Cardiovascular effects of constant rate infusions of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized at equipotent doses of sevoflurane.

PubMed

Moran-Muñoz, Rafael; Valverde, Alexander; Ibancovichi, J A; Acevedo-Arcique, Carlos M; Recillas-Morales, Sergio; Sanchez-Aparicio, Pedro; Osorio-Avalos, Jorge; Chavez-Monteagudo, Julio Raul

2017-07-01

This study evaluated the cardiovascular effects of a constant rate infusion (CRI) of lidocaine, lidocaine and dexmedetomidine, and dexmedetomidine in dogs anesthetized with sevoflurane at equipotent doses. Treatments consisted of T1-Lidocaine [loading dose 2 mg/kg body weight (BW), IV, and CRI of 100 μg/kg BW per min] at 1.4% end-tidal of sevoflurane (FE SEV ); T2-Dexmedetomidine (loading dose 2 μg/kg BW, IV, and CRI of 2 μg/kg BW per hour) and FE SEV 1.1%; and T3-Lidocaine-Dexmedetomidine using the same doses of T1 and T2 and FE SEV 0.8%. Constant rate infusion of lidocaine did not induce any cardiovascular changes; lidocaine and dexmedetomidine resulted in cardiovascular effects similar to dexmedetomidine alone. These effects were characterized by a significant ( P < 0.001) decrease in heart rate, cardiac output, cardiac index, oxygen delivery, and pulmonary vascular resistance index, and a significant ( P < 0.001) increase in mean and diastolic arterial pressure, systemic vascular resistance index, pulmonary arterial occlusion pressure and oxygen extraction ratio, compared with baseline values. In conclusion, a CRI of lidocaine combined with dexmedetomidine produces significant cardiovascular changes similar to those observed with dexmedetomidine alone.

Circadian gene expression in peripheral blood leukocytes of rotating night shift nurses.

PubMed

Reszka, Edyta; Peplonska, Beata; Wieczorek, Edyta; Sobala, Wojciech; Bukowska, Agnieszka; Gromadzinska, Jolanta; Lie, Jenny-Anne; Kjuus, Helge; Wasowicz, Wojciech

2013-03-01

It has been hypothesized that the underlying mechanism of elevated breast cancer risk among long-term, night-working women involves circadian genes expression alteration caused by exposure to light at night and/or irregular work hours. The aim of the present study was to determine the effect of rotating night shift work on expression of selected core circadian genes. The cross-sectional study was conducted on 184 matched nurses and midwives, who currently work either day or rotating night shifts, to determine the effect of irregular work at night on circadian gene expression in peripheral blood leukocytes. Transcript levels of BMAL1, CLOCK, CRY1, CRY2, PER1, PER2, and PER3 were determined by means of quantitative real-time polymerase chain reaction (PCR). After adjusting for hour of blood collection, there were no statistically significant changes of investigated circadian genes among nurses and midwives currently working rotating night shifts compared to nurses working day shifts. The highest expression of PER1 messenger ribonucleic acid (mRNA) was observed for women currently working shifts who had worked >15 years in rotating night shift work. PER1 gene expression was associated with the lifetime duration of rotating night shift work among women currently working night shifts (P=0.04). PER1 and PER3 transcript levels in blood leukocytes were significantly down-regulated in the later versus early hours of the morning between 06.00-10.00 hours (β-coefficient -0.226, P=0.001 and β-coefficient -0.181, P<0.0001, respectively). These results suggest that current rotating night shift work does not affect circadian gene expression in human circulating leukocytes. In analysis of the peripheral clock in human studies, the hour of blood collection should be precisely specified.

Potential Cost-Effectiveness of Prenatal Distribution of Misoprostol for Prevention of Postpartum Hemorrhage in Uganda

PubMed Central

Lubinga, Solomon J.; Atukunda, Esther C.; Wasswa-Ssalongo, George; Babigumira, Joseph B.

2015-01-01

Background In settings where home birth rates are high, prenatal distribution of misoprostol has been advocated as a strategy to increase access to uterotonics during the third stage of labor to prevent postpartum hemorrhage (PPH). Our objective was to project the potential cost-effectiveness of this strategy in Uganda from both governmental (the relevant payer) and modified societal perspectives. Methods and Findings To compare prenatal misoprostol distribution to status quo (no misoprostol distribution), we developed a decision analytic model that tracked the delivery pathways of a cohort of pregnant women from the prenatal period, labor to delivery without complications or delivery with PPH, and successful treatment or death. Delivery pathway parameters were derived from the Uganda Demographic and Health Survey. Incidence of PPH, treatment efficacy, adverse event and case fatality rates, access to misoprostol, and health resource use and cost data were obtained from published literature and supplemented with expert opinion where necessary. We computed the expected incidence of PPH, mortality, disability adjusted life years (DALYs), costs and incremental cost effectiveness ratios (ICERs). We conducted univariate and probabilistic sensitivity analyses to examine robustness of our results. In the base-case analysis, misoprostol distribution lowered the expected incidence of PPH by 1.0% (95% credibility interval (CrI): 0.55%, 1.95%), mortality by 0.08% (95% CrI: 0.04%, 0.13%) and DALYs by 0.02 (95% CrI: 0.01, 0.03). Mean costs were higher with prenatal misoprostol distribution from governmental by US$3.3 (95% CrI: 2.1, 4.2) and modified societal (by US$1.3; 95% CrI: -1.6, 2.8) perspectives. ICERs were US$191 (95% CrI: 82, 443) per DALY averted from a governmental perspective, and US$73 (95% CI: -86, 256) per DALY averted from a modified societal perspective. Conclusions Prenatal distribution of misoprostol is potentially cost-effective in Uganda and should be considered for national-level scale up for prevention of PPH. PMID:26560140

Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study

PubMed Central

Zhu, Yong; Stevens, Richard G.; Hoffman, Aaron E.; FitzGerald, Liesel M.; Kwon, Erika M.; Ostrander, Elaine A.; Davis, Scott; Zheng, Tongzhang; Stanford, Janet L.

2010-01-01

Circadian genes are responsible for maintaining the ancient adaptation of a 24-hour circadian rhythm and influence a variety of cancer-related biological pathways, including the regulation of sex hormone levels. However, few studies have been undertaken to investigate the role of circadian genes in the development of prostate cancer, the most common cancer type among men (excluding non-melanoma skin cancer). The current genetic association study tested the circadian gene hypothesis in relation to prostate cancer by genotyping a total of 41 tagging and amino acid altering SNPs in ten circadian-related genes in a population-based case-control study of Caucasian men (N=1,308 cases and 1,266 controls). Our results showed that at least one SNP in nine core circadian genes (rs885747 and rs2289591 in PER1, rs7602358 in PER2, rs1012477 in PER3, rs1534891 in CSNK1E, rs12315175 in CRY1, rs2292912 in CRY2, rs7950226 in ARNTL, rs11133373 in CLOCK, and rs1369481, rs895521, and rs17024926 in NPAS2) was significantly associated with susceptibility to prostate cancer (either overall risk or risk of aggressive disease), and the risk estimate for four SNPs in three genes (rs885747 and rs2289591 in PER1, rs1012477 in PER3 and rs11133373 in CLOCK) varied by disease aggressiveness. Further analyses of haplotypes were consistent with these genotyping results. Findings from this candidate gene association study support the hypothesis of a link between genetic variants in circadian genes and prostate cancer risk, warranting further confirmation and mechanistic investigation of circadian biomarkers in prostate tumorigenesis. PMID:19934327

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yang; National Institute of Biological Sciences, Beijing 102206; Xiong, Wei

Although a deficiency in CRY1 or CRY2 correlates with a shorter or longer circadian period, the regulation of CRY proteins in the circadian period has not been well studied. In this study, we found that both CRY1 and CRY2 were able to rescue oscillation in CRY null cells and that they displayed different periods. Furthermore, we demonstrated that protein nuclear import rates, not protein stability, regulate the period-length at the cellular level. Co-transfection of CRY1 and CRY2 in various ratios in the same cells gives rise to the predicted period length in a dose-dependent manner. Given the distinct characteristics ofmore » the C-terminal tails of the CRY1 and CRY2 proteins, our study addresses a long-standing hypothesis that the ratio of these two CRY molecules affects the clock period. - Highlights: • Rhythmic CRY2, like CRY1, in the correct CRY1 phase is sufficient to rescue clock oscillation in CRY null cells. • The short-period mammalian CRY2 protein is more stable than the CRY1 protein. • The N-terminal polypeptide of CRY2 contributes to its stability and Per2 repression, but it does not affect the period. • The C-terminal tails of CRYs regulate their protein stability and nuclear import, but the import rate governs the period. • The ratio, rather than the absolute amounts of CRY1 and CRY2 proteins, determines the period in mammalian cells.« less

PRKCDBP (CAVIN3) and CRY2 associate with major depressive disorder.

PubMed

Kovanen, Leena; Donner, Kati; Kaunisto, Mari; Partonen, Timo

2017-01-01

Dysfunctions in the intrinsic clocks are suggested in patients with depressive disorders. The cryptochrome circadian clocks 1 and 2 (CRY1 and CRY2) proteins modulate circadian rhythms in a cell and influence emotional reactions and mood in an individual. The protein kinase C delta binding protein (PRKCDBP, or CAVIN3), similar to the serum deprivation response protein (SDPR, or CAVIN2), reduces metabolic stability of the PER2-CRY2 transcription factor complex that plays a role in the circadian rhythm synchronization. Our aim was to study SDPR, PRKCDBP, CRY1 and CRY2 genetic variants in depressive disorders. The sample included 5910 Finnish individuals assessed with the Munich-Composite International Diagnostic Interview (M-CIDI) in year 2000. In year 2011, 3424 individuals were assessed again. After genotype quality control, there were 383 subjects with major depressive disorder, 166 with dysthymia, and 479 with depressive disorders (major depressive disorder, dysthymia or both), and 4154 healthy controls. A total of 48 single-nucleotide polymorphisms from SDPR, PRKCDBP, CRY1 and CRY2 genes were analyzed using logistic regression models controlling for age and gender. The earlier reported association of CRY2 variants with dysthymia was confirmed and extended to major depressive disorder (q<0.05). In addition, novel associations of PRKCDBP rs1488864 with depressive disorders (q=0.02) and with major depressive disorder in specific (q=0.007) were found. The number of cases was moderate and coverage of PRKCDB was limited. CRY2 and PRKCDBP variants may be risk factors of major depressive disorder and provide information for diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Caregiving and early infant crying in a danish community.

PubMed

Alvarez, Marissa

2004-04-01

Maternal caregiving and fussing/crying in Danish infants at 3, 6, and 12 weeks were examined using self-report scales and 24-hour behavior diaries. Mothers reported practices commonly associated with responsive caregiving: frequent feeding, prompt response to infant cries, and considerable time holding the infant. Fuss/cry durations peaked in the first 2 months, were highest in evenings, and decreased approximately 50% by 12 weeks. Fussing was the majority behavior, and 9.2% of the infants fussed and cried more than 3 hours per day. In contrast with other Western studies, 24-hour fuss/cry durations were lower, and fussing accounted for up to 80% of total distress. Danish caregiving practices may partially explain the lower durations of infant distress and the lower ratio of cry to fuss. However, some infants fuss/cry a great deal despite sensitive care, which may reflect individual differences in infant maturation of behavior regulation.

Estimating Foodborne Gastroenteritis, Australia

PubMed Central

Kirk, Martyn D.; Becker, Niels; Gregory, Joy E.; Unicomb, Leanne; Millard, Geoffrey; Stafford, Russell; Lalor, Karin

2005-01-01

We estimated for Australia the number of cases, hospitalizations, and deaths due to foodborne gastroenteritis in a typical year, circa 2000. The total amount of infectious gastroenteritis was measured by using a national telephone survey. The foodborne proportion was estimated from Australian data on each of 16 pathogens. To account for uncertainty, we used simulation techniques to calculate 95% credibility intervals (CrI). The estimate of incidence of gastroenteritis in Australia is 17.2 million (95% confidence interval 14.5–19.9 million) cases per year. We estimate that 32% (95% CrI 24%–40%) are foodborne, which equals 0.3 (95% CrI 0.2–0.4) episodes per person, or 5.4 million (95% CrI 4.0–6.9 million) cases annually in Australia. Norovirus, enteropathogenic Escherichia coli, Campylobacter spp., and Salmonella spp. cause the most illnesses. In addition, foodborne gastroenteritis causes ≈15,000 (95% CrI 11,000–18,000) hospitalizations and 80 (95% CrI 40–120) deaths annually. This study highlights global public health concerns about foodborne diseases and the need for standardized methods, including assessment of uncertainty, for international comparison. PMID:16102316

Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial.

PubMed

Indrio, Flavia; Di Mauro, Antonio; Riezzo, Giuseppe; Civardi, Elisa; Intini, Cristina; Corvaglia, Luigi; Ballardini, Elisa; Bisceglia, Massimo; Cinquetti, Mauro; Brazzoduro, Emanuela; Del Vecchio, Antonio; Tafuri, Silvio; Francavilla, Ruggiero

2014-03-01

Infantile colic, gastroesophageal reflux, and constipation are the most common functional gastrointestinal disorders that lead to referral to a pediatrician during the first 6 months of life and are often responsible for hospitalization, feeding changes, use of drugs, parental anxiety, and loss of parental working days with relevant social consequences. To investigate whether oral supplementation with Lactobacillus reuteri DSM 17938 during the first 3 months of life can reduce the onset of colic, gastroesophageal reflux, and constipation in term newborns and thereby reduce the socioeconomic impact of these conditions. A prospective, multicenter, double-masked, placebo-controlled randomized clinical trial was performed on term newborns (age <1 week) born at 9 different neonatal units in Italy between September 1, 2010, and October 30, 2012. Parents were asked to record in a structured diary the number of episodes of regurgitation, duration of inconsolable crying (minutes per day), number of evacuations per day, number of visits to pediatricians, feeding changes, hospitalizations, visits to a pediatric emergency department for a perceived health emergency, pharmacologic interventions, and loss of parental working days. In total, 589 infants were randomly allocated to receive L reuteri DSM 17938 or placebo daily for 90 days. Prophylactic use of probiotic. Reduction of daily crying time, regurgitation, and constipation during the first 3 months of life. Cost-benefit analysis of the probiotic supplementation. At 3 months of age, the mean duration of crying time (38 vs 71 minutes; P < .01), the mean number of regurgitations per day (2.9 vs 4.6; P < .01), and the mean number of evacuations per day (4.2 vs 3.6; P < .01) for the L reuteri DSM 17938 and placebo groups, respectively, were significantly different. The use of L reuteri DSM 17938 resulted in an estimated mean savings per patient of €88 (US $118.71) for the family and an additional €104 (US $140.30) for the community. Prophylactic use of L reuteri DSM 17938 during the first 3 months of life reduced the onset of functional gastrointestinal disorders and reduced private and public costs for the management of this condition. clinicaltrials.gov Identifier: NCT01235884.

Role of monochromatic light on daily variation of clock gene expression in the pineal gland of chick.

PubMed

Jiang, Nan; Wang, Zixu; Cao, Jing; Dong, Yulan; Chen, Yaoxing

2016-11-01

The avian pineal gland is a master clock that can receive external photic cues and translate them into output rhythms. To clarify whether a shift in light wavelength can influence the circadian expression in chick pineal gland, a total of 240 Arbor Acre male broilers were exposed to white light (WL), red light (RL), green light (GL) or blue light (BL). After 2weeks light illumination, circadian expressions of seven core clock genes in pineal gland and the level of melatonin in plasma were examined. The results showed after illumination with monochromatic light, 24h profiles of all clock gene mRNAs retained circadian oscillation, except that RL tended to disrupt the rhythm of cCry2. Compared to WL, BL advanced the acrophases of the negative elements (cCry1, cCry2, cPer2 and cPer3) by 0.1-1.5h and delayed those of positive elements (cClock, cBmal1 and cBmal2) by 0.2-0.8h. And, RL advanced all clock genes except cClock and cPer2 by 0.3-2.1h, while GL delayed all clock genes by 0.5-1.5h except cBmal2. Meanwhile, GL increased the amplitude and mesor of positive and reduced both parameters of negative clock genes, but RL showed the opposite pattern. Although the acrophase of plasma melatonin was advanced by both GL and RL, the melatonin level was significantly increased in GL and decreased in RL. This tendency was consistent with the variations in the positive clock gene mRNA levels under monochromatic light and contrasted with those of negative clock genes. Therefore, we speculate that GL may enhance positive clock genes expression, leading to melatonin synthesis, whereas RL may enhance negative genes expression, suppressing melatonin synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons.

PubMed

Oosterman, Johanneke E; Belsham, Denise D

2016-01-01

Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. It is unclear if nutrients can directly control clock gene expression. We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. Per2 and Bmal1 mRNAs were assessed every 3 hours over 36 hours. Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. Glucose had no significant effect on phospho-GSK3β, whereas AMPK phosphorylation was altered. Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation.

Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons

PubMed Central

Oosterman, Johanneke E.; Belsham, Denise D.

2016-01-01

Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. It is unclear if nutrients can directly control clock gene expression. We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. Per2 and Bmal1 mRNAs were assessed every 3 hours over 36 hours. Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. Glucose had no significant effect on phospho-GSK3β, whereas AMPK phosphorylation was altered. Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation. PMID:26784927

Knockout-Rescue Embryonic Stem Cell-Derived Mouse Reveals Circadian-Period Control by Quality and Quantity of CRY1.

PubMed

Ode, Koji L; Ukai, Hideki; Susaki, Etsuo A; Narumi, Ryohei; Matsumoto, Katsuhiko; Hara, Junko; Koide, Naoshi; Abe, Takaya; Kanemaki, Masato T; Kiyonari, Hiroshi; Ueda, Hiroki R

2017-01-05

To conduct comprehensive characterization of molecular properties in organisms, we established an efficient method to produce knockout (KO)-rescue mice within a single generation. We applied this method to produce 20 strains of almost completely embryonic stem cell (ESC)-derived mice ("ES mice") rescued with wild-type and mutant Cry1 gene under a Cry1 -/- :Cry2 -/- background. A series of both phosphorylation-mimetic and non-phosphorylation-mimetic CRY1 mutants revealed that multisite phosphorylation of CRY1 can serve as a cumulative timer in the mammalian circadian clock. KO-rescue ES mice also revealed that CRY1-PER2 interaction confers a robust circadian rhythmicity in mice. Surprisingly, in contrast to theoretical predictions from canonical transcription/translation feedback loops, the residues surrounding the flexible P loop and C-lid domains of CRY1 determine circadian period without changing the degradation rate of CRY1. These results suggest that CRY1 determines circadian period through both its degradation-dependent and -independent pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Safety assessment of Cry1C protein from genetically modified rice according to the national standards of PR China for a new food resource.

PubMed

Cao, Sishuo; He, Xiaoyun; Xu, Wentao; Ran, Wenjun; Liang, Lixing; Luo, YunBo; Yuan, Yanfang; Zhang, Nan; Zhou, Xin; Huang, Kunlun

2010-12-01

The Cry1C protein produced in Escherichia coli was used for in vitro evaluation and animal studies to support the safety assessment of GM food or feed products containing the Cry1C protein. The Cry1C protein does not have any sequence homology with known allergens or toxins. Although the Cry1C protein was heat stable it was rapidly degraded in vitro with simulated gastric or intestinal fluids. It did not cause adverse effects in mice as administered by gavage at a high level dosage of 5 g (Cry1C protein)/kg body weight. The mutagenicity of this protein was evaluated according to the national standards of People's Republic of China (PR China) for a new food resource. In mutagenic tests, the Cry1C protein caused<4 micronucleated cells per 1000 cells, <16 sperm abnormalities per 1000 cells and was not associated with any increased mutations in the Ames test. Taken together, these data indicate that the Cry1C protein is not a potential allergen or toxin. Copyright © 2010 Elsevier Inc. All rights reserved.

Mechanisms of Breast Cancer in Shift Workers: DNA Methylation in Five Core Circadian Genes in Nurses Working Night Shifts.

PubMed

Samulin Erdem, Johanna; Skare, Øivind; Petersen-Øverleir, Marte; Notø, Heidi Ødegaard; Lie, Jenny-Anne S; Reszka, Edyta; Pepłońska, Beata; Zienolddiny, Shanbeh

2017-01-01

Shift work has been suggested to be associated with breast cancer risk, and circadian disruption in shift workers is hypothesized as one of the mechanisms of increased cancer risk. There is, however, insufficient molecular evidence supporting this hypothesis. Using the quantitative methodology of pyrosequencing, epigenetic changes in 5-methyl cytosine (5mC) in five circadian genes CLOCK , BMAL1 , CRY1, PER1 and PER2 in female nurses working night shift work (278 breast cancer cases, 280 controls) were analyzed. In breast cancer cases, a medium exposure to night work was associated with increased methylation levels of the CLOCK (p=0.050), BMAL1 (p=0.001) and CRY1 (p=0.040) genes, compared with controls. Within the cases, analysis of the effects of shift work on the methylation patterns showed that methylation of CRY1 was lower in those who had worked night shift and had a high exposure (p=0.006) compared with cases that had worked only days. For cases with a medium exposure to night work, an increase in BMAL1 (p=0.003) and PER1 (p=0.035) methylation was observed compared with day working (unexposed) cases. The methylation levels of the five core circadian genes were also analyzed in relation to the estrogen and progesterone receptors status of the tumors in the cases, and no correlations were observed. Furthermore, nineteen polymorphisms in the five circadian genes were assessed for their effects on the methylation levels of the respective genes, but no associations were found. In summary, our data suggest that epigenetic regulation of CLOCK , BMAL1, CRY1 and PER1 may contribute to breast cancer in shift workers.

Mechanisms of Breast Cancer in Shift Workers: DNA Methylation in Five Core Circadian Genes in Nurses Working Night Shifts

PubMed Central

Samulin Erdem, Johanna; Skare, Øivind; Petersen-Øverleir, Marte; Notø, Heidi Ødegaard; Lie, Jenny-Anne S.; Reszka, Edyta; Pepłońska, Beata; Zienolddiny, Shanbeh

2017-01-01

Shift work has been suggested to be associated with breast cancer risk, and circadian disruption in shift workers is hypothesized as one of the mechanisms of increased cancer risk. There is, however, insufficient molecular evidence supporting this hypothesis. Using the quantitative methodology of pyrosequencing, epigenetic changes in 5-methyl cytosine (5mC) in five circadian genes CLOCK, BMAL1, CRY1, PER1 and PER2 in female nurses working night shift work (278 breast cancer cases, 280 controls) were analyzed. In breast cancer cases, a medium exposure to night work was associated with increased methylation levels of the CLOCK (p=0.050), BMAL1 (p=0.001) and CRY1 (p=0.040) genes, compared with controls. Within the cases, analysis of the effects of shift work on the methylation patterns showed that methylation of CRY1 was lower in those who had worked night shift and had a high exposure (p=0.006) compared with cases that had worked only days. For cases with a medium exposure to night work, an increase in BMAL1 (p=0.003) and PER1 (p=0.035) methylation was observed compared with day working (unexposed) cases. The methylation levels of the five core circadian genes were also analyzed in relation to the estrogen and progesterone receptors status of the tumors in the cases, and no correlations were observed. Furthermore, nineteen polymorphisms in the five circadian genes were assessed for their effects on the methylation levels of the respective genes, but no associations were found. In summary, our data suggest that epigenetic regulation of CLOCK, BMAL1, CRY1 and PER1 may contribute to breast cancer in shift workers. PMID:28928877

Inconsolable infant crying and maternal postpartum depressive symptoms.

PubMed

Radesky, Jenny S; Zuckerman, Barry; Silverstein, Michael; Rivara, Frederick P; Barr, Marilyn; Taylor, James A; Lengua, Liliana J; Barr, Ronald G

2013-06-01

To quantify the extent to which maternal report of inconsolable infant crying, rather than colic (defined by Wessel's criteria of daily duration of fussing and crying >3 hours), is associated with maternal postpartum depressive symptoms. Participants were 587 mothers who were recruited shortly before or after delivery and followed longitudinally. At 5 to 6 weeks postpartum, mothers recorded the duration and mode (fussing, crying, or inconsolable crying) of their infant's distress by using the Baby's Day Diary. The Edinburgh Postnatal Depression Scale (EPDS) was administered at enrollment and at 8 weeks postpartum. Using regression models that included baseline EPDS scores and multiple confounders, we examined associations of colic and inconsolable crying with later maternal EPDS scores at 8 weeks postpartum. Sixty mothers (10%) met the EPDS threshold for "possible depression" (score ≥9) at 8 weeks postpartum. For mothers reporting >20 minutes of inconsolable crying per day, the adjusted odds ratio for an EPDS score ≥9 was 4.0 (95% confidence interval: 2.0-8.1), whereas the adjusted odds ratio for possible depression in mothers whose infants had colic was 2.0 (95% confidence interval: 1.1-3.7). These associations persisted after adjusting for baseline depression symptoms. Maternal report of inconsolable infant crying may have a stronger association with postpartum depressive symptoms than infant colic. Asking a mother about her ability to soothe her infant may be more relevant for potential intervention than questions about crying and fussing duration alone.

Effects of 2 different medetomidine infusion rates on selected neurohormonal and metabolic parameters in dogs

PubMed Central

Lamont, Leigh; Burton, Shelley; Caines, Deanne; Masaoud, Elmabrok; Troncy, Eric

2012-01-01

The effects of 2 different 8-hour continuous rate infusions (CRIs) of medetomidine on epinephrine, norepinephrine, cortisol, glucose, and insulin levels were investigated in 6 healthy dogs. Each dog received both treatments and a control as follows: MED1 = 2 μg/kg bodyweight (BW) loading dose followed by 1 μg/kg BW per hour CRI; MED2 = 4 μg/kg BW loading dose followed by 2 μg/kg BW per hour CRI; and CONTROL = saline bolus followed by a saline CRI. Both infusion rates of medetomidine decreased norepinephrine levels throughout the infusion compared to CONTROL. While norepinephrine levels tended to be lower with the MED2 treatment compared to the MED1, this difference was not significant. No differences in epinephrine, cortisol, glucose, or insulin were documented among any of the treatments at any time point. At the low doses used in this study, both CRIs of medetomidine decreased norepinephrine levels over the 8-hour infusion period, while no effects were observed on epinephrine, cortisol, glucose, and insulin. PMID:23024457

Headache, idiopathic intracranial hypertension and slipped capital femoral epiphysis during growth hormone treatment: a safety update from the KIGS database.

PubMed

Darendeliler, Feyza; Karagiannis, Georgios; Wilton, Patrick

2007-01-01

Several uncommon adverse effects may be related to growth hormone (GH) treatment. Three potential side effects, headache, idiopathic intracranial hypertension (IIH) and slipped capital femoral epiphysis (SCFE), will be discussed. Data from 57,968 children in the KIGS (Pfizer International Growth Study database) were analyzed to determine the effects of recombinant human GH (Genotropin) on these side effects. The diagnostic groups were idiopathic GH deficiency (IGHD) (n = 27,690), congenital GHD (CGHD) (n = 2,547), craniopharyngioma (n = 1,155), cranial tumours (n = 2,203), Turner syndrome (TS) (n = 6,092), idiopathic short stature (ISS) (n = 5,286), small for gestational age (SGA) (n = 2,973), chronic renal insufficiency (CRI) (n = 1,753) and Prader-Willi syndrome (PWS) (n = 1,368). Total incidence (per 100,000 treatment years) of headache was 793.5 (n = 569). The incidence was significantly higher in the groups of patients with craniopharyngiomas, CGHD and cranial tumours than in the other diagnostic groups (p < 0.05 for all). IIH occurred in 41 children resulting in a total incidence (per 100,000 treatment years) of 27.7. The incidence (per 100,000 treatment years) was significantly lower in patients with IGHD (12.2) than in those with TS (56.4) (p = 0.0004), CGHD (54.5) (p = 0.0064), PWS (68.3) (p = 0.0263) and CRI (147.8) (p < 0.001). No cases of IIH were reported in the ISS group of patients. The median duration from onset of GH therapy to IIH ranged from 0.01 to 1.3 years in various diagnostic groups. SCFE was observed in a total of 52 children resulting in a total incidence (per 100,000 treatment years) of 73.4. The incidence (per 100,000 treatment years) was significantly lower in patients with IGHD (18.3) and in those children with ISS (14.5) than in the TS (84.5), cranial tumours (86.1) and craniopharyngioma groups (120.5) (p < 0.05 for all). No cases of SCFE were reported in the SGA and PWS groups. The median duration from onset of GH therapy to SCFE ranged from 0.4 to 2.5 years. The incidences of IIH and SCFE in this analysis are lower than the values reported in previous KIGS analyses and comparable to other databases. Patients with TS, organic GHD, PWS and CRI seem to be more prone to these side effects.

Sleep quality and methylation status of core circadian rhythm genes among nurses and midwives.

PubMed

Bukowska-Damska, Agnieszka; Reszka, Edyta; Kaluzny, Pawel; Wieczorek, Edyta; Przybek, Monika; Zienolddiny, Shanbeh; Peplonska, Beata

2017-01-01

ABSTARCT Poor sleep quality or sleep restriction is associated with sleepiness and concentration problems. Moreover, chronic sleep restriction may affect metabolism, hormone secretion patterns and inflammatory responses. Limited recent reports suggest a potential link between sleep deprivation and epigenetic effects such as changes in DNA methylation profiles. The aim of the present study was to assess the potential association between poor sleep quality or sleep duration and the levels of 5-methylcytosine in the promoter regions of PER1, PER2, PER3, BMAL1, CLOCK, CRY1 CRY2 and NPAS2 genes, taking into account rotating night work and chronotype as potential confounders or modifiers. A cross-sectional study was conducted on 710 nurses and midwives (347 working on rotating nights and 363 working only during the day) aged 40-60 years. Data from in-person interviews about sleep quality, chronotype and potential confounders were used. Sleep quality and chronotype were assessed using Pittsburgh Sleep Quality Questionnaire (PSQI) and Morningness-Eveningness Questionnaire (MEQ), respectively. Morning blood samples were collected. The methylation status of the circadian rhythm genes was determined via quantitative methylation-specific real-time PCR assays (qMSP) reactions using DNA samples derived from leucocytes. The proportional odds regression model was fitted to quantify the relationship between methylation index (MI) as the dependent variable and sleep quality or sleep duration as the explanatory variable. Analyses were carried out for the total population as well as for subgroups of women stratified by the current system of work (rotating night shift/day work) and chronotype (morning type/intermediate type/evening type). A potential modifying effect of the system of work or the chronotype was examined using the likelihood ratio test. No significant findings were observed in the total study population. Subgroup analyses revealed two statistically significant associations between a shorter sleep duration and 1) methylation level in PER2 among day workers, especially those with the morning chronotype (OR = 2.31, 95%CI:1.24-4.33), and 2) methylation level in CRY2 among subjects with the intermediate chronotype, particularly among day workers (OR = 0.52, 95%CI:0.28-0.96). The study results demonstrated a positive association between average sleep duration of less than 6 hours and the methylation level of PER2 among morning chronotype subjects, and an inverse association for CRY2 among intermediate chronotype subjects, but only among day workers. Both the system of work and the chronotype turned out to be important confounders and modifiers in a number of analyses, making it necessary to consider them as potential covariates in future research on sleep deficiency outcomes. Further studies are warranted to explore this under-investigated topic.

Effects of external magnetic field and out-of-plane strain on magneto-optical Kerr spectra in CrI3 monolayer.

PubMed

Guo, Guanxing; Bi, Gang; Cai, Chunfeng; Wu, Huizhen

2018-07-18

Magnetic semiconductors based on two-dimensional (2D) crystals have attracted attention owing to their intrinsic ferromagnetism and have potential for spintronic devices. Here, full-potential linearized augmented plane wave plus local orbitals method is used to explore the structural, electronic, magnetic, and magneto-optical properties of CrI 3 monolayer. Our first-principles calculations show that CrI 3 monolayer is a ferromagnetic indirect semiconductor with spin-up and spin-down band gaps of 1.23 and 1.90 eV, respectively, and a magnetic moment of 2.93 [Formula: see text] per Cr atom. Based on the macroscopic linear response theory, we systematically study the influences of external magnetic field and out-of-plane strain on the magneto-optical Kerr effect spectra in CrI 3 monolayer. The Kerr rotation of CrI 3 monolayer at 1.96 eV photon energy is [Formula: see text], which is consistent with the recent experiments. We find that the Kerr rotation reaches its maximum when the external magnetic field is perpendicular to CrI 3 plane, while it is almost zero on turning the magnetic field in the plane. This result as well as the sizable magnetocrystalline anisotropy energy (MAE) of 0.79 meV verifies that CrI 3 monolayer has a strong magnetic anisotropy with an out-of-plane easy axis. Further, applying out-of-plane compressive and tensile strain upon CrI 3 monolayer, we observe a redshift of the Kerr rotation spectra with the increase of the strain and the peak values of the Kerr rotation increase correspondingly. The rich electronic and magnetic properties, especially the magneto-optical spectra, render CrI 3 monolayer a promising 2D magnetic material for applications from sensing to data storage.

Overexpression of the Bacillus thuringiensis (Bt) Cry2Aa2 protein in chloroplasts confers resistance to plants against susceptible and Bt-resistant insects

PubMed Central

Kota, Madhuri; Daniell, Henry; Varma, Sam; Garczynski, Stephen F.; Gould, Fred; Moar, William J.

1999-01-01

Evolving levels of resistance in insects to the bioinsecticide Bacillus thuringiensis (Bt) can be dramatically reduced through the genetic engineering of chloroplasts in plants. When transgenic tobacco leaves expressing Cry2Aa2 protoxin in chloroplasts were fed to susceptible, Cry1A-resistant (20,000- to 40,000-fold) and Cry2Aa2-resistant (330- to 393-fold) tobacco budworm Heliothis virescens, cotton bollworm Helicoverpa zea, and the beet armyworm Spodoptera exigua, 100% mortality was observed against all insect species and strains. Cry2Aa2 was chosen for this study because of its toxicity to many economically important insect pests, relatively low levels of cross-resistance against Cry1A-resistant insects, and its expression as a protoxin instead of a toxin because of its relatively small size (65 kDa). Southern blot analysis confirmed stable integration of cry2Aa2 into all of the chloroplast genomes (5,000–10,000 copies per cell) of transgenic plants. Transformed tobacco leaves expressed Cry2Aa2 protoxin at levels between 2% and 3% of total soluble protein, 20- to 30-fold higher levels than current commercial nuclear transgenic plants. These results suggest that plants expressing high levels of a nonhomologous Bt protein should be able to overcome or at the very least, significantly delay, broad spectrum Bt-resistance development in the field. PMID:10051556

The First Cry2Ac-Type Protein Toxic to Helicoverpa armigera: Cloning and Overexpression of Cry2ac7 Gene from SBS-BT1 Strain of Bacillus thuringiensis

PubMed Central

Saleem, Faiza; Shakoori, Abdul Rauf

2017-01-01

The Cry (crystal) proteins from Bacillus thuringiensis are known to have toxicity against a variety of insects and have been exploited to control insect pests through transgenic plants and biopesticides. B. thuringiensis SBS BT-1 carrying the cry2 genes was isolated from soil samples in Pakistan. The 2-kb full length cry2Ac gene was cloned, sequenced, and submitted to the EMBL DNA database (Accession No. AM292031). For expression analysis, Escherichia coli DH5α was transformed with the fragment sub-cloned in pET22b expression vector using NdeI and HindIII restriction sites, and later confirmed by restriction endonuclease analysis. To assess the toxicity of Cry2Ac7 protein against lepidopteran and dipteran insects, BL21 (codon plus) strain of E. coli was further transformed with the recombinant plasmid. The 65-kDa protein was expressed in the form of inclusion bodies up to 180 OD units per liter of the medium. Inclusions were washed with a buffer containing 1.5% Triton-X 100 and >90% pure Cry2Ac7 was obtained. The inclusion bodies were dissolved in 50 mM K2CO3 (pH 11.5), dialyzed, and freeze-dried. This freeze-dried protein as well as inclusion bodies were used in bioassays against larvae of Helicoverpa armigera and Musca domestica. The freeze-dried protein was toxic to H. armigera larvae with an LC50 value of 131 ng/mL. However, Cry2Ac7 produced in E. coli did not show any mortality to M. domestica larvae. This is the first report of Cry2Ac protein toxic to H. armigera. PMID:29099767

Photoperiod regulates multiple gene expression in the suprachiasmatic nuclei and pars tuberalis of the Siberian hamster (Phodopus sungorus).

PubMed

Johnston, Jonathan D; Ebling, Francis J P; Hazlerigg, David G

2005-06-01

Photoperiod regulates the seasonal physiology of many mammals living in temperate latitudes. Photoperiodic information is decoded by the master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus and then transduced via pineal melatonin secretion. This neurochemical signal is interpreted by tissues expressing melatonin receptors (e.g. the pituitary pars tuberalis, PT) to drive physiological changes. In this study we analysed the photoperiodic regulation of the circadian clockwork in the SCN and PT of the Siberian hamster. Female hamsters were exposed to either long or short photoperiod for 8 weeks and sampled at 2-h intervals across the 24-h cycle. In the SCN, rhythmic expression of the clock genes Per1, Per2, Cry1, Rev-erbalpha, and the clock-controlled genes arginine vasopressin (AVP) and d-element binding protein (DBP) was modulated by photoperiod. All of these E-box-containing genes tracked dawn, with earlier peak mRNA expression in long, compared to short, photoperiod. This response occurred irrespective of the presence of additional regulatory cis-elements, suggesting photoperiodic regulation of SCN gene expression through a common E-box-related mechanism. In long photoperiod, expression of Cry1 and Per1 in the PT tracked the onset and offset of melatonin secretion, respectively. However, whereas Cry1 tracked melatonin onset in short period, Per1 expression was not detectably rhythmic. We therefore propose that, in the SCN, photoperiodic regulation of clock gene expression primarily occurs via E-boxes, whereas melatonin-driven signal transduction drives the phasing of a subset of clock genes in the PT, independently of the E-box.

The Macrophage Activation Induced by Bacillus thuringiensis Cry1Ac Protoxin Involves ERK1/2 and p38 Pathways and the Interaction with Cell-Surface-HSP70.

PubMed

Rubio-Infante, Nestor; Ilhuicatzi-Alvarado, Damaris; Torres-Martínez, Marilu; Reyes-Grajeda, Juan Pablo; Nava-Acosta, Raúl; González-González, Edith; Moreno-Fierros, Leticia

2018-01-01

Here, we aimed to further characterize the mechanisms involved in protoxin (p) Cry1Ac-induced macrophage activation. We demonstrated that pCry1Ac induces MAPK ERK1/2, p38, and JNK phosphorylation in RAW264.7 macrophages. Because MAPK activation is mainly triggered via ligand-receptor interactions, we focused on the identification of potential pCry1Ac-receptor proteins. Flow cytometry and confocal analysis showed specific saturable pCry1Ac-binding to the macrophage surface and evidenced its internalization via the clathrin-pathway. We performed immunoprecipitation assays and identified by MALDI-TOF-TOF several possible pCry1Ac-binding proteins, such as heat shock proteins (HSPs), vimentin, α-enolase, and actin; whose interaction and presence was confirmed, respectively, by ligand blot and Western blot assays. We also detected cell-surface (cs) pCry1Ac-HSP70 colocalization, so HSP70 was chosen for further characterization. Co-immunoprecipitation with HSP70 antibodies followed by Western blot confirmed the pCry1Ac-HSP70 interaction. Furthermore, pretreatment of RAW264.7 cells with HSP70 antibodies reduced pCry1Ac-induced ERK1 phosphorylation and MCP-1 production; thus suggest the functional participation of csHSP70 in pCry1Ac-induced macrophage activation. csHSP70 also was evaluated in peritoneal-cavity (PerC) macrophages of untreated BALB/c mice, interestingly it was found that the predominant population namely large-peritoneal-macrophages (LPM) displayed csHSP70 + hi. Furthermore, the dynamics of PerC macrophage subsets, LPM, and small-peritoneal macrophages (SPM) were evaluated in response to in vivo pCry1Ac stimuli in presence or not of phenylethynesulfonamide (PES) a functional HSP70 inhibitor. It was found that pCry1Ac increased the proportion of SPM CD11b + F4/80 + lowMHCII + csHSP70 + low and markedly reduced the amount of LPM CD11b + F4/80 + hiMHCII-csHSP70 + hi; while PES, partially suppressed this pCry1Ac-induced effect, further suggesting the participation of HSP70 in macrophage activation process. J. Cell. Biochem. 119: 580-598, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Functional polymorphisms of circadian negative feedback regulation genes are associated with clinical outcome in hepatocellular carcinoma patients receiving radical resection.

PubMed

Zhang, Zhaohui; Ma, Fei; Zhou, Feng; Chen, Yibing; Wang, Xiaoyan; Zhang, Hongxin; Zhu, Yong; Bi, Jianwei; Zhang, Yiguan

2014-12-01

Previous studies have demonstrated that circadian negative feedback loop genes play an important role in the development and progression of many cancers. However, the associations between single-nucleotide polymorphisms (SNPs) in these genes and the clinical outcomes of hepatocellular carcinoma (HCC) after surgical resection have not been studied so far. Thirteen functional SNPs in circadian genes were genotyped using the Sequenom iPLEX genotyping system in a cohort of 489 Chinese HCC patients who received radical resection. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Cumulative effect analysis and survival tree analysis were used for the multiple SNPs analysis. Four individual SNPs, including rs3027178 in PER1, rs228669 and rs2640908 in PER3 and rs3809236 in CRY1, were significantly associated with overall survival (OS) of HCC patients, and three SNPs, including rs3027178 in PER1, rs228729 in PER3 and rs3809236 in CRY1, were significantly associated with recurrence-free survival (RFS). Moreover, we observed a cumulative effect of significant SNPs on OS and RFS (P for trend < 0.001 for both). Survival tree analysis indicated that wild genotype of rs228729 in PER3 was the primary risk factor contributing to HCC patients' RFS. Our study suggests that the polymorphisms in circadian negative feedback loop genes may serve as independent prognostic biomarkers in predicting clinical outcomes for HCC patients who received radical resection. Further studies with different ethnicities are needed to validate our findings and generalize its clinical utility.

Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study.

PubMed

DeAngelo, Daniel J; Stock, Wendy; Stein, Anthony S; Shustov, Andrei; Liedtke, Michaela; Schiffer, Charles A; Vandendries, Erik; Liau, Katherine; Ananthakrishnan, Revathi; Boni, Joseph; Laird, A Douglas; Fostvedt, Luke; Kantarjian, Hagop M; Advani, Anjali S

2017-06-27

This study evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of inotuzumab ozogamicin (InO) for CD22-positive relapsed/refractory acute lymphoblastic leukemia. In phase 1, patients received InO 1.2 (n = 3), 1.6 (n = 12), or 1.8 (n = 9) mg/m 2 per cycle on days 1, 8, and 15 over a 28-day cycle (≤6 cycles). The recommended phase 2 dose (RP2D) was confirmed (expansion cohort; n = 13); safety and activity of InO were assessed in patients receiving the RP2D in phase 2 (n = 35) and in all treated patients (n = 72). The RP2D was 1.8 mg/m 2 per cycle (0.8 mg/m 2 on day 1; 0.5 mg/m 2 on days 8 and 15), with reduction to 1.6 mg/m 2 per cycle after complete remission (CR) or CR with incomplete marrow recovery (CRi). Treatment-related toxicities were primarily cytopenias. Four patients experienced treatment-related venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS; 1 fatal). Two VOD/SOS events occurred during treatment without intervening transplant; of 24 patients proceeding to poststudy transplant, 2 experienced VOD/SOS after transplant. Forty-nine (68%) patients had CR/CRi, with 41 (84%) achieving minimal residual disease (MRD) negativity. Median progression-free survival was 3.9 (95% confidence interval, 2.9-5.4) months; median overall survival was 7.4 (5.7-9.2) months for all treated patients, with median 23.7 (range, 6.8-29.8) months of follow-up for all treated patients alive at data cutoff. Achievement of MRD negativity was associated with higher InO exposure. InO was well tolerated and demonstrated high single-agent activity and MRD-negativity rates. This trial was registered at www.clinicaltrials.gov as #NCT01363297.

A Transport and Diffusion Model for Smoke Munitions.

DTIC Science & Technology

1979-08-01

oo cri r^ <a- CM «1- »*■ l-H CO in en oo in cri vo Tt 4- CO CO i-) CM tD Z LU —I ts Z O LU Z2 O _l Q (_> =3 O LU _l S» O I-H I...DX * ^ Pox -xceMTPOO/^*^11-) + DY*CP(»y - ycr»JTP(^J)/<SVdti- s = -BA t- apis- zstA/Jj/JiCr))1’ ct = C--^*cJ //=• ^cc - ue. -zr) GO TD s5?? P...50 FORMAT(1101 PRINT m.NRPV 14 FORMAT! IHQ , •NUMBER Of ROUNDS PER VOLLEY ’.It/ ? IHO.-IDEAL IMPACT POINTS •/ ’ •O".’ NO. •,6X

Multi-state trials of Bt sweet corn varieties for control of the corn earworm (Lepidoptera: Noctuidae).

PubMed

Shelton, A M; Olmstead, D L; Burkness, E C; Hutchison, W D; Dively, G; Welty, C; Sparks, A N

2013-10-01

Field tests in 2010-2011 were performed in New York, Minnesota, Maryland, Ohio, and Georgia to compare Bt sweet corn lines expressing Cry1A.105 + Cry2Ab2 and Cry1Ab with their non-Bt isolines, with and without the use of foliar insecticides. The primary insect pest in all locations during the trial years was Heliocoverpa zea (Boddie), which is becoming the most serious insect pest of sweet corn in the United States. At harvest, the ears were measured for marketability according to fresh market and processing standards. For fresh market and processing, least squares regression showed significant effects of protein expression, state, and insecticide frequency. There was a significant effect of year for fresh market but not for processing. The model also showed significant effects of H. zea per ear by protein expression. Sweet corn containing two genes (Cry1A.105 + Cry2Ab2) and a single gene (Cry1Ab) provided high marketability, and both Bt varieties significantly outperformed the traditional non-Bt isolines in nearly all cases regardless of insecticide application frequency. For pest suppression of H. zea, plants expressing Bt proteins consistently performed better than non-Bt isoline plants, even those sprayed at conventional insecticide frequencies. Where comparisons in the same state were made between Cry1A.105 + Cry2Ab2 and Cry1Ab plants for fresh market, the product expressing Cry1A.105 + Cry2Ab2 provided better protection and resulted in less variability in control. Overall, these results indicate Cry1A.105 + Cry2Ab2 and Cry1Ab plants are suitable for fresh market and processing corn production across a diversity of growing regions and years. Our results demonstrate that Bt sweet corn has the potential to significantly reduce the use of conventional insecticides against lepidopteran pests and, in turn, reduce occupational and environmental risks that arise from intensive insecticide use.

Sleep loss reduces the DNA-binding of BMAL1, CLOCK, and NPAS2 to specific clock genes in the mouse cerebral cortex.

PubMed

Mongrain, Valérie; La Spada, Francesco; Curie, Thomas; Franken, Paul

2011-01-01

We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP), we first showed that, as reported for the liver, DNA-binding of CLOCK and BMAL1 to target clock genes changes in function of time-of-day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset), -6, -12, and -18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and -6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven.

Sleep Loss Reduces the DNA-Binding of BMAL1, CLOCK, and NPAS2 to Specific Clock Genes in the Mouse Cerebral Cortex

PubMed Central

Curie, Thomas; Franken, Paul

2011-01-01

We have previously demonstrated that clock genes contribute to the homeostatic aspect of sleep regulation. Indeed, mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock gene expression in the forebrain. Here, we investigate a possible mechanism by which sleep deprivation (SD) could alter clock gene expression by quantifying DNA-binding of the core-clock transcription factors CLOCK, NPAS2, and BMAL1 to the cis-regulatory sequences of target clock genes in mice. Using chromatin immunoprecipitation (ChIP), we first showed that, as reported for the liver, DNA-binding of CLOCK and BMAL1 to target clock genes changes in function of time-of-day in the cerebral cortex. Tissue extracts were collected at ZT0 (light onset), −6, −12, and −18, and DNA enrichment of E-box or E'-box containing sequences was measured by qPCR. CLOCK and BMAL1 binding to Cry1, Dbp, Per1, and Per2 depended on time-of-day, with maximum values reached at around ZT6. We then observed that SD, performed between ZT0 and −6, significantly decreased DNA-binding of CLOCK and BMAL1 to Dbp, consistent with the observed decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was also decreased by SD, although SD is known to increase Per2 expression in the cortex. DNA-binding to Per1 and Cry1 was not affected by SD. Our results show that the sleep-wake history can affect the clock molecular machinery directly at the level of chromatin binding thereby altering the cortical expression of Dbp and Per2 and likely other targets. Although the precise dynamics of the relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive, the results also suggest that part of the reported circadian changes in DNA-binding of core clock components in tissues peripheral to the suprachiasmatic nuclei could, in fact, be sleep-wake driven. PMID:22039518

Circadian Clock Protein Content and Daily Rhythm of Locomotor Activity Are Altered after Chronic Exposure to Lead in Rat

PubMed Central

Sabbar, Mariam; Dkhissi-Benyahya, Ouria; Benazzouz, Abdelhamid; Lakhdar-Ghazal, Nouria

2017-01-01

Lead exposure has been reported to produce many clinical features, including parkinsonism. However, its consequences on the circadian rhythms are still unknown. Here we aimed to examine the circadian rhythms of locomotor activity following lead intoxication and investigate the mechanisms by which lead may induce alterations of circadian rhythms in rats. Male Wistar rats were injected with lead or sodium acetate (10 mg/kg/day, i.p.) during 4 weeks. Both groups were tested in the “open field” to quantify the exploratory activity and in the rotarod to evaluate motor coordination. Then, animals were submitted to continuous 24 h recordings of locomotor activity under 14/10 Light/dark (14/10 LD) cycle and in complete darkness (DD). At the end of experiments, the clock proteins BMAL1, PER1-2, and CRY1-2 were assayed in the suprachiasmatic nucleus (SCN) using immunohistochemistry. We showed that lead significantly reduced the number of crossing in the open field, impaired motor coordination and altered the daily locomotor activity rhythm. When the LD cycle was advanced by 6 h, both groups adjusted their daily locomotor activity to the new LD cycle with high onset variability in lead-intoxicated rats compared to controls. Lead also led to a decrease in the number of immunoreactive cells (ir-) of BMAL1, PER1, and PER2 without affecting the number of ir-CRY1 and ir-CRY2 cells in the SCN. Our data provide strong evidence that lead intoxication disturbs the rhythm of locomotor activity and alters clock proteins expression in the SCN. They contribute to the understanding of the mechanism by which lead induce circadian rhythms disturbances. PMID:28970786

Development and validation of real-time PCR screening methods for detection of cry1A.105 and cry2Ab2 genes in genetically modified organisms.

