Impaired counterregulation during hypoglycemia in type 1 diabetes (T1D) is partly due to inadequate pancreatic islet alpha-cell glucagon secretion. We hypothesized that hypoglycemia can be prevented in autoimmune T1D by selective somatostatin receptor type 2 (SSTR2) antagonism of alpha cells to relieve SSTR2 inhibition, thereby increasing glucagon secretion. Diabetic biobreeding diabetes prone (BBDP) rats (D) vs non-diabetic BBDP (N) rats, underwent infusion of vehicle or SSTR2 antagonist (SSTR2a) during insulin-induced hypoglycaemia. D rats, treated with SSTR2a, needed little or no glucose to maintain hypoglycemia. To monitor real-time glucagon secretory response directly, we developed the technique of thin slices of the pancreas from D and N rats as well as normal human pancreas, subjected to perifusion with vehicle vs SSTR2a. SSTR2a treatment enhanced glucagon secretion in N and D rats and human pancreas. We conclude that SSTR2 antagonism can enhance hypoglycemia-stimulated glucagon release sufficient to achieve normoglycemic control.

Dietary proteins from Atlantic salmon and cod have previously been shown to have antidiabetic effects. Since dietary proteins are digested into small peptides before being absorbed through the intestinal mucosa, it is reasonable to deduce that the antidiabetic effect is due to enzymatically-digested peptides rather than the proteins themselves. The aim of this study was to develop a protocol to recover peptides with antidiabetic effects from salmon and cod protein digests and then scale up and optimize the salmon protein hydrolysate production process for industrial-scale production. The peptide mixtures were screened using cell culture assays for insulin-modulating activities and were further fractionated and purified for the final identification. Total yields of salmon and cod protein hydrolysates (<1 kDa) as measured by Kjeldahl nitrogen were 16.9% and 40.1%, respectively. The production process used for the salmon protein hydrolysate (<1 kDa) showed good reproducibility and potential for the industrial-scale production.

Hypoglycemia is one of the most serious acute complications in intensively treated diabetes. Recurrent hypoglycemia predisposes individuals to subsequent hypoglycemia, and diminished counterregulatory hormone responses increase this threat. Elevated pancreatic and/or circulating somatostatin has been reported in diabetic humans and animals, and we postulated that excessive somatostatin contributes to the attenuation of counterregulatory hormone release during hypoglycemia in diabetes. It is known that somatostatin suppresses stimulated secretion of glucagon, epinephrine, and corticosterone. We hypothesized that selective somatostatin receptor type 2 (SSTR2) antagonism would: (Study 1) improve hormone counterregulation to hypoglycemia, and (Study 2) ameliorate hypoglycemia in recurrently hypoglycemic rats. Using both high (10 U/kg) and low (5 U/kg) dose insulin to induce hypoglycemia, we demonstrate that inhibiting the action of somatostatin on SSTR2 normalizes the severely attenuated glucagon and corticosterone responses to acute hypoglycemia in diabetic rats. These improvements were specific to diabetes since SSTR2 antagonism did not increase these hormones in non-diabetic rats in response to hypoglycemia. In the absence of hypoglycemia, SSTR2 antagonist neither markedly alters glycemia nor causes sustained elevations in counterregulatory hormones in diabetic animals. Diabetic rats exhibit up to 65% and 75% more pancreatic and plasma somatostatin than non-diabetic rats following hypoglycemia, respectively. Despite improvements of glucagon and corticosterone, expression of gluconeogenic enzymes PEPCK1 and G6Pase was unaltered. SSTR2 antagonism reduced the glucose requirement during a hypoglycemic clamp induced with a lower dose of insulin. In recurrently hypoglycemic diabetic rats, we demonstrate that SSTR2 antagonist treatment reduces the depth and duration of hypoglycemia and promotes the recovery to euglycemia, without affecting the glycemia-lowering effect of insulin. This amelioration of hypoglycemia by SSTR2 antagonism may be attributable in part to the observed modest improvements of glucagon, epinephrine, and corticosterone counterregulation following recurrent hypoglycemia. These results implicate an important role for increased pancreatic, and possibly circulating, somatostatin in defective hypoglycemic counterregulation in diabetes.

