Antibodies against glutamic acid decarboxylase and indices of insulin resistance and insulin secretion in nondiabetic adults: a cross-sectional study

PubMed Central

Mendivil, Carlos O; Toloza, Freddy JK; Ricardo-Silgado, Maria L; Morales-Álvarez, Martha C; Mantilla-Rivas, Jose O; Pinzón-Cortés, Jairo A; Lemus, Hernán N

2017-01-01

Background Autoimmunity against insulin-producing beta cells from pancreatic islets is a common phenomenon in type 1 diabetes and latent autoimmune diabetes in adults. Some reports have also related beta-cell autoimmunity to insulin resistance (IR) in type 2 diabetes. However, the extent to which autoimmunity against components of beta cells is present and relates to IR and insulin secretion in nondiabetic adults is uncertain. Aim To explore the association between antibodies against glutamic acid decarboxylase (GADA), a major antigen from beta cells, and indices of whole-body IR and beta-cell capacity/insulin secretion in adults who do not have diabetes. Methods We studied 81 adults of both sexes aged 30–70, without known diabetes or any autoimmune disease. Participants underwent an oral glucose tolerance test (OGTT) with determination of plasma glucose and insulin at 0, 30, 60, 90, and 120 minutes. From these results we calculated indices of insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] and incremental area under the insulin curve [iAUCins]) and insulin secretion (corrected insulin response at 30 minutes and HOMA beta-cell%). GADAs were measured in fasting plasma using immunoenzymatic methods. Results We found an overall prevalence of GADA positivity of 21.3%, without differences by sex and no correlation with age. GADA titers did not change monotonically across quartiles of any of the IR or insulin secretion indices studies. GADA did not correlate linearly with fasting IR expressed as HOMA-IR (Spearman’s r=−0.18, p=0.10) or postabsorptive IR expressed as iAUCins (r=−0.15, p=0.18), but did show a trend toward a negative correlation with insulin secretory capacity expressed by the HOMA-beta cell% index (r=−0.20, p=0.07). Hemoglobin A1c, body mass index, and waist circumference were not associated with GADA titers. Conclusion GADA positivity is frequent and likely related to impaired beta-cell function among adults

The prevalence of early subclinical somatic neuropathy in children and adolescents with Type 1 diabetes mellitus and its association with the persistence of autoantibodies to glutamic acid decarboxylase (GAD) and islet antigen-2 (IA-2).

PubMed

Louraki, Maria; Katsalouli, Marina; Kanaka-Gantenbein, Christina; Kafassi, Nikolitsa; Critselis, Eleni; Kallinikou, Dimitra; Tsentidis, Charalampos; Karavanaki, Kyriaki

2016-07-01

To evaluate the prevalence of early somatic neuropathy in children and adolescents with Type 1 diabetes mellitus (Type 1 DM) and its association with the presence of glutamic acid decarboxylase and islet antigen-2 autoantibodies (GADA and IA-2A). A cross-sectional study was conducted in a hospital-based cohort of pediatric Type 1 DM patients (n=85, mean(±SD) age: 13.5±3.4years, mean(±SD) disease duration 5.5±3.4years). Peripheral neuropathy was assessed with nerve conduction studies (NCS). GADA and IA-2A titers were measured with radioligand assays. Among the study population, 34.1% had at least one abnormal electrophysiological parameter, although predominantly asymptomatic. The highest rates of abnormality were detected in sensory peroneal nerve (25.9%) followed by sural nerve (15.3%). Affected patients were not different in terms of age, diabetes duration or glycaemic control. Among the participants, 62.4% had positive GADA, 58.8% positive IA-2A and 42.4% double antibody positivity. Abnormal NCS correlated neither with GADA nor with IA-2A levels or positivity. However lower sensory nerve action potential in the peroneal nerve, indicative of early axonal dysfunction, was observed in patients with GADA or IA-2A positivity. Absence of both antibodies was associated with better action potentials in all the examined nerves of the lower limbs. Impaired indices of subclinical peripheral primarily sensory neuropathy were present among one third of Type 1 DM children and adolescents, with no impact of diabetes duration or glycaemic control. GADA and IA-2A seem to be involved in the development of axonal degeneration, in a pathway which remains to be identified. Copyright © 2016. Published by Elsevier Ireland Ltd.

Assessment of the effects of glutamic acid decarboxylase antibodies and trace elements on cognitive performance in older adults.

PubMed

Alghadir, Ahmad H; Gabr, Sami A; Al-Eisa, Einas S

2015-01-01

Homeostatic imbalance of trace elements such as iron (Fe), copper (Cu), and zinc (Zn) demonstrated adverse effects on brain function among older adults. The present study aimed to investigate the effects of trace elements and the presence of anti-glutamic acid decarboxylase antibodies (GADAs) in human cognitive abilities among healthy older adults. A total of 100 healthy subjects (65 males, 35 females; age range; 64-96 years) were recruited for this study. Based on Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) score, the participants were classified according to cognitive performance into normal (n=45), moderate (n=30), and severe (n=25). Cognitive functioning, leisure-time physical activity (LTPA), serum trace elements - Fe, Cu, Zn, Zn/Cu, and GADAs were assessed using LOTCA battery, pre-validated physical activity (PA) questionnaire, atomic absorption, and immunoassay techniques, respectively. Approximately 45% of the study population (n=45) had normal distribution of cognitive function and 55% of the study population (n=55) had abnormal cognitive function; they were classified into moderate (score 62-92) and severe (score 31-62). There was a significant reduction in the level of Zn and Zn/Cu ratio along with an increase in the level of Fe, Cu, and anti-GADAs in subjects of severe (P=0.01) and moderate (P=0.01) cognitive performance. LOTCA-cognitive scores correlated positively with sex, HbA(1c), Fe, Cu, Zn, and Zn/Cu ratio, and negatively with age, PA, body mass index, and anti-GADAs. Significant inter-correlation was reported between serum trace element concentrations and anti-GADAs which suggest producing a cognitive decline via oxidative and neural damage mechanism. This study found significant associations among trace elements, anti-GADAs, and cognitive function in older adults. The homeostatic balance of trace elements should be recommended among older adults for better cognitive performance.

Alcohol and the risk for latent autoimmune diabetes in adults: results based on Swedish ESTRID study.

PubMed

Rasouli, Bahareh; Andersson, Tomas; Carlsson, Per-Ola; Dorkhan, Mozhgan; Grill, Valdemar; Groop, Leif; Martinell, Mats; Tuomi, Tiinamaja; Carlsson, Sofia

2014-11-01

Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with the risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. A population-based case-control study was carried out to investigate the association of alcohol consumption and the risk of LADA. We used data from the ESTRID case-control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies (GADAs) positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged ≥35. Logistic regression was used to estimate the odds ratios (ORs) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% CI 0.92-0.99 for every 5-g increment in daily intake). Similar results were observed for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA levels (OR 0.85, 95% CI 0.76-0.94/5 g alcohol per day), whereas no association was observed with LADA having high GADA levels (OR 1.00, 95% CI 0.94-1.06/5 g per day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (P=0.0312), and a 10% reduction in homeostasis model assessment of insulin resistance (P=0.0418). Our findings indicate that alcohol intake may reduce the risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity. © 2014 The authors.

Phenotypic and environmental factors associated with elevated autoantibodies at clinical onset of paediatric type 1 diabetes mellitus.

PubMed

Ponsonby, Anne-Louise; Pezic, Angela; Cameron, Fergus J; Rodda, Christine; Ellis, Justine A; Kemp, Andrew S; Carlin, John; Dwyer, Terence

2012-01-01

To examine possible determinants of autoantibody levels at type 1 diabetes mellitus (T1DM) onset. We assessed levels of glutamic acid decarboxylase 65 islet cell antigen (GADA) and anti-insulin antibodies (IAA) in 247 incident T1DM cases presenting <15 years of age in Melbourne from 1st March 2008 to 30th June 2010. 58.9% (142/241) of cases were GADA seropositive and 42.3% (94/222) were IAA seropositive. Factors associated with elevated IAA antibodies included younger age and red hair phenotype. Factors associated with elevated GAD antibodies included lower birthweight and recent eczema. Intriguingly, low recent or past sun exposure was only associated with elevated GADA levels among children presenting at age <5 years, not older (difference in effect, p<0.05 for 4 of 5 associations). These findings show that environmental and phenotypic factors are associated with autoantibody levels at time of presentation for T1DM. We recommend such environmental and phenoytypic factors should be examined in further detail.

Characterization of human organ donors testing positive for type 1 diabetes-associated autoantibodies

PubMed Central

Wiberg, A; Granstam, A; Ingvast, S; Härkönen, T; Knip, M; Korsgren, O; Skog, O

2015-01-01

In this study we aim to describe the characteristics of non-diabetic organ donors with circulating diabetes-associated autoantibodies collected within the Nordic Network for Islet Transplantation. One thousand and thirty organ donors have been screened in Uppsala for antibodies against glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A). The 32 non-diabetic donors that tested positive for GADA (3·3% of all non-diabetic donors) were studied in more detail, together with 32 matched controls. Mean age among the autoantibody-positive donors was 52·6 (range 21–74), family history of type 1 diabetes (T1D) was unknown, and no donor was genetically predisposed for T1D regarding the human leucocyte antigen (HLA) locus. Subjects were analysed for islet cell antibodies (ICA), insulin autoantibodies (IAA) and zinc transporter 8 antibodies (ZnT8A), and pancreas morphology and clinical data were examined. Eight non-diabetic donors tested positive for two antibodies and one donor tested positive for four antibodies. No insulitis or other signs of a diabetic process were found in any of the donors. While inflammatory cells were present in all donors, subjects with high GADA titres had significantly higher CD45 cell numbers in exocrine tissue than controls. The extent of fibrosis was more pronounced in autoantibody-positive donors, even in subjects with lower GADA titres. Notably, it is possible that events not related directly to T1D (e.g. subclinical pancreatitis) may induce autoantibodies in some cases. PMID:26313035

The association of cytotoxic T-lymphocyte antigen-4 + 49A/G and CT60 polymorphisms with type 1 diabetes and latent autoimmune diabetes in Chinese adults.

PubMed

Jin, P; Xiang, B; Huang, G; Zhou, Z

2015-02-01

The aim of this study was to investigate the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) + 49A/G and CT60 polymorphisms with latent autoimmune diabetes in adults (LADA) and the genetic differences between LADA, type 1 diabetes (T1DM), and type 2 diabetes (T2DM) in a Chinese population. A total of 231 LADA, 402 T1DM, and 330 T2DM patients as well as 482 nondiabetic controls were recruited in the study. CTLA-4 + 49A/G and CT60 polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The level of glutamic acid decarboxylase antibodies (GADAs) was detected by a radioligand binding assay. The CTLA-4 + 49A/G risk genotype GG was most frequent in T1DM patients (45.3%), followed by LADA patients (44.2%) and T2DM patients (38.8%). Significantly higher frequencies of the risk genotype GG were observed in the T1DM (OR = 1.532, 95% CI 1.168-2.010, P = 0.002) and LADA patients (OR = 1.464, 95% CI 1.063-2.017, P = 0.019). The frequencies of the CTLA-4 CT60 risk genotype GG were 65.2, 61.9, 58.5, and 56.4% in the T1DM, LADA, T2DM, and control groups, respectively. The CTLA-4 CT60 GG risk genotypes were only associated with T1DM (OR = 1.445, 95% CI 1.1-1.898, P = 0.008). Compared with controls, patients having a high titer of GADA (GADA ≥ 180 IU/ml) had higher frequencies of the GG risk genotype of CTLA-4 + 49 A/G (49.4% vs. 35.1% OR = 1.807, 95% CI 1.125-2.903, P = 0.014), but there was no difference between patients having a low titer of GADA and controls. The CTLA-4 + 49 A/G polymorphism confers genetic susceptibility to LADA and T1DM, while the CTLA-4 CT60 polymorphism is only associated with T1DM in Chinese population. The CTLA-4 + 49 A/G genotype distribution in LADA is associated with the GADA level.

