Combined report on the institutions under the control of the Iowa Department of Human Services for the five years ended June 30, 2013

Combined report on the institutions under the control of the Iowa Department of Human Services for the five years ended June 30, 2013

Combined report on the institutions under the control of the Iowa Department of Corrections for the five years ended June 30, 2013

Combined report on the institutions under the control of the Iowa Department of Corrections for the five years ended June 30, 2013

Glucagon-like peptide-I and the control of insulin secretion in the normal state and in NIDDM.

Potentiation of glucose-induced insulin secretion by intestinal factors has been described for many years. Today, two major peptides with potent insulinotropic action have been recognized: gastric inhibitory peptide and truncated forms of glucagon-like peptide I, GLP-I(7-37) or the related GLP-I(7-36)amide. These hormones have specific beta-cell receptors that are coupled to production of cAMP and activation of cAMP-dependent protein kinase. Elevation in intracellular cAMP levels is required to mediate the glucoincretin effect of these hormones: the potentiation of insulin secretion in the presence of stimulatory concentrations of glucose. In addition, circulating glucoincretins maintain basal levels of cAMP, which are necessary to keep beta-cells in a glucose-competent state. Interactions between glucoincretin signaling and glucose-induced insulin secretion may result from the phosphorylation of key elements of the glucose signaling pathway by cAMP-dependent protein kinase. These include the ATP-dependent K+ channel, the Ca++ channel, or elements of the secretory machinery itself. In NIDDM, the glucoincretin effect is reduced. However, basal or stimulated gastric inhibitory peptide and glucagon-like peptide I levels are normal or even elevated, suggesting that signals induced by these hormones on the beta-cells are probably altered. At pharmacological doses, infusion of glucagon-like peptide I but not gastric inhibitory peptide, can ameliorate postprandial insulin secretory response in NIDDM patients. Agonists of the glucagon-like peptide I receptor have been proposed as new therapeutic agents in NIDDM.

Central glucose sensing and the control of energy homeostasis

Glucose is an important signal that regulates glucose and energy homeostasis but its precise physiological role and signaling mechanism in the brain are still uncompletely understood. Over the recent years we have investigated the possibility that central glucose sensing may share functional similarities with glucose sensing by pancreatic beta-cells, in particular a requirement for the expression of the glucose transporter Glut2. Using mice with genetic inactivation of Glut2, but rescued pancreatic beta-cell function by transgenic expression of a glucose transporter, we have established that extrapancreatic glucose sensors are involved: i) in the control of glucagon secretion in response to hypoglycemia, ii) in the control of feeding and iii) of energy expenditure. We have more recently shown that central Glut2-dependent glucose sensors are involved in the regulation of NPY and POMC expression by arcuate nucleus neurons and that the sensitivity to leptin of these neurons is enhanced by Glut2-dependent glucose sensors. Using mice with genetic tagging of Glut2-expressing cells, we determined that the NPY and POMC neurons did not express Glut2 but were connected to Glut2 expressing neurons located most probably outside of the arcuate nucleus. We are now defining the electrophysiological behavior of these Glut2 expressing neurons. Our data provide an initial map of glucose sensing neurons expressing Glut2 and link these neurons with the control of specific physiological function.

Urotensin-II System in Genetic Control of Blood Pressure and Renal Function.

Urotensin-II controls ion/water homeostasis in fish and vascular tone in rodents. We hypothesised that common genetic variants in urotensin-II pathway genes are associated with human blood pressure or renal function. We performed family-based analysis of association between blood pressure, glomerular filtration and genes of the urotensin-II pathway (urotensin-II, urotensin-II related peptide, urotensin-II receptor) saturated with 28 tagging single nucleotide polymorphisms in 2024 individuals from 520 families; followed by an independent replication in 420 families and 7545 unrelated subjects. The expression studies of the urotensin-II pathway were carried out in 97 human kidneys. Phylogenetic evolutionary analysis was conducted in 17 vertebrate species. One single nucleotide polymorphism (rs531485 in urotensin-II gene) was associated with adjusted estimated glomerular filtration rate in the discovery cohort (p = 0.0005). It showed no association with estimated glomerular filtration rate in the combined replication resource of 8724 subjects from 6 populations. Expression of urotensin-II and its receptor showed strong linear correlation (r = 0.86, p<0.0001). There was no difference in renal expression of urotensin-II system between hypertensive and normotensive subjects. Evolutionary analysis revealed accumulation of mutations in urotensin-II since the divergence of primates and weaker conservation of urotensin-II receptor in primates than in lower vertebrates. Our data suggest that urotensin-II system genes are unlikely to play a major role in genetic control of human blood pressure or renal function. The signatures of evolutionary forces acting on urotensin-II system indicate that it may have evolved towards loss of function since the divergence of primates.

Hormonal control of spermatogenesis in men: therapeutic aspects in hypogonadotropic hypogonadism.