A method for designing low-density parity-check (LDPC) codes for bandwidth-efficient high-order coded modulation is proposed. Code structure utilizes the multi-edge-type LDPC code ensemble to achieve an improved match between codeword bit protection ca- pabilities and modulation bit-channel capacities over existing LDPC coded modulation techniques. The multi-dimensional EXIT vector field for the specific multi-edge parame- terization is developed for the analysis and design of code ensembles. A multi-dimensional EXIT decoding convergence condition is derived to enable efficient optimization. Code design results in terms of ensemble thresholds and finite-length Monte-Carlo simulations indicate that the new technique improves on the state-of-the-art performance, with sig- nificantly lower design and implementation complexity.

Impaired counterregulation during hypoglycemia in type 1 diabetes (T1D) is partly due to inadequate pancreatic islet alpha-cell glucagon secretion. We hypothesized that hypoglycemia can be prevented in autoimmune T1D by selective somatostatin receptor type 2 (SSTR2) antagonism of alpha cells to relieve SSTR2 inhibition, thereby increasing glucagon secretion. Diabetic biobreeding diabetes prone (BBDP) rats (D) vs non-diabetic BBDP (N) rats, underwent infusion of vehicle or SSTR2 antagonist (SSTR2a) during insulin-induced hypoglycaemia. D rats, treated with SSTR2a, needed little or no glucose to maintain hypoglycemia. To monitor real-time glucagon secretory response directly, we developed the technique of thin slices of the pancreas from D and N rats as well as normal human pancreas, subjected to perifusion with vehicle vs SSTR2a. SSTR2a treatment enhanced glucagon secretion in N and D rats and human pancreas. We conclude that SSTR2 antagonism can enhance hypoglycemia-stimulated glucagon release sufficient to achieve normoglycemic control.

Successful pathogens like Pseudomonas syringae translocate type III effector proteins (T3SE) into host cells. Plant hosts react by specifically recognizing these effectors via R proteins that trigger defense responses. The T3SE family HopZ1 has evolved into three allelic forms as a result of diversifying selection. In this thesis, I investigated how virulence and immune-eliciting functions are determined in HopZ1a and HopZ1b in Arabidopsis. Mutational analysis of HopZ1a identified ten residues important for immune elicitation and at least three are involved in virulence functions. These results suggest that distinct key amino acid residues in HopZ1a mediate the two activities. The closely related HopZ1b T3SE elicits an inconsistent immune response in Arabidopsis. We found that HopZ1b-triggered immune response involves a TIR-type R protein and plastid-derived SA. Together, these results highlight an uncharacterized ETI response to the HopZ1 family of T3SEs.

Tottering and leaner mutant mice carry mutations in the pore-forming subunit (1A) of P/Q-type (CaV 2.1) voltage-gated calcium ion (Ca2+) channels that result in reduced Ca2+ current density. Since Ca2+ influx via voltage-dependent Ca2+ channels regulates important Ca2+-dependent neuronal processes including neurotransmitter release and synaptogenesis, we assessed effects of these mutations on hippocampus volume, neuronal density, neuronal morphology of hippocampal pyramidal cells in adult (six-month-old) mice, and adult neurogenesis in three-week-old and six-month-old mice. Hippocampal volume and neuronal density were assessed using hematoxylin and eosin stained serial sections. Neuronal morphology was assessed using Golgi-Cox staining as well as ultrastructural assessment using transmission electron microscopy. Adult hippocampal neurogenesis was assessed using standard 5-bromo-2’-deoxyuridine (BrdU) labeling with fluorescent immunohistochemistry (IHC) and proliferating cell nuclear antigen (PCNA) with diaminobenzidine IHC. To determine neuron and astrocyte survival, we used fluorescent double labeling for neurons with BrdU-neuronal nuclei IHC or astrocytes using BrdU-glial fibrillary acidic protein, respectively. Fluoro-Jade histochemistry was used to assess numbers of degenerating cells in the dentate gyrus subgranular zone. Decreased hippocampus volume was observed in tottering female mice and increased dentate hilar and CA1 cell density in mutant mice compared to wild type mice. Cell proliferation was increased in the hilus and combined CA3, CA2 and CA1 regions of mutant mice compared to wild type mice. Decreased total dendritic length and decreased number of dendritic intersections was observed in tottering mice compared to wild type mice. The decrease in dendritic arborization of tottering mice occurred at the concentric circles close to the neuronal cell body indicating that basal dendrites of CA1 pyramidal neurons are reduced. Taken together, P/Q-type voltage gated calcium channel mutation has age variable influence on adult hippocampal cell proliferation, and it altered neuronal morphology in terms of dendritic complexity in tottering mice, while the leaner mutation reduced mitochondrial density.

