Occurrence Rates of Electromagnetic Ion Cyclotron (EMIC) Waves With Rising Tones in the Van Allen Probes Data Set.

In Fourier time-frequency power spectrograms of satellite magnetic field data, electromagnetic ion cyclotron (EMIC) waves may feature discrete, rising tone structures that rapidly increase in frequency. Using data from the Van Allen Probes Electric and Magnetic Field Instrument Suite and Integrated Science (EMFISIS) fluxgate magnetometer, we conducted a statistical study of EMIC waves from September 2012 through June 2016. We compared the occurrence rates and spatial distributions for all EMIC waves with those for rising tone EMIC waves as a function of magnetic local time (MLT) and L shell, as well as a function of R XY and Z in solar-magnetic (SM) coordinates. Overall, EMIC waves occurred during 2.4% of the time period considered, but rising tone EMIC waves were only found during 0.2% of the time period considered. About 7%-8% of the minutes of orbital coverage with H+ or He+ band EMIC waves had rising tones. The regions of peak occurrence rates for H+ and He+ band waves, as well as waves with rising tones, were found in the noon and dusk sectors for 4 < L < 6. The preferred regions for H+ waves as a function of R XY and Z SM suggest an association with magnetospheric compressions near noon and interactions between plumes and the ring current near dusk. Peak occurrence rates for O+ band waves were found between 2 < L < 4 at all MLT, and over a wide range of L shells near dusk. No rising tones were found in the O+ band.

Oxygen torus and its coincidence with EMIC wave in the deep inner magnetosphere: Van Allen Probe B and Arase observations.

We investigate the longitudinal structure of the oxygen torus in the inner magnetosphere for a specific event found on 12 September 2017, using simultaneous observations from the Van Allen Probe B and Arase satellites. It is found that Probe B observed a clear enhancement in the average plasma mass (M) up to 3-4 amu at L = 3.3-3.6 and magnetic local time (MLT) = 9.0 h. In the afternoon sector at MLT ~ 16.0 h, both Probe B and Arase found no clear enhancements in M. This result suggests that the oxygen torus does not extend over all MLT but is skewed toward the dawn. Since a similar result has been reported for another event of the oxygen torus in a previous study, a crescent-shaped torus or a pinched torus centered around dawn may be a general feature of the O+ density enhancement in the inner magnetosphere. We newly find that an electromagnetic ion cyclotron (EMIC) wave in the H+ band appeared coincidently with the oxygen torus. From the lower cutoff frequency of the EMIC wave, the ion composition of the oxygen torus is estimated to be 80.6% H+, 3.4% He+, and 16.0% O+. According to the linearized dispersion relation for EMIC waves, both He+ and O+ ions inhibit EMIC wave growth and the stabilizing effect is stronger for He+ than O+. Therefore, when the H+ fraction or M is constant, the denser O+ ions are naturally accompanied by the more tenuous He+ ions, resulting in a weaker stabilizing effect (i.e., larger growth rate). From the Probe B observations, we find that the growth rate becomes larger in the oxygen torus than in the adjacent regions in the plasma trough and the plasmasphere.

Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1-mutant myelodysplastic syndromes.

The splicing factor SF3B1 is the most frequently mutated gene in myelodysplastic syndromes (MDS), and is strongly associated with the presence of ring sideroblasts (RS). We have performed a systematic analysis of cryptic splicing abnormalities from RNA sequencing data on hematopoietic stem cells (HSCs) of SF3B1-mutant MDS cases with RS. Aberrant splicing events in many downstream target genes were identified and cryptic 3' splice site usage was a frequent event in SF3B1-mutant MDS. The iron transporter ABCB7 is a well-recognized candidate gene showing marked downregulation in MDS with RS. Our analysis unveiled aberrant ABCB7 splicing, due to usage of an alternative 3' splice site in MDS patient samples, giving rise to a premature termination codon in the ABCB7 mRNA. Treatment of cultured SF3B1-mutant MDS erythroblasts and a CRISPR/Cas9-generated SF3B1-mutant cell line with the nonsense-mediated decay (NMD) inhibitor cycloheximide showed that the aberrantly spliced ABCB7 transcript is targeted by NMD. We describe cryptic splicing events in the HSCs of SF3B1-mutant MDS, and our data support a model in which NMD-induced downregulation of the iron exporter ABCB7 mRNA transcript resulting from aberrant splicing caused by mutant SF3B1 underlies the increased mitochondrial iron accumulation found in MDS patients with RS.

Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells.

The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34(+) cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicing/processing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34(+) cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.

Is bisphosphonate-related osteonecrosis of the jaw an infection? A histological and microbiological ten-year summary.

The role of infection in the etiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is poorly understood. Large-scale epidemiological descriptions of the histology and microbiology of BRONJ are not found in the literature. Herein, we present a systematic review of BRONJ histology and microbiology (including demographics, immunocompromised associations, clinical signs and symptoms, disease severity, antibiotic and surgical treatments, and recovery status) validating that infection should still be considered a prime component in the multifactorial disease.

Ghrelin receptor regulates HFCS-induced adipose inflammation and insulin resistance.

BACKGROUND AND OBJECTIVES: High fructose corn syrup (HFCS) is the most commonly used sweetener in the United States. Some studies show that HFCS consumption correlates with obesity and insulin resistance, while other studies are in disagreement. Owing to conflicting and insufficient scientific evidence, the safety of HFCS consumption remains controversial. SUBJECTS/METHODS: We investigated the metabolic consequences of mice fed a (a) regular diet, (b) 'Western' high-fat diet or (c) regular diet supplemented with 8% HFCS in drinking water (to mimic soft drinks) for 10 months. Adipose tissue macrophages (ATMs) have emerged as a major pathogenic factor for obesity and insulin resistance. ATMs consist of proinflammatory F4/80(+)CD11c(+) macrophages and anti-inflammatory F4/80(+)CD11c(-) macrophages. In this study, we assessed the effects of HFCS on ATMs in intra-abdominal fat. RESULTS: We found that HFCS feeding in mice induced more severe adipose inflammation and insulin resistance than even the higher-calorie-containing 'Western' high-fat diet, and these HFCS-induced deleterious effects were independent of calorie intake or body fat content. We showed that similar to 'Western' high-fat diet, HFCS triggered a robust increase of both proinflammatory ATMs and anti-inflammatory ATMs in intra-abdominal fat. Remarkably, however, the anti-inflammatory ATMs were much less abundant in HFCS-fed mice than in high-fat-fed mice. Furthermore, we showed that deletion of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) ameliorates HFCS-induced adipose inflammation and insulin resistance. HFCS-fed GHS-R-null mice exhibit decreased proinflammatory ATMs in intra-abdominal fat, reduced adipose inflammation and attenuated liver steatosis. CONCLUSION: Our studies demonstrate that HFCS has detrimental effects on metabolism, suggesting that dietary guidelines on HFCS consumption for Americans may need to be revisited. GHS-R deletion mitigates the effects of HFCS on adipose inflammation and insulin resistance, suggesting that GHS-R antagonists may represent a novel therapy for insulin resistance.

Resolution of oblique-plane images in sectioning microscopy.

Live biological specimens exhibit time-varying behavior on the microscale in all three dimensions. Although scanning confocal and two-photon microscopes are able to record three-dimensional image stacks through these specimens, they do so at relatively low speeds which limits the time resolution of the biological processes that can be observed. One way to improve the data acquisition rate is to image only the regions of a specimen that are of interest and so researchers have recently begun to acquire two-dimensional images of inclined planes or surfaces extending significantly into the z-direction. As the resolution is not uniform in x, y and z, the images possess non-isotropic resolution. We explore this theoretically and show that images of an oblique plane may contain spectral content that could not have been generated by specimen features lying wholly within the plane but must instead arise from a spatial variation in another direction. In some cases we find that the image contains frequencies three times higher than the resolution limit for in-plane features. We confirm this finding through numerical simulations and experiments on a novel, oblique-plane imaging system and suggest that care be taken in the interpretation of such images.

Inheritance of Resistance to Meloidoygne incognita in Primitive Cotton Accessions from Mexico.