Screening of ZnT8 autoantibodies in the diagnosis of autoimmune diabetes in a large French cohort.

PubMed

Garnier, Lorna; Marchand, Lucien; Benoit, Marine; Nicolino, Marc; Bendelac, Nathalie; Wright, Catherine; Moulin, Philippe; Lombard, Christine; Thivolet, Charles; Fabien, Nicole

2018-03-01

Evaluate the added value of screening anti-ZnT8 antibodies (ZnT8A) in addition to the classical anti-GAD (GADA) and anti-IA-2 (IA-2A) antibodies for the diagnosis of type-1 diabetes (T1D) within a large cohort of both children and adults. Retrospective 2-year study including 516 patients (215 children, 301 adults) who had blood tests at diabetes onset and/or for diabetes classification. ZnT8A, GADA, and IA-2A were analyzed in all samples. Among those individuals included, 142 (28%) were ZnT8A-positive. A total of 228/516 suffered from T1D, of whom 110 (48%) were ZnT8A-positive and 166 (73%) GADA and/or IA-2A positive. When adding ZnT8A to GADA/IA-2A, 184 (81%) patients were positive for ≥1 Ab. Regarding the 122 patients at T1D onset, 75 (61%) were positive for ZnT8A and the proportion of patients with T1D with ≥1 Ab reached 89%. The highest prevalence of ZnT8A was observed in children aged 6-10years. Fourteen of the 124 patients positive for ZnT8A with a known clinical diagnosis suffered from a disease other than T1D. ZnT8A should be included in routine evaluation at diabetes onset and is a valuable biological marker to classify newly-diagnosed diabetics. The predictive value in our high-risk subjects has to be confirmed. Copyright © 2018 Elsevier B.V. All rights reserved.

Lack of Evidence for a Role of Islet Autoimmunity in the Aetiology of Canine Diabetes Mellitus

PubMed Central

Landegren, Nils; Grimelius, Lars; von Euler, Henrik; Sundberg, Katarina; Lindblad-Toh, Kerstin; Lobell, Anna; Hedhammar, Åke; Andersson, Göran; Hansson-Hamlin, Helene; Lernmark, Åke; Kämpe, Olle

2014-01-01

Aims/Hypothesis Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported. Methods Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide. Results None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted. Conclusions/Interpretations Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus. PMID:25153886

Insulin autoantibody could help to screen latent autoimmune diabetes in adults in phenotypic type 2 diabetes mellitus in Chinese.

PubMed

Huang, Gan; Wang, Xia; Li, Zhangwei; Li, Hui; Li, Xia; Zhou, Zhiguang

2012-10-01

Latent autoimmune diabetes in adults (LADA) is characterized by a relatively mild diabetes onset, autoantibody positivity, and eventual requirement for insulin therapy. Glutamic acid decarboxylase autoantibodies (GADA) or cytoplasmic islet cell autoantibodies (ICA) play a key role in distinguishing LADA from type 2 diabetes mellitus (T2DM) in clinical practice. The aim of our research was to determine whether insulin autoantibody (IAA) has some additional value in diagnosing LADA. We analyzed IAA, GADA, and IA-2A (antibodies to insulinoma-associated antigen-2) in 1,003 newly diagnosed phenotypic T2DM patients, 110 type 1 diabetes mellitus (T1DM) patients, and 317 normal controls to survey the prevalence of IAA in phenotypic T2DM patients and the overlapping positivity of IAA with other autoantibodies. Sera were drawn within 7 days from the start of insulin therapy. Results showed that 3.39% of the newly diagnosed phenotypic T2DM, 0.95% of normal control (χ(2) = 5.3, P < 0.05), and 21.82% of T1DM (χ(2) = 68.2, P < 0.001) were positive for IAA at diagnosis. The combination frequency of three antibodies was 10.47%, which was higher than any single antibody testing. Combination testing of IAA with GADA and IA-2A could improve LADA diagnose rate by 2.39% than that of GADA and IA-2A. IAA-positive subjects had diabetes family history more common compared to its matched group (67.6% vs. 14.7%, P = 0.000). Postprandial C-peptide in IAA-positive group tended to be lower, but the difference was not statistically significant (P = 0.084). We concluded that IAA can be used to screen LADA in phenotypic T2DM in the Chinese population.

Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects?

PubMed Central

Fouts, Alexandra; Pyle, Laura; Yu, Liping; Miao, Dongmei; Michels, Aaron; Krischer, Jeffrey; Sosenko, Jay; Gottlieb, Peter

2016-01-01

OBJECTIVE To explore whether electrochemiluminescence (ECL) assays can help improve prediction of time to type 1 diabetes in the TrialNet autoantibody-positive population. RESEARCH DESIGN AND METHODS TrialNet subjects who were positive for one or more autoantibodies (microinsulin autoantibody, GAD65 autoantibody [GADA], IA-2A, and ZnT8A) with available ECL-insulin autoantibody (IAA) and ECL-GADA data at their initial visit were analyzed; after a median follow-up of 24 months, 177 of these 1,287 subjects developed diabetes. RESULTS Univariate analyses showed that autoantibodies by radioimmunoassays (RIAs), ECL-IAA, ECL-GADA, age, sex, number of positive autoantibodies, presence of HLA DR3/4-DQ8 genotype, HbA1c, and oral glucose tolerance test (OGTT) measurements were all significantly associated with progression to diabetes. Subjects who were ECL positive had a risk of progression to diabetes within 6 years of 58% compared with 5% for the ECL-negative subjects (P < 0.0001). Multivariate Cox proportional hazards models were compared, with the base model including age, sex, OGTT measurements, and number of positive autoantibodies by RIAs. The model with positivity for ECL-GADA and/or ECL-IAA was the best, and factors that remained significantly associated with time to diabetes were area under the curve (AUC) C-peptide, fasting C-peptide, AUC glucose, number of positive autoantibodies by RIAs, and ECL positivity. Adding ECL to the Diabetes Prevention Trial risk score (DPTRS) improved the receiver operating characteristic curves with AUC of 0.83 (P < 0.0001). CONCLUSIONS ECL assays improved the ability to predict time to diabetes in these autoantibody-positive relatives at risk for developing diabetes. These findings might be helpful in the design and eligibility criteria for prevention trials in the future. PMID:27456836

Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects?

PubMed

Fouts, Alexandra; Pyle, Laura; Yu, Liping; Miao, Dongmei; Michels, Aaron; Krischer, Jeffrey; Sosenko, Jay; Gottlieb, Peter; Steck, Andrea K

2016-10-01

To explore whether electrochemiluminescence (ECL) assays can help improve prediction of time to type 1 diabetes in the TrialNet autoantibody-positive population. TrialNet subjects who were positive for one or more autoantibodies (microinsulin autoantibody, GAD65 autoantibody [GADA], IA-2A, and ZnT8A) with available ECL-insulin autoantibody (IAA) and ECL-GADA data at their initial visit were analyzed; after a median follow-up of 24 months, 177 of these 1,287 subjects developed diabetes. Univariate analyses showed that autoantibodies by radioimmunoassays (RIAs), ECL-IAA, ECL-GADA, age, sex, number of positive autoantibodies, presence of HLA DR3/4-DQ8 genotype, HbA1c, and oral glucose tolerance test (OGTT) measurements were all significantly associated with progression to diabetes. Subjects who were ECL positive had a risk of progression to diabetes within 6 years of 58% compared with 5% for the ECL-negative subjects (P < 0.0001). Multivariate Cox proportional hazards models were compared, with the base model including age, sex, OGTT measurements, and number of positive autoantibodies by RIAs. The model with positivity for ECL-GADA and/or ECL-IAA was the best, and factors that remained significantly associated with time to diabetes were area under the curve (AUC) C-peptide, fasting C-peptide, AUC glucose, number of positive autoantibodies by RIAs, and ECL positivity. Adding ECL to the Diabetes Prevention Trial risk score (DPTRS) improved the receiver operating characteristic curves with AUC of 0.83 (P < 0.0001). ECL assays improved the ability to predict time to diabetes in these autoantibody-positive relatives at risk for developing diabetes. These findings might be helpful in the design and eligibility criteria for prevention trials in the future. © 2016 by the American Diabetes Association.

4. Detail of the south side of the building showing ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. Detail of the south side of the building showing the decorative-brick cornice, typical double-hung window, and chimneys. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

1. View toward the southwest corner of the building after ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. View toward the southwest corner of the building after the 1950s-applied facade was removed. Remnants of this facade still remain above the parapet. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

16. Detail of original wainscot in the dining room. The ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

16. Detail of original wainscot in the dining room. The wainscot panels are flat (not beveled) and are painted along the edge to simulate a raised (beveled) panel. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

Lack of antibodies to NMDAR or VGKC-complex in GAD and cardiolipin antibody-positive refractory epilepsy.

PubMed

Liimatainen, Suvi; Peltola, Jukka; Hietaharju, Aki; Sabater, Lidia; Lang, Bethan

2014-03-01

Over the last few years autoantibodies against neuronal proteins have been identified in several forms of autoimmune encephalitis and epilepsy. NMDA receptor (NMDAR) and voltage gated potassium channel (VGKC) complex antibodies are mainly associated with limbic encephalitis (LE) whereas glutamic acid decarboxylase antibodies (GADA) and anticardiolipin (ACL) antibodies are more commonly detected in patients with chronic epilepsy. Clinical features vary between these antibodies suggesting the specificity of different neuronal antibodies in seizures. Serum samples of 14 GADA positive and 24 ACL positive patients with refractory epilepsy were analyzed for the presence of VGKC or NMDAR antibodies. No positive VGKC or NMDAR antibodies were found in these patients. The results confirm the different significance of these neuronal antibodies in seizure disorders. Different autoantibodies have different significance in seizures and probably have different pathophysiological mechanisms of actions. Copyright © 2014 Elsevier B.V. All rights reserved.

3. View toward the southeast corner of the building showing ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. View toward the southeast corner of the building showing the south (alley) side on the left and the east (suballey) side on the right. The second story contained 'furnished rooms.' Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

Teaching Intersectional and Transnational Feminisms through Fiction and Film

ERIC Educational Resources Information Center

Mahrouse, Gada

2016-01-01

Author Gada Mahrouse begins this article by saying that the terms "intersectional" and "transnational" are widely misunderstood and misused by academics. She writes that the first, "intersectionality," has become a buzzword, not only in feminist courses but also in mainstream disciplines and areas of research. She…

Dairy Streptococcus thermophilus improves cell viability of Lactobacillus brevis NPS-QW-145 and its γ-aminobutyric acid biosynthesis ability in milk.