The project describes the development and standardization of the Myers-Briggs Type Indicator into the Greek language. Statistical properties of the Greek version were comparable to those of the original American version providing evidence of its adequacy as a psychometric tool. The comparison of the distribution of types of Greek university students (N = 946) with that of French Canadians, and Americans showed a preference for "thinking" and "perceiving". Further, gender associated preferences for thinking and feeling evident in the American and French Canadian norms were also present in the Greek data.

Mardin&amp / #8217 / s unique stone architecture has evolved within various ethnical and religious communities. Regardless of its hybrid nature, with the effect of topography, the fabric has a uniform character. The interventions made to the city during the last century have repeated fragments of stereotype apartment building instead of sustaining traditional typologies (building types with living unit, aiwan, arcade, terrace and courtyard). Typological difference of these interventions has caused an incongruous hybridization and deterioration in the fabric. Hybridization in architecture, for Felipe Hernandez, is not only diversity of architectural styles and materials. Furthermore, it is a cultural issue related with changes in the society. Mardin confronts hybridization because the traditional buildings are incapable of embracing contemporary functions. This has been exemplified with G&ouml / z&uuml / House and neighboring buildings. Late interventions are distinguished from the historical ones according to typological differences. This study accepts hybrid as a problem but also as a fact / thus aims to regenerate it. The historical types, accepted as original, are interpreted with a contemporary sense in reference to debates on sustaining urban form with new buildings and theories on typology which define it as open to creativity, vague in form and reproducible. This is exemplified by a proposal, an infill in the fabric. Spatial sequence of the proposal refers to traditional plan typologies while these spaces embrace contemporary functions and their architectonic expression refers to contemporary architecture. So, in relation to the facts of the present context the proposal fulfills its spatial expectations while respecting physical context.

Both type 2 diabetes (T2D) and the the metabolic syndrome (MetS) have been shown to increase the risk of cardiovascular disease (CVD). Inflammation and insulin resistance have each been associated with the development of MetS and the onset of T2D as well as the risk of CVD. Inflammation and insulin resistance are therefore suitable targets for public health initiatives and interventions in persons at risk for or living with CVD. Physical inactivity is a major risk factor for CVD as well as MetS and T2D. Conversely, increased physical activity is associated with improved health outcomes for individuals with a high risk for developing CVD. Two possible mechanisms for the deleterious effects of inactivity on health are inflammation and insulin resistance. Researchers have hypothesized that increased adiposity and reduced fitness are partially responsible for the associations between inactivity, inflammation, and insulin resistance. However, these relationships have not been studied extensively in overweight/obese individuals, who are often unfit and sedentary. The purpose of this study was to further examine the relationship between baseline measures of walking activity and sedentary behavior, and inflammation and insulin resistance in a sample of adults with type 2 diabetes and/or metabolic syndrome. This thesis examined baseline data from participants enrolled in either of two studies of patients with T2D (n = 116) or MetS without T2D (n = 126). Participants included low income men and women (not pregnant or nursing) between the ages of 18 and 70 who either show depressed affect (BDI > 11), and were overweight (BMI ≥ 27 kg/m2) and had type 2 diabetes or had at least 3 components of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) classification of the metabolic syndrome (MetS). Structural equation modeling was used to determine if physical inactivity is associated with inflammation or insulin resistance in these conditions. Possible mediational roles of adiposity and low cardiorespiratory fitness were also examined. Additional analyses were conducted to determine if these relationships can be estimated equally in MetS and T2D conditions. Activity was indirectly related to abdominal adiposity via an indirect, positive association with cardiorespiratory fitness. Abdominal adiposity was positively related to both inflammation and insulin resistance. There were no direct associations between activity and inflammation or insulin resistance in this population. Therefore, walking may be negatively related to cardiovascular risk, insofar as it reduces abdominal adiposity.