Few sources of resistance to root-knot nematodes (Meloidogyne incognita) in upland cotton (Gossypium hirsutum) have been utilized to develop resistant cultivars, making this resistance vulnerable to virulence in the pathogen population. The objectives of this study were to determine the inheritance of resistance in five primitive accessions of G. hirsutum (TX1174, TX1440, TX2076, TX2079, and TX2107) and to determine allelic relations with the genes for resistance in the genotypes Clevewilt-6 (CW) and Wild Mexico Jack Jones (WMJJ). A half-diallel experimental design was used to create 28 populations from crosses among these seven sources of resistance and the susceptible cultivar DeltaPine 90 (DP90). Resistance to M. incognita was measured as eggs per g roots in the parents, F(1) and F(2) generations of each cross. The resistance in CW and WMJJ was inherited as recessive traits, as reported previously for CW, whereas the resistance in the TX accessions was inherited as a dominant trait. Chi square analysis of segregation of resistance in the F(2) was used to estimate the numbers of genes that conditioned resistance. Resistance in CW and WMJJ appeared to be a multigenic trait whereas the resistance in the TX accessions best fit either a one or two gene model. The TX accessions were screened with nine SSR markers linked to resistance loci in other cotton genotypes. The TX accessions lacked the allele amplified by SSR marker CR316 and linked to resistance in CW and other resistant genotypes derived from this source. Four of five TX genotypes lacked the amplification products from the marker BNL1231 that is also associated with the resistant allele on Chromosome 11 in WMJJ, CW, NemX, M120 RNR and Auburn 634 RNR. However, all five TX genotypes produced the same amplification products from three SSR markers linked to the resistant allele on Chromosome 14 in M120 RNR and M240 RNR. The TX accessions have unique resistance genes that are likely to be useful in efforts to develop resistant cotton cultivars with increased durability.

Modeling the steady-state deformation of the solid phase of articular cartilage.

The transient response of articular cartilage (AC) to compressive loads has been described by complex multicomponent models. However, the steady-state behaviour is determined by the collagen network which is heterogeneous through the depth of the tissue, a characteristic which is omitted from most theoretical models. Experimental data are now available on the local responses of the network to compressive loads and the aim of this study was to develop minimal models capable of simulating this behaviour. A series of finite element models (FEMs) of AC under load were developed of increasing complexity, assuming the AC was i) completely homogeneous, ii) layered and isotropic and iii) layered and anisotropic. The geometry of the layered cartilage model was based on the recent experimental data. It is shown that a layered transversely isotropic elastic model is required to accurately recreate the experimental data. Stress distributions within the models are analysed, and the relevance of this work to transient modeling of AC is discussed. The work presented is a fundamental step forward in the understanding of the distribution of local physiological stresses and strains in AC, and has applications in modeling chondrocyte mechanotransduction as well as the effects of pathogenesis.

Atherogenic diet-induced hepatitis is partially dependent on murine TLR4.

Diets high in cholesterol and cholate such as the Paigen diet have been used to study atherogenesis, lithogenesis, and proinflammatory microvascular changes induced by nutritional hypercholesterolemia. Although these diets lead to chronic hepatic inflammation and fibrosis, the early inflammatory changes have been poorly characterized. TLR4, a known receptor for LPS, is also a receptor for a variety of endogenous ligands and has been implicated in atheroma formation. Here, we specifically examined the early inflammatory response of the liver to the atherogenic (ATH) diet and the possible contribution of TLR4. Animals fed the high-cholesterol/cholate diet for 3 weeks developed a significant, predominantly mononuclear leukocyte infiltration in the liver, hepatic steatosis, elevated hepatic expression of MCP-1, RANTES, and MIP-2, and increased serum levels of liver enzymes. In TLR4-deleted animals, there was a 30% attenuation in the serum alanine transaminase levels and a 50% reduction in the leukocyte infiltration with a fourfold reduction in chemokine expression. In contrast, hepatic steatosis did not differ from wild-type controls. TLR2 deletion had no effect on diet-induced hepatitis but increased the amount of steatosis. We conclude that the early inflammatory liver injury but not hepatic lipid loading induced by the ATH diet in mice is mediated in part by TLR4.

A magnetic reconnection X-line extending more than 390 Earth radii in the solar wind.