PubMed

Dinon, Andréia Z; Prins, Theo W; van Dijk, Jeroen P; Arisi, Ana Carolina M; Scholtens, Ingrid M J; Kok, Esther J

2011-05-01

Primers and probes were developed for the element-specific detection of cry1A.105 and cry2Ab2 genes, based on their DNA sequence as present in GM maize MON89034. Cry genes are present in many genetically modified (GM) plants and they are important targets for developing GMO element-specific detection methods. Element-specific methods can be of use to screen for the presence of GMOs in food and feed supply chains. Moreover, a combination of GMO elements may indicate the potential presence of unapproved GMOs (UGMs). Primer-probe combinations were evaluated in terms of specificity, efficiency and limit of detection. Except for specificity, the complete experiment was performed in 9 PCR runs, on 9 different days and by testing 8 DNA concentrations. The results showed a high specificity and efficiency for cry1A.105 and cry2Ab2 detection. The limit of detection was between 0.05 and 0.01 ng DNA per PCR reaction for both assays. These data confirm the applicability of these new primer-probe combinations for element detection that can contribute to the screening for GM and UGM crops in food and feed samples.

Manual therapy for unsettled, distressed and excessively crying infants: a systematic review and meta-analyses.

PubMed

Carnes, Dawn; Plunkett, Austin; Ellwood, Julie; Miles, Clare

2018-01-24

To conduct a systematic review and meta-analyses to assess the effect of manual therapy interventions for healthy but unsettled, distressed and excessively crying infants and to provide information to help clinicians and parents inform decisions about care. We reviewed published peer-reviewed primary research articles in the last 26 years from nine databases (Medline Ovid, Embase, Web of Science, Physiotherapy Evidence Database, Osteopathic Medicine Digital Repository , Cochrane (all databases), Index of Chiropractic Literature, Open Access Theses and Dissertations and Cumulative Index to Nursing and Allied Health Literature). Our inclusion criteria were: manual therapy (by regulated or registered professionals) of unsettled, distressed and excessively crying infants who were otherwise healthy and treated in a primary care setting. Outcomes of interest were: crying, feeding, sleep, parent-child relations, parent experience/satisfaction and parent-reported global change. Nineteen studies were selected for full review: seven randomised controlled trials, seven case series, three cohort studies, one service evaluation study and one qualitative study.We found moderate strength evidence for the effectiveness of manual therapy on: reduction in crying time (favourable: -1.27 hours per day (95% CI -2.19 to -0.36)), sleep (inconclusive), parent-child relations (inconclusive) and global improvement (no effect). The risk of reported adverse events was low: seven non-serious events per 1000 infants exposed to manual therapy (n=1308) and 110 per 1000 in those not exposed. Some small benefits were found, but whether these are meaningful to parents remains unclear as does the mechanisms of action. Manual therapy appears relatively safe. CRD42016037353. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Manual therapy for unsettled, distressed and excessively crying infants: a systematic review and meta-analyses

PubMed Central

Carnes, Dawn; Plunkett, Austin; Ellwood, Julie; Miles, Clare

2018-01-01

Objective To conduct a systematic review and meta-analyses to assess the effect of manual therapy interventions for healthy but unsettled, distressed and excessively crying infants and to provide information to help clinicians and parents inform decisions about care. Methods We reviewed published peer-reviewed primary research articles in the last 26 years from nine databases (Medline Ovid, Embase, Web of Science, Physiotherapy Evidence Database, Osteopathic Medicine Digital Repository, Cochrane (all databases), Index of Chiropractic Literature, Open Access Theses and Dissertations and Cumulative Index to Nursing and Allied Health Literature). Our inclusion criteria were: manual therapy (by regulated or registered professionals) of unsettled, distressed and excessively crying infants who were otherwise healthy and treated in a primary care setting. Outcomes of interest were: crying, feeding, sleep, parent–child relations, parent experience/satisfaction and parent-reported global change. Results Nineteen studies were selected for full review: seven randomised controlled trials, seven case series, three cohort studies, one service evaluation study and one qualitative study. We found moderate strength evidence for the effectiveness of manual therapy on: reduction in crying time (favourable: −1.27 hours per day (95% CI −2.19 to –0.36)), sleep (inconclusive), parent–child relations (inconclusive) and global improvement (no effect). The risk of reported adverse events was low: seven non-serious events per 1000 infants exposed to manual therapy (n=1308) and 110 per 1000 in those not exposed. Conclusions Some small benefits were found, but whether these are meaningful to parents remains unclear as does the mechanisms of action. Manual therapy appears relatively safe. PROSPERO registration number CRD42016037353. PMID:29371279

Relationship between fine particulate matter, weather condition and daily non-accidental mortality in Shanghai, China: A Bayesian approach.

PubMed

Fang, Xin; Fang, Bo; Wang, Chunfang; Xia, Tian; Bottai, Matteo; Fang, Fang; Cao, Yang

2017-01-01

There are concerns that the reported association of ambient fine particulate matter (PM2.5) with mortality might be a mixture of PM2.5 and weather conditions. We evaluated the effects of extreme weather conditions and weather types on mortality as well as their interactions with PM2.5 concentrations in a time series study. Daily non-accidental deaths, individual demographic information, daily average PM2.5 concentrations and meteorological data between 2012 and 2014 were obtained from Shanghai, China. Days with extreme weather conditions were identified. Six synoptic weather types (SWTs) were generated. The generalized additive model was set up to link the mortality with PM2.5 and weather conditions. Parameter estimation was based on Bayesian methods using both the Jeffreys' prior and an informative normal prior in a sensitivity analysis. We estimate the percent increase in non-accidental mortality per 10 μg/m3 increase in PM2.5 concentration and constructed corresponding 95% credible interval (CrI). In total, 336,379 non-accidental deaths occurred during the study period. Average daily deaths were 307. The results indicated that per 10 μg/m3 increase in daily average PM2.5 concentration alone corresponded to 0.26-0.35% increase in daily non-accidental mortality in Shanghai. Statistically significant positive associations between PM2.5 and mortality were found for favorable SWTs when considering the interaction between PM2.5 and SWTs. The greatest effect was found in hot dry SWT (percent increase = 1.28, 95% CrI: 0.72, 1.83), followed by warm humid SWT (percent increase = 0.64, 95% CrI: 0.15, 1.13). The effect of PM2.5 on non-accidental mortality differed under specific extreme weather conditions and SWTs. Environmental policies and actions should take into account the interrelationship between the two hazardous exposures.

Relationship between fine particulate matter, weather condition and daily non-accidental mortality in Shanghai, China: A Bayesian approach

PubMed Central

Wang, Chunfang; Xia, Tian; Bottai, Matteo; Fang, Fang; Cao, Yang

2017-01-01

There are concerns that the reported association of ambient fine particulate matter (PM2.5) with mortality might be a mixture of PM2.5 and weather conditions. We evaluated the effects of extreme weather conditions and weather types on mortality as well as their interactions with PM2.5 concentrations in a time series study. Daily non-accidental deaths, individual demographic information, daily average PM2.5 concentrations and meteorological data between 2012 and 2014 were obtained from Shanghai, China. Days with extreme weather conditions were identified. Six synoptic weather types (SWTs) were generated. The generalized additive model was set up to link the mortality with PM2.5 and weather conditions. Parameter estimation was based on Bayesian methods using both the Jeffreys’ prior and an informative normal prior in a sensitivity analysis. We estimate the percent increase in non-accidental mortality per 10 μg/m3 increase in PM2.5 concentration and constructed corresponding 95% credible interval (CrI). In total, 336,379 non-accidental deaths occurred during the study period. Average daily deaths were 307. The results indicated that per 10 μg/m3 increase in daily average PM2.5 concentration alone corresponded to 0.26–0.35% increase in daily non-accidental mortality in Shanghai. Statistically significant positive associations between PM2.5 and mortality were found for favorable SWTs when considering the interaction between PM2.5 and SWTs. The greatest effect was found in hot dry SWT (percent increase = 1.28, 95% CrI: 0.72, 1.83), followed by warm humid SWT (percent increase = 0.64, 95% CrI: 0.15, 1.13). The effect of PM2.5 on non-accidental mortality differed under specific extreme weather conditions and SWTs. Environmental policies and actions should take into account the interrelationship between the two hazardous exposures. PMID:29121092

Effect of monochromatic light on circadian rhythmic expression of clock genes in the hypothalamus of chick.

PubMed

Jiang, Nan; Wang, Zixu; Cao, Jing; Dong, Yulan; Chen, Yaoxing

2017-08-01

To clarify the effect of monochromatic light on circadian clock gene expression in chick hypothalamus, a total 240 newly hatched chickens were reared under blue light (BL), green light (GL), red light (RL) and white light (WL), respectively. On the post-hatched day 14, 24-h profiles of seven core clock genes (cClock, cBmal1, cBmal2, cCry1, cCry2, cPer2 and cPer3) were measured at six time points (CT 0, CT 4, CT 8, CT 12, CT 16, CT 20, circadian time). We found all these clock genes expressed with a significant rhythmicity in different light wavelength groups. Meanwhile, cClock and cBmal1 showed a high level under GL, and followed a corresponding high expression of cCry1. However, RL decreased the expression levels of these genes. Be consistent with the mRNA level, CLOCK and BMAL1 proteins also showed a high level under GL. The CLOCK-like immunoreactive neurons were observed not only in the SCN, but also in the non-SCN brain region such as the nucleus anterior medialis hypothalami, the periventricularis nucleus, the paraventricular nucleus and the median eminence. All these results are consistent with the auto-regulatory circadian feedback loop, and indicate that GL may play an important role on the circadian time generation and development in the chick hypothalamus. Our results also suggest that the circadian clock in the chick hypothalamus such as non-SCN brain region were involved in the regulation of photo information. Copyright © 2017 Elsevier B.V. All rights reserved.

Do educational materials change knowledge and behaviour about crying and shaken baby syndrome? A randomized controlled trial.

PubMed

Barr, Ronald G; Barr, Marilyn; Fujiwara, Takeo; Conway, Jocelyn; Catherine, Nicole; Brant, Rollin

2009-03-31

Shaken baby syndrome often occurs after shaking in response to crying bouts. We questioned whether the use of the educational materials from the Period of PURPLE Crying program would change maternal knowledge and behaviour related to shaking. We performed a randomized controlled trial in which 1279 mothers received materials from the Period of PURPLE Crying program or control materials during a home visit by a nurse by 2 weeks after the birth of their child. At 5 weeks, the mothers completed a diary to record their behaviour and their infants' behaviour. Two months after giving birth, the mothers completed a telephone survey to assess their knowledge and behaviour. The mean score (range 0-100 points) for knowledge about infant crying was greater among mothers who received the PURPLE materials (63.8 points) than among mothers who received the control materials (58.4 points) (difference 5.4 points, 95% confidence interval [CI] 4.1 to 6.5 points). The mean scores were similar for both groups for shaking knowledge and reported maternal responses to crying, inconsolable crying and self-talk responses. Compared with mothers who received control materials, mothers who received the PURPLE materials reported sharing information about walking away if frustrated more often (51.5% v. 38.5%, difference 13.0%, 95% CI 6.9% to 19.2%), the dangers of shaking (49.3% v. 36.4%, difference 12.9%, 95% CI 6.8% to 19.0%), and infant crying (67.6% v. 60.0%, difference 7.6%, 95% CI 1.7% to 13.5%). Walking away during inconsolable crying was significantly higher among mothers who received the PURPLE materials than among those who received control materials (0.067 v. 0.039 events per day, rate ratio 1.7, 95% CI 1.1 to 2.6). The receipt of the Period of PURPLE Crying materials led to higher maternal scores for knowledge about infant crying and for some behaviours considered to be important for the prevention of shaking.

Do educational materials change knowledge and behaviour about crying and shaken baby syndrome? A randomized controlled trial

PubMed Central

Barr, Ronald G.; Barr, Marilyn; Fujiwara, Takeo; Conway, Jocelyn; Catherine, Nicole; Brant, Rollin

2009-01-01

Background Shaken baby syndrome often occurs after shaking in response to crying bouts. We questioned whether the use of the educational materials from the Period of PURPLE Crying program would change maternal knowledge and behaviour related to shaking. Methods We performed a randomized controlled trial in which 1279 mothers received materials from the Period of PURPLE Crying program or control materials during a home visit by a nurse by 2 weeks after the birth of their child. At 5 weeks, the mothers completed a diary to record their behaviour and their infants' behaviour. Two months after giving birth, the mothers completed a telephone survey to assess their knowledge and behaviour. Results The mean score (range 0–100 points) for knowledge about infant crying was greater among mothers who received the PURPLE materials (63.8 points) than among mothers who received the control materials (58.4 points) (difference 5.4 points, 95% confidence interval [CI] 4.1 to 6.5 points). The mean scores were similar for both groups for shaking knowledge and reported maternal responses to crying, inconsolable crying and self-talk responses. Compared with mothers who received control materials, mothers who received the PURPLE materials reported sharing information about walking away if frustrated more often (51.5% v. 38.5%, difference 13.0%, 95% CI 6.9% to 19.2%), the dangers of shaking (49.3% v. 36.4%, difference 12.9%, 95% CI 6.8% to 19.0%), and infant crying (67.6% v. 60.0%, difference 7.6%, 95% CI 1.7% to 13.5%). Walking away during inconsolable crying was significantly higher among mothers who received the PURPLE materials than among those who received control materials (0.067 v. 0.039 events per day, rate ratio 1.7, 95% CI 1.1 to 2.6). Interpretation The receipt of the Period of PURPLE Crying materials led to higher maternal scores for knowledge about infant crying and for some behaviours considered to be important for the prevention of shaking. (ClinicalTrials.gov trial register no. NCT00175422.) PMID:19255065

Moonlight controls lunar-phase-dependency and regular oscillation of clock gene expressions in a lunar-synchronized spawner fish, Goldlined spinefoot.

PubMed

Takeuchi, Yuki; Kabutomori, Ryo; Yamauchi, Chihiro; Miyagi, Hitomi; Takemura, Akihiro; Okano, Keiko; Okano, Toshiyuki

2018-04-18

Goldlined spinefoot, Siganus guttatus, inhabits tropical and subtropical waters and synchronizes its spawning around the first quarter moon likely using an hourglass-like lunar timer. In previous studies, we have found that clock genes (Cryptochrome3 and Period1) could play the role of state variable in the diencephalon when determining the lunar phase for spawning. Here, we identified three Cry, two Per, two Clock, and two Bmal genes in S. guttatus and investigated their expression patterns in the diencephalon and pituitary gland. We further evaluated the effect on their expression patterns by daily interruptions of moonlight stimuli for 1 lunar cycle beginning at the new moon. It significantly modified the expression patterns in many of the examined clock(-related) genes including Cry3 in the diencephalon and/or pituitary gland. Acute interruptions of moonlight around the waxing gibbous moon upregulated nocturnal expressions of Cry1b and Cry2 in the diencephalon and pituitary gland, respectively, but did not affect expression levels of the other clock genes. These results highlighted the importance of repetitive moonlight illumination for stable or lunar-phase-specific daily expression of clock genes in the next lunar cycle that may be important for the lunar-phase-synchronized spawning on the next first quarter moon.

Correspondence of High Levels of Beta-Exotoxin I and the Presence of cry1B in Bacillus thuringiensis

PubMed Central

Espinasse, Sylvain; Gohar, Michel; Chaufaux, Josette; Buisson, Christophe; Perchat, Stéphane; Sanchis, Vincent

2002-01-01

Examination of 640 natural isolates of Bacillus thuringiensis showed that the 58 strains (9%) whose supernatants were toxic to Anthonomus grandis (Coleoptera: Curculionidae) produced between 10 and 175 μg of β-exotoxin I per ml. We also found that 55 (46%) of a sample of 118 strains whose culture supernatants were not toxic to A. grandis nevertheless produced between 2 and 5 μg/ml. However, these amounts of β-exotoxin I were below the threshold for detectable toxicity against this insect species. Secretion of large amounts of β-exotoxin I was strongly associated with the presence of cry1B and vip2 genes in the 640 natural B. thuringiensis isolates studied. We concluded that strains carrying cry1B and vip2 genes also possess, on the same plasmid, genetic determinants necessary to promote high levels of production of β-exotoxin I. PMID:12200263

Thyroxine differentially modulates the peripheral clock: lessons from the human hair follicle.

PubMed

Hardman, Jonathan A; Haslam, Iain S; Farjo, Nilofer; Farjo, Bessam; Paus, Ralf

2015-01-01

The human hair follicle (HF) exhibits peripheral clock activity, with knock-down of clock genes (BMAL1 and PER1) prolonging active hair growth (anagen) and increasing pigmentation. Similarly, thyroid hormones prolong anagen and stimulate pigmentation in cultured human HFs. In addition they are recognized as key regulators of the central clock that controls circadian rhythmicity. Therefore, we asked whether thyroxine (T4) also influences peripheral clock activity in the human HF. Over 24 hours we found a significant reduction in protein levels of BMAL1 and PER1, with their transcript levels also decreasing significantly. Furthermore, while all clock genes maintained their rhythmicity in both the control and T4 treated HFs, there was a significant reduction in the amplitude of BMAL1 and PER1 in T4 (100 nM) treated HFs. Accompanying this, cell-cycle progression marker Cyclin D1 was also assessed appearing to show an induced circadian rhythmicity by T4 however, this was not significant. Contrary to short term cultures, after 6 days, transcript and/or protein levels of all core clock genes (BMAL1, PER1, clock, CRY1, CRY2) were up-regulated in T4 treated HFs. BMAL1 and PER1 mRNA was also up-regulated in the HF bulge, the location of HF epithelial stem cells. Together this provides the first direct evidence that T4 modulates the expression of the peripheral molecular clock. Thus, patients with thyroid dysfunction may also show a disordered peripheral clock, which raises the possibility that short term, pulsatile treatment with T4 might permit one to modulate circadian activity in peripheral tissues as a target to treat clock-related disease.

Toward a detailed computational model for the mammalian circadian clock

NASA Astrophysics Data System (ADS)

Leloup, Jean-Christophe; Goldbeter, Albert

2003-06-01

We present a computational model for the mammalian circadian clock based on the intertwined positive and negative regulatory loops involving the Per, Cry, Bmal1, Clock, and Rev-Erb genes. In agreement with experimental observations, the model can give rise to sustained circadian oscillations in continuous darkness, characterized by an antiphase relationship between Per/Cry/Rev-Erb and Bmal1 mRNAs. Sustained oscillations correspond to the rhythms autonomously generated by suprachiasmatic nuclei. For other parameter values, damped oscillations can also be obtained in the model. These oscillations, which transform into sustained oscillations when coupled to a periodic signal, correspond to rhythms produced by peripheral tissues. When incorporating the light-induced expression of the Per gene, the model accounts for entrainment of the oscillations by light-dark cycles. Simulations show that the phase of the oscillations can then vary by several hours with relatively minor changes in parameter values. Such a lability of the phase could account for physiological disorders related to circadian rhythms in humans, such as advanced or delayed sleep phase syndrome, whereas the lack of entrainment by light-dark cycles can be related to the non-24h sleep-wake syndrome. The model uncovers the possible existence of multiple sources of oscillatory behavior. Thus, in conditions where the indirect negative autoregulation of Per and Cry expression is inoperative, the model indicates the possibility that sustained oscillations might still arise from the negative autoregulation of Bmal1 expression.

Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome.

PubMed

Möller-Levet, Carla S; Archer, Simon N; Bucca, Giselda; Laing, Emma E; Slak, Ana; Kabiljo, Renata; Lo, June C Y; Santhi, Nayantara; von Schantz, Malcolm; Smith, Colin P; Dijk, Derk-Jan

2013-03-19

Insufficient sleep and circadian rhythm disruption are associated with negative health outcomes, including obesity, cardiovascular disease, and cognitive impairment, but the mechanisms involved remain largely unexplored. Twenty-six participants were exposed to 1 wk of insufficient sleep (sleep-restriction condition 5.70 h, SEM = 0.03 sleep per 24 h) and 1 wk of sufficient sleep (control condition 8.50 h sleep, SEM = 0.11). Immediately following each condition, 10 whole-blood RNA samples were collected from each participant, while controlling for the effects of light, activity, and food, during a period of total sleep deprivation. Transcriptome analysis revealed that 711 genes were up- or down-regulated by insufficient sleep. Insufficient sleep also reduced the number of genes with a circadian expression profile from 1,855 to 1,481, reduced the circadian amplitude of these genes, and led to an increase in the number of genes that responded to subsequent total sleep deprivation from 122 to 856. Genes affected by insufficient sleep were associated with circadian rhythms (PER1, PER2, PER3, CRY2, CLOCK, NR1D1, NR1D2, RORA, DEC1, CSNK1E), sleep homeostasis (IL6, STAT3, KCNV2, CAMK2D), oxidative stress (PRDX2, PRDX5), and metabolism (SLC2A3, SLC2A5, GHRL, ABCA1). Biological processes affected included chromatin modification, gene-expression regulation, macromolecular metabolism, and inflammatory, immune and stress responses. Thus, insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism.

Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis.

PubMed

Rudnicka, Alicja R; Jarrar, Zakariya; Wormald, Richard; Cook, Derek G; Fletcher, Astrid; Owen, Christopher G

2012-03-01

To obtain prevalence estimates of age-related macular degeneration (AMD; late, geographic atrophy, neovascular) by age and gender amongst populations of European ancestry taking into account study design and time trends. Systematic review of population-based studies published by September 2010 with quantitative estimates of geographic atrophy (GA), neovascular (NV), and late AMD prevalence. Studies were identified by a literature search of MEDLINE (from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases. Data from 25 published studies (57 173 subjects: 455 with GA, 464 with NVAMD, and 1571 with late AMD). Bayesian meta-regression of the log odds of AMD with age, gender, and year of study allowing for differences in study design characteristics, to estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals (CrI). Log odds and prevalence of AMD. There was considerable heterogeneity in prevalence rates between studies; for late AMD, 20% of the variability in prevalence rates was explained by differences in age and 50% by study characteristics. The prevalence of AMD increased exponentially with age (odds ratio [OR], 4.2 per decade; 95% CrI, 3.8-4.6), which did not differ by gender. There was some evidence to suggest higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0-1.5). Compared with studies using fundus imaging and international classification systems, studies using fundus imaging with alternative classifications were more likely (OR, 2.7; 95% CrI, 1.1-2.8), and studies using alternative classifications without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI, 1.3-7.8). There was no good evidence of trends in AMD prevalence over time. Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%-2.0%) at 70 years of age, rising to 5.6% (95% CrI, 3.9%-7.7%) at age 80 and 20% (95% CrI, 14%-27%) at age 90. Studies using recognized classifications systems with fundus photography reported the lowest prevalences of AMD taking account of age and gender, and were stable over time, with a potentially higher risk of NVAMD for women. These prevalence estimates can be used to guide health service provision in populations of European ancestry. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Excessive infant crying doubles the risk of mood and behavioral problems at age 5: evidence for mediation by maternal characteristics.

PubMed

Smarius, Laetitia Joanna Clara Antonia; Strieder, Thea G A; Loomans, Eva M; Doreleijers, Theo A H; Vrijkotte, Tanja G M; Gemke, Reinoud J; van Eijsden, Manon

2017-03-01

The onset of behavioral problems starts in early life. This study examined whether excessive infant crying (maternal ratings) is a determinant of emotional and behavioral problems at age 5-6 years. In the Amsterdam Born Children and their Development (ABCD) study, a large prospective, observational, population-based multiethnic birth cohort, excessive infant crying (crying for three or more hours per 24 h day over the past week) during the 13th week after birth (range 11-25 weeks, SD 2 weeks), maternal burden of infant care and maternal aggressive behavior (either angry speaking, or physical aggression) was assessed using a questionnaire. Children's behavioral and emotional problems at the age of 5-6 were assessed by Goodman's Strengths and Difficulties Questionnaire (SDQ), by the subscale of generalized anxiety of the preschool anxiety scale (PAS), and by the Short Mood and Feelings Questionnaire (SMFQ). Inclusion criterion was singleton birth. Exclusion criteria were preterm born babies or congenital disorders. Among 3389 children, excessive infant crying (n = 102) was associated with a twofold increased risk of the overall problem behavior, conduct problems, hyperactivity, and mood problems at the age of 5-6 [ORs between 1.75 (95 % CI 1.09-2.81) and 2.12 (95 % CI 1.30-3.46)]. This association was mediated by maternal burden of infant care (change in odds' ratio 1-17 %) and maternal aggressive behavior (change in odds' ratio 4-10 %). There was no effect modification by the child's gender or maternal parity. Excessive infant crying was not associated with general anxiety problems. Excessive infant crying doubles the risk of behavioral, hyperactivity, and mood problems at the age of 5-6, as reported by their mother. Maternal burden of infant care partially mediates the association between excessive crying and behavioral and mood problems. Special care for mothers with a high burden of care for their excessive crying infant, notwithstanding their own good health, can be a feasible strategy for possible prevention of mood and behavioral problems in their children later in life.

Does Cry1Ab protein affect learning performances of the honey bee Apis mellifera L. (Hymenoptera, Apidae)?

PubMed

Ramirez-Romero, R; Desneux, N; Decourtye, A; Chaffiol, A; Pham-Delègue, M H

2008-06-01

Genetically modified Bt crops are increasingly used worldwide but side effects and especially sublethal effects on beneficial insects remain poorly studied. Honey bees are beneficial insects for natural and cultivated ecosystems through pollination. The goal of the present study was to assess potential effects of two concentrations of Cry1Ab protein (3 and 5000 ppb) on young adult honey bees. Following a complementary bioassay, our experiments evaluated effects of the Cry1Ab on three major life traits of young adult honey bees: (a) survival of honey bees during sub-chronic exposure to Cry1Ab, (b) feeding behaviour, and (c) learning performance at the time that honey bees become foragers. The latter effect was tested using the proboscis extension reflex (PER) procedure. The same effects were also tested using a chemical pesticide, imidacloprid, as positive reference. The tested concentrations of Cry1Ab protein did not cause lethal effects on honey bees. However, honey bee feeding behaviour was affected when exposed to the highest concentration of Cry1Ab protein, with honey bees taking longer to imbibe the contaminated syrup. Moreover, honey bees exposed to 5000 ppb of Cry1Ab had disturbed learning performances. Honey bees continued to respond to a conditioned odour even in the absence of a food reward. Our results show that transgenic crops expressing Cry1Ab protein at 5000 ppb may affect food consumption or learning processes and thereby may impact honey bee foraging efficiency. The implications of these results are discussed in terms of risks of transgenic Bt crops for honey bees.

Forecasting US ivacaftor outcomes and cost in cystic fibrosis patients with the G551D mutation.

PubMed

Dilokthornsakul, Piyameth; Hansen, Ryan N; Campbell, Jonathan D

2016-06-01

Ivacaftor, a breakthrough treatment for cystic fibrosis (CF) patients with the G551D genetic mutation, lacks long-term clinical and cost projections. This study forecasted outcomes and cost by comparing ivacaftor plus usual care versus usual care alone.A lifetime Markov model was conducted from a US payer perspective. The model consisted of five health states: 1) forced expiratory volume in 1 s (FEV1) % pred ≥70%, 2) 40%≤ FEV1 % pred <70%, 3) FEV1 % pred <40%, 4) lung transplantation and 5) death. All inputs were extracted from published literature. Budget impact was also estimated. We estimated ivacaftor's improvement in outcomes compared with a non-CF referent population.Ivacaftor was associated with 18.25 (95% credible interval (CrI) 13.71-22.20) additional life-years and 15.03 (95% CrI 11.13-18.73) additional quality-adjusted life-years (QALYs). Ivacaftor was associated with improvements in survival and QALYs equivalent to 68% and 56%, respectively, for the survival and QALY gaps between CF usual care and their non-CF peers. The incremental lifetime cost was $3 374 584. The budget impact was $0.087 per member per month.Ivacaftor increased life-years and QALYs in CF patients with the G551D mutation, and moved morbidity and mortality closer to that of their non-CF peers. Ivacaftor costs much more than usual care, but comes at a relatively limited budget impact. Copyright ©ERS 2016.

Assessing the impact of Cry1Ab-expressing corn pollen on monarch butterfly larvae in field studies

PubMed Central

Stanley-Horn, Diane E.; Dively, Galen P.; Hellmich, Richard L.; Mattila, Heather R.; Sears, Mark K.; Rose, Robyn; Jesse, Laura C. H.; Losey, John E.; Obrycki, John J.; Lewis, Les

2001-01-01

Survival and growth of monarch larvae, Danaus plexippus (L.), after exposure to either Cry1Ab-expressing pollen from three Bacillus thuringiensis (Bt) corn (Zea mays L.) events differing in toxin expression or to the insecticide, λ-cyhalothrin, were examined in field studies. First instars exposed to low doses (≈22 grains per cm2) of event-176 pollen gained 18% less weight than those exposed to Bt11 or Mon810 pollen after a 5-day exposure period. Larvae exposed to 67 pollen grains per cm2 on milkweed leaves from within an event-176 field exhibited 60% lower survivorship and 42% less weight gain compared with those exposed to leaves from outside the field. In contrast, Bt11 pollen had no effect on growth to adulthood or survival of first or third instars exposed for 5 days to ≈55 and 97 pollen grains per cm2, respectively. Similarly, no differences in larval survivorship were observed after a 4-day exposure period to leaves with 504–586 (within fields) or 18–22 (outside the field) pollen grains per cm2 collected from Bt11 and non-Bt sweet-corn fields. However, survivorship and weight gain were drastically reduced in non-Bt fields treated with λ-cyhalothrin. The effects of Bt11 and Mon810 pollen on the survivorship of larvae feeding 14 to 22 days on milkweeds in fields were negligible. Further studies should examine the lifetime and reproductive impact of Bt11 and Mon810 pollen on monarchs after long-term exposure to naturally deposited pollen. PMID:11559839

Association between the Severity of Influenza A(H7N9) Virus Infections and Length of the Incubation Period.

PubMed

Virlogeux, Victor; Yang, Juan; Fang, Vicky J; Feng, Luzhao; Tsang, Tim K; Jiang, Hui; Wu, Peng; Zheng, Jiandong; Lau, Eric H Y; Qin, Ying; Peng, Zhibin; Peiris, J S Malik; Yu, Hongjie; Cowling, Benjamin J

2016-01-01

In early 2013, a novel avian-origin influenza A(H7N9) virus emerged in China, and has caused sporadic human infections. The incubation period is the delay from infection until onset of symptoms, and varies from person to person. Few previous studies have examined whether the duration of the incubation period correlates with subsequent disease severity. We analyzed data of period of exposure on 395 human cases of laboratory-confirmed influenza A(H7N9) virus infection in China in a Bayesian framework using a Weibull distribution. We found a longer incubation period for the 173 fatal cases with a mean of 3.7 days (95% credibility interval, CrI: 3.4-4.1), compared to a mean of 3.3 days (95% CrI: 2.9-3.6) for the 222 non-fatal cases, and the difference in means was marginally significant at 0.47 days (95% CrI: -0.04, 0.99). There was a statistically significant correlation between a longer incubation period and an increased risk of death after adjustment for age, sex, geographical location and underlying medical conditions (adjusted odds ratio 1.70 per day increase in incubation period; 95% credibility interval 1.47-1.97). We found a significant association between a longer incubation period and a greater risk of death among human H7N9 cases. The underlying biological mechanisms leading to this association deserve further exploration.

Feedback repression is required for mammalian circadian clock function.

PubMed

Sato, Trey K; Yamada, Rikuhiro G; Ukai, Hideki; Baggs, Julie E; Miraglia, Loren J; Kobayashi, Tetsuya J; Welsh, David K; Kay, Steve A; Ueda, Hiroki R; Hogenesch, John B

2006-03-01

Direct evidence for the requirement of transcriptional feedback repression in circadian clock function has been elusive. Here, we developed a molecular genetic screen in mammalian cells to identify mutants of the circadian transcriptional activators CLOCK and BMAL1, which were uncoupled from CRYPTOCHROME (CRY)-mediated transcriptional repression. Notably, mutations in the PER-ARNT-SIM domain of CLOCK and the C terminus of BMAL1 resulted in synergistic insensitivity through reduced physical interactions with CRY. Coexpression of these mutant proteins in cultured fibroblasts caused arrhythmic phenotypes in population and single-cell assays. These data demonstrate that CRY-mediated repression of the CLOCK/BMAL1 complex activity is required for maintenance of circadian rhythmicity and provide formal proof that transcriptional feedback is required for mammalian clock function.

Cross-resistance to purified Bt proteins, Bt corn and Bt cotton in a Cry2Ab2-corn resistant strain of Spodoptera frugiperda.

PubMed

Yang, Fei; Kerns, David L; Head, Graham P; Price, Paula; Huang, Fangneng

2017-12-01

Gene-pyramiding by combining two or more dissimilar Bacillus thuringiensis (Bt) proteins into a crop has been used to delay insect resistance. The durability of gene-pyramiding can be reduced by cross-resistance. Fall armyworm, Spodoptera frugiperda, is a major target pest of the Cry2Ab2 protein used in pyramided Bt corn and cotton. Here, we provide the first experimental evaluation of cross-resistance in S. frugiperda selected with Cry2Ab2 corn to multiple Bt sources including purified Bt proteins, Bt corn and Bt cotton. Concentration - response bioassays showed that resistance ratios for Cry2Ab2-resistant (RR) relative to Cry2Ab2-susceptible (SS) S. frugiperda were -1.4 for Cry1F, 1.2 for Cry1A.105, >26.7 for Cry2Ab2, >10.0 for Cry2Ae and -1.1 for Vip3A. Larvae of Cry2Ab2-heterozygous (RS), SS and RR S. frugiperda were all susceptible to Bt corn and Bt cotton containing Cry1 (Cry1F or Cry1A.105) and/or Vip3A proteins. Pyramided Bt cotton containing Cry1Ac + Cry2Ab2 or Cry1Ab + Cry2Ae were also effective against SS and RS, but not RR. These findings suggest that Cry2Ab2-corn-selected S. frugiperda is not cross-resistant to Cry1F, Cry1A.105 or Vip3A protein, or corn and cotton plants containing these Bt proteins, but it can cause strong cross-resistance to Cry2Ae and Bt crops expressing similar Bt proteins. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN

PubMed Central

Ono, Daisuke; Honma, Sato; Honma, Ken-ichi

2016-01-01

The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2−/−). VIP and arginine vasopressin (AVP) signaling showed redundancy in expressing the tissue-level circadian rhythm in the SCN. AVP synthesis was significantly attenuated in the Cry1,2−/− SCN, which contributes to aperiodicity in the adult mice together with an attenuation of VIP signaling as a natural process of ontogeny. The SCN network consists of multiple clusters of cellular circadian rhythms that are differentially integrated by AVP and VIP signaling, depending on the postnatal period. PMID:27626074

Diversity of Bacillus thuringiensis strains in the maize and bean phylloplane and their respective soils in Colombia.

PubMed

Jara, S; Maduell, P; Orduz, S

2006-07-01

To evaluate the distribution of Bacillus thuringiensis strains from maize and bean phylloplane and their respective soils. B. thuringiensis was isolated from the phylloplane and soil of maize and bean from three municipalities in Antioquia, Colombia. Ninety six samples of phylloplane and 24 of soil were analyzed. A total of 214 isolates were obtained from 96 phylloplane samples while 59 isolates were recovered from 24 soil samples. Sixty five per cent and 12% of the phylloplane and soil isolates, respectively, showed activity against Spodoptera frugiperda. These isolates contained delta-endotoxin proteins of 57 and 130 kDa. The most toxic isolates against S. frugiperda had the genotype cry1Aa, cry1Ac, cry1B, and cry1D. In contrast, 27% of the phylloplane isolates and 88% of the soil isolates were active against Culex quinquefasciatus and had protein profiles similar to B. thuringiensis serovar. medellin and B. thuringiensis serovar. israelensis. The most active isolates contain cry4 and cry11 genes. The predominant population of B. thuringiensis on the phylloplane harbored the cry1 gene and was active against S. frugiperda, whereas in soil, isolates harboring cry11 gene and active against C. quinquefasciatus were the majority. The predominance of specific B. thuringiensis populations, both on the leaves and in the soil, suggests the presence of selection in B. thuringiensis populations on the studied environment.

Association between the Severity of Influenza A(H7N9) Virus Infections and Length of the Incubation Period

PubMed Central

Fang, Vicky J.; Feng, Luzhao; Tsang, Tim K.; Jiang, Hui; Wu, Peng; Zheng, Jiandong; Lau, Eric H. Y.; Qin, Ying; Peng, Zhibin; Peiris, J. S. Malik; Yu, Hongjie; Cowling, Benjamin J.

2016-01-01

Background In early 2013, a novel avian-origin influenza A(H7N9) virus emerged in China, and has caused sporadic human infections. The incubation period is the delay from infection until onset of symptoms, and varies from person to person. Few previous studies have examined whether the duration of the incubation period correlates with subsequent disease severity. Methods and Findings We analyzed data of period of exposure on 395 human cases of laboratory-confirmed influenza A(H7N9) virus infection in China in a Bayesian framework using a Weibull distribution. We found a longer incubation period for the 173 fatal cases with a mean of 3.7 days (95% credibility interval, CrI: 3.4–4.1), compared to a mean of 3.3 days (95% CrI: 2.9–3.6) for the 222 non-fatal cases, and the difference in means was marginally significant at 0.47 days (95% CrI: -0.04, 0.99). There was a statistically significant correlation between a longer incubation period and an increased risk of death after adjustment for age, sex, geographical location and underlying medical conditions (adjusted odds ratio 1.70 per day increase in incubation period; 95% credibility interval 1.47–1.97). Conclusions We found a significant association between a longer incubation period and a greater risk of death among human H7N9 cases. The underlying biological mechanisms leading to this association deserve further exploration. PMID:26885816

Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men.

PubMed

Cedernaes, Jonathan; Osler, Megan E; Voisin, Sarah; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Zierath, Juleen R; Schiöth, Helgi B; Benedict, Christian

2015-09-01

Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (-18%; P = .033) and CRY1 (-22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011). Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.

Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies.

PubMed

Mocellin, Simone; Tropea, Saveria; Benna, Clara; Rossi, Carlo Riccardo

2018-02-19

Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs). Single nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n = 12,160; controls, n = 16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method. Data were also available for the following subgroups: estrogen receptor negative breast cancer, aggressive prostate cancer, squamous lung carcinoma and lung adenocarcinoma. We found a highly significant statistical association between circadian pathway genetic variation and the risk of breast (pathway P value = 1.9 × 10 -6 ; top gene RORA, gene P value = 0.0003), prostate (pathway P value = 4.1 × 10 -6 ; top gene ARNTL, gene P value = 0.0002) and lung cancer (pathway P value = 6.9 × 10 -7 ; top gene RORA, gene P value = 2.0 × 10 -6 ), as well as all their subgroups. Out of 17 genes investigated, 15 were found to be significantly associated with the risk of cancer: four genes were shared by all three malignancies (ARNTL, CLOCK, RORA and RORB), two by breast and lung cancer (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3), whereas four genes were specific for lung cancer (ARNTL2, CSNK1E, NR1D2 and PER2) and two for breast cancer (PER1, RORC). Our findings, based on the largest series ever utilized for ARTP-based gene and pathway analysis, support the hypothesis that circadian pathway genetic variation is involved in cancer predisposition.

Growth performance and carcass characteristics of growing ram lambs fed sweet sorghum bagasse-based complete rations varying in roughage-to-concentrate ratios.

PubMed

Kumari, Nagireddy Nalini; Reddy, Yerradoddi Ramana; Blummel, Michel; Nagalakshmi, Devanaboyina; Monika, Thamatam; Reddy, Belum Venkata Subba; Reddy, Chintalapani Ravinder

2013-02-01

Different roughage-to-concentrate ratios of sweet sorghum bagasse (SSB) (a by-product of the biofuel industry)-based complete diets were assessed. Twenty four growing Nellore × Deccani ram lambs aged about 3 months (average body wt., 10.62 ± 0.25 kg) were randomly allotted to four complete rations (CR) varying in roughage-to-concentrate ratios viz. 60:40 (CR-I), 50:50 (CR-II), 40:60 (CR-III) and 30:70(CR-IV) for a period of 180 days. The feed intake was comparable among the lambs fed different experimental complete diets. Average daily weight gain (in grams) was 77.31 ± 4.90, 81.76 ± 5.16, 85.83 ± 2.83 and 86.30 ± 3.25, and feed conversion ratio (in kilograms of feed per kilogram gain) averaged 11.42 ± 0.68, 10.57 ± 0.64, 10.17 ± 0.37 and 9.96 ± 0.38 in ram lambs fed CR-I, CR-II, CR-III and CR-IV rations, respectively. Statistically, differences in daily weight gain and feed conversion ratio among the lambs fed four experimental rations were not significant (P > 0.05). The cost per kilogram gain was significantly (P < 0.01) higher in ram lambs fed CR-IV and CR-III rations compared to CR-I ration, and it was comparable between CR-I and CR-II rations. Dressing percentage averaged 44.90 ± 0.15, 42.57 ± 0.72, 43.67 ± 0.16 and 44.42 ± 0.76 for the respective diets. No significant difference and trend was observed in preslaughter weight, empty body weight, carcass weights, dressing percentage, wholesale cuts and edible and non-edible portions of experimental animals. Similarly, no significant variation could be seen in bone and meat yield (in per cent) and their ratios in various wholesale cuts among the dietary treatments. The roughage-to-concentrate ratio did not affect the chemical composition of meat; however, the fat content of meat was linearly increased with increase in the proportion of concentrate in the diets. The results of the experiment indicated that SSB can be included at 60 % level in the complete diet for economical mutton production from growing Nellore × Deccani ram lambs.

Circadian expression of clock genes in human oral mucosa and skin: association with specific cell-cycle phases.

PubMed

Bjarnason, G A; Jordan, R C; Wood, P A; Li, Q; Lincoln, D W; Sothern, R B; Hrushesky, W J; Ben-David, Y

2001-05-01

We studied the relative RNA expression of clock genes throughout one 24-hour period in biopsies obtained from the oral mucosa and skin from eight healthy diurnally active male study participants. We found that the human clock genes hClock, hTim, hPer1, hCry1, and hBmal1 are expressed in oral mucosa and skin, with a circadian profile consistent with that found in the suprachiasmatic nuclei and the peripheral tissues of rodents. hPer1, hCry1, and hBmal1 have a rhythmic expression, peaking early in the morning, in late afternoon, and at night, respectively, whereas hClock and hTim are not rhythmic. This is the first human study to show a circadian profile of expression for all five clock genes as documented in rodents, suggesting their functional importance in man. In concurrent oral mucosa biopsies, thymidylate synthase enzyme activity, a marker for DNA synthesis, had a circadian variation with peak activity in early afternoon, coinciding with the timing of S phase in our previous study on cell-cycle timing in human oral mucosa. The major peak in hPer1 expression occurs at the same time of day as the peak in G(1) phase in oral mucosa, suggesting a possible link between the circadian clock and the mammalian cell cycle.

Bt Proteins Have No Detrimental Effects on Larvae of the Green Lacewing, Chrysopa pallens (Rambur) (Neuroptera: Chrysopidae).

PubMed

Ali, I; Zhang, S; Muhammad, M S; Iqbal, M; Cui, J-J J-J

2018-06-01

Biosafety of a genetically modified crop is required to be assessed prior to its commercialization. For this, a suitable artificial diet was developed and used to establish a dietary exposure test for assessing the toxicity of midgut-active Bt insecticidal proteins on Chrysopa pallens (Rambur). Subsequently, this dietary exposure test was used to evaluate the toxicity of the proteins Cry1Ab, Cry1Ac, Cry1Ah, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, and Vip3Aa on C. pallens larvae. Temporal stability, bioactivity, and the intake of the insecticidal proteins were confirmed by enzyme-linked immunosorbent assay and a sensitive-insect bioassay. The life history characteristics, such as survival, pupation, adult emergence, 7-day larval weight, larval developmental time, and emerged male and female fresh weights remained unaffected, when C. pallens were fed the pure artificial diet (negative control) and the artificial diets containing 200 μg/g of each purified protein: Cry1Ab, Cry1Ac, Cry1Ah, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, or Vip3Aa. On the contrary, all of the life history characteristics of C. pallens larvae were adversely affected when fed artificial diet containing boric acid (positive control). The results demonstrate that diets containing the tested concentrations of Cry1Ab, Cry1Ac, Cry1Ah, Cry1Ca, Cry1F, Cry2Aa, Cry2Ab, and Vip3Aa have null effects on C. pallens larvae. The outcome indicates that genetically modified crops expressing the tested Bt proteins are safe for the lacewing, C. pallens.

Hand hygiene with soap and water is superior to alcohol rub and antiseptic wipes for removal of Clostridium difficile.

PubMed

Oughton, Matthew T; Loo, Vivian G; Dendukuri, Nandini; Fenn, Susan; Libman, Michael D

2009-10-01

To evaluate common hand hygiene methods for efficacy in removing Clostridium difficile. Randomized crossover comparison among 10 volunteers with hands experimentally contaminated by nontoxigenic C. difficile. Interventions included warm water with plain soap, cold water with plain soap, warm water with antibacterial soap, antiseptic hand wipes, alcohol-based handrub, and a control involving no intervention. All interventions were evaluated for mean reduction in colony-forming units (CFUs) under 2 contamination protocols: "whole hand" and "palmar surface." Results were analyzed according to a Bayesian approach, by using hierarchical models adjusted for multiple observations. Under the whole-hand protocol, the greatest adjusted mean reductions were achieved by warm water with plain soap (2.14 log(10) CFU/mL [95% credible interval (CrI), 1.74-2.54 log(10) CFU/mL]), cold water with plain soap (1.88 log(10) CFU/mL [95% CrI, 1.48-2.28 log(10) CFU/mL), and warm water with antibacterial soap (1.51 log(10) CFU/mL [95% CrI, 1.12-1.91 log(10) CFU/mL]), followed by antiseptic hand wipes (0.57 log(10) CFU/mL [95% CrI, 0.17-0.96 log(10) CFU/mL]). Alcohol-based handrub (0.06 log(10) CFU/mL [95% CrI, -0.34 to 0.45 log(10) CFU/mL]) was equivalent to no intervention. Under the palmar surface protocol, warm water with plain soap, cold water with plain soap, and warm water with antibacterial soap again yielded the greatest mean reductions, followed by antiseptic hand wipes (26.6, 26.6, 26.6, and 21.9 CFUs per plate, respectively), when compared with alcohol-based handrub. Hypothenar (odds ratio, 10.98 [95% CrI, 1.96-37.65]) and thenar (odds ratio, 6.99 [95% CrI, 1.25-23.41]) surfaces were more likely than fingertips to remain heavily contaminated after handwashing. Handwashing with soap and water showed the greatest efficacy in removing C. difficile and should be performed preferentially over the use of alcohol-based handrubs when contact with C. difficile is suspected or likely.

Effects of continuous white light and 12h white-12h blue light-cycles on the expression of clock genes in diencephalon, liver, and skeletal muscle in chicks.

PubMed

Honda, Kazuhisa; Kondo, Makoto; Hiramoto, Daichi; Saneyasu, Takaoki; Kamisoyama, Hiroshi

2017-05-01

The core circadian clock mechanism relies on a feedback loop comprised of clock genes, such as the brain and muscle Arnt-like 1 (Bmal1), chriptochrome 1 (Cry1), and period 3 (Per3). Exposure to the light-dark cycle synchronizes the master circadian clock in the brain, and which then synchronizes circadian clocks in peripheral tissues. Birds have long been used as a model for the investigation of circadian rhythm in human neurobiology. In the present study, we examined the effects of continuous light and the combination of white and blue light on the expression of clock genes (Bmal1, Cry1, and Per3) in the central and peripheral tissues in chicks. Seventy two day-old male chicks were weighed, allocated to three groups and maintained under three light schedules: 12h white light-12h dark-cycles group (control); 24h white light group (WW group); 12h white light-12h blue light-cycles group (WB group). The mRNA levels of clock genes in the diencephalon were significantly different between the control and WW groups. On the other hand, the alteration in the mRNA levels of clock genes was similar between the control and WB groups. Similar phenomena were observed in the liver and skeletal muscle (biceps femoris). These results suggest that 12h white-12h blue light-cycles did not disrupt the circadian rhythm of clock gene expression in chicks. Copyright © 2017 Elsevier Inc. All rights reserved.

