The Axial Double Probe (ADP) instrument measures the DC to ∼100 kHz electric field along the spin axis of the Magnetospheric Multiscale (MMS) spacecraft (Burch et al., Space Sci. Rev.,
2014, this ...issue
), completing the vector electric field when combined with the spin plane double probes (SDP) (Torbert et al., Space Sci. Rev.,
2014, this issue
, Lindqvist et al., Space Sci. Rev.,
2014, this issue
). Two cylindrical sensors are separated by over 30 m tip-to-tip, the longest baseline on an axial DC electric field ever attempted in space. The ADP on each of the spacecraft consists of two identical, 12.67 m graphite coilable booms with second, smaller 2.25 m booms mounted on their ends. A significant effort was carried out to assure that the potential field of the MMS spacecraft acts equally on the two sensors and that photo- and secondary electron currents do not vary over the spacecraft spin. The ADP on MMS is expected to measure DC electric field with a precision of ∼1 mV/m, a resolution of ∼25 μV/m, and a range of ∼±1 V/m in most of the plasma environments MMS will encounter. The Digital Signal Processing (DSP) units on the MMS spacecraft are designed to perform analog conditioning, analog-to-digital (A/D) conversion, and digital processing on the ADP, SDP, and search coil magnetometer (SCM) (Le Contel et al., Space Sci. Rev.,
2014, this issue
) signals. The DSP units include digital filters, spectral processing, a high-speed burst memory, a solitary structure detector, and data compression. The DSP uses precision analog processing with, in most cases, >100 dB in dynamic range, better that −80 dB common mode rejection in electric field (
E
) signal processing, and better that −80 dB cross talk between the
E
and SCM (
B
) signals. The A/D conversion is at 16 bits with ∼1/4 LSB accuracy and ∼1 LSB noise. The digital signal processing is powerful and highly flexible allowing for maximum scientific return under a limited telemetry volume. The ADP and DSP are described in this article.
The Spin-plane double probe instrument (SDP) is part of the FIELDS instrument suite of the Magnetospheric Multiscale mission (MMS). Together with the Axial double probe instrument (ADP) and the ...Electron Drift Instrument (EDI), SDP will measure the 3-D electric field with an accuracy of 0.5 mV/m over the frequency range from DC to 100 kHz. SDP consists of 4 biased spherical probes extended on 60 m long wire booms 90
∘
apart in the spin plane, giving a 120 m baseline for each of the two spin-plane electric field components. The mechanical and electrical design of SDP is described, together with results from ground tests and calibration of the instrument.
Insulin resistance (IR) is a complex trait with multiple genetic and environmental components. Confounded by large differences between the sexes, environment, and disease pathology, the genetic basis ...of IR has been difficult to dissect. Here we examine IR and related traits in a diverse population of more than 100 unique male and female inbred mouse strains after feeding a diet rich in fat and refined carbohydrates. Our results show dramatic variation in IR among strains of mice and widespread differences between sexes that are dependent on genotype. We uncover more than 15 genome-wide significant loci and validate a gene, Agpat5, associated with IR. We also integrate plasma metabolite levels and global gene expression from liver and adipose tissue to identify metabolite quantitative trait loci (mQTL) and expression QTL (eQTL), respectively. Our results provide a resource for analysis of interactions between diet, sex, and genetic background in IR.
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•Dramatic variation in insulin resistance among inbred strains of mice•Widespread sex differences in insulin resistance that is dependent on genotype•Identification of 15 genetic loci associated with HOMA-IR and related traits•Identification and validation of Agpat5, a gene associated with insulin resistance
Using a systems genetics analysis across more than 100 mouse strains to tackle the complex genetic basis of insulin resistance (IR), Parks et al. reveal interactions between diet, sex, and genetic background and identify multiple IR-associated genetic loci, further validating Agpat5 as a genetic factor contributing to IR.
Obesity is a highly heritable disease driven by complex interactions between genetic and environmental factors. Human genome-wide association studies (GWAS) have identified a number of loci ...contributing to obesity; however, a major limitation of these studies is the inability to assess environmental interactions common to obesity. Using a systems genetics approach, we measured obesity traits, global gene expression, and gut microbiota composition in response to a high-fat/high-sucrose (HF/HS) diet of more than 100 inbred strains of mice. Here we show that HF/HS feeding promotes robust, strain-specific changes in obesity that are not accounted for by food intake and provide evidence for a genetically determined set point for obesity. GWAS analysis identified 11 genome-wide significant loci associated with obesity traits, several of which overlap with loci identified in human studies. We also show strong relationships between genotype and gut microbiota plasticity during HF/HS feeding and identify gut microbial phylotypes associated with obesity.
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► Detailed analysis of diet-induced obesity in more than 100 inbred mouse strains ► Identification of 11 genetic loci associated with obesity and dietary responsiveness ► Significant overlap between mouse loci with human GWAS loci for obesity ► Strain-specific shifts in gut microbiota composition in response to dietary intervention
The Search-Coil Magnetometer for MMS Le Contel, O.; Leroy, P.; Roux, A. ...
