists have attempted to characterize gene pools and conserve the diversity observed in domestic crops, ...livestock, zoos and (more recently) natural populations. Recently, some authors have claimed that the importance of genetic diversity in conservation biology has been greatly overstated. Here, we argue that a voluminous literature indicates otherwise. We address four main points made by detractors of genetic diversity's role in conservation by using published literature to firmly establish that genetic diversity is intimately tied to evolutionary fitness, and that the associated demographic consequences are of paramount importance to many conservation efforts. We think that responsible management in the Anthropocene should, whenever possible, include the conservation of ecosystems, communities, populations and individuals, and their underlying genetic diversity.
We use electrical detection, in combination with microwave transmission, to investigate both resonant and nonresonant magnon-photon coupling at room temperature. Spin pumping in a dynamically coupled ...magnon-photon system is found to be distinctly different from previous experiments. Characteristic coupling features such as modes anticrossing, linewidth evolution, peculiar line shape, and resonance broadening are systematically measured and consistently analyzed by a theoretical model set on the foundation of classical electrodynamic coupling. Our experimental and theoretical approach paves the way for pursuing microwave coherent manipulation of pure spin current via the combination of spin pumping and magnon-photon coupling.
Mitochondrial dysfunction may be an important, if not essential, component of human glaucoma. Using transcriptomics followed by molecular and neurobiological techniques, we have recently demonstrated ...that mitochondrial dysfunction within retinal ganglion cells is an early feature in the DBA/2J mouse model of inherited glaucoma. Guided by these findings, we discovered that the retinal level of nicotinamide adenine dinucleotide (NAD, a key molecule for mitochondrial health) declines in an age-dependent manner. We hypothesized that this decline in NAD renders retinal ganglion cells susceptible to damage during periods of elevated intraocular pressure. To replete NAD levels in this glaucoma, we administered nicotinamide (the amide of vitamin B3). At the lowest dose tested, nicotinamide robustly protected from glaucoma (~70% of eyes had no detectable glaucomatous neurodegeneration). At this dose, nicotinamide had no influence on intraocular pressure and so its effect was neuroprotective. At the highest dose tested, 93% of eyes had no detectable glaucoma. This represents a ~10-fold decrease in the risk of developing glaucoma. At this dose, intraocular pressure still became elevated but there was a reduction in the degree of elevation showing an additional benefit. Thus, nicotinamide is unexpectedly potent at preventing this glaucoma and is an attractive option for glaucoma therapeutics. Our findings demonstrate the promise for both preventing and treating glaucoma by interventions that bolster metabolism during increasing age and during periods of elevated intraocular pressure. Nicotinamide prevents age-related declines in NAD (a decline that occurs in different genetic contexts and species). NAD precursors are reported to protect from a variety of neurodegenerative conditions. Thus, nicotinamide may provide a much needed neuroprotective treatment against human glaucoma. This manuscript summarizes human data implicating mitochondria in glaucoma, and argues for studies to further assess the safety and efficacy of nicotinamide in human glaucoma care.
The risk of glaucoma increases significantly with age and exposure to elevated intraocular pressure, two factors linked with neuroinflammation. The complement cascade is a complex immune process with ...many bioactive end-products, including mediators of inflammation. Complement cascade activation has been shown in glaucoma patients and models of glaucoma. However, the function of complement-mediated inflammation in glaucoma is largely untested. Here, the complement peptide C3a receptor 1 was genetically disrupted in DBA/2J mice, an ocular hypertensive model of glaucoma, to test its contribution to neurodegeneration.
A null allele of C3ar1 was backcrossed into DBA/2J mice. Development of iris disease, ocular hypertension, optic nerve degeneration, retinal ganglion cell activity, loss of RGCs, and myeloid cell infiltration in C3ar1-deficient and sufficient DBA/2J mice were compared across multiple ages. RNA sequencing was performed on microglia from primary culture to determine global effects of C3ar1 on microglia gene expression.
Deficiency in C3ar1 lowered the risk of degeneration in ocular hypertensive mice without affecting intraocular pressure elevation at 10.5 months of age. Differences were found in the percentage of mice affected, but not in individual characteristics of disease progression. The protective effect of C3ar1 deficiency was then overcome by additional aging and ocular hypertensive injury. Microglia and other myeloid-derived cells were the primary cells identified that express C3ar1. In the absence of C3ar1, microglial expression of genes associated with neuroinflammation and other immune functions were differentially expressed compared to WT. A network analysis of these data suggested that the IL10 signaling pathway is a major interaction partner of C3AR1 signaling in microglia.
C3AR1 was identified as a damaging neuroinflammatory factor. These data help suggest complement activation causes glaucomatous neurodegeneration through multiple mechanisms, including inflammation. Microglia and infiltrating myeloid cells expressed high levels of C3ar1 and are the primary candidates to mediate its effects. C3AR1 appeared to be a major regulator of microglia reactivity and neuroinflammatory function due to its interaction with IL10 signaling and other immune related pathways. Targeting myeloid-derived cells and C3AR1 signaling with therapies is expected to add to or improve neuroprotective therapeutic strategies.