PubMed

Wu, Qinglong; Law, Yee-Song; Shah, Nagendra P

2015-08-06

Most high γ-aminobutyric acid (GABA) producers are Lactobacillus brevis of plant origin, which may be not able to ferment milk well due to its poor proteolytic nature as evidenced by the absence of genes encoding extracellular proteinases in its genome. In the present study, two glutamic acid decarboxylase (GAD) genes, gadA and gadB, were found in high GABA-producing L. brevis NPS-QW-145. Co-culturing of this organism with conventional dairy starters was carried out to manufacture GABA-rich fermented milk. It was observed that all the selected strains of Streptococcus thermophilus, but not Lactobacillus delbrueckii subsp. bulgaricus, improved the viability of L. brevis NPS-QW-145 in milk. Only certain strains of S. thermophilus improved the gadA mRNA level in L. brevis NPS-QW-145, thus enhanced GABA biosynthesis by the latter. These results suggest that certain S. thermophilus strains are highly recommended to co-culture with high GABA producer for manufacturing GABA-rich fermented milk.

18. The west end of the dining room contains four ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. The west end of the dining room contains four windows that overlook Central Avenue. As other millwork in the restaurant, these windows were originally finished with stain and varnish. Transoms retain their original operators. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

Sex as a determinant of type 1 diabetes at diagnosis.

PubMed

Turtinen, Maaret; Härkönen, Taina; Parkkola, Anna; Ilonen, Jorma; Knip, Mikael

2018-06-03

The present study tested the hypothesis that girls have a more aggressive disease process than boys at the diagnosis of type 1 diabetes (T1D). Demographic and clinical characteristics, the humoral autoantibody profile, and the genetic risk assessed by the presence of human leukocyte antigen DR-DQ haplotypes were analyzed in terms of sex in 4993 children and adolescents diagnosed with T1D between January 2003 and December 2016. A clear male preponderance (56.6%) was observed in our cohort and boys were significantly older than girls at clinical diagnosis (mean 8.3 vs 7.7 years, P < .001). Age-adjusted analyses showed a poorer metabolic decompensation in girls than boys at diagnosis. Boys tested more often positive for autoantibodies against insulin autoantibodies (P = .008), islet antigen-2 autoantibodies (P = .033), and zinc transporter 8 autoantibodies (P = .027), whereas girls had a higher frequency of glutamic acid decarboxylase autoantibodies (GADA) (P < .001) and higher GADA (P < .001) and islet cell antibody titers (P = .001). We did not find any significant differences in the genetic risk profile between girls and boys. Our data show that the metabolic derangement is more severe in girls already at diagnosis of T1D and this finding is independent of age. The immunologic aggressiveness of the disease is more variable as the predominance of different autoantibodies varies between sexes with a higher frequency of GADA in girls, while the 3 other biochemical autoantibodies were more common in boys. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of Age and Antibody Type on Progression From Single to Multiple Autoantibodies in Type 1 Diabetes Relatives.

PubMed

Bosi, Emanuele; Boulware, David C; Becker, Dorothy J; Buckner, Jane H; Geyer, Susan; Gottlieb, Peter A; Henderson, Courtney; Kinderman, Amanda; Sosenko, Jay M; Steck, Andrea K; Bingley, Polly J

2017-08-01

Islet autoantibodies are markers of type 1 diabetes, and an increase in number of autoantibodies detected during the preclinical phase predicts progression to overt disease. To refine the effect of age in relation to islet antibody type on progression from single to multiple autoantibodies in relatives of people with type 1 diabetes. We examined 994 relatives with normal glucose tolerance who were positive for a single autoantibody, followed prospectively in the TrialNet Pathway to Prevention. Antibodies to glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated antigen 2, and zinc transporter 8 and islet cell antibodies were tested every 6 to 12 months. The primary outcome was confirmed development of multiple autoantibodies. Age was categorized as <8 years, 8 to 11 years, 12 to 17 years, and ≥18 years, and optimal age breakpoints were identified by recursive partitioning analysis. After median follow-up of 2 years, 141 relatives had developed at least one additional autoantibodies. Five-year risk was inversely related to age, but the pattern differed by antibody type: Relatives with GADA showed a gradual decrease in risk over the four age groups, whereas relatives with IAA showed a sharp decrease above age 8 years. Recursive partitioning analysis identified age breakpoints at 14 years in relatives with GADA and at 4 years in relatives with IAA. In relatives with IAA, spread of islet autoimmunity is largely limited to early childhood, whereas immune responses initially directed at glutamic acid decarboxylase can mature over a longer period. These differences have important implications for monitoring these patients and for designing prevention trials. Copyright © 2017 Endocrine Society

Survival and expression of acid resistance genes in Shiga toxin-producing Escherichia coli acid adapted in pineapple juice and exposed to synthetic gastric fluid

USDA-ARS?s Scientific Manuscript database

Aims: The aim of this research was to examine relative transcriptional expression of acid resistance (AR) genes, rpoS, gadA and adiA, in O157:H7 and non-O157 Shiga toxin-producing Escherichia coli (STEC) serotypes after adaptation to pineapple juice (PJ) and subsequently to determine survival with e...

Predictors of Progression From the Appearance of Islet Autoantibodies to Early Childhood Diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY).

PubMed

Steck, Andrea K; Vehik, Kendra; Bonifacio, Ezio; Lernmark, Ake; Ziegler, Anette-G; Hagopian, William A; She, JinXiong; Simell, Olli; Akolkar, Beena; Krischer, Jeffrey; Schatz, Desmond; Rewers, Marian J

2015-05-01

While it is known that there is progression to diabetes in <10 years in 70% of children with two or more islet autoantibodies, predictors of the progression to diabetes are only partially defined. The Environmental Determinants of Diabetes in the Young (TEDDY) study has observed 8,503 children who were at increased genetic risk for autoimmune diabetes. Insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and insulinoma-associated protein 2 autoantibodies (IA-2As) were measured every 3 months until 4 years of age and every 6 months thereafter; if results were positive, the autoantibodies were measured every 3 months. Life table analysis revealed that the cumulative incidence of diabetes by 5 years since the appearance of the first autoantibody differed significantly by the number of positive autoantibodies (47%, 36%, and 11%, respectively, in those with three autoantibodies, two autoantibodies, and one autoantibody, P < 0.001). In time-varying survival models adjusted for first-degree relative status, number of autoantibodies, age at first persistent confirmed autoantibodies, and HLA genotypes, higher mean IAA and IA-2A levels were associated with an increased risk of type 1 diabetes in children who were persistently autoantibody positive (IAAs: hazard ratio [HR] 8.1 [95% CI 4.6-14.2]; IA-2A: HR 7.4 [95% CI 4.3-12.6]; P < 0.0001]). The mean GADA level did not significantly affect the risk of diabetes. In the TEDDY study, children who have progressed to diabetes usually expressed two or more autoantibodies. Higher IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

9. Typical 'furnished rooms' overlook the Washington Street alley. Each ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. Typical 'furnished rooms' overlook the Washington Street alley. Each has two double-hung windows that are fitted with roller-shade brackets. The plaster was formulated with lime and is heavily laden with animal hair. Each room is provided with a stove-pipe connection. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

11. An abandoned electrical system was found under the pressedsteel ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. An abandoned electrical system was found under the pressed-steel ceiling. For some undetermined reason the pattern of the ceiling panels has 'photographed' onto the cardboard substrate. Two different panel designs were utilized in a checkerboard pattern. One panel of each design remains in place. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

6. Detail of the west side showing the original brick ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. Detail of the west side showing the original brick detailing. The Roman bricks in the first story were installed in the 1950s. The heavy wood mullions are original and support a wood beam that carries the second-story brick facade. Remnants of the 1950s facade still remain above the parapet. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

12. Examples of the elaborate and plain pressedsteel ceiling panels, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. Examples of the elaborate and plain pressed-steel ceiling panels, here removed to the exterior of the building for photographing. A segment of the cornice has been placed above the larger panel. The panel on the left is comprised of four square components; the panel on the right is a single piece. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

17. The south wall of the dining room has an ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. The south wall of the dining room has an original wood wainscot similar to the one present on the north wall. However, in lieu of windows it appears to have been constructed with mirrors, which are no longer in place. The electrical boxes are nonoriginal elements. Simulated panel bevels are readily apparent in this view. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

Islet cell autoantibodies in African patients with Type 1 and Type 2 diabetes in Dar es Salaam Tanzania: a cross sectional study

PubMed Central

Lutale, JJK; Thordarson, H; Holm, PI; Eide, GE; Vetvik, K

2007-01-01

Background The aim of the present study was to assess the occurrence of glutamic acid decarboxylase autoantibodies (GADA) and insulinoma antigen 2 autoantibodies (IA2A) among patients of African origin in Dar es Salaam, Tanzania and to compare the occurrence of autoimmune mediated Type 1 diabetes with findings previously reported from the same place and from other African diabetic populations. Methods Two hundred and forty five patients from the diabetic clinic at Muhimbili Hospital were recruited for a cross sectional study. Patients were clinically classified into groups with Type 1 (T1D) and Type 2 diabetes (T2D); there were 94 patients with T1D and 151 with T2D. Autoantibodies for GAD and IA2 were measured with an assay based on radioligand binding. Fasting and random blood glucose, HbA1c, and C-peptide levels were also determined. Results Of the patients with T1D, 28 (29.8%) were GADA positive and 20 (21.3%) were IA2A positive. The overall occurrence of any autoantibody was 42.6%. The GAD and IA2 autoantibodies were detected more frequently among patients with T1D than among patients with T2D (P < 0.001). A higher autoantibody prevalence was observed with combined GADA and IA2A measurements compared to individual autoantibody measurements; 40 (42.6%) patients with T1D versus 11 (7.3%) with T2D had at least one positive autoantibody titer. There was no correlation between duration of disease and detection of autoantibodies in patients with T1D. There was a strong association with family history of diabetes among the autoantibody positive versus autoantibody negative patients with T1D (p < 0.01). Conclusion The prevalence of GAD and IA2 autoantibodies among African patients with T1D in Dar es Salaam was the same as that reported previously for South Africa and Ethiopia. It was much higher than the prevalence of islet cell autoantibodies (ICA) reported from the same clinic about 15 years ago. For unknown reasons the prevalence of pancreatic related autoantibodies

Rising Incidence of Type 1 Diabetes Is Associated With Altered Immunophenotype at Diagnosis

PubMed Central

Long, Anna E.; Gillespie, Kathleen M.; Rokni, Saba; Bingley, Polly J.; Williams, Alistair J.K.

2012-01-01

The incidence of type 1 diabetes has increased rapidly over recent decades, particularly in young children. We aimed to determine whether this rise was associated with changes in patterns of humoral islet autoimmunity at diagnosis. Autoantibodies to insulin (IAA), GAD (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) were measured by radioimmunoassay in sera collected from children and young adults with newly diagnosed type 1 diabetes between 1985 and 2002. The influence of date of diagnosis on prevalence and level of autoantibodies was investigated by logistic regression with adjustment for age and HLA class II genetic risk. Prevalence of IA-2A and ZnT8A increased significantly over the period studied, and this was mirrored by raised levels of IA-2A, ZnT8A, and IA-2β autoantibodies (IA-2βA). IAA and GADA prevalence and levels did not change. Increases in IA-2A, ZnT8A, and IA-2βA at diagnosis during a period of rising incidence suggest that the process leading to type 1 diabetes is now characterized by a more intense humoral autoimmune response. Understanding how changes in environment or lifestyle alter the humoral autoimmune response to islet antigens should help explain why the incidence of type 1 diabetes is increasing and may suggest new strategies for preventing disease. PMID:22315309

Sparse representation and Bayesian detection of genome copy number alterations from microarray data.

