Effects of aircraft noise on human activities

The effects of aircrft noise on human activities was investigated by developing a battery of tasks (1) representative of a range of human activities and (2) sensitive to the disruptive effects of noise. The noise used were recordings of jet aircraft and helicopter sounds at three lvels of loudness--60, 70, and 80 dB(A). Experiment 1 investigated 12 different cognitive tasks, along with two intelligibility tasks included to validate that the noises were being effective. Interference with intelligibility was essentially the same as found in the research literature, but only inconsistent effects were found on either accuracy or latency of performance on the cognitive tasks. When the tasks were grouped into four categories (Intelligibility, Matching, Verbal, and Arithmetic), reliable differences in rated annoyingness of the noises were related to the task category and to the type of noise (jet or helicopter)

Quantitation of mitochondrial dynamics by photolabeling of individual organelles shows that mitochondrial fusion is blocked during the Bax activation phase of apoptosis

A dynamic balance of organelle fusion and fission regulates mitochondrial morphology. During apoptosis this balance is altered, leading to an extensive fragmentation of the mitochondria. Here, we describe a novel assay of mitochondrial dynamics based on confocal imaging of cells expressing a mitochondrial matrix–targeted photoactivable green fluorescent protein that enables detection and quantification of organelle fusion in living cells. Using this assay, we visualize and quantitate mitochondrial fusion rates in healthy and apoptotic cells. During apoptosis, mitochondrial fusion is blocked independently of caspase activation. The block in mitochondrial fusion occurs within the same time range as Bax coalescence on the mitochondria and outer mitochondrial membrane permeabilization, and it may be a consequence of Bax/Bak activation during apoptosis

Optical frequency measurement of the 1S-3S two-photon transition in hydrogen

This article reports the first optical frequency measurement of the $1\mathrm{S}-3\mathrm{S}$ transition in hydrogen. The excitation of this transition occurs at a wavelength of 205 nm which is obtained with two frequency doubling stages of a titanium sapphire laser at 820 nm. Its frequency is measured with an optical frequency comb. The second-order Doppler effect is evaluated from the observation of the motional Stark effect due to a transverse magnetic field perpendicular to the atomic beam. The measured value of the $1\mathrm{S}_{1/2}(F=1)-3\mathrm{S}_{1/2}(F=1)$ frequency splitting is $2 922 742 936.729 (13) \mathrm{MHz}$ with a relative uncertainty of $4.5\times10^{-12}$. After the measurement of the $1\mathrm{S}-2\mathrm{S}$ frequency, this result is the most precise of the optical frequencies in hydrogen

SUMOylation of the mitochondrial fission protein Drpl occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle

Dynamin‐related protein (Drp) 1 is a key regulator of mitochondrial fission and is composed of GTP‐binding, Middle, insert B, and C‐terminal GTPase effector (GED) domains. Drpl associates with mitochondrial fission sites and promotes membrane constriction through its intrinsic GTPase activity. The mechanisms that regulate Drpl activity remain poorly understood but are likely to involve reversible post‐translational modifications, such as conjugation of small ubiquitin‐like modifier (SUMO) proteins. Through a detailed analysis, we find that Drpl interacts with the SUMO‐conjugating enzyme Ubc9 via multiple regions and demonstrate that Drpl is a direct target of SUMO modification by all three SUMO isoforms. While Drpl does not harbor consensus SUMOylation sequences, our analysis identified2 clusters of lysine residues within the B domain that serve as noncanonical conjugation sites. Although initial analysis indicates that mitochondrial recruitment of ectopically expressed Drpl in response to staurosporine is unaffected by loss of SUMOylation, we find that Drpl SUMOylation is enhanced in the context of the K38A mutation. This dominant‐negative mutant, which is deficient in GTP binding and hydrolysis, does not associate with mitochondria and prevents normal mitochondrial fission. This finding suggests that SUMOylation of Drpl is linked to its activity cycle and is influenced by Drpl localization.—Figueroa‐Romero, C., Iniguez‐Lluhi, J. A., Stadler, J., Chang, C.‐R., Arnoult, D., Keller, P. J., Hong, Y., Blackstone, C., Feldman, E. L. SUMOylation of the mitochondrial fission protein Drpl occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle. FASEB J. 23, 3917–3927 (2009). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154272/1/fsb2fj09136630.pd

Block of death-receptor apoptosis protects mouse cytomegalovirus from macrophages and is a determinant of virulence in immunodeficient hosts.

