Discovery of nonautonomous modulators of activated Ras.

Communication between mesodermal cells and epithelial cells is fundamental to normal animal development and is frequently disrupted in cancer. However, the genes and processes that mediate this communication are incompletely understood. To identify genes that mediate this communication and alter the proliferation of cells with an oncogenic Ras genotype, we carried out a tissue-specific genome-wide RNAi screen in Caenorhabditis elegans animals bearing a let-60(n1046gf) (RasG13E) allele.

The glucose-sensing transcription factor MLX balances metabolism and stress to suppress apoptosis and maintain spermatogenesis.

Male germ cell (GC) production is a metabolically driven and apoptosis-prone process. Here, we show that the glucose-sensing transcription factor (TF) MAX-Like protein X (MLX) and its binding partner MondoA are both required for male fertility in the mouse, as well as survival of human tumor cells derived from the male germ line. Loss of Mlx results in altered metabolism as well as activation of multiple stress pathways and GC apoptosis in the testes.

Perihamate-Peripisiform-Transtriquetrum Axial Ulnar Fracture Dislocation of the Hand With an Associated Perilunate Injury.

Axial fracture-dislocations are rare, high-energy injuries. Although cases of axial fracture-dislocations are reported in the literature, there are few reports of a patient who suffered a combined perilunate injury with an ulnar axial dislocation of the hand. This case report describes the anatomical injury and operative treatment of a patient who suffered this injury and discusses the importance of associated soft tissue management.

Human Genetic Determinants of Viral Diseases.

Much progress has been made in the identification of specific human gene variants that contribute to enhanced susceptibility or resistance to viral diseases. Herein we review multiple discoveries made with genome-wide or candidate gene approaches that have revealed significant insights into virus-host interactions. Genetic factors that have been identified include genes encoding virus receptors, receptor-modifying enzymes, and a wide variety of innate and adaptive immunity-related proteins.

Discovery of Stromal Regulatory Networks that Suppress Ras-Sensitized Epithelial Cell Proliferation.

Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation.

Mouse BAZ1A (ACF1) is dispensable for double-strand break repair but is essential for averting improper gene expression during spermatogenesis.

ATP-dependent chromatin remodelers control DNA access for transcription, recombination, and other processes. Acf1 (also known as BAZ1A in mammals) is a defining subunit of the conserved ISWI-family chromatin remodelers ACF and CHRAC, first purified over 15 years ago from Drosophila melanogaster embryos. Much is known about biochemical properties of ACF and CHRAC, which move nucleosomes in vitro and in vivo to establish ordered chromatin arrays.

Temperature and length scale dependence of solvophobic solvation in a single-site water-like liquid.

The temperature and length scale dependence of solvation properties of spherical hard solvophobic solutes is investigated in the Jagla liquid, a simple liquid that consists of particles interacting via a spherically symmetric potential combining a hard core repulsion and a longer ranged soft core interaction, yet exhibits water-like anomalies. The results are compared with equivalent calculations for a model of a typical atomic liquid, the Lennard-Jones potential, and with predictions for hydrophobic solvation in water using the cavity equation of state and the extended simple point charge model. We find that the Jagla liquid captures the qualitative thermodynamic behavior of hydrophobic hydration as a function of temperature for both small and large length scale solutes.

Predicting cavity formation free energy: how far is the Gaussian approximation valid?

We examine the range of validity of the Gaussian model for various water-like liquids whose intermolecular potentials differ from SPC/E water, to provide insight into the temperature dependence of the hydrophobic effect for small hard sphere solutes. We find that low compressibility liquids that have more close-packed network structures show much larger deviations from Gaussian fluctuations for low or zero occupancies relative to more compressible fluids with more open networks. Water appears to be a unique molecular fluid in possessing equilibrium density fluctuations that are faithfully described by the Gaussian theory.

Selective killing of K-ras mutant cancer cells by small molecule inducers of oxidative stress.

Activating K-RAS mutations are the most frequent oncogenic mutations in human cancer. Numerous downstream signaling pathways have been shown to be deregulated by oncogenic K-ras. However, to date there are still no effective targeted therapies for this genetically defined subset of patients.

Mouse TRIP13/PCH2 is required for recombination and normal higher-order chromosome structure during meiosis.

Accurate chromosome segregation during meiosis requires that homologous chromosomes pair and become physically connected so that they can orient properly on the meiosis I spindle. These connections are formed by homologous recombination closely integrated with the development of meiosis-specific, higher-order chromosome structures. The yeast Pch2 protein has emerged as an important factor with roles in both recombination and chromosome structure formation, but recent analysis suggested that TRIP13, the mouse Pch2 ortholog, is not required for the same processes.

Two genes in Arabidopsis thaliana encoding GDP-L-galactose phosphorylase are required for ascorbate biosynthesis and seedling viability.