Magnetic reconnection in a current sheet converts magnetic energy into particle energy, a process that is important in many laboratory, space and astrophysical contexts. It is not known at present whether reconnection is fundamentally a process that can occur over an extended region in space or whether it is patchy and unpredictable in nature. Frequent reports of small-scale flux ropes and flow channels associated with reconnection in the Earth's magnetosphere raise the possibility that reconnection is intrinsically patchy, with each reconnection X-line (the line along which oppositely directed magnetic field lines reconnect) extending at most a few Earth radii (R(E)), even though the associated current sheets span many tens or hundreds of R(E). Here we report three-spacecraft observations of accelerated flow associated with reconnection in a current sheet embedded in the solar wind flow, where the reconnection X-line extended at least 390R(E) (or 2.5 x 10(6) km). Observations of this and 27 similar events imply that reconnection is fundamentally a large-scale process. Patchy reconnection observed in the Earth's magnetosphere is therefore likely to be a geophysical effect associated with fluctuating boundary conditions, rather than a fundamental property of reconnection. Our observations also reveal, surprisingly, that reconnection can operate in a quasi-steady-state manner even when undriven by the external flow.

Feeding a corn oil/sucrose-enriched diet enhances steatohepatitis in sedentary rats.

The current study investigated the combined effects of feeding a high-fat/high-sucrose (HF/HS) diet to rodents rendered sedentary via hindlimb unloading (HU). For 3 wk before HU, male Wistar rats were fed chow or a diet in which 32% of calories were derived from corn oil fat and 48% of calories from sucrose. Feeding continued during an additional 3-wk period of HU. Subsequently, blood samples were collected for determination of circulating leukocyte counts, insulin levels, and portal vein endotoxin. Inflammation, necrosis, and steatosis were assessed in formalin-fixed liver sections. No biochemical or histological evidence of injury was observed in control rats fed chow or HF/HS. HU increased circulating neutrophils and resulted in hyperinsulinemia. Mild hepatic fat accumulation and minimal focal necroinflammation were observed in this group. Feeding HF/HS during HU exacerbated hyperinsulinemia, hepatic steatosis, Kupffer cell content, and cytokine expression. Significant portal endotoxemia was noted in HU rats but was not influenced by HF/HS diet. On the other hand, feeding HF/HS significantly enhanced lipid peroxidation end products in liver of HU rats by approximately threefold compared with chow-fed rats. In summary, these findings demonstrate that feeding a high-calorie diet potentiates steatosis and injury in sedentary HU rats. Mechanisms underlying enhanced injury most likely involved lipid peroxidation. Importantly, these findings suggest that dietary manipulation combined with physical inactivity can be used to model steatohepatitis.

Spatial correlation of solar-wind turbulence from two-point measurements.

Interplanetary turbulence, the best studied case of low frequency plasma turbulence, is the only directly quantified instance of astrophysical turbulence. Here, magnetic field correlation analysis, using for the first time only proper two-point, single time measurements, provides a key step in unraveling the space-time structure of interplanetary turbulence. Simultaneous magnetic field data from the Wind, ACE, and Cluster spacecraft are analyzed to determine the correlation (outer) scale, and the Taylor microscale near Earth's orbit.

Regulation of alternative splicing by PTB and associated factors.

PTB (polypyrimidine tract-binding protein) is a repressive regulator of alternative splicing. We have investigated the role of PTB in three model alternative splicing systems. In the alpha-actinin gene, PTB represses the SM (smooth muscle) exon by binding to key sites in the polypyrimidine tract. Repressive binding to these sites is assisted by co-operative binding to additional downstream sites. SM exon splicing can be activated by CELF proteins, which also bind co-operatively to interspersed sites and displace PTB from the pyrimidine tract. Exon 11 of PTB pre-mRNA is repressed by PTB in an autoregulatory feedback loop. Exon 11-skipped RNA gets degraded through nonsense-mediated decay. Less than 1% of steady-state PTB mRNA is represented by this isoform, but inhibition of nonsense-mediated decay by RNA interference against Upf1 shows that at least 20% of PTB RNA is consumed by this pathway. This represents a widespread but under-appreciated role of alternative splicing in the quantitative regulation of gene expression, an important addition to its role as a generator of protein isoform diversity. Repression of alpha-tropomyosin exon 3 is an exceptional example of PTB regulation, because repression only occurs at high levels in SM cells, despite the fact that PTB is widely expressed. In this case, a PTB-interacting cofactor, raver1, appears to play an important role. By the use of 'tethering' assays, we have identified discrete domains within both PTB and raver1 that mediate their repressive activities on this splicing event.

Spectral distribution of the cross helicity in the solar wind.