Moderate Versus Light Pressure Massage Therapy Leads to Greater Weight Gain in Preterm Infants

PubMed Central

Field, Tiffany; Diego, Miguel A.; Hernandez-Reif, Maria; Deeds, Osvelia; Figuereido, Barbara

2007-01-01

Sixty-eight preterm infants (M GA=3Owks.) were randomly assigned to a moderate or to a light pressure massage therapy group to receive 15 massages 3 times per day for 5 days. Behavior state, stress behaviors and heart rate were recorded for 15 minutes before and during the first 15-minute therapy session. Weight gain was recorded over the 5 day therapy period. The moderate versus light pressure massage group gained significantly more weight per day. During the behavior observations the moderate versus light pressure massage group showed significantly lower increases from the pre-session to the session recording on: 1) active sleep; 2) fussing; 3) crying; 4) movement; and 5) stress behavior (hiccupping). They also showed a smaller decrease in deep sleep, a greater decrease in heart rate and a greater increase in vagal tone. Thus, the moderate pressure massage therapy group appeared to be more relaxed and less aroused than the light pressure massage group which may have contributed to the greater weight gain of the moderate pressure massage therapy group. PMID:17138310

Probiotics to improve outcomes of colic in the community: Protocol for the Baby Biotics randomised controlled trial

PubMed Central

2012-01-01

Background Infant colic, characterised by excessive crying/fussing for no apparent cause, affects up to 20% of infants under three months of age and is a great burden to families, health professionals and the health system. One promising approach to improving its management is the use of oral probiotics. The Baby Biotics trial aims to determine whether the probiotic Lactobacillus reuteri DSM 17938 is effective in reducing crying in infants less than three months old (<13.0 weeks) with infant colic when compared to placebo. Methods/Design Design: Double-blind, placebo-controlled randomised trial in Melbourne, Australia. Participants: 160 breast and formula fed infants less than three months old who present either to clinical or community services and meet Wessel’s criteria of crying and/or fussing. Intervention: Oral once-daily Lactobacillus reuteri (1x108 cfu) versus placebo for one month. Primary outcome: Infant crying/fussing time per 24 hours at one month. Secondary outcomes: i) number of episodes of infant crying/fussing per 24 hours and ii) infant sleep duration per 24 hours (at 7, 14, 21, 28 days and 6 months); iii) maternal mental health scores, iv) family functioning scores, v) parent quality adjusted life years scores, and vi) intervention cost-effectiveness (at one and six months); and vii) infant faecal microbiota diversity, viii) infant faecal calprotectin levels and ix) Eschericia coli load (at one month only). Analysis: Primary and secondary outcomes for the intervention versus control groups will be compared with t tests and non-parametric tests for continuous data and chi squared tests for dichotomous data. Regression models will be used to adjust for potential confounding factors. Intention-to-treat analysis will be applied. Discussion An effective, practical and acceptable intervention for infant colic would represent a major clinical advance. Because our trial includes breast and formula-fed babies, our results should generalise to most babies with colic. If cost-effective, the intervention’s simplicity is such that it could be widely taken up as a new standard of care in the primary and secondary care sectors. Trial Registration Current Controlled Trials ISRCTN95287767 PMID:22928654

Arabidopsis Casein Kinase1 Proteins CK1.3 and CK1.4 Phosphorylate Cryptochrome2 to Regulate Blue Light Signaling[C][W

PubMed Central

Tan, Shu-Tang; Dai, Cheng; Liu, Hong-Tao; Xue, Hong-Wei

2013-01-01

Casein kinase1 (CK1) plays crucial roles in regulating growth and development via phosphorylating various substrates throughout the eukaryote kingdom. Blue light is crucial for normal growth of both plants and animals, and blue light receptor cryptochrome2 (CRY2) undergoes blue light–dependent phosphorylation and degradation in planta. To study the function of plant CK1s, systematic genetic analysis showed that deficiency of two paralogous Arabidopsis thaliana CK1s, CK1.3 and CK1.4, caused shortened hypocotyls, especially under blue light, while overexpression of either CK1.3 or CK1.4 resulted in the insensitive response to blue light and delayed flowering under long-day conditions. CK1.3 or CK1.4 act dependently on CRY2, and overexpression of CK1.3 or CK1.4 significantly suppresses the hypersensitive response to blue light by CRY2 overexpression. Biochemical studies showed that CK1.3 and CK1.4 directly phosphorylate CRY2 at Ser-587 and Thr-603 in vitro and negatively regulate CRY2 stability in planta, which are stimulated by blue light, further confirming the crucial roles of CK1.3 and CK1.4 in blue light responses through phosphorylating CRY2. Interestingly, expression of CK1.3 and CK1.4 is stimulated by blue light and feedback regulated by CRY2-mediated signaling. These results provide direct evidence for CRY2 phosphorylation and informative clues on the mechanisms of CRY2-mediated light responses. PMID:23897926

Bt Jute Expressing Fused δ-Endotoxin Cry1Ab/Ac for Resistance to Lepidopteran Pests

PubMed Central

Majumder, Shuvobrata; Sarkar, Chirabrata; Saha, Prosanta; Gotyal, Bheemanna S.; Satpathy, Subrata; Datta, Karabi; Datta, Swapan K.

2018-01-01

Jute (Corchorus sp.) is naturally occurring, biodegradable, lignocellulosic-long, silky, golden shiny fiber producing plant that has great demands globally. Paper and textile industries are interested in jute because of the easy availability, non-toxicity and high yield of cellulosic biomass produced per acre in cultivation. Jute is the major and most industrially used bast fiber-producing crop in the world and it needs protection from insect pest infestation that decreases its yield and quality. Single locus integration of the synthetically fused cry1Ab/Ac gene of Bacillus thuringiensis (Bt) in Corchorus capsularis (JRC 321) by Agrobacterium tumefaciens-mediated shoot tip transformation provided 5 potent Bt jute lines BT1, BT2, BT4, BT7 and BT8. These lines consistently expressed the Cry1Ab/Ac endotoxin ranging from 0.16 to 0.35 ng/mg of leaf, in the following generations (analyzed upto T4). The effect of Cry1Ab/Ac endotoxin was studied against 3 major Lepidopteran pests of jute- semilooper (Anomis sabulifera Guenee), hairy caterpillar (Spilarctia obliqua Walker) and indigo caterpillar (Spodoptera exigua Hubner) by detached leaf and whole plant insect bioassay on greenhouse-grown transgenic plants. Results confirm that larvae feeding on transgenic plants had lower food consumption, body size, body weight and dry weight of excreta compared to non-transgenic controls. Insect mortality range among transgenic feeders was 66–100% for semilooper and hairy caterpillar and 87.50% for indigo caterpillar. Apart from insect resistance, the transgenic plants were at par with control plants in terms of agronomic parameters and fiber quality. Hence, these Bt jutes in the field would survive Lepidopteran pest infestation, minimize harmful pesticide usage and yield good quality fiber. PMID:29354143

Highly Efficient Small Form Factor LED Retrofit Lamp

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steven Allen; Fred Palmer; Ming Li

2011-09-11

This report summarizes work to develop a high efficiency LED-based MR16 lamp downlight at OSRAM SYLVANIA under US Department of Energy contract DE-EE0000611. A new multichip LED package, electronic driver, and reflector optic were developed for these lamps. At steady-state, the lamp luminous flux was 409 lumens (lm), luminous efficacy of 87 lumens per watt (LPW), CRI (Ra) of 87, and R9 of 85 at a correlated color temperature (CCT) of 3285K. The LED alone achieved 120 lumens per watt efficacy and 600 lumen flux output at 25 C. The driver had 90% electrical conversion efficiency while maintaining excellent powermore » quality with power factor >0.90 at a power of only 5 watts. Compared to similar existing MR16 lamps using LED sources, these lamps had much higher efficacy and color quality. The objective of this work was to demonstrate a LED-based MR16 retrofit lamp for replacement of 35W halogen MR16 lamps having (1) luminous flux of 500 lumens, (2) luminous efficacy of 100 lumens per watt, (3) beam angle less than 40{sup o} and center beam candlepower of at least 1000 candelas, and (4) excellent color quality.« less

Cost-effectiveness of Skin Cancer Referral and Consultation Using Teledermoscopy in Australia.

PubMed

Snoswell, Centaine L; Caffery, Liam J; Whitty, Jennifer A; Soyer, H Peter; Gordon, Louisa G

2018-06-01

International literature has shown that teledermoscopy referral may be a viable method for skin cancer referral; however, no economic investigations have occurred in Australia. To assess the cost-effectiveness of teledermoscopy as a referral mechanism for skin cancer diagnosis and management in Australia. Cost-effectiveness analysis using a decision-analytic model of Australian primary care, informed by publicly available data. We compared the costs of teledermoscopy referral (electronic referral containing digital dermoscopic images) vs usual care (a written referral letter) for specialist dermatologist review of a suspected skin cancer. Cost and time in days to clinical resolution, where clinical resolution was defined as diagnosis by a dermatologist or excision by a general practitioner. Probabilistic sensitivity analysis was performed to examine the uncertainty of the main results. Findings from the decision-analytic model showed that the mean time to clinical resolution was 9 days (range, 1-50 days) with teledermoscopy referral compared with 35 days (range, 0-138 days) with usual care alone (difference, 26 days; 95% credible interval [CrI], 13-38 days). The estimated mean cost difference between teledermoscopy referral (A$318.39) vs usual care (A$263.75) was A$54.64 (95% CrI, A$22.69-A$97.35) per person. The incremental cost per day saved to clinical resolution was A$2.10 (95% CrI, A$0.87-A$5.29). Using teledermoscopy for skin cancer referral and triage in Australia would cost A$54.64 extra per case on average but would result in clinical resolution 26 days sooner than usual care. Implementation recommendations depend on the preferences of the Australian health system decision makers for either lower cost or expedited clinical resolution. Further research around the clinical significance of expedited clinical resolution and its importance for patients could inform implementation recommendations for the Australian setting.

Potential cost-effectiveness of supervised injection facilities in Toronto and Ottawa, Canada.

PubMed

Enns, Eva A; Zaric, Gregory S; Strike, Carol J; Jairam, Jennifer A; Kolla, Gillian; Bayoumi, Ahmed M

2016-03-01

Supervised injection facilities (legally sanctioned spaces for supervised consumption of illicitly obtained drugs) are controversial public health interventions. We determined the optimal number of facilities in two Canadian cities using health economic methods. Dynamic compartmental model of HIV and hepatitis C transmission through sexual contact and sharing of drug use equipment. Toronto and Ottawa, Canada. Simulated population of each city. Zero to five supervised injection facilities. Direct health-care costs and quality-adjusted life-years (QALYs) over 20 years, discounted at 5% per year; incremental cost-effectiveness ratios. In Toronto, one facility cost $4.1 million and resulted in a gain of 385 QALYs over 20 years, for an incremental cost-effectiveness ratio (ICER) of $10,763 per QALY [95% credible interval (95CrI): cost-saving to $278,311]. Establishing one facility in Ottawa had an ICER of $6127 per QALY (95CrI: cost-saving to $179,272). At a $50,000 per QALY threshold, three facilities would be cost-effective in Toronto and two in Ottawa. The probability that establishing three, four, or five facilities in Toronto was cost-effective was 17, 21, and 41%, respectively. Establishing one, two, or three facilities in Ottawa was cost-effective with 13, 35, and 41% probability, respectively. Establishing no facility was unlikely to be the most cost-effective option (14% in Toronto and 10% in Ottawa). In both cities, results were robust if the reduction in needle-sharing among clients of the facilities was at least 50% and fixed operating costs were less than $2.0 million. Using a $50,000 per quality-adjusted life-years threshold for cost-effectiveness, it is likely to be cost-effective to establish at least three legally sanctioned spaces for supervised injection of illicitly obtained drugs in Toronto, Canada and two in Ottawa, Canada. © 2015 Society for the Study of Addiction.

Application Summary Report 22: LED MR16 Lamps

DOE Office of Scientific and Technical Information (OSTI.GOV)

Royer, Michael P.

2014-07-23

This report analyzes the independently tested photometric performance of 27 LED MR16 lamps. It describes initial performance based on light output, efficacy, distribution, color quality, electrical characteristics, and form factor, with comparisons to a selection of benchmark halogen MR16s and ENERGY STAR qualification thresholds. Three types of products were targeted. First, CALiPER sought 3000 K lamps with the highest rated lumen output (i.e., at least 500 lm) or a claim of equivalency to a 50 W halogen MR16 or higher. The test results indicate that while the initial performance of LED MR16s has improved across the board, market-available products stillmore » do not produce the lumen output and center beam intensity of typical 50 W halogen MR16 lamps. In fact, most of the 18 lamps in this category had lower lumen output and center beam intensity than a typical 35 W halogen MR16 lamp. Second, CALiPER sought lamps with a CRI of 90 or greater. Only four manufacturers were identified with a product in this category. CALiPER testing confirmed the performance of these lamps, which are a good option for applications where high color fidelity is needed. A vast majority of the LED MR16 lamps have a CRI in the low 80s; this is generally acceptable for ambient lighting, but may not always be acceptable for focal lighting. For typical LED packages, there is a fundamental tradeoff between CRI and efficacy, but the lamps in the high-CRI group in this report still offer comparable performance to the rest of the Series 22 products in other performance areas. Finally, CALiPER sought lamps with a narrow distribution, denoted as a beam angle less than 15°. Five such lamps were purchased. Notably, no lamp was identified as having high lumen output (500 lumens or greater), high CRI (90 or greater), a narrow distribution (15° or less), and an efficacy greater than 60 lm/W. This would be an important achievement for LED MR16s especially if output could reach approximately 700 800 lumens, or the approximate equivalent of a 50 W halogen MR16 lamp. Many factors beyond photometric performance should be considered during specification. For example, performance over time, transformer and dimmer compatibility, and total system performance are all critical to a successful installation. Subsequent CALiPER reports will investigate more complex issues.« less

The Blue Light-Dependent Polyubiquitination and Degradation of Arabidopsis Cryptochrome2 Requires Multiple E3 Ubiquitin Ligases.

PubMed

Liu, Qing; Wang, Qin; Liu, Bin; Wang, Wei; Wang, Xu; Park, Joon; Yang, Zhenming; Du, Xinglin; Bian, Mingdi; Lin, Chentao

2016-10-01

Cryptochromes are blue light receptors regulated by light-dependent ubiquitination and degradation in both plant and animal lineages. The Arabidopsis genome encodes two cryptochromes, CRY1 and CRY2, of which CRY2 undergoes blue light-dependent ubiquitination and 26S proteasome-dependent degradation. The molecular mechanism regulating blue light-dependent proteolysis of CRY2 is still not fully understood. We found that the F-box proteins ZEITLUPE (ZTL) and Lov Kelch Protein2 (LKP2), which mediate blue light suppression of degradation of the CRY2 signaling partner CIB1, are not required for the blue light-dependent CRY2 degradation. We further showed that the previously reported function of the COP1-SPA1 protein complex in blue light-dependent CRY2 degradation is more likely to be attributable to its cullin 4 (CUL4)-based E3 ubiquitin ligase activity than its activity as the cryptochrome signaling partner. However, the blue light-dependent CRY2 degradation is only partially impaired in the cul4 mutant, the cop1-5 null mutant and the spa1234 quadruple mutant, suggesting a possible involvement of additional E3 ubiquitin ligases in the regulation of CRY2. Consistent with this hypothesis, we demonstrated that the blue light-dependent CRY2 degradation is significantly impaired in the temperature-sensitive cul1 mutant allele (axr6-3), especially under the non-permissive temperature. Based on these and other results presented, we propose that photoexcited CRY2 undergoes Lys48-linked polyubiquitination catalyzed by the CUL4- and CUL1-based E3 ubiquitin ligases. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cry3Bb1-Resistant Western Corn Rootworm, Diabrotica virgifera virgifera (LeConte) Does Not Exhibit Cross-Resistance to DvSnf7 dsRNA.

PubMed

Moar, William; Khajuria, Chitvan; Pleau, Michael; Ilagan, Oliver; Chen, Mao; Jiang, Changjian; Price, Paula; McNulty, Brian; Clark, Thomas; Head, Graham

2017-01-01

There is a continuing need to express new insect control compounds in transgenic maize against western corn rootworm, Diabrotica virgifera virgifera (LeConte) (WCR). In this study three experiments were conducted to determine cross-resistance between the new insecticidal DvSnf7 dsRNA, and Bacillus thuringiensis (Bt) Cry3Bb1; used to control WCR since 2003, with field-evolved resistance being reported. Laboratory susceptible and Cry3Bb1-resistant WCR were evaluated against DvSnf7 dsRNA in larval diet-incorporation bioassays. Additionally, the susceptibility of seven field and one field-derived WCR populations to DvSnf7 (and Cry3Bb1) was assessed in larval diet-overlay bioassays. Finally, beetle emergence of laboratory susceptible and Cry3Bb1-resistant WCR was evaluated with maize plants in the greenhouse expressing Cry3Bb1, Cry34Ab1/Cry35Ab1, or DvSnf7 dsRNA singly, or in combination. The Cry3Bb1-resistant colony had slight but significantly (2.7-fold; P<0.05) decreased susceptibility to DvSnf7 compared to the susceptible colony, but when repeated using a field-derived WCR population selected for reduced Cry3Bb1 susceptibility, there was no significant difference (P<0.05) in DvSnf7 susceptibility compared to that same susceptible population. Additionally, this 2.7-fold difference in susceptibility falls within the range of DvSnf7 susceptibility among the seven field populations tested. Additionally, there was no correlation between susceptibility to DvSnf7 and Cry3Bb1 for all populations evaluated. In greenhouse studies, there were no significant differences (P<0.05) between beetle emergence of susceptible and Cry3Bb1-resistant colonies on DvSnf7 and Cry34Ab1/Cry35Ab1, and between DvSnf7 and MON 87411 (DvSnf7 + Cry3Bb1) for the Cry3Bb1-resistant colony. These results demonstrate no cross-resistance between DvSnf7 and Cry3Bb1 against WCR. Therefore, pyramiding DvSnf7 with Bt proteins such as Cry3Bb1 and Cry34Ab1/Cry35Ab1 will provide a valuable IRM tool against WCR that will increase the durability of these Bt proteins. These results also illustrate the importance of using appropriate bioassay methods when characterizing field-evolved resistant WCR populations.

Cry3Bb1-Resistant Western Corn Rootworm, Diabrotica virgifera virgifera (LeConte) Does Not Exhibit Cross-Resistance to DvSnf7 dsRNA

PubMed Central

Khajuria, Chitvan; Pleau, Michael; Ilagan, Oliver; Chen, Mao; Jiang, Changjian; Price, Paula; McNulty, Brian; Clark, Thomas; Head, Graham

2017-01-01

Background and Methodology There is a continuing need to express new insect control compounds in transgenic maize against western corn rootworm, Diabrotica virgifera virgifera (LeConte) (WCR). In this study three experiments were conducted to determine cross-resistance between the new insecticidal DvSnf7 dsRNA, and Bacillus thuringiensis (Bt) Cry3Bb1; used to control WCR since 2003, with field-evolved resistance being reported. Laboratory susceptible and Cry3Bb1-resistant WCR were evaluated against DvSnf7 dsRNA in larval diet-incorporation bioassays. Additionally, the susceptibility of seven field and one field-derived WCR populations to DvSnf7 (and Cry3Bb1) was assessed in larval diet-overlay bioassays. Finally, beetle emergence of laboratory susceptible and Cry3Bb1-resistant WCR was evaluated with maize plants in the greenhouse expressing Cry3Bb1, Cry34Ab1/Cry35Ab1, or DvSnf7 dsRNA singly, or in combination. Principal Findings and Conclusions The Cry3Bb1-resistant colony had slight but significantly (2.7-fold; P<0.05) decreased susceptibility to DvSnf7 compared to the susceptible colony, but when repeated using a field-derived WCR population selected for reduced Cry3Bb1 susceptibility, there was no significant difference (P<0.05) in DvSnf7 susceptibility compared to that same susceptible population. Additionally, this 2.7-fold difference in susceptibility falls within the range of DvSnf7 susceptibility among the seven field populations tested. Additionally, there was no correlation between susceptibility to DvSnf7 and Cry3Bb1 for all populations evaluated. In greenhouse studies, there were no significant differences (P<0.05) between beetle emergence of susceptible and Cry3Bb1-resistant colonies on DvSnf7 and Cry34Ab1/Cry35Ab1, and between DvSnf7 and MON 87411 (DvSnf7 + Cry3Bb1) for the Cry3Bb1-resistant colony. These results demonstrate no cross-resistance between DvSnf7 and Cry3Bb1 against WCR. Therefore, pyramiding DvSnf7 with Bt proteins such as Cry3Bb1 and Cry34Ab1/Cry35Ab1 will provide a valuable IRM tool against WCR that will increase the durability of these Bt proteins. These results also illustrate the importance of using appropriate bioassay methods when characterizing field-evolved resistant WCR populations. PMID:28060922

JPRS Report, Soviet Union, Military Affairs.

DTIC Science & Technology

1988-10-11

had relatively the smallest army in the world (in the number of servicemen per 1 million pop - ulation). But they also cried then about "Red" milita...of inadequacy and the "volatility" of their actions. An Afghan vet kills a punk , hating his philosophy and way of life. An Afghan vet makes a fuss

Crystal Structure of the CLOCK Transactivation Domain Exon19 in Complex with a Repressor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, Zhiqiang; Su, Lijing; Pei, Jimin

In the canonical clock model, CLOCK:BMAL1-mediated transcriptional activation is feedback regulated by its repressors CRY and PER and, in association with other coregulators, ultimately generates oscillatory gene expression patterns. How CLOCK:BMAL1 interacts with coregulator(s) is not well understood. Here we report the crystal structures of the mouse CLOCK transactivating domain Exon19 in complex with CIPC, a potent circadian repressor that functions independently of CRY and PER. The Exon19:CIPC complex adopts a three-helical coiled-coil bundle conformation containing two Exon19 helices and one CIPC. Unique to Exon19:CIPC, three highly conserved polar residues, Asn341 of CIPC and Gln544 of the two Exon19 helices,more » are located at the mid-section of the coiled-coil bundle interior and form hydrogen bonds with each other. Combining results from protein database search, sequence analysis, and mutagenesis studies, we discovered for the first time that CLOCK Exon19:CIPC interaction is a conserved transcription regulatory mechanism among mammals, fish, flies, and other invertebrates.« less

Performance and cross-crop resistance of Cry1F-maize selected Spodoptera frugiperda on transgenic Bt cotton: implications for resistance management

PubMed Central

Yang, Fei; Kerns, David L.; Brown, Sebe; Kurtz, Ryan; Dennehy, Tim; Braxton, Bo; Head, Graham; Huang, Fangneng

2016-01-01

Transgenic crops producing Bacillus thuringiensis (Bt) proteins have become a primary tool in pest management. Due to the intensive use of Bt crops, resistance of the fall armyworm, Spodoptera frugiperda, to Cry1F maize has occurred in Puerto Rico, Brazil, and some areas of the southeastern U.S. The sustainability of Bt crops faces a great challenge because the Cry1F-maize resistant S. frugiperda may also infest other Bt crops in multiple cropping ecosystems. Here we examined the survival and plant injury of a S. frugiperda population selected with Cry1F maize on three single-gene and five pyramided Bt cotton products. Larvae of Cry1F-susceptible (SS), -heterozygous (RS), and -resistant (RR) genotypes of S. frugiperda were all susceptible to the pyramided cotton containing Cry1Ac/Cry2Ab, Cry1Ac/Cry1F/Vip3A, Cry1Ab/Cry2Ae, or Cry1Ab/Cry2Ae/Vip3A, and the single-gene Cry2Ae cotton. Pyramided cotton containing Cry1Ac/Cry1F was effective against SS and RS, but not for RR. These findings show that the Cry1F-maize selected S. frugiperda can cause cross-crop resistance to other Bt crops expressing similar insecticidal proteins. Resistance management and pest management programs that utilize diversify mortality factors must be implemented to ensure the sustainability of Bt crops. This is especially important in areas where resistance to single-gene Bt crops is already widespread. PMID:27301612

Performance and cross-crop resistance of Cry1F-maize selected Spodoptera frugiperda on transgenic Bt cotton: implications for resistance management.

PubMed

Yang, Fei; Kerns, David L; Brown, Sebe; Kurtz, Ryan; Dennehy, Tim; Braxton, Bo; Head, Graham; Huang, Fangneng

2016-06-15

Transgenic crops producing Bacillus thuringiensis (Bt) proteins have become a primary tool in pest management. Due to the intensive use of Bt crops, resistance of the fall armyworm, Spodoptera frugiperda, to Cry1F maize has occurred in Puerto Rico, Brazil, and some areas of the southeastern U.S. The sustainability of Bt crops faces a great challenge because the Cry1F-maize resistant S. frugiperda may also infest other Bt crops in multiple cropping ecosystems. Here we examined the survival and plant injury of a S. frugiperda population selected with Cry1F maize on three single-gene and five pyramided Bt cotton products. Larvae of Cry1F-susceptible (SS), -heterozygous (RS), and -resistant (RR) genotypes of S. frugiperda were all susceptible to the pyramided cotton containing Cry1Ac/Cry2Ab, Cry1Ac/Cry1F/Vip3A, Cry1Ab/Cry2Ae, or Cry1Ab/Cry2Ae/Vip3A, and the single-gene Cry2Ae cotton. Pyramided cotton containing Cry1Ac/Cry1F was effective against SS and RS, but not for RR. These findings show that the Cry1F-maize selected S. frugiperda can cause cross-crop resistance to other Bt crops expressing similar insecticidal proteins. Resistance management and pest management programs that utilize diversify mortality factors must be implemented to ensure the sustainability of Bt crops. This is especially important in areas where resistance to single-gene Bt crops is already widespread.

Frequency of Cry1F Non-Recessive Resistance Alleles in North Carolina Field Populations of Spodoptera frugiperda (Lepidoptera: Noctuidae)

PubMed Central

Li, Guoping; Reisig, Dominic; Miao, Jin; Gould, Fred; Huang, Fangneng; Feng, Hongqiang

2016-01-01

Fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is a target species of transgenic corn (Zea mays L.) that expresses single and pyramided Bacillus thuringiensis (Bt) toxin. In 2014, S. frugiperda were collected from a light trap in North Carolina, and a total of 212 F1/F2 isofemale lines of S. frugiperda were screened for resistance to Bt and non-Bt corn. All of the 212 isolines were susceptible to corn tissue expressing Cry1A.105 + Cry2Ab, Cry1F + Cry1A.105 + Cry2Ab, and Cry1F + Cry1Ab + Vip3Aa20. Growth rate bioassays were performed to isolate non-recessive Bt resistance alleles. Seven individuals out of the 212 isofemale lines carried major non-recessive alleles conferring resistance to Cry1F. A pooled colony was created from the seven individuals. This colony was 151.21 times more resistant to Cry1F than a known-susceptible population and was also resistant to Cry1A.105, but was not resistant to Cry2Ab and Vip3Aa20. The results demonstrate that field populations of S. frugiperda collected from North Carolina are generally susceptible to Cry1F, but that some individuals carry resistant alleles. The data generated in this study can be used as baseline data for resistance monitoring. PMID:27119741

Frequency of Cry1F Non-Recessive Resistance Alleles in North Carolina Field Populations of Spodoptera frugiperda (Lepidoptera: Noctuidae).

PubMed

Li, Guoping; Reisig, Dominic; Miao, Jin; Gould, Fred; Huang, Fangneng; Feng, Hongqiang

2016-01-01

Fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is a target species of transgenic corn (Zea mays L.) that expresses single and pyramided Bacillus thuringiensis (Bt) toxin. In 2014, S. frugiperda were collected from a light trap in North Carolina, and a total of 212 F1/F2 isofemale lines of S. frugiperda were screened for resistance to Bt and non-Bt corn. All of the 212 isolines were susceptible to corn tissue expressing Cry1A.105 + Cry2Ab, Cry1F + Cry1A.105 + Cry2Ab, and Cry1F + Cry1Ab + Vip3Aa20. Growth rate bioassays were performed to isolate non-recessive Bt resistance alleles. Seven individuals out of the 212 isofemale lines carried major non-recessive alleles conferring resistance to Cry1F. A pooled colony was created from the seven individuals. This colony was 151.21 times more resistant to Cry1F than a known-susceptible population and was also resistant to Cry1A.105, but was not resistant to Cry2Ab and Vip3Aa20. The results demonstrate that field populations of S. frugiperda collected from North Carolina are generally susceptible to Cry1F, but that some individuals carry resistant alleles. The data generated in this study can be used as baseline data for resistance monitoring.

The cost-effectiveness of Welcome to Medicare visual acuity screening and a possible alternative welcome to medicare eye evaluation among persons without diagnosed diabetes mellitus.

PubMed

Rein, David B; Wittenborn, John S; Zhang, Xinzhi; Hoerger, Thomas J; Zhang, Ping; Klein, Barbara Eden Kobrin; Lee, Kris E; Klein, Ronald; Saaddine, Jinan B

2012-05-01

To estimate the cost-effectiveness of visual acuity screening performed in primary care settings and of dilated eye evaluations performed by an eye care professional among new Medicare enrollees with no diagnosed eye disorders. Medicare currently reimburses visual acuity screening for new enrollees during their initial preventive primary care health check, but dilated eye evaluations may be a more cost-effective policy. Monte Carlo cost-effectiveness simulation model with a total of 50 000 simulated patients with demographic characteristics matched to persons 65 years of age in the US population. Compared with no screening policy, dilated eye evaluations increased quality-adjusted life-years(QALYs) by 0.008 (95% credible interval [CrI], 0.005-0.011) and increased costs by $94 (95% CrI, −$35 to$222). A visual acuity screening increased QALYs in less than 95% of the simulations (0.001 [95% CrI, −0.002 to 0.004) and increased total costs by $32 (95% CrI, −$97 to $159) per person. The incremental cost-effectiveness ratio of a visual acuity screening and an eye examination compared with no screening were $29 000 and$12 000 per QALY gained, respectively. At a willingness-to-pay value of $15 000 or more per QALY gained, a dilated eye evaluation was the policy option most likely to be cost-effective. The currently recommended visual acuity screening showed limited efficacy and cost-effectiveness compared with no screening. In contrast, anew policy of reimbursement for Welcome to Medicare dilated eye evaluations was highly cost-effective.

The Cost-effectiveness of Welcome to Medicare Visual Acuity Screening and a Possible Alternative Welcome to Medicare Eye Evaluation Among Persons Without Diagnosed Diabetes Mellitus

PubMed Central

Rein, David B.; Wittenborn, John S.; Zhang, Xinzhi; Hoerger, Thomas J.; Zhang, Ping; Klein, Barbara Eden Kobrin; Lee, Kris E.; Klein, Ronald; Saaddine, Jinan B.

2013-01-01

Objective To estimate the cost-effectiveness of visual acuity screening performed in primary care settings and of dilated eye evaluations performed by an eye care professional among new Medicare enrollees with no diagnosed eye disorders. Medicare currently reimburses visual acuity screening for new enrollees during their initial preventive primary care health check, but dilated eye evaluations may be a more cost-effective policy. Design Monte Carlo cost-effectiveness simulation model with a total of 50 000 simulated patients with demographic characteristics matched to persons 65 years of age in the US population. Results Compared with no screening policy, dilated eye evaluations increased quality-adjusted life-years (QALYs) by 0.008 (95% credible interval [CrI], 0.005–0.011) and increased costs by $94 (95% CrI, −$35 to $222). A visual acuity screening increased QALYs in less than 95% of the simulations (0.001 [95% CrI, −0.002 to 0.004) and increased total costs by $32 (95% CrI, −$97 to $159) per person. The incremental cost-effectiveness ratio of a visual acuity screening and an eye examination compared with no screening were $29 000 and $12 000 per QALY gained, respectively. At a willingness-to-pay value of $15 000 or more per QALY gained, a dilated eye evaluation was the policy option most likely to be cost-effective. Conclusions The currently recommended visual acuity screening showed limited efficacy and cost-effectiveness compared with no screening. In contrast, a new policy of reimbursement for Welcome to Medicare dilated eye evaluations was highly cost-effective. PMID:22232367

MBD5 haploinsufficiency is associated with sleep disturbance and disrupts circadian pathways common to Smith-Magenis and fragile X syndromes.

PubMed

Mullegama, Sureni V; Pugliesi, Loren; Burns, Brooke; Shah, Zalak; Tahir, Raiha; Gu, Yanghong; Nelson, David L; Elsea, Sarah H

2015-06-01

Individuals with autism spectrum disorders (ASD) who have an identifiable single-gene neurodevelopmental disorder (NDD), such as fragile X syndrome (FXS, FMR1), Smith-Magenis syndrome (SMS, RAI1), or 2q23.1 deletion syndrome (del 2q23.1, MBD5) share phenotypic features, including a high prevalence of sleep disturbance. We describe the circadian deficits in del 2q23.1 through caregiver surveys in which we identify several frequent sleep anomalies, including night/early awakenings, coughing/snoring loudly, and difficulty falling asleep. We couple these findings with studies on the molecular analysis of the circadian deficits associated with haploinsufficiency of MBD5 in which circadian gene mRNA levels of NR1D2, PER1, PER2, and PER3 were altered in del 2q23.1 lymphoblastoid cell lines (LCLs), signifying that haploinsufficiency of MBD5 can result in dysregulation of circadian rhythm gene expression. These findings were further supported by expression microarrays of MBD5 siRNA knockdown cells that showed significantly altered expression of additional circadian rhythm signaling pathway genes. Based on the common sleep phenotypes observed in del 2q23.1, SMS, and FXS patients, we explored the possibility that MBD5, RAI1, and FMR1 function in overlapping circadian rhythm pathways. Bioinformatic analysis identified conserved putative E boxes in MBD5 and RAI1, and expression levels of NR1D2 and CRY2 were significantly reduced in patient LCLs. Circadian and mTOR signaling pathways, both associated with sleep disturbance, were altered in both MBD5 and RAI1 knockdown microarray data, overlapping with findings associated with FMR1. These data support phenotypic and molecular overlaps across these syndromes that may be exploited to provide therapeutic intervention for multiple disorders.

Diurnal expression of clock genes in pineal gland and brain and plasma levels of melatonin and cortisol in Atlantic salmon parr and smolts.

PubMed

Huang, Tien-sheng; Ruoff, Peter; Fjelldal, Per G

2010-10-01

In Atlantic salmon, the preadaptation to a marine life, i.e., parr-smolt transformation, and melatonin production in the pineal gland are regulated by the photoperiod. However, the clock genes have never been studied in the pineal gland of this species. The aim of the present study was to describe the diurnal expression of clock genes (Per1-like, Cry2, and Clock) in the pineal gland and brain of Atlantic salmon parr and smolts in freshwater, as well as plasma levels of melatonin and cortisol. By employing an out-of-season smolt production model, the parr-smolt transformation was induced by subjecting triplicate groups of parr to 6 wks (wks 0 to 6) under a 12 h:12 h light-dark (LD) regime followed by 6 wks (wks 6 to 12) of continuous light (LL). The measured clock genes in both pineal gland and brain and the plasma levels of melatonin and cortisol showed significant daily variations in parr under LD in wk 6, whereas these rhythms were abolished in smolts under LL in wk 12. In parr, the pineal Per1-like and Cry2 expression peaked in the dark phase, whereas the pineal Clock expression was elevated during the light phase. Although this study presents novel findings on the clock gene system in the teleost pineal gland, the role of this system in the regulation of smoltification needs to be studied in more detail.

Cost-effectiveness analysis of N95 respirators and medical masks to protect healthcare workers in China from respiratory infections.

PubMed

Mukerji, Shohini; MacIntyre, C Raina; Seale, Holly; Wang, Quanyi; Yang, Peng; Wang, Xiaoli; Newall, Anthony T

2017-07-03

There are substantial differences between the costs of medical masks and N95 respirators. Cost-effectiveness analysis is required to assist decision-makers evaluating alternative healthcare worker (HCW) mask/respirator strategies. This study aims to compare the cost-effectiveness of N95 respirators and medical masks for protecting HCWs in Beijing, China. We developed a cost-effectiveness analysis model utilising efficacy and resource use data from two cluster randomised clinical trials assessing various mask/respirator strategies conducted in HCWs in Level 2 and 3 Beijing hospitals for the 2008-09 and 2009-10 influenza seasons. The main outcome measure was the incremental cost-effectiveness ratio (ICER) per clinical respiratory illness (CRI) case prevented. We used a societal perspective which included intervention costs, the healthcare costs of CRI in HCWs and absenteeism costs. The incremental cost to prevent a CRI case with continuous use of N95 respirators when compared to medical masks ranged from US $490-$1230 (approx. 3000-7600 RMB). One-way sensitivity analysis indicated that the CRI attack rate and intervention effectiveness had the greatest impact on cost-effectiveness. The determination of cost-effectiveness for mask/respirator strategies will depend on the willingness to pay to prevent a CRI case in a HCW, which will vary between countries. In the case of a highly pathogenic pandemic, respirator use in HCWs would likely be a cost-effective intervention.

Effects of long-term feeding of genetically modified corn (event MON810) on the performance of lactating dairy cows.

PubMed

Steinke, K; Guertler, P; Paul, V; Wiedemann, S; Ettle, T; Albrecht, C; Meyer, H H D; Spiekers, H; Schwarz, F J

2010-10-01

A long-term study over 25 months was conducted to evaluate the effects of genetically modified corn on performance of lactating dairy cows. Thirty-six dairy cows were assigned to two feeding groups and fed with diets based on whole-crop silage, kernels and whole-crop cobs from Bt-corn (Bt-MON810) or its isogenic not genetically modified counterpart (CON) as main components. The study included two consecutive lactations. There were no differences in the chemical composition and estimated net energy content of Bt-MON810 and CON corn components and diets. CON feed samples were negative for the presence of Cry1Ab protein, while in Bt-MON810 feed samples the Cry1Ab protein was detected. Cows fed Bt-MON810 corn had a daily Cry1Ab protein intake of 6.0 mg in the first lactation and 6.1 mg in the second lactation of the trial. Dry matter intake (DMI) was 18.8 and 20.7 kg/cow per day in the first and the second lactation of the trial, with no treatment differences. Similarly, milk yield (23.8 and 29.0 kg/cow per day in the first and the second lactation of the trial) was not affected by dietary treatment. There were no consistent effects of feeding MON810 or its isogenic CON on milk composition or body condition. Thus, the present long-term study demonstrated the compositional and nutritional equivalence of Bt-MON810 and its isogenic CON. © 2010 Blackwell Verlag GmbH.

National survey of Australian paediatricians' approach to infant crying.

PubMed

Rimer, Romi; Hiscock, Harriet

2014-03-01

Persistent crying in infancy (i.e. crying that lasts for more than 3 h a day for more than 3 days per week for at least 3 weeks) is widespread. Although there is no gold standard approach to its management, guidelines exist with common management principles. This study aims to document how Australian general paediatricians (i) assess and manage persistent crying compared with published guidelines; (ii) screen for and manage associated post-natal depression; and (iii) rate their training in this area. Online survey were administered to all 394 members of the Australian Paediatric Research Network in November 2011 to February 2012. Members are predominantly general paediatricians. A total of 168 paediatricians (45%) responded. The majority (n = 96 (69%)) take one session to assess infant crying and at least two sessions to manage it (n = 106 (79%)). Specific approaches are not always evidence based (e.g. use of antacids/simethicone by 8%) and do not follow available guidelines. Most paediatricians routinely asked about maternal (n = 120 (88%)) but not paternal (n = 51 (33%)) mental health. Paediatricians typically received training around this issue before rather than after gaining formal paediatric qualifications (61% vs. 37%, respectively) and rate their training as satisfactory (67%). Despite this, only 39% feel very confident in managing infant crying. The lack of a gold standard approach to managing persistent infant crying has likely contributed to a lack of uniform care among Australian general paediatricians. Given that most paediatricians do not feel very confident in dealing with this problem, there is a scope for further training supported by evidence-based guidelines. © 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Moderate versus light pressure massage therapy leads to greater weight gain in preterm infants.

PubMed

Field, Tiffany; Diego, Miguel A; Hernandez-Reif, Maria; Deeds, Osvelia; Figuereido, Barbara

2006-12-01

Sixty-eight preterm infants (M GA=30 weeks) were randomly assigned to a moderate or to a light pressure massage therapy group to receive 15 massages three times per day for 5 days. Behavior state, stress behaviors and heart rate were recorded for 15min before and during the first 15-min therapy session. Weight gain was recorded over the 5-day therapy period. The moderate versus light pressure massage group gained significantly more weight per day. During the behavior observations the moderate versus light pressure massage group showed significantly lower increases from the pre-session to the session recording on: (1) active sleep; (2) fussing; (3) crying; (4) movement; and (5) stress behavior (hiccupping). They also showed a smaller decrease in deep sleep, a greater decrease in heart rate and a greater increase in vagal tone. Thus, the moderate pressure massage therapy group appeared to be more relaxed and less aroused than the light pressure massage group which may have contributed to the greater weight gain of the moderate pressure massage therapy group.

PDF-modulated visual inputs and cryptochrome define diurnal behavior in Drosophila.

PubMed

Cusumano, Paola; Klarsfeld, André; Chélot, Elisabeth; Picot, Marie; Richier, Benjamin; Rouyer, François

2009-11-01

Morning and evening circadian oscillators control the bimodal activity of Drosophila in light-dark cycles. The lateral neurons evening oscillator (LN-EO) is important for promoting diurnal activity at dusk. We found that the LN-EO autonomously synchronized to light-dark cycles through either the cryptochrome (CRY) that it expressed or the visual system. In conditions in which CRY was not activated, flies depleted for pigment-dispersing factor (PDF) or its receptor lost the evening activity and displayed reversed PER oscillations in the LN-EO. Rescue experiments indicated that normal PER cycling and the presence of evening activity relied on PDF secretion from the large ventral lateral neurons and PDF receptor function in the LN-EO. The LN-EO thus integrates light inputs and PDF signaling to control Drosophila diurnal behavior, revealing a new clock-independent function for PDF.

Development of a Dynamic Time Sharing Scheduled Environment Final Report CRADA No. TC-824-94E

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jette, M.; Caliga, D.

Massively parallel computers, such as the Cray T3D, have historically supported resource sharing solely with space sharing. In that method, multiple problems are solved by executing them on distinct processors. This project developed a dynamic time- and space-sharing scheduler to achieve greater interactivity and throughput than could be achieved with space-sharing alone. CRI and LLNL worked together on the design, testing, and review aspects of this project. There were separate software deliverables. CFU implemented a general purpose scheduling system as per the design specifications. LLNL ported the local gang scheduler software to the LLNL Cray T3D. In this approach, processorsmore » are allocated simultaneously to aU components of a parallel program (in a “gang”). Program execution is preempted as needed to provide for interactivity. Programs are also reIocated to different processors as needed to efficiently pack the computer’s torus of processors. In phase one, CRI developed an interface specification after discussions with LLNL for systemlevel software supporting a time- and space-sharing environment on the LLNL T3D. The two parties also discussed interface specifications for external control tools (such as scheduling policy tools, system administration tools) and applications programs. CRI assumed responsibility for the writing and implementation of all the necessary system software in this phase. In phase two, CRI implemented job-rolling on the Cray T3D, a mechanism for preempting a program, saving its state to disk, and later restoring its state to memory for continued execution. LLNL ported its gang scheduler to the LLNL T3D utilizing the CRI interface implemented in phases one and two. During phase three, the functionality and effectiveness of the LLNL gang scheduler was assessed to provide input to CRI time- and space-sharing, efforts. CRI will utilize this information in the development of general schedulers suitable for other sites and future architectures.« less

Inheritance of Cry1F resistance, cross-resistance and frequency of resistant alleles in Spodoptera frugiperda (Lepidoptera: Noctuidae).

PubMed

Vélez, A M; Spencer, T A; Alves, A P; Moellenbeck, D; Meagher, R L; Chirakkal, H; Siegfried, B D

2013-12-01

Transgenic maize, Zea maize L., expressing the Cry1F protein from Bacillus thuringiensis has been registered for Spodoptera frugiperda (J. E. Smith) control since 2003. Unexpected damage to Cry1F maize was reported in 2006 in Puerto Rico and Cry1F resistance in S. frugiperda was documented. The inheritance of Cry1F resistance was characterized in a S. frugiperda resistant strain originating from Puerto Rico, which displayed >289-fold resistance to purified Cry1F. Concentration-response bioassays of reciprocal crosses of resistant and susceptible parental populations indicated that resistance is recessive and autosomal. Bioassays of the backcross of the F1 generation crossed with the resistant parental strain suggest that a single locus is responsible for resistance. In addition, cross-resistance to Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry2Aa and Vip3Aa was assessed in the Cry1F-resistant strain. There was no significant cross-resistance to Cry1Aa, Cry1Ba and Cry2Aa, although only limited effects were observed in the susceptible strain. Vip3Aa was highly effective against susceptible and resistant insects indicating no cross-resistance with Cry1F. In contrast, low levels of cross-resistance were observed for both Cry1Ab and Cry1Ac. Because the resistance is recessive and conferred by a single locus, an F1 screening assay was used to measure the frequency of Cry1F-resistant alleles from populations of Florida and Texas in 2010 and 2011. A total frequency of resistant alleles of 0.13 and 0.02 was found for Florida and Texas populations, respectively, indicating resistant alleles could be found in US populations, although there have been no reports of reduced efficacy of Cry1F-expressing plants.

Circadian gene variants and susceptibility to type 2 diabetes: a pilot study.

PubMed

Kelly, M Ann; Rees, Simon D; Hydrie, M Zafar I; Shera, A Samad; Bellary, Srikanth; O'Hare, J Paul; Kumar, Sudhesh; Taheri, Shahrad; Basit, Abdul; Barnett, Anthony H

2012-01-01

Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants. The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732) and without (N = 1780) type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium) and white European cohorts (DIAGRAM+) using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66-0.86], p = 3.18 × 10(-5)), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07-1.39], p = 0.003). Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01-1.08], p = 0.008 and OR = 0.95 [0.91-0.99], p = 0.015 respectively). None of the selected circadian gene variants was associated with type 2 diabetes with study-wide significance after meta-analysis. The nominal association observed with the CRY2 SNP, however, complements previous findings and confirms a role for this locus in disease susceptibility.

Genomics and relative expression analysis identifies key genes associated with high female to male flower ratio in Jatropha curcas L.

PubMed

Gangwar, Manali; Sood, Hemant; Chauhan, Rajinder Singh

2016-04-01

Jatropha curcas, has been projected as a major source of biodiesel due to high seed oil content (42 %). A major roadblock for commercialization of Jatropha-based biodiesel is low seed yield per inflorescence, which is affected by low female to male flower ratio (1:25-30). Molecular dissection of female flower development by analyzing genes involved in phase transitions and floral organ development is, therefore, crucial for increasing seed yield. Expression analysis of 42 genes implicated in floral organ development and sex determination was done at six floral developmental stages of a J. curcas genotype (IC561235) with inherently higher female to male flower ratio (1:8-10). Relative expression analysis of these genes was done on low ratio genotype. Genes TFL1, SUP, AP1, CRY2, CUC2, CKX1, TAA1 and PIN1 were associated with reproductive phase transition. Further, genes CUC2, TAA1, CKX1 and PIN1 were associated with female flowering while SUP and CRY2 in female flower transition. Relative expression of these genes with respect to low female flower ratio genotype showed up to ~7 folds increase in transcript abundance of SUP, TAA1, CRY2 and CKX1 genes in intermediate buds but not a significant increase (~1.25 folds) in female flowers, thereby suggesting that these genes possibly play a significant role in increased transition towards female flowering by promoting abortion of male flower primordia. The outcome of study has implications in feedstock improvement of J. curcas through functional validation and eventual utilization of key genes associated with female flowering.

The blue light-induced interaction of cryptochrome 1 with COP1 requires SPA proteins during Arabidopsis light signaling.

PubMed

Holtkotte, Xu; Ponnu, Jathish; Ahmad, Margaret; Hoecker, Ute

2017-10-01

Plants constantly adjust their growth, development and metabolism to the ambient light environment. Blue light is sensed by the Arabidopsis photoreceptors CRY1 and CRY2 which subsequently initiate light signal transduction by repressing the COP1/SPA E3 ubiquitin ligase. While the interaction between cryptochromes and SPA is blue light-dependent, it was proposed that CRY1 interacts with COP1 constitutively, i.e. also in darkness. Here, our in vivo co-immunoprecipitation experiments suggest that CRY1 and CRY2 form a complex with COP1 only after seedlings were exposed to blue light. No association between COP1 and CRY1 or CRY2 was observed in dark-grown seedlings. Thus, our results suggest that cryptochromes bind the COP1/SPA complex after photoactivation by blue light. In a spa quadruple mutant that is devoid of all four SPA proteins, CRY1 and COP1 did not interact in vivo, neither in dark-grown nor in blue light-grown seedlings. Hence, SPA proteins are required for the high-affinity interaction between CRY1 and COP1 in blue light. Yeast three-hybrid experiments also show that SPA1 enhances the CRY1-COP1 interaction. The coiled-coil domain of SPA1 which is responsible for COP1-binding was necessary to mediate a CRY1-SPA1 interaction in vivo, implying that-in turn-COP1 may be necessary for a CRY1-SPA1 complex formation. Hence, SPA1 and COP1 may act cooperatively in recognizing and binding photoactivated CRY1. In contrast, the blue light-induced association between CRY2 and COP1 was not dependent on SPA proteins in vivo. Similarly, ΔCC-SPA1 interacted with CRY2, though with a much lower affinity than wild-type SPA1. In total, our results demonstrate that CRY1 and CRY2 strongly differ in their blue light-induced interaction with the COP1/SPA complex.

Chemical composition of phosphorites of the Phosphoria Formation

USGS Publications Warehouse

Gulbrandsen, R.A.

1966-01-01

The chemical composition, both major and minor constituents, of 60 samples of phosphorite from the Phosphoria Formation was determined. Major constituents of the average phosphorite are, by weight per cent: SiO2, 11??9; Al2O3, 1??7; Fe2O3,1??1; MgO, 0??3; CaO, 44??0; Na2O, 0??6; K2O, 0??5; total H2O, 2??2; H2O-, 0??6; TiO2, 0??1; P2O5, 30??5; CO2, 2??2; SO3, 1??8; F, 3??1; organic matter, 2??1; and oil, 0??2. Uranium averages 0??009 per cent. The phosphate mineral is basically apatite, Ca5(PO4)3F, with small but significant and variable substitutions-Na, Sr, U and Th for Ca, and CO3 and SO4 for PO4. Rare metals not associated with apatite are associated principally with the organic-matter component of the rocks. This group includes As, Ag, Cd, Cr, Cu, Mo, Ni, Sb, Se, V and Zn. Chromium is the most abundant, having a modal abundance of 0??1 per cent and a maximum concentration of 0??3 per cent. The average phosphorite is composed of approximately 80 per cent apatite, 10 per cent quartz, 5 per cent muscovite-illite, 2 per cent organic matter, 1 per cent dolomite-calcite, 1 per cent iron oxide, and 1 per cent other components. It is texturally a medium-grained pellet phosphorite. ?? 1966.

Locally advanced squamous cell carcinoma of the head and neck: A systematic review and Bayesian network meta-analysis of the currently available treatment options.

PubMed

Iocca, Oreste; Farcomeni, Alessio; Di Rocco, Arianna; Di Maio, Pasquale; Golusinski, Paweł; Pardiñas López, Simón; Savo, Alfredo; Pellini, Raul; Spriano, Giuseppe

2018-05-01

There are still many unresolved questions in the management of locally advanced Head and Neck Cancer (HNC). Many chemotherapeutic drugs and radiotherapy fractionation schemes are available and not all have been evaluated in head-to-head clinical trials. This systematic review and Bayesian network meta-analysis aims to compare the available treatment strategies and chemotherapeutic options for locally advanced HNC. We performed a search on bibliography databases, trials registries and meetings proceedings for published and unpublished randomized trials from January 1st 2000 to December 1st 2017. Trials had to compare systemic interventions and radiotherapy (RT) approaches for locally advanced, non-metastatic HNC. Trials recruiting patients whose surgery was the first treatment option, sample size less than 20 per arm or that did not use randomization for treatment allocation were excluded from the analysis. Summary estimates on Overall survival (OS), Progression-free survival (PFS) and toxicity outcomes (grade 3-4 mucositis and neutropenia) were extracted from the included studies on a predefined database sheet. Bias was assessed through the Chocrane risk of bias assessment tool. We performed a set of pair-wise meta-analyses using a random effect model. We also performed a random effect network meta-analysis under a Bayesian framework. From the 57 included trials, including 15,723 patients, was possible to conduct analysis on 26 treatments for OS, 22 treatments for PFS and 10 treatments for toxicity. In terms of OS Concurrent chemoradiotherapy (CCRT) with cisplatin (HR 0.70, 95% CrI [credible interval] 0.62-0.78) and cetuximab on top of CCRT (HR 0.7, 95% CrI 0.5-0.97) are clearly superior to conventional RT alone. Induction chemotherapy (IC) with cisplatin and fluorouracil (HR 0.74, 95% CrI 0.52-0.95), IC with docetaxel, cisplatin, fluorouracil (HR 0.55, 95% CrI 0.54-0.89) and IC with paclitaxel, cisplatin, fluorouracil (HR 0.55, 95% CrI 0.34-0.89) before CCRT are all superior to conventional RT. CCRT with cisplatin is also superior to altered fractionation RT (HR 0.74, 95% CrI 0.64-0.84). Altered fractionation RT is not superior to conventional RT (HR 0.95, 95% CrI 0.85-1.06). Regarding PFS, CCRT with cisplatin (HR 0.72, 95% CrI 0.63-0.83), cisplatin and fluorouracil (HR 0.67, 95% CrI 0.5-0.88), carboplatin (HR 0.63, 95% CrI 0.46-0.87), carboplatin and fluorouracil (HR 0.75, 95% CrI 0.56-1), IC with cisplatin and fluorouracil (HR 0.59, 95% CrI 0.45-0.78), IC with docetaxel, cisplatin and fluorouracil (HR 0.53, 95% CrI 0.41-0.68) and IC with paclitaxel, cisplatin and fluorouracil (HR 0.59, 95% CrI 0.35-0.99) are superior to conventional RT and altered fractionation RT. IC with docetaxel, cisplatin and fluorouracil shows a significant superiority against CCRT with cisplatin (HR 0.73 95% CrI 0.58-0.92). Altered fractionation RT is not superior to conventional RT (HR 0.91, 95% CrI 0.81-1.02). Altered fractionation increases the risk of developing grade 3-4 mucositis compared to conventional RT (OR 3.74 95% 1.64-8.67) INTERPRETATION: CCRT with cisplatin remains the gold standard of treatment. Taxane based IC regimens may have a impact on locally advanced disease. Altered fractionation RT is inferior to CCRT and also does not seem to be meaningfully better than conventionally fractionated RT alone. Its role in locally advanced disease should be reevaluated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis.

PubMed

Mitra, Souvik; Florez, Ivan D; Tamayo, Maria E; Mbuagbaw, Lawrence; Vanniyasingam, Thuva; Veroniki, Areti Angeliki; Zea, Adriana M; Zhang, Yuan; Sadeghirad, Behnam; Thabane, Lehana

2018-03-27

Despite increasing emphasis on conservative management of patent ductus arteriosus (PDA) in preterm infants, different pharmacotherapeutic interventions are used to treat those developing a hemodynamically significant PDA. To estimate the relative likelihood of hemodynamically significant PDA closure with common pharmacotherapeutic interventions and to compare adverse event rates. The databases of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until August 15, 2015, and updated on December 31, 2017, along with conference proceedings up to December 2017. Randomized clinical trials that enrolled preterm infants with a gestational age younger than 37 weeks treated with intravenous or oral indomethacin, ibuprofen, or acetaminophen vs each other, placebo, or no treatment for a clinically or echocardiographically diagnosed hemodynamically significant PDA. Data were independently extracted in pairs by 6 reviewers and synthesized with Bayesian random-effects network meta-analyses. Primary outcome: hemodynamically significant PDA closure; secondary: included surgical closure, mortality, necrotizing enterocolitis, and intraventricular hemorrhage. In 68 randomized clinical trials of 4802 infants, 14 different variations of indomethacin, ibuprofen, or acetaminophen were used as treatment modalities. The overall PDA closure rate was 67.4% (2867 of 4256 infants). A high dose of oral ibuprofen was associated with a significantly higher odds of PDA closure vs a standard dose of intravenous ibuprofen (odds ratio [OR], 3.59; 95% credible interval [CrI], 1.64-8.17; absolute risk difference, 199 [95% CrI, 95-258] more per 1000 infants) and a standard dose of intravenous indomethacin (OR, 2.35 [95% CrI, 1.08-5.31]; absolute risk difference, 124 [95% CrI, 14-188] more per 1000 infants). Based on the ranking statistics, a high dose of oral ibuprofen ranked as the best pharmacotherapeutic option for PDA closure (mean surface under the cumulative ranking [SUCRA] curve, 0.89 [SD, 0.12]) and to prevent surgical PDA ligation (mean SUCRA, 0.98 [SD, 0.08]). There was no significant difference in the odds of mortality, necrotizing enterocolitis, or intraventricular hemorrhage with use of placebo or no treatment compared with any of the other treatment modalities. A high dose of oral ibuprofen was associated with a higher likelihood of hemodynamically significant PDA closure vs standard doses of intravenous ibuprofen or intravenous indomethacin; placebo or no treatment did not significantly change the likelihood of mortality, necrotizing enterocolitis, or intraventricular hemorrhage. PROSPERO Identifier: CRD42015015797.

Influence of calcareous soil on Cry3Bb1 expression and efficacy in the field.

PubMed

Wangila, David S; Valencia J, Arnubio; Wang, Haichuan; Siegfried, Blair D; Meinke, Lance J

2017-06-01

Greater than expected injury by western corn rootworm (WCR) (Diabrotica virgifera virgifera LeConte) to Cry3Bb1 expressing maize hybrids (Zea mays L.) has been reported in southwestern Nebraska. Affected areas of some fields are often associated with high pH calcareous soils where maize growth is poor and iron chlorosis is common. As part of a comprehensive study to understand potential causes of unexpected injury, experiments were conducted during 2013 and 2014 to ascertain whether the calcareous soil conditions and associated poor maize growth negatively affect the expression of Cry3Bb1. Quantitative determination of Cry3Bb1 protein expression levels in root tissues was carried out on plants at V5-V6 growth stage using the enzyme-linked immunosorbent assay. Cry3Bb1 and non-Bt near isoline maize hybrids were artificially infested with Cry3Bb1-susceptible WCR eggs to measure survival and efficacy of Cry3Bb1 maize in calcareous and non-calcareous soils. Results showed that there was not a significant difference in expression of Cry3Bb1 protein between plants from calcareous and non-calcareous soils (18.9-21.2 µg/g fresh weight). Western corn rootworm survival was about sevenfold greater from the non-Bt isoline than Cry3Bb1 maize indicating that Cry3Bb1 performed as expected when infested with a Cry3Bb1 susceptible rootworm population. When survival from calcareous and non-calcareous soils was compared, no significant differences were observed in each soil. A significant positive correlation between soil pH and expression of Cry3Bb1 protein in roots was detected from samples collected in 2014 but not in 2013. No such correlation was found between soil pH and survival of WCR. Results suggest that Cry3Bb1 expression levels were sufficient to provide adequate root protection against WCR regardless of soil environment, indicating that lowered Cry3Bb1 expression is not a contributing factor to the greater than expected WCR injury observed in some southwestern Nebraska maize fields.

Quantification of toxins in a Cry1Ac + CpTI cotton cultivar and its potential effects on the honey bee Apis mellifera L.

PubMed

Han, Peng; Niu, Chang-Ying; Lei, Chao-Liang; Cui, Jin-Jie; Desneux, Nicolas

2010-11-01

Transgenic Cry1Ac + CpTI cotton (CCRI41) is increasingly planted throughout China. However, negative effects of this cultivar on the honey bee Apis mellifera L., the most important pollinator for cultivated ecosystem, remained poorly investigated. The objective of our study was to evaluate the potential side effects of transgenic Cry1Ac + CpTI pollen from cotton on young adult honey bees A. mellifera L. Two points emphasized the significance of our study: (1) A higher expression level of insecticidal protein Cry1Ac in pollen tissues was detected (when compared with previous reports). In particular, Cry1Ac protein was detected at 300 ± 4.52 ng g(-1) [part per billion (ppb)] in pollen collected in July, (2) Effects on chronic mortality and feeding behaviour in honey bees were evaluated using a no-choice dietary feeding protocol with treated pollen, which guarantee the highest exposure level to bees potentially occurring in natural conditions (worst case scenario). Tests were also conducted using imidacloprid-treated pollen at a concentration of 48 ppb as positive control for sublethal effect on feeding behaviour. Our results suggested that Cry1Ac + CpTI pollen carried no lethal risk for honey bees. However, during a 7-day oral exposure to the various treatments (transgenic, imidacloprid-treated and control), honey bee feeding behaviour was disturbed and bees consumed significantly less CCRI41 cotton pollen than in the control group in which bees were exposed to conventional cotton pollen. It may indicate an antifeedant effect of CCRI41 pollen on honey bees and thus bees may be at risk because of large areas are planted with transgenic Bt cotton in China. This is the first report suggesting a potential sublethal effect of CCRI41 cotton pollen on honey bees. The implications of the results are discussed in terms of risk assessment for bees as well as for directions of future work involving risk assessment of CCRI41 cotton.

Effectiveness of Mentha piperita in the Treatment of Infantile Colic: A Crossover Study

PubMed Central

Alves, João Guilherme Bezerra; de Brito, Rita de Cássia Coelho Moraes; Cavalcanti, Telma Samila

2012-01-01

Background. Infantile colic is a distressing and common condition for which there is no proven standard treatment. Objective. To compare the efficacy of Mentha piperita with simethicone in treatment for infantile colic. Methods. A double-blind crossover study was performed with 30 infants attending IMIP, Recife, Brazil. They were randomized to use Mentha piperita or simethicone in the treatment of infantile colic during 7 days with each drug. Primary outcomes were mother_s opinion about responses to the treatment, number of daily episodes of colic, and time spent crying, measured by a chronometer. Mann-Whitney and chi-square tests were used to compare the results. This study was previously approved by the Ethical Committee in Research at IMIP. Results. At baseline daily episodes of infantile colic was 3.9 (±1.1) and the mean crying time per day was 192 minutes (±51.6). At the end of the study daily episodes of colic fell to 1.6 (±0.6) and the crying duration decreased to 111 (±28) minutes. All mothers reported decrease of frequency and duration of the episodes of infantile colic and there were no differences between responses to Mentha piperita and simethicone. Conclusions. These findings suggest that Mentha piperita may be used to help control infantile colic. However, these results must be repeated by others studies. PMID:22844342

Multiple assays indicate varying levels of cross resistance of Cry3Bb1-selected field populations of the western corn rootworm to mCry3A, eCry3.1Ab, and Cry34/35Ab1

USDA-ARS?s Scientific Manuscript database

Minnesota populations of the western corn rootworm (WCR) surviving Cry3Bb1-expressing corn in the field and WCR populations assumed to be susceptible to all Bt proteins were evaluated for susceptibility to Cry3Bb1, mCry3A, eCry3.1Ab, and Cry34/35Ab1 in diet assays and three different plant-based ass...

Circadian rhythmicity and light sensitivity of the zebrafish brain.

PubMed

Moore, Helen A; Whitmore, David

2014-01-01

Traditionally, circadian clocks have been thought of as a neurobiological phenomenon. This view changed somewhat over recent years with the discovery of peripheral tissue circadian oscillators. In mammals, however, the suprachiasmatic nucleus (SCN) in the hypothalamus still retains the critical role of a central synchronizer of biological timing. Zebrafish, in contrast, have always reflected a more highly decentralized level of clock organization, as individual cells and tissues contain directly light responsive circadian pacemakers. As a consequence, clock function in the zebrafish brain has remained largely unexplored, and the precise organization of rhythmic and light-sensitive neurons within the brain is unknown. To address this issue, we used the period3 (per3)-luciferase transgenic zebrafish to confirm that multiple brain regions contain endogenous circadian oscillators that are directly light responsive. In addition, in situ hybridization revealed localised neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as numerous hypothalamic nuclei, the periventricular grey zone (PGZ) of the optic tectum, and granular cells of the rhombencephalon. To further investigate the light sensitive properties of neurons, expression of c-fos, a marker for neuronal activity, was examined. c-fos mRNA was upregulated in response to changing light conditions in different nuclei within the zebrafish brain. Furthermore, under constant dark (DD) conditions, c-fos shows a significant circadian oscillation. Taken together, these results show that there are numerous areas of the zebrafish central nervous system, which contain deep brain photoreceptors and directly light-entrainable circadian pacemakers. However, there are also multiple brain nuclei, which possess neither, demonstrating a degree of pacemaker complexity that was not previously appreciated.

Circadian Rhythmicity and Light Sensitivity of the Zebrafish Brain

PubMed Central

Moore, Helen A.; Whitmore, David

2014-01-01

Traditionally, circadian clocks have been thought of as a neurobiological phenomenon. This view changed somewhat over recent years with the discovery of peripheral tissue circadian oscillators. In mammals, however, the suprachiasmatic nucleus (SCN) in the hypothalamus still retains the critical role of a central synchronizer of biological timing. Zebrafish, in contrast, have always reflected a more highly decentralized level of clock organization, as individual cells and tissues contain directly light responsive circadian pacemakers. As a consequence, clock function in the zebrafish brain has remained largely unexplored, and the precise organization of rhythmic and light-sensitive neurons within the brain is unknown. To address this issue, we used the period3 (per3)-luciferase transgenic zebrafish to confirm that multiple brain regions contain endogenous circadian oscillators that are directly light responsive. In addition, in situ hybridization revealed localised neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as numerous hypothalamic nuclei, the periventricular grey zone (PGZ) of the optic tectum, and granular cells of the rhombencephalon. To further investigate the light sensitive properties of neurons, expression of c-fos, a marker for neuronal activity, was examined. c-fos mRNA was upregulated in response to changing light conditions in different nuclei within the zebrafish brain. Furthermore, under constant dark (DD) conditions, c-fos shows a significant circadian oscillation. Taken together, these results show that there are numerous areas of the zebrafish central nervous system, which contain deep brain photoreceptors and directly light-entrainable circadian pacemakers. However, there are also multiple brain nuclei, which possess neither, demonstrating a degree of pacemaker complexity that was not previously appreciated. PMID:24465943

Characteristics of non-fatal abusive head trauma among children in the USA, 2003--2008: application of the CDC operational case definition to national hospital inpatient data.

PubMed

Parks, Sharyn; Sugerman, David; Xu, Likang; Coronado, Victor

2012-12-01

An International Classification of Diseases code-based case definition for non-fatal abusive head trauma (AHT) in children <5 years of age was developed in March 2008 by an expert panel convened at the Centers for Disease Control and Prevention (CDC). This study presents an application of the CDC recommended operational case definition of AHT to US hospital inpatient data to characterise the AHT hospitalisation rate for children <5 years of age. Nationwide Inpatient Sample (NIS) data from the Healthcare Cost and Utilisation Project from 2003 to 2008 were examined. Inspection of the NIS data resulted in the identification of an estimated 10 555 non-fatal AHT hospitalisations with 9595 classified as definite/presumptive AHT and 960 classified as probable AHT. The non-fatal AHT rate was highest among children aged <1 year (32.3 per 100 000) with a peak in hospitalisations between 1 and 3 months of age. Non-fatal AHT hospitalisation rates for children <2 years of age were higher for boys (21.9 per 100 000) than girls (15.3 per 100 000). The non-fatal AHT hospitalisation rate showed little variation across seasons. To reduce the burden of AHT in the USA, a preventable public health problem, concerted prevention efforts targeting populations at risk should be implemented. This report demonstrates a model procedure for using the new CDC definition for public health surveillance and research purposes. Such findings can be used to inform parents and providers about AHT (eg, dangers of shaking, strategies for managing infant crying) as well as to monitor better the impact of prevention strategies over time.

Characteristics of non-fatal abusive head trauma among children in the USA, 2003–2008: application of the CDC operational case definition to national hospital inpatient data

PubMed Central

Parks, Sharyn; Sugerman, David; Xu, Likang; Coronado, Victor

2016-01-01

Objective An International Classification of Diseases code-based case definition for non-fatal abusive head trauma (AHT) in children <5 years of age was developed in March 2008 by an expert panel convened at the Centers for Disease Control and Prevention (CDC). This study presents an application of the CDC recommended operational case definition of AHT to US hospital inpatient data to characterise the AHT hospitalisation rate for children <5 years of age. Methods Nationwide Inpatient Sample (NIS) data from the Healthcare Cost and Utilisation Project from 2003 to 2008 were examined. Results Inspection of the NIS data resulted in the identification of an estimated 10 555 non-fatal AHT hospitalisations with 9595 classified as definite/presumptive AHT and 960 classified as probable AHT. The non-fatal AHT rate was highest among children aged <1 year (32.3 per 100 000) with a peak in hospitalisations between 1 and 3 months of age. Non-fatal AHT hospitalisation rates for children <2 years of age were higher for boys (21.9 per 100 000) than girls (15.3 per 100 000). The non-fatal AHT hospitalisation rate showed little variation across seasons. Conclusions To reduce the burden of AHT in the USA, a preventable public health problem, concerted prevention efforts targeting populations at risk should be implemented. This report demonstrates a model procedure for using the new CDC definition for public health surveillance and research purposes. Such findings can be used to inform parents and providers about AHT (eg, dangers of shaking, strategies for managing infant crying) as well as to monitor better the impact of prevention strategies over time. PMID:22328632

Characterization of Phlebotomus papatasi peritrophins, and the role of PpPer1 in Leishmania major survival in its natural vector.

PubMed

Coutinho-Abreu, Iliano V; Sharma, Narinder K; Robles-Murguia, Maricela; Ramalho-Ortigao, Marcelo

2013-01-01

The peritrophic matrix (PM) plays a key role in compartmentalization of the blood meal and as barrier to pathogens in many disease vectors. To establish an infection in sand flies, Leishmania must escape from the endoperitrophic space to prevent excretion with remnants of the blood meal digestion. In spite of the role played regarding Leishmania survival, little is known about sand fly PM molecular components and structural organization. We characterized three peritrophins (PpPer1, PpPer2, and PpPer3) from Phlebotomus papatasi. PpPer1 and PpPer2 display, respectively, four and one chitin-binding domains (CBDs). PpPer3 on the other hand has two CBDs, one mucin-like domain, and a putative domain with hallmarks of a CBD, but with changes in key amino acids. Temporal and spatial expression analyses show that PpPer1 is expressed specifically in the female midgut after blood feeding. PpPer2 and PpPer3 mRNAs were constitutively expressed in midgut and hindgut, with PpPer3 also being expressed in Malpighian tubules. PpPer2 was the only gene expressed in developmental stages. Interestingly, PpPer1 and PpPer3 expression are regulated by Le. major infection. Recombinant PpPer1, PpPer2 and PpPer3 were obtained and shown to display similar biochemical profiles as the native; we also show that PpPer1 and PpPer2 are able to bind chitin. Knockdown of PpPer1 led to a 44% reduction in protein, which in spite of producing an effect on the percentage of infected sand flies, resulted in a 39% increase of parasite load at 48 h. Our data suggest that PpPer1 is a component for the P. papatasi PM and likely involved in the PM role as barrier against Le. major infection.

Transgenic pigeonpea events expressing Cry1Ac and Cry2Aa exhibit resistance to Helicoverpa armigera.

PubMed

Ghosh, Gourab; Ganguly, Shreeparna; Purohit, Arnab; Chaudhuri, Rituparna Kundu; Das, Sampa; Chakraborti, Dipankar

2017-07-01

Independent transgenic pigeonpea events were developed using two cry genes. Transgenic Cry2Aa-pigeonpea was established for the first time. Selected transgenic events demonstrated 100% mortality of Helicoverpa armigera in successive generations. Lepidopteran insect Helicoverpa armigera is the major yield constraint of food legume pigeonpea. The present study was aimed to develop H. armigera-resistant transgenic pigeonpea, selected on the basis of transgene expression and phenotyping. Agrobacterium tumefaciens-mediated transformation of embryonic axis explants of pigeonpea cv UPAS 120 was performed using two separate binary vectors carrying synthetic Bacillus thuringiensis insecticidal crystal protein genes, cry1Ac and cry2Aa. T 0 transformants were selected on the basis of PCR and protein expression profile. T 1 events were exclusively selected on the basis of expression and monogenic character for cry, validated through Western and Southern blot analyses, respectively. Independently transformed 12 Cry1Ac and 11 Cry2Aa single-copy events were developed. The level of Cry-protein expression in T 1 transgenic events was 0.140-0.175% of total soluble protein. Expressed Cry1Ac and Cry2Aa proteins in transgenic pigeonpea exhibited significant weight loss of second-fourth instar larvae of H. armigera and ultimately 80-100% mortality in detached leaf bioassay. Selected Cry-transgenic pigeonpea events, established at T 2 generation, inherited insect-resistant phenotype. Immunohistofluorescence localization in T 3 plants demonstrated constitutive accumulation of Cry1Ac and Cry2Aa in leaf tissues of respective transgenic events. This study is the first report of transgenic pigeonpea development, where stable integration, effective expression and biological activity of two Cry proteins were demonstrated in subsequent three generations (T 0 , T 1, and T 2 ). These studies will contribute to biotechnological breeding programmes of pigeonpea for its genetic improvement.

A novel cry2Ab gene from the indigenous isolate Bacillus thuringiensis subsp. kurstaki.

PubMed

Sevim, Ali; Eryüzlü, Emine; Demirbağ, Zihni; Demir, Ismail

2012-01-01

A novel cry2Ab gene was cloned and sequenced from the indigenous isolate of Bacillus thuringiensis subsp. kurstaki. This gene was designated as cry2Ab25 and its sequence revealed an open reading frame of 1,902 bp encoding a 633 aa protein with calculated molecular mass of 70 kDa and pI value of 8.98. The amino acid sequence of the Cry2Ab25 protein was compared with previously known Cry2Ab toxins, and the phylogenetic relationships among them were determined. The deduced amino acid sequence of the Cry2Ab25 protein showed 99% homology to the known Cry2Ab proteins, except for Cry2Ab10 and Cry2Ab12 with 97% homology, and a variation in one amino acid residue in comparison with all known Cry2Ab proteins. The cry2Ab25 gene was expressed in Escherichia coli BL21(DE3) cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that the Cry2Ab25 protein is about 70 kDa. The toxin expressed in BL21(DE3) exhibited high toxicity against Malacosoma neustria and Rhagoletis cerasi with 73% and 75% mortality after 5 days of treatment, respectively.

Activity of Bacillus thuringiensis Cry1Ie2, Cry2Ac7, and Cry7Ab3 proteins against Anticarsia gemmatalis, Chrysodeixis includens and Ceratoma trifurcata

USDA-ARS?s Scientific Manuscript database

Transgenic soybeans producing the Cry1Ac insecticidal protein from the bacterium Bacillus thuringiensis (or “Bt”) are currently used to control larvae of the velvetbean caterpillar (Anticarsia gemmatalis Hübner) and the soybean looper [Chrysodeixis includens (Walker)]. The main threat to the sustain...

Field Trial Performance of Herculex XTRA (Cry34Ab1/Cry35Ab1) and SmartStax (Cry34Ab1/Cry35Ab1 + Cry3Bb1) Hybrids and Soil Insecticides Against Western and Northern Corn Rootworms (Coleoptera: Chrysomelidae).

PubMed

Johnson, K D; Campbell, L A; Lepping, M D; Rule, D M

2017-06-01

Western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), and northern corn rootworm, Diabrotica barberi Smith and Lawrence (Coleoptera: Chrysomelidae), are important insect pests in corn, Zea mays L. For more than a decade, growers have been using transgenic plants expressing proteins from the bacterium Bacillus thuringiensis (Bt) to protect corn roots from feeding. In 2011, western corn rootworm populations were reported to have developed resistance to Bt hybrids expressing Cry3Bb1 and later found to be cross-resistant to hybrids expressing mCry3A and eCry3.1Ab. The identification of resistance to Cry3 (Cry3Bb1, mCry3A, and eCry3.1Ab) hybrids led to concerns about durability and efficacy of products with single traits and of products containing a pyramid of a Cry3 protein and the binary Bt proteins Cry34Ab1 and Cry35Ab1. From 2012 to 2014, 43 field trials were conducted across the central United States to estimate root protection provided by plants expressing Cry34Ab1/Cry35Ab1 alone (Herculex RW) or pyramided with Cry3Bb1 (SmartStax). These technologies were evaluated with and without soil-applied insecticides to determine if additional management measures provided benefit where Cry3 performance was reduced. Trials were categorized for analysis based on rootworm damage levels on Cry3-expressing hybrids and rootworm feeding pressure within each trial. Across scenarios, Cry34Ab1/Cry35Ab1 hybrids provided excellent root protection. Pyramided traits provided greater root and yield protection than non-Bt plus a soil-applied insecticide, and only in trials where larval feeding pressure exceeded two nodes of damage did Cry34Ab1/Cry35Ab1 single-trait hybrids and pyramided hybrids show greater root protection from the addition of soil-applied insecticides. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lactobacillus reuteri (American Type Culture Collection Strain 55730) versus simethicone in the treatment of infantile colic: a prospective randomized study.

PubMed

Savino, Francesco; Pelle, Emanuela; Palumeri, Elisabetta; Oggero, Roberto; Miniero, Roberto

2007-01-01

The goal was to test the hypothesis that oral administration of Lactobacillus reuteri in a prospective randomized study would improve symptoms of infantile colic. Ninety breastfed colicky infants were assigned randomly to receive either the probiotic L. reuteri (10(8) live bacteria per day) or simethicone (60 mg/day) each day for 28 days. The mothers avoided cow's milk in their diet. Parents monitored daily crying times and adverse effects by using a questionnaire. Eighty-three infants completed the trial: 41 in the probiotic group and 42 in the simethicone group. The infants were similar regarding gestational age, birth weight, gender, and crying time at baseline. Daily median crying times in the probiotic and simethicone groups were 159 minutes/day and 177 minutes/day, respectively, on the seventh day and 51 minutes/day and 145 minutes/day on the 28th day. On day 28, 39 patients (95%) were responders in the probiotic group and 3 patients (7%) were responders in the simethicone group. No adverse effects were reported. In our cohort, L. reuteri improved colicky symptoms in breastfed infants within 1 week of treatment, compared with simethicone, which suggests that probiotics may have a role in the treatment of infantile colic.

21 CFR 556.540 - Progesterone.

Code of Federal Regulations, 2010 CFR

2010-04-01

... animals: (a) In uncooked edible tissues of steers and calves: (1) 3 parts per billion for muscle. (2) 12 parts per billion for fat. (3) 9 parts per billion for kidney. (4) 6 parts per billion for liver. (b) In uncooked edible tissues of lambs: (1) 3 parts per billion for muscle. (2) 15 parts per billion for fat...

Development of Monoclonal Antibodies Recognizing Linear Epitope: Illustration by Three Bacillus thuringiensis Crystal Proteins of Genetically Modified Cotton, Maize, and Tobacco.

PubMed

Cao, Zhen; Zhang, Wei; Ning, Xiangxue; Wang, Baomin; Liu, Yunjun; Li, Qing X

2017-11-22

Bacillus thuringiensis Cry1Ac, Cry1Ia1, and Cry1Ie are δ-endotoxin insecticidal proteins widely implemented in genetically modified organisms (GMO), such as cotton, maize, and potato. Western blot assay integrates electrophoresis separation power and antibody high specificity for monitoring specific exogenous proteins expressed in GMO. Procedures for evoking monoclonal antibody (mAb) for Western blot were poorly documented. In the present study, Cry1Ac partially denatured at 100 °C for 5 min was used as an immunogen to develop mAbs selectively recognizing a linear epitope of Cry1Ac for Western blot. mAb 5E9C6 and 3E6E2 selected with sandwich ELISA strongly recognized the heat semidenatured Cry1Ac. Particularly, 3E6E2 recognized both E. coli and cotton seed expressed Cry1Ac in Western blot. Such strategy of using partially denatured proteins as immunogens and using sandwich ELISA for mAb screening was also successfully demonstrated with production of mAbs against Cry1Ie for Western blot assay in maize.

40 CFR Table 1 to Subpart Ddddd of... - Emission Limits for New or Reconstructed Boilers and Process Heaters

Code of Federal Regulations, 2013 CFR

2013-07-01

.... HCl 2.2E-02 lb per MMBtu of heat input 2.5E-02 lb per MMBtu of steam output or 0.28 lb per MWh For... basis corrected to 3 percent oxygen, 30-day rolling average) 1.2E-01 lb per MMBtu of steam output or 1.5... per MMBtu of steam output or 4.2E-01 lb per MWh; or (2.7E-05 lb per MMBtu of steam output or 3.7E-04...

Susceptibility of northern corn rootworm Diabrotica barberi (Coleoptera: Chrysomelidae) to mCry3A and eCry3.1Ab Bacillus thuringiensis proteins.

PubMed

Oyediran, Isaac O; Matthews, Phillip; Palekar, Narendra; French, Wade; Conville, Jared; Burd, Tony

2016-12-01

The susceptibility of the northern corn rootworm Diabrotica barberi (Smith & Lawrence) to mCry3A and eCry3.1Ab proteins derived from Bacillus thuringiensis (Bt) was determined using a diet bioassay. Northern corn rootworm neonates were exposed to different concentrations of mCry3A and eCry3.1Ab, incorporated into artificial diet. Larval mortality was evaluated after 7 d. The mCry3A and eCry3.1Ab proteins were found to be toxic to the northern corn rootworm larvae. The LC 50 and LC 99 values for mCry3A were 5.13 and 2482.31 μg/mL, respectively. For eCry3.1Ab, the LC 50 and LC 99 values were 0.49 and 213.01 μg/mL. Based on the estimated lethal concentrations, eCry3.1Ab protein was more efficacious to northern corn rootworm larvae than mCry3A. These lethal concentration values will be used as diagnostic doses for routine annual monitoring for change in susceptibility of field collected northern corn rootworm to mCry3A, and eCry3.1Ab toxins. © 2015 Institute of Zoology, Chinese Academy of Sciences.

Familial factors responsible for persistent crying-induced asthma: a case report.

PubMed

Weinstein, A G

1987-10-01

Crying behavior of the asthmatic child may induce wheezing symptoms. This may be a clinical problem for families with asthmatic children who exhibit frequent and persistent crying behavior. This case report identifies behaviors by the child and parents that may be responsible for continual crying. Child factors include (1) "spoiled" personality, (2) poor self-image, (3) biologic sensitivity to foods, medication, and environmental allergens producing irritability. Parental factors include poor disciplinary practices secondary to (1) disrupted home life, (2) guilt, and (3) overprotective behavior. Identification of these factors may be helpful in establishing clinical management strategies to reduce crying-induced asthma.

Analysis of cross-resistance to Vip3 proteins in eight insect colonies, from four insect species, selected for resistance to Bacillus thuringiensis insecticidal proteins.

PubMed

Gomis-Cebolla, Joaquín; Wang, Yuequin; Quan, Yudong; He, Kanglai; Walsh, Tom; James, Bill; Downes, Sharon; Kain, Wendy; Wang, Ping; Leonard, Kathy; Morgan, Tom; Oppert, Brenda; Ferré, Juan

2018-05-16

Bacillus thuringiensis Vip3 proteins are synthesized and secreted during the vegetative growth phase. They are activated by gut proteases, recognize and bind to midgut receptors, form pores and lyse cells. We tested the susceptibility to Vip3Aa and Vip3Ca of Cry1A-, Cry2A-, Dipel- and Vip3-resistant insect colonies from different species to determine whether resistance to other insecticidal proteins confers cross-resistance to Vip3 proteins. As expected, the colonies resistant to Cry1A proteins, Dipel (Helicoverpa armigera, Trichoplusia ni, Ostrinia furnacalis and Plodia interpunctella) or Cry2Ab (H. armigera and T. ni) were not cross-resistant to Vip3 proteins. In contrast, H. armigera colonies resistant to Vip3Aa or Vip3Aa/Cry2Ab showed cross-resistance to the Vip3Ca protein. Moreover, the Vip3Ca protein was highly toxic to O. furnacalis (LC 50 not significantly different from that of Cry1Ab), whereas the Vip3Aa protein only showed moderate growth inhibition at the highest concentration tested (100 µg/g of diet). These results extend the cross-resistance studies between Vip3 and Cry proteins, show for the first time cross-resistance between proteins within the Vip3 subfamily, and points to O. furnacalis as a target for the Vip3Ca protein. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of a diet containing genetically modified rice expressing the Cry1Ab/1Ac protein (Bacillus thuringiensis toxin) on broiler chickens.

PubMed

Li, Zeyang; Gao, Yang; Zhang, Minhong; Feng, Jinghai; Xiong, Yandan

2015-01-01

The aim of this study was to evaluate the effect of feeding Bacillus thuringiensis (Bt) rice expressing the Cry1Ab/1Ac protein on broiler chicken. The genetically modified (GM) Bt rice was compared with the corresponding non-GM rice regarding performance of feeding groups, their health status, relative organ weights, biochemical serum parameters and occurrence of Cry1Ab/1Ac gene fragments. One hundred and eighty day-old Arbor Acres female broilers with the same health condition were randomly allocated to the two treatments (6 replicate cages with 15 broilers in each cage per treatment). They received diets containing GM rice (GM group) or its parental non-GM rice (non-GM group) at 52-57% of the air-dried diet for 42 days. The results show that the transgenic rice had a similar nutrient composition as the non-GM rice and had no adverse effects on chicken growth, biochemical serum parameters and necropsy during the 42-day feeding period. In birds fed the GM rice, no transgenic gene fragments were detected in the samples of blood, liver, kidneys, spleen, jejunum, ileum, duodenum and muscle tissue. In conclusion, the results suggest that Bt rice expressing Cry1Ab/1Ac protein has no adverse effects on broiler chicken. Therefore, it can be considered as safe and used as feed source for broiler chicken.

Shared Midgut Binding Sites for Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac and Cry1Fa Proteins from Bacillus thuringiensis in Two Important Corn Pests, Ostrinia nubilalis and Spodoptera frugiperda

PubMed Central

Hernández-Rodríguez, Carmen Sara; Hernández-Martínez, Patricia; Van Rie, Jeroen; Escriche, Baltasar; Ferré, Juan

2013-01-01

First generation of insect-protected transgenic corn (Bt-corn) was based on the expression of Cry1Ab or Cry1Fa proteins. Currently, the trend is the combination of two or more genes expressing proteins that bind to different targets. In addition to broadening the spectrum of action, this strategy helps to delay the evolution of resistance in exposed insect populations. One of such examples is the combination of Cry1A.105 with Cry1Fa and Cry2Ab to control O. nubilalis and S. frugiperda. Cry1A.105 is a chimeric protein with domains I and II and the C-terminal half of the protein from Cry1Ac, and domain III almost identical to Cry1Fa. The aim of the present study was to determine whether the chimeric Cry1A.105 has shared binding sites either with Cry1A proteins, with Cry1Fa, or with both, in O. nubilalis and in S. frugiperda. Brush-border membrane vesicles (BBMV) from last instar larval midguts were used in competition binding assays with 125I-labeled Cry1A.105, Cry1Ab, and Cry1Fa, and unlabeled Cry1A.105, Cry1Aa, Cry1Ab, Cry1Ac, Cry1Fa, Cry2Ab and Cry2Ae. The results showed that Cry1A.105, Cry1Ab, Cry1Ac and Cry1Fa competed with high affinity for the same binding sites in both insect species. However, Cry2Ab and Cry2Ae did not compete for the binding sites of Cry1 proteins. Therefore, according to our results, the development of cross-resistance among Cry1Ab/Ac, Cry1A.105, and Cry1Fa proteins is possible in these two insect species if the alteration of shared binding sites occurs. Conversely, cross-resistance between these proteins and Cry2A proteins is very unlikely in such case. PMID:23861865

Bacillus thuringiensis delta-endotoxin binding to brush border membrane vesicles of rice stem borers.

PubMed

Alcantara, Edwin P; Aguda, Remedios M; Curtiss, April; Dean, Donald H; Cohen, Michael B

2004-04-01

The receptor binding step in the molecular mode of action of five delta-endotoxins (Cry1Ab, Cry1Ac, Cry1C, Cry2A, and Cry9C) from Bacillus thuringiensis was examined to find toxins with different receptor sites in the midgut of the striped stem borer (SSB) Chilo suppressalis (Walker) and yellow stem borer (YSB) Scirpophaga incertulas (Walker) (Lepidoptera: Pyralidae). Homologous competition assays were used to estimate binding affinities (K(com)) of (125)I-labelled toxins to brush border membrane vesicles (BBMV). The SSB BBMV affinities in decreasing order was: Cry1Ab = Cry1Ac > Cry9C > Cry2A > Cry1C. In YSB, the order of decreasing affinities was: Cry1Ac > Cry1Ab > Cry9C = Cry2A > Cry1C. The number of binding sites (B(max)) estimated by homologous competition binding among the Cry toxins did not affect toxin binding affinity (K(com)) to both insect midgut BBMVs. Results of the heterologous competition binding assays suggest that Cry1Ab and Cry1Ac compete for the same binding sites in SSB and YSB. Other toxins bind with weak (Cry1C, Cry2A) or no affinity (Cry9C) to Cry1Ab and Cry1Ac binding sites in both species. Cry2A had the lowest toxicity to 10-day-old SSB and Cry1Ab and Cry1Ac were the most toxic. Taken together, the results of this study show that Cry1Ab or Cry1Ac could be combined with either Cry1C, Cry2A, or Cry9C for more durable resistance in transgenic rice. Cry1Ab should not be used together with Cry1Ac because a mutation in one receptor site could diminish binding of both toxins. Copyright 2004 Wiley-Liss, Inc.

Development of monoclonal antibody-based sensitive ELISA for the determination of Cry1Ie protein in transgenic plant.

PubMed

Zhang, Yuwen; Zhang, Wei; Liu, Yan; Wang, Jianhua; Wang, Guoying; Liu, Yunjun

2016-11-01

Cry1Ie is a kind of Bacillus thuringiensis (Bt) toxin protein which has a different action model than the Cry1Ab and Cry1Ac protein. The transgenic maize expressing Cry1Ie might be commercially used in the near future and it is urgent to develop a method to detect Cry1Ie protein in transgenic plants and their products. To develop an ELISA method, Cry1Ie protein was expressed in Escherichia coli strain Transetta DE3, purified with the Ni-NTA spin columns, and then validated by sequencing. Bioassay results showed that the purified Cry1Ie protein was highly toxic to the Asian corn borer. The polyclonal antibody (pAb) and the specific monoclonal antibody (mAb) 1G 4 2D 6 were generated from rabbit and mice which were immunized with Cry1Ie protein, respectively. Western blotting of crude Cry1Ie protein extracts was established by employing mAb 1G 4 2D 6 , whereas the mAb 1G 4 2D 6 negligibly recognized other Bt proteins. Sandwich ELISA against Cry1Ie protein was established by coating with pAb and detecting with mAb 1G 4 2D 6 . The limit of detection (LOD), the limit of quantification (LOQ), and the quantification range of the assay in different matrices of maize plant were determined as 0.27-0.51, 0.29-0.78, and 0.45-15.71 ng/mL, respectively. Recoveries of Cry1Ie protein spiked in different maize tissues ranged from 75.1 to 99.5 %. The established sandwich ELISA was verified using transgenic maize overexpressing Cry1Ie. The results in this study suggested that the established ELISA method is effective for detecting Cry1Ie protein in transgenic plants.

Trojan Horse Strategy for Non-invasive Interference of Clock Gene in the Oyster Crassostrea gigas.

PubMed

Payton, Laura; Perrigault, Mickael; Bourdineaud, Jean-Paul; Marcel, Anjara; Massabuau, Jean-Charles; Tran, Damien

2017-08-01

RNA interference is a powerful method to inhibit specific gene expression. Recently, silencing target genes by feeding has been successfully carried out in nematodes, insects, and small aquatic organisms. A non-invasive feeding-based RNA interference is reported here for the first time in a mollusk bivalve, the pacific oyster Crassostrea gigas. In this Trojan horse strategy, the unicellular alga Heterocapsa triquetra is the food supply used as a vector to feed oysters with Escherichia coli strain HT115 engineered to express the double-stranded RNA targeting gene. To test the efficacy of the method, the Clock gene, a central gene of the circadian clock, was targeted for knockout. Results demonstrated specific and systemic efficiency of the Trojan horse strategy in reducing Clock mRNA abundance. Consequences of Clock disruption were observed in Clock-related genes (Bmal, Tim1, Per, Cry1, Cry2, Rev.-erb, and Ror) and triploid oysters were more sensitive than diploid to the interference. This non-invasive approach shows an involvement of the circadian clock in oyster bioaccumulation of toxins produced by the harmful alga Alexandrium minutum.

Efficacy of Genetically Modified Bt Toxins Alone and in Combinations Against Pink Bollworm Resistant to Cry1Ac and Cry2Ab

PubMed Central

Tabashnik, Bruce E.; Fabrick, Jeffrey A.; Unnithan, Gopalan C.; Yelich, Alex J.; Masson, Luke; Zhang, Jie; Bravo, Alejandra; Soberón, Mario

2013-01-01

Evolution of resistance in pests threatens the long-term efficacy of insecticidal proteins from Bacillus thuringiensis (Bt) used in sprays and transgenic crops. Previous work showed that genetically modified Bt toxins Cry1AbMod and Cry1AcMod effectively countered resistance to native Bt toxins Cry1Ab and Cry1Ac in some pests, including pink bollworm (Pectinophora gossypiella). Here we report that Cry1AbMod and Cry1AcMod were also effective against a laboratory-selected strain of pink bollworm resistant to Cry2Ab as well as to Cry1Ab and Cry1Ac. Resistance ratios based on the concentration of toxin killing 50% of larvae for the resistant strain relative to a susceptible strain were 210 for Cry2Ab, 270 for Cry1Ab, and 310 for Cry1Ac, but only 1.6 for Cry1AbMod and 2.1 for Cry1AcMod. To evaluate the interactions among toxins, we tested combinations of Cry1AbMod, Cry1Ac, and Cry2Ab. For both the resistant and susceptible strains, the net results across all concentrations tested showed slight but significant synergism between Cry1AbMod and Cry2Ab, whereas the other combinations of toxins did not show consistent synergism or antagonism. The results suggest that the modified toxins might be useful for controlling populations of pink bollworm resistant to Cry1Ac, Cry2Ab, or both. PMID:24244692

Circadian Gene Variants and Susceptibility to Type 2 Diabetes: A Pilot Study

PubMed Central

Kelly, M. Ann; Rees, Simon D.; Hydrie, M. Zafar I.; Shera, A. Samad; Bellary, Srikanth; O’Hare, J. Paul; Kumar, Sudhesh; Taheri, Shahrad; Basit, Abdul; Barnett, Anthony H.

2012-01-01

Background Disruption of endogenous circadian rhythms has been shown to increase the risk of developing type 2 diabetes, suggesting that circadian genes might play a role in determining disease susceptibility. We present the results of a pilot study investigating the association between type 2 diabetes and selected single nucleotide polymorphisms (SNPs) in/near nine circadian genes. The variants were chosen based on their previously reported association with prostate cancer, a disease that has been suggested to have a genetic link with type 2 diabetes through a number of shared inherited risk determinants. Methodology/Principal Findings The pilot study was performed using two genetically homogeneous Punjabi cohorts, one resident in the United Kingdom and one indigenous to Pakistan. Subjects with (N = 1732) and without (N = 1780) type 2 diabetes were genotyped for thirteen circadian variants using a competitive allele-specific polymerase chain reaction method. Associations between the SNPs and type 2 diabetes were investigated using logistic regression. The results were also combined with in silico data from other South Asian datasets (SAT2D consortium) and white European cohorts (DIAGRAM+) using meta-analysis. The rs7602358G allele near PER2 was negatively associated with type 2 diabetes in our Punjabi cohorts (combined odds ratio [OR] = 0.75 [0.66–0.86], p = 3.18×10−5), while the BMAL1 rs11022775T allele was associated with an increased risk of the disease (combined OR = 1.22 [1.07–1.39], p = 0.003). Neither of these associations was replicated in the SAT2D or DIAGRAM+ datasets, however. Meta-analysis of all the cohorts identified disease associations with two variants, rs2292912 in CRY2 and rs12315175 near CRY1, although statistical significance was nominal (combined OR = 1.05 [1.01–1.08], p = 0.008 and OR = 0.95 [0.91–0.99], p = 0.015 respectively). Conclusions/significance None of the selected circadian gene variants was associated with type 2 diabetes with study-wide significance after meta-analysis. The nominal association observed with the CRY2 SNP, however, complements previous findings and confirms a role for this locus in disease susceptibility. PMID:22485135

Intractable diarrhoea of infancy and its management: modified cost effective treatment.

