Transient neonatal diabetes mellitus with macroglossia diagnosed by methylation specific PCR (MS-PCR)

Transient neonatal diabetes mellitus (TNDM) has been associated with paternal uniparental isodisomy of chromosome 6, paternally inherited duplication of 6q24, or a methylation defect at a CpG island of the ZAC or HYMAI gene. We experienced a case of TNDM in which the patient presented with hyperglycemia, macroglossia, and intrauterine growth retardation, caused by a paternally derived HYMAI. An 18-day-old female infant was admitted to the hospital because of macroglossia and recurrent hyperglycemia. In addition to the macroglossia, she also presented with large fontanelles, micrognathia, and prominent eyes. Serum glucose levels were 200&amp&#59;#8211&#59;300 mg/dL and they improved spontaneously 2 days after admission. To identify the presence of a maternal methylated allele, bisulfite-treated genomic DNA from peripheral blood was prepared and digested with BssHII after polymerase chain reaction (PCR) amplification with methylation-specific HYMAI primers. PCR and restriction fragment length polymorphism analysis showed that the patient had only the paternal origin of the HYMA1 gene. TNDM is associated with a methylation defect in chromosome 6, suggesting that an imprinted gene on chromosome 6 is responsible for this phenotype

Self-control of epileptic seizures by nonpharmacological strategies

Despite the unpredictability of epileptic seizures, many patients report that they can anticipate seizure occurrence. Using certain alert symptoms (i.e., auras, prodromes, precipitant factors), patients can adopt behaviors to avoid injury during and after the seizure or may implement spontaneous cognitive and emotional strategies to try to control the seizure itself. From the patient's view point, potential means of enhancing seizure prediction and developing seizure control supports are seen as very important issues, especially when the epilepsy is drug-resistant. In this review, we first describe how some patients anticipate their seizures and whether this is effective in terms of seizure prediction. Secondly, we examine how these anticipatory elements might help patients to prevent or control their seizures and how the patient's neuropsychological profile, specifically parameters of perceived self-control (PSC) and locus of control (LOC), might impact these strategies and quality of life (QOL). Thirdly, we review the external supports that can help patients to better predict seizures. Finally, we look at nonpharmacological means of increasing perceived self-control and achieving potential reduction of seizure frequency (i.e., stress-based and arousal-based strategies). In the past few years, various approaches for detection and control of seizures have gained greater interest, but more research is needed to confirm a positive effect on seizure frequency as well as on QOL

Phosphoproteomic Profiling of In Vivo Signaling in Liver by the Mammalian Target of Rapamycin Complex 1 (mTORC1)

Our understanding of signal transduction networks in the physiological context of an organism remains limited, partly due to the technical challenge of identifying serine/threonine phosphorylated peptides from complex tissue samples. In the present study, we focused on signaling through the mammalian target of rapamycin (mTOR) complex 1 (mTORC1), which is at the center of a nutrient- and growth factor-responsive cell signaling network. Though studied extensively, the mechanisms involved in many mTORC1 biological functions remain poorly understood.We developed a phosphoproteomic strategy to purify, enrich and identify phosphopeptides from rat liver homogenates. Using the anticancer drug rapamycin, the only known target of which is mTORC1, we characterized signaling in liver from rats in which the complex was maximally activated by refeeding following 48 hr of starvation. Using protein and peptide fractionation methods, TiO(2) affinity purification of phosphopeptides and mass spectrometry, we reproducibly identified and quantified over four thousand phosphopeptides. Along with 5 known rapamycin-sensitive phosphorylation events, we identified 62 new rapamycin-responsive candidate phosphorylation sites. Among these were PRAS40, gephyrin, and AMP kinase 2. We observed similar proportions of increased and reduced phosphorylation in response to rapamycin. Gene ontology analysis revealed over-representation of mTOR pathway components among rapamycin-sensitive phosphopeptide candidates.In addition to identifying potential new mTORC1-mediated phosphorylation events, and providing information relevant to the biology of this signaling network, our experimental and analytical approaches indicate the feasibility of large-scale phosphoproteomic profiling of tissue samples to study physiological signaling events in vivo

The evolution of technology within a simple computer model. Complexity 11/5:pp-pp