There are a variety of theoretical and observational indications that fluctuation energy in astrophysical and space plasma turbulence is distributed anisotropically in space relative to the magnetic field direction. The cross helicity, represented by correlations between velocity and magnetic field fluctuations, enters a magnetohydrodynamic description on equal footing with the energy, but its anisotropy has not been examined in the same degree of detail. Here we employ Advanced Coronal Explorer data to examine the rotational symmetry of the cross helicity. We find that the normalized cross helicity is associated more or less equally with all angular components of the fluctuations. This favors turbulence models that allow for cross communication between parallel and perpendicular wave numbers, suggesting that "wavelike" and "turbulencelike" fluctuations are strongly coupled.

Genetic mapping and QTL analysis of fiber-related traits in cotton ( Gossypium).

Cotton, the leading natural fiber crop, is largely produced by two primary cultivated allotetraploid species known as Upland or American cotton ( Gossypium hirsutum L.) and Pima or Egyptian cotton ( G. barbadense L.). The allotetraploid species diverged from each other and from their diploid progenitors (A or D genome) through selection and domestication after polyploidization. To analyze cotton AD genomes and dissect agronomic traits, we have developed a genetic map in an F2 population derived from interspecific hybrids between G. hirsutum L. cv. Acala-44 and G. barbadense L. cv. Pima S-7. A total of 392 genetic loci, including 333 amplified fragment length polymorphisms (AFLPs), 47 simple sequence repeats (SSRs), and 12 restriction fragment length polymorphisms (RFLPs), were mapped in 42 linkage groups, which span 3,287 cM and cover approximately 70% of the genome. Using chromosomal aneuploid interspecific hybrids and a set of 29 RFLP and SSR framework markers, we assigned 19 linkage groups involving 223 loci to 12 chromosomes. Comparing four pairs of homoeologous chromosomes, we found that with one exception linkage distances in the A-subgenome chromosomes were larger than those in their D-subgenome homoeologues, reflecting higher recombination frequencies and/or larger chromosomes in the A subgenome. Segregation distortion was observed in 30 out of 392 loci mapped in cotton. Moreover, approximately 29% of the RFLPs behaved as dominant loci, which may result from rapid genomic changes. The cotton genetic map was used for quantitative trait loci (QTL) analysis using composite interval mapping and permutation tests. We detected seven QTLs for six fiber-related traits; five of these were distributed among A-subgenome chromosomes, the genome donor of fiber traits. The detection of QTLs in both the A subgenome in this study and the D subgenome in a previous study suggests that fiber-related traits are controlled by the genes in homoeologous genomes, which are subjected to selection and domestication. Some chromosomes contain clusters of QTLs and presumably contribute to the large amount of phenotypic variation that is present for fiber-related traits.

Endotoxemia and hepatic injury in a rodent model of hindlimb unloading.

Hindlimb unloading (HU) is known to induce physiological alterations in various organ systems that mimic some responses observed after exposure to microgravity. In the present study, the effects of up to 4 wk of HU on the liver were assessed in male Wistar rats and two mouse strains: endotoxin-sensitive C57BL/6 mice and endotoxin-resistant C3H/HEJ mice. Plasma levels of endotoxin, a known stimulator of hepatic injury, were measured in portal and systemic blood samples. Endotoxin was elevated by approximately 50% in portal blood samples of mice and rats but was not detectable in systemic blood. This low-grade portal endotoxemia was associated with hepatic injury in rats and C57BL/6 mice as indicated by inflammation and elevated serum transaminase activities. Blood levels of the cytokine TNF-alpha were increased by approximately 50% in C57BL/6 mice; no significant elevation of this cytokine was detected in rats. Messenger RNA levels of the acute-phase proteins serum amyloid A, haptoglobin, and lipopolysaccharide binding protein were significantly enhanced after 3 wk of HU in endotoxin-sensitive rodents. In contrast, no histological changes or significant increases in serum enzyme activity were detected after HU in C3H/HEJ mice despite portal endotoxin levels of 222 +/- 83.4 pg/ml. At the 3-wk time point, expression of acute-phase proteins was not elevated in C3H/HEJ mice; however, expression after 4 wk of HU was similar to endotoxin-sensitive rodents. In conclusion, these findings indicate that HU induced mild portal endotoxemia, which contributed to the observed hepatic injury in endotoxin-sensitive rodents.