PubMed

Pique-Regi, Roger; Monso-Varona, Jordi; Ortega, Antonio; Seeger, Robert C; Triche, Timothy J; Asgharzadeh, Shahab

2008-02-01

Genomic instability in cancer leads to abnormal genome copy number alterations (CNA) that are associated with the development and behavior of tumors. Advances in microarray technology have allowed for greater resolution in detection of DNA copy number changes (amplifications or deletions) across the genome. However, the increase in number of measured signals and accompanying noise from the array probes present a challenge in accurate and fast identification of breakpoints that define CNA. This article proposes a novel detection technique that exploits the use of piece wise constant (PWC) vectors to represent genome copy number and sparse Bayesian learning (SBL) to detect CNA breakpoints. First, a compact linear algebra representation for the genome copy number is developed from normalized probe intensities. Second, SBL is applied and optimized to infer locations where copy number changes occur. Third, a backward elimination (BE) procedure is used to rank the inferred breakpoints; and a cut-off point can be efficiently adjusted in this procedure to control for the false discovery rate (FDR). The performance of our algorithm is evaluated using simulated and real genome datasets and compared to other existing techniques. Our approach achieves the highest accuracy and lowest FDR while improving computational speed by several orders of magnitude. The proposed algorithm has been developed into a free standing software application (GADA, Genome Alteration Detection Algorithm). http://biron.usc.edu/~piquereg/GADA

Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults

PubMed Central

Niegowska, Magdalena; Delitala, Alessandro; Pes, Giovanni Mario; Delitala, Giuseppe

2017-01-01

Latent Autoimmune Diabetes in Adults (LADA) is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of type 2 diabetes (T2D) with the presence of islet cell antigens detected in type 1 diabetes (T1D). Heterogeneous clinical picture have led to the classification of patients based on the levels of antibodies against glutamic acid decarboxylase 65 (GADA) that correlate with clinical phenotypes closer to T1D or T2D when GADA titers are high or low, respectively. To date, LADA etiology remains elusive despite numerous studies investigating on genetic predisposition and environmental risk factors. To our knowledge, this is the first study aimed at evaluation of a putative role played by Mycobacterium avium subsp. paratuberculosis (MAP) as an infective agent in LADA pathogenesis. MAP is known to cause chronic enteritis in ruminants and has been associated with autoimmune disorders in humans. We analyzed seroreactivity of 223 Sardinian LADA subjects and 182 healthy volunteers against MAP-derived peptides and their human homologs of proinsulin and zinc transporter 8 protein. A significantly elevated positivity for MAP/proinsulin was detected among patients, with the highest prevalence in the 32-41-year-old T1D-like LADA subgroup, supporting our hypothesis of a possible MAP contribution in the development of autoimmunity. PMID:28472070

Systematic Analysis of γ-Aminobutyric Acid (GABA) Metabolism and Function in the Social Amoeba Dictyostelium discoideum*

PubMed Central

Wu, Yuantai; Janetopoulos, Chris

2013-01-01

While GABA has been suggested to regulate spore encapsulation in the social amoeba Dictyostelium discoideum, the metabolic profile and other potential functions of GABA during development remain unclear. In this study, we investigated the homeostasis of GABA metabolism by disrupting genes related to GABA metabolism and signaling. Extracellular levels of GABA are tightly regulated during early development, and GABA is generated by the glutamate decarboxylase, GadB, during growth and in early development. However, overexpression of the prespore-specific homologue, GadA, in the presence of GadB reduces production of extracellular GABA. Perturbation of extracellular GABA levels delays the process of aggregation. Cytosolic GABA is degraded by the GABA transaminase, GabT, in the mitochondria. Disruption of a putative vesicular GABA transporter (vGAT) homologue DdvGAT reduces secreted GABA. We identified the GABAB receptor-like family member GrlB as the major GABA receptor during early development, and either disruption or overexpression of GrlB delays aggregation. This delay is likely the result of an abolished pre-starvation response and late expression of several “early” developmental genes. Distinct genes are employed for GABA generation during sporulation. During sporulation, GadA alone is required for generating GABA and DdvGAT is likely responsible for GABA secretion. GrlE but not GrlB is the GABA receptor during late development. PMID:23548898

Effect of simultaneous vaccination with H1N1 and GAD-alum on GAD65-induced immune response.

PubMed

Tavira, Beatriz; Cheramy, Mikael; Axelsson, Stina; Åkerman, Linda; Ludvigsson, Johnny; Casas, Rosaura

2017-07-01

A European Phase III trial of GAD formulated with aluminium hydroxide (GAD-alum) failed to reach its primary endpoint (preservation of stimulated C-peptide secretion from baseline to 15 months in type 1 diabetes patients), but subgroup analysis showed a clinical effect when participants from Nordic countries were excluded, raising concern as to whether the mass vaccination of the Swedish and Finnish populations with the Pandemrix influenza vaccine could have influenced the study outcomes. In the current study, we aimed to assess whether Pandemrix vaccination affects the specific immune responses induced by GAD-alum and the C-peptide response. In this secondary analysis, we analysed data acquired from the Swedish participants in the Phase III GAD-alum trial who received subcutaneous GAD-alum vaccination (two doses, n = 43; four doses, n = 46) or placebo (n = 48). GAD autoantibodies (GADA) and H1N1 autoantibodies, GAD 65 -induced cytokine secretion and change in fasting and stimulated C-peptide levels from baseline to 15 months were analysed with respect to the relative time between H1N1 vaccination and the first injection of GAD-alum. GADA levels at 15 months were associated with the relative time between GAD-alum and Pandemrix administration in participants who received two doses of the GAD-alum vaccine (p = 0.015, r = 0.4). Both in participants treated with two doses and four doses of GAD-alum, GADA levels were higher when the relative time between vaccines was ≥210 days (p < 0.05). In the group that received two doses of GAD-alum, levels of several GAD 65 -induced cytokines were higher in participants who received the H1N1 vaccination and the first GAD-alum injection at least 150 days apart, and the change in fasting and stimulated C-peptide at 15 months was associated with the relative time between vaccines. Neither of these effects were observed in individuals who received four doses of GAD-alum. In individuals who received two doses of GAD

Humoral Responses to Islet Antigen-2 and Zinc Transporter 8 Are Attenuated in Patients Carrying HLA-A*24 Alleles at the Onset of Type 1 Diabetes

PubMed Central

Long, Anna E.; Gillespie, Kathleen M.; Aitken, Rachel J.; Goode, Julia C.; Bingley, Polly J.; Williams, Alistair J.K.

2013-01-01

The HLA-A*24 allele has shown negative associations with autoantibodies to islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8) in patients with established type 1 diabetes. Understanding how this HLA class I allele affects humoral islet autoimmunity gives new insights into disease pathogenesis. We therefore investigated the epitope specificity of associations between HLA-A*24 and islet autoantibodies at disease onset. HLA-A*24 genotype and autoantibody responses to insulin (IAA), glutamate decarboxylase (GADA), IA-2, IA-2β, and ZnT8 were analyzed in samples collected from patients with recent-onset type 1 diabetes. After correction for age, sex, and HLA class II genotype, HLA-A*24 was shown to be a negative determinant of IA-2A and ZnT8A. These effects were epitope specific. Antibodies targeting the protein tyrosine phosphatase domains of IA-2 and IA-2β, but not the IA-2 juxtamembrane region, were less common in patients carrying HLA-A*24 alleles. The prevalence of ZnT8A specific or cross-reactive with the ZnT8 tryptophan-325 polymorphic residue, but not those specific to arginine-325, was reduced in HLA-A*24-positive patients. No associations were found between HLA-A*24 and IAA or GADA. Association of an HLA class I susceptibility allele with altered islet autoantibody phenotype at diagnosis suggests CD8 T-cell and/or natural killer cell–mediated killing modulates humoral autoimmune responses. PMID:23396399

Early prediction of autoimmune (type 1) diabetes.

PubMed

Regnell, Simon E; Lernmark, Åke

2017-08-01

Underlying type 1 diabetes is a genetic aetiology dominated by the influence of specific HLA haplotypes involving primarily the class II DR-DQ region. In genetically predisposed children with the DR4-DQ8 haplotype, exogenous factors, yet to be identified, are thought to trigger an autoimmune reaction against insulin, signalled by insulin autoantibodies as the first autoantibody to appear. In children with the DR3-DQ2 haplotype, the triggering reaction is primarily against GAD signalled by GAD autoantibodies (GADA) as the first-appearing autoantibody. The incidence rate of insulin autoantibodies as the first-appearing autoantibody peaks during the first years of life and declines thereafter. The incidence rate of GADA as the first-appearing autoantibody peaks later but does not decline. The first autoantibody may variably be followed, in an apparently non-HLA-associated pathogenesis, by a second, third or fourth autoantibody. Although not all persons with a single type of autoantibody progress to diabetes, the presence of multiple autoantibodies seems invariably to be followed by loss of functional beta cell mass and eventually by dysglycaemia and symptoms. Infiltration of mononuclear cells in and around the islets appears to be a late phenomenon appearing in the multiple-autoantibody-positive with dysglycaemia. As our understanding of the aetiology and pathogenesis of type 1 diabetes advances, the improved capability for early prediction should guide new strategies for the prevention of type 1 diabetes.

Department of the Army Justification of Estimates for Fiscal Year 1984 Submitted to Congress January 1983. Procurement Programs, Aircraft, Missiles, Weapons & Tracked Combat Vehicles, Ammunition and Other National Guard Equipment. Part 3.

