No evidence of direct association between GLUT4 and glycogen in human skeletal muscle

Previous studies have demonstrated that exercise increases whole body and skeletal muscle insulin sensitivity that is linked with increased GLUT4 at the plasma membrane following insulin stimulation and associated with muscle glycogen depletion. To assess the potential direct association between muscle glycogen and GLUT4, seven untrained, male subjects exercised for 60 min at ~75% VO2 peak, with muscle samples obtained by percutaneous needle biopsy immediately before and after exercise. Exercise reduced muscle glycogen content by ~43%. An ultracentrifugation protocol resulted in a ~2-3-fold enriched glycogen fraction from muscle samples for analysis. Total GLUT4 content was unaltered by exercise and we were unable to detect any GLUT4 in glycogen fractions, either with or without amylase treatment. In skinned muscle fiber segments, there was very little, if any, GLUT4 detected in wash solutions, except following exposure to 1% Triton X-100. Amylase treatment of single fibers did not increase GLUT4 in the wash solution and there were no differences in GLUT4 content between fibers obtained before or after exercise for any of the wash treatments. Our results indicate no direct association between GLUT4 and glycogen in human skeletal muscle, before or after exercise, and suggest that alterations in GLUT4 translocation associated with exercise-induced muscle glycogen depletion are mediated via other mechanisms

Effect of Pulsed or Continuous Delivery of Salt on Sensory Perception Over Short Time Intervals

Salt in the human diet is a major risk factor for hypertension and many countries have set targets to reduce salt consumption. Technological solutions are being sought to lower the salt content of processed foods without altering their taste. In this study, the approach was to deliver salt solutions in pulses of different concentrations to determine whether a pulsed delivery profile affected sensory perception of salt. Nine different salt profiles were delivered by a Dynataste device and a trained panel assessed their saltiness using time–intensity and single-score sensory techniques. The profile duration (15 s) was designed to match eating conditions and the effects of intensity and duration of the pulses on sensory perception were investigated. Sensory results from the profiles delivered in either water or in a bouillon base were not statistically different. Maximum perceived salt intensities and the area under the time– intensity curves correlated well with the overall perceived saltiness intensity despite the stimulus being delivered as several pulses. The overall saltiness scores for profiles delivering the same overall amount of sodium were statistically not different from one another suggesting that, in this system, pulsed delivery did not enhance salt perception but the overall amount of salt delivered in each profile did affect sensory perception

Formation and Propagation of Matter Wave Soliton Trains

Attraction between atoms in a Bose-Einstein-Condensate renders the condensate unstable to collapse. Confinement in an atom trap, however, can stabilize the condensate for a limited number of atoms, as was observed with 7Li, but beyond this number, the condensate collapses. Attractive condensates constrained to one-dimensional motion are predicted to form stable solitons for which the attractive interactions exactly compensate for the wave packet dispersion. Here we report the formation or bright solitons of 7Li atoms created in a quasi-1D optical trap. The solitons are created from a stable Bose-Einstein condensate by magnetically tuning the interactions from repulsive to attractive. We observe a soliton train, containing many solitons. The solitons are set in motion by offsetting the optical potential and are observed to propagate in the potential for many oscillatory cycles without spreading. Repulsive interactions between neighboring solitons are inferred from their motion

Warning signs for stabilizing global CO2 emissions

Carbon dioxide (CO2) emissions from fossil fuels and industry comprise ~90% of all CO2 emissions from human activities. For the last three years, such emissions were stable, despite continuing growth in the global economy. Many positive trends contributed to this unique hiatus, including reduced coal use in China and elsewhere, continuing gains in energy efficiency, and a boom in low-carbon renewables such as wind and solar. However, the temporary hiatus appears to have ended in 2017. For 2017, we project emissions growth of 2.0% (range: 0.8%−3.0%) from 2016 levels (leap-year adjusted), reaching a record 36.8 ± 2 Gt CO2. Economic projections suggest further emissions growth in 2018 is likely. Time is running out on our ability to keep global average temperature increases below 2 °C and, even more immediately, anything close to 1.5 °C

The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283

Global energy growth is outpacing decarbonization

Recent reports have highlighted the challenge of keeping global average temperatures below 2 °C and—even more so—1.5 °C (IPCC 2018). Fossil-fuel burning and cement production release ~90% of all CO2 emissions from human activities. After a three-year hiatus with stable global emissions (Jackson et al 2016; Le Quéré C et al 2018a ; IEA 2018), CO2 emissions grew by 1.6% in 2017 to 36.2 Gt (billion tonnes), and are expected to grow a further 2.7% in 2018 (range: 1.8%–3.7%) to a record 37.1 ± 2 Gt CO2 (Le Quéré et al 2018b). Additional increases in 2019 remain uncertain but appear likely because of persistent growth in oil and natural gas use and strong growth projected for the global economy. Coal use has slowed markedly in the last few years, potentially peaking, but its future trajectory remains uncertain. Despite positive progress in ~19 countries whose economies have grown over the last decade and their emissions have declined, growth in energy use from fossil-fuel sources is still outpacing the rise of low-carbon sources and activities. A robust global economy, insufficient emission reductions in developed countries, and a need for increased energy use in developing countries where per capita emissions remain far below those of wealthier nations will continue to put upward pressure on CO2 emissions. Peak emissions will occur only when total fossil CO2 emissions finally start to decline despite growth in global energy consumption, with fossil energy production replaced by rapidly growing low- or no-carbon technologies

Genotype and Gene Expression Associations with Immune Function in Drosophila

It is now well established that natural populations of Drosophila melanogaster harbor substantial genetic variation associated with physiological measures of immune function. In no case, however, have intermediate measures of immune function, such as transcriptional activity of immune-related genes, been tested as mediators of phenotypic variation in immunity. In this study, we measured bacterial load sustained after infection of D. melanogaster with Serratia marcescens, Providencia rettgeri, Enterococcus faecalis, and Lactococcus lactis in a panel of 94 third-chromosome substitution lines. We also measured transcriptional levels of 329 immune-related genes eight hours after infection with E. faecalis and S. marcescens in lines from the phenotypic tails of the test panel. We genotyped the substitution lines at 137 polymorphic markers distributed across 25 genes in order to test for statistical associations among genotype, bacterial load, and transcriptional dynamics. We find that genetic polymorphisms in the pathogen recognition genes (and particularly in PGRP-LC, GNBP1, and GNBP2) are most significantly associated with variation in bacterial load. We also find that overall transcriptional induction of effector proteins is a significant predictor of bacterial load after infection with E. faecalis, and that a marker upstream of the recognition gene PGRP-SD is statistically associated with variation in both bacterial load and transcriptional induction of effector proteins. These results show that polymorphism in genes near the top of the immune system signaling cascade can have a disproportionate effect on organismal phenotype due to the amplification of minor effects through the cascade