Short Subjects: The Paperless Office: Hope for the Future or a Grand Illusion?

Despite this early promise of the paperless office, the volume of paper in corporate offices continues to grow annually at alarming rates. Advances in technology have not eliminated paper from the office environment but have actually increased the amount of paper which is generated. Paperwork continues to be the largest overhead expense in business today

The Prostaglandin F Synthase Activity of the Human Aldose Reductase AKR1B1 Brings New Lenses to Look at Pathologic Conditions

Prostaglandins are important regulators of female reproductive functions to which aldose reductases exhibiting hydroxysteroid dehydrogenase activity also contribute. Our work on the regulation of reproductive function by prostaglandins (PGs), lead us to the discovery that AKR1B5 and later AKR1B1were highly efficient and physiologically relevant PGF synthases. PGE2 and PGF2α are the main prostanoids produced in the human endometrium and proper balance in their relative production is important for normal menstruation and optimal fertility. Recent evidence suggests that PGE2/EP2 and PGF2α/FP may constitute a functional dyad with physiological relevance comparable to the prostacyclin-thromboxane dyad in the vascular system. We have recently reported that AKR1B1 was expressed and modulated in association with PGF2α production in response to IL-1β in the human endometrium. In the present study, we show that the human AKR1B1 (gene ID: 231) also known as ALDR1 or ALR2 is a functional PGF2α synthase in different models of living cells and tissues. Using human endometrial cells, prostate, and vascular smooth muscle cells, cardiomyocytes and endothelial cells we demonstrate that IL-1β is able to up regulate COX-2 and AKR1B1 proteins as well as PGF2α production under normal glucose concentrations. We show that the promoter activity of AKR1B1 gene is increased by IL-1β particularly around the multiple stress response region containing two putative antioxidant response elements adjacent to TonE and AP1. We also show that AKR1B1 is able to regulate PGE2 production through PGF2α acting on its FP receptor and that aldose reductase inhibitors like alrestatin, Statil (ponalrestat), and EBPC exhibit distinct and characteristic inhibition of PGF2α production in different cell models. The PGF synthase activity of AKR1B1 represents a new and important target to regulate ischemic and inflammatory responses associated with several human pathologies

The spindle position checkpoint is coordinated by the Elm1 kinase

Localization and activation of Elm1 at the bud neck coordinates SPC activity with mother–daughter polarity during cell division

Advances in gene therapy for muscular dystrophies

Duchenne muscular dystrophy (DMD) is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments

Progress in muscular dystrophy research with special emphasis on gene therapy

Duchenne muscular dystrophy (DMD) is an X-linked, progressive muscle-wasting disease caused by mutations in the DMD gene. Since the disease was described by physicians in the 19th century, information about the subject has been accumulated. One author (Sugita) was one of the coworkers who first reported that the serum creatine kinase (CK) level is elevated in progressive muscular dystrophy patients. Even 50 years after that first report, an elevated serum CK level is still the most useful marker in the diagnosis of DMD, a sensitive index of the state of skeletal muscle, and useful to evaluate therapeutic effects. In the latter half of this article, we describe recent progress in the therapy of DMD, with an emphasis on gene therapies, particularly exon skipping

Representing Fitness Landscapes by Valued Constraints to Understand the Complexity of Local Search

Local search is widely used to solve combinatorial optimisation problems and to model biological evolution, but the performance of local search algorithms on different kinds of fitness landscapes is poorly understood. Here we introduce a natural approach to modelling fitness landscapes using valued constraints. This allows us to investigate minimal representations (normal forms) and to consider the effects of the structure of the constraint graph on the tractability of local search. First, we show that for fitness landscapes representable by binary Boolean valued constraints there is a minimal necessary constraint graph that can be easily computed. Second, we consider landscapes as equivalent if they allow the same (improving) local search moves; we show that a minimal normal form still exists, but is NP-hard to compute. Next we consider the complexity of local search on fitness landscapes modelled by valued constraints with restricted forms of constraint graph. In the binary Boolean case, we prove that a tree-structured constraint graph gives a tight quadratic bound on the number of improving moves made by any local search; hence, any landscape that can be represented by such a model will be tractable for local search. We build two families of examples to show that both the conditions in our tractability result are essential. With domain size three, even just a path of binary constraints can model a landscape with an exponentially long sequence of improving moves. With a treewidth two constraint graph, even with a maximum degree of three, binary Boolean constraints can model a landscape with an exponentially long sequence of improving moves