DTIC Science & Technology

1983-01-01

Massachusetts Avenue ASA(RDI&A) (21672) 1 APA only Washington, DC 20314 ASA(M&RA) (21594) 1 DANA-WSN (3B455) 6 SALL (2C638) 24 MIPA only Comander 2 DACA ...BUL (3A652) 14 DAA-WSW (3D455) 7 US Army Material & Readiness DACA -BUF (33663) 10 PWTCV only Comand DACA -ZIA (23664) 1 DANA-CS (31432) 2 ATTN: DRCSM...mount for Obtigntiost Idwaitflaoan Gada Its2I-20.01 06 procwaaont actions prormodi -- ............ ---- 119112 actual 120 oat. 2664 at. 2061 actual 12663

10. View (looking west) of the ground floor in the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. View (looking west) of the ground floor in the south segment of the building. The door opening is on the Central Avenue sidewalk. The ground floor had two noteworthy pressed-steel ceilings, an elaborate one in the larger west room and a plain one in the smaller 'back room.' Most of the elaborate ceiling panels were removed when a suspended ceiling (here removed) was installed. The plain ceiling is still in-tact above the suspended ceiling. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

15. The second story in the north segment of the ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

15. The second story in the north segment of the building was originally constructed as a restaurant. The north wall of the dining room retains the original wood wainscot and double-hung windows. At some undetermined time, a building was constructed on the adjacent property; blocking the windows in the dining room. Several chimneys with stove-pipe connections occur in the room. The members seen on the floor are part of a system recently installed to support the failing roof. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

13. The south segment of the building has a stone ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

13. The south segment of the building has a stone basement. The alley wall had a number of areaway windows that are now infilled with bricks. These areaways were subsequently filled with earth, probably when the alley was paved. Here the first-floor joists are seen with a make-shift support beam and column. The basement floor originally was part earth and part wood. Some of the earth floor is now covered with a concrete slab; the wood floor remains. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

14. View toward the northwest corner of the basement in ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. View toward the northwest corner of the basement in the north segment of the building. Portions of the basement floor are earth, and portions are concrete. For some undetermined reason an unbonded, narrow panel of brick occurs in the west (left) wall. A corbeled brick footing is seen under this panel, as if the panel is carrying a concentrated load. An identical element occurs to the left, outside the camera's view. These 'columns' may support the second-story brick facade over the ground floor store windows. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

8. Several of the rental rooms are joined by doors, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Several of the rental rooms are joined by doors, and each room is accessed from the corridor. Originally, the transoms were glazed. When a central heating/cooling system was installed, the transoms were modified to accommodate air grilles that are supplied by a duct located in the corridor. The five-panel door and wood wainscot are original features. However, the wainscot does not occur in every room. The lath and plaster partitions and the wood flooring are typical of the original construction. Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

Clinical and biological characteristics of diabetic patients under age 40 in Cameroon: relation to autoantibody status and comparison with Belgian patients

PubMed Central

Asanghanwa, Milca; Gorus, Frans K.; Weets, Ilse; der Auwera, Bart V.; Aminkeng, Folefac; Mbunwe, Eric; Goubert, Patrick; Verhaeghen, Katrijn; Sobngwi, Eugene; Wenzlau, Janet M.; Hutton, John C.; Pipeleers, Daniel G.; Keymeulen, Bart; Mbanya, Jean-Claude N.; Schravendijk, Chris v.

2014-01-01

Aims We investigated the prevalence of diabetes autoantibodies (Abs) in Cameroonian patients and controls, assessed their contribution in disease classification and compared results with data from Belgium. Methods Abs against GAD (GADA), IA-2 (IA-2A) and zinc transporter 8 (ZnT8A) were assessed in 302 recently diagnosed Cameroonian patients with diabetes and 184 control subjects without diabetes aged below 40 years. Results Only 27 (9%) Cameroonian patients were younger than 15 years. Overall, 29% of patients presented at least one diabetes-associated antibody versus 9% in healthy controls (24% versus 7% for GADA (p < 0.001), 10% versus 3% for IA-2A (p < 0.006); 4% versus 2% for ZnT8A). Ab+ patients had lower C-peptide levels (p < 0.001), were more often insulin-treated (p < 0.002) and were as frequently diagnosed with type 1 diabetes as Ab− patients. Only 43% of Ab+ patients aged 15–39 years were clinically classified as having type 1 diabetes in Cameroon vs 96% in Belgium (p < 0.001). Not one Ab+ Cameroonian patient carried HLA-DQ2/DQ8 genotype versus 23% of Belgian Ab+ patients (p < 0.001). Younger age at diagnosis and antibody positivity were independent predictors of insulin therapy. Ab+ Cameroonian patients were older (p < 0.001), had higher BMI (p < 0.001) and lower Ab titers than Belgian Ab+ patients. In ketonuric patients, prevalence of autoantibodies was similar as in non-ketonuric patients. Conclusions In Cameroonian patients with diabetes aged under 40 years, antibody-positivity is not clearly related to disease phenotype, but may help predict the need for insulin treatment. PMID:24332797

Identification of novel autoantibodies in type 1 diabetic patients using a high-density protein microarray.

PubMed

Koo, Bo Kyung; Chae, Sehyun; Kim, Kristine M; Kang, Min Jueng; Kim, Eunhee G; Kwak, Soo Heon; Jung, Hye Seung; Cho, Young Min; Choi, Sung Hee; Park, Young Joo; Shin, Choong Ho; Jang, Hak C; Shin, Chan Soo; Hwang, Daehee; Yi, Eugene C; Park, Kyong Soo

2014-09-01

Autoantibodies can facilitate diagnostic and therapeutic means for type 1 diabetes (T1DM). We profiled autoantibodies from serum samples of 16 T1DM patients, 16 type 2 diabetic (T2DM) patients, and 27 healthy control subjects with normal glucose tolerance (NGT) by using protein microarrays containing 9,480 proteins. Two novel autoantibodies, anti-EEF1A1 and anti-UBE2L3, were selected from microarrays followed by immunofluorescence staining of pancreas. We then tested the validity of the candidates by ELISA in two independent test cohorts: 1) 95 adults with T1DM, 49 with T2DM, 11 with latent autoimmune diabetes in adults (LADA), 20 with Graves disease, and 66 with NGT and 2) 33 children with T1DM and 34 healthy children. Concentrations of these autoantibodies were significantly higher in T1DM patients than in NGT and T2DM subjects (P < 0.01), which was also confirmed in the test cohort of children (P < 0.05). Prevalence of anti-EEF1A1 and anti-UBE2L3 antibodies was 29.5% and 35.8% in T1DM, respectively. Of note, 40.9% of T1DM patients who lack anti-GAD antibodies (GADA) had anti-EEF1A1 and/or anti-UBE2L3 antibodies. These were also detected in patients with fulminant T1DM but not LADA. Our approach identified autoantibodies that can provide a new dimension of information indicative of T1DM independent of GADA and new insights into diagnosis and classification of T1DM. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Rituximab selectively suppresses specific islet antibodies.

PubMed

Yu, Liping; Herold, Kevan; Krause-Steinrauf, Heidi; McGee, Paula L; Bundy, Brian; Pugliese, Alberto; Krischer, Jeff; Eisenbarth, George S

2011-10-01

The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P < 0.0001). In the subgroup (n = 6) treated within 50 days of diabetes, IAAs were markedly suppressed by rituximab in all patients for 1 year and for four patients as long as 3 years despite continuing insulin therapy. Independent of rituximab treatment, the mean level of IAAs at study entry was markedly lower (P = 0.035) for patients who maintained C-peptide levels during the first year of follow-up in both rituximab-treated and placebo groups. A single course of rituximab differentially suppresses IAAs, clearly blocking IAAs for >1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific

19. At its east end, the dining room is separated ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

19. At its east end, the dining room is separated from the kitchen by a service room. On the south side of this room is an entrance to a rest room (left) and a dumb waiter (right). A large hoisting pulley is seen at the top of the shaft. Most of the apparatus is missing, but that which remains appears to be of a manual (non-electric) Type. An original lighting fixture, the only one encountered in the building, is seen near the center of the view. The service entrance into the dining room is located at the far right; the door into the kitchen is at the far left (almost in the margin of the photograph). Credit GADA/MRM. - Stroud Building, 31-33 North Central Avenue, Phoenix, Maricopa County, AZ

Data warehouse model for monitoring key performance indicators (KPIs) using goal oriented approach

NASA Astrophysics Data System (ADS)

Abdullah, Mohammed Thajeel; Ta'a, Azman; Bakar, Muhamad Shahbani Abu

2016-08-01

The growth and development of universities, just as other organizations, depend on their abilities to strategically plan and implement development blueprints which are in line with their vision and mission statements. The actualizations of these statements, which are often designed into goals and sub-goals and linked to their respective actors are better measured by defining key performance indicators (KPIs) of the university. The proposes ReGADaK, which is an extended the GRAnD approach highlights the facts, dimensions, attributes, measures and KPIs of the organization. The measures from the goal analysis of this unit serve as the basis of developing the related university's KPIs. The proposed data warehouse schema is evaluated through expert review, prototyping and usability evaluation. The findings from the evaluation processes suggest that the proposed data warehouse schema is suitable for monitoring the University's KPIs.

High prevalence of antithyroid peroxidase and antiparietal cell antibodies among patients with type 1 diabetes mellitus attending a tertiary diabetes centre in South Africa.

PubMed

Paruk, Imran M; Ganie, Yasmeen; Maharaj, Sureka; Pirie, Fraser J; Naidoo, Vasudevan G; Nkwanyana, Ntombifikile M; Dinnematin, Hilary L; Ramdial, Pratistadevi K; Motala, Ayesha A

2017-06-01

Data on the prevalence of autoimmune thyroid disease (AITD) and gastric autoimmunity in type 1 diabetes mellitus (T1DM) in Africa are limited. The aim of this study was to assess the prevalence of antithyroid peroxidase (TPO-A) and antiparietal cell antibody (PCA) in patients with T1DM at a tertiary diabetes clinic in Durban, South Africa. This was a cross-sectional observational study among subjects attending the adult T1DM clinic at Inkosi Albert Luthuli Hospital. Information about history and clinical examination was collected. Blood tests included glutamic acid decarboxylase antibody (GADA), TPO-A, PCA, vitamin B 12 , folate, ferritin, thyroid stimulating hormone (TSH), free thyroxine, lipids and HbA1c. A total of 202 (M:F, 90:112) patients were recruited. The ethnic composition was African (black) (56.4%; n=114), Indian (31.7%; n=64), white (4.5%; n=9) and coloured (mixed race) (7.4%; n=15). Mean age and mean duration of diabetes were 26.4±11.4 and 10.7±9.1 years, respectively. Mean body mass index was 21.6±6.3 kg/m 2 . GADA was positive in 63.37% (n=128). The prevalence of TPO-A was 18.9% (n=39) and PCA 8.9% (n=17). The prevalence of overt hypothyroidism, subclinical hypothyroidism and Graves' disease was 10.9%, 2.5% and 1.5%, respectively; vitamin B 12 deficiency was noted in 3.5% (n=7) and iron deficiency in 19.3% (n=39). Among patients with T1DM in this study, there was a high prevalence of coexistent AITD and gastric autoimmunity. Screening for hypothyroidism and thyroid autoimmunity should be undertaken in all patients at initial presentation. However, to assess the feasibility and optimal timing of subsequent testing in the African setting with limited resources, more collaborative research with longitudinal studies is required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Positive autoantibodies to ZnT8 indicate elevated risk for additional autoimmune conditions in patients with Addison's disease.

