Multiple Roles of Integrin-Linked Kinase in Epidermal Development, Maturation and Pigmentation Revealed by Molecular Profiling

Integrin-linked kinase (ILK) is an important scaffold protein that mediates a variety of cellular responses to integrin stimulation by extracellular matrix proteins. Mice with epidermis-restricted inactivation of the Ilk gene exhibit pleiotropic phenotypic defects, including impaired hair follicle morphogenesis, reduced epidermal adhesion to the basement membrane, compromised epidermal integrity, as well as wasting and failure to thrive leading to perinatal death. To better understand the underlying molecular mechanisms that cause such a broad range of alterations, we investigated the impact of Ilk gene inactivation on the epidermis transcriptome. Microarray analysis showed over 700 differentially regulated mRNAs encoding proteins involved in multiple aspects of epidermal function, including keratinocyte differentiation and barrier formation, inflammation, regeneration after injury, and fundamental epidermal developmental pathways. These studies also revealed potential effects on genes not previously implicated in ILK functions, including those important for melanocyte and melanoblast development and function, regulation of cytoskeletal dynamics, and homeobox genes. This study shows that ILK is a critical regulator of multiple aspects of epidermal function and homeostasis, and reveals the previously unreported involvement of ILK not only in epidermal differentiation and barrier formation, but also in melanocyte genesis and function

A case of minimal change nephrotic syndrome with immunoglobulin A nephropathy transitioned to focal segmental glomerulosclerosis

A 50-year-old woman with a 1-month history of lower extremity edema and a 5 kg weight increase was admitted to our hospital with suspected nephrotic syndrome in October 1999. Urine protein level was 3.5 g per day, 10-15 erythrocytes in urine per high-power field, and serum albumin level 2.5 g/dl. Furthermore, an accumulation of pleural effusion was confirmed by chest X-ray. The results of a renal biopsy indicated slight mesangial proliferation in the glomeruli by light microscopy, and an immunofluorescence study confirmed the deposition of immunoglobulin (Ig) A and C3 in the mesangial area. Diffuse attenuation of foot processes and dense deposits in the mesangial area were observed by electron microscopy. Treatment with 40 mg/day of prednisolone was effective, and proteinuria was negative 1 month later. Because of this course, we diagnosed minimal change nephrotic syndrome complicated by mild-proliferative IgA nephropathy. In November 2000, there was a relapse of nephrotic syndrome, which was believed to be induced by an influenza vaccination, but response to increased steroid treatment was favorable, and proteinuria disappeared on day 13 of steroid increase. A second relapse in May 2001, showed steroid resistance with renal insufficiency, and an increase in the selectivity index to 0.195. Light microscopy revealed focal sclerotic lesions of the glomeruli, and an immunofluorescence study revealed attenuation of mesangial IgA and C3 deposition. These findings led to the diagnosis that minimal change nephrotic syndrome had transitioned to focal segmental glomerulosclerosis, whereby mesangial IgA deposition was reduced by immunosuppressive treatment. Subsequently, her renal function gradually worsened to the point of end-stage renal failure by 27 months after the second relapse of nephrotic syndrome

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe