Conference on the Federal Sentencing Guidelines, Panel 3: The Allocation of Discretion Under the Guidelines

The guidelines have shifted the locus of discretion from the judge to the prosecutor. This transfer has drastically changed sentencing because the prosecutor\u27s role is very different from the judge\u27s role. Before the guidelines, the prosecutor\u27s role in sentencing was minimal. The prosecutor could put a cap on the sentence by accepting a plea to a charge with a low maximum, but there was virtually no instance in which the charge would put a floor under the judge\u27s sentence. The judge, on the other hand, could sentence however he liked. Not only was the judge\u27s decision correct because it was final – there was no appellate review of sentences within the statutory maximum – it was correct because there was no law by which it could be called incorrect. Absent a few factors that were statutorily excluded from consideration, the judge could take into account any factor he thought relevant, and weigh it to whatever degree he thought it counted. The judge could be harsh or lenient, a retributivist or a utilitarian, a believer in deterrence or rehabilitation

Golgi derived PI(4)P-containing vesicle drives late steps of mitochondrial division

Mitochondrial plasticity is a key regulator of cell fate decisions. Mitochondrial division involves Dynamin-related protein-1 (Drp1) oligomerization, which constricts membranes at endoplasmic reticulum (ER) contact sites. The mechanisms driving the final steps of mitochondrial division are still unclear. Here, we found that microdomains of phosphatidylinositol 4-phosphate (PI(4)P) on Trans-Golgi network (TGN) vesicles were recruited to mitochondria-ER contact sites and could drive mitochondrial division downstream of Drp1. The loss of the small GTPase ADP-ribosylation factor 1 (Arf1) or its effector, phosphatidylinositol 4-kinase IIIβ (PI(4)KIIIβ) in different mammalian cell lines, prevented PI(4)P generation and led to a hyperfused and branched mitochondrial network, marked with extended mitochondrial constriction sites. Thus, recruitment of TGN-PI(4)P-containing vesicles at mitochondria-ER contact sites may trigger final events leading to mitochondrial scission.This work was supported by the Canadian Institutes of Health Research Operating Grants Program (CIHR grant 68833 to H.M.M.), the Medical Research Council (MRC grants MC_UU_00015/7 and RG89175 to J.P.), the Isaac Newton Trust (grant RG89529 to J.P.), and the Wellcome Trust Institutional Strategic Support Fund (grant RG89305 to J.P.). H.M.M. is a Canada Research Chair. S.N. and L.-C.T. are recipients of Daiichi Sankyo Foundation of Life Science and Ramon Areces postdoctoral fellowships, respectively. L.T. was supported by an MRC-funded graduate student fellowship. V.P was supported by the European Union’s Horizon 2020 research and innovation program (MITODYN-749926)

Long-term Impact of sewage sludge application on rhizobium leguminosarum biovar trifolii: an evaluation using meta-analysis

The Long-Term Sludge Experiment (LTSE) began in 1994 at nine UK field sites as part of continuing research into the effects of sludge-borne heavy metals on soil fertility. The long-term effects of Zn, Cu, and Cd on the most probable numbers of cells (MPN) of Rhizobium leguminosarum biovar trifolii were monitored for 8 yr in sludge-amended soils. To assess the statutory limits set by the UK Sludge (Use in Agriculture) Regulations, the experimental data were reviewed using statistical methods of meta-analysis. Previous LTSE studies have focused predominantly on statistical significance rather than effect size, whereas meta-analysis focuses on the magnitude and direction of an effect, i.e., the practical significance rather than its statistical significance. Results showed Zn to be the most toxic element causing an overall significant decrease in Rhizobium MPN of −26.6% during the LTSE. The effect of Cu showed no significant effect on Rhizobium MPN at concentrations below the UK limits, although a −5% decrease in Rhizobium MPN was observed in soils where total Cu ranged from 100 to <135 mg kg−1. Overall, there was nothing to indicate that Cd had a significant effect on Rhizobium MPN below the current UK statutory limit. In summary, the UK statutory limit for Zn appears to be insufficient for protecting Rhizobium from Zn toxicity effects