PubMed

Fichna, Marta; Rogowicz-Frontczak, Anita; Żurawek, Magdalena; Fichna, Piotr; Gryczyńska, Maria; Zozulińska-Ziółkiewicz, Dorota; Ruchała, Marek

2016-07-01

Autoimmune Addison's disease (AAD) associates with exceptional susceptibility to develop other autoimmune conditions, including type 1 diabetes (T1D), marked by positive serum autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated protein 2 (IA-2A). Zinc transporter 8 (ZnT8) is a new T1D autoantigen, encoded by the SLC30A8 gene. Its polymorphic variant rs13266634C/T seems associated with the occurrence of serum ZnT8 antibodies (ZnT8A). This study was designed to determine the prevalence of serum ZnT8A and their clinical implication in 140 AAD patients. Other beta cell and thyroid-specific autoantibodies were also investigated, and ZnT8A results were confronted with the rs13266634 genotype. ZnT8A were detectable in 8.5 %, GADA in 20.7 %, IA-2A in 5.7 %, IAA in 1.6 % and various anti-thyroid antibodies in 7.1-67.8 % individuals. Type 1 diabetes was found in 10 % AAD patients. ZnT8A were positive in 57.1 % of T1D patients and 3.4 % non-diabetic AAD. Analysis of ZnT8A enabled to identify autoimmunity in two (14.3 %) T1D individuals previously classified as autoantibody-negative. ZnT8A-positive patients revealed significantly higher number of autoimmune conditions (p < 0.001), increased prevalence of T1D (p < 0.001) and other beta cell-specific autoantibodies. Carriers of the rs13266634 T-allele displayed increased frequency (p = 0.006) and higher titres of ZnT8A (p = 0.002). Our study demonstrates high incidence of ZnT8A in AAD patients. ZnT8A are associated with coexisting T1D and predictive of T1D in non-diabetic subjects. Moreover, positive ZnT8A in AAD indicate elevated risk for additional autoimmune conditions. Autoantibodies to beta cell antigens, comprising ZnT8, could be included in routine screening panels in AAD.

Characterisation of rapid progressors to type 1 diabetes among children with HLA-conferred disease susceptibility.

PubMed

Pöllänen, Petra M; Lempainen, Johanna; Laine, Antti-Pekka; Toppari, Jorma; Veijola, Riitta; Vähäsalo, Paula; Ilonen, Jorma; Siljander, Heli; Knip, Mikael

2017-07-01

In this study, we aimed to characterise rapid progressors to type 1 diabetes among children recruited from the general population, on the basis of HLA-conferred disease susceptibility. We monitored 7410 HLA-predisposed children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study for the development of beta cell autoimmunity and type 1 diabetes from birth over a median follow-up time of 16.2 years (range 0.9-21.1 years). Islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD (GADA) and islet antigen 2 (IA-2A) were assessed as markers of beta cell autoimmunity. Rapid progression was defined as progression to clinical type 1 diabetes within 1.5 years of autoantibody seroconversion. We analysed the association between rapid progression and demographic and autoantibody characteristics as well as genetic markers, including 25 non-HLA SNPs predisposing to type 1 diabetes. Altogether, 1550 children (21%) tested positive for at least one diabetes-associated autoantibody in at least two samples, and 248 (16%) of seroconverters progressed to type 1 diabetes by the end of 2015. The median time from seroconversion to diagnosis was 0.51 years in rapid progressors (n = 42, 17%) and 5.4 years in slower progressors. Rapid progression was observed both among young (<5 years) and early pubertal children (>7 years), resulting in a double-peak distribution of seroconversion age. Compared with slower progressors, rapid progressors had a higher frequency of positivity for multiple (≥2) autoantibodies and had higher titres of ICA, IAA and IA-2A at seroconversion, and there was a higher prevalence of the secretor genotype in the FUT2 gene among those carrying the high-risk HLA genotype. Compared with autoantibody-positive non-progressors, rapid progressors were younger, were more likely to carry the high-risk HLA genotype and a predisposing SNP in the PTPN22 gene, had higher frequency of ICA, IAA, GADA and IA-2A positivity and

Restoration of GABA production machinery in Lactobacillus brevis by accessible carbohydrates, anaerobiosis and early acidification.

PubMed

Wu, Qinglong; Shah, Nagendra P

2018-02-01

Lactobacillus brevis is an efficient cell factory for producing bioactive γ-aminobutyric acid (GABA) by its gad operon-encoded glutamic acid decarboxylase (GAD) system. However, little mechanistic insights have been reported on the effects of carbohydrate, oxygen and early acidification on GABA production machinery in Lb. brevis. In the present study, GABA production from Lb. brevis was enhanced by accessible carbohydrates. Fast growth of this organism was stimulated by maltose and xylose. However, its GABA production was highly suppressed by oxygen exposure, but was fully restored by anaerobiosis that up-regulated the expression of gad operon in Lb. brevis cells. Although the level of cytosolic acidity was suitable for the functioning of GadA and GadB, early acidification of the medium (ipH 5 and ipH 4) restored GABA synthesis strictly in aerated cells of Lb. brevis because the expression of gad operon was not up-regulated in them. We conclude that GABA production machinery in Lb. brevis could be restored by accessible carbohydrates, anaerobiosis and early acidification. This will be of interest for controlling fermentation for synthesis of GABA and manufacturing GABA-rich fermented vegetables. Copyright © 2017. Published by Elsevier Ltd.

Assessment of Wind Shear and Wind Energy Potential in the Baltic Sea Region of Latvia

NASA Astrophysics Data System (ADS)

Bezrukovs, V.; Bezrukovs, Vl.; Zacepins, A.; Komashilovs, V.

2015-04-01

The paper is devoted to the investigation into the wind energy potential based on long-term observations of the wind speed and energy density fluctuations at heights from 10 to 160 m on the Baltic Sea coast of Latvia. During the observations (2004 - 2013), the wind speed and direction values were measured, and the statistical database was accumulated using a LOGGER 9200 Symphonie measuring systems mounted on 60 m masts - one on the western coast and another on the north-east of Latvia. From June 2011 to May 2012, these measurements were complemented with the data for the heights from 40 to 160 m obtained by means of a ZephIR lidar and with the metrological data provided by "Latvian Environment, Geology and Meteorology Centre" for the same period. The graphs of seasonal fluctuations in the wind speed were obtained for the heights up to 160 m by measurements over the period of 2007 - 2013. The results of the research on the wind speed distribution up to 200 m are promising for evaluation of the wind energy potential of Latvia and will be helpful in assessment of prospective sites for construction of WPPs. Zinātniskais raksts ir veltīts pētījumam par vēja enerģijas potenciālu Latvijas teritorijā, Baltijas jūras piekrastē, balstoties uz ilgtermiņa vēja ātruma un vēja enerģijas blīvuma svārstību novērojumiem no 10 līdz 160 metriem augstumā. Vēja ātruma un vēja virziena mērījumu dati tika iegūti un apkopoti statistiskajā datubāzē laika periodā no 2004 līdz 2013. gadam, izmantojot mērīšanas sistēmu LOGGER 9200 Symphonie, kas bija ierīkotā uz 60 metru augsta masta - viena rietumu piekrastē un otra Latvijas ziemeļu-austrumos. No 2011. gada jūnija līdz 2012. gada maijam mērījumu datubāze tika papildināta ar datiem, kas tika iegūti ar lidaruZephIR augstumos no 40 līdz 160 metriem, un datiem no "Latvijas Vides, ģeoloģijas un meteoroloģijas centra" tam pašam laika periodam. Analizējot mērījumus 2007. g.-2013. g., grafiki ar

Physiological adaptation of Escherichia coli after transfer onto refrigerated ground meat and other solid matrices: a molecular approach.

PubMed

Guernec, Anthony; Robichaud-Rincon, Philippe; Saucier, Linda

2012-10-01

Bacteria on meat are subjected to specific living conditions that differ drastically from typical laboratory procedures in synthetic media. This study was undertaken to determine the behavior of bacteria when transferred from a rich-liquid medium to solid matrices, as is the case during microbial process validation. Escherichia coli cultured in Brain-Heart Infusion (BHI) broth to different growth phases were inoculated in ground beef (GB) and stored at 5°C for 12 days or spread onto BHI agar and cooked meat medium (CMM), and incubated at 37°C for several hours. We monitored cell densities and the expression of σ factors and genes under their control over time. The initial growth phase of the inoculum influenced growth resumption after transfer onto BHI agar and CMM. Whatever the solid matrix, bacteria adapted to their new environment and did not perceive stress immediately after inoculation. During this period, the σ(E) and σ(H) regulons were not activated and rpoD mRNA levels adjusted quickly. The rpoS and gadA mRNA levels did not increase after inoculation on solid surfaces and displayed normal growth-dependent modifications. After transfer onto GB, dnaK and groEL gene expression was affected more by the low temperature than by the composition of a meat environment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Reduced Histone H3 Lysine 9 Methylation Contributes to the Pathogenesis of Latent Autoimmune Diabetes in Adults via Regulation of SUV39H2 and KDM4C.

PubMed

Liu, Xi-Yu; Li, Hong

2017-01-01

Aims . Latent autoimmune diabetes in adults (LADA) is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity. Methods . Blood CD4 + T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status. Results . Reduced global H3 lysine 9 methylation was observed in LADA patients' CD4 + T lymphocytes, compared to healthy controls ( P < 0.05). H3 lysine 4 methylation was not statistically different. The reduced H3 lysine 9 methylation was associated with GADA titer but not correlated with glycosylated hemoglobin (HbA1c). When the LADA patient group was divided into those with complication and those without, relatively reduced global H3 lysine 9 methylation was observed in LADA patients with complication ( P < 0.05). The expression of histone methyltransferase SUV39H2 for H3 lysine 9 methylation was downregulated in LADA patients, and the expression of histone demethylase KDM4C which made H3 lysine 9 demethylation was upregulated. Conclusion . The reduction of histone H3 lysine 9 methylation which may due to the downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C was found in CD4 + T lymphocytes of LADA patients.

PA01.01. A clinical study on the effect of paneeya kshara in the management of asmari w.s.r. to urinary calculi

PubMed Central

Chakradhar, K V

2012-01-01

Purpose: In Ayurveda, the diseases asmari was described under asta maha gada by Susrutha. This shows how difficult this disease to treat medically or surgically. According to modern science, various deposits of urological salts precipitate and form the calculi. The prevalence of these disease urinary calculi is about 3% of population with 1% of highly exploitable with severe agony and complications. The management in contemporary modern science is toughest approach because it may solve the problem temporarily but cannot render preventing or recurrence. Hence there is need to evaluate a better remedy. Here the kshara described by susrutha is selected and the yava kshara is chosen for study. Method: Total of 10 patients was selected from the SV ayurvedic college, Tirupati after subjecting to selection criteria based on inclusion and exclusion criteria. These 10 patients are given with yava kshara as paneeya kshara with the dose of 250 mg once in week for 4 weeks. The observations are noted and results were assessed on the basis of subjective (scoring prepared for symptomatology for pain, burning micturition, dysuria, tenderness in renal angle, haematuria, microscopic analysis of urine) and objective (kub usg) parameters. And then they are subjected for statistical validity. Result: It is found to be the yava kshara (paneeya kshara) is effective reducing the symptoms and producing remarkable benefit to patient. Conclusion: Even though it is difficult to treat the disease asmari, the yava kshara shown significant result and definitely be simple to use and cost effective management.

Impact of waste disposal on health of a poor urban community in Zimbambwe.

PubMed

Makoni, F S; Ndamba, J; Mbati, P A; Manase, G

2004-08-01

To assess excreta and waste disposal facilities available and their impact on sanitation related diseases in Epworth, an informal settlement on the outskirts of Harare. Descriptive cross-sectional survey. This was a community based study of Epworth informal settlement. A total of 308 households were interviewed. Participating households were randomly selected from the three communities of Epworth. Secondary medical archival data on diarrhoeal disease prevalence was collected from local clinics and district health offices in the study areas. Only 7% of households were connected to the sewer system. The study revealed that in Zinyengere extension 13% had no toilet facilities, 48% had simple pits and 37% had Blair VIP latrines. In Overspill 2% had no toilet facilities, 28% had simple latrines and 36% had Blair VIP latrines while in New Gada 20% had no toilet facilities, 24% had simple pits and 23% had Blair VIP latrines. Although a significant percentage had latrines (83.2%), over 50% of the population were not satisfied with the toilet facilities they were using. All the respondents expressed dissatisfaction with their domestic waste disposal practices with 46.6% admitting to have indiscriminately dumped waste. According to the community, diarrhoeal diseases were the most prevalent diseases (50%) related to poor sanitation. Health statistics also indicated that diarrhoea was a major problem in this community. It is recommended that households and the local authorities concentrate on improving the provision of toilets, water and waste disposal facilities as a way of improving the health state of the community.

Analytical Treatment of Forecasts of Electric Energy Consumption in Latvia

NASA Astrophysics Data System (ADS)

Balodis, M.; Gavars, V.; Andersons, J.

2014-06-01

In the paper, the changes in electric energy consumption are analyzed as associated with structural changes in the Latvian economy of postsocialistic period. To the analysis, a particular approach is applied, which consists in comparison of the basic and specific electricity consumption indices in West-, Central-, and East-European states for the time span of 1990-2010, with differences and tendencies of changes revealed. Tendencies of the type are determined for the electric energy consumption in Latvia, and recommendations are given for the use of such indices in the relevant forecasts. Rakstā apskatītas elektroenerģijas patēriņa izmaiņas, kas saistītas ar Latvijas postsociālisma perioda ekonomikas strukturālām izmaiņām. Rakstā dota Latvijas galveno elektroenerģijas patēriņa indikatoru analīze, lietojot īpašu pieeju - Rietumeiropas, Centrāleiropas un Austrumeiropas valstu indikatoru salīdzinājumu. Analizēts periods no 1990. gada līdz 2010. gadam. Salīdzināti Eiropas valstu grupu īpatnējie elektroenerģijas patēriņa indikatori un noskaidrotas to atšķirības un izmaiņu tendences. Noteiktas elektroenerģijas patēriņa izmaiņu tendences Latvijā. Dotas rekomendācijas par šo indikatoru izmantošanu elektroenerģijas patēriņa prognozēšanā. 07.05.2014.

Distinct Transcriptional Profiles and Phenotypes Exhibited by Escherichia coli O157:H7 Isolates Related to the 2006 Spinach-Associated Outbreak

PubMed Central

Kyle, Jennifer L.; Huynh, Steven; Carter, Michelle Q.; Brandl, Maria T.; Mandrell, Robert E.

2012-01-01

In 2006, a large outbreak of Escherichia coli O157:H7 was linked to the consumption of ready-to-eat bagged baby spinach in the United States. The likely sources of preharvest spinach contamination were soil and water that became contaminated via cattle or feral pigs in the proximity of the spinach fields. In this study, we compared the transcriptional profiles of 12 E. coli O157:H7 isolates that possess the same two-enzyme pulsed-field gel electrophoresis (PFGE) profile and are related temporally or geographically to the above outbreak. These E. coli O157:H7 isolates included three clinical isolates, five isolates from separate bags of spinach, and single isolates from pasture soil, river water, cow feces, and a feral pig. The three clinical isolates and two spinach bag isolates grown in cultures to stationary phase showed decreased expression of many σS-regulated genes, including gadA, osmE, osmY, and katE, compared with the soil, water, cow, feral pig, and the other three spinach bag isolates. The decreased expression of these σS-regulated genes was correlated with the decreased resistance of the isolates to acid stress, osmotic stress, and oxidative stress but increases in scavenging ability. We also observed that intraisolate variability was much more pronounced among the clinical and spinach isolates than among the environmental isolates. Together, the transcriptional and phenotypic differences of the spinach outbreak isolates of E. coli O157:H7 support the hypothesis that some variants within the spinach bag retained characteristics of the preharvest isolates, whereas other variants with altered gene expression and phenotypes infected the human host. PMID:22081562

Copy number variation signature to predict human ancestry

PubMed Central

2012-01-01

Background Copy number variations (CNVs) are genomic structural variants that are found in healthy populations and have been observed to be associated with disease susceptibility. Existing methods for CNV detection are often performed on a sample-by-sample basis, which is not ideal for large datasets where common CNVs must be estimated by comparing the frequency of CNVs in the individual samples. Here we describe a simple and novel approach to locate genome-wide CNVs common to a specific population, using human ancestry as the phenotype. Results We utilized our previously published Genome Alteration Detection Analysis (GADA) algorithm to identify common ancestry CNVs (caCNVs) and built a caCNV model to predict population structure. We identified a 73 caCNV signature using a training set of 225 healthy individuals from European, Asian, and African ancestry. The signature was validated on an independent test set of 300 individuals with similar ancestral background. The error rate in predicting ancestry in this test set was 2% using the 73 caCNV signature. Among the caCNVs identified, several were previously confirmed experimentally to vary by ancestry. Our signature also contains a caCNV region with a single microRNA (MIR270), which represents the first reported variation of microRNA by ancestry. Conclusions We developed a new methodology to identify common CNVs and demonstrated its performance by building a caCNV signature to predict human ancestry with high accuracy. The utility of our approach could be extended to large case–control studies to identify CNV signatures for other phenotypes such as disease susceptibility and drug response. PMID:23270563

Testing for monogenic diabetes among children and adolescents with antibody-negative clinically defined Type 1 diabetes.

PubMed

Rubio-Cabezas, O; Edghill, E L; Argente, J; Hattersley, A T

2009-10-01

Monogenic diabetes is frequently misdiagnosed as Type 1 diabetes. We aimed to screen for undiagnosed monogenic diabetes in a cohort of children who had a clinical diagnosis of Type 1 diabetes but were pancreatic autoantibody-negative. We studied 252 patients diagnosed clinically with Type 1 diabetes between 6 months and 17 years of age. Pancreatic autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase antibodies (GADA) and/or insulinoma-associated antigen-2 antibodies (IA2A)] were absent in 25 cases (9.9%). The most frequent genes involved in monogenic diabetes [KCNJ11 and INS for neonatal diabetes and HNF1A and HNF4A for maturity-onset diabetes of the young (MODY)] were directly sequenced. Two of the 25 (8%) antibody-negative patients had de novo heterozygous mutations in INS; c.94G>A (G32S) and c.265C>T (R89C). The two patients presented with non-ketotic hyperglycaemia at 8 and 11 months of age. In contrast, the four antibody-positive patients who presented at a similar age (6-12 months) had a more severe metabolic derangement, manifested as ketosis in all four cases, with ketoacidosis in two. At ages 15 and 5 years, both INS mutation patients were prescribed a replacement dose of insulin with good glycaemic control [glycated haemoglobin (HbA(1c)) 7.0 and 7.2%]. No mutations were found in KCNJ11, HNF1A or HNF4A. The identification of patients with monogenic diabetes from children with clinically defined Type 1 diabetes may be helped by clinical criteria including the absence of pancreatic autoantibodies.

The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients.

PubMed

Sosenko, Jay M; Skyler, Jay S; Palmer, Jerry P; Krischer, Jeffrey P; Yu, Liping; Mahon, Jeffrey; Beam, Craig A; Boulware, David C; Rafkin, Lisa; Schatz, Desmond; Eisenbarth, George

2013-09-01

We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity. The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23-3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78-0.90] at 2 years, 0.81 [0.74-0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded from the risk score model. The combination of the ABRS and the previously validated Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) predicted T1D more accurately (0.93 [0.88-0.98] at 2 years, 0.91 [0.83-0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons). These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels of multiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D.

Sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes.

PubMed

Löfvenborg, Josefin E; Andersson, Tomas; Carlsson, Per-Ola; Dorkhan, Mozhgan; Groop, Leif; Martinell, Mats; Tuomi, Tiinamaija; Wolk, Alicja; Carlsson, Sofia

2016-12-01

Sweetened beverage intake is associated with increased risk of type 2 diabetes, but its association with autoimmune diabetes is unclear. We aimed to investigate sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA); autoimmune diabetes with features of type 2 diabetes. Data from a Swedish population-based study was used, including incident cases of LADA (n = 357) and type 2 diabetes (n = 1136) and randomly selected controls (n = 1371). Diabetes classification was based on onset age (≥35), glutamic acid decarboxylase autoantibodies (GADA) and C-peptide. Sweetened beverage intake information was derived from a validated food frequency questionnaire. ORs adjusted for age, sex, family history of diabetes, education, lifestyle, diet, energy intake and BMI were estimated using logistic regression. Daily intake of >2 servings of sweetened beverages (consumed by 6% of participants) was associated with increased risk of LADA (OR: 1.99, 95% CI: 1.11-3.56), and for each 200 mL daily serving, OR was 1.15 (95% CI: 1.02-1.29). Findings were similar for sugar-sweetened (OR: 1.18, 95% CI: 1.00-1.39) and artificially sweetened beverages (OR: 1.12, 95% CI: 0.95-1.32). Similarly, each daily serving increment in total sweetened beverage conferred 20% higher type 2 diabetes risk (95% CI: 1.07-1.34). In type 2 diabetes patients, high consumers displayed higher HOMA-IR levels (4.5 vs 3.5, P = 0.0002), but lower HOMA-B levels (55 vs 70, P = 0.0378) than non-consumers. Similar tendencies were seen in LADA. High intake of sweetened beverages was associated with increased risk of LADA. The observed relationship resembled that with type 2 diabetes, suggesting common pathways possibly involving insulin resistance. © 2016 European Society of Endocrinology.

Induction of Escherichia coli into a VBNC state through chlorination/chloramination and differences in characteristics of the bacterium between states.

PubMed

Chen, Sheng; Li, Xi; Wang, Yahong; Zeng, Jie; Ye, Chengsong; Li, Xianping; Guo, Lizheng; Zhang, Shenghua; Yu, Xin

2018-05-30

Many pathogens can enter into a viable but nonculturable (VBNC) state in response to harsh environmental stresses. Bacteria in this state can retain certain features of viable cells, such as cellular integrity, metabolic activity, or virulence and may present health risks associated with drinking water. In this study, we investigated the ability of chlorination and chloramination, which are widely used methods to disinfect drinking water, to induce Escherichia coli into a VBNC state. After treatment with chlorine and chloramine at concentrations of 1, 2, 3, and 4 mg/L, the counts of culturable E. coli cells decreased from 10 6  CFU/mL to 0 CFU/mL at 5-60 min post treatment. Meanwhile, viable cell counts were still approximately 10 3 -10 5  cells/mL. These viable E. coli cells may be induced into a VBNC state by chlorination and chloramination. Scanning electron microscopy and laser confocal microscopy showed that some bacteria maintained cellular integrity, but the average length of VBNC cells was less than that of culturable cells. Respiratory activity of VBNC cells decreased approximately 50% relative to that of culturable cells. We also used heavy water (D 2 O) combined with Raman microspectroscopy to show that E. coli in a VBNC state retained metabolic activity involving water (e.g. condensation reactions) at the single-cell level. Furthermore, soxR, gadA, and katG genes remained highly expressed, suggesting that VBNC cells were physiologically active. Finally, resuscitation of VBNC cells induced by chlorine in Luria-Bertani (LB) broth was identified by calculating the generation time. Results of this study will facilitate a better understanding of the health risks associated with VBNC bacteria and the development of more effective strategies for drinking water disinfection. Copyright © 2018. Published by Elsevier Ltd.