PubMed

Thapa, B R

1994-06-01

One-hundred-twenty infants under 1 year of age suffering from intractable diarrhoea were studied. They had received prior treatment in the form of antimicrobials (100 per cent), stool binding substance (50 percent), antimotility agents (50 per cent), and intravenous (IV) fluids (33 per cent). One-third of them had been hospitalised in peripheral hospitals. All of them had diarrhoea of more than 2 weeks' duration, protein energy malnutrition and were very ill. In addition vomiting, dehydration, fever, paralytic ileus, perianal excoriation and rectal prolapse were present in 44, 23, 33, 9, 47, and 3 per cent of the infants, respectively. Anaemia, multiple vitamin deficiencies, and pedal oedema were seen in 70, 10, and 3 per cent of infants, respectively. The infections documented were septicaemia (22 per cent), bronchopneumonia (6 per cent), meningitis (4 per cent), urinary tract infection (3 per cent) and acute supporative otitis media in 2 per cent of infants. Fifty-three per cent of infants had secondary lactose intolerance. Intolerance to milk protein, milk protein and soyabean and milk protein, as well as soyabean and chicken was seen in 4, 2, and 1 per cent cases, respectively. Aetiological agents isolated from stool culture were E. coli, (18 per cent), Klebsiella species (9 per cent), Shigella species (6 per cent), Salmonella typhimurium (2 per cent), Cholera mitschikom (1 per cent), Giardia lamblia (6 per cent), cryptosporidium (1 per cent), and E. histolytica (1 per cent). Candida albicans was grown in 18 per cent of infants. Pseudomembranous colitis was documented in 2 per cent cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Construction of an Immunized Rabbit Phage Display Library for Selecting High Activity against Bacillus thuringiensis Cry1F Toxin Single-Chain Antibodies.

PubMed

Xu, Chongxin; Zhang, Cunzheng; Zhong, Jianfeng; Hu, Hui; Luo, Shimin; Liu, Xiaoqin; Zhang, Xiao; Liu, Yuan; Liu, Xianjin

2017-07-26

In the present study, a Cry1F-immunized rabbit phage display library (6.96 × 10 8 cfu/mL) was constructed for selecting high activity of anti-Cry1F toxin single-chain antibody (a single-chain variable fragment, scFv) by biopanning. A total of 16 positive monoclonal phage scFv's were obtained after 4 rounds of panning, which were identified by enzyme-linked immunosorbent assay (ELISA), polymerized chain reaction, and DNA sequencing. The most positive phage scFv (named RF4) was expressed in Escherichia coli HB2151, and a soluble protein of approximately 30 kDa was purified with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An indirect competitive ELISA (IC-ELISA) was established on the basis of purified soluble RF4-scFv for Cry1F toxin. It indicated the 50% inhibition of the control (IC 50 ) was 11.56 ng/mL and the detection limit (IC 10 ) was 0.18 ng/mL and showed weak cross-reactivities for Cry1Ab (2.8%), Cry1Ac (1.3%), and Cry1B, Cry1C, Cry1Ie, and Cry2A (less than 0.1%). It was found that IC-ELISA detected Cry1F toxin spiked in rice, wheat, corn, and soil samples with good accuracy, stability, and repeatability. The recoveries were in the range of 80.2-99.6%, and the coefficients of variation were in the range of 2.5-10.0%. These results showed that IC-ELISA based on scFv from the immunized rabbit phage display library was promising for specific detection of Cry1F toxin in agroproducts and environmental samples.

Fer Cryin' Out Loud--There is a Sex Difference.

ERIC Educational Resources Information Center

Lombardo, William K.; And Others

1983-01-01

A study found sex differences in: (1) frequency and intensity of crying, (2) likelihood of crying independent of the presence of others, (3) likelihood of crying independent of the level of intimacy of observers or type of crying stimulus, and (4) in postcrying affect. (CMG)

Psychotherapy for Major Depressive Disorder and Generalized Anxiety Disorder: A Health Technology Assessment.

PubMed

2017-01-01

Major depressive disorder and generalized anxiety disorder are among the most commonly diagnosed mental illnesses in Canada; both are associated with a high societal and economic burden. Treatment for major depressive disorder and generalized anxiety disorder consists of pharmacological and psychological interventions. Three commonly used psychological interventions are cognitive behavioural therapy (CBT), interpersonal therapy, and supportive therapy. The objectives of this report were to assess the effectiveness and safety of these types of therapy for the treatment of adults with major depressive disorder and/or generalized anxiety disorder, to assess the cost-effectiveness of structured psychotherapy (CBT or interpersonal therapy), to calculate the budget impact of publicly funding structured psychotherapy, and to gain a greater understanding of the experiences of people with major depressive disorder and/or generalized anxiety disorder. We performed a literature search on October 27, 2016, for systematic reviews that compared CBT, interpersonal therapy, or supportive therapy with usual care, waitlist control, or pharmacotherapy in adult outpatients with major depressive disorder and/or generalized anxiety disorder. We developed an individual-level state-transition probabilistic model for a cohort of adult outpatients aged 18 to 75 years with a primary diagnosis of major depressive disorder to determine the cost-effectiveness of individual or group CBT (as a representative form of structured psychotherapy) versus usual care. We also estimated the 5-year budget impact of publicly funding structured psychotherapy in Ontario. Finally, we interviewed people with major depressive disorder and/or generalized anxiety disorder to better understand the impact of their condition on their daily lives and their experience with different treatment options, including psychotherapy. Interpersonal therapy compared with usual care reduced posttreatment major depressive disorder scores (standardized mean difference [SMD]: 0.24, 95% confidence interval [CI]: -0.47 to -0.02) and reduced relapse/recurrence in patients with major depressive disorder (relative risk [RR]: 0.41, 95% CI: 0.27-0.63). Supportive therapy compared with usual care improved major depressive disorder scores (SMD: 0.58, 95% CI: 0.45-0.72) and increased posttreatment recovery (odds ratio [OR]: 2.71, 95% CI: 1.19-6.16) in patients with major depressive disorder. CBT compared with usual care increased response (OR: 1.58, 95% CI: 1.11-2.26) and recovery (OR: 3.42, 95% CI: 1.98-5.93) in patients with major depressive disorder and decreased relapse/recurrence (RR: 0.68, 95% CI: 0.65-0.87]). For patients with generalized anxiety disorder, CBT improved symptoms posttreatment (SMD: 0.80, 95% CI: 0.67-0.93), improved clinical response posttreatment (RR: 0.64, 95% CI: 0.55-0.74), and improved quality-of-life scores (SMD: 0.44, 95% CI: 0.06-0.82). There was a significant difference in posttreatment recovery (OR: 1.98, 95% CI: 1.11-3.54) and mean major depressive disorder symptom scores (weighted mean difference: -3.07, 95% CI: -4.69 to -1.45) for patients who received individual versus group CBT. Details about the providers of psychotherapy were rarely reported in the systematic reviews we examined.In the base case probabilistic cost-utility analysis, compared with usual care, both group and individual CBT were associated with increased survival: 0.11 quality-adjusted life-years (QALYs) (95% credible interval [CrI]: 0.03-0.22) and 0.12 QALYs (95% CrI: 0.03-0.25), respectively.Group CBT provided by nonphysicians was associated with the smallest increase in discounted costs: $401 (95% CrI: $1,177 to 1,665). Group CBT provided by physicians, individual CBT provided by nonphysicians, and individual CBT provided by physicians were associated with the incremental costs of $1,805 (95% CrI: 65-3,516), $3,168 (95% CrI: 889-5,624), and $5,311 (95% CrI: 2,539-8,938), respectively. The corresponding incremental cost-effectiveness ratio (ICER) was lowest for group CBT provided by nonphysicians ($3,715/QALY gained) and highest for individual CBT provided by physicians ($43,443/QALY gained). In the analysis that ranked best strategies, individual CBT versus group CBT provided by nonphysicians yielded an ICER of $192,618 per QALY. The probability of group CBT provided by nonphysicians being cost-effective versus usual care was greater than 95% for all willingness-to-pay thresholds over $20,000 per QALY and was around 88% for individual CBT provided by physicians at a threshold of $100,000 per QALY.We estimated that adding structured psychotherapy to usual care over the next 5 years would result in a net budget impact of $68 million to $529 million, depending on a range of factors. We also estimated that to provide structured psychotherapy to all adults with major depressive disorder (alone or combined with generalized anxiety disorder) in Ontario by 2021, an estimated 500 therapists would be needed to provide group therapy, and 2,934 therapists would be needed to provide individual therapy.People with major depressive disorder and/or generalized anxiety disorder with whom we spoke reported finding psychotherapy effective, but they also reported experiencing a large number of barriers that prevented them from finding effective psychotherapy in a timely manner. Participants reported wanting more freedom to choose the type of psychotherapy they received. Compared with usual care, treatment with CBT, interpersonal therapy, or supportive therapy significantly reduces depression symptoms posttreatment. CBT significantly reduces anxiety symptoms posttreatment in patients with generalized anxiety disorder.Compared with usual care, treatment with structured psychotherapy (CBT or interpersonal therapy) represents good value for money for adults with major depressive disorder and/or generalized anxiety disorder. The most affordable option is group structured psychotherapy provided by nonphysicians, with the selective use of individual structured psychotherapy provided by nonphysicians or physicians for those who would benefit most from it (i.e., patients who are not engaging well with or adhering to group therapy).

Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis.

PubMed

Hazlewood, Glen S; Rezaie, Ali; Borman, Meredith; Panaccione, Remo; Ghosh, Subrata; Seow, Cynthia H; Kuenzig, Ellen; Tomlinson, George; Siegel, Corey A; Melmed, Gil Y; Kaplan, Gilaad G

2015-02-01

There is controversy regarding the best treatment for patients with Crohn's disease because of the lack of direct comparative trials. We compared therapies for induction and maintenance of remission in patients with Crohn's disease, based on direct and indirect evidence. We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Central databases, through June 2014. We identified randomized controlled trials (N = 39) comparing methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab, certolizumab, vedolizumab, or combined therapies with placebo or an active agent for induction and maintenance of remission in adult patients with Crohn's disease. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% credible interval (CrI). Infliximab, the combination of infliximab and azathioprine (infliximab + azathioprine), adalimumab, and vedolizumab were superior to placebo for induction of remission. In pair-wise comparisons of anti-tumor necrosis factor agents, infliximab + azathioprine (OR, 3.1; 95% CrI, 1.4-7.7) and adalimumab (OR, 2.1; 95% CrI, 1.0-4.6) were superior to certolizumab for induction of remission. All treatments were superior to placebo for maintaining remission, except for the combination of infliximab and methotrexate. Adalimumab, infliximab, and infliximab + azathioprine were superior to azathioprine/6-mercaptopurine: adalimumab (OR, 2.9; 95% CrI, 1.6-5.1), infliximab (OR, 1.6; 95% CrI, 1.0-2.5), infliximab + azathioprine (OR, 3.0; 95% CrI, 1.7-5.5) for maintenance of remission. Adalimumab and infliximab + azathioprine were superior to certolizumab: adalimumab (OR, 2.5; 95% CrI, 1.4-4.6) and infliximab + azathioprine (OR, 2.6; 95% CrI, 1.3-6.0). Adalimumab was superior to vedolizumab (OR, 2.4; 95% CrI, 1.2-4.6). Based on a network meta-analysis, adalimumab and infliximab + azathioprine are the most effective therapies for induction and maintenance of remission of Crohn's disease. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Intraperitoneal Continuous-Rate Infusion for the Maintenance of Anesthesia in Laboratory Mice (Mus musculus)

PubMed Central

Erickson, Rebecca L; Terzi, Matthew C; Jaber, Samer M; Hankenson, F Claire; McKinstry-Wu, Andrew; Kelz, Max B; Marx, James O

2016-01-01

Intraperitoneal injectable anesthetics are often used to achieve surgical anesthesia in laboratory mice. Because bolus redosing of injectable anesthetics can cause unacceptably high mortality, we evaluated intraperitoneal continuous-rate infusion (CRI) of ketamine with or without xylazine for maintaining surgical anesthesia for an extended period of time. Anesthesia was induced in male C57BL/6J mice by using ketamine (80 mg/kg) and xylazine (8 mg/kg) without or with acepromazine at 0.1 mg/kg or 0.5 mg/kg. At 10 min after induction, CRI for 90 min was initiated and comprised 25%, 50%, or 100% of the initial ketamine dose per hour or 50% of the initial doses of both ketamine and xylazine. Anesthetic regimens were compared on the basis of animal immobility, continuous surgical depth of anesthesia as determined by the absence of a pedal withdrawal reflex, and mortality. Consistent with previous studies, the response to anesthetics was highly variable. Regimens that provided the longest continuous surgical plane of anesthesia with minimal mortality were ketamine–xylazine–acepromazine (0.1 mg/kg) with CRI of 100% of the initial ketamine dose and ketamine–xylazine–acepromazine (0.5 mg/kg) with CRI of 50% of the initial ketamine and xylazine doses. In addition, heart rate and respiratory rate did not increase consistently in response to a noxious stimulus during CRI anesthesia, even when mice exhibited a positive pedal withdrawal reflex, suggesting that these parameters are unreliable indicators of anesthetic depth during ketamine–xylazine anesthesia in mice. We conclude that intraperitoneal CRI anesthesia in mice prolongs injectable anesthesia more consistently and with lower mortality than does bolus redosing. PMID:27657709

Draft Genome Sequences of Two Bacillus thuringiensis Strains and Characterization of a Putative 41.9-kDa Insecticidal Toxin

PubMed Central

Palma, Leopoldo; Muñoz, Delia; Berry, Colin; Murillo, Jesús; Caballero, Primitivo

2014-01-01

In this work, we report the genome sequencing of two Bacillus thuringiensis strains using Illumina next-generation sequencing technology (NGS). Strain Hu4-2, toxic to many lepidopteran pest species and to some mosquitoes, encoded genes for two insecticidal crystal (Cry) proteins, cry1Ia and cry9Ea, and a vegetative insecticidal protein (Vip) gene, vip3Ca2. Strain Leapi01 contained genes coding for seven Cry proteins (cry1Aa, cry1Ca, cry1Da, cry2Ab, cry9Ea and two cry1Ia gene variants) and a vip3 gene (vip3Aa10). A putative novel insecticidal protein gene 1143 bp long was found in both strains, whose sequences exhibited 100% nucleotide identity. The predicted protein showed 57 and 100% pairwise identity to protein sequence 72 from a patented Bt strain (US8318900) and to a putative 41.9-kDa insecticidal toxin from Bacillus cereus, respectively. The 41.9-kDa protein, containing a C-terminal 6× HisTag fusion, was expressed in Escherichia coli and tested for the first time against four lepidopteran species (Mamestra brassicae, Ostrinia nubilalis, Spodoptera frugiperda and S. littoralis) and the green-peach aphid Myzus persicae at doses as high as 4.8 µg/cm2 and 1.5 mg/mL, respectively. At these protein concentrations, the recombinant 41.9-kDa protein caused no mortality or symptoms of impaired growth against any of the insects tested, suggesting that these species are outside the protein’s target range or that the protein may not, in fact, be toxic. While the use of the polymerase chain reaction has allowed a significant increase in the number of Bt insecticidal genes characterized to date, novel NGS technologies promise a much faster, cheaper and efficient screening of Bt pesticidal proteins. PMID:24784323

Milk Sweetened with Xylitol: A Proof-of-Principle Caries Prevention Randomized Clinical Trial.

PubMed

Chi, Donald L; Zegarra, Graciela; Vasquez Huerta, Elsa C; Castillo, Jorge L; Milgrom, Peter; Roberts, Marilyn C; Cabrera-Matta, Ailin R; Merino, Ana P

2016-09-15

To evaluate the efficacy of xylitol-sweetened milk as a caries-preventive strategy. In this nine-month prospective proof-of-principle trial, Peruvian schoolchildren were randomized to one of five different milk groups: (1) eight g of xylitol per 200 mL milk once per day; (2) four g of xylitol per 100 mL milk twice per day; (3) eight g of sorbitol per 200 mL milk once per day; (4) four g of sorbitol per 100 mL milk twice per day; or (5) eight g of sucrose per 200 mL milk once per day. The primary outcome was plaque mutans streptococci (MS) at nine months. A secondary outcome was caries incidence. We hypothesized that children in the xylitol groups would have a greater MS decline and lower caries incidence. One hundred fifty-three children were randomized in the intent-to-treat analyses. Children receiving xylitol had a greater decline in MS than children receiving sucrose (P=0.02) but were not different from children receiving sorbitol (P=0.07). Dental caries incidence for xylitol once per day or twice per day was 5.3±3.4 and 4.3±4.0 surfaces, respectively, compared to sorbitol once per day, sorbitol twice per day, or sucrose (4.1±2.8, 3.7±4.2, and 3.2±3.4 surfaces, respectively). There were no differences in caries incidence between xylitol and sucrose (rate ratio [RR] = 1.51; 95 percent confidence interval [CI] = 0.88, 2.59; P=0.13) or between xylitol and sorbitol (RR = 1.28; 95 percent CI = 0.90, 1.83; P=0.16). Xylitol-sweetened milk significantly reduced mutans streptococci levels compared to sucrose-sweetened milk, but differences in caries incidence were not detected.

Understanding Crying in Infancy. Selected Papers Number 43.

ERIC Educational Resources Information Center

Hope, Margaret

Presented are practical ideas parents can use to prevent and manage excessive crying during their infant's first year. Designed to foster the development of children's physical and emotional independence, the ideas discussed concern (1) the changing functions of crying throughout the infant's first year, (2) causes of crying, (3) the intellectual…

Laboratory evaluation of transgenic Populus davidiana×Populus bolleana expressing Cry1Ac + SCK, Cry1Ah3, and Cry9Aa3 genes against gypsy moth and fall webworm.

PubMed

Ding, Liping; Chen, Yajuan; Wei, Xiaoli; Ni, Mi; Zhang, Jiewei; Wang, Hongzhi; Zhu, Zhen; Wei, Jianhua

2017-01-01

Transgenic poplar lines 'Shanxin' (Populus davidiana×Populus bolleana) were generated via Agrobacterium-mediated transformation. The transgenic lines carried the expression cassettes of Cry1Ac + SCK, Cry1Ah3, and Cry9Aa3, respectively. The expression levels of the exogenous insect resistance genes in the transgenic lines were determined by Q-PCR and Western blot. Leaves of the transgenic lines were used for insect feeding bioassays on first instar larvae of the gypsy moth (Lymantria dispar) and fall webworm (Hyphantria cunea). At 5 d of feeding, the mean mortalities of larvae feeding on Cry1Ac + SCK and Cry1Ah3 transgenic poplars leaves were 97% and 91%, while mortality on Cry9Aa3 transgenic lines was about 49%. All gypsy moth and fall webworm larvae were killed in 7-9 days after feeding on leaves from Cry1Ac + SCK or Cry1Ah3 transgenic poplars, while all the fall webworm larvae were killed in 11 days and about 80% of gypsy moth larvae were dead in 14 days after feeding on those from Cry9Aa3 transgenic lines. It was concluded that the transgenic lines of Cry1Ac + SCK and Cry1Ah3 were highly toxic to larvae of both insect species while lines with Cry9Aa3 had lower toxicity,and H. cunea larvae are more sensitive to the insecticidal proteins compared to L. dispar. Transgenic poplar lines toxic to L. dispar and H. cunea could be used to provide Lepidoptera pest resistance to selected strains of poplar trees.

75 FR 57778 - Issuance of an Experimental Use Permit

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-22

...) necessary for its production in Event TC1507 corn. There are 10.213 kilograms (kg) of eCry3.1Ab, 11.14 grams of Cry1Ab, 8,145 grams of Cry34Ab1, 112.1 grams of Cry35Ab1, 280.6 grams of Vip3Aa20, 217.9 grams of mCry3A, and 177.5 grams of Cry1F proteins in 69,473 kg seeds on 7,311 acres (3,830 PIP and 3,481 non...

40 CFR 86.1105-87 - Emission standards for which nonconformance penalties are available.

Code of Federal Regulations, 2014 CFR

2014-07-01

... engine oxides of nitrogen standard of 5.0 grams per brake horsepower-hour. (i) For petroleum-fueled light... § 86.1113-87(a): (1) COC50: $830. (2) COC90: $946. (3) MC50: $1,167 per gram per brake horsepower-hour...-87(a): (1) COC50: $905. (2) COC90: $1,453. (3) MC50: $1,417 per gram per brake horsepower-hour. (4) F...

Decline in Kidney Function among Apparently Healthy Young Adults at Risk of Mesoamerican Nephropathy.

PubMed

Gonzalez-Quiroz, Marvin; Smpokou, Evangelia-Theano; Silverwood, Richard J; Camacho, Armando; Faber, Dorien; Garcia, Brenda La Rosa; Oomatia, Amin; Hill, Michael; Glaser, Jason; Le Blond, Jennifer; Wesseling, Catharina; Aragon, Aurora; Smeeth, Liam; Pearce, Neil; Nitsch, Dorothea; Caplin, Ben

2018-06-15

Background Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease. Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men ( n =263) and a random sample of women ( n =87) ages 18-30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors. Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m 2 ; -0.6 ml/min per 1.73 m 2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m 2 ; -18.2 ml/min per 1.73 m 2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m 2 ; -3.8 ml/min per 1.73 m 2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m 2 ; -0.6 ml/min per 1.73 m 2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m 2 ; -14.6 ml/min per 1.73 m 2 per year; n =3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline. Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease. Copyright © 2018 by the American Society of Nephrology.

Modelling and Analysis of the Feeding Regimen Induced Entrainment of Hepatocyte Circadian Oscillators Using Petri Nets

PubMed Central

Tareen, Samar Hayat Khan; Ahmad, Jamil

2015-01-01

Circadian rhythms are certain periodic behaviours exhibited by living organism at different levels, including cellular and system-wide scales. Recent studies have found that the circadian rhythms of several peripheral organs in mammals, such as the liver, are able to entrain their clocks to received signals independent of other system level clocks, in particular when responding to signals generated during feeding. These studies have found SIRT1, PARP1, and HSF1 proteins to be the major influencers of the core CLOCKBMAL1:PER-CRY circadian clock. These entities, along with abstracted feeding induced signals were modelled collectively in this study using Petri Nets. The properties of the model show that the circadian system itself is strongly robust, and is able to continually evolve. The modelled feeding regimens suggest that the usual 3 meals/day and 2 meals/day feeding regimens are beneficial with any more or less meals/day negatively affecting the system. PMID:25789928

[Consumption of hand-hygiene products in health establishments in the west of France].

PubMed

Branger, B; Senechal, H; Bataillon, S; Ertzscheid, M A; Baron, R; Borgey, F; Thibon, P; Van Der Mee, N; Girard, N; Wiesel, M; Avril, C; Coulomb, F; Chaperon, J; Lejeune, B

2005-06-01

The study had for aim to investigate hand hygiene product use in French hospitals between 2000 and 2003. A questionnaire was sent in 2002 and 2 more in 2003 and 2004 (for 2000 to 2003) requiring data on type of hospital, number of beds, staff members, admissions and patient-day, litres of mild soap, antiseptic soap and alcohol-based rub used and price per litre. Indices were calculated accordingly. 574 hospitals answered over the 4 year period (average 143 per year) representing an average of 50 000 beds/year, 80 000 full-time staff positions, 1.2 million admissions and 16 millions patient-days. The median consumption of mild soap was 3.8 l per bed, 2.7 l per staff member, 2.4 l per 100 admissions, and 10.6 ml per patient-day. The median consumption of antiseptic soap was 1 l per bed, 0.8 l per staff member, 4.8 l per 100 admissions, and 3.2 ml per patient-day. The median consumption of alcohol-based rub (HAS) was 0.3 l per bed, 0.3 l per staff-member, 1.5 l per admission, and 0.9 l per patient-day. Between 2000 and 2003, HAS use significantly increased from 69 to 88% (a relative increase of 31%) and the median consumption increased from 0.5 ml to 1.5 ml per patient-day. 370 fully completed grids gave a number of 7 opportunities per patient-day with less than 1 for HAS. The best indicator for an infection control practitioners is the quantity of alcohol-based solution in ml/patient-day and HAS per patient-day is the reference.

INDIVIDUAL BLOOD DIFFERENCES IN MEXICAN INDIANS, WITH SPECIAL REFERENCE TO THE Rh BLOOD TYPES AND Hr FACTOR

PubMed Central

Wiener, Alexander S.; Zepeda, J. Preciado; Sonn, Eve B.; Polivka, H. R.

1945-01-01

98 Mexican Indians were tested for the blood properties A-B-O, A1-A2, M-N, P, Rh'-Rh''-Rh0-rh, and Hr. Of the 98 Indians, 90.8 per cent belonged to group 0, 6.1 per cent belonged to A1, and 3.1 per cent to group B. There were 61.2 per cent of type M, 3.1 per cent of type N, and 35.7 per cent of type MN. Of the 95 Mexican Indians tested with anti-P serum, 21.1 per cent were found to lack the P agglutinogen. In tests for the Rh blood types, 48.0 per cent of the Indians were found to belong to type Rh1, 9.2 per cent to type Rh2, 41.8 per cent to type Rh1Rh2, and 1 per cent to type Rh0. There were no bloods giving intermediate reactions. Of the 95 Indians tested for the Hr factor 44.2 per cent were found to lack this property. The reactions for the Rh blood types and Hr factor were correlated with each other and the results supported the conclusion of Race et al. that in addition to the six standard allelic genes and the so called intermediate genes, there is one or possibly two genes having the property of determining agglutinogens which react with anti-Rh' and anti-Rh'' sera, but not with anti-Hr serum. This gene (or genes) appears to be relatively common among Mexican Indians (approximately 3.3 per cent) in contrast to its rareness in white individuals. PMID:19871476

Production and Characterization of Bacillus thuringiensis Cry1Ac-Resistant Cotton Bollworm Helicoverpa zea (Boddie)▿

PubMed Central

Anilkumar, Konasale J.; Rodrigo-Simón, Ana; Ferré, Juan; Pusztai-Carey, Marianne; Sivasupramaniam, Sakuntala; Moar, William J.

2008-01-01

Laboratory-selected Bacillus thuringiensis-resistant colonies are important tools for elucidating B. thuringiensis resistance mechanisms. However, cotton bollworm, Helicoverpa zea, a target pest of transgenic corn and cotton expressing B. thuringiensis Cry1Ac (Bt corn and cotton), has proven difficult to select for stable resistance. Two populations of H. zea (AR and MR), resistant to the B. thuringiensis protein found in all commercial Bt cotton varieties (Cry1Ac), were established by selection with Cry1Ac activated toxin (AR) or MVP II (MR). Cry1Ac toxin reflects the form ingested by H. zea when feeding on Bt cotton, whereas MVP II is a Cry1Ac formulation used for resistance selection and monitoring. The resistance ratio (RR) for AR exceeded 100-fold after 11 generations and has been maintained at this level for nine generations. This is the first report of stable Cry1Ac resistance in H. zea. MR crashed after 11 generations, reaching only an RR of 12. AR was only partially cross-resistant to MVP II, suggesting that MVP II does not have the same Cry1Ac selection pressure as Cry1Ac toxin against H. zea and that proteases may be involved with resistance. AR was highly cross-resistant to Cry1Ab toxin but only slightly cross-resistant to Cry1Ab expressing corn leaf powder. AR was not cross-resistant to Cry2Aa2, Cry2Ab2-expressing corn leaf powder, Vip3A, and cypermethrin. Toxin-binding assays showed no significant differences, indicating that resistance was not linked to a reduction in binding. These results aid in understanding why this pest has not evolved B. thuringiensis resistance, and highlight the need to choose carefully the form of B. thuringiensis protein used in experiments. PMID:18024681

How to Calm Children through Massage.

ERIC Educational Resources Information Center

Bernal, Gilda Rios

1997-01-01

Studied the impact of massage three times per week on infants' adjustment to a group care setting. Subjects were infants from at-risk Chilean homes who displayed negative emotional behaviors. Found that massaged infants showed less repetitive crying, more tranquil sleep and muscular relaxation, better social adjustment, and improved feeding…

Resistance to dual-gene Bt maize in Spodoptera frugiperda: selection, inheritance, and cross-resistance to other transgenic events

PubMed Central

Santos-Amaya, Oscar F.; Rodrigues, João V. C.; Souza, Thadeu C.; Tavares, Clébson S.; Campos, Silverio O.; Guedes, Raul N.C.; Pereira, Eliseu J.G.

2015-01-01

Transgenic crop “pyramids” producing two or more Bacillus thuringiensis (Bt) toxins active against the same pest are used to delay evolution of resistance in insect pest populations. Laboratory and greenhouse experiments were performed with fall armyworm, Spodoptera frugiperda, to characterize resistance to Bt maize producing Cry1A.105 and Cry2Ab and test some assumptions of the “pyramid” resistance management strategy. Selection of a field-derived strain of S. frugiperda already resistant to Cry1F maize with Cry1A.105 + Cry2Ab maize for ten generations produced resistance that allowed the larvae to colonize and complete the life cycle on these Bt maize plants. Greenhouse experiments revealed that the resistance was completely recessive (Dx = 0), incomplete, autosomal, and without maternal effects or cross-resistance to the Vip3Aa20 toxin produced in other Bt maize events. This profile of resistance supports some of the assumptions of the pyramid strategy for resistance management. However, laboratory experiments with purified Bt toxin and plant leaf tissue showed that resistance to Cry1A.105 + Cry2Ab2 maize further increased resistance to Cry1Fa, which indicates that populations of fall armyworm have high potential for developing resistance to some currently available pyramided maize used against this pest, especially where resistance to Cry1Fa was reported in the field. PMID:26675246

Resistance to dual-gene Bt maize in Spodoptera frugiperda: selection, inheritance, and cross-resistance to other transgenic events.

PubMed

Santos-Amaya, Oscar F; Rodrigues, João V C; Souza, Thadeu C; Tavares, Clébson S; Campos, Silverio O; Guedes, Raul N C; Pereira, Eliseu J G

2015-12-17

Transgenic crop "pyramids" producing two or more Bacillus thuringiensis (Bt) toxins active against the same pest are used to delay evolution of resistance in insect pest populations. Laboratory and greenhouse experiments were performed with fall armyworm, Spodoptera frugiperda, to characterize resistance to Bt maize producing Cry1A.105 and Cry2Ab and test some assumptions of the "pyramid" resistance management strategy. Selection of a field-derived strain of S. frugiperda already resistant to Cry1F maize with Cry1A.105 + Cry2Ab maize for ten generations produced resistance that allowed the larvae to colonize and complete the life cycle on these Bt maize plants. Greenhouse experiments revealed that the resistance was completely recessive (Dx = 0), incomplete, autosomal, and without maternal effects or cross-resistance to the Vip3Aa20 toxin produced in other Bt maize events. This profile of resistance supports some of the assumptions of the pyramid strategy for resistance management. However, laboratory experiments with purified Bt toxin and plant leaf tissue showed that resistance to Cry1A.105 + Cry2Ab2 maize further increased resistance to Cry1Fa, which indicates that populations of fall armyworm have high potential for developing resistance to some currently available pyramided maize used against this pest, especially where resistance to Cry1Fa was reported in the field.

[Living conditions and pattern of acute poisonings in Oslo].

PubMed

Kolvik, Hallgeir Mæsel; Heyerdahl, Fridtjof; Bjørnaas, Mari Asphjell; Hovda, Knut Erik; Jacobsen, Dag; Ekeberg, Øivind

2011-08-09

Hospitalized patients with acute poisoning come from all classes of society. The relationship between living conditions and pattern of poisoning is, however, unclear. The aim of this study was to examine the connection between living conditions in Oslo and the pattern of acute poisonings, measured by incidence, main toxic agents and intention. A one-year multi-centre study with prospective inclusion of all patients ≥ 18 years of age with a registered address in Oslo admitted to an Oslo hospital with acute poisoning from 1 April 2003 through 31 March 2004. The 15 city districts were grouped into three, according to the official living conditions index in Oslo: city district group 1 (best living conditions), city district group 2 (average living conditions) and city district group 3 (most difficult living conditions). Of a total of 947 patients admitted with acute poisoning as their main diagnosis in the study period, 691 were included in the study, 660 of whom had self-inflicted poisoning. In city district group 3, the annual incidence of acute poisonings was 2.14 per 1000 inhabitants, significantly higher than city district group 2, with 1.50 (p < 0.001), and city district group 1, with 1.36 (p < 0.001). Measured as intention assessed by the treating physician, suicidal and drug related poisonings and those induced by a "cry for help" were more common in city district group 3 (0.74, 0.59 and 0.74 per 1000 inhabitants, respectively) than in city district group 2 (0.62, 0.40 and 0.41, respectively) and city district group 1 (0.52, 0.32 and 0.45, respectively). The main toxic agents were predominantly benzodiazepines (20 %), ethanol (18 %) and paracetamol (12 %). There were no statistically significant differences in the distribution of main toxic agents between the city district groups. The findings show a social gradient, with the highest incidence of poisonings in the city district group with the most difficult living conditions.

40 CFR Table 2 to Subpart Ddddd of... - Emission Limits for Existing Boilers and Process Heaters

Code of Federal Regulations, 2013 CFR

2013-07-01

... runduration . . . 1. Units in all subcategories designed to burn solid fuel a. HCl 2.2E-02 lb per MMBtu of...-02 lb per MMBtu of heat input; or (5.3E-05 lb per MMBtu of heat input) 4.2E-02 lb per MMBtu of steam... lb per MMBtu of heat input) 4.3E-02 lb per MMBtu of steam output or 5.2E-01 lb per MWh; or (2.8E-04...

Effectiveness of 3 per cent boric acid in 70 per cent alcohol versus 1 per cent clotrimazole solution in otomycosis patients: a randomised, controlled trial.

PubMed

Romsaithong, S; Tomanakan, K; Tangsawad, W; Thanaviratananich, S

2016-09-01

To compare the clinical effectiveness and adverse events for 3 per cent boric acid in 70 per cent alcohol versus 1 per cent clotrimazole solution in the treatment of otomycosis. A total of 120 otomycosis patients were randomly assigned to receive either 1 per cent clotrimazole solution (intervention group) or 3 per cent boric acid in 70 per cent alcohol (control group) at the Khon Kaen Hospital ENT out-patient department. Treatment effectiveness was determined based on the otomicroscopic absence of fungus one week after therapy, following a single application of treatment. After 1 week of treatment, there were data for 109 participants, 54 in the clotrimazole group and 55 in the boric acid group. The absolute difference in cure rates between 1 per cent clotrimazole solution and 3 per cent boric acid in 70 per cent alcohol was 17.9 per cent (95 per cent confidence interval, 2.3 to 33.5; p = 0.028) and the number needed to treat was 6 (95 per cent confidence interval, 3.0 to 43.4). Adverse events for the two agents were comparable. One per cent clotrimazole solution is more effective than 3 per cent boric acid in 70 per cent alcohol for otomycosis treatment.

Management of osteoarthritis in general practice in Australia.

PubMed

Brand, Caroline A; Harrison, Christopher; Tropea, Joanne; Hinman, Rana S; Britt, Helena; Bennell, Kim

2014-04-01

To describe management of osteoarthritis (OA) of the hip (OA-hip) and knee (OA-knee) by Australian general practitioners (GPs). We analyzed data from the Bettering the Evaluation and Care of Health program, from April 1, 2005 to March 31, 2010. Patient and GP characteristics and encounter management data were extracted. Data were classified by the International Classification of Primary Care, version 2, and summarized using descriptive statistics and 95% confidence intervals around point estimates. There were 489,900 GP encounters at which OA was managed (rate of 26.4 per 1,000 encounters). OA-hip was managed at a rate of 2.3 per 1,000 encounters (n = 1,106, 8.6% OA) and OA-knee at a rate of 6.2 per 1,000 (n = 3,058, 23.7% OA). The encounter management rate per 1,000 for OA-hip was higher among non-metropolitan dwellers (2.85 per 1,000 versus 1.97 per 1,000) and lower for non-English-speaking people (1.53 per 1,000 encounters versus 2.39 per 1,000). The rate for OA-knee was higher for non-English-speaking background (8.50 per 1,000 encounters versus 6.24 per 1,000) and lower among indigenous people (3.16 per 1,000 encounters versus 6.46 per 1,000). Referral to an orthopedic surgeon was the most frequently used nonpharmacologic management (OA-knee 17.4 per 100 contacts and OA-hip 17.7 per 100), followed by advice, education, and counselling. As first-line treatment, medication prescription rates (OA-knee 78.7 per 100 contacts and OA-hip 73.2 per 100) were substantially higher than rates of lifestyle management (OA-knee 20.7 per 100 contacts and OA-hip 14.8 per 100). OA-hip and OA-knee encounters and management differ. Nonpharmacologic treatments as first-line management were low compared with pharmacologic management rates, and surgical referral rates were high. However, lack of longitudinal data limits definitive assessment of appropriateness of care. Copyright © 2014 by the American College of Rheumatology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ton, My K.; Richman, Eric E.; Gilbride, Theresa L.

In August 2008 the Pacific Northwest National Laboratory (PNNL) conducted a light emitting diode (LED) residential lighting demonstration project for the U.S. Department of Energy (DOE), Office of Building Technologies, as part of DOE’s Solid State Lighting (SSL) Technology Demonstration Gateway Program. Two lighting technologies, an LED replacement for downlight lamps (bulbs) and an LED undercabinet lighting fixture, were tested in the demonstration which was conducted in two homes built for the 2008 Tour of Homes in Eugene, Oregon. The homes were built by the Lane County Home Builders Association (HBA), and Future B Homes. The Energy Trust of Oregonmore » (ETO) also participated in the demonstration project. The LED downlight product, the LR6, made by Cree LED Lighting Solutions acts as a screw-in replacement for incandescent and halogen bulbs in recessed can downlights. The second product tested is Phillips/Color Kinetics’ eW® Profile Powercore undercabinet fixture designed to mount under kitchen cabinets to illuminate the countertop and backsplash surfaces. Quantitative and qualitative measurements of light performance and electrical power usage were taken at each site before and after initially installed halogen and incandescent lamps were replaced with the LED products. Energy savings and simple paybacks were also calculated and builders who toured the homes were surveyed for their responses to the LED products. The LED downlight product drew 12 Watts of power, cutting energy use by 82% compared to the 65W incandescent lamp and by 84% compared to the 75W halogen lamp. The LED undercabinet fixture drew 10 watts, cutting energy use by 83% to 90% compared to the halogen product, which was tested at two power settings: a low power 60W setting and a high power 105W setting. The LED downlight consistently provided more light than the halogen and incandescent lamps in horizontal measurements at counter height and floor level. It also outperformed in vertical illuminance measurements taken on the walls, indicating better lateral dispersion of the light. The undercabinet fixture’s light output was midway between the low and high power halogen undercabinet fixture light outputs (35.8 foot candle versus 13.4 fc and 53.4 fc) but it produced a more uniform light (max/min ratio of 7.0 versus 10.8). The color correlated temperature (CCT, the blue or yellowness) of the LED light correlated well with the halogen and incandescent lights (2675 K vs 2700 K). The color rendering of the LED downlight also correlated well at 92 CRI compared to 100 CRI for the halogen and incandescent lamps. The LED undercabinet fixture had measures of 2880 K CCT and 71 CRI compared to the 2700 K and 100 CRI scores for the halogen undercabinet fixture. Builders who toured the homes were surveyed; they gave the LED downlight high marks for brightness, said the undercabinet improved shadows and glare and said both products improved overall visibility, home appearance, and home value. Paybacks on the LED downlight ranged from 7.6 years (assuming electricity cost of 11 c/kWh) to 13.5 years (at 5C/kWh). Paybacks on the LED undercabinet fixture in a new home ranged from 4.4 years (11c/kWh electricity) to 7.6 years (5c/kWh) based on product costs of $95 per LED downlight and $140 per LED undercabinet fixture at 3 hrs per day of usage for the downlight and 2 hrs per day for the undercabinet lighting.« less

Molecular and phylogenetic analyses reveal mammalian-like clockwork in the honey bee (Apis mellifera) and shed new light on the molecular evolution of the circadian clock.

PubMed

Rubin, Elad B; Shemesh, Yair; Cohen, Mira; Elgavish, Sharona; Robertson, Hugh M; Bloch, Guy

2006-11-01

The circadian clock of the honey bee is implicated in ecologically relevant complex behaviors. These include time sensing, time-compensated sun-compass navigation, and social behaviors such as coordination of activity, dance language communication, and division of labor. The molecular underpinnings of the bee circadian clock are largely unknown. We show that clock gene structure and expression pattern in the honey bee are more similar to the mouse than to Drosophila. The honey bee genome does not encode an ortholog of Drosophila Timeless (Tim1), has only the mammalian type Cryptochrome (Cry-m), and has a single ortholog for each of the other canonical "clock genes." In foragers that typically have strong circadian rhythms, brain mRNA levels of amCry, but not amTim as in Drosophila, consistently oscillate with strong amplitude and a phase similar to amPeriod (amPer) under both light-dark and constant darkness illumination regimes. In contrast to Drosophila, the honey bee amCYC protein contains a transactivation domain and its brain transcript levels oscillate at virtually an anti-phase to amPer, as it does in the mouse. Phylogenetic analyses indicate that the basal insect lineage had both the mammalian and Drosophila types of Cry and Tim. Our results suggest that during evolution, Drosophila diverged from the ancestral insect clock and specialized in using a set of clock gene orthologs that was lost by both mammals and bees, which in turn converged and specialized in the other set. These findings illustrate a previously unappreciated diversity of insect clockwork and raise critical questions concerning the evolution and functional significance of species-specific variation in molecular clockwork.

Use of a pooled clone method to isolate a novel Bacillus thuringiensis Cry2A toxin with activity against Ostrinia furnacalis.

PubMed

Shu, Changlong; Zhang, Jingtao; Chen, Guihua; Liang, Gemei; He, Kanglai; Crickmore, Neil; Huang, Dafang; Zhang, Jie; Song, Fuping

2013-09-01

A pooled clone method was developed to screen for cry2A genes. This metagenomic method avoids the need to analyse isolated Bacillus thuringiensis strains by performing gene specific PCR on plasmid-enriched DNA prepared from a pooled soil sample. Using this approach the novel holotype gene cry2Ah1 was cloned and characterized. The toxin gene was over-expressed in Escherichia coli Rosetta (DE3) and the expressed toxin accumulated in both the soluble and insoluble fractions. The soluble Cry2Ah1 was found to have a weight loss activity against Ostrinia furnacalis, and a growth inhibitory activity to both Cry1Ac-susceptible and resistant Helicoverpa armigera populations. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of lymphatic drainage and local cryo exposition regeneration after high-intensive exercises

PubMed Central

Behringer, Michael; Jedlicka, Diana; McCourt, Molly; Ring, Matthias; Mester, Joachim

2016-01-01

Summary Background Recovery from exercise and competition is important in sports medicine, particularly when rest periods are short. The objective is to determine the efficacy of cryo exposition (CRY) and manual lymphatic drainage (MLD) to hasten short term recovery of muscle performance after eccentric contractions. Methods In a randomized controlled trial, 30 healthy sport students (21 males, 9 females; age: 25.7±2.8 years) performed 4×20 eccentric contractions of knee extensors, followed by 30 min MLD, CRY, or rest (RST) under controlled laboratory environment. Maximal voluntary contractions (MVC), electrically induced muscle fatigue (FI), and electrically induced tetani (EIT) at low (T2: 20 Hz) and high frequencies were tested. Results Force decline and recovery kinetics regarding MVC, FI, and EIT did not differ significantly (p<0.05) between groups. That is, 24 h after the intervention, MVC (MLD: 80.9±5.5%; CRY: 81.1±8.5%; RST: 83.5±7.3%), FI (MLD: 83.2±23.7%; CRY: 81.2±38.8%; RST: 93.2±22.9%), and EIT (T1: MLD: 53.0±29.5%; CRY: 39.0±32.9%; RST: 46.3±26.1%; T2: MLD: 84.2±27.2%; CRY: 64.2±24.2%; RST: 66.6±22.3%) were similarly depressed irrespective of applied treatments. Conclusion Neither CRY nor MLD hastened the recovery of muscle performance, when applied for 30 min. Identification number of the Primary Registry Network: DRKS00007608. PMID:27900297

40 CFR Table 6 to Subpart Cccc of... - Emission Limitations for Energy Recovery Units That Commenced Construction After June 4, 2010, or...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Biomass—6.2 parts per million dry volumeCoal—650 parts per million dry volume 3-run average (1 hour... Biomass—290 parts per million dry volumeCoal—340 parts per million dry volume 3-run average (1 hour... volume Biomass—240 parts per million dry volumeCoal—95 parts per million dry volume 3-run average (1 hour...

Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.

PubMed

Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

2014-01-01

From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH.

Altered Dynamics in the Circadian Oscillation of Clock Genes in Dermal Fibroblasts of Patients Suffering from Idiopathic Hypersomnia

PubMed Central

Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

2014-01-01

From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues – mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep – wake rhythms in IH. PMID:24454829

Past Decline Versus Current eGFR and Subsequent Mortality Risk.

PubMed

Naimark, David M J; Grams, Morgan E; Matsushita, Kunihiro; Black, Corri; Drion, Iefke; Fox, Caroline S; Inker, Lesley A; Ishani, Areef; Jee, Sun Ha; Kitamura, Akihiko; Lea, Janice P; Nally, Joseph; Peralta, Carmen Alicia; Rothenbacher, Dietrich; Ryu, Seungho; Tonelli, Marcello; Yatsuya, Hiroshi; Coresh, Josef; Gansevoort, Ron T; Warnock, David G; Woodward, Mark; de Jong, Paul E

2016-08-01

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m(2) per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR. Copyright © 2016 by the American Society of Nephrology.

Single amino acid insertions in extracellular loop 2 of Bombyx mori ABCC2 disrupt its receptor function for Bacillus thuringiensis Cry1Ab and Cry1Ac but not Cry1Aa toxins.

PubMed

Tanaka, Shiho; Miyamoto, Kazuhisa; Noda, Hiroaki; Endo, Haruka; Kikuta, Shingo; Sato, Ryoichi

2016-04-01

In a previous report, seven Cry1Ab-resistant strains were identified in the silkworm, Bombyx mori; these strains were shown to have a tyrosine insertion at position 234 in extracellular loop 2 of the ABC transporter C2 (BmABCC2). This insertion was confirmed to destroy the receptor function of BmABCC2 and confer the strains resistance against Cry1Ab and Cry1Ac. However, these strains were susceptible to Cry1Aa. In this report, we examined the mechanisms of the loss of receptor function of the transporter by expressing mutations in Sf9 cells. After replacement of one or two of the five amino acid residues in loop 2 of the susceptible BmABCC2 gene [BmABCC2_S] with alanine, cells still showed susceptibility, retaining the receptor function. Five mutants with single amino acid insertions at position 234 in BmABCC2 were also generated, resulting in loop 2 having six amino acids, which corresponds to replacing the tyrosine insertion in the resistant BmABCC2 gene [BmABCC2_R(+(234)Y)] with another amino acid. All five mutants exhibited loss of function against Cry1Ab and Cry1Ac. These results suggest that the amino acid sequence in loop 2 is less important than the loop size (five vs. six amino acids) or loop structure for Cry1Ab and Cry1Ac activity. Several domain-swapped mutant toxins were then generated among Cry1Aa, Cry1Ab, and Cry1Ac, which are composed of three domains. Swapped mutants containing domain II of Cry1Ab or Cry1Ac did not kill Sf9 cells expressing BmABCC2_R(+(234)Y), suggesting that domain II of the Cry toxin is related to the interaction with the receptor function of BmABCC2. This also suggests that different reactions against Bt-toxins in some B. mori strains, that is, Cry1Ab resistance or Cry1Aa susceptibility, are attributable to structural differences in domain II of Cry1A toxins. Copyright © 2016. Published by Elsevier Inc.

Compared to Canadians, U.S. physicians spend nearly four times as much money interacting with payers.

PubMed

Zimmerman, Christina

2011-11-01

(1) In Canadian office practices, physi­cians spent 2.2 hours per week interacting with payers, nurses spent 2.5 hours, and clerical staff spent 15.9 hours. In U.S. practices, physicians spent 3.4 hours per week interacting with payers, nurses spent 20.6 hours, and clerical staff spent 53.1 hours. (2) Canadian physician practices spent $22,205 per physician per year on interactions with health plans. U.S. physician practices spent $82,975 per physician per year. (3) U.S. physician practices spend $60,770 per physician per year more (approximately four times as much) than their Canadian counterparts.

Sepsis: the LightCycler SeptiFast Test MGRADE®, SepsiTest™ and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi - a systematic review and economic evaluation.

