Systems Biology of the Clock in Neurospora crassa

A model-driven discovery process, Computing Life, is used to identify an ensemble of genetic networks that describe the biological clock. A clock mechanism involving the genes white-collar-1 and white-collar-2 (wc-1 and wc-2) that encode a transcriptional activator (as well as a blue-light receptor) and an oscillator frequency (frq) that encodes a cyclin that deactivates the activator is used to guide this discovery process through three cycles of microarray experiments. Central to this discovery process is a new methodology for the rational design of a Maximally Informative Next Experiment (MINE), based on the genetic network ensemble. In each experimentation cycle, the MINE approach is used to select the most informative new experiment in order to mine for clock-controlled genes, the outputs of the clock. As much as 25% of the N. crassa transcriptome appears to be under clock-control. Clock outputs include genes with products in DNA metabolism, ribosome biogenesis in RNA metabolism, cell cycle, protein metabolism, transport, carbon metabolism, isoprenoid (including carotenoid) biosynthesis, development, and varied signaling processes. Genes under the transcription factor complex WCC ( = WC-1/WC-2) control were resolved into four classes, circadian only (612 genes), light-responsive only (396), both circadian and light-responsive (328), and neither circadian nor light-responsive (987). In each of three cycles of microarray experiments data support that wc-1 and wc-2 are auto-regulated by WCC. Among 11,000 N. crassa genes a total of 295 genes, including a large fraction of phosphatases/kinases, appear to be under the immediate control of the FRQ oscillator as validated by 4 independent microarray experiments. Ribosomal RNA processing and assembly rather than its transcription appears to be under clock control, suggesting a new mechanism for the post-transcriptional control of clock-controlled genes

Reversal of childhood idiopathic scoliosis in an adult, without surgery: a case report and literature review

<p>Abstract</p> <p>Background</p> <p>Some patients with mild or moderate thoracic scoliosis (Cobb angle <50-60 degrees) suffer disproportionate impairment of pulmonary function associated with deformities in the sagittal plane and reduced flexibility of the spine and chest cage. Long-term improvement in the clinical signs and symptoms of childhood onset scoliosis in an adult, without surgical intervention, has not been documented previously.</p> <p>Case presentation</p> <p>A diagnosis of thoracic scoliosis (Cobb angle 45 degrees) with pectus excavatum and thoracic hypokyphosis in a female patient (DOB 9/17/52) was made in June 1964. Immediate spinal fusion was strongly recommended, but the patient elected a daily home exercise program taught during a 6-week period of training by a physical therapist. This regime was carried out through 1992, with daily aerobic exercise added in 1974. The Cobb angle of the primary thoracic curvature remained unchanged. Ongoing clinical symptoms included dyspnea at rest and recurrent respiratory infections. A period of multimodal treatment with clinical monitoring and treatment by an osteopathic physician was initiated when the patient was 40 years old. This included deep tissue massage (1992-1996); outpatient psychological therapy (1992-1993); a daily home exercise program focused on mobilization of the chest wall (1992-2005); and manipulative medicine (1994-1995, 1999-2000). Progressive improvement in chest wall excursion, increased thoracic kyphosis, and resolution of long-standing respiratory symptoms occurred concomitant with a >10 degree decrease in Cobb angle magnitude of the primary thoracic curvature.</p> <p>Conclusion</p> <p>This report documents improved chest wall function and resolution of respiratory symptoms in response to nonsurgical approaches in an adult female, diagnosed at age eleven years with idiopathic scoliosis.</p

External Learning Opportunities and the Diffusion of Process Innovations to Small Firms: The Case of Programmable Automation

In this chapter, we are concerned with explaining which types of firms have failed to adopt well-known improvements in process technology. This problem has, of course, been the underlying concern of all studies of diffusion “to rationalize why, if a new technology is superior, it is not taken up by all potential adopters” (Stoneman, 1983). Drawing on various theoretical perspectives, we identify a number of different barriers to adoption. With data collected from a 1987 nationally representative sample of US establishments in 21 metal-working and machinery manufacturing industries, we then construct a multivariate logistic regression model to empirically test for the effects of these factors on the likelihood of adoption of a particular process innovation, namely programmable automation (PA) machine tools

Calcium dependence of prejunctional inhibitory effects of adenosine and acetylcholine on adrenergic neurotransmission in canine saphenous veins

In canine blood vessels acetylcholine and adenosine inhibit the exocytotic release of norepinephrine during nerve stimulation. The present experiments were designed to determine the Ca2+ dependence of these prejunctional effects. Segments of canine saphenous veins were mounted for isometric tension recording in organ chambers filled with Krebs-Ringer or Tyrode solution. Altering the Ca2+ concentration of the solution did not affect the inhibitory response to acetylcholine during nerve stimulation; the prejunctional potency of adenosine was inversely related to the Ca2+ concentration of the bath content. The ionophore A23187 caused contractions which were inhibited by phentolamine, verapamil, and adenosine but were augmented by acetylcholine. Helical strips of dog saphenous veins were incubated in [3H]norepinephrine and mounted for superfusion and determination of [3H]norepinephrine in the superfusate. A23187 increased the overflow of [3H]norepinephrine. Acetylcholine augmented this efflux; by contrast adenosine decreased the release induced by the ionophore. The results demonstrate that the prejunctional effect of acetylcholine was not due to direct interference with the availability of Ca2+ for the electro-secretory process in adrenergic nerve terminals and suggest that adenosine interferes either with the coupling role of the activator ion or its extrusion from the neuroplasm.link_to_subscribed_fulltex

Breast Implants: the Good, the Bad and the Ugly

This advanced review will discuss the history of implants used in breast reconstruction and augmentation, the most frequently performed plastic surgery today. Currently, only silicone rubber-based silica nanocomposite implants are available in the United States. The most prevalent issues involving breast implants include capsular contracture, gel bleed, implant rupture, and infection. In the past, studies have also been reported which linked breast implants to increased incidence of systemic diseases such as autoimmune disease, various forms of cancer, and psychological disease. The goal of this review is to survey the literature from the perspective of material science. It is also largely unnoticed that nanotechnology is involved: the silicone rubber shell is reinforced with nanosilica so implants appear to be homogeneous and crystal clear. We are hoping that this review will contribute to a better understanding of the controversial issues and motivate material scientists and medical doctors to work together to develop alternatives based on new nanotechnology for the women who opt for a device made of synthetic materials. WIREs Nanomed Nanobiotechnol 2012, 4:153–168. doi: 10.1002/wnan.16