Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

ARTD1/PARP1 Negatively Regulates Glycolysis by Inhibiting Hexokinase 1 Independent of NAD(+) Depletion

ARTD1 (PARP1) is a key enzyme involved in DNA repair through the synthesis of poly(ADP-ribose) (PAR) in response to strand breaks, and it plays an important role in cell death following excessive DNA damage. ARTD1-induced cell death is associated with NAD(+) depletion and ATP loss; however, the molecular mechanism of ARTD1-mediated energy collapse remains elusive. Using real-time metabolic measurements, we compared the effects of ARTD1 activation and direct NAD(+) depletion. We found that ARTD1-mediated PAR synthesis, but not direct NAD(+) depletion, resulted in a block to glycolysis and ATP loss. We then established a proteomics-based PAR interactome after DNA damage and identified hexokinase 1 (HK1) as a PAR binding protein. HK1 activity is suppressed following nuclear ARTD1 activation and binding by PAR. These findings help explain how prolonged activation of ARTD1 triggers energy collapse and cell death, revealing insight into the importance of nucleus-to-mitochondria communication via ARTD1 activation.

Global Production, CSR and Human Rights: The Courts of Public Opinion and the Social License to Operate

This paper takes at its starting point the responsibility placed upon corporations by the United Nations’ Protect, Respect and Remedy Framework as elaborated upon by the Guiding Principles on Business and Human Rights to respect human rights. The overt pragmatism and knowledge of the complex business relationships that are embedded in global production led John Ruggie, the author of the Framework, to adopt a structure for the relationship between human rights and business that built on the existing practices of Corporate Social Responsibility (CSR). His intention was that these practices should be developed to embrace respect for human rights by exhorting corporations to move from “the era of declaratory CSR” to showing a demonstrable policy commitment to respect for human rights. The prime motivation for corporations to do this was, according to Ruggie, because the responsibility to respect was one that would be guarded and judged by the “courts of public opinion” as part of the social expectations imposed upon corporations or to put it another way as a condition of a corporation’s social license to operate.
This article sets out the background context to the Framework and examines the structures that it puts forward. In its third and final section the article looks at how the Framework requires a corporation’s social license to be assembled and how and by whom that social license will be judged. The success or failure of the Framework in persuading corporations to respect human rights is tied to whether “the courts of public opinion” can use their “naming and shaming power” effectively.

Properties of extragalactic dust inferred from linear polarimetry of Type Ia Supernovae

Aims
The aim of this paper is twofold: 1) to investigate the properties of extragalactic dust and compare them to what is seen in the Galaxy; 2) to address in an independent way the problem of the anomalous extinction curves reported for reddened Type Ia Supernovae (SN) in connection to the environments in which they explode. 

Methods
The properties of the dust are derived from the wavelength dependence of the continuum polarization observed in four reddened Type Ia SN: 1986G, 2006X, 2008fp, and 2014J. The method is based on the observed fact that Type Ia SN have a negligible intrinsic continuum polarization. This and their large luminosity makes them ideal tools to probe the dust properties in extragalactic environments.

Results
All four objects are characterized by exceptionally low total-to-selective absorption ratios (R<inf>V</inf>) and display an anomalous interstellar polarization law, characterized by very blue polarization peaks. In all cases the polarization position angle is well aligned with the local spiral structure. While SN 1986G is compatible with the most extreme cases of interstellar polarization known in the Galaxy, SN 2006X, 2008fp, and 2014J show unprecedented behaviours. The observed deviations do not appear to be connected to selection effects related to the relatively large amounts of reddening characterizing the objects in the sample.

Conclusions
The dust responsible for the polarization of these four SN is most likely of interstellar nature. The polarization properties can be interpreted in terms of a significantly enhanced abundance of small grains. The anomalous behaviour is apparently associated with the properties of the galactic environment in which the SN explode, rather than with the progenitor system from which they originate. For the extreme case of SN 2014J, we cannot exclude the contribution of light scattered by local material; however, the observed polarization properties require an ad hoc geometrical dust distribution.