PubMed

Stevenson, Matt; Pandor, Abdullah; Martyn-St James, Marrissa; Rafia, Rachid; Uttley, Lesley; Stevens, John; Sanderson, Jean; Wong, Ruth; Perkins, Gavin D; McMullan, Ronan; Dark, Paul

2016-06-01

Sepsis can lead to multiple organ failure and death. Timely and appropriate treatment can reduce in-hospital mortality and morbidity. To determine the clinical effectiveness and cost-effectiveness of three tests [LightCycler SeptiFast Test MGRADE(®) (Roche Diagnostics, Risch-Rotkreuz, Switzerland); SepsiTest(TM) (Molzym Molecular Diagnostics, Bremen, Germany); and the IRIDICA BAC BSI assay (Abbott Diagnostics, Lake Forest, IL, USA)] for the rapid identification of bloodstream bacteria and fungi in patients with suspected sepsis compared with standard practice (blood culture with or without matrix-absorbed laser desorption/ionisation time-of-flight mass spectrometry). Thirteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from January 2006 to May 2015 and supplemented by hand-searching relevant articles. A systematic review and meta-analysis of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. A decision tree was used to estimate the costs and quality-adjusted life-years (QALYs) associated with each test; all other parameters were estimated from published sources. The model was populated with evidence from the systematic review or individual studies, if this was considered more appropriate (base case 1). In a secondary analysis, estimates (based on experience and opinion) from seven clinicians regarding the benefits of earlier test results were sought (base case 2). A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Scenario analyses were used to assess uncertainty. For the review of diagnostic test accuracy, 62 studies of varying methodological quality were included. A meta-analysis of 54 studies comparing SeptiFast with blood culture found that SeptiFast had an estimated summary specificity of 0.86 [95% credible interval (CrI) 0.84 to 0.89] and sensitivity of 0.65 (95% CrI 0.60 to 0.71). Four studies comparing SepsiTest with blood culture found that SepsiTest had an estimated summary specificity of 0.86 (95% CrI 0.78 to 0.92) and sensitivity of 0.48 (95% CrI 0.21 to 0.74), and four studies comparing IRIDICA with blood culture found that IRIDICA had an estimated summary specificity of 0.84 (95% CrI 0.71 to 0.92) and sensitivity of 0.81 (95% CrI 0.69 to 0.90). Owing to the deficiencies in study quality for all interventions, diagnostic accuracy data should be treated with caution. No randomised clinical trial evidence was identified that indicated that any of the tests significantly improved key patient outcomes, such as mortality or duration in an intensive care unit or hospital. Base case 1 estimated that none of the three tests provided a benefit to patients compared with standard practice and thus all tests were dominated. In contrast, in base case 2 it was estimated that all cost per QALY-gained values were below £20,000; the IRIDICA BAC BSI assay had the highest estimated incremental net benefit, but results from base case 2 should be treated with caution as these are not evidence based. Robust data to accurately assess the clinical effectiveness and cost-effectiveness of the interventions are currently unavailable. The clinical effectiveness and cost-effectiveness of the interventions cannot be reliably determined with the current evidence base. Appropriate studies, which allow information from the tests to be implemented in clinical practice, are required. This study is registered as PROSPERO CRD42015016724. The National Institute for Health Research Health Technology Assessment programme.

Exploring the Landscape of Diazabicyclooctane (DBO) Inhibition: Avibactam Inactivation of PER-2 β-Lactamase.

PubMed

Ruggiero, Melina; Papp-Wallace, Krisztina M; Taracila, Magdalena A; Mojica, Maria F; Bethel, Christopher R; Rudin, Susan D; Zeiser, Elise T; Gutkind, Gabriel; Bonomo, Robert A; Power, Pablo

2017-06-01

PER β-lactamases are an emerging family of extended-spectrum β-lactamases (ESBL) found in Gram-negative bacteria. PER β-lactamases are unique among class A enzymes as they possess an inverted omega (Ω) loop and extended B3 β-strand. These singular structural features are hypothesized to contribute to their hydrolytic profile against oxyimino-cephalosporins (e.g., cefotaxime and ceftazidime). Here, we tested the ability of avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor to inactivate PER-2. Interestingly, the PER-2 inhibition constants (i.e., k 2 / K = 2 × 10 3 ± 0.1 × 10 3 M -1 s -1 , where k 2 is the rate constant for acylation (carbamylation) and K is the equilibrium constant) that were obtained when AVI was tested were reminiscent of values observed testing the inhibition by AVI of class C and D β-lactamases (i.e., k 2 / K range of ≈10 3 M -1 s -1 ) and not class A β-lactamases (i.e., k 2 / K range, 10 4 to 10 5 M -1 s -1 ). Once AVI was bound, a stable complex with PER-2 was observed via mass spectrometry (e.g., 31,389 ± 3 atomic mass units [amu] → 31,604 ± 3 amu for 24 h). Molecular modeling of PER-2 with AVI showed that the carbonyl of AVI was located in the oxyanion hole of the β-lactamase and that the sulfate of AVI formed interactions with the β-lactam carboxylate binding site of the PER-2 β-lactamase (R220 and T237). However, hydrophobic patches near the PER-2 active site (by Ser70 and B3-B4 β-strands) were observed and may affect the binding of necessary catalytic water molecules, thus slowing acylation ( k 2 / K ) of AVI onto PER-2. Similar electrostatics and hydrophobicity of the active site were also observed between OXA-48 and PER-2, while CTX-M-15 was more hydrophilic. To demonstrate the ability of AVI to overcome the enhanced cephalosporinase activity of PER-2 β-lactamase, we tested different β-lactam-AVI combinations. By lowering MICs to ≤2 mg/liter, the ceftaroline-AVI combination could represent a favorable therapeutic option against Enterobacteriaceae expressing bla PER-2 Our studies define the inactivation of the PER-2 ESBL by AVI and suggest that the biophysical properties of the active site contribute to determining the efficiency of inactivation. Copyright © 2017 American Society for Microbiology.

Molecular characterization of Bacillus thuringiensis isolated from diverse habitats of India.

PubMed

Patel, Ketan D; Chudasama, Chaitanyasinh J; Ingle, Sanjay S

2012-08-01

Bacillus thuringiensis (Bt) strains were isolated from 94 samples from different geographical regions. Novel types of crystalline inclusion bodies were observed from some of the isolates. Crystalline inclusions of bipyramidal, spherical and cuboidal morphology were found produced by most of the isolates. Isolate GS12 showed crystal on one side of spore while isolate GM108 formed crystals on both termini of spore. Isolate GN31 produced large sized bipyramidal crystals. SDS-PAGE analysis of the spore crystal suspension showed major protein bands in the range of 29 and 140 kDa. Two new serovars of Bt viz. GS4 and GN24 having H3abce and H3ab serotype respectively were isolated. Toxicity comparable to the reference strain Bacillus thuringiensis subs. kurstaki (Btk) HD-1 was observed for the isolates GM20, GM17 and MP3 against larvae of Helicoverpa armigera. Some of the isolates harboring cry genes like cry1Ac and cry2 did not show any toxicity towards H. armigera while most of the isolates were harboring cry1, cry1Ac and cry2 gene. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Response to Infant Cry in Clinically Depressed and Non-Depressed Mothers

PubMed Central

Manian, Nanmathi; Truzzi, Anna; Bornstein, Marc H.

2017-01-01

Background Bowlby and Ainsworth hypothesized that maternal responsiveness is displayed in the context of infant distress. Depressed mothers are less responsive to infant distress vocalizations (cry) than non-depressed mothers. The present study focuses on acoustical components of infant cry that give rise to responsive caregiving in clinically depressed (n = 30) compared with non-depressed mothers (n = 30) in the natural setting of the home. Methods Analyses of infant and mother behaviors followed three paths: (1) tests of group differences in acoustic characteristics of infant cry, (2) tests of group differences of mothers’ behaviors during their infant’s crying, and (3) tree-based modeling to ascertain which variable(s) best predict maternal behaviors during infant cry. Results (1) Infants of depressed mothers cried as frequently and for equal durations as infants of non-depressed mothers; however, infants of depressed mothers cried with a higher fundamental frequency (f0) and in a more restricted range of f0. (2) Depressed mothers fed, rocked, and touched their crying infants less than non-depressed mothers, and depressed mothers were less responsive to their infants overall. (3) Novel tree-based analyses confirmed that depressed mothers engaged in less caregiving during their infants’ cry and indicated that depressed mothers responded only to cries at higher f0s and shorter durations. Older non-depressed mothers were the most interactive with infants. Conclusions Clinical depression affects maternal responsiveness during infant cry, leading to patterns of action that appear poorly attuned to infant needs. PMID:28046020

21 CFR 556.160 - Clopidol.

Code of Federal Regulations, 2010 CFR

2010-04-01

... part per million. (b) In chickens and turkeys: (1) 15 parts per million in uncooked liver and kidney... in uncooked kidney. (2) 1.5 parts per million in uncooked liver. (3) 0.2 part per million in uncooked...

21 CFR 556.160 - Clopidol.

Code of Federal Regulations, 2011 CFR

2011-04-01

... part per million. (b) In chickens and turkeys: (1) 15 parts per million in uncooked liver and kidney... in uncooked kidney. (2) 1.5 parts per million in uncooked liver. (3) 0.2 part per million in uncooked...

Toxicity and Binding Studies of Bacillus thuringiensis Cry1Ac, Cry1F, Cry1C, and Cry2A Proteins in the Soybean Pests Anticarsia gemmatalis and Chrysodeixis (Pseudoplusia) includens.

PubMed

Bel, Yolanda; Sheets, Joel J; Tan, Sek Yee; Narva, Kenneth E; Escriche, Baltasar

2017-06-01

Anticarsia gemmatalis (velvetbean caterpillar) and Chrysodeixis includens (soybean looper, formerly named Pseudoplusia includens ) are two important defoliating insects of soybeans. Both lepidopteran pests are controlled mainly with synthetic insecticides. Alternative control strategies, such as biopesticides based on the Bacillus thuringiensis (Bt) toxins or transgenic plants expressing Bt toxins, can be used and are increasingly being adopted. Studies on the insect susceptibilities and modes of action of the different Bt toxins are crucial to determine management strategies to control the pests and to delay outbreaks of insect resistance. In the present study, the susceptibilities of both soybean pests to the Bt toxins Cry1Ac, Cry1Fa, Cry1Ca, and Cry2Aa have been investigated. Bioassays performed in first-instar larvae showed that both insects are susceptible to all these toxins. Competition-binding studies carried out with Cry1Ac and Cry1Fa 125 -iodine labeled proteins demonstrated the presence of specific binding sites for both of them on the midgut brush border membrane vesicles (BBMVs) of both A. gemmatalis and C. includens Competition-binding experiments and specific-binding inhibition studies performed with selected sugars and lectins indicated that Cry1Ac and Cry1Fa share some, but not all, binding sites in the midguts of both insects. Also, the Cry1Ac- or Cry1Fa-binding sites were not shared with Cry1Ca or Cry2Aa in either soybean pest. This study contributes to the knowledge of Bt toxicity and midgut toxin binding sites in A. gemmatalis and C. includens and sheds light on the cross-resistance potential of Cry1Ac, Cry1Fa, Cry1Ca, and Cry2Aa Bt proteins as candidate proteins for Bt-pyramided crops. IMPORTANCE In the present study, the toxicity and the mode of action of the Bacillus thuringiensis (Bt) toxins Cry1Ac, Cry1Fa, Cry1Ca, and Cry2Aa in Anticarsia gemmatalis and Chrysodeixis includens (important defoliating pests of soybeans) have been investigated. These studies are crucial for determining management strategies for pest control. Bioassays showed that both insects were susceptible to the toxins. Competition-binding studies demonstrated the presence of Cry1Fa- and Cry1Ac-specific binding sites in the midguts of both pests. These results, together with the results from binding inhibition studies performed with sugars and lectins, indicated that Cry1Ac and Cry1Fa share some, but not all, binding sites, and that they were not shared with Cry1Ca or Cry2Aa in either soybean pest. This study contributes to the knowledge of Bt toxicity in A. gemmatalis and C. includens and sheds light on the cross-resistance potential of Cry1Ac, Cry1Fa, Cry1Ca, and Cry2Aa Bt proteins as candidate proteins for Bt-pyramided crops. Copyright © 2017 Bel et al.

Dominant resistance to Bt cotton and minor cross-resistance to Bt toxin Cry2Ab in cotton bollworm from China

PubMed Central

Jin, Lin; Wei, Yiyun; Zhang, Lei; Yang, Yihua; Tabashnik, Bruce E; Wu, Yidong

2013-01-01

Evolution of resistance by insect pests threatens the long-term benefits of transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt). Previous work has detected increases in the frequency of resistance to Bt toxin Cry1Ac in populations of cotton bollworm, Helicoverpa armigera, from northern China where Bt cotton producing Cry1Ac has been grown extensively for more than a decade. Confirming that trend, we report evidence from 2011 showing that the percentage of individuals resistant to a diagnostic concentration of Cry1Ac was significantly higher in two populations from different provinces of northern China (1.4% and 2.3%) compared with previously tested susceptible field populations (0%). We isolated two resistant strains: one from each of the two field-selected populations. Relative to a susceptible strain, the two strains had 460- and 1200-fold resistance to Cry1Ac, respectively. Both strains had dominant resistance to a diagnostic concentration of Cry1Ac in diet and to Bt cotton leaves containing Cry1Ac. Both strains had low, but significant cross-resistance to Cry2Ab (4.2- and 5.9-fold), which is used widely as the second toxin in two-toxin Bt cotton. Compared with resistance in other strains of H. armigera, the resistance in the two strains characterized here may be especially difficult to suppress. PMID:24478804

Transgenic rice expressing the cry2AX1 gene confers resistance to multiple lepidopteran pests.

PubMed

Chakraborty, M; Reddy, P Sairam; Mustafa, G; Rajesh, G; Narasu, V M Laxmi; Udayasuriyan, V; Rana, Debashis

2016-10-01

A chimeric Bacillus thuringiensis toxin (Bt) gene, cry2AX1was cloned in a bi-selectable marker free binary vector construct. The cry2AX1 gene, driven by the Chrysanthemum rbcS1 promoter, was introduced into JK1044R, the restorer line (Oryza sativa L. ssp. Indica) of a notified commercially grown rice hybrid in India, by Agrobacterium-mediated transformation. Its effect against two major lepidopteran insect pests viz., yellow stem borer (YSB) Scirpophaga incertulas, rice leaf folder (RLF) Cnaphalocrocis medinalis and one minor insect pest, oriental army worm (OAW) Mythimna separata was demonstrated through bioassays of transgenic rice plants under laboratory and greenhouse conditions. The rbcS1 promoter with chloroplast signal peptide was used to avoid Cry2AX1 protein expression in rice seed endosperm tissue. A total of 37 independent transformants were generated, of which after preliminary molecular characterization and YSB bioassay screening, five events were selected for their protein expression and bioefficacy against all three rice insect. One elite transgenic rice line, BtE15, was identified with Cry2AX1 expression ranging from 0.68 to 1.34 µg g(-1) leaf fresh weight and with 80-92 % levels of resistance against rice pests at the vegetative and reproductive stages. Increase in Cry2AX1 protein concentration was also observed with crop maturity. The Cry2AX1protein concentration in the de-husked seeds was negligible (as low as 2.7-3.6 ng g(-1)). These results indicate the potential application of cry2AX1 gene in rice for protection against YSB, RLF and OAW.

Mutagen Sensitivity, Apoptosis, and Polymorphism in DNA Repair as Measures of Prostate Cancer Risk

DTIC Science & Technology

2006-02-01

replacement, energy, or high-protein beverages such as Instant Breakfast, Ensure, Slimfast, Sustacal or others? NEVER (GO TO QUESTION 7) 1 time per...other noodles ? NEVER (GO TO QUESTION 61) 1–6 times per year 2 times per week 7–11 times per year 3–4 times per week 1 time per month 5...other noodles , how much did you usually eat? Less than 1 cup 1 to 3 cups More than 3 cups 60b. How often did you eat your pasta, spaghetti

A Novel Tenebrio molitor Cadherin Is a Functional Receptor for Bacillus thuringiensis Cry3Aa Toxin*

PubMed Central

Fabrick, Jeff; Oppert, Cris; Lorenzen, Marcé D.; Morris, Kaley; Oppert, Brenda; Jurat-Fuentes, Juan Luis

2009-01-01

Cry toxins produced by the bacterium Bacillus thuringiensis are effective biological insecticides. Cadherin-like proteins have been reported as functional Cry1A toxin receptors in Lepidoptera. Here we present data that demonstrate that a coleopteran cadherin is a functional Cry3Aa toxin receptor. The Cry3Aa receptor cadherin was cloned from Tenebrio molitor larval midgut mRNA, and the predicted protein, TmCad1, has domain structure and a putative toxin binding region similar to those in lepidopteran cadherin B. thuringiensis receptors. A peptide containing the putative toxin binding region from TmCad1 bound specifically to Cry3Aa and promoted the formation of Cry3Aa toxin oligomers, proposed to be mediators of toxicity in lepidopterans. Injection of TmCad1-specific double-stranded RNA into T. molitor larvae resulted in knockdown of the TmCad1 transcript and conferred resistance to Cry3Aa toxicity. These data demonstrate the functional role of TmCad1 as a Cry3Aa receptor in T. molitor and reveal similarities between the mode of action of Cry toxins in Lepidoptera and Coleoptera. PMID:19416969

Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events

PubMed Central

Khera, Rohan; Murad, Mohammad Hassan; Chandar, Apoorva K.; Dulai, Parambir S.; Wang, Zhen; Prokop, Larry J.; Loomba, Rohit; Camilleri, Michael; Singh, Siddharth

2017-01-01

IMPORTANCE Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. OBJECTIVE To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis. DATA SOURCES MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries. STUDY SELECTION Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration–approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo. DATA EXTRACTION AND SYNTHESIS Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria. MAIN OUTCOMES AND MEASURES Proportions of patients with at least 5%weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year. RESULTS Twenty-eight randomized clinical trials with 29018 patients (median age, 46 years; 74%women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23%of placebo participants had at least 5%weight loss vs 75%of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95%credible interval [CrI], 6.63–12.85; SUCRA, 0.95), 63%of participants taking liraglutide (OR, 5.54; 95%CrI, 4.16–7.78; SUCRA, 0.83), 55%taking naltrexone-bupropion (OR, 3.96; 95%CrI, 3.03–5.11; SUCRA, 0.60), 49%taking lorcaserin (OR, 3.10; 95%CrI, 2.38–4.05; SUCRA, 0.39), and 44%taking orlistat (OR, 2.70; 95%CrI, 2.34–3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year—phentermine-topiramate, 8.8 kg (95%CrI, −10.20 to −7.42 kg); liraglutide, 5.3 kg (95%CrI, −6.06 to −4.52 kg); naltrexone-bupropion, 5.0 kg (95%CrI, −5.94 to −3.96 kg); lorcaserin, 3.2 kg (95%CrI, −3.97 to −2.46 kg); and orlistat, 2.6 kg (95%CrI, −3.04 to −2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95%CrI, 2.11–4.23) and naltrexone-bupropion (OR, 2.64; 95%CrI, 2.10–3.35) were associated with the highest odds of adverse event–related treatment discontinuation. High attrition rates (30%–45%in all trials) were associated with lower confidence in estimates. CONCLUSIONS AND RELEVANCE Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5%weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5%weight loss. PMID:27299618

Network Meta-Analysis of the Efficacy of Acupuncture, Alpha-blockers and Antibiotics on Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Qin, Zongshi; Wu, Jiani; Tian, Jinhui; Zhou, Jing; Liu, Yali; Liu, Zhishun

2016-01-01

Alpha-blockers and antibiotics are most commonly used to treat chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in clinical practice. Currently, increasing evidence also suggests acupuncture as an effective strategy. This network meta-analysis intended to assess the comparative efficacy and safety of acupuncture, alpha-blockers and antibiotics for CP/CPPS. Twelve trials involving 1203 participants were included. Based on decreases in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, a network meta-analysis indicated that electro-acupuncture (standard mean difference [SMD]: 4.29; 95% credible interval [CrI], 1.96–6.65), acupuncture (SMD: 3.69; 95% CrI, 0.27–7.17), alpha-blockers (SMD: 1.85; 95% CrI, 1.07–2.64), antibiotics (SMD: 2.66; 95% CrI, 1.57–3.76), and dual therapy (SMD: 3.20; 95% CrI, 1.95–4.42) are superior to placebo in decreasing this score. Additionally, electro-acupuncture (SMD: 2.44; 95% CrI, 0.08–4.83) and dual therapy (SMD: 1.35; 95% CrI, 0.07–2.62) were more effective than alpha-blockers in decreasing the total NIH-CPSI total score. Other network meta-analyses did not show significant differences between interventions other placebo. The incidence of adverse events of acupuncture was relatively rare (5.4%) compared with placebo (17.1%), alpha-blockers (24.9%), antibiotics (31%) and dual therapy (48.6%). Overall, rank tests and safety analyses indicate that electro-acupuncture/acupuncture may be recommended for the treatment of CP/CPPS. PMID:27759111

The acute and temporary modulation of PERIOD genes by hydrocortisone in healthy subjects.

PubMed

Yurtsever, Türkan; Schilling, Thomas M; Kölsch, Monika; Turner, Jonathan D; Meyer, Jobst; Schächinger, Hartmut; Schote, Andrea B

2016-01-01

The physiological stress system and the circadian clock system communicate with each other at different signaling levels. The steroid hormone cortisol, the end-effector of the hypothalamus-pituitary-adrenal axis, is released in response to stress and acts as a mediator in circadian rhythms. We determined the effect of escalating cortisol doses on the expression of PERIOD genes (PER1, PER2 and PER3) in healthy subjects and analyzed whether the glucocorticoid receptor (GR) is involved in the cortisol-mediated PERIOD gene expression. Forty participants (50% males and 50% females) were randomly assigned to groups receiving a saline placebo solution or 3 mg, 6 mg, 12 mg and 24 mg of hydrocortisone. Blood was drawn every 15 min to measure quantitative gene expression of PER1, PER2 and PER3. A potential role of the GR was determined by an ex vivo study stimulating whole blood with hydrocortisone and RU486 (a GR antagonist). As a result, moderate doses of hydrocortisone produced an acute and temporary induction of PER1 and PER3 mRNA levels, whereas PER2 was not responsive to the hormone administration. The cortisol-dependent induction of PER1 was blocked by the GR antagonist in whole blood after treatment with hydrocortisone and RU486 ex vivo. In conclusion, acute pharmacological stress modulated the expression of PER1 and PER3 in whole blood temporarily in our short-term sampling design, suggesting that these circadian genes mediate stable molecular mechanisms in the periphery.

29 CFR 1926.54 - Nonionizing radiation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... above: (1) Direct staring: 1 micro-watt per square centimeter; (2) Incidental observing: 1 milliwatt per square centimeter; (3) Diffused reflected light: 21/2 watts per square centimeter. (k) Laser unit in... exposed to microwave power densities in excess of 10 milliwatts per square centimeter. ...

29 CFR 1926.54 - Nonionizing radiation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... above: (1) Direct staring: 1 micro-watt per square centimeter; (2) Incidental observing: 1 milliwatt per square centimeter; (3) Diffused reflected light: 21/2 watts per square centimeter. (k) Laser unit in... exposed to microwave power densities in excess of 10 milliwatts per square centimeter. ...

29 CFR 1926.54 - Nonionizing radiation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... above: (1) Direct staring: 1 micro-watt per square centimeter; (2) Incidental observing: 1 milliwatt per square centimeter; (3) Diffused reflected light: 21/2 watts per square centimeter. (k) Laser unit in... exposed to microwave power densities in excess of 10 milliwatts per square centimeter. ...

29 CFR 1926.54 - Nonionizing radiation.

Code of Federal Regulations, 2012 CFR

2012-07-01

... above: (1) Direct staring: 1 micro-watt per square centimeter; (2) Incidental observing: 1 milliwatt per square centimeter; (3) Diffused reflected light: 21/2 watts per square centimeter. (k) Laser unit in... exposed to microwave power densities in excess of 10 milliwatts per square centimeter. ...

A health economic evaluation of screening and treatment in patients with adolescent idiopathic scoliosis.

PubMed

Adobor, Raphael D; Joranger, Paal; Steen, Harald; Navrud, Ståle; Brox, Jens Ivar

2014-01-01

Adolescent idiopathic scoliosis can progress and affect the health related quality of life of the patients. Research shows that screening is effective in early detection, which allows for bracing and reduced surgical rates, and may save costs, but is still controversial from a health economic perspective. Model based cost minimisation analysis using hospital's costs, administrative data, and market prices to estimate costs in screening, bracing and surgical treatment. Uncertainty was characterised by deterministic and probabilistic sensitivity analyses. Time horizon was 6 years from first screening at 11 years of age. To compare estimated costs in screening and non-screening scenarios (reduced treatment rates of 90%, 80%, 70% of screening, and non-screening Norway 2012). Data was based on screening and treatment costs in primary health care and in hospital care settings. Participants were 4000, 12-year old children screened in Norway, 115190 children screened in Hong Kong and 112 children treated for scoliosis in Norway in 2012. We assumed equivalent outcome of health related quality of life, and compared only relative costs in screening and non-screening settings. Incremental cost was defined as positive when a non-screening scenario was more expensive relative to screening. Screening per child was € 8.4 (95% CrI 6.6 to10.6), € 10350 (8690 to 12180) per patient braced, and € 45880 (39040 to 55400) per child operated. Incremental cost per child in non-screening scenario of 90% treatment rate was € 13.3 (1 to 27), increasing from € 1.3 (-8 to 11) to € 27.6 (14 to 44) as surgical rates relative to bracing increased from 40% to 80%. For the 80% treatment rate non-screening scenario, incremental cost was € 5.5 (-6 to 18) when screening all, and € 11.3 (2 to 22) when screening girls only. For the non-screening Norwegian scenario, incremental cost per child was € -0.1(-14 to 16). Bracing and surgery were the main cost drivers and contributed most to uncertainty. With the assumptions applied in the present study, screening is cost saving when performed in girls only, and when it leads to reduced treatment rates. Cost of surgery was dominating in non-screening whilst cost of bracing was dominating in screening. The economic gain of screening increases when it leads to higher rates of bracing and reduced surgical rates.

Toxin Gene Contents and Activity of Bacillus thuringiensis Strains Against Two Sugarcane Borer Species, Diatraea saccharalis (F.) and D. flavipennella (Box).

PubMed

Silva, L M; Silva, M C; Silva, S M F A; Alves, R C; Siqueira, H A A; Marques, E J

2018-04-01

Bacillus thuringiensis (Berliner) bears essential characteristics in the control of insect pests, such as its unique mode of action, which confers specificity and selectivity. This study assessed cry gene contents from Bt strains and their entomotoxicity against Diatraea saccharalis (F.) and Diatraea flavipennella (Box) (Lepidoptera: Crambidae). Bioassays with Bt strains were performed against neonates to evaluate their lethal and sublethal activities and were further analyzed by PCR, using primers to identify toxin genes. For D. saccharalis and D. flavipennella, 16 and 18 strains showed over 30% larval mortality in the 7th day, respectively. The LC 50 values of strains for D. saccharalis varied from 0.08 × 10 5 (LIIT-0105) to 4104 × 10 5 (LIIT-2707) spores + crystals mL -1 . For D. flavipennella, the LC 50 values of strains varied from 0.40 × 10 5 (LIIT-2707) to 542 × 10 5 (LIIT-2109) spores + crystals mL -1 . For the LIIT-0105 strain, which was the most toxic to D. saccharalis, the genes cry1Aa, cry1Ab, cry1Ac, cry1B, cry1C, cry1D, cry1F, cry1I, cry2Aa, cry2Ab, cry8, and cry9C were detected, whereas for the strain LIIT-2707, which was the most toxic to D. flavipennella, detected genes were cry1Aa, cry1Ab, cry1Ac, cry1B, cry1D, cry1F, cry1I, cry2Aa, cry2Ab, and cry9. The toxicity data and toxin gene content in these strains of Bt suggest a great variability of activity with potential to be used in the development of novel biopesticides or as source of resistance genes that can be expressed in plants to control pests.

A Western Corn Rootworm Cadherin-like Protein is not Involved in the Binding and Toxicity of Cry34/35Ab1 and Cry3Aa Bacillus Thuringiensis Proteins

USDA-ARS?s Scientific Manuscript database

The western corn rootworm (WCR) Diabrotica virgifera virgifera LeConte is an important insect pest of corn. Bacillus thuringiensis (Bt) insecticidal proteins Cry3Aa (as mCry3A) and Cry34Ab1/Cry35Ab1 have been expressed in transgenic corn and are used to control the insect in the U.S. To date, there ...

Environmental Assessment: Convert Slow Routes 300 and 301 to Instrument Routes

DTIC Science & Technology

2007-07-01

in the number of eggs, nestlings , or successful fledglings per nest. Table 4-3 summarizes the success and productivity results from the study. Table...Average eggs per nest 3.47 3.56 Average nestlings per nest 2.27 2.28 Average young/occupied per nest 1.84 1.80 Average young/successful per nest...Gardnervi ll e, State of Nevada, and that the annexed is a full, true and correct copy of # 921278 attached advertisement . Public Meeting - Proposed

Decreased health care utilization and health care costs in the inpatient and emergency department setting following initiation of ketogenic diet in pediatric patients: The experience in Ontario, Canada.

PubMed

Whiting, Sharon; Donner, Elizabeth; RamachandranNair, Rajesh; Grabowski, Jennifer; Jetté, Nathalie; Duque, Daniel Rodriguez

2017-03-01

To assess the change in inpatient and emergency department utilization and health care costs in children on the ketogenic diet for treatment of epilepsy. Data on children with epilepsy initiated on the ketogenic diet (KD) Jan 1, 2000 and Dec 31, 2010 at Ontario pediatric hospitals were linked to province wide inpatient, emergency department (ED) data at the Institute for Clinical Evaluative Sciences. ED and inpatient visits and costs for this cohort were compared for a maximum of 2 years (730days) prior to diet initiation and for a maximum of 2 years (730days) following diet initiation. KD patient were compared to matched group of children with epilepsy who did not receive the ketogenic diet (no KD). Children on the KD experienced a mean decrease in ED visits of 2.5 visits per person per year [95% CI (1.5-3.4)], and a mean decrease of 0.8 inpatient visits per person per year [95% CI (0.3-1.3)], following diet initiation. They had a mean decrease in ED costs of $630 [95% CI (249-1012)] per person per year and a median decrease in inpatient costs of $1059 [IQR: 7890; p<0.001] per child per year. Compared with the no KD children, children on the diet experienced a mean reduction of 2.1 ED visits per child per year [95% CI (1.0-3.2)] and a mean decrease of 0.6 [95% CI (0.1-1.1)] inpatient visits per child per year. Patients on the KD experienced a reduction of $442 [95% CI (34.4-850)] per child per year more in ED costs than the matched group. The ketogenic diet group had greater median decrease in inpatient costs per child per year than the matched group [p<0.001]. Patients initiated on ketogenic diet, experienced decreased ED and inpatient visits as well as costs following diet initiation in Ontario, Canada. Copyright © 2017 Elsevier B.V. All rights reserved.

PxAPN5 serves as a functional receptor of Cry2Ab in Plutella xylostella (L.) and its binding domain analysis.

PubMed

Pan, Zhi-Zhen; Xu, Lian; Liu, Bo; Zhang, Jing; Chen, Zheng; Chen, Qing-Xi; Zhu, Yu-Jing

2017-12-01

Lepidopteran midgut aminopeptidases N (APNs) are widely studied for their potential roles as one of the receptors for Bacillus thuringiensis (Bt) crystal toxins. In the present study, a loss of function analyses by RNAi (RNA interference) silencing of the Plutella xylostella APN5 (PxAPN5), a binding protein of Bt crystal toxin Cry2Ab, were performed. The knocking down of PxAPN5 in P. xylostella larvae greatly reduced their susceptibility to Cry2Ab and led to a decrease of Cry2Ab binding to P. xylostella midgut. Four truncated fragments of PxAPN5 were further constructed and expressed in Escherichia coli (E.coli) to find the binding region of PxAPN5 to Cry2Ab. The ligand blot result indicated that D1 domain (residues 1-262) and D3 domain (residues 510-620) of PxAPN5 could specially bind to Cry2Ab. Copyright © 2017 Elsevier B.V. All rights reserved.

Non Target Effect of Cry1 Ab and Cry Ab x Cry3 Bb1 Bt Transgenic Maize on Orius Insidiosus (Hemiptera: Anthocoridae) Abundance

USDA-ARS?s Scientific Manuscript database

Non-target effects of Cry1Ab x CP4 EPSPS and Cry1Ab + Cry3Bb1 x CP4 EPSPS Bt transgenic new maize hybrids on insidious flower bugs [Orius insidiosus (Say)] was studied in Nebraska (Mead, C lay Center, and Concord) during 2007 and 2008. The Bt effect was compared to CP4 EPSPS maize (isoline), convent...

Antimicrobial resistance and phylogenetic groups in isolates of Escherichia coli from seagulls at the Berlengas nature reserve.

PubMed

Radhouani, H; Poeta, P; Igrejas, G; Gonçalves, A; Vinué, L; Torres, C

2009-08-01

Fifty-three faecal samples from yellow-legged gulls (Larus cachinnans) at the Berlengas nature reserve in Portugal were cultured on Levine agar plates not supplemented with antimicrobial agents, and one Escherichia coli colony was isolated and identified from each sample. The percentages of resistant isolates for each of the drugs were ampicillin (43.4 per cent), tetracycline (39.6 per cent), nalidixic acid (34.0 per cent), streptomycin (32.1 per cent), trimethoprim-sulfamethoxazole (SXT) (26.4 per cent), ciprofloxacin (18.9 per cent), chloramphenicol (18.9 per cent), gentamicin (7.5 per cent), tobramycin (7.5 per cent) amikacin (5.7 per cent) and amoxicillin-clavulanic acid (1.9 per cent). All the isolates were susceptible to cefoxitin, ceftazidime, cefotaxime, aztreonam and imipenem. The following resistance genes were detected: bla(TEM) (17 of 23 ampicillin-resistant isolates), tet(A) and/or tet(B) (18 of 21 tetracycline-resistant isolates), aadA (12 of 17 streptomycin-resistant isolates), cmlA (all chloramphenicol-resistant isolates), aac(3)-II with or without aac(3)-IV (all four gentamicin-resistant isolates), and sul1 and/or sul2 and/or sul3 (all 14 SXT-resistant isolates). The intI1 gene was detected in 10 of 14 SXT-resistant isolates, and three of them also contained class 2 integrons; four different gene cassette arrangements were identified among class 1 integrons (aadA, dfrA1+aadA1, dfrA12+orfF+aadA2 and sat+psp+aadA2) and one among the class 2 integrons (dfrA1+sat+aadA1). Ninety per cent of the isolates were included in the A or B1 phylogenetic groups.

Identification of Cha o 3 homolog Cry j 4 from Cryptomeria japonica (Japanese cedar) pollen: Limitation of the present Japanese cedar-specific ASIT.

PubMed

Osada, Toshihiro; Tanaka, Yuki; Yamada, Akira; Sasaki, Eiji; Utsugi, Teruhiro

2018-03-07

About one-third of the Japanese population suffers from Japanese cedar pollinosis, which is frequently accompanied by Japanese cypress pollinosis. Recently, a novel major Japanese cypress pollen allergen, Cha o 3, was discovered. However, whether a Cha o 3 homolog is present in Japanese cedar pollen remains to be determined. Western blot analysis was performed using Cha o 3-specific antiserum. In addition, cloning of the gene encoding Cry j 4 was conducted using total cDNA from the male flower of Japanese cedar trees. Allergen potency and cross-reactivity were investigated using a T-cell proliferation assay, basophil activation test, and ImmunoCAP inhibition assay. A low amount of Cha o 3 homolog protein was detected in Japanese cedar pollen extract. The deduced amino acid sequence of Cry j 4 showed 84% identity to that of Cha o 3. Cross-reactivity between Cry j 4 and Cha o 3 was observed at the T cell and IgE levels. Cry j 4 was discovered as a counterpart allergen of Cha o 3 in Japanese cedar pollen, with a relationship similar to that between Cry j 1-Cha o 1 and Cry j 2-Cha o 2. Our findings also suggest that allergen-specific immunotherapy (ASIT) using Japanese cedar pollen extract does not induce adequate immune tolerance to Cha o 3 due to the low amount of Cry j 4 in Japanese cedar pollen. Therefore, ASIT using Cha o 3 or cypress pollen extract coupled with Japanese cedar pollen extract is required in order to optimally control allergy symptoms during Japanese cypress pollen season. Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

A Comprehensive Evaluation of a Novel Color Range Indicator in Multiple Blood Glucose Meters Demonstrates Improved Glucose Range Interpretation and Awareness in Subjects With Type 1 and Type 2 Diabetes.

PubMed

Grady, Mike; Katz, Laurence B; Cameron, Hilary; Levy, Brian L

2016-11-01

We previously demonstrated that people with type 2 diabetes (T2DM) can improve their ability to categorize blood glucose (BG) results into low, in range, or high glycemic ranges after experiencing a color range indicator (CRI or ColorSure™ Technology) in a single meter. This study examined whether a CRI was effective in people with type 1 (T1) or T2DM when used in 3 glucose meters. A total of 179 subjects (139 T2DM and 40 T1DM) classified BG values as low, in range, or high based on individual current knowledge. Subjects then experienced the CRI which showed whether different BG values were low, in range, or high. After CRI interaction, subjects repeated the classification. Following interaction with the CRI, subjects significantly improved their ability to categorize BG results into low, in range, and high glycemic ranges by 27.9% (T2DM) and 27.2% (T1DM) (each P < .001). Improvement was not accompanied by an increase in time spent categorizing results. There was no difference in classification ability between subjects with T1 or T2DM. There was also no correlation between HbA1c, numeracy level, test frequency, or duration of diabetes and the ability to correctly classify results. Subjects agreed the CRI feature helped them easily interpret glucose values and improved their awareness of glucose ranges. Interaction with a CRI improved the ability of subjects with T1 and T2DM to interpret and categorize BG values into recommended glycemic ranges, irrespective of the glucose meter providing the CRI insights. © 2016 Diabetes Technology Society.

Chilo suppressalis and Sesamia inferens display different susceptibility responses to Cry1A insecticidal proteins.

PubMed

Li, Bo; Xu, Yangyang; Han, Cao; Han, Lanzhi; Hou, Maolin; Peng, Yufa

2015-10-01

Chilo suppressalis and Sesamia inferens are important lepidopteran rice pests that occur concurrently in rice-growing areas of China. The development of transgenic rice expressing Cry1A insecticidal proteins has provided a useful strategy for controlling these pests. This study evaluated the baseline susceptibilities of C. suppressalis and S. inferens to Cry1A, as well as their responses to selection with Cry1A. Wide geographic variation in susceptibility was observed across all field populations. Within a given population, the LC50 of both Cry1Ab and Cry1Ac against S. inferens was drastically higher than that of C. suppressalis. Large LC50 differences (74.6-fold) were detected between the two species for Cry1Ab in the Poyang population, while small differences (3.6-fold) were detected for Cry1Ac in the Changsha population. The Cry1Ac LC50 of C. suppressalis and S. inferens increased 8.4- and 4.4-fold after 21 and eight selection generations respectively. Additionally, the estimated realised heritabilities (h(2) ) of Cry1Ac tolerance were 0.11 in C. suppressalis and 0.292 in S. inferens. S. inferens exhibited a significantly lower susceptibility and more rapidly evolved resistance to Cry1A compared with C. suppressalis. Therefore, S. inferens is more likely to evolve increased resistance, which threatens the sustainability of rice expressing Cry1A protein. © 2014 Society of Chemical Industry.

AuBr3-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars.

PubMed

Rajput, Jayashree; Hotha, Srinivas; Vangala, Madhuri

2018-01-01

Herein we report, for the first time, the successful anomeric azidation of per- O -acetylated and per- O -benzoylated sugars by catalytic amounts of oxophilic AuBr 3 in good to excellent yields. The method is applicable to a wide range of easily accessible per- O -acetylated and per- O -benzoylated sugars. While reaction with per- O -acetylated and per- O -benzoylated monosaccharides was complete within 1-3 h at room temperature, the per- O -benzoylated disaccharides needed 2-3 h of heating at 55 °C.

42 CFR 84.104 - Gas tightness test; minimum requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 1 1 Walks at 4.8 km. (3 miles) per hour 2 8 10 Pulls 20 kg. (45 pound) weight to 5 feet 30 times in... times respectively. Walks at 4.8 km. (3 miles) per hour 3 5 3 4 8 12 18 Sampling and readings 2 2 2 2 2 Walks at 4.8 km. (3 miles) per hour 3 5 8 12 18 Sampling and readings 2 2 2 2 2 Walks at 4.8 km. (3...

42 CFR 84.104 - Gas tightness test; minimum requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 1 1 Walks at 4.8 km. (3 miles) per hour 2 8 10 Pulls 20 kg. (45 pound) weight to 5 feet 30 times in... times respectively. Walks at 4.8 km. (3 miles) per hour 3 5 3 4 8 12 18 Sampling and readings 2 2 2 2 2 Walks at 4.8 km. (3 miles) per hour 3 5 8 12 18 Sampling and readings 2 2 2 2 2 Walks at 4.8 km. (3...

42 CFR 84.104 - Gas tightness test; minimum requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 1 1 Walks at 4.8 km. (3 miles) per hour 2 8 10 Pulls 20 kg. (45 pound) weight to 5 feet 30 times in... times respectively. Walks at 4.8 km. (3 miles) per hour 3 5 3 4 8 12 18 Sampling and readings 2 2 2 2 2 Walks at 4.8 km. (3 miles) per hour 3 5 8 12 18 Sampling and readings 2 2 2 2 2 Walks at 4.8 km. (3...

Cry1F Resistance in Fall Armyworm Spodoptera frugiperda: Single Gene versus Pyramided Bt Maize

PubMed Central

Huang, Fangneng; Qureshi, Jawwad A.; Meagher, Robert L.; Reisig, Dominic D.; Head, Graham P.; Andow, David A.; Ni, Xinzi; Kerns, David; Buntin, G. David; Niu, Ying; Yang, Fei; Dangal, Vikash

2014-01-01

Evolution of insect resistance to transgenic crops containing Bacillus thuringiensis (Bt) genes is a serious threat to the sustainability of this technology. However, field resistance related to the reduced efficacy of Bt maize has not been documented in any lepidopteran pest in the mainland U.S. after 18 years of intensive Bt maize planting. Here we report compelling evidence of field resistance in the fall armyworm, Spodoptera frugiperda (J.E. Smith), to Cry1F maize (TC 3507) in the southeastern region of the U.S. An F2 screen showed a surprisingly high (0.293) Cry1F resistance allele frequency in a population collected in 2011 from non-Bt maize in south Florida. Field populations from non-Bt maize in 2012–2013 exhibited 18.8-fold to >85.4-fold resistance to purified Cry1F protein and those collected from unexpectedly damaged Bt maize plants at several locations in Florida and North Carolina had >85.4-fold resistance. In addition, reduced efficacy and control failure of Cry1F maize against natural populations of S. frugiperda were documented in field trials using Cry1F-based and pyramided Bt maize products in south Florida. The Cry1F-resistant S. frugiperda also showed a low level of cross-resistance to Cry1A.105 and related maize products, but not to Cry2Ab2 or Vip3A. The occurrence of Cry1F resistance in the U.S. mainland populations of S. frugiperda likely represents migration of insects from Puerto Rico, indicating the great challenges faced in achieving effective resistance management for long-distance migratory pests like S. frugiperda. PMID:25401494

Cry1F resistance in fall armyworm Spodoptera frugiperda: single gene versus pyramided Bt maize.

PubMed

Huang, Fangneng; Qureshi, Jawwad A; Meagher, Robert L; Reisig, Dominic D; Head, Graham P; Andow, David A; Ni, Xinzi; Kerns, David; Buntin, G David; Niu, Ying; Yang, Fei; Dangal, Vikash

2014-01-01

Evolution of insect resistance to transgenic crops containing Bacillus thuringiensis (Bt) genes is a serious threat to the sustainability of this technology. However, field resistance related to the reduced efficacy of Bt maize has not been documented in any lepidopteran pest in the mainland U.S. after 18 years of intensive Bt maize planting. Here we report compelling evidence of field resistance in the fall armyworm, Spodoptera frugiperda (J.E. Smith), to Cry1F maize (TC 3507) in the southeastern region of the U.S. An F2 screen showed a surprisingly high (0.293) Cry1F resistance allele frequency in a population collected in 2011 from non-Bt maize in south Florida. Field populations from non-Bt maize in 2012-2013 exhibited 18.8-fold to >85.4-fold resistance to purified Cry1F protein and those collected from unexpectedly damaged Bt maize plants at several locations in Florida and North Carolina had >85.4-fold resistance. In addition, reduced efficacy and control failure of Cry1F maize against natural populations of S. frugiperda were documented in field trials using Cry1F-based and pyramided Bt maize products in south Florida. The Cry1F-resistant S. frugiperda also showed a low level of cross-resistance to Cry1A.105 and related maize products, but not to Cry2Ab2 or Vip3A. The occurrence of Cry1F resistance in the U.S. mainland populations of S. frugiperda likely represents migration of insects from Puerto Rico, indicating the great challenges faced in achieving effective resistance management for long-distance migratory pests like S. frugiperda.

Psychotherapy for Major Depressive Disorder and Generalized Anxiety Disorder: A Health Technology Assessment

PubMed Central

McMartin, Kristen; Gajic-Veljanoski, Olga; Wells, David; Higgins, Caroline; Walter, Melissa

2017-01-01

Background Major depressive disorder and generalized anxiety disorder are among the most commonly diagnosed mental illnesses in Canada; both are associated with a high societal and economic burden. Treatment for major depressive disorder and generalized anxiety disorder consists of pharmacological and psychological interventions. Three commonly used psychological interventions are cognitive behavioural therapy (CBT), interpersonal therapy, and supportive therapy. The objectives of this report were to assess the effectiveness and safety of these types of therapy for the treatment of adults with major depressive disorder and/or generalized anxiety disorder, to assess the cost-effectiveness of structured psychotherapy (CBT or interpersonal therapy), to calculate the budget impact of publicly funding structured psychotherapy, and to gain a greater understanding of the experiences of people with major depressive disorder and/or generalized anxiety disorder. Methods We performed a literature search on October 27, 2016, for systematic reviews that compared CBT, interpersonal therapy, or supportive therapy with usual care, waitlist control, or pharmacotherapy in adult outpatients with major depressive disorder and/or generalized anxiety disorder. We developed an individual-level state-transition probabilistic model for a cohort of adult outpatients aged 18 to 75 years with a primary diagnosis of major depressive disorder to determine the cost-effectiveness of individual or group CBT (as a representative form of structured psychotherapy) versus usual care. We also estimated the 5-year budget impact of publicly funding structured psychotherapy in Ontario. Finally, we interviewed people with major depressive disorder and/or generalized anxiety disorder to better understand the impact of their condition on their daily lives and their experience with different treatment options, including psychotherapy. Results Interpersonal therapy compared with usual care reduced posttreatment major depressive disorder scores (standardized mean difference [SMD]: 0.24, 95% confidence interval [CI]: −0.47 to −0.02) and reduced relapse/recurrence in patients with major depressive disorder (relative risk [RR]: 0.41, 95% CI: 0.27–0.63). Supportive therapy compared with usual care improved major depressive disorder scores (SMD: 0.58, 95% CI: 0.45–0.72) and increased posttreatment recovery (odds ratio [OR]: 2.71, 95% CI: 1.19–6.16) in patients with major depressive disorder. CBT compared with usual care increased response (OR: 1.58, 95% CI: 1.11–2.26) and recovery (OR: 3.42, 95% CI: 1.98–5.93) in patients with major depressive disorder and decreased relapse/recurrence (RR: 0.68, 95% CI: 0.65–0.87]). For patients with generalized anxiety disorder, CBT improved symptoms posttreatment (SMD: 0.80, 95% CI: 0.67–0.93), improved clinical response posttreatment (RR: 0.64, 95% CI: 0.55–0.74), and improved quality-of-life scores (SMD: 0.44, 95% CI: 0.06–0.82). There was a significant difference in posttreatment recovery (OR: 1.98, 95% CI: 1.11–3.54) and mean major depressive disorder symptom scores (weighted mean difference: −3.07, 95% CI: −4.69 to −1.45) for patients who received individual versus group CBT. Details about the providers of psychotherapy were rarely reported in the systematic reviews we examined. In the base case probabilistic cost–utility analysis, compared with usual care, both group and individual CBT were associated with increased survival: 0.11 quality-adjusted life-years (QALYs) (95% credible interval [CrI]: 0.03–0.22) and 0.12 QALYs (95% CrI: 0.03–0.25), respectively. Group CBT provided by nonphysicians was associated with the smallest increase in discounted costs: $401 (95% CrI: $1,177 to 1,665). Group CBT provided by physicians, individual CBT provided by nonphysicians, and individual CBT provided by physicians were associated with the incremental costs of $1,805 (95% CrI: 65–3,516), $3,168 (95% CrI: 889–5,624), and $5,311 (95% CrI: 2,539–8,938), respectively. The corresponding incremental cost-effectiveness ratio (ICER) was lowest for group CBT provided by nonphysicians ($3,715/QALY gained) and highest for individual CBT provided by physicians ($43,443/QALY gained). In the analysis that ranked best strategies, individual CBT versus group CBT provided by nonphysicians yielded an ICER of $192,618 per QALY. The probability of group CBT provided by nonphysicians being cost-effective versus usual care was greater than 95% for all willingness-to-pay thresholds over $20,000 per QALY and was around 88% for individual CBT provided by physicians at a threshold of $100,000 per QALY. We estimated that adding structured psychotherapy to usual care over the next 5 years would result in a net budget impact of $68 million to $529 million, depending on a range of factors. We also estimated that to provide structured psychotherapy to all adults with major depressive disorder (alone or combined with generalized anxiety disorder) in Ontario by 2021, an estimated 500 therapists would be needed to provide group therapy, and 2,934 therapists would be needed to provide individual therapy. People with major depressive disorder and/or generalized anxiety disorder with whom we spoke reported finding psychotherapy effective, but they also reported experiencing a large number of barriers that prevented them from finding effective psychotherapy in a timely manner. Participants reported wanting more freedom to choose the type of psychotherapy they received. Conclusions Compared with usual care, treatment with CBT, interpersonal therapy, or supportive therapy significantly reduces depression symptoms posttreatment. CBT significantly reduces anxiety symptoms posttreatment in patients with generalized anxiety disorder. Compared with usual care, treatment with structured psychotherapy (CBT or interpersonal therapy) represents good value for money for adults with major depressive disorder and/or generalized anxiety disorder. The most affordable option is group structured psychotherapy provided by nonphysicians, with the selective use of individual structured psychotherapy provided by nonphysicians or physicians for those who would benefit most from it (i.e., patients who are not engaging well with or adhering to group therapy). PMID:29213344

Effects of fructo-oligosaccharide-supplemented infant cereal: a double-blind, randomized trial.

