Functional Inactivation of Drosophila GCK Orthologs Causes Genomic Instability and Oxidative Stress in a Fly Model of MODY-2

Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.     

A 0.18-/spl mu/m SiGe BiCMOS receiver and transmitter chipset for SONET OC-768 transmission systems

A 43-Gb/s receiver (Rx) and transmitter (Tx) chip set for SONET OC-768 transmission systems is reported. Both ICs are implemented in a 0.18-/spl mu/m SiGe BiCMOS technology featuring 120-GHz f/sub T/ and 100 GHz f/sub max/. The Rx includes a limiting amplifier, a half-rate clock and data recovery unit, a 1:4 demultiplexer, a frequency acquisition aid, and a frequency lock detector. Input sensitivity for a bit-error rate less than 10/sup -9/ is 40 mV and jitter generation better than 230 fs rms. The IC dissipates 2.4 W from a -3.6-V supply voltage. The Tx integrates a half-rate clock multiplier unit with a 4:1 multiplexer. Measured clock jitter generation is better than 170 fs rms. The IC consumes 2.3 W from a -3.6-V supply voltage.     

Treatment of radiation-induced nervous system injury with heparin and warfarin

When radiation is used to treat nervous system cancer, exposure of adjacent normal nervous system tissue is unavoidable, and radiation-induced injury may occur. Acute injury is usually mild and transient, but late forms of radiation-induced nervous system injury are usually progressive and debilitating. Treatment with corticosteroids, surgery, and antioxidants is often ineffective. We treated 11 patients with late radiation-induced nervous system injuries (eight with cerebral radionecrosis, one with a myelopathy, and two with plexopathies, all unresponsive to dexamethasone and prednisone) with full anticoagulation. Some recovery of function occurred in five of the eight patients with cerebral radionecrosis, and all the patients with myelopathy or plexopathy. Anticoagulation was continued for 3 to 6 months. In one patient with cerebral radionecrosis, symptoms recurred after discontinuation of anticoagulation and disappeared again after reinstitution of treatment. We hypothesize that anticoagulation may arrest and reverse small-vessel endothelial injury--the fundamental lesion of radiation necrosis--and produce clinical improvement in some patients.     

Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors

The majority of pituitary tumors are of monoclonal origin; however, the molecular basis for their formation is poorly understood. Somatic mutations in the alpha-subunit of the GTP-binding protein, Gs alpha (gsp oncogene) have been found in about one third of GH-secreting tumors. Mutations in another alpha-subunit of a GTP-binding protein, Gi2 alpha (gip mutations) have been described in other endocrine tumors. In this study, we examined 21 nonfunctioning pituitary tumors and 4 macroprolactinomas for gsp mutations and 27 nonfunctioning tumors and 4 macroprolactinomas for gip mutations. Using the polymerase chain reaction and denaturing gradient gel electrophoresis, 2 nonfunctioning pituitary tumors displayed migration abnormalities when the Gs alpha-gene was analyzed. Sequence analysis of these abnormally migrating polymerase chain reaction products revealed two previously known gsp mutations: arginine at codon 201 altered to cysteine, and glutamine at codon 227 changed to leucine. No gip mutations could be demonstrated. These findings emphasize the monoclonal origin of nonfunctioning pituitary tumors and suggest that cAMP may play a role in tumorigenesis of nonfunctioning pituitary tumors.     

Psychosocial factors in sunbathing and sunscreen use.