[Clinical parameters for molecular testing of Maturity Onset Diabetes of the Young (MODY)].

PubMed

Datz, N; Nestoris, C; von Schütz, W; Danne, T; Driesel, A J; Maringa, M; Kordonouri, O

2011-05-01

Monogenic forms of diabetes are often diagnosed by chance, due to the variety of clinical presentation and limited experience of the diabetologists with this kind of diabetes. Aim of this study was to evaluate clinical parameters for an efficient screening. Clinical parameters were: negative diabetes-specific antibodies at onset of diabetes, positive family history of diabetes, and low to moderate insulin requirements after one year of diabetes treatment. Molecular testing was performed through sequencing of the programming regions of HNF-4alpha (MODY 1), glucokinase (MODY 2) and HNF-1alpha/TCF1 (MODY 3) and in one patient the HNF-1beta/TCF2 region (MODY 5). 39 of 292 patients treated with insulin were negative for GADA and IA2A, and 8 (20.5%) patients fulfilled both other criteria. Positive molecular results were found in five (63%) patients (two with MODY 2, two with MODY 3, one with MODY 5). At diabetes onset, the mean age of the 5 patients with MODY was 10.6 ± 5.3 yrs (range 2.6-15 yrs), HbA(1c) was 8.4 ± 3.1 % (6.5-13.9%), mean diabetes duration until diagnosis of MODY was 3.3 ± 3.6 yrs (0.8-9.6 yrs) with insulin requirements of 0.44 ± 0.17 U/kg/d (0.2-0.6 U/kg/d). Patients with MODY 3 were changed from insulin to repaglinide, those with MODY 2 were recommended discontinuing insulin treatment. In patients with negative diabetes-specific antibodies at onset of diabetes, with a positive family history, and low to moderate insulin needs a genetic screening for MODY is indicated. Watchful consideration of these clinical parameters may lead to an early genetic testing, and to an adequate treatment. © Georg Thieme Verlag KG Stuttgart · New York.

Family-Based Benchmarking of Copy Number Variation Detection Software.

PubMed

Nutsua, Marcel Elie; Fischer, Annegret; Nebel, Almut; Hofmann, Sylvia; Schreiber, Stefan; Krawczak, Michael; Nothnagel, Michael

2015-01-01

The analysis of structural variants, in particular of copy-number variations (CNVs), has proven valuable in unraveling the genetic basis of human diseases. Hence, a large number of algorithms have been developed for the detection of CNVs in SNP array signal intensity data. Using the European and African HapMap trio data, we undertook a comparative evaluation of six commonly used CNV detection software tools, namely Affymetrix Power Tools (APT), QuantiSNP, PennCNV, GLAD, R-gada and VEGA, and assessed their level of pair-wise prediction concordance. The tool-specific CNV prediction accuracy was assessed in silico by way of intra-familial validation. Software tools differed greatly in terms of the number and length of the CNVs predicted as well as the number of markers included in a CNV. All software tools predicted substantially more deletions than duplications. Intra-familial validation revealed consistently low levels of prediction accuracy as measured by the proportion of validated CNVs (34-60%). Moreover, up to 20% of apparent family-based validations were found to be due to chance alone. Software using Hidden Markov models (HMM) showed a trend to predict fewer CNVs than segmentation-based algorithms albeit with greater validity. PennCNV yielded the highest prediction accuracy (60.9%). Finally, the pairwise concordance of CNV prediction was found to vary widely with the software tools involved. We recommend HMM-based software, in particular PennCNV, rather than segmentation-based algorithms when validity is the primary concern of CNV detection. QuantiSNP may be used as an additional tool to detect sets of CNVs not detectable by the other tools. Our study also reemphasizes the need for laboratory-based validation, such as qPCR, of CNVs predicted in silico.

The Prediction of Type 1 Diabetes by Multiple Autoantibody Levels and Their Incorporation Into an Autoantibody Risk Score in Relatives of Type 1 Diabetic Patients

PubMed Central

Sosenko, Jay M.; Skyler, Jay S.; Palmer, Jerry P.; Krischer, Jeffrey P.; Yu, Liping; Mahon, Jeffrey; Beam, Craig A.; Boulware, David C.; Rafkin, Lisa; Schatz, Desmond; Eisenbarth, George

2013-01-01

OBJECTIVE We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity. RESULTS The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23–3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78–0.90] at 2 years, 0.81 [0.74–0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded from the risk score model. The combination of the ABRS and the previously validated Diabetes Prevention Trial–Type 1 Risk Score (DPTRS) predicted T1D more accurately (0.93 [0.88–0.98] at 2 years, 0.91 [0.83–0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons). CONCLUSIONS These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels of multiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D. PMID:23818528

The JPSS Ground Project Algorithm Verification, Test and Evaluation System

NASA Astrophysics Data System (ADS)

Vicente, G. A.; Jain, P.; Chander, G.; Nguyen, V. T.; Dixon, V.

2016-12-01

The Government Resource for Algorithm Verification, Independent Test, and Evaluation (GRAVITE) is an operational system that provides services to the Suomi National Polar-orbiting Partnership (S-NPP) Mission. It is also a unique environment for Calibration/Validation (Cal/Val) and Data Quality Assessment (DQA) of the Join Polar Satellite System (JPSS) mission data products. GRAVITE provides a fast and direct access to the data and products created by the Interface Data Processing Segment (IDPS), the NASA/NOAA operational system that converts Raw Data Records (RDR's) generated by sensors on the S-NPP into calibrated geo-located Sensor Data Records (SDR's) and generates Mission Unique Products (MUPS). It also facilitates algorithm investigation, integration, checkouts and tuning, instrument and product calibration and data quality support, monitoring and data/products distribution. GRAVITE is the portal for the latest S-NPP and JPSS baselined Processing Coefficient Tables (PCT's) and Look-Up-Tables (LUT's) and hosts a number DQA offline tools that takes advantage of the proximity to the near-real time data flows. It also contains a set of automated and ad-hoc Cal/Val tools used for algorithm analysis and updates, including an instance of the IDPS called GRAVITE Algorithm Development Area (G-ADA), that has the latest installation of the IDPS algorithms running in an identical software and hardware platforms. Two other important GRAVITE component are the Investigator-led Processing System (IPS) and the Investigator Computing Facility (ICF). The IPS is a dedicated environment where authorized users run automated scripts called Product Generation Executables (PGE's) to support Cal/Val and data quality assurance offline. This data-rich and data-driven service holds its own distribution system and allows operators to retrieve science data products. The ICF is a workspace where users can share computing applications and resources and have full access to libraries and

HLA-typing, clinical, and immunological characterization of youth with type 2 diabetes mellitus phenotype from the German/Austrian DPV database.

PubMed

Awa, Wendy L; Boehm, Bernard O; Rosinger, Silke; Achenbach, Peter; Ziegler, Anette G; Krause, Stephanie; Meissner, Thomas; Wiegand, Susanne; Reinehr, Thomas; Kapellen, Thomas; Karges, Beate; Eiermann, Thomas; Schober, Edith; Holl, Reinhard W

2013-12-01

To characterize the clinical and immunological features of HLA-typed youth with pediatric onset of type 2 diabetes mellitus (T2DM). One hundred and seven patients with clinically diagnosed T2DM (aged ≤20 yr at diagnosis) were examined. DNA and serum, obtained after a median diabetes duration of 2.2 (Q1-Q3: 0.8-4.6) yr, were used for centralized HLA-typing and autoantibody (GADA, IA-2A, ZnT8A) measurements. 64.6% of patients were female and median age at diagnosis was 13.8 (Q1-Q3: 11.6-15.4) yr. Patients were obese [median body mass index-standard deviation score (BMI-SDS): 2.6 (2.0-3.1)], 88.0% had a family history of diabetes and 40.2% a migration background. Islet autoantibodies were detected in 16 (15.0%), among which 7 (6.5%) had multiple islet autoantibodies. Autoantibody positive patients had poorer metabolic control than autoantibody negative patients [glycosylated hemoglobin A1c (HbA1c): 8.1 (6.9-10.1) % vs. 6.6 (5.9-8.0) %; p = 0.033], while patients with HLA-DR genetic risk had higher BMI-SDS than those with HLA-DRXX [2.6 (2.4-3.7) vs. 2.4 (1.7-2.9); p = 0.007]. Metabolic syndrome (61.7%), microalbuminuria (13.4%), and retinopathy (3.9%) were diagnosed. Therapies used were lifestyle only (35.5%), oral anti-diabetics (OAD) only (43.3 %), insulin +  OAD (15.9%) and insulin only (5.6%). Patients with β-cell autoimmunity or HLA-DR genetic risk more frequently used insulin than confirmed T2DM patients (50.0 vs. 22.0%; p = 0.037) and less often had diabetic relatives (61.1 vs. 86.0%; p = 0.030). T2DM was confirmed in about 90% of patients while about 10% with β-cell autoimmunity or HLA-DR genetic risk likely had either T1.5DM or 'double diabetes' or an unknown diabetes type. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhanced productivity of gamma-amino butyric acid by cascade modifications of a whole-cell biocatalyst.

PubMed

Yang, Xinwei; Ke, Chongrong; Zhu, Jiangming; Wang, Yan; Zeng, Wenchao; Huang, Jianzhong

2018-04-01

We previously developed a gamma-amino butyric acid (GABA)-producing strain of Escherichia coli, leading to production of 614.15 g/L GABA at 45 °C from L-glutamic acid (L-Glu) with a productivity of 40.94 g/L/h by three successive whole-cell conversion cycles. However, the increase in pH caused by the accumulation of GABA resulted in inactivation of the biocatalyst and consequently led to relatively lower productivity. In this study, by overcoming the major problem associated with the increase in pH during the production process, a more efficient biocatalyst was obtained through cascade modifications of the previously reported E. coli strain. First, we introduced four amino acid mutations to the codon-optimized GadB protein from Lactococcus lactis to shift its decarboxylation activity toward a neutral pH, resulting in 306.65 g/L of GABA with 99.14 mol% conversion yield and 69.8% increase in GABA productivity. Second, we promoted transportation of L-Glu and GABA by removing the genomic region encoding the C-plug of GadC (a glutamate/GABA antiporter) to allow its transport path to remain open at a neutral pH, which improved the GABA productivity by 16.8% with 99.3 mol% conversion of 3 M L-Glu. Third, we enhanced the expression of soluble GadB by introducing the GroESL molecular chaperones, leading to 20.2% improvement in GABA productivity, with 307.40 g/L of GABA and a 61.48 g/L/h productivity obtained in one cycle. Finally, we inhibited the degradation of GABA by inactivation of gadA and gadB from the E. coli genome, which resulted in almost no GABA degradation after 40 h. After the cascade system modifications, the engineered recombinant E. coli strain achieved a 44.04 g/L/h productivity with a 99.6 mol% conversion of 3 M L-Glu in a 5-L bioreactor, about twofold increase in productivity compared to the starting strain. This increase represents the highest GABA productivity by whole-cell bioconversion using L-Glu as a substrate in one cycle observed