During the first two trimesters of intrauterine life, fetal sex steroid production is driven by maternal human chorionic gonadotropin (hCG). The HPG axis is activated around the third trimester and remains active for the first 6-months of neonatal life. This so-called mini-puberty is a developmental window that has profound effects on future potential for fertility. In early puberty, GnRH secretion is reactivated first at night and then night and day. Pulsatile GnRH stimulates both LH and FSH, which induce maturation of the seminiferous tubules and Leydig cells. Congenital hypogonadotropic hypogonadism (CHH) results from GnRH deficiency. Men with CHH lack the mini-pubertal and pubertal periods of Sertoli Cell proliferation and thus present with prepubertal testes (<4mL) and low inhibin serum levels --reflecting diminished SC numbers. To induce full maturation of the testes, GnRH-deficient patients can be treated with either pulsatile GnRH, hCG or combined gonadotropin therapy (FSH+hCG). Fertility outcomes with each of these regimens are highly variable. Recently, a randomized, open label treatment study (n=13) addressed the question of whether a sequential treatment with FSH alone prior to LH and FSH (via GnRH pump) could enhance fertility outcomes. All men receiving the sequential treatment developed sperm in the ejaculate, whereas 2/6 men in the other group remained azoospermic. A large, multicenter clinical trial is needed to definitively prove the optimal treatment approach for severe CHH.

Regulation of antibiotic production in root-colonizing Peudomonas spp. and relevance for biological control of plant disease.

Certain strains of fluorescent pseudomonads are important biological components of agricultural soils that are suppressive to diseases caused by pathogenic fungi on crop plants. The biocontrol abilities of such strains depend essentially on aggressive root colonization, induction of systemic resistance in the plant, and the production of diffusible or volatile antifungal antibiotics. Evidence that these compounds are produced in situ is based on their chemical extraction from the rhizosphere and on the expression of antibiotic biosynthetic genes in the producer strains colonizing plant roots. Well-characterized antibiotics with biocontrol properties include phenazines, 2,4-diacetylphloroglucinol, pyoluteorin, pyrrolnitrin, lipopeptides, and hydrogen cyanide. In vitro, optimal production of these compounds occurs at high cell densities and during conditions of restricted growth, involving (i) a number of transcriptional regulators, which are mostly pathway-specific, and (ii) the GacS/GacA two-component system, which globally exerts a positive effect on the production of extracellular metabolites at a posttranscriptional level. Small untranslated RNAs have important roles in the GacS/GacA signal transduction pathway. One challenge in future biocontrol research involves development of new strategies to overcome the broad toxicity and lack of antifungal specificity displayed by most biocontrol antibiotics studied so far.

Pharmacogenetics of CYP1A2 activity and inducibility in smokers and exsmokers.

BACKGROUND: There is a high interindividual variability in cytochrome P4501A2 (CYP1A2) activity and in its inducibility by smoking, only poorly explained by known CYP1A2 polymorphisms. We aimed to study the contribution of other regulatory pathways, including transcription factors and nuclear receptors, toward this variability. METHODS: CYP1A2 activity was determined by the paraxanthine/caffeine ratio in 184 smokers and in 113 of them who were abstinent for 4 weeks. Participants were genotyped for 22 polymorphisms in 12 genes. RESULTS: A significant influence on CYP1A2 inducibility was observed for the NR1I3 rs2502815 (P=0.0026), rs4073054 (P=0.029), NR2B1 rs3818740 (P=0.0045), rs3132297 (P=0.036), AhR rs2282885 (P=0.040), rs2066853 (P=0.019), NR1I1 rs2228570 (P=0.037), and NR1I2 rs1523130 (P=0.044) polymorphisms. Among these, the NR1I3 rs2502815 (P=0.0045), rs4073054 (P=0.048), and NR2B1 rs3818740 (P=0.031) also influenced CYP1A2 basal activity. CONCLUSION: This is the first in-vivo demonstration of the influence of genes involved in CYP1A2 regulatory pathways on its basal activity and inducibility by smoking. These results need to be confirmed by other studies.

Protease modulation of the activity of the epithelial sodium channel expressed in Xenopus oocytes.

We have investigated the effect of extracellular proteases on the amiloride-sensitive Na+ current (INa) in Xenopus oocytes expressing the three subunits alpha, beta, and gamma of the rat or Xenopus epithelial Na+ channel (ENaC). Low concentrations of trypsin (2 microg/ml) induced a large increase of INa within a few minutes, an effect that was fully prevented by soybean trypsin inhibitor, but not by amiloride. A similar effect was observed with chymotrypsin, but not with kallikrein. The trypsin-induced increase of INa was observed with Xenopus and rat ENaC, and was very large (approximately 20-fold) with the channel obtained by coexpression of the alpha subunit of Xenopus ENaC with the beta and gamma subunits of rat ENaC. The effect of trypsin was selective for ENaC, as shown by the absence of effect on the current due to expression of the K+ channel ROMK2. The effect of trypsin was not prevented by intracellular injection of EGTA nor by pretreatment with GTP-gammaS, suggesting that this effect was not mediated by G proteins. Measurement of the channel protein expression at the oocyte surface by antibody binding to a FLAG epitope showed that the effect of trypsin was not accompanied by an increase in the channel protein density, indicating that proteolysis modified the activity of the channel present at the oocyte surface rather than the cell surface expression. At the single channel level, in the cell-attached mode, more active channels were observed in the patch when trypsin was present in the pipette, while no change in channel activity could be detected when trypsin was added to the bath solution around the patch pipette. We conclude that extracellular proteases are able to increase the open probability of the epithelial sodium channel by an effect that does not occur through activation of a G protein-coupled receptor, but rather through proteolysis of a protein that is either a constitutive part of the channel itself or closely associated with it.