The inhibition of death-receptor apoptosis is a conserved viral function. The murine cytomegalovirus (MCMV) gene M36 is a sequence and functional homologue of the human cytomegalovirus gene UL36, and it encodes an inhibitor of apoptosis that binds to caspase-8, blocks downstream signaling and thus contributes to viral fitness in macrophages and in vivo. Here we show a direct link between the inability of mutants lacking the M36 gene (ΔM36) to inhibit apoptosis, poor viral growth in macrophage cell cultures and viral in vivo fitness and virulence. ΔM36 grew poorly in RAG1 knockout mice and in RAG/IL-2-receptor common gamma chain double knockout mice (RAGγC(-/-)), but the depletion of macrophages in either mouse strain rescued the growth of ΔM36 to almost wild-type levels. This was consistent with the observation that activated macrophages were sufficient to impair ΔM36 growth in vitro. Namely, spiking fibroblast cell cultures with activated macrophages had a suppressive effect on ΔM36 growth, which could be reverted by z-VAD-fmk, a chemical apoptosis inhibitor. TNFα from activated macrophages synergized with IFNγ in target cells to inhibit ΔM36 growth. Hence, our data show that poor ΔM36 growth in macrophages does not reflect a defect in tropism, but rather a defect in the suppression of antiviral mediators secreted by macrophages. To the best of our knowledge, this shows for the first time an immune evasion mechanism that protects MCMV selectively from the antiviral activity of macrophages, and thus critically contributes to viral pathogenicity in the immunocompromised host devoid of the adaptive immune system

Electrical spin injection into p-doped quantum dots through a tunnel barrier

We have demonstrated by electroluminescence the injection of spin polarized electrons through Co/Al2O3/GaAs tunnel barrier into p-doped InAs/GaAs quantum dots embedded in a PIN GaAs light emitting diode. The spin relaxation processes in the p-doped quantum dots are characterized independently by optical measurements (time and polarization resolved photoluminescence). The measured electroluminescence circular polarization is about 15 % at low temperature in a 2T magnetic field, leading to an estimation of the electrical spin injection yield of 35%. Moreover, this electroluminescence circular polarization is stable up to 70 K.Comment: 6 pages, 4 figure

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

Metabolic myopathy presenting with polyarteritis nodosa: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, we describe for the first time a patient in whom an unusual metabolic myopathy was identified after failure to respond to curative therapy for a systemic vasculitis, polyarteritis nodosa. We hope this report will heighten awareness of common metabolic myopathies that may present later in life. It also speculates on the potential relationship between metabolic myopathy and systemic vasculitis.</p> <p>Case presentation</p> <p>A 78-year-old African-American woman with a two-year history of progressive fatigue and exercise intolerance presented to our facility with new skin lesions and profound muscle weakness. Skin and muscle biopsies demonstrated a medium-sized artery vasculitis consistent with polyarteritis nodosa. Biochemical studies of the muscle revealed diminished cytochrome C oxidase activity (0.78 μmol/minute/g tissue; normal range 1.03 to 3.83 μmol/minute/g tissue), elevated acid maltase activity (23.39 μmol/minute/g tissue; normal range 1.74 to 9.98 μmol/minute/g tissue) and elevated neutral maltase activity (35.89 μmol/minute/g tissue; normal range 4.35 to 16.03 μmol/minute/g tissue). Treatment for polyarteritis nodosa with prednisone and cyclophosphamide resulted in minimal symptomatic improvement. Additional management with a diet low in complex carbohydrates and ubiquinone, creatine, carnitine, folic acid, α-lipoic acid and ribose resulted in dramatic clinical improvement.</p> <p>Conclusions</p> <p>Our patient's initial symptoms of fatigue, exercise intolerance and progressive weakness were likely related to her complex metabolic myopathy involving both the mitochondrial respiratory chain and glycogen storage pathways. Management of our patient required treatment of both the polyarteritis nodosa as well as metabolic myopathy. Metabolic myopathies are common and should be considered in any patient with exercise intolerance. Metabolic myopathies may complicate the management of various disease states.</p

Toxoplasma Effector MAF1 Mediates Recruitment of Host Mitochondria and Impacts the Host Response

Recent information has revealed the functional diversity and importance of mitochondria in many cellular processes including orchestrating the innate immune response. Intriguingly, several infectious agents, such as Toxoplasma, Legionella, and Chlamydia, have been reported to grow within vacuoles surrounded by host mitochondria. Although many hypotheses have been proposed for the existence of host mitochondrial association (HMA), the causes and biological consequences of HMA have remained unanswered. Here we show that HMA is present in type I and III strains of Toxoplasma but missing in type II strains, both in vitro and in vivo. Analysis of F1 progeny from a type II×III cross revealed that HMA is a Mendelian trait that we could map. We use bioinformatics to select potential candidates and experimentally identify the polymorphic parasite protein involved, mitochondrial association factor 1 (MAF1). We show that introducing the type I (HMA+) MAF1 allele into type II (HMA-) parasites results in conversion to HMA+ and deletion of MAF1 in type I parasites results in a loss of HMA. We observe that the loss and gain of HMA are associated with alterations in the transcription of host cell immune genes and the in vivo cytokine response during murine infection. Lastly, we use exogenous expression of MAF1 to show that it binds host mitochondria and thus MAF1 is the parasite protein directly responsible for HMA. Our findings suggest that association with host mitochondria may represent a novel means by which Toxoplasma tachyzoites manipulate the host. The existence of naturally occurring HMA+ and HMA- strains of Toxoplasma, Legionella, and Chlamydia indicates the existence of evolutionary niches where HMA is either advantageous or disadvantageous, likely reflecting tradeoffs in metabolism, immune regulation, and other functions of mitochondria. © 2014 Pernas et al