Effect of chronic supplementation with methylsulfonylmethane on oxidative stress following acute exercise in untrained healthy men

Objective  This study was conducted to assess the effects of chronic daily methylsulfonylmethane (MSM) supplementation on known markers of oxidative stress following acute bouts of exercise in untrained healthy young men. Methods  Eighteen untrained men volunteered for this study. Participants were randomized in a double-blind placebo-controlled fashion into two groups: MSM (n = 9) and placebo (n = 9). The participants took supplementation or placebo daily for 10 days before running. Participants ran 14 km. The MSM supplementation was prepared in water at 50 mg/kg body weight. The placebo group received water. Serum malondialdehyde (MDA), protein carbonyl (PC) and plasma oxidized glutathione (GSSG) were measured as markers of oxidative stress. The plasma-reduced glutathione (GSH) level and the GSH/GSSG ratio were determined as markers of plasma antioxidant capacity. Key Findings  Acute exercise led to elevated levels of serum MDA, PC and plasma GSSG. MSM supplementation maintained PC, MDA and GSSG at lower levels after exercise than the placebo. The plasma level of GSH and the ratio of GSH/GSSG were significantly higher in the MSM supplemented group. Conclusions  These results suggest that chronic daily oral supplementation of MSM has alleviating effects on known markers of oxidative stress following acute bouts of exercise in healthy young men

Delay discounting and under-valuing of recent information predict poorer adherence to social distancing measures during the COVID-19 pandemic

The COVID-19 pandemic has brought about unprecedented global changes in individual and collective behaviour. To reduce the spread of the virus, public health bodies have promoted social distancing measures while attempting to mitigate their mental health consequences. The current study aimed to identify cognitive predictors of social distancing adherence and mental health symptoms, using computational models derived from delay discounting (the preference for smaller, immediate rewards over larger, delayed rewards) and patch foraging (the ability to trade-off between exploiting a known resource and exploring an unknown one). In a representative sample of the UK population (N = 442), we find that steeper delay discounting predicted poorer adherence to social distancing measures and greater sensitivity to reward magnitude during delay discounting predicted higher levels of anxiety symptoms. Furthermore, under-valuing recently sampled information during foraging independently predicted greater violation of lockdown guidance. Our results suggest that those who show greater discounting of delayed rewards struggle to maintain social distancing. Further, those who adapt faster to new information are better equipped to change their behaviour in response to public health measures. These findings can inform interventions that seek to increase compliance with social distancing measures whilst minimising negative repercussions for mental health

Yeast arginine methyltransferase Hmt1p regulates transcription elongation and termination by methylating Npl3p

The heterogeneous nuclear ribonucleoprotein Npl3p of budding yeast is a substrate of arginine methyltransferase Hmt1p, but the role of Hmt1p in regulating Npl3p’s functions in transcription antitermination and elongation were unknown. We found that mutants lacking Hmt1p methyltransferase activity exhibit reduced recruitment of Npl3p, but elevated recruitment of a component of mRNA cleavage/termination factor CFI, to the activated GAL10-GAL7 locus. Consistent with this, hmt1 mutants displayed increased termination at the defective gal10-Δ56 terminator. Remarkably, hmt1Δ cells also exhibit diminished recruitment of elongation factor Tho2p and a reduced rate of transcription elongation in vivo. Importantly, the defects in Npl3p and Tho2p recruitment, antitermination and elongation in hmt1Δ cells all were mitigated by substitutions in Npl3p RGG repeats that functionally mimic arginine methylation by Hmt1p. Thus, Hmt1p promotes elongation and suppresses termination at cryptic terminators by methylating RGG repeats in Npl3p. As Hmt1p stimulates dissociation of Tho2p from an Npl3p-mRNP complex, it could act to recycle these elongation and antitermination factors back to sites of ongoing transcription