Plants synthesize ascorbate from guanosine diphosphate (GDP)-mannose via L-galactose/L-gulose, although uronic acids have also been proposed as precursors. Genes encoding all the enzymes of the GDP-mannose pathway have previously been identified, with the exception of the step that converts GDP-L-galactose to L-galactose 1-P. We show that a GDP-L-galactose phosphorylase, encoded by the Arabidopsis thaliana VTC2 gene, catalyses this step in the ascorbate biosynthetic pathway.

A quantitative trait loci analysis of zinc hyperaccumulation in Arabidopsis halleri.

The mechanisms of metal hyperaccumulation are still not understood, so we conducted a quantitative trait locus (QTL) analysis of zinc (Zn) hyperaccumulation in Arabidopsis halleri, in a cross between this and its sister species, A. petraea, in order to determine the number and approximate location of the genomic regions significantly contributing to this adaptation. An F2 cross between the two species was made, and the leaf Zn concentration of 92 individuals was measured at both low (10 microm) and high (100 microm) Zn concentrations.

Sprouty-2 regulates oncogenic K-ras in lung development and tumorigenesis.

Somatic activation of Ras occurs frequently in human cancers, including one-third of lung cancers. Activating Ras mutations also occur in the germline, leading to complex developmental syndromes. The precise mechanism by which Ras activation results in human disease is uncertain.

Comparison of gene expression in segregating families identifies genes and genomic regions involved in a novel adaptation, zinc hyperaccumulation.

One of the challenges of comparative genomics is to identify specific genetic changes associated with the evolution of a novel adaptation or trait. We need to be able to disassociate the genes involved with a particular character from all the other genetic changes that take place as lineages diverge. Here we show that by comparing the transcriptional profile of segregating families with that of parent species differing in a novel trait, it is possible to narrow down substantially the list of potential target genes.

Arabidopsis thaliana VTC4 encodes L-galactose-1-P phosphatase, a plant ascorbic acid biosynthetic enzyme.

In plants, a proposed ascorbate (vitamin C) biosynthesis pathway occurs via GDP-D-mannose (GDP-D-Man), GDP-L-galactose (GDP-L-Gal), and L-galactose. However, the steps involved in the synthesis of L-Gal from GDP-L-Gal in planta are not fully characterized. Here we present evidence for an in vivo role for L-Gal-1-P phosphatase in plant ascorbate biosynthesis.

The computer in office medical practice.

There will continue to be change and evolution in the medical office environment. As voice recognition systems continue to improve, instant creation of office notes with the absence of dictation may be commonplace. As medical and computer technology evolves, we must continue to evaluate the many new computer systems that can assist us in our clinical office practice.

Four-year follow-up results of lumbar spine arthrodesis using the Bagby and Kuslich lumbar fusion cage.

Study Design: This was a prospective multicenter clinical trial of a lumbar interbody fusion cage with a minimum of 4 years' follow-up.

Objectives: To determine whether the early positive clinical results in fusions with lumbar cages, such as the Bagby and Kuslich (BAK) cage, are maintained beyond 2 years.

Summary Of Background Data: Threaded cages have been used increasingly for the treatment of symptomatic degenerative intervertebral disc disease.

Tomography versus computed tomography for assessing step off in intraarticular distal radial fractures.

Computed tomography scans have supplanted conventional tomography for many applications and often are considered the imaging study of choice for assessing intraarticular distal radial fractures. Concern about cost containment in healthcare delivery prompts the question of whether the two studies provide comparable information and at what cost. Common intraarticular distal radial fractures were created in 12 lightly embalmed cadaveric specimens.

The Bagby and Kuslich method of lumbar interbody fusion. History, techniques, and 2-year follow-up results of a United States prospective, multicenter trial.

Study Design: A prospective, multicenter trial of the Bagby and Kuslich method of lumbar interbody stabilization for chronic discogenic low back pain, with follow-up evaluation at 3 months, 6 months, and yearly thereafter, with independent radiographic analysis.

Objectives: To report the history of development, the surgical techniques, and results of the Bagby and Kuslich method when used to manage discogenic pain of the lumbar spine in humans.

Summary Of Background Data: Disabling chronic low back pain frequently is resistant to conservative management.

MRI of the Stener lesion.

Objective: To assess the utility of MR in detecting surgically induced Stener lesions (displaced thumb ulnar collateral ligaments) in cadaveric models.

Design: Six cadaver thumbs had ulnar collateral ligament (UCL) tears created surgically. MR examinations (2D STIR and 3D GRASS) were performed identically on all specimens both before displacement (non-Stener) and after displacement (Stener lesion) of the UCL.

Acceleration of ventricular tachycardia following propofol in a patient with heterotopic cardiac transplant. Cardioversion of ventricular tachycardia in the native heart.

A 52-year-old Caucasian male underwent heterotopic cardiac transplant and subsequently developed a ventricular tachycardia in his native heart. The arrhythmia was successfully treated by cardioversion, despite an increased rate associated with induction of anaesthesia with propofol. The method of synchronised cardioversion is described and a possible hypothesis for the acceleration of ventricular tachycardia following induction is discussed.