Variation in _PNPLA3_ is associated with outcomes in alcoholic liver disease

Two recent genome-wide association studies have described associations of SNP variants in _PNPLA3_ with nonalcoholic fatty liver and plasma liver enzyme levels in population based cohorts. We investigated the contributions of these variants to clinical outcomes in Mestizo subjects with a history of excessive alcohol consumption. We show that non-synonymous variant rs738409[G] (I148M) in _PNPLA3_ is strongly associated with alcoholic liver disease and progression to alcoholic cirrhosis (unadjusted OR = 2.25, P = 1.7x10^-10^; ancestry-adjusted OR = 1.79, P = 1.9x10^-5^)

Local Public Services in Wisconsin: Alternatives for Municipalities with a Focus on Privatization

Both rural and urban municipal officials, faced with increased local resistance to higher taxes, increasing expenditure needs, weakening financial support from higher levels of government, and the growing pressure to "do more with less" have accelerated their search for alternative ways of delivering local public services. The downsizing of government has been brought to the forefront of public discussion in part due to the general conservative shift at the federal and state level and the need to maintain a balanced budget at the local level. Related private sector trends downsizing middle management as a means to become "leaner and meaner," reducing duplication and waste, and increasing earnings, profit levels, and returns to investors. At the same time many local public officials are faced with rising costs to maintain an aging infrastructure, accommodating the needs of special populations, satisfying rules and regulations imposed by higher levels of government, funding new investments to meet the demands of a growing economy in some instances, or maintaining critical services in the face declining economies. In short, the rules of the game for effective management of local governments have changed.

Double-impulse magnetic focusing of launched cold atoms.

We have theoretically investigated three-dimensional focusing of a launched cloud of cold atoms using a pair of magnetic lens pulses (the alternate-gradient method). Individual lenses focus radially and defocus axially or vice versa. The performance of the two possible pulse sequences are compared and found to be ideal for loading both 'pancake' and 'sausage' shaped magnetic/optical microtraps. It is shown that focusing aberrations are considerably smaller for double-impulse magnetic lenses compared to single-impulse magnetic lenses. An analysis of clouds focused by the double-impulse technique is presented

Viewers base estimates of face matching accuracy on their own familiarity: Explaining the photo-ID paradox

Matching two different images of a face is a very easy task for familiar viewers, but much harder for unfamiliar viewers. Despite this, use of photo-ID is widespread, and people appear not to know how unreliable it is. We present a series of experiments investigating bias both when performing a matching task and when predicting other people’s performance. Participants saw pairs of faces and were asked to make a same/different judgement, after which they were asked to predict how well other people, unfamiliar with these faces, would perform. In four experiments we show different groups of participants familiar and unfamiliar faces, manipulating this in different ways: celebrities in experiments 1 to 3 and personally familiar faces in experiment 4. The results consistently show that people match images of familiar faces more accurately than unfamiliar faces. However, people also reliably predict that the faces they themselves know will be more accurately matched by different viewers. This bias is discussed in the context of current theoretical debates about face recognition, and we suggest that it may underlie the continued use of photo-ID, despite the availability of evidence about its unreliability

Rats Genetically Selected for High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin by Upregulation of Hepatic Biliverdin Reductase-A (BVRA) and Suppression of UGT1A1

Exercise in humans and animals increases plasma bilirubin levels, but the mechanism by which this occurs is unknown. In the present study, we utilized rats genetically selected for high capacity running (HCR) and low capacity running (LCR) to determine pathways in the liver that aerobic exercise modifies to control plasma bilirubin. The HCR rats, compared to the LCR, exhibited significantly higher levels of plasma bilirubin and the hepatic enzyme that produces it, biliverdin reductase-A (BVRA). The HCR also had reduced expression of the glucuronyl hepatic enzyme UGT1A1, which lowers plasma bilirubin. Recently, bilirubin has been shown to activate the peroxisome proliferator-activated receptor-α (PPARα), a ligand-induced transcription factor, and the higher bilirubin HCR rats had significantly increased PPARα-target genes Fgf21, Abcd3, and Gys2. These are known to promote liver function and glycogen storage, which we found by Periodic acid–Schiff (PAS) staining that hepatic glycogen content was higher in the HCR versus the LCR. Our results demonstrate that exercise stimulates pathways that raise plasma bilirubin through alterations in hepatic enzymes involved in bilirubin synthesis and metabolism, improving liver function, and glycogen content. These mechanisms may explain the beneficial effects of exercise on plasma bilirubin levels and health in humans