Introduced species often colonize regions that have vastly different ecological and environmental conditions than those found in their native range. As such, species introductions can provide a ...deeper understanding into the process of adaptive evolution. In the 1880s, steelhead trout (Oncorhynchus mykiss) from California were introduced into Lake Michigan (Laurentian Great Lakes, North America) where they established naturally reproducing populations. In their native range, steelhead hatch in rivers, migrate to the ocean and return to freshwater to spawn. Steelhead in Lake Michigan continue to swim up rivers to spawn, but now treat the freshwater environment of the Great Lakes as a surrogate ocean. To examine the effects of this introduction, we sequenced the genomes of 264 fish. By comparing steelhead from Lake Michigan to steelhead from their ancestral range, we determined that the introduction led to consistent reductions in genetic diversity across all 29 chromosomes. Despite this reduction in genetic diversity, three chromosomal regions were associated with rapid genetic adaptation to the novel environment. The first region contained functional changes to ceramide kinase, which likely altered metabolic and wound‐healing rates in Lake Michigan steelhead. The second and third regions encoded carbonic anhydrases and a solute carrier protein, both of which are critical for osmoregulation, and demonstrate how steelhead physiologically adapted to freshwater. Furthermore, the contemporary release of diverse hatchery strains into the lake increased genetic diversity but reduced the signature of genetic adaptation. This study illustrates that species can rapidly adapt to novel environments despite genome‐wide reductions in genetic diversity.
see also the Perspective by Seeb et al.
Glaucoma is the leading cause of irreversible vision loss. Ocular hypertension is a major risk factor for glaucoma and recent work has demonstrated critical early neuroinflammatory insults occur in ...the optic nerve head following ocular hypertension. Microglia and infiltrating monocytes are likely candidates to drive these neuroinflammatory insults. However, the exact molecular identity / transcriptomic profile of microglia following ocular hypertensive insults is unknown. To elucidate the molecular identity of microglia after long-term exposure to ocular hypertension, we used a mouse model of glaucoma (DBA/2 J). We performed RNA-sequencing of microglia mRNA from the optic nerve head at a time point following ocular hypertensive insults, but preceding detectable neurodegeneration (with microglia identified as being CD45
/CD11b
/CD11c
). Furthermore, RNA-sequencing was performed on optic nerve head microglia from mice treated with radiation therapy, a potent therapy preventing neuroinflammatory insults. Transcriptomic profiling of optic nerve head microglia mRNA identifies metabolic priming with marked changes in mitochondrial gene expression, and changes to phagocytosis, inflammatory, and sensome pathways. The data predict that many functions of microglia that help maintain tissue homeostasis are affected. Comparative analysis of these data with data from previously published whole optic nerve head tissue or monocyte-only samples from DBA/2 J mice demonstrate that many of the neuroinflammatory signatures in these data sets arise from infiltrating monocytes and not reactive microglia. Finally, our data demonstrate that prophylactic radiation therapy of DBA/2 J mice potently abolishes these microglia metabolic transcriptomic changes at the same time points. Together, our data provide a unique resource for the community to help drive further hypothesis generation and testing in glaucoma.
Hospitalizations in pulmonary arterial hypertension (PAH) are common and are often for cardiac conditions. Using the National (Nationwide) Inpatient Sample (NIS), we examined characteristics and ...mortality of primary cardiac hospitalizations in PAH from 2001 to 2014.
Adult hospitalizations with any diagnosis code for PAH were identified. Primary cardiac disease was defined as a primary discharge diagnosis of congestive heart failure (CHF), pulmonary heart disease, coronary atherosclerosis, acute myocardial infarction, dysrhythmia, conduction disorder, cardiomyopathy or carditis, heart valve disorder, or cardiac arrest. Temporal trends, characteristics, and in-hospital mortality were analyzed.
From 2001 to 2014, there were 207,095 hospitalizations in PAH, of which 100,509 (48.5%) carried a primary cardiac diagnosis. Most primary cardiac hospitalizations in PAH were for CHF, and pneumonia was the most common primary non-cardiac diagnosis. Over the study period, primary cardiac hospitalizations in PAH fell from 52.9% to 41.4% (p < 0.001). CHF was the most frequent primary cardiac diagnosis associated with death, with sepsis representing the most common primary non-cardiac disease (1,226; 25.0%). Overall, the mortality in primary cardiac hospitalizations in PAH was 5.3% (vs. in primary non-cardiac, 6.9%, p < 0.001). On multivariable analysis, a primary cardiac discharge diagnosis remained associated with a decreased risk of death (odds ratio 0.85, p = 0.010).
Primary cardiac hospitalizations in PAH are common and are associated with decreased mortality compared to admissions for primary non-cardiac diagnoses.
•In a large U.S. database, 48.5% of PAH hospitalizations were for cardiac diagnoses.•From 2001 to 2014, there was a decrease in admissions in PAH for cardiac diagnoses.•The mortality in cardiac hospitalizations in PAH was 5.3% (vs. 6.8% in non-cardiac).•PAH admissions for cardiac diagnoses were associated with decreased risk of death.
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