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. METHODS: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ(2) tests or Fisher exact tests for categorical variables. RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date

Galaxy Zoo: The Environmental Dependence of Bars and Bulges in Disc Galaxies

We present an analysis of the environmental dependence of bars and bulges in disc galaxies, using a volume-limited catalogue of 15810 galaxies at z<0.06 from the Sloan Digital Sky Survey with visual morphologies from the Galaxy Zoo 2 project. We find that the likelihood of having a bar, or bulge, in disc galaxies increases when the galaxies have redder (optical) colours and larger stellar masses, and observe a transition in the bar and bulge likelihoods, such that massive disc galaxies are more likely to host bars and bulges. We use galaxy clustering methods to demonstrate statistically significant environmental correlations of barred, and bulge-dominated, galaxies, from projected separations of 150 kpc/h to 3 Mpc/h. These environmental correlations appear to be independent of each other: i.e., bulge-dominated disc galaxies exhibit a significant bar-environment correlation, and barred disc galaxies show a bulge-environment correlation. We demonstrate that approximately half (50 +/- 10%) of the bar-environment correlation can be explained by the fact that more massive dark matter haloes host redder disc galaxies, which are then more likely to have bars. Likewise, we show that the environmental dependence of stellar mass can only explain a small fraction (25 +/- 10%) of the bar-environment correlation. Therefore, a significant fraction of our observed environmental dependence of barred galaxies is not due to colour or stellar mass dependences, and hence could be due to another galaxy property. Finally, by analyzing the projected clustering of barred and unbarred disc galaxies with halo occupation models, we argue that barred galaxies are in slightly higher-mass haloes than unbarred ones, and some of them (approximately 25%) are satellite galaxies in groups. We also discuss implications about the effects of minor mergers and interactions on bar formation.Comment: 20 pages, 18 figures; references updated; published in MNRA

Customizable views on semantically integrated networks for systems biology

Motivation: The rise of high-throughput technologies in the post-genomic era has led to the production of large amounts of biological data. Many of these datasets are freely available on the Internet. Making optimal use of these data is a significant challenge for bioinformaticians. Various strategies for integrating data have been proposed to address this challenge. One of the most promising approaches is the development of semantically rich integrated datasets. Although well suited to computational manipulation, such integrated datasets are typically too large and complex for easy visualization and interactive exploration

Spatial Dynamics of Human-Origin H1 Influenza A Virus in North American Swine

The emergence and rapid global spread of the swine-origin H1N1/09 pandemic influenza A virus in humans underscores the importance of swine populations as reservoirs for genetically diverse influenza viruses with the potential to infect humans. However, despite their significance for animal and human health, relatively little is known about the phylogeography of swine influenza viruses in the United States. This study utilizes an expansive data set of hemagglutinin (HA1) sequences (n = 1516) from swine influenza viruses collected in North America during the period 2003–2010. With these data we investigate the spatial dissemination of a novel influenza virus of the H1 subtype that was introduced into the North American swine population via two separate human-to-swine transmission events around 2003. Bayesian phylogeographic analysis reveals that the spatial dissemination of this influenza virus in the US swine population follows long-distance swine movements from the Southern US to the Midwest, a corn-rich commercial center that imports millions of swine annually. Hence, multiple genetically diverse influenza viruses are introduced and co-circulate in the Midwest, providing the opportunity for genomic reassortment. Overall, the Midwest serves primarily as an ecological sink for swine influenza in the US, with sources of virus genetic diversity instead located in the Southeast (mainly North Carolina) and South-central (mainly Oklahoma) regions. Understanding the importance of long-distance pig transportation in the evolution and spatial dissemination of the influenza virus in swine may inform future strategies for the surveillance and control of influenza, and perhaps other swine pathogens