PubMed

Moore, Nancy; Chao, Cewin; Yang, Li-Ping; Storm, Heidi; Oliva-Hemker, Maria; Saavedra, Jose M

2003-09-01

Fructo-oligosaccharides (FOS) may have potential benefits, since they exhibit many soluble dietary fibre-like properties. Foods currently available for weaning infants are generally low in fibre content and lack these potential benefits. Data documenting tolerance of FOS in weaning foods are greatly lacking. Our present objective was to evaluate the tolerance and gastrointestinal effects of FOS-supplemented infant cereal used as a daily addition to the diet of healthy infants. Healthy infants were randomly assigned to receive either 0.75 g FOS per serving of cereal or placebo for 28 d. The primary outcome of interest was gastrointestinal tolerance, which was assessed by daily parental reporting of functional variables for 28 d, including stool patterns and signs and symptoms of gastrointestinal tolerance. Secondary outcomes were also measured including: cereal intake (g cereal and g FOS/d), stool pH, changes in anthropometric measurements and adverse events. The study population included a total of fifty-six infants, age range 16.2-46.2 weeks with a mean age of 32.5 (sd 8.9) weeks; twenty-nine infants were randomized to the control group (age 31.8 (sd 9.0) weeks) and twenty-seven to the FOS-supplemented group (34.7 (sd 8.9) weeks). Average daily total intake per infant and average intake per serving were similar in both groups. Average FOS consumption was 0.74 (sd 0.39) g/d and as high as 3.00 g/d. Stool consistency was less likely to be described as 'hard', and more likely to be described as 'soft' or 'loose', in the FOS v. control group. The mean number of stools per infant was 1.99 (sd 0.62) per d in the FOS-supplemented group compared with 1.58 (sd 0.66) in the control group (P=0.02). There were no differences between the groups in reporting for crying, spitting-up or colic. No differences were found for stool pH. FOS-supplements added to cereal were well tolerated in doses of up to 3.00 g/d. FOS consumption led to more regular and softer stools, without diarrhoea, as well as less-reported frequency of symptoms associated with constipation such as hard stools or skipped days without stool. The present study is one of few studies documenting tolerance to increased fibre intake in the form of FOS as part of a weaning food.

Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking

PubMed Central

Gorenz, Annika; Shaikh, Maliha; Desai, Vishal; Kaminsky, Thomas; Van Den Berg, Jolice; Murphy, Terrence; Raeisi, Shohreh; Fogg, Louis; Vitaterna, Martha Hotz; Forsyth, Christopher; Turek, Fred; Burgess, Helen J.; Keshavarzian, Ali

2016-01-01

Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20–30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption. PMID:27198191

40 CFR Table 2 to Subpart Ffff of... - Model Rule-Emission Limitations

Code of Federal Regulations, 2011 CFR

2011-07-01

... micrograms per dry standard cubic meter 3-run average (1 hour minimum sample time per run) Method 29 of appendix A of this part. 2. Carbon monoxide 40 parts per million by dry volume 3-run average (1 hour minimum sample time per run during performance test), and 12-hour rolling averages measured using CEMS b...

40 CFR Table 2 to Subpart Ffff of... - Model Rule-Emission Limitations

Code of Federal Regulations, 2010 CFR

2010-07-01

... micrograms per dry standard cubic meter 3-run average (1 hour minimum sample time per run) Method 29 of appendix A of this part. 2. Carbon monoxide 40 parts per million by dry volume 3-run average (1 hour minimum sample time per run during performance test), and 12-hour rolling averages measured using CEMS b...

40 CFR Table 2 to Subpart Dddd of... - Model Rule-Emission Limitations

Code of Federal Regulations, 2011 CFR

2011-07-01

... this part) Carbon monoxide 157 parts per million by dry volume 3-run average (1 hour minimum sample... per million by dry volume 3-run average (1 hour minimum sample time per run) Performance test (Method... appendix A of this part) Oxides of nitrogen 388 parts per million by dry volume 3-run average (1 hour...

IgE-dependent activation of human mast cells and fMLP-mediated activation of human eosinophils is controlled by the circadian clock.

PubMed

Baumann, Anja; Feilhauer, Katharina; Bischoff, Stephan C; Froy, Oren; Lorentz, Axel

2015-03-01

Symptoms of allergic attacks frequently exhibit diurnal variations. Accordingly, we could recently demonstrate that mast cells and eosinophils - known as major effector cells of allergic diseases - showed an intact circadian clock. Here, we analyzed the role of the circadian clock in the functionality of mast cells and eosinophils. Human intestinal mast cells (hiMC) were isolated from intestinal mucosa; human eosinophils were isolated from peripheral blood. HiMC and eosinophils were synchronized by dexamethasone before stimulation every 4h around the circadian cycle by FcɛRI crosslinking or fMLP, respectively. Signaling molecule activation was examined using Western blot, mRNA expression by real-time RT-PCR, and mediator release by multiplex analysis. CXCL8 and CCL2 were expressed and released in a circadian manner by both hiMC and eosinophils in response to activation. Moreover, phosphorylation of ERK1/2, known to be involved in activation of hiMC and eosinophils, showed circadian rhythms in both cell types. Interestingly, all clock genes hPer1, hPer2, hCry1, hBmal1, and hClock were expressed in a similar circadian pattern in activated and unstimulated cells indicating that the local clock controls hiMC and eosinophils and subsequently allergic reactions but not vice versa. Copyright © 2014 Elsevier Ltd. All rights reserved.

40 CFR Table 1 to Subpart Eeee of... - Emission Limitations

Code of Federal Regulations, 2011 CFR

2011-07-01

... determiningcompliance using this method 1. Cadmium 18 micrograms per dry standard cubic meter 3-run average (1 hour minimum sample time per run) Method 29 of appendix A of this part. 2. Carbon monoxide 40 parts per million by dry volume 3-run average (1 hour minimum sample time per run during performance test), and 12-hour...

40 CFR Table 1 to Subpart Eeee of... - Emission Limitations

Code of Federal Regulations, 2010 CFR

2010-07-01

... determiningcompliance using this method 1. Cadmium 18 micrograms per dry standard cubic meter 3-run average (1 hour minimum sample time per run) Method 29 of appendix A of this part. 2. Carbon monoxide 40 parts per million by dry volume 3-run average (1 hour minimum sample time per run during performance test), and 12-hour...

Use of Bt-resistant caterpillars to assess the effect of Cry proteins on beneficial natural enemies

USDA-ARS?s Scientific Manuscript database

A concern related to the use of insect-resistant Bt-transgenic plants is their potential to harm non-target organisms, especially natural enemies of important crop pests. A few studies purporting to show negative effects of Bt plants on non-target organisms had tremendous negative effects on the per...

A high-throughput liquid bead array-based screening technology for Bt presence in GMO manipulation.

PubMed

Fu, Wei; Wang, Huiyu; Wang, Chenguang; Mei, Lin; Lin, Xiangmei; Han, Xueqing; Zhu, Shuifang

2016-03-15

The number of species and planting areas of genetically modified organisms (GMOs) has been rapidly developed during the past ten years. For the purpose of GMO inspection, quarantine and manipulation, we have now devised a high-throughput Bt-based GMOs screening method based on the liquid bead array. This novel method is based on the direct competitive recognition between biotinylated antibodies and beads-coupled antigens, searching for Bt presence in samples if it contains Bt Cry1 Aa, Bt Cry1 Ab, Bt Cry1 Ac, Bt Cry1 Ah, Bt Cry1 B, Bt Cry1 C, Bt Cry1 F, Bt Cry2 A, Bt Cry3 or Bt Cry9 C. Our method has a wide GMO species coverage so that more than 90% of the whole commercialized GMO species can be identified throughout the world. Under our optimization, specificity, sensitivity, repeatability and availability validation, the method shows a high specificity and 10-50 ng/mL sensitivity of quantification. We then assessed more than 1800 samples in the field and food market to prove capacity of our method in performing a high throughput screening work for GMO manipulation. Our method offers an applicant platform for further inspection and research on GMO plants. Copyright © 2015 Elsevier B.V. All rights reserved.

Adsorption of transgenic insecticidal Cry1Ab protein to SiO2. 2. Patch-controlled electrostatic attraction.

PubMed

Madliger, Michael; Sander, Michael; Schwarzenbach, René P

2010-12-01

Adsorption governs the fate of Cry proteins from genetically modified Bt crops in soils. The effect of ionic strength (I) on the adsorption of Cry1Ab (isoelectric point IEP(Cry1Ab) ≈ 6) to negatively charged quartz (SiO(2)) and positively charged poly-L-lysine (PLL) was investigated at pH 5 to 8, using quartz crystal microbalance with dissipation monitoring and optical waveguide lightmode spectroscopy. Cry1Ab adsorbed via positively and negatively charged surface patches to SiO(2) and PLL, respectively. This patch controlled electrostatic attraction (PCEA) explains the observed increase in Cry1Ab adsorption to sorbents that carried the same net charge as the protein (SiO(2) at pH > IEP(Cry1Ab) and PLL at pH < IEP(Cry1Ab)) with decreasing I. In contrast, the adsorption of two reference proteins, BSA and HEWL, with different adsorption mechanism, were little affected by similar changes of I. Consistent with PCEA, Cry1Ab desorption from SiO(2) at pH > IEP(Cry1Ab) increased with increasing I and pH. Weak Cry1Ab-SiO(2) PCEA above pH 7 resulted in reversible, concentration dependent adsorption. Solution depletion experiments showed that PCEA also governed Cry1Ab adsorption to SiO(2) particles at environmentally relevant concentrations (a few ng mL(-1)). These results imply that models describing Cry1Ab adsorption to charged surfaces in soils need to account for the nonuniform surface charge distribution of the protein.

IA Channels Encoded by Kv1.4 and Kv4.2 Regulate Circadian Period of PER2 Expression in the Suprachiasmatic Nucleus.

PubMed

Granados-Fuentes, Daniel; Hermanstyne, Tracey O; Carrasquillo, Yarimar; Nerbonne, Jeanne M; Herzog, Erik D

2015-10-01

Neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in mammals, display daily rhythms in electrical activity with more depolarized resting potentials and higher firing rates during the day than at night. Although these daily variations in the electrical properties of SCN neurons are required for circadian rhythms in physiology and behavior, the mechanisms linking changes in neuronal excitability to the molecular clock are not known. Recently, we reported that mice deficient for either Kcna4 (Kv1.4(-/-)) or Kcnd2 (Kv4.2(-/-); but not Kcnd3, Kv4.3(-/-)), voltage-gated K(+) (Kv) channel pore-forming subunits that encode subthreshold, rapidly activating, and inactivating K(+) currents (IA), have shortened (0.5 h) circadian periods in SCN firing and in locomotor activity compared with wild-type (WT) mice. In the experiments here, we used a mouse (Per2(Luc)) line engineered with a bioluminescent reporter construct, PERIOD2::LUCIFERASE (PER2::LUC), replacing the endogenous Per2 locus, to test the hypothesis that the loss of Kv1.4- or Kv4.2-encoded IA channels also modifies circadian rhythms in the expression of the clock protein PERIOD2 (PER2). We found that SCN explants from Kv1.4(-/-)Per2(Luc) and Kv4.2(-/-) Per2(Luc), but not Kv4.3(-/-)Per2(Luc), mice have significantly shorter (by approximately 0.5 h) circadian periods in PER2 rhythms, compared with explants from Per2(Luc) mice, revealing that the membrane properties of SCN neurons feedback to regulate clock (PER2) expression. The combined loss of both Kv1.4- and Kv4.2-encoded IA channels in Kv1.4(-/-)/Kv4.2(-/-)Per2(Luc) SCN explants did not result in any further alterations in PER2 rhythms. Interestingly, however, mice lacking both Kv1.4 and Kv4.2 show a striking (approximately 1.8 h) advance in their daily activity onset in a light cycle compared with WT mice, suggesting additional roles for Kv1.4- and Kv4.2-encoded IA channels in controlling the light-dependent responses of neurons within and/or outside of the SCN to regulate circadian phase of daily activity. © 2015 The Author(s).

75 FR 3234 - Issuance of an Experimental Use Permit

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-20

... The quantity authorized equates to 68,066 pounds of corn seed [containing 62 grams (0.137 pounds) of Cry1F protein, 787 grams (1.74 pounds) of Cry34Ab1 and Cry35Ab1 proteins, 27 grams (0.060 pounds) of Cry1Ab protein, 347 grams (0.765 pounds) of Vip3Aa20 protein, and 11 grams (0.024 pounds) of mCry3A...

Role of clay minerals in the transportation of iron

USGS Publications Warehouse

Carroll, D.

1958-01-01

The clay minerals have iron associated with them in several ways: 1. (1) as an essential constituent 2. (2) as a minor constituent within the crystal lattice where it is in isomorphous substitution and 3. (3) as iron oxide on the surface of the mineral platelets. Nontronite, "hydromica," some chlorites, vermiculite, glauconite and chamosite contain iron as an essential constituent. Kaolinite and halloysite have no site within the lattice for iron, but in certain environments iron oxide (goethite or hematite) is intimately associated as a coating on the micelles. Analyses of clay minerals show that the content of Fe2O3 varies: 29 per cent (nontronite), 7??3 per cent (griffithite), 4.5 per cent ("hydromica"), 5.5 per cent (chlorite), 4 per cent (vermiculite) and 18 per cent (glauconite). The FeO content is: 40 per cent (chamosite), 7.8 per cent (griffithite), 1-2 per cent ("hydromica"), 3 per cent (glauconite) and 2 per cent (chlorite). The iron associated with the clay minerals remains stable in the environment in which the minerals occur, but if either pH or Eh or both are changed the iron may be affected. Change of environment will cause: 1. (1) removal of iron by reduction of Fe3+ to Fe2+; 2. (2) ion-exchange reactions; 3. (3) instability of the crystal lattice. Experiments using bacterial activity to produce reducing conditions with kaolinite and halloysite coated with iron oxides and with nontronite in which ferric iron is in the octahedral position within the lattice showed that ferric oxide is removed at Eh +0??215 in fresh water and at Eh +0.098 in sea water. Hematite, goethite, and indefinite iron oxides were removed at different rates. Red ferric oxides were changed to black indefinite noncrystalline ferrous sulphide at Eh -0.020 but reverted to ferric oxide under oxidizing conditions. Nontronite turned bright green under reducing conditions and some of the ferrous iron remained within the lattice on a return to oxidizing conditions. Bacterial activity seems to be necessary for maintaining reducing conditions in the environments studied. ?? 1958.

Cryptochrome and Period Proteins Are Regulated by the CLOCK/BMAL1 Gene: Crosstalk between the PPARs/RXRα-Regulated and CLOCK/BMAL1-Regulated Systems

PubMed Central

Nakamura, Koh-ichi; Inoue, Ikuo; Takahashi, Seiichiro; Komoda, Tsugikazu; Katayama, Shigehiro

2008-01-01

Feeding and the circadian system regulate lipid absorption and metabolism, and the expression of enzymes involved in lipid metabolism is believed to be directly controlled by the clock system. To investigate the interaction between the lipid metabolism system and the circadian system, we analyzed the effect of a CLOCK/BMAL1 heterodimer on the transcriptional regulation of PPAR-controlled genes through PPAR response elements (PPREs). Transcription of acyl-CoA oxidase, cellular retinol binding protein II (CRBPII), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase was altered by CLOCK/BMAL1, and transcriptional activity via PPRE by PPARs/RXRα was enhanced by CLOCK/BMAL1 and/or by PPARs ligand/activators. We also found that CLOCK/BMAL1-mediated transcription of period (PER) and cryptochrome (CRY) was modulated by PPARα/RXRα. These results suggest that there may be crosstalk between the PPARs/RXRα-regulated system and the CLOCK/BMAL1-regulated system. PMID:18317514

Frequency of alleles conferring resistance to a Bacillus thuringiensis toxin in a Philippine population of Scirpophaga incertulas (Lepidoptera: Pyralidae).

PubMed

Bentur, J S; Andow, D A; Cohen, M B; Romena, A M; Gould, F

2000-10-01

Using the F2 screen methodology, we estimated the frequency of alleles conferring resistance to the Cry1Ab toxin of Bacillus thuringiensis Berliner in a Philippine population of the stem borer Scirpophaga incertulas (Walker). Evaluation of >450 isofemale lines for survival of F2 larvae on cry1Ab plants did not detect the presence of an allele conferring a high level of resistance. The frequency of such an allele in the sampled population was conservatively estimated to be <3.6 x 10(-3) with 95% confidence and a detection probability of 94%. However, there was evidence of the presence of alleles conferring partial resistance to Cry1Ab. The frequency of alleles for partial resistance was estimated as 4.8 x 10(-3) with a 95% CI between 1.3 x 10(-3) and 1.04 x 10(-2) and a detection probability of 94%. Our results suggest that the frequency of alleles conferring resistance to Cry1Ab in the population of S. incertulas sampled is not too high to preclude successful implementation of the high dose/refuge resistance management strategy.

Exploring the Landscape of Diazabicyclooctane (DBO) Inhibition: Avibactam Inactivation of PER-2 β-Lactamase

PubMed Central

Ruggiero, Melina; Papp-Wallace, Krisztina M.; Taracila, Magdalena A.; Mojica, Maria F.; Bethel, Christopher R.; Rudin, Susan D.; Zeiser, Elise T.; Gutkind, Gabriel

2017-01-01

ABSTRACT PER β-lactamases are an emerging family of extended-spectrum β-lactamases (ESBL) found in Gram-negative bacteria. PER β-lactamases are unique among class A enzymes as they possess an inverted omega (Ω) loop and extended B3 β-strand. These singular structural features are hypothesized to contribute to their hydrolytic profile against oxyimino-cephalosporins (e.g., cefotaxime and ceftazidime). Here, we tested the ability of avibactam (AVI), a novel non-β-lactam β-lactamase inhibitor to inactivate PER-2. Interestingly, the PER-2 inhibition constants (i.e., k2/K = 2 × 103 ± 0.1 × 103 M−1 s−1, where k2 is the rate constant for acylation (carbamylation) and K is the equilibrium constant) that were obtained when AVI was tested were reminiscent of values observed testing the inhibition by AVI of class C and D β-lactamases (i.e., k2/K range of ≈103 M−1 s−1) and not class A β-lactamases (i.e., k2/K range, 104 to 105 M−1 s−1). Once AVI was bound, a stable complex with PER-2 was observed via mass spectrometry (e.g., 31,389 ± 3 atomic mass units [amu] → 31,604 ± 3 amu for 24 h). Molecular modeling of PER-2 with AVI showed that the carbonyl of AVI was located in the oxyanion hole of the β-lactamase and that the sulfate of AVI formed interactions with the β-lactam carboxylate binding site of the PER-2 β-lactamase (R220 and T237). However, hydrophobic patches near the PER-2 active site (by Ser70 and B3-B4 β-strands) were observed and may affect the binding of necessary catalytic water molecules, thus slowing acylation (k2/K) of AVI onto PER-2. Similar electrostatics and hydrophobicity of the active site were also observed between OXA-48 and PER-2, while CTX-M-15 was more hydrophilic. To demonstrate the ability of AVI to overcome the enhanced cephalosporinase activity of PER-2 β-lactamase, we tested different β-lactam–AVI combinations. By lowering MICs to ≤2 mg/liter, the ceftaroline-AVI combination could represent a favorable therapeutic option against Enterobacteriaceae expressing blaPER-2. Our studies define the inactivation of the PER-2 ESBL by AVI and suggest that the biophysical properties of the active site contribute to determining the efficiency of inactivation. PMID:28348157

Effective dominance of resistance of Spodoptera frugiperda to Bt maize and cotton varieties: implications for resistance management

PubMed Central

Horikoshi, Renato J.; Bernardi, Daniel; Bernardi, Oderlei; Malaquias, José B.; Okuma, Daniela M.; Miraldo, Leonardo L.; Amaral, Fernando S. de A. e; Omoto, Celso

2016-01-01

The resistance of fall armyworm (FAW), Spodoptera frugiperda, has been characterized to some Cry and Vip3A proteins of Bacillus thuringiensis (Bt) expressed in transgenic maize in Brazil. Here we evaluated the effective dominance of resistance based on the survival of neonates from selected Bt-resistant, heterozygous, and susceptible (Sus) strains of FAW on different Bt maize and cotton varieties. High survival of strains resistant to the Cry1F (HX-R), Cry1A.105/Cry2Ab (VT-R) and Cry1A.105/Cry2Ab/Cry1F (PW-R) proteins was detected on Herculex, YieldGard VT PRO and PowerCore maize. Our Vip3A-resistant strain (Vip-R) exhibited high survival on Herculex, Agrisure Viptera and Agrisure Viptera 3 maize. However, the heterozygous from HX-R × Sus, VT-R × Sus, PW-R × Sus and Vip-R × Sus had complete mortality on YieldGard VT PRO, PowerCore, Agrisure Viptera, and Agrisure Viptera 3, whereas the HX-R × Sus and Vip-R × Sus strains survived on Herculex maize. On Bt cotton, the HX-R, VT-R and PW-R strains exhibited high survival on Bollgard II. All resistant strains survived on WideStrike, but only PW-R and Vip-R × Sus survived on TwinLink. Our study provides useful data to aid in the understanding of the effectiveness of the refuge strategy for Insect Resistance Management of Bt plants. PMID:27721425

Effective dominance of resistance of Spodoptera frugiperda to Bt maize and cotton varieties: implications for resistance management

NASA Astrophysics Data System (ADS)

Horikoshi, Renato J.; Bernardi, Daniel; Bernardi, Oderlei; Malaquias, José B.; Okuma, Daniela M.; Miraldo, Leonardo L.; Amaral, Fernando S. De A. E.; Omoto, Celso

2016-10-01

The resistance of fall armyworm (FAW), Spodoptera frugiperda, has been characterized to some Cry and Vip3A proteins of Bacillus thuringiensis (Bt) expressed in transgenic maize in Brazil. Here we evaluated the effective dominance of resistance based on the survival of neonates from selected Bt-resistant, heterozygous, and susceptible (Sus) strains of FAW on different Bt maize and cotton varieties. High survival of strains resistant to the Cry1F (HX-R), Cry1A.105/Cry2Ab (VT-R) and Cry1A.105/Cry2Ab/Cry1F (PW-R) proteins was detected on Herculex, YieldGard VT PRO and PowerCore maize. Our Vip3A-resistant strain (Vip-R) exhibited high survival on Herculex, Agrisure Viptera and Agrisure Viptera 3 maize. However, the heterozygous from HX-R × Sus, VT-R × Sus, PW-R × Sus and Vip-R × Sus had complete mortality on YieldGard VT PRO, PowerCore, Agrisure Viptera, and Agrisure Viptera 3, whereas the HX-R × Sus and Vip-R × Sus strains survived on Herculex maize. On Bt cotton, the HX-R, VT-R and PW-R strains exhibited high survival on Bollgard II. All resistant strains survived on WideStrike, but only PW-R and Vip-R × Sus survived on TwinLink. Our study provides useful data to aid in the understanding of the effectiveness of the refuge strategy for Insect Resistance Management of Bt plants.

Altered energy intake and the amplitude of the body temperature rhythm are associated with changes in phase, but not amplitude, of clock gene expression in the rat suprachiasmatic nucleus in vivo.

PubMed

Goh, Grace H; Mark, Peter J; Maloney, Shane K

2016-01-01

Circadian rhythms in mammals are driven by a central clock in the suprachiasmatic nucleus (SCN). In vitro, temperature cycles within the physiological range can act as potent entraining cues for biological clocks. We altered the body temperature (Tc) rhythm in rats by manipulating energy intake (EI) to determine whether EI-induced changes in Tc oscillations are associated with changes in SCN clock gene rhythms in vivo. Male Wistar rats (n = 16 per diet) were maintained on either an ad libitum diet (CON), a high energy cafeteria diet (CAF), or a calorie restricted diet (CR), and Tc was recorded every 30 min for 6-7 weeks. SCN tissue was harvested from rats at zeitgeber time (ZT) 0, ZT6, ZT12, or ZT18. Expression of the clock genes Bmal1, Per2, Cry1, and Rev-erbα, the heat shock transcription factor Hsf1, and the heat shock protein Hsp90aa1, were determined using qPCR. The circadian profile of gene expression for each gene was characterized using cosinor analysis. Compared to the CON rats, the amplitude of Tc was decreased in CAF rats by 0.1 °C (p < 0.001), and increased in CR rats by 0.3 °C (p < 0.001). The amplitude of Hsp90aa1 expression was lowest in CAF rats and highest in CR rats (p = 0.045), but the amplitude of all of the clock genes and Hsf1 were unaffected by diet (p > 0.25). Compared to CON, phase advances of the Tc, Bmal1, and Per2 rhythms were observed with CR feeding (p < 0.05), but CAF feeding elicited no significant changes in phase. The present results indicate that in vivo, the SCN is largely resistant to entrainment by EI-induced changes in the Tc rhythm, although some phase entrainment may occur.

Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer

PubMed Central

WANG, ZHAOXIA; LI, LI; WANG, YANG

2016-01-01

The aim of the present study was to evaluate the association between Period2 (Per2) and the occurrence and development of ovarian cancer, in addition to evaluating the effect of this gene on the growth and metastasis of ovarian cancer in nude mice xenograft models. The detection of Per2 by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting methods at various stages of ovarian cancer in tumor tissue samples was conducted. Nude mice xenograft models of ovarian cancer were constructed using an ovarian cancer cell line and, using a gene transfection technique, exogenous infusion of the recombinant gene, Per2, was performed. To assess for the successful and stable expression of Per2 in the tumor tissue, levels of Per2 expression in the nude mice xenograft models were detected by RT-qPCR. During the experimental period, the tumor volumes were measured every three days. Two weeks following treatment cessation, the nude mice were sacrificed and the tumor weight and volume were measured. Furthermore, detection of the changes in expression levels of metastasis-associated gene 1 (MTA-1) and tumor metastasis suppressor gene, non-metastasis protein 23-H1 (nm23-H1), and the expression change of autophagy-associated signal transduction pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) kinase were analyzed. The findings demonstrated that with ovarian cancer stage development, the expression of Per2 gradually reduced or ceased. In addition, exogenous Per2 was successfully and stably expressed in nude mice tumor tissue samples. Furthermore, in the Per2 overexpression group, MTA-1 protein expression was significantly reduced when compared with the phosphate-buffered saline (PBS) control and empty plasmid groups, while nm23-H1 protein expression was significantly higher when compared with those two groups. The expression levels of PI3K and PKB kinase, which are marker proteins of the autophagy associated signaling pathway PI3K/PKB, were significantly downregulated, when compared with the PBS control and empty plasmid groups (P<0.001). Thus, it was demonstrated that Per2 is closely associated with the development of ovarian cancer, and late-stage ovarian cancer is associated with Per2 mutation or deletion. Per2 overexpression, via exogenous infusion reduced the ovarian cancer growth rate, which was demonstrated by a significant increase in the tumor inhibition rate. In addition, Per2 may inhibit the expression of MTA-1 and promote the expression of nm23-H1 to restrict ovarian tumor growth and metastasis. Finally, it is hypothesized that Per2 affects autophagy by interfering with the PI3K/PKB signaling pathway, causing inhibition of tumor angiogenesis in order to inhibit tumor growth. PMID:27082164

Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer.

PubMed

Wang, Zhaoxia; Li, Li; Wang, Yang

2016-06-01

The aim of the present study was to evaluate the association between Period2 (Per2) and the occurrence and development of ovarian cancer, in addition to evaluating the effect of this gene on the growth and metastasis of ovarian cancer in nude mice xenograft models. The detection of Per2 by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting methods at various stages of ovarian cancer in tumor tissue samples was conducted. Nude mice xenograft models of ovarian cancer were constructed using an ovarian cancer cell line and, using a gene transfection technique, exogenous infusion of the recombinant gene, Per2, was performed. To assess for the successful and stable expression of Per2 in the tumor tissue, levels of Per2 expression in the nude mice xenograft models were detected by RT‑qPCR. During the experimental period, the tumor volumes were measured every three days. Two weeks following treatment cessation, the nude mice were sacrificed and the tumor weight and volume were measured. Furthermore, detection of the changes in expression levels of metastasis‑associated gene 1 (MTA‑1) and tumor metastasis suppressor gene, non‑metastasis protein 23‑H1 (nm23‑H1), and the expression change of autophagy‑associated signal transduction pathway, phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (PKB) kinase were analyzed. The findings demonstrated that with ovarian cancer stage development, the expression of Per2 gradually reduced or ceased. In addition, exogenous Per2 was successfully and stably expressed in nude mice tumor tissue samples. Furthermore, in the Per2 overexpression group, MTA‑1 protein expression was significantly reduced when compared with the phosphate‑buffered saline (PBS) control and empty plasmid groups, while nm23‑H1 protein expression was significantly higher when compared with those two groups. The expression levels of PI3K and PKB kinase, which are marker proteins of the autophagy associated signaling pathway PI3K/PKB, were significantly downregulated, when compared with the PBS control and empty plasmid groups (P<0.001). Thus, it was demonstrated that Per2 is closely associated with the development of ovarian cancer, and late‑stage ovarian cancer is associated with Per2 mutation or deletion. Per2 overexpression, via exogenous infusion reduced the ovarian cancer growth rate, which was demonstrated by a significant increase in the tumor inhibition rate. In addition, Per2 may inhibit the expression of MTA‑1 and promote the expression of nm23‑H1 to restrict ovarian tumor growth and metastasis. Finally, it is hypothesized that Per2 affects autophagy by interfering with the PI3K/PKB signaling pathway, causing inhibition of tumor angiogenesis in order to inhibit tumor growth.

Increased toxicity of Bacillus thuringiensis Cry3Aa against Crioceris quatuordecimpunctata, Phaedon brassicae and Colaphellus bowringi by a Tenebrio molitor cadherin fragment.

PubMed

Gao, Yulin; Jurat-Fuentes, Juan Luis; Oppert, Brenda; Fabrick, Jeffrey A; Liu, Chenxi; Gao, Jianhua; Lei, Zhongren

2011-09-01

Biopesticides containing Cry insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) are effective against many lepidopteran pests, but there is a lack of Bt-based pesticides for efficient control of important coleopteran pests. Based on the reported increase in Bt toxin oligomerization by a polypeptide from the Cry3Aa receptor cadherin in Tenebrio molitor (Coleoptera: Tenebrionidae), it was hypothesized that this cadherin peptide, rTmCad1p, would enhance Cry3Aa toxicity towards coleopteran larvae. To test this hypothesis, the relative toxicity of Cry3Aa, with or without rTmCad1p, against damaging chrysomelid vegetable pests of China was evaluated. Cry3Aa toxicity was evaluated in the spotted asparagus beetle (Crioceris quatuordecimpunctata), cabbage leaf beetle (Colaphellus bowringi) and daikon leaf beetle (Phaedon brassicae). To assess the effect of rTmCad1p on Cry3Aa toxicity, neonate larvae were fed Cry3Aa toxin alone or in combination with increasing amounts of rTmCad1p. The data demonstrated that Cry3Aa toxicity was significantly increased in all three vegetable pests, resulting in as much as a 15.3-fold increase in larval mortality. The application of rTmCad1p to enhance Cry3Aa insecticidal activity has potential for use in increasing range and activity levels against coleopteran pests displaying low susceptibility to Bt-based biopesticides. Copyright © 2011 Society of Chemical Industry.

Identification of a New cry1I-Type Gene as a Candidate for Gene Pyramiding in Corn To Control Ostrinia Species Larvae

PubMed Central

Zhao, Can; Abdelgaffar, Heba M.; Pan, Hongyu; Song, Fuping

2015-01-01

Pyramiding of diverse cry toxin genes from Bacillus thuringiensis with different modes of action is a desirable strategy to delay the evolution of resistance in the European corn borer (Ostrinia nubilalis). Considering the dependency of susceptibility to Cry toxins on toxin binding to receptors in the midgut of target pests, a diverse mode of action is commonly defined as recognition of unique binding sites in the target insect. In this study, we present a novel cry1Ie toxin gene (cry1Ie2) as a candidate for pyramiding with Cry1Ab or Cry1Fa in corn to control Ostrinia species larvae. The new toxin gene encodes an 81-kDa protein that is processed to a protease-resistant core form of approximately 55 kDa by trypsin digestion. The purified protoxin displayed high toxicity to Ostrinia furnacalis and O. nubilalis larvae but low to no activity against Spodoptera or heliothine species or the coleopteran Tenebrio molitor. Results of binding assays with 125I-labeled Cry1Ab toxin and brush border membrane vesicles from O. nubilalis larvae demonstrated that Cry1Ie2 does not recognize the Cry1Ab binding sites in that insect. Reciprocal competition binding assays with biotin-labeled Cry1Ie2 confirmed the lack of shared sites with Cry1Ab or Cry1Fa in O. nubilalis brush border membrane vesicles. These data support Cry1Ie2 as a good candidate for pyramiding with Cry1Ab or Cry1Fa in corn to increase the control of O. nubilalis and reduce the risk of resistance evolution. PMID:25795679

Identification of a New cry1I-Type Gene as a Candidate for Gene Pyramiding in Corn To Control Ostrinia Species Larvae.

PubMed

Zhao, Can; Jurat-Fuentes, Juan Luis; Abdelgaffar, Heba M; Pan, Hongyu; Song, Fuping; Zhang, Jie

2015-06-01

Pyramiding of diverse cry toxin genes from Bacillus thuringiensis with different modes of action is a desirable strategy to delay the evolution of resistance in the European corn borer (Ostrinia nubilalis). Considering the dependency of susceptibility to Cry toxins on toxin binding to receptors in the midgut of target pests, a diverse mode of action is commonly defined as recognition of unique binding sites in the target insect. In this study, we present a novel cry1Ie toxin gene (cry1Ie2) as a candidate for pyramiding with Cry1Ab or Cry1Fa in corn to control Ostrinia species larvae. The new toxin gene encodes an 81-kDa protein that is processed to a protease-resistant core form of approximately 55 kDa by trypsin digestion. The purified protoxin displayed high toxicity to Ostrinia furnacalis and O. nubilalis larvae but low to no activity against Spodoptera or heliothine species or the coleopteran Tenebrio molitor. Results of binding assays with (125)I-labeled Cry1Ab toxin and brush border membrane vesicles from O. nubilalis larvae demonstrated that Cry1Ie2 does not recognize the Cry1Ab binding sites in that insect. Reciprocal competition binding assays with biotin-labeled Cry1Ie2 confirmed the lack of shared sites with Cry1Ab or Cry1Fa in O. nubilalis brush border membrane vesicles. These data support Cry1Ie2 as a good candidate for pyramiding with Cry1Ab or Cry1Fa in corn to increase the control of O. nubilalis and reduce the risk of resistance evolution. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effects of age on segregation of the X and Y chromosomes in cultured lymphocytes from Chinese men.

PubMed

Song, Yaxian; Chen, Qian; Zhang, Zhen; Hou, Heli; Zhang, Ding; Shi, Qinghua

2009-08-01

Chromosome malsegregation in binucleated lymphocytes is a useful endpoint to evaluate age effect on genetic stability. However, the investigations on chromosome malsegregation in binucleated lymphocytes from Chinese are scarce. In this study, peripheral blood lymphocytes were collected from 14 old (60-70 years) and 10 young (22-26 years) healthy Chinese men. To detect malsegregation of the sex chromosomes, multi-color fluorescence in situ hybridization (FISH) was performed on binucleated lymphocytes, cytokinesis-blocked by cytochalasin B at the first mitosis after phytohaemagglutinin stimulation. Compared with that in young men, a significant increase in frequencies of loss of chromosome X (9.2 +/- 3.2 per thousand vs. 1.1 +/- 0.9 per thousand, P < 0.001) and Y (2.5 +/- 1.9 per thousand vs. 0.2 +/- 0.3 per thousand, P < 0.001) was found in old men. Similarly, nondisjunction of chromosome X (16.5 +/- 3.4 per thousand vs. 3.5 +/- 1.1 per thousand, P < 0.001) and Y (7.2 +/- 2.6 per thousand vs. 2.4 +/- 1.3 per thousand, P < 0.001) occurred more frequently in old men than in young men. Regardless of donor's age, nondisjunction is more prevalent than loss for both chromosome X and Y. The frequencies of observed simultaneous malsegregation were relatively higher than the expected, suggesting an association between malsegregation. These results indicated that in Chinese men, malsegregation of the sex chromosomes increases with age in an associated fashion, and nondisjunction accounts for the majority of spontaneous chromosome malsegregation.

Resistance to Bacillus thuringiensis Toxin Cry2Ab in Trichoplusia ni Is Conferred by a Novel Genetic Mechanism

PubMed Central

Song, Xiaozhao; Kain, Wendy; Cassidy, Douglas

2015-01-01

The resistance to the Bacillus thuringiensis (Bt) toxin Cry2Ab in a greenhouse-originated Trichoplusia ni strain resistant to both Bt toxins Cry1Ac and Cry2Ab was characterized. Biological assays determined that the Cry2Ab resistance in the T. ni strain was a monogenic recessive trait independent of Cry1Ac resistance, and there existed no significant cross-resistance between Cry1Ac and Cry2Ab in T. ni. From the dual-toxin-resistant T. ni strain, a strain resistant to Cry2Ab only was isolated, and the Cry2Ab resistance trait was introgressed into a susceptible laboratory strain to facilitate comparative analysis of the Cry2Ab resistance with the susceptible T. ni strain. Results from biochemical analysis showed no significant difference between the Cry2Ab-resistant and -susceptible T. ni larvae in midgut proteases, including caseinolytic proteolytic activity and zymogram profile and serine protease activities, in midgut aminopeptidase and alkaline phosphatase activity, and in midgut esterases and hemolymph plasma melanization activity. For analysis of genetic linkage of Cry2Ab resistance with potential Cry toxin receptor genes, molecular markers for the midgut cadherin, alkaline phosphatase (ALP), and aminopeptidase N (APN) genes were identified between the original greenhouse-derived dual-toxin-resistant and the susceptible laboratory T. ni strains. Genetic linkage analysis showed that the Cry2Ab resistance in T. ni was not genetically associated with the midgut genes coding for the cadherin, ALP, and 6 APNs (APN1 to APN6) nor associated with the ABC transporter gene ABCC2. Therefore, the Cry2Ab resistance in T. ni is conferred by a novel but unknown genetic mechanism. PMID:26025894

Hypertension in Israeli adolescents: prevalence according to weight, sex and parental origin.

PubMed Central

Shohat, M; Shohat, T; Mimouni, M; Nitzan, M; Danon, Y L

1989-01-01

We studied the prevalence of hypertension in 57,499 male and 35,803 female Israeli military recruits and its relation with sex, weight, and parents' ethnic origin. The overall prevalence of systolic hypertension (greater than 140 mmHg) was 1.75 per cent for males and 0.32 per cent for females. The prevalence of diastolic hypertension (greater than 90 mmHg) was 0.41 per cent for males and 0.06 per cent for females. For males, the prevalence of systolic and diastolic hypertension increased with weight, exponentially. Males of Ashkenazi origin had a significantly higher prevalence of hypertension (systolic 2.52 per cent, diastolic 0.55 per cent) compared with those of Sephardi origin (systolic 1.12 per cent, diastolic 0.3 per cent). The prevalence of adolescents with systolic or diastolic blood pressure greater than the mean +2SD of each weight group ranged between 1.5-2.3 per cent. PMID:2705591

40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

Evidence of Field-Evolved Resistance of Spodoptera frugiperda to Bt Corn Expressing Cry1F in Brazil That Is Still Sensitive to Modified Bt Toxins

PubMed Central

Monnerat, Rose; Martins, Erica; Macedo, Cristina; Queiroz, Paulo; Praça, Lilian; Soares, Carlos Marcelo; Moreira, Helio; Grisi, Isabella; Silva, Joseane; Soberon, Mario; Bravo, Alejandra

2015-01-01

Brazil ranked second only to the United States in hectares planted to genetically modified crops in 2013. Recently corn producers in the Cerrado region reported that the control of Spodoptera frugiperda with Bt corn expressing Cry1Fa has decreased, forcing them to use chemicals to reduce the damage caused by this insect pest. A colony of S. frugiperda was established from individuals collected in 2013 from Cry1Fa corn plants (SfBt) in Brazil and shown to have at least more than ten-fold higher resistance levels compared with a susceptible colony (Sflab). Laboratory assays on corn leaves showed that in contrast to SfLab population, the SfBt larvae were able to survive by feeding on Cry1Fa corn leaves. The SfBt population was maintained without selection for eight generations and shown to maintain high levels of resistance to Cry1Fa toxin. SfBt showed higher cross-resistance to Cry1Aa than to Cry1Ab or Cry1Ac toxins. As previously reported, Cry1A toxins competed the binding of Cry1Fa to brush border membrane vesicles (BBMV) from SfLab insects, explaining cross-resistance to Cry1A toxins. In contrast Cry2A toxins did not compete Cry1Fa binding to SfLab-BBMV and no cross-resistance to Cry2A was observed, although Cry2A toxins show low toxicity to S. frugiperda. Bioassays with Cry1AbMod and Cry1AcMod show that they are highly active against both the SfLab and the SfBt populations. The bioassay data reported here show that insects collected from Cry1Fa corn in the Cerrado region were resistant to Cry1Fa suggesting that resistance contributed to field failures of Cry1Fa corn to control S. frugiperda. PMID:25830928

Evidence of field-evolved resistance of Spodoptera frugiperda to Bt corn expressing Cry1F in Brazil that is still sensitive to modified Bt toxins.

PubMed

Monnerat, Rose; Martins, Erica; Macedo, Cristina; Queiroz, Paulo; Praça, Lilian; Soares, Carlos Marcelo; Moreira, Helio; Grisi, Isabella; Silva, Joseane; Soberon, Mario; Bravo, Alejandra

2015-01-01

Brazil ranked second only to the United States in hectares planted to genetically modified crops in 2013. Recently corn producers in the Cerrado region reported that the control of Spodoptera frugiperda with Bt corn expressing Cry1Fa has decreased, forcing them to use chemicals to reduce the damage caused by this insect pest. A colony of S. frugiperda was established from individuals collected in 2013 from Cry1Fa corn plants (SfBt) in Brazil and shown to have at least more than ten-fold higher resistance levels compared with a susceptible colony (Sflab). Laboratory assays on corn leaves showed that in contrast to SfLab population, the SfBt larvae were able to survive by feeding on Cry1Fa corn leaves. The SfBt population was maintained without selection for eight generations and shown to maintain high levels of resistance to Cry1Fa toxin. SfBt showed higher cross-resistance to Cry1Aa than to Cry1Ab or Cry1Ac toxins. As previously reported, Cry1A toxins competed the binding of Cry1Fa to brush border membrane vesicles (BBMV) from SfLab insects, explaining cross-resistance to Cry1A toxins. In contrast Cry2A toxins did not compete Cry1Fa binding to SfLab-BBMV and no cross-resistance to Cry2A was observed, although Cry2A toxins show low toxicity to S. frugiperda. Bioassays with Cry1AbMod and Cry1AcMod show that they are highly active against both the SfLab and the SfBt populations. The bioassay data reported here show that insects collected from Cry1Fa corn in the Cerrado region were resistant to Cry1Fa suggesting that resistance contributed to field failures of Cry1Fa corn to control S. frugiperda.

Growth of historical Sitka spruce plantations at Unalaska Bay, Alaska.

Treesearch

J. Alden; D. Bruce

1989-01-01

Sitka spruce (Picea sitchensis (Bong.) Carr.) grew an estimated 37 cubic feet of stemwood per acre per year (2.6 m3·ha-1·yr-1) in remnant World War II plantations on Amaknak Island and 38 cubic feet of stemwood per acre per year (2.7 m3·ha-1·yr-1) in an early 19th century grove on Expedition Island, 520 miles (837 km) southwest of natural tree...

46 CFR 28.550 - Icing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... south of 66° South latitude must be assumed to be at least: (1) 6.14 pounds per square foot (30 Kilograms per square meter) of horizontal projected area which corresponds to a thickness of 1.3 inches (33 millimeters); and (2) 3.07 pounds per square foot (15 Kilograms per square meter) of vertical projected area...

Identification of Bacillus thuringiensis Cry3Aa toxin domain II loop 1 as the binding site of Tenebrio molitor cadherin repeat CR12.

PubMed

Zúñiga-Navarrete, Fernando; Gómez, Isabel; Peña, Guadalupe; Amaro, Itzel; Ortíz, Ernesto; Becerril, Baltazar; Ibarra, Jorge E; Bravo, Alejandra; Soberón, Mario

2015-04-01

Bacillus thuringiensis Cry toxins exert their toxic effect by specific recognition of larval midgut proteins leading to oligomerization of the toxin, membrane insertion and pore formation. The exposed domain II loop regions of Cry toxins have been shown to be involved in receptor binding. Insect cadherins have shown to be functionally involved in toxin binding facilitating toxin oligomerization. Here, we isolated a VHH (VHHA5) antibody by phage display that binds Cry3Aa loop 1 and competed with the binding of Cry3Aa to Tenebrio molitor brush border membranes. VHHA5 also competed with the binding of Cry3Aa to a cadherin fragment (CR12) that was previously shown to be involved in binding and toxicity of Cry3Aa, indicating that Cry3Aa binds CR12 through domain II loop 1. Moreover, we show that a loop 1 mutant, previously characterized to have increased toxicity to T. molitor, displayed a correlative enhanced binding affinity to T. molitor CR12 and to VHHA5. These results show that Cry3Aa domain II loop 1 is a binding site of CR12 T. molitor cadherin. Copyright © 2015 Elsevier Ltd. All rights reserved.

21 CFR 558.363 - Narasin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... this section are as follows: (1) To 000986: 36, 45, 54, 72, and 90 grams per pound, paragraph (d)(1)(i) of this section. (2) [Reserved] (3) To 000986: 36 grams per pound, with 36 grams per pound nicarbazin, paragraph (d)(1)(iii) of this section. (4) To 016592: 36, 45, 54, 72, and 90 grams per pound, with 2 and 10...

Immunotoxicological Evaluation of Corn Genetically Modified with Bacillus thuringiensis Cry1Ah Gene by a 30-Day Feeding Study in BALB/c Mice

PubMed Central

Song, Yan; Liang, Chunlai; Wang, Wei; Fang, Jin; Sun, Nana; Jia, Xudong; Li, Ning

2014-01-01

This study was to investigate the immunotoxicological potential of corn genetically modified (GM) with Bacillus thuringiensis (Bt) Cry1Ah gene in BALB/c mice. Female BALB/c mice were randomly assigned to one of the four groups: the negative control group, the parental corn group, the GM corn group and the positive control group with 10 mice per group. Mice in the GM corn group and the parental corn group were fed with diets containing 70% corresponding corn for 30 days. Mice in the negative control group and the positive control group were fed with AIN93G diet, administered with saline or 200 mg/kg of cyclophosphamide (CY) via intraperitoneal injection 24 h before the termination of the study, respectively. At the end of the study, the immunotoxicological effects of the GM corn were evaluated through immunopathology parameters including body and organ weights, hematology and clinical chemistry parameters, histological examination, peripheral blood lymphocytes phenotype; humoral immunity including antibody plaque-forming cell, serum immunoglobulin, cytokine and half hemolysis value; cellular immunity such as mitogen-induced splenocyte proliferation, cytotoxic T-lymphocyte reaction, delayed-type hypersensitivity reaction; non-specific immunity including phagocytic activities of phagocytes, natural killer cell activity. A single dose of cyclophosphamide (200 mg/kg bw) was found to have significant adverse effects on immunopathology, cellular immunity, and humoral immunity in mice. The corn genetically modified with Bt Cry1Ah gene is considered consistent with the parental corn in terms of immunopathology, humoral immunity, cellular immunity and non-specific immunity. No adverse immunotoxicological effects of GM corn with Bt Cry1Ah gene were found when feeding mice for 30 days. PMID:24520311

Synergism and Antagonism between Bacillus thuringiensis Vip3A and Cry1 Proteins in Heliothis virescens, Diatraea saccharalis and Spodoptera frugiperda

PubMed Central

Lemes, Ana Rita Nunes; Davolos, Camila Chiaradia; Legori, Paula Cristina Brunini Crialesi; Fernandes, Odair Aparecido; Ferré, Juan; Lemos, Manoel Victor Franco; Desiderio, Janete Apparecida

2014-01-01

Second generation Bt crops (insect resistant crops carrying Bacillus thuringiensis genes) combine more than one gene that codes for insecticidal proteins in the same plant to provide better control of agricultural pests. Some of the new combinations involve co-expression of cry and vip genes. Because Cry and Vip proteins have different midgut targets and possibly different mechanisms of toxicity, it is important to evaluate possible synergistic or antagonistic interactions between these two classes of toxins. Three members of the Cry1 class of proteins and three from the Vip3A class were tested against Heliothis virescens for possible interactions. At the level of LC50, Cry1Ac was the most active protein, whereas the rest of proteins tested were similarly active. However, at the level of LC90, Cry1Aa and Cry1Ca were the least active proteins, and Cry1Ac and Vip3A proteins were not significantly different. Under the experimental conditions used in this study, we found an antagonistic effect of Cry1Ca with the three Vip3A proteins. The interaction between Cry1Ca and Vip3Aa was also tested on two other species of Lepidoptera. Whereas antagonism was observed in Spodoptera frugiperda, synergism was found in Diatraea saccharalis. In all cases, the interaction between Vip3A and Cry1 proteins was more evident at the LC90 level than at the LC50 level. The fact that the same combination of proteins may result in a synergistic or an antagonistic interaction may be an indication that there are different types of interactions within the host, depending on the insect species tested. PMID:25275646

On-line gas chromatography combustion/pyrolysis isotope ratio mass spectrometry (HRGC-C/P-IRMS) of pineapple (Ananas comosus L. Merr.) volatiles.