Advanced Telecommunications and Signal Processing Program

Contains an introduction, and reports on seven research projects.Advanced Telecommunications Research ProgramAT&T FellowshipINTEL FellowshipU.S. Navy - Office of Naval Research NDSEG Graduate FellowshipMaryland Procurement Office Contract MDA904-93-C-418

Genetic variants in the MRPS30 region and postmenopausal breast cancer risk

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Advanced Telecommunications and Signal Processing Program

Contains an introduction and reports on seven research projects.Advanced Telecommunications Research ProgramAT&T FellowshipGEM FellowshipU.S. Federal Bureau of InvestigationLucent Technologies FellowshipCharles S. Draper LaboratoryU.S. Navy - Office of Naval Research NDSEG Graduate Fellowshi

Fish and tetrapod communities across a marine to brackish salinity gradient in the Pennsylvanian (early Moscovian) Minto Formation of New Brunswick, Canada, and their palaeoecological and palaeogeographical implications

Euryhaline adaptations in Pennsylvanian vertebrates allowed them to inhabit the marine to freshwater spectrum. This is illustrated by new assemblages of fish and tetrapods from the early Moscovian Minto Formation of New Brunswick, Canada. Fish include chondrichthyans (xenacanthids and the enigmatic Ageleodus), acanthodians (gyracanthids and acanthodiforms), sarcopterygians (rhizodontids, megalichthyids and dipnoans), and actinopterygians (eurynotiforms). Tetrapods include small- to medium-sized, and largely aquatic, stem tetrapods (colosteids) and anthracosaurs (embolomeres). A key finding is that the parautochthonous fossil assemblages are preserved across a salinity gradient, with diversity (measured by the Simpson Index) declining from open marine environments, through brackish embayments, and reaching a nadir in tidal estuaries. Chondrichthyans dominate the entire salinity spectrum (65% of fossils), a distribution that demonstrates a euryhaline mode of life, and one large predatory chondrichthyan, Orthacanthus, may have practised filial cannibalism in coastal nurseries because its heteropolar coprolites contain juvenile xenacanthid teeth. In contrast, other fish communities were more common in open marine settings while tetrapods were more common in coastal brackish waters. While all these faunas were also likely to have been euryhaline, their osmoregulation was, perhaps, less versatile. The demonstration of widespread euryhalinity among fish and aquatic tetrapods explains why Pennsylvanian faunas generally show a cosmopolitan biogeography because taxa were able to disperse via seaways. It also resolves the paradox of enriched strontium isotopic signatures observed in these faunas because organisms would have been, at times, exposed to continental water bodies as well. Therefore, our new findings contribute to the long-running debate about the ecology of Pennsylvanian fishes and tetrapods

Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity

Prosurvival Bcl-2–like proteins, like Bcl-w, are thought to function on organelles such as the mitochondrion and to be targeted to them by their hydrophobic COOH-terminal domain. We unexpectedly found, however, that the membrane association of Bcl-w was enhanced during apoptosis. In healthy cells, Bcl-w was loosely attached to the mitochondrial membrane, but it was converted into an integral membrane protein by cytotoxic signals that induce binding of BH3-only proteins, such as Bim, or by the addition of BH3 peptides to lysates. As the structure of Bcl-w has revealed that its COOH-terminal domain occupies the hydrophobic groove where BH3 ligands bind, displacement of that domain by a BH3 ligand would displace the hydrophobic COOH-terminal residues, allowing their insertion into the membrane. To determine whether BH3 ligation is sufficient to induce the enhanced membrane affinity, or to render Bcl-w proapoptotic, we mimicked their complex by tethering the Bim BH3 domain to the NH2 terminus of Bcl-w. The chimera indeed bound avidly to membranes, in a fashion requiring the COOH-terminal domain, but neither promoted nor inhibited apoptosis. These results suggest that ligation of a proapoptotic BH3-only protein alters the conformation of Bcl-w, enhances membrane association, and neutralizes its survival function