Space Science Reviews,
03/2016, Letnik:
199, Številka:
1-4
Journal Article, Book Review
Recenzirano
Odprti dostop
The tri-axial search-coil magnetometer (SCM) belongs to the FIELDS instrumentation suite on the Magnetospheric Multiscale (MMS) mission (Torbert et al. in Space Sci. Rev. (
2014
), this issue). It ...provides the three magnetic components of the waves from 1 Hz to 6 kHz in particular in the key regions of the Earth’s magnetosphere namely the subsolar region and the magnetotail. Magnetospheric plasmas being collisionless, such a measurement is crucial as the electromagnetic waves are thought to provide a way to ensure the conversion from magnetic to thermal and kinetic energies allowing local or global reconfigurations of the Earth’s magnetic field. The analog waveforms provided by the SCM are digitized and processed inside the digital signal processor (DSP), within the Central Electronics Box (CEB), together with the electric field data provided by the spin-plane double probe (SDP) and the axial double probe (ADP). On-board calibration signal provided by DSP allows the verification of the SCM transfer function once per orbit. Magnetic waveforms and on-board spectra computed by DSP are available at different time resolution depending on the selected mode. The SCM design is described in details as well as the different steps of the ground and in-flight calibrations.
Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the ...observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content. Using genome-wide association, we identified Tnni3k as one gene that influences variation in this composition and demonstrated that Tnni3k knockout resulted in elevated MNDCM content and increased cardiomyocyte proliferation after injury. Reciprocally, overexpression of Tnni3k in zebrafish promoted cardiomyocyte polyploidization and compromised heart regeneration. Our results corroborate the relevance of MNDCMs in heart regeneration. Moreover, they imply that intrinsic heart regeneration is not limited nor uniform in all individuals, but rather is a variable trait influenced by multiple genes.
BACKGROUND—Although metabolic reprogramming is critical in the pathogenesis of heart failure, studies to date have focused principally on fatty acid and glucose metabolism. Contribution of amino acid ...metabolic regulation in the disease remains understudied.
METHODS AND RESULTS—Transcriptomic and metabolomic analyses were performed in mouse failing heart induced by pressure overload. Suppression of branched-chain amino acid (BCAA) catabolic gene expression along with concomitant tissue accumulation of branched-chain α-keto acids was identified as a significant signature of metabolic reprogramming in mouse failing hearts and validated to be shared in human cardiomyopathy hearts. Molecular and genetic evidence identified the transcription factor Krüppel-like factor 15 as a key upstream regulator of the BCAA catabolic regulation in the heart. Studies using a genetic mouse model revealed that BCAA catabolic defect promoted heart failure associated with induced oxidative stress and metabolic disturbance in response to mechanical overload. Mechanistically, elevated branched-chain α-keto acids directly suppressed respiration and induced superoxide production in isolated mitochondria. Finally, pharmacological enhancement of branched-chain α-keto acid dehydrogenase activity significantly blunted cardiac dysfunction after pressure overload.
CONCLUSIONS—BCAA catabolic defect is a metabolic hallmark of failing heart resulting from Krüppel-like factor 15–mediated transcriptional reprogramming. BCAA catabolic defect imposes a previously unappreciated significant contribution to heart failure.
Isoproterenol is used widely for inducing heart failure in mice. Isoproterenol is a nonselective beta-adrenergic agonist. The acute model mimics stress-induced cardiomyopathy. The chronic model ...mimics advanced heart failure in humans. In this chapter, we describe a protocol that we used to induce heart failure in 100+ strains of inbred mice. Techniques on surgical pump implantation and echocardiography are described in detail. We also discuss the impact of drug dosage, duration, mortality, age, gender, and strain on cardiac remodeling responses. The success of model creation may be assessed by echocardiogram or molecular markers. This chapter may be relevant to those who are interested in using this heart failure model.
The Hybrid Mouse Diversity Panel (HMDP) is a collection of approximately 100 well-characterized inbred strains of mice that can be used to analyze the genetic and environmental factors underlying ...complex traits. While not nearly as powerful for mapping genetic loci contributing to the traits as human genome-wide association studies, it has some important advantages. First, environmental factors can be controlled. Second, relevant tissues are accessible for global molecular phenotyping. Finally, because inbred strains are renewable, results from separate studies can be integrated. Thus far, the HMDP has been studied for traits relevant to obesity, diabetes, atherosclerosis, osteoporosis, heart failure, immune regulation, fatty liver disease, and host-gut microbiota interactions. High-throughput technologies have been used to examine the genomes, epigenomes, transcriptomes, proteomes, metabolomes, and microbiomes of the mice under various environmental conditions. All of the published data are available and can be readily used to formulate hypotheses about genes, pathways and interactions.
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