New technologies are constructed from components that previously exist; and in turn these new technologies offer themselves as possible components – building blocks – for the construction of further new technologies. In this sense, technology (the collection of mechanical devices and methods available to a culture) builds itself out of itself. Thus in 1912 the amplifier circuit was constructed from the already existing triode vacuum tube in combination with other circuit components. The amplifier in turn made possible the oscillator, and this with other components made possible the heterodyne mixer; these components in conjunction with other standard ones went on to make possible continuous wave radio transmission and reception, which made possible radio broadcasting. In its collective sense, technology forms a set – a network – of elements from which novel elements can be constructed. And over time, this set builds out by bootstrapping itself from simple elements to more complicated ones, and from few building-block elements to many. In this paper we model this buildout of technology and examine its properties within a simple artificial system. We define a technology (singular) as a means to fulfill a purpose. Such a means may be instantiated as a physical device, or a method, or an industrial process, or an algorithm. Each technology executes at least one function and in this sense we can call it an executable. All technologies are put togethe

What it takes to understand and cure a living system: computational systems biology and a systems biology-driven pharmacokinetics–pharmacodynamics platform

The utility of model repositories is discussed in the context of systems biology (SB). It is shown how such repositories, and in particular their live versions, can be used for computational SB: we calculate the robustness of the yeast glycolytic network with respect to perturbations of one of its enzyme activities and one transport system. The robustness with respect to perturbations in the key enzyme phosphofructokinase is surprisingly large. We then note the upcoming convergence of pharmacokinetics–pharmacodynamics (PK–PD) and bottom-up SB. In PK alone, quite a few one-, two- or more compartment models provide valuable initial guesses and insights into the absorption, distribution, metabolism and excretion of particular drugs. These models are phenomenological however, forbidding implementation of molecule-based tools and network information. In order to facilitate a fruitful synergy between SB and PK–PD, and between PK and PD, we present a new platform that combines standard phenomenological models used in the PK/PD field with mechanism-based SB models and approaches

Nonalcoholic Fatty Liver Disease Is Associated With Arterial Distensibility and Carotid Intima-Media Thickness: (from the Multi-Ethnic Study of Atherosclerosis)

Nonalcoholic fatty liver disease (NAFLD) is considered a potential independent risk factor for cardiovascular disease (CVD). The Multi-Ethnic Study of Atherosclerosis cohort enrolled 6,814 adults without previous CVD. We excluded 2,692 participants who had missing variables, were heavy drinkers, or history of steroid use and/or chronic liver disease. NAFLD was defined using noncontrast cardiac CT and a liver/spleen Hounsfield Unit attenuation ratio 0 were used as markers of subclinical CVD. A multivariate robust linear regression and logistic regression analysis were done to evaluate the association of NAFLD and this subclinical CVD markers. Our analysis of 4,123 participants showed 55% were female with a mean age of 63 (±10) years, 39% white, 10% Chinese, 28% black, and 23% were Hispanic. The prevalence of NAFLD was 17% (n = 729). Patients with NAFLD had higher distensibility coefficient and higher CIMT. Multivariate linear regression analysis showed the presence of NAFLD was associated with both the common carotid and internal carotid IMT and logCAC. Logistic analysis showed an independent association with CAC \u3e 0 (odds ratio [OR] 1.44 95% confidence interval [CI] 1.18, 1.75) and CIMT \u3e 1 mm (OR 1.30 95% 1.08, 1.56). When stratified by race the association with CIMT \u3e 1 mm was significant in whites (OR 1.37 95% 1.00, 1.90) and Hispanic (OR 1.53 95% 1.08, 2. 17) and CAC \u3e 0 was significant in Hispanics (OR 1.52 95% 1.06, 2.19). In conclusion, NAFLD is modestly associated with carotid IMT and coronary artery calcification in a multiethnic population

Secondary sexual trait size reveals competitive fertilization success in Drosophila bipectinata Duda

The evolution of male secondary sexual traits traditionally has been ascribed to precopulatory sexual selection. In contrast, the importance of postcopulatory sexual selection for the evolution of secondary sexual traits is uncertain, and what little evidence exists for this process to contribute to the evolution of such traits is mixed. Here we test the hypothesis in Drosophila bipectinata Duda that the male sex comb, a rapidly evolving secondary sexual trait, is under positive postcopulatory sexual selection. We extracted replicate genetic lines exhibiting relatively large and small sex comb size from a natural population. Males from these lines were subjected to an assay of competitive fertilization ability, measured as P 2, the proportion of a female's clutch of eggs fertilized by the second male to mate. Males with the largest sex combs sired more offspring than less ornamented individuals, demonstrating for the first time in any Drosophila species that postcopulatory sexual selection favors increasing sex comb size. This study identifies a postcopulatory selective mechanism that may be contributing to the evolutionary diversification of a secondary sexual trait. Copyright 2009, Oxford University Press.