Interviewed 120 sunbathing and nonsunbathing beachgoers about their health practices, knowledge about skin cancer, moods, and social rewards obtained through sunbathing. Ss also completed personality questionnaires. Data were considered using a theoretical perspective combining aspects of health belief, social influence, social learning, and risk-taking models. Results indicate that sunbathing was related to having a positive attitude toward risk taking, having little knowledge about skin cancer, reporting a relaxed mood, having friends who sunbathe, and engaging in activities related to maintaining a positive physical appearance. Sunscreen use was related to sex, having knowledge about skin cancer, knowing people who have had cancer, and reporting high levels of anxiety. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mutual coupling of two collocated orthogonally oriented circular thin-wire loops

Coupling between two collocated orthogonal circular thin-wire loops is analyzed in this paper. Two coupled integral equations for the loop currents are derived and their solution in general form is found in terms of Fourier series. An analytical expression for currents induced through the mutual coupling is obtained for the case when all loop current harmonics higher than first can be ignored. It is found that strong coupling can exist for all loop current harmonics, except for the fundamental. It is also found that coupling for orthogonal collocated loop antennas depends on the relative locations of the loop terminals.     

First-class extents

Adding environments as first-class entities to a language can greatly enhance its expressiveness. But first-class environments rely on identifiers, the syntax of variables, and thus do not mesh well with lexically-scoped languages. We present first-class extents as an alternative. First-class extents are founded upon lexical variables with dynamic extent. They are defined directly on the variables themselves rather than on their syntax. They therefore do not cause variable name capturing problems that plague first-class environments. Moreover, distinguishing variables from locations allows first-class extents to be orthogonal to imperative and control features.     

Family, peer, and neighborhood influences on academic achievement among African-American adolescents: one-year prospective effects

Using a 1-year prospective design, this study examined the influence of family status variables (family income, parental education, family structure), parenting variables (maternal support and restrictive control), peer support, and neighborhood risk on the school performance of 120 African American junior high school students. In addition to main effects of these variables, neighborhood risk was examined as a moderator of the effects of parenting and peer support. Family status variables were not predictive of adolescent school performance as indexed by self-reported grade point average. Maternal support at Time 1 was prospectively related to adolescent grades at Time 2. Neighborhood risk was related to lower grades, while peer support predicted better grades in the prospective analyses. Neighborhood risk also moderated the effects of maternal restrictive control and peer support on adolescent grades in prospective analyses. These findings highlight the importance of an ecological approach to the problem of academic underachievement within the African American Community.     

Playing with pets and longevity among older people.

Models of the relations between contact with pets and better health are examined in an archival prospective study using data derived from the longitudinal study initiated by Terman in 1921 (current N?=?343 men, 300 women) . In survival analyses of documented longevity, playing with pets in 1977 (M age?=?67 years) was not associated with mortality risk through 1991 for the total sample nor for those who were unmarried or those who were less satisfied with their human relationships. Playing with pets was not associated with health-prone attributes or healthy behaviors such as personality, social ties, education, and smoking. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Serum IgA antibodies from patients with coeliac disease react strongly with human brain blood-vessel structures

BACKGROUND: Our objective was to determine the possible presence of IgA antibodies directed against human central nervous system (CNS) structures in sera from coeliac disease (CD) patients. METHODS: Serum samples were collected from 4 patients with active CD on a gluten-containing diet, 11 biopsy-proven CD patients on a gluten-free diet (GFD), and 52 non-coeliac gastrointestinal controls. In all patients IgA antigliadin antibody (AGA) titres were determined with enzyme-linked immunoassay (ELISA), and IgA antiendomysium antibodies (EMA) with indirect immunofluorescence on human umbilical cord. Cryostat sections of human brain occipital cortex were incubated with the patients' sera and subsequently labelled with anti-human IgA fluorescein conjugate. RESULTS: All sera from patients with active CD on a gluten-containing diet yielded positive results in both the IgG-AGA and EMA test and in indirect immunofluorescence on brain tissue, disclosing a strong fluorescence over blood-vessels structures. All sera from CD patients on a GFD and from non-coeliac gastrointestinal controls gave a negative result on both the EMA test and the immunofluorescence reaction on human brain. CONCLUSIONS: Sera from patients with active CD contain IgA antibodies that react with human brain vessel structures, giving intense fluorescence. These antibodies are not present in sera from coeliac patients on a GFD or non-coeliac controls. This finding might be involved in the abnormal nervous system manifestations frequently described in association with coeliac disease.