De novo variation in bipolar disorder.

Bipolar disorder (BD) is a common, highly heritable disorder that affects 1-2% of the world's population. To date, most genetic studies of BD have focused on common gene variation, and while robustly associated loci have been identified, a substantial proportion of the heritability remains missing and could be partially attributable to rare variation. In this study, we apply a de novo paradigm in BD to identify newly arisen variants that have yet to undergo natural selection and may represent highly pathogenic variants.

ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy.

Diseases of ectopic calcification of the vascular wall range from lethal orphan diseases such as generalized arterial calcification of infancy (GACI), to common diseases such as hardening of the arteries associated with aging and calciphylaxis of chronic kidney disease (CKD). GACI is a lethal orphan disease in which infants calcify the internal elastic lamina of their medium and large arteries and expire of cardiac failure as neonates, while calciphylaxis of CKD is a ubiquitous vascular calcification in patients with renal failure. Both disorders are characterized by vascular Mönckeburg's sclerosis accompanied by decreased concentrations of plasma inorganic pyrophosphate (PPi).

Molecular basis of purinergic signal metabolism by ectonucleotide pyrophosphatase/phosphodiesterases 4 and 1 and implications in stroke.

NPP4 is a type I extracellular membrane protein on brain vascular endothelium inducing platelet aggregation via the hydrolysis of Ap3A, whereas NPP1 is a type II extracellular membrane protein principally present on the surface of chondrocytes that regulates tissue mineralization. To understand the metabolism of purinergic signals resulting in the physiologic activities of the two enzymes, we report the high resolution crystal structure of human NPP4 and explore the molecular basis of its substrate specificity with NPP1. Both enzymes cleave Ap3A, but only NPP1 can hydrolyze ATP.

Loss and grief in the workplace: the challenge of leadership.

There is no part of human existence that loss and grief do not reach, and the workplace is no exception to this. This article is therefore concerned with some of the implications of loss and grief in work settings in general and for workplace leaders in particular. By way of example, it explores in particular the needs of bereaved caregivers returning to work and the potential for stigma to emerge in relation to employment and bereavement.

Risk factors for elevated blood lead levels among African refugee children in New Hampshire, 2004.

Objectives: Surveillance blood lead screening of refugee children resettled in Manchester, NH, in 2004 revealed that 39 (42%) of 92 children had elevated levels (>or=10 microg/dL) after resettlement. Furthermore, 27/92 children (29%) had nonelevated screening blood lead levels on arrival (BLL1) but had elevated follow-up blood lead levels 3-6 months after settlement (BLL2). The main objective was to identify risk factors for increasing lead levels among refugee children after resettlement in Manchester in 2004.

Bacterial peptidoglycan-associated lipoprotein: a naturally occurring toll-like receptor 2 agonist that is shed into serum and has synergy with lipopolysaccharide.

Sepsis is initiated by interactions between microbial products and host inflammatory cells. Toll-like receptors (TLRs) are central innate immune mediators of sepsis that recognize different components of microorganisms. Peptidoglycan-associated lipoprotein (PAL) is a ubiquitous gram-negative bacterial outer-membrane protein that is shed by bacteria into the circulation of septic animals.

Murein lipoprotein, peptidoglycan-associated lipoprotein, and outer membrane protein A are present in purified rough and smooth lipopolysaccharides.

Purified lipopolysaccharides (LPSs) have been used for many decades to gain insight into processes that occur during sepsis. Previous studies indicate that purified LPSs often contain trace protein contaminants. To identify protein contaminants of LPSs, we performed immunoblotting using, as antigen, purified LPS from various species of bacteria and, as primary antibodies, anti-murein lipoprotein (MLP), peptidoglycan-associated lipoprotein (PAL), and outer membrane protein A (OmpA).

Bacterial peptidoglycan-associated lipoprotein is released into the bloodstream in gram-negative sepsis and causes inflammation and death in mice.

Gram-negative bacterial sepsis commonly causes organ dysfunction and death in humans. Although circulating bacterial toxins trigger inflammation in sepsis, little is known about the composition of bacterial products released into the blood during sepsis or the contribution of various bacterial components to the pathogenesis of sepsis. We have shown that diverse Gram-negative bacteria release bacterial peptidoglycan-associated lipoprotein (PAL) into serum.

Outer membrane protein A, peptidoglycan-associated lipoprotein, and murein lipoprotein are released by Escherichia coli bacteria into serum.

Complexes containing lipopolysaccharide (LPS) and three outer membrane proteins (OMPs) are released by gram-negative bacteria incubated in human serum and into the circulation in an experimental model of sepsis. The same OMPs are bound by immunoglobulin G (IgG) in the cross-protective antiserum raised to Escherichia coli J5 (anti-J5 IgG). This study was performed to identify the three OMPs.

Release of gram-negative outer-membrane proteins into human serum and septic rat blood and their interactions with immunoglobulin in antiserum to Escherichia coli J5.

Prior studies indicate that 3 bacterial outer-membrane proteins (OMPs) are released into serum associated with lipopolysaccharide (LPS) and are bound by IgG in antiserum to Escherichia coli J5 (anti-J5 IgG). The present studies analyzed the interaction of the OMPs with anti-J5 IgG and evaluated their release in an infected burn model of gram-negative sepsis. Affinity purification studies were performed on filtrates of bacteria incubated in human serum and plasma from rats with sepsis by use of O chain-specific anti-LPS IgG and anti-J5 IgG.