Impact of physical activity on activity of daily living in moderate to severe dementia: a critical review

The objectives of this study were to describe the different modalities of physical activity programs designed for moderate to severe dementia and to identify their impact on functional independence in activities of daily living (ADL). A critical review of randomized controlled trials related to the impact of physical activity programs in moderately to severely demented persons on ADL performance and meta-analysis of the identified studies were performed. Among the 303 identified articles, five responded to the selection criteria. Four out of the five studies demonstrated limited methodological quality. In one high-quality study, physical activity programs significantly delayed deterioration of ADL performance. The program components and ADL assessment tools vary widely across studies. Although the proposed treatments have not proven their efficiency in improving the ADL status of the patients, they were able to limit the decline in ADL functioning. Future research is warranted in order to identify clinically relevant modalities for physical activity programs for people with moderate to severe dementia.

Modeling and control of electromechanical systems

The material presented in the these notes covers the sessions Modelling of electromechanical systems, Passive control theory I and Passive control theory II of the II EURON/GEOPLEX Summer School on Modelling and Control of Complex Dynamical Systems.We start with a general description of what an electromechanical system is from a network modelling point of view. Next, a general formulation in terms of PHDS is introduced, and some of the previous electromechanical systems are rewritten in this formalism. Power converters, which are variable structure systems (VSS), can also be given a PHDS form.We conclude the modelling part of these lectures with a rather complex example, showing the interconnection of subsystems from several domains, namely an arrangement to temporally store the surplus energy in a section of a metropolitan transportation system based on dc motor vehicles, using either arrays of supercapacitors or an electric poweredflywheel. The second part of the lectures addresses control of PHD systems. We first present the idea of control as power connection of a plant and a controller. Next we discuss how to circumvent this obstacle and present the basic ideas of Interconnection and Damping Assignment (IDA) passivity-based control of PHD systems.

Combined report on the institutions under the control of the Iowa Department of Human Services for the five years ended June 30, 2014

Combined report on the institutions under the control of the Iowa Department of Human Services for the five years ended June 30, 2014

Combined report on the institutions under the control of the Iowa Department of Corrections for the five years ended June 30, 2014

Combined report on the institutions under the control of the Iowa Department of Corrections for the five years ended June 30, 2014

Genetic control of grain yield and nitrogen use efficiency in tropical maize

The objectives of this work were to study the genetic control of grain yield (GY) and nitrogen (N) use efficiency (NUE, grain yield/N applied) and its primary components, N uptake efficiency (NUpE, N uptake/N applied) and N utilization efficiency (NUtE, grain yield/N uptake), in maize grown in environments with high and low N availability. Experiments with 31 maize genotypes (28 hybrid crosses and three controls) were carried out in soils with high and low N rates, in the southeast of the state of Minas Gerais, Brazil. There was a reduction of 23.2% in average GY for maize grown in soil with low N, in comparison to that obtained with high N. There were 26.5, 199 and 400% increases in NUtE, NUpE, and NUE, respectively, for maize grown with low N. The general combining ability (GCA) and specific combining ability (SCA) were significant for GY, NUE and NUpE for maize grown in high N soil. Only GCA was significant for NUpE for maize grown in low N soil. The GCA and SCA for NUtE were not significant in either environment. Additive and non-additive genetic effects are responsible for the genetic control of NUE and GY for maize grown in soils with high N availability, although additive effects are more important.

Remote Control of Mobile Devices in Android Platform

Remote control systems are a very useful element to control and monitor devices quickly and easily. This paper proposes a new architecture for remote control of Android mobile devices, analyzing the different alternatives and seeking the optimal solution in each case. Although the area of remote control, in case of mobile devices, has been little explored, it may provide important advantages for testing software and hardware developments in several real devices. It can also allow an efficient management of various devices of different types, perform forensic security tasks, etc ... The main idea behind the proposed architecture was the design of a system to be used as a platform which provides the services needed to perform remote control of mobile devices. As a result of this research, a proof of concept was implemented. An Android application running a group of server programs on the device, connected to the network or USB interface, depending on availability. This servers can be controlled through a small client written in Java and runnable both on desktop and web systems.