PubMed

Preston, Christina; Richling, Elke; Elss, Sandra; Appel, Markus; Heckel, Frank; Hartlieb, Ariane; Schreier, Peter

2003-12-31

By use of extracts prepared by liquid-liquid separation of the volatiles from self-prepared juices of pineapple fruits (Ananas comosus) (n = 14) as well as commercial pineapple recovery aromas/water phases (n = 3), on-line capillary gas chromatography-isotope ratio mass spectrometry was employed in the combustion (C) and the pyrolysis (P) modes (HRGC-C/P-IRMS) to determine the delta(13)C(VPDB) and delta(2)H(VSMOW) values of selected pineapple flavor constituents. In addition to methyl 2-methylbutanoate 1, ethyl 2-methylbutanoate 2, methyl hexanoate 3, ethyl hexanoate 4, and 2,5-dimethyl-4-methoxy-3[2H]-furanone 5, each originating from the fruit, the delta(13)C(VPDB) and delta(2)H(VSMOW) data of commercial synthetic 1-5 and "natural" (biotechnologically derived) 1-4 were determined. With delta(13)C(VPDB) data of pineapple volatiles 1-4 varying from -12.8 to -24.4 per thousand, the range expected for CAM metabolism was observed. Compound 5 showed higher depletion from -20.9 to -28.6 per thousand. A similar situation was given for the delta(2)H(VSMOW) values of 3-5 from pineapple ranging from -118 to -191 per thousand, whereas 1 and 2 showed higher depleted values from -184 to -263 per thousand. In nearly all cases, analytical differentiation of 1-5 from pineapple and natural as well as synthetic origin was possible. In general, natural and synthetic 1-5 exhibited delta(13)C(VPDB) data ranging from -11.8 to -32.2 per thousand and -22.7 to -35.9 per thousand, respectively. Their delta(2)H(VSMOW) data were in the range from -242 to -323 per thousand and -49 to -163 per thousand, respectively.

Phototropins But Not Cryptochromes Mediate the Blue Light-Specific Promotion of Stomatal Conductance, While Both Enhance Photosynthesis and Transpiration under Full Sunlight12[C][W][OA

PubMed Central

Boccalandro, Hernán E.; Giordano, Carla V.; Ploschuk, Edmundo L.; Piccoli, Patricia N.; Bottini, Rubén; Casal, Jorge J.

2012-01-01

Leaf epidermal peels of Arabidopsis (Arabidopsis thaliana) mutants lacking either phototropins 1 and 2 (phot1 and phot2) or cryptochromes 1 and 2 (cry1 and cry2) exposed to a background of red light show severely impaired stomatal opening responses to blue light. Since phot and cry are UV-A/blue light photoreceptors, they may be involved in the perception of the blue light-specific signal that induces the aperture of the stomatal pores. In leaf epidermal peels, the blue light-specific effect saturates at low irradiances; therefore, it is considered to operate mainly under the low irradiance of dawn, dusk, or deep canopies. Conversely, we show that both phot1 phot2 and cry1 cry2 have reduced stomatal conductance, transpiration, and photosynthesis, particularly under the high irradiance of full sunlight at midday. These mutants show compromised responses of stomatal conductance to irradiance. However, the effects of phot and cry on photosynthesis were largely nonstomatic. While the stomatal conductance phenotype of phot1 phot2 was blue light specific, cry1 cry2 showed reduced stomatal conductance not only in response to blue light, but also in response to red light. The levels of abscisic acid were elevated in cry1 cry2. We conclude that considering their effects at high irradiances cry and phot are critical for the control of transpiration and photosynthesis rates in the field. The effects of cry on stomatal conductance are largely indirect and involve the control of abscisic acid levels. PMID:22147516

Phototropins but not cryptochromes mediate the blue light-specific promotion of stomatal conductance, while both enhance photosynthesis and transpiration under full sunlight.

PubMed

Boccalandro, Hernán E; Giordano, Carla V; Ploschuk, Edmundo L; Piccoli, Patricia N; Bottini, Rubén; Casal, Jorge J

2012-03-01

Leaf epidermal peels of Arabidopsis (Arabidopsis thaliana) mutants lacking either phototropins 1 and 2 (phot1 and phot2) or cryptochromes 1 and 2 (cry1 and cry2) exposed to a background of red light show severely impaired stomatal opening responses to blue light. Since phot and cry are UV-A/blue light photoreceptors, they may be involved in the perception of the blue light-specific signal that induces the aperture of the stomatal pores. In leaf epidermal peels, the blue light-specific effect saturates at low irradiances; therefore, it is considered to operate mainly under the low irradiance of dawn, dusk, or deep canopies. Conversely, we show that both phot1 phot2 and cry1 cry2 have reduced stomatal conductance, transpiration, and photosynthesis, particularly under the high irradiance of full sunlight at midday. These mutants show compromised responses of stomatal conductance to irradiance. However, the effects of phot and cry on photosynthesis were largely nonstomatic. While the stomatal conductance phenotype of phot1 phot2 was blue light specific, cry1 cry2 showed reduced stomatal conductance not only in response to blue light, but also in response to red light. The levels of abscisic acid were elevated in cry1 cry2. We conclude that considering their effects at high irradiances cry and phot are critical for the control of transpiration and photosynthesis rates in the field. The effects of cry on stomatal conductance are largely indirect and involve the control of abscisic acid levels.

Recognition of O6-benzyl-2′-deoxyguanosine by a perimidinone-derived synthetic nucleoside: a DNA interstrand stacking interaction

PubMed Central

Kowal, Ewa A.; Lad, Rahul R.; Pallan, Pradeep S.; Dhummakupt, Elizabeth; Wawrzak, Zdzislaw; Egli, Martin; Sturla, Shana J.; Stone, Michael P.

2013-01-01

The 2′-deoxynucleoside containing the synthetic base 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-1H-perimidin-2(3H)-one] (dPer) recognizes in DNA the O6-benzyl-2′-deoxyguanosine nucleoside (O6-Bn-dG), formed by exposure to N-benzylmethylnitrosamine. Herein, we show how dPer distinguishes between O6-Bn-dG and dG in DNA. The structure of the modified Dickerson–Drew dodecamer (DDD) in which guanine at position G4 has been replaced by O6-Bn-dG and cytosine C9 has been replaced with dPer to form the modified O6-Bn-dG:dPer (DDD-XY) duplex [5′-d(C1G2C3X4A5A6T7T8Y9G10C11G12)-3′]2 (X = O6-Bn-dG, Y = dPer) reveals that dPer intercalates into the duplex and adopts the syn conformation about the glycosyl bond. This provides a binding pocket that allows the benzyl group of O6-Bn-dG to intercalate between Per and thymine of the 3′-neighbor A:T base pair. Nuclear magnetic resonance data suggest that a similar intercalative recognition mechanism applies in this sequence in solution. However, in solution, the benzyl ring of O6-Bn-dG undergoes rotation on the nuclear magnetic resonance time scale. In contrast, the structure of the modified DDD in which cytosine at position C9 is replaced with dPer to form the dG:dPer (DDD-GY) [5′-d(C1G2C3G4A5A6T7T8Y9G10C11G12)-3′]2 duplex (Y = dPer) reveals that dPer adopts the anti conformation about the glycosyl bond and forms a less stable wobble pairing interaction with guanine. PMID:23748954

21 CFR 520.2240a - Sulfaethoxypyridazine drinking water.

Code of Federal Regulations, 2014 CFR

2014-04-01

...—(i) Amount. 1.9 to 3.8 grams per gallon (0.05 percent to 0.1 percent). (ii) Indications for use... cholerasuis infection. (iii) Limitations. Administer 3.8 grams per gallon for first day followed by 1.9 grams... veterinarian. (2) Cattle—(i) Amount. 2.5 grams per gallon (0.066 percent). (ii) Indications for use. Treatment...

21 CFR 520.2240a - Sulfaethoxypyridazine drinking water.

Code of Federal Regulations, 2012 CFR

2012-04-01

...—(i) Amount. 1.9 to 3.8 grams per gallon (0.05 percent to 0.1 percent). (ii) Indications for use... cholerasuis infection. (iii) Limitations. Administer 3.8 grams per gallon for first day followed by 1.9 grams... veterinarian. (2) Cattle—(i) Amount. 2.5 grams per gallon (0.066 percent). (ii) Indications for use. Treatment...

Effect of Stacked Insecticidal Cry Proteins from Maize Pollen on Nurse Bees (Apis mellifera carnica) and Their Gut Bacteria

PubMed Central

Härtel, Stephan; Näther, Astrid; Dohrmann, Anja B.; Steffan-Dewenter, Ingolf; Tebbe, Christoph C.

2013-01-01

Honey bee pollination is a key ecosystem service to nature and agriculture. However, biosafety research on genetically modified crops rarely considers effects on nurse bees from intact colonies, even though they receive and primarily process the largest amount of pollen. The objective of this study was to analyze the response of nurse bees and their gut bacteria to pollen from Bt maize expressing three different insecticidal Cry proteins (Cry1A.105, Cry2Ab2, and Cry3Bb1). Naturally Cry proteins are produced by bacteria (Bacillus thuringiensis). Colonies of Apis mellifera carnica were kept during anthesis in flight cages on field plots with the Bt maize, two different conventionally bred maize varieties, and without cages, 1-km outside of the experimental maize field to allow ad libitum foraging to mixed pollen sources. During their 10-days life span, the consumption of Bt maize pollen had no effect on their survival rate, body weight and rates of pollen digestion compared to the conventional maize varieties. As indicated by ELISA-quantification of Cry1A.105 and Cry3Bb1, more than 98% of the recombinant proteins were degraded. Bacterial population sizes in the gut were not affected by the genetic modification. Bt-maize, conventional varieties and mixed pollen sources selected for significantly different bacterial communities which were, however, composed of the same dominant members, including Proteobacteria in the midgut and Lactobacillus sp. and Bifidobacterium sp. in the hindgut. Surprisingly, Cry proteins from natural sources, most likely B. thuringiensis, were detected in bees with no exposure to Bt maize. The natural occurrence of Cry proteins and the lack of detectable effects on nurse bees and their gut bacteria give no indication for harmful effects of this Bt maize on nurse honey bees. PMID:23533634

Effect of stacked insecticidal Cry proteins from maize pollen on nurse bees (Apis mellifera carnica) and their gut bacteria.

PubMed

Hendriksma, Harmen P; Küting, Meike; Härtel, Stephan; Näther, Astrid; Dohrmann, Anja B; Steffan-Dewenter, Ingolf; Tebbe, Christoph C

2013-01-01

Honey bee pollination is a key ecosystem service to nature and agriculture. However, biosafety research on genetically modified crops rarely considers effects on nurse bees from intact colonies, even though they receive and primarily process the largest amount of pollen. The objective of this study was to analyze the response of nurse bees and their gut bacteria to pollen from Bt maize expressing three different insecticidal Cry proteins (Cry1A.105, Cry2Ab2, and Cry3Bb1). Naturally Cry proteins are produced by bacteria (Bacillus thuringiensis). Colonies of Apis mellifera carnica were kept during anthesis in flight cages on field plots with the Bt maize, two different conventionally bred maize varieties, and without cages, 1-km outside of the experimental maize field to allow ad libitum foraging to mixed pollen sources. During their 10-days life span, the consumption of Bt maize pollen had no effect on their survival rate, body weight and rates of pollen digestion compared to the conventional maize varieties. As indicated by ELISA-quantification of Cry1A.105 and Cry3Bb1, more than 98% of the recombinant proteins were degraded. Bacterial population sizes in the gut were not affected by the genetic modification. Bt-maize, conventional varieties and mixed pollen sources selected for significantly different bacterial communities which were, however, composed of the same dominant members, including Proteobacteria in the midgut and Lactobacillus sp. and Bifidobacterium sp. in the hindgut. Surprisingly, Cry proteins from natural sources, most likely B. thuringiensis, were detected in bees with no exposure to Bt maize. The natural occurrence of Cry proteins and the lack of detectable effects on nurse bees and their gut bacteria give no indication for harmful effects of this Bt maize on nurse honey bees.

Modeling the patient and health system impacts of alternative xpert® MTB/RIF algorithms for the diagnosis of pulmonary tuberculosis in Addis Ababa, Ethiopia.

PubMed

Tesfaye, Abraham; Fiseha, Daniel; Assefa, Dawit; Klinkenberg, Eveline; Balanco, Silvia; Langley, Ivor

2017-05-02

To reduce global tuberculosis (TB) burden, the active disease must be diagnosed quickly and accurately and patients should be treated and cured. In Ethiopia, TB diagnosis mainly relies on spot-morning-spot (SMS) sputum sample smear analysis using Ziehl-Neelsen staining techniques (ZN). Since 2014 targeted use of xpert has been implemented. New diagnostic techniques have higher sensitivity and are likely to detect more cases if routinely implemented. The objective of our study was to project the effects of alternative diagnostic algorithms on the patient, health system, and costs, and identify cost-effective algorithms that increase TB case detection in Addis Ababa, Ethiopia. An observational quantitative modeling framework was applied using the Virtual Implementation approach. The model was designed to represent the operational and epidemiological context of Addis Ababa, the capital city of Ethiopia. We compared eight diagnostic algorithm with ZN microscopy, light emitting diode (LED) fluorescence microscopy and Xpert MTB/RIF. Interventions with an annualized cost per averted disability adjusted life year (DALY) of less than the Gross Domestic Product (GDP) per capita are considered cost-effective interventions. With a cost lower than the average per-capita GDP (US$690 for Ethiopia) for each averted disability adjusted life year (DALY), three of the modeled algorithms are cost-effective. Implementing them would have important patient, health system, and population-level effects in the context of Addis Ababa ❖ The full roll-out of Xpert MTB/RIF as the primary test for all presumptive TB cases would avert 91170 DALYs (95% credible interval [CrI] 54888 - 127448) with an additional health system cost of US$ 11.6 million over the next 10 years. The incremental cost-effectiveness ratio (ICER) is $370 per DALY averted. ❖ Same day LED fluorescence microscopy for all presumptive TB cases combined with Xpert MTB/RIF targeted to HIV-positive and High multidrug resistant (MDR) risk groups would avert 73600 DALYs( 95% CrI 48373 - 99214) with an additional cost of US$5.1 million over the next 10 years. The ICER is $169per DALY averted. ❖ Same-day LED fluorescence microscopy for all presumptive TB cases (and no Xpert MTB/RIF) would avert 43580 DALYs with a reduction cost of US$ 0.2 million over the next 10years. The ICER is $13 per DALY averted. The full roll-out of Xpert MTB/RIF is predicted to be the best option to substantially reduce the TB burden in Addis Ababa and is considered cost effective. However, the investment cost to implement this is far beyond the budget of the national TB control program. Targeted use of Xpert MTB/RIF for HIV positive and high MDR risk groups with same-day LED fluorescence microscopy for all other presumptive TB cases is an affordable alternative.

Synthetic Polymer Affinity Ligand for Bacillus thuringiensis ( Bt) Cry1Ab/Ac Protein: The Use of Biomimicry Based on the Bt Protein-Insect Receptor Binding Mechanism.

PubMed

Liu, Mingming; Huang, Rong; Weisman, Adam; Yu, Xiaoyang; Lee, Shih-Hui; Chen, Yalu; Huang, Chao; Hu, Senhua; Chen, Xiuhua; Tan, Wenfeng; Liu, Fan; Chen, Hao; Shea, Kenneth J

2018-05-24

We report a novel strategy for creating abiotic Bacillus thuringiensis ( Bt) protein affinity ligands by biomimicry of the recognition process that takes place between Bt Cry1Ab/Ac proteins and insect receptor cadherin-like Bt-R 1 proteins. Guided by this strategy, a library of synthetic polymer nanoparticles (NPs) was prepared and screened for binding to three epitopes 280 FRGSAQGIEGS 290 , 368 RRPFNIGINNQQ 379 and 436 FRSGFSNSSVSIIR 449 located in loop α8, loop 2 and loop 3 of domain II of Bt Cry1Ab/Ac proteins. A negatively charged and hydrophilic nanoparticle (NP12) was found to have high affinity to one of the epitopes, 368 RRPFNIGINNQQ 379 . This same NP also had specific binding ability to both Bt Cry1Ab and Bt Cry1Ac, proteins that share the same epitope, but very low affinity to Bt Cry2A, Bt Cry1C and Bt Cry1F closely related proteins that lack epitope homology. To locate possible NP- Bt Cry1Ab/Ac interaction sites, NP12 was used as a competitive inhibitor to block the binding of 865 NITIHITDTNNK 876 , a specific recognition site in insect receptor Bt-R 1 , to 368 RRPFNIGINNQQ 379 . The inhibition by NP12 reached as high as 84%, indicating that NP12 binds to Bt Cry1Ab/Ac proteins mainly via 368 RRPFNIGINNQQ 379 . This epitope region was then utilized as a "target" or "bait" for the separation and concentration of Bt Cry1Ac protein from the extract of transgenic Bt cotton leaves by NP12. This strategy, based on the antigen-receptor recognition mechanism, can be extended to other biotoxins and pathogen proteins when designing biomimic alternatives to natural protein affinity ligands.

21 CFR 558.355 - Monensin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... only), 44, 45, 60, or 90.7 grams per pound for use as in paragraphs (f)(1)(i) and (f)(4) of this section. (2) To 000986: 110 grams per lb., paragraphs (f)(1) (i), (iii), (iv), (v), (ix), and (x). (3) To 000986: 44 grams per lb. with 18 grams per lb. of roxarsone, 110 grams per lb. with 45 grams per lb. of...

Low LBNP Tolerance in Men is Associated With Attenuated Activation of Renin-Angiotensin System

NASA Technical Reports Server (NTRS)

Greenleaf, John E.; Petersen, T. W.; Gabrielsen, A.; Pump, B.; Bie, P.; Christensen, N.-J.; Warberg, J.; Videbaeck, R.; Simonson, S. R.; Norsk, P.;

Molecular and Insecticidal Characterization of a Novel Cry-Related Protein from Bacillus Thuringiensis Toxic against Myzus persicae

PubMed Central

Palma, Leopoldo; Muñoz, Delia; Berry, Colin; Murillo, Jesús; Ruiz de Escudero, Iñigo; Caballero, Primitivo

2014-01-01

This study describes the insecticidal activity of a novel Bacillus thuringiensis Cry-related protein with a deduced 799 amino acid sequence (~89 kDa) and ~19% pairwise identity to the 95-kDa-aphidicidal protein (sequence number 204) from patent US 8318900 and ~40% pairwise identity to the cancer cell killing Cry proteins (parasporins Cry41Ab1 and Cry41Aa1), respectively. This novel Cry-related protein contained the five conserved amino acid blocks and the three conserved domains commonly found in 3-domain Cry proteins. The protein exhibited toxic activity against the green peach aphid, Myzus persicae (Sulzer) (Homoptera: Aphididae) with the lowest mean lethal concentration (LC50 = 32.7 μg/mL) reported to date for a given Cry protein and this insect species, whereas it had no lethal toxicity against the Lepidoptera of the family Noctuidae Helicoverpa armigera (Hübner), Mamestra brassicae (L.), Spodoptera exigua (Hübner), S. frugiperda (J.E. Smith) and S. littoralis (Boisduval), at concentrations as high as ~3.5 μg/cm2. This novel Cry-related protein may become a promising environmentally friendly tool for the biological control of M. persicae and possibly also for other sap sucking insect pests. PMID:25384108

Bacillus thuringiensis Cry3Aa protoxin intoxication of Tenebrio molitor induces widespread changes in the expression of serine peptidase transcripts.

PubMed

Oppert, Brenda; Martynov, Alexander G; Elpidina, Elena N

2012-09-01

The yellow mealworm, Tenebrio molitor, is a pest of stored grain products and is sensitive to the Bacillus thuringiensis (Bt) Cry3Aa toxin. As digestive peptidases are a determining factor in Cry toxicity and resistance, we evaluated the expression of peptidase transcripts in the midgut of T. molitor larvae fed either a control or Cry3Aa protoxin diet for 24 h (RNA-Seq), or in larvae exposed to the protoxin for 6, 12, or 24 h (microarrays). Cysteine peptidase transcripts (9) were similar to cathepsins B, L, and K, and their expression did not vary more than 2.5-fold in control and Cry3Aa-treated larvae. Serine peptidase transcripts (48) included trypsin, chymotrypsin and chymotrypsin-like, elastase 1-like, and unclassified serine peptidases, as well as homologs lacking functional amino acids. Highly expressed trypsin and chymotrypsin transcripts were severely repressed, and most serine peptidase transcripts were expressed 2- to 15-fold lower in Cry3Aa-treated larvae. Many serine peptidase and homolog transcripts were found only in control larvae. However, expression of a few serine peptidase transcripts was increased or found only in Cry3Aa-treated larvae. Therefore, Bt intoxication significantly impacted the expression of serine peptidases, potentially important in protoxin processing, while the insect maintained the production of critical digestive cysteine peptidases. Published by Elsevier Inc.

CryJ-LAMP DNA Vaccines for Japanese Red Cedar Allergy Induce Robust Th1-Type Immune Responses in Murine Model

PubMed Central

Connolly, Michael; Marketon, Anthony

2016-01-01

Allergies caused by Japanese Red Cedar (JRC) pollen affect up to a third of Japanese people, necessitating development of an effective therapeutic. We utilized the lysosomal targeting property of lysosomal-associated membrane protein-1 (LAMP-1) to make DNA vaccines that encode LAMP-1 and the sequences of immunodominant allergen CryJ1 or CryJ2 from the JRC pollen. This novel strategy is designed to skew the CD4 T cell responses to the target allergens towards a nonallergenic Th1 response. CryJ1-LAMP and CryJ2-LAMP were administrated to BALB/c mice and antigen-specific Th1-type IgG2a and Th2-type IgG1 antibodies, as well as IgE antibodies, were assayed longitudinally. We also isolated different T cell populations from immunized mice and adoptively transferred them into naïve mice followed by CryJ1/CryJ2 protein boosts. We demonstrated that CryJ-LAMP immunized mice produce high levels of IFN-γ and anti-CryJ1 or anti-CryJ2 IgG2a antibodies and low levels of IgE antibodies, suggesting that a Th1 response was induced. In addition, we found that CD4+ T cells are the immunological effectors of DNA vaccination in this allergy model. Together, our results suggest the CryJ-LAMP Vaccine has a potential as an effective therapeutic for JRC induced allergy by skewing Th1/Th2 responses. PMID:27239481

Authenticity assessment of gamma- and delta-decalactone from prunus fruits by gas chromatography combustion/pyrolysis isotope ratio mass spectrometry (GC-C/P-IRMS).

PubMed

Tamura, Hirotoshi; Appel, Markus; Richling, Elke; Schreier, Peter

2005-06-29

Authenticity assessment of gamma-decalactone (1) and delta-decalactone (2) from peach (Prunus persica var. persica), apricot (Prunus armeniaca), and nectarine (Prunus persica var. nectarina) was performed using gas chromatography-isotope ratio mass spectrometry (GC-IRMS) in the combustion (C) and pyrolysis (P) mode. In addition, commercially available synthetic (nature-identical) 1 and 2 as well as biotechnologically produced samples (declared to be "natural") were characterized by their delta(2)H(V)(-)(SMOW) and delta(13)C(V)(-)(PDB) values. For the Prunus fruits under study, rather narrow ranges of delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW) data of 1, varying from - 34.6 per thousand to - 38.4 per thousand and -160 per thousand to -206 per thousand, respectively, were obtained. Synthetic references of 1 showed delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW) data ranging from -27.4 per thousand to -28.3 per thousand and -151 per thousand to -184 per thousand, respectively. Samples of 1 declared to be "natural" exhibited ranges from -28.1 per thousand to -29.2 per thousand and -192 per thousand to -286 per thousand for delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW), respectively. For 2 from peach, apricot, and nectarine, delta(13)C(V)(-)(PDB) values ranging from -34.0 per thousand to -37.9 per thousand were determined; the delta(2)H(V)(-)(SMOW) values ranged from -171 per thousand to -228 per thousand. The delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW) data for synthetic 2 were -28.2 per thousand and -171 per thousand, respectively, that is, similar to those of 2 from "natural" origin, ranging from -27.7 per thousand to -30.1 per thousand and -185 per thousand to -230 per thousand for delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW), respectively. GC-C/P-IRMS allowed clear-cut analytical differentiation of the synthetic and "ex-plant" origin of 1 and 2, whereas narrow ranges of delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW) data were found for samples of synthetic and "natural" origin.

A Study of Gibberellin Homeostasis and Cryptochrome-Mediated Blue Light Inhibition of Hypocotyl Elongation1[W][OA

PubMed Central

Zhao, Xiaoying; Yu, Xuhong; Foo, Eloise; Symons, Gregory M.; Lopez, Javier; Bendehakkalu, Krishnaprasad T.; Xiang, Jing; Weller, James L.; Liu, Xuanming; Reid, James B.; Lin, Chentao

2007-01-01

Cryptochromes mediate blue light-dependent photomorphogenic responses, such as inhibition of hypocotyl elongation. To investigate the underlying mechanism, we analyzed a genetic suppressor, scc7-D (suppressors of cry1cry2), which suppressed the long-hypocotyl phenotype of the cry1cry2 (cryptochrome1/cryptochrome2) mutant in a light-dependent but wavelength-independent manner. scc7-D is a gain-of-expression allele of the GA2ox8 gene encoding a gibberellin (GA)-inactivating enzyme, GA 2-oxidase. Although scc7-D is hypersensitive to light, transgenic seedlings expressing GA2ox at a level higher than scc7-D showed a constitutive photomorphogenic phenotype, confirming a general role of GA2ox and GA in the suppression of hypocotyl elongation. Prompted by this result, we investigated blue light regulation of mRNA expression of the GA metabolic and catabolic genes. We demonstrated that cryptochromes are required for the blue light regulation of GA2ox1, GA20ox1, and GA3ox1 expression in transient induction, continuous illumination, and photoperiodic conditions. The kinetics of cryptochrome induction of GA2ox1 expression and cryptochrome suppression of GA20ox1 or GA3ox1 expression correlate with the cryptochrome-dependent transient reduction of GA4 in etiolated wild-type seedlings exposed to blue light. Therefore we propose that in deetiolating seedlings, cryptochromes mediate blue light regulation of GA catabolic/metabolic genes, which affect GA levels and hypocotyl elongation. Surprisingly, no significant change in the GA4 content was detected in the whole shoot samples of the wild-type or cry1cry2 seedlings grown in the dark or continuous blue light, suggesting that cryptochromes may also regulate GA responsiveness and/or trigger cell- or tissue-specific changes of the level of bioactive GAs. PMID:17644628

Incorporation of excess wild-type and mutant tRNA(3Lys) into human immunodeficiency virus type 1.

PubMed Central

Huang, Y; Mak, J; Cao, Q; Li, Z; Wainberg, M A; Kleiman, L

1994-01-01

Human immunodeficiency virus (HIV) particles produced in COS-7 cells transfected with HIV type 1 (HIV-1) proviral DNA contain 8 molecules of tRNA(3Lys) per 2 molecules of genomic RNA and 12 molecules of tRNA1,2Lys per 2 molecules of genomic RNA. When COS-7 cells are transfected with a plasmid containing both HIV-1 proviral DNA and a human tRNA3Lys gene, there is a large increase in the amount of cytoplasmic tRNA3Lys per microgram of total cellular RNA, and the tRNA3Lys content in the virus increases from 8 to 17 molecules per 2 molecules of genomic RNA. However, the total number of tRNALys molecules per 2 molecules of genomic RNA remains constant at 20; i.e., the viral tRNA1,2Lys content decreases from 12 to 3 molecules per 2 molecules of genomic RNA. All detectable tRNA3Lys is aminoacylated in the cytoplasm of infected cells and deacylated in the virus. When COS-7 cells are transfected with a plasmid containing both HIV-1 proviral DNA and a mutant amber suppressor tRNA3Lys gene (in which the anticodon is changed from TTT to CTA), there is also a large increase in the relative concentration of cytoplasmic tRNA3Lys, and the tRNA3Lys content in the virus increases from 8 to 15 molecules per 2 molecules of genomic RNA, with a decrease in viral tRNA1,2Lys from 12 to 5 molecules per 2 molecules of genomic RNA. Thus, the total number of molecules of tRNALys in the virion remains at 20. The alteration of the anticodon has little effect on the viral packaging of this mutant tRNA in spite of the fact that it no longer contains the modified base mcm 5s2U at position 34, and its ability to be aminoacylated is significantly impaired compared with that of wild-type tRNA3Lys. Viral particles which have incorporated either excess wild-type tRNA3Lys or mutant suppressor tRNA3Lys show no differences in viral infectivity compared with wild-type HIV-1. Images PMID:7966556

Incidence and Progression of Chronic Kidney Disease in Black and White Individuals with Type 2 Diabetes.

PubMed

Gerber, Claire; Cai, Xuan; Lee, Jungwha; Craven, Timothy; Scialla, Julia; Souma, Nao; Srivastava, Anand; Mehta, Rupal; Paluch, Amanda; Hodakowski, Alexander; Frazier, Rebecca; Carnethon, Mercedes R; Wolf, Myles Selig; Isakova, Tamara

2018-06-07

Type 2 diabetes and associated CKD disproportionately affect blacks. It is uncertain if racial disparities in type 2 diabetes-associated CKD are driven by biologic factors that influence propensity to CKD or by differences in type 2 diabetes care. We conducted a post hoc analysis of 1937 black and 6372 white participants of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to examine associations of black race with change in eGFR and risks of developing microalbuminuria, macroalbuminuria, incident CKD (eGFR<60 ml/min per 1.73m 2 , ≥25% decrease from baseline eGFR, and eGFR slope <-1.6 ml/min per 1.73 m 2 per year), and kidney failure or serum creatinine >3.3 mg/dl. During a median follow-up that ranged between 4.4 and 4.7 years, 278 black participants (58 per 1000 person-years) and 981 white participants (55 per 1000 person-years) developed microalbuminuria, 122 black participants (16 per 1000 person-years) and 374 white participants (14 per 1000 person-years) developed macroalbuminuria, 111 black participants (21 per 1000 person-years) and 499 white participants (28 per 1000 person-years) developed incident CKD, and 59 black participants (seven per 1000 person-years) and 178 white participants (six per 1000 person-years) developed kidney failure or serum creatinine >3.3 mg/dl. Compared with white participants, black participants had lower risks of incident CKD (hazard ratio, 0.73; 95% confidence intervals, 0.57 to 0.92). There were no significant differences by race in eGFR decline or in risks of microalbuminuria, macroalbuminuria, and kidney failure or of serum creatinine >3.3 mg/dl. Black participants enrolled in a randomized controlled trial had lower rates of incident CKD compared with white participants. Rates of eGFR decline, microalbuminuria, macroalbuminuria, and kidney failure did not vary by race. Copyright © 2018 by the American Society of Nephrology.

Blood rheology and 2,3-diphosphoglycerate levels after erythropoietin treatment.

PubMed

Crowley, J P; Chazan, J A; Metzger, J B; Pono, L; Valeri, C R

1993-01-01

Twenty-seven transfusion dependent patients with end-stage renal disease on long-term dialysis had blood cell counts, serum chemistries, blood pressure, and whole blood viscosity measured, as well as having transfusion requirements assessed. Three months after the institution of recombinant human erythropoietin (rHU-EPO) (75 u per kg per wk), there was an 88 percent fall in transfusion requirement. After four months, the hematocrit increased from 24 +/- 3.8 to 25.6 +/- 4.2 percent, mean corpuscular volume from 93 +/- 4.9 to 97 +/- 6.6 fl, 2-3-diphosphoglycerate (2,3-DPG) from 13.2 +/- 3.2 to 15.6 +/- 4.3 microM per g of Hb. Whole blood viscosity fell from 14.1 +/- 2.1 to 12.7 +/- 2.3 seconds, and ferritin levels fell from 3282 +/- 3889 to 2131 +/- 2441 ng per ml. In eight patients in whom the dose of rHU-EPO was further increased by up to 50 units per kg three times weekly for three months, the hematocrit rose further to 29.3 +/- 3.0 percent and the rise in hematocrit was accompanied by a further increase in 2,3-DPG to 17.9 +/- 2.8 microM per g of Hb (p < 0.03). There were no major side effects or vascular complications.

THE TOTAL LUMINOUS EFFICIENCY OF LUMINOUS BACTERIA

PubMed Central

Harvey, E. Newton

1925-01-01

Methods are described for measuring the light emitted by an emulsion of luminous bacteria of given thickness, and calculating the light emitted by a single bacterium, measuring 1.1 x 2.2 micra, provided there is no absorption of light in the emulsion. At the same time, the oxygen consumed by a single bacterium was measured by recording the time for the bacteria to use up .9 of the oxygen dissolved in sea water from air (20 per cent oxygen). The luminescence intensity does not diminish until the oxygen concentration falls below 2 per cent, when the luminescence diminishes rapidly. Above 2 per cent oxygen (when the oxygen dissolving in sea water from pure oxygen at 760 mm. Hg pressure = 100 per cent) the bacteria use equal amounts of oxygen in equal times, while below 2 per cent oxygen it seems very likely that rate of oxygen absorption is proportional to oxygen concentration. By measuring the time for a tube of luminous bacteria of known concentration saturated with air (20 per cent oxygen) to begin to darken (2 per cent oxygen) we can calculate the oxygen absorbed by one bacterium per second. The bacteria per cc. are counted on a blood counting slide or by a centrifugal method, after measuring the volume of a single bacterium (1.695 x 10–12 cc.). Both methods gave results in good agreement with each other. The maximum value for the light from a single bacterium was 24 x 10–14 lumens or 1.9 x 10–14 candles. The maximum value for lumen-seconds per mg. of oxygen absorbed was 14. The average value for lumen-seconds per mg. O2 was 9.25. The maximum values were selected in calculating the efficiency of light production, since some of the bacteria counted may not be producing light, although they may still be using oxygen. The "diet" of the bacteria was 60 per cent glycerol and 40 per cent peptone. To oxidize this mixture each mg. of oxygen would yield 3.38 gm. calories or 14.1 watts per second. 1 lumen per watt is therefore produced by a normal bacterium which emits 14 lumen-seconds per mg. O2 absorbed. Since the maximum lumens per watt are 640, representing 100 per cent efficiency, the total luminous efficiency if .00156. As some of the oxygen is used in respiratory oxidation which may have nothing to do with luminescence, the luminescence efficiency must be higher than 1 lumen per watt. Experiments with KCN show that this substance may reduce the oxygen consumption to 1/20 of its former value while reducing the luminescence intensity only ¼. A partial separation of respiratory from luminescence oxidations is therefore effected by KCN, and our efficiency becomes 5 lumens per watt, or .0078. This is an over-all efficiency, based on the energy value of the "fuel" of the bacteria, regarded as a power plant for producing light. It compares very favorably with the 1.6 lumens per watt of a tungsten vacuum lamp or the 3.9 lumens per watt of a tungsten nitrogen lamp, if we correct the usual values for these illuminants, based on watts at the lamp terminals, for a 20 per cent efficiency of the power plant converting the energy of coal fuel into electric current. The specific luminous emission of the bacteria is 3.14 x 10–6 lumens per cm2. One bacterium absorbs 215,000 molecules of oxygen per second and emits 1,280 quanta of light at λmax = 510µµ. If we suppose that a molecule of oxygen uniting with luminous material gives rise to the emission of 1 quantum of light energy, only 1/168 of the oxygen absorbed is used in luminescence. On this basis the efficiency becomes 168 lumens per watt or 26.2 per cent. PMID:19872192

Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior.

PubMed

Schaufler, Jörg; Ronovsky, Marianne; Savalli, Giorgia; Cabatic, Maureen; Sartori, Simone B; Singewald, Nicolas; Pollak, Daniela D

2016-01-01

Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs - also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated. The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular level were examined using mice selectively bred for high anxiety-related and co-segregating depression-like behavior (HAB) and normal anxiety/depression behavior mice (NAB). The length of the circadian period was increased in fluoxetine-treated HAB as compared to NAB mice while the number of activity bouts and light-induced entrainment were comparable. No difference in hippocampal Cry2 expression, previously reported to be dysbalanced in untreated HAB mice, was observed, while Per2 and Per3 mRNA levels were higher in HAB mice under fluoxetine treatment. The present findings provide evidence that fluoxetine treatment normalizes disrupted circadian locomotor activity and clock gene expression in a genetic mouse model of high trait anxiety and depression. An interaction between the molecular mechanisms mediating the antidepressant response to fluoxetine and the endogenous regulation of circadian rhythms in genetically based mood and anxiety disorders is proposed.

No tears in heaven: did the media create the pseudo-phenomenon “altitude-adjusted lachrymosity syndrome (AALS)”?

PubMed Central

Lancashire, Lee

2018-01-01

Objective In the media, numerous public figures have reported involuntary emotional outbursts arising from watching films on planes, resembling neurological phenomena such as pseudobulbar affect. Putative risk factors put forward include altitude, mild hypoxia, or alcohol. Our objective was to determine whether watching a film on an airplane is really more likely to induce involuntary, uncontrollable, or surprising crying than watching one on the ground, described in some social media as “altitude-adjusted lachrymosity syndrome” (AALS), or whether this is a pseudo-phenomena. Methods Amazon Mechanical Turk survey participants (N = 1,084) living in the United States who had watched a film on a plane in the past 12 months were invited to complete an online survey. The main outcome measures were likelihood of crying in a logistic regression model including location of viewing, age, gender, genre of film, subjective film rating, annual household income, watching a “guilty pleasure” film, drinking alcohol, feeling tired or jetlagged, or having a recent emotional life event. Results About one in four films induced crying. Watching a film on a plane per se does not appear to induce involuntary crying. Significant predictors of crying included dramas or family films, a recent life event, watching a “guilty pleasure”, high film ratings, and female gender. Medical conditions, age, income, alcohol use, and feeling tired or jetlagged were not significant. Conclusion People reporting the pseudo-phenomena of AALS are most likely experiencing “dramatically heightened exposure”, watching as many films on a plane in a week’s return trip as they would in a year at the cinema. Such perceptions are probably magnified by confirmation bias and further mentions in social media. PMID:29632743

Risk Factors for Hepatitis C Virus Reinfection After Sustained Virologic Response in Patients Coinfected With HIV

PubMed Central

Young, Jim; Rossi, Carmine; Gill, John; Walmsley, Sharon; Cooper, Curtis; Cox, Joseph; Martel-Laferriere, Valerie; Conway, Brian; Pick, Neora; Vachon, Marie-Louise

2017-01-01

Abstract Background. Highly effective hepatitis C virus (HCV) therapies have spurred a scale-up of treatment to populations at greater risk of reinfection after sustained virologic response (SVR). Reinfection may be higher in HIV–HCV coinfection, but prior studies have considered small selected populations. We assessed risk factors for reinfection after SVR in a representative cohort of Canadian coinfected patients in clinical care. Methods. All patients achieving SVR after HCV treatment were followed with HCV RNA measurements every 6 months in a prospective cohort study. We used Bayesian Cox regression to estimate reinfection rates according to patient reported injection drug use (IDU) and sexual activity among men who have sex with men (MSM). Results. Of 497 patients treated for HCV, 257 achieved SVR and had at least 1 subsequent RNA measurement. During 589 person-years of follow-up (PYFU) after SVR, 18 (7%) became HCV RNA positive. The adjusted reinfection rate (per 1000 PYFU) in the first year after SVR was highest in those who reported high-frequency IDU (58; 95% credible interval [CrI], 18–134) followed by MSM reporting high-risk sexual activity (26; 95% CrI, 6–66) and low-frequency IDU (22; 95% CrI, 4–68). The rate in low-risk MSM (16; 95% CrI, 4–38) was similar to that in reference patients (10; 95% CrI, 4–20). Reinfection rates did not diminish with time. Conclusions. HCV reinfection rates varied according to risk. Measures are needed to reduce risk behaviors and increase monitoring in high-risk IDU and MSM if HCV elimination targets are to be realized. PMID:28199495

No tears in heaven: did the media create the pseudo-phenomenon "altitude-adjusted lachrymosity syndrome (AALS)"?

PubMed

Wicks, Paul; Lancashire, Lee

2018-01-01

In the media, numerous public figures have reported involuntary emotional outbursts arising from watching films on planes, resembling neurological phenomena such as pseudobulbar affect. Putative risk factors put forward include altitude, mild hypoxia, or alcohol. Our objective was to determine whether watching a film on an airplane is really more likely to induce involuntary, uncontrollable, or surprising crying than watching one on the ground, described in some social media as "altitude-adjusted lachrymosity syndrome" (AALS), or whether this is a pseudo-phenomena. Amazon Mechanical Turk survey participants ( N  = 1,084) living in the United States who had watched a film on a plane in the past 12 months were invited to complete an online survey. The main outcome measures were likelihood of crying in a logistic regression model including location of viewing, age, gender, genre of film, subjective film rating, annual household income, watching a "guilty pleasure" film, drinking alcohol, feeling tired or jetlagged, or having a recent emotional life event. About one in four films induced crying. Watching a film on a plane per se does not appear to induce involuntary crying. Significant predictors of crying included dramas or family films, a recent life event, watching a "guilty pleasure", high film ratings, and female gender. Medical conditions, age, income, alcohol use, and feeling tired or jetlagged were not significant. People reporting the pseudo-phenomena of AALS are most likely experiencing "dramatically heightened exposure", watching as many films on a plane in a week's return trip as they would in a year at the cinema. Such perceptions are probably magnified by confirmation bias and further mentions in social media.

Consumption of Bt Rice Pollen Containing Cry1C or Cry2A Protein Poses a Low to Negligible Risk to the Silkworm Bombyx mori (Lepidoptera: Bombyxidae)

PubMed Central

Yang, Yan; Liu, Yue; Cao, Fengqin; Chen, Xiuping; Cheng, Lisheng; Romeis, Jörg; Li, Yunhe; Peng, Yufa

2014-01-01

By consuming mulberry leaves covered with pollen from nearby genetically engineered, insect-resistant rice lines producing Cry proteins derived from Bacillus thuringiensis (Bt), larvae of the domestic silkworm, Bombyx mori (Linnaeus) (Lepidoptera: Bombyxidae), could be exposed to insecticidal proteins. Laboratory experiments were conducted to assess the potential effects of Cry1C- or Cry2A-producing transgenic rice (T1C-19, T2A-1) pollen on B. mori fitness. In a short-term assay, B. mori larvae were fed mulberry leaves covered with different densities of pollen from Bt rice lines or their corresponding near isoline (control) for the first 3 d and then were fed mulberry leaves without pollen. No effect was detected on any life table parameter, even at 1800 pollen grains/cm2 leaf, which is much higher than the mean natural density of rice pollen on leaves of mulberry trees near paddy fields. In a long-term assay, the larvae were fed Bt and control pollen in the same way but for their entire larval stage (approximately 27 d). Bt pollen densities ≥150 grains/cm2 leaf reduced 14-d larval weight, increased larval development time, and reduced adult eclosion rate. ELISA analyses showed that 72.6% of the Cry protein was still detected in the pollen grains excreted with the feces. The low exposure of silkworm larvae to Cry proteins when feeding Bt rice pollen may be the explanation for the relatively low toxicity detected in the current study. Although the results demonstrate that B. mori larvae are sensitive to Cry1C and Cry2A proteins, the exposure levels that harmed the larvae in the current study are far greater than natural exposure levels. We therefore conclude that consumption of Bt rice pollen will pose a low to negligible risk to B. mori. PMID:25014054

Cytotoxicity and binding profiles of activated Cry1Ac and Cry2Ab to three insect cell lines

USDA-ARS?s Scientific Manuscript database

While Cry1Ac has been known to bind with larval midgut proteins cadherin, APN (amino peptidase N), ALP (alkaline phosphatase) and ABCC2 (ATP-binding cassette transporter subfamily C2), little is known about the receptors of Cry2Ab. To provide a clue to the receptors of Cry2Ab, we tested the baselin...

Polycystic Ovary Syndrome

PubMed Central

McCartney, Christopher R.; Marshall, John C.

2017-01-01

A 22-year-old woman reports having hirsutism and irregular menses. She describes unpredictable and infrequent menses (five or six per year) since menarche at 11 years of age. Dark, coarse facial hair began to develop at 13 years of age. The symptoms worsened after she gained weight in college. The physical examination includes a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 29, blood pressure of 135/85 mm Hg, and moderate hirsutism without virilization. Laboratory tests reveal a total testosterone level of 65 ng per deciliter (2.3 nmol per liter) (assay reference range, 14 to 53 ng per deciliter [0.5 to 1.8 nmol per liter]), calculated free testosterone level of 15.3 pg per milliliter (53.1 pmol per liter) (assay reference range, 0.6 to 6.8 pg per milliliter [2.1 to 23.6 pmol per liter]), and glycated hemoglobin level of 5.7% (normal value, ≤5.6%). How should this case be evaluated and managed? PMID:27406348

Field‐evolved resistance to Bt maize in sugarcane borer (Diatraea saccharalis) in Argentina

PubMed Central

Grimi, Damián A; Ramos, María Laura; Machado, Marcos; Ocampo, Federico; Willse, Alan; Martinelli, Samuel; Head, Graham

2018-01-01

Abstract BACKGROUND Maize technologies expressing Bacillus thuringiensis (Bt) insecticidal proteins are widely used in Argentina to control sugarcane borer (Diatraea saccharalis Fabricius). Unexpected D. saccharalis damage was observed to Bt maize events TC1507 (expressing Cry1F) and MON 89034 × MON 88017 (expressing Cry1A.105 and Cry2Ab2) in an isolated area of San Luis Province. Diatraea saccharalis larvae were sampled from MON 89034 × MON 88017 fields in the area to generate a resistant strain (RR), which was subsequently characterized in plant and diet bioassays. RESULTS Survivorship of the RR strain was high on TC1507 leaf tissue, intermediate on MON 89034 × MON 88017, and low on MON 810 (expressing Cry1Ab). The RR strain had high resistance to Cry1A.105 (186.74‐fold) and no resistance to Cry2Ab2 in diet bioassays. These results indicate resistance to Cry1F and Cry1A.105 (and likely cross‐resistance between them) but not to Cry1Ab or Cry2Ab2. Resistance to MON 89034 × MON 88017 was functionally recessive. Reviews of grower records suggest that resistance initially evolved to Cry1F, conferring cross‐resistance to Cry1A.105, with low refuge compliance as the primary cause. A mitigation plan was implemented in San Luis that included technology rotation, field monitoring, and grower education on best management practices (BMPs) including refuges. CONCLUSION In the affected area, the resistance to Cry1F and Cry1A.105 is being managed effectively through use of MON 89034 × MON 88017 and MON 810 in combination with BMPs, and no spread of resistance to other regions has been observed. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID:29095565

Cross-Resistance between Cry1 Proteins in Fall Armyworm (Spodoptera frugiperda) May Affect the Durability of Current Pyramided Bt Maize Hybrids in Brazil

PubMed Central

Bernardi, Daniel; Salmeron, Eloisa; Horikoshi, Renato Jun; Bernardi, Oderlei; Dourado, Patrick Marques; Carvalho, Renato Assis; Martinelli, Samuel; Head, Graham P.; Omoto, Celso

2015-01-01

Genetically modified plants expressing insecticidal proteins from Bacillus thuringiensis (Bt) offer valuable options for managing insect pests with considerable environmental and economic benefits. Despite the benefits provided by Bt crops, the continuous expression of these insecticidal proteins imposes strong selection for resistance in target pest populations. Bt maize (Zea mays) hybrids have been successful in controlling fall armyworm (Spodoptera frugiperda), the main maize pest in Brazil since 2008; however, field-evolved resistance to the protein Cry1F has recently been reported. Therefore it is important to assess the possibility of cross-resistance between Cry1F and other Cry proteins expressed in Bt maize hybrids. In this study, an F2 screen followed by subsequent selection on MON 89034 maize was used to select an S. frugiperda strain (RR) able to survive on the Bt maize event MON 89034, which expresses the Cry1A.105 and Cry2Ab2 proteins. Field-collected insects from maize expressing the Cry1F protein (event TC1507) represented most of the positive (resistance allele-containing) (iso)families found. The RR strain showed high levels of resistance to Cry1F, which apparently also conferred high levels of cross resistance to Cry1A.105 and Cry1Ab, but had only low-level (10-fold) resistance to Cry2Ab2. Life history studies to investigate fitness costs associated with the resistance in RR strain revealed only small reductions in reproductive rate when compared to susceptible and heterozygous strains, but the RR strain produced 32.2% and 28.4% fewer females from each female relative to the SS and RS (pooled) strains, respectively. Consistent with the lack of significant resistance to Cry2Ab2, MON 89034 maize in combination with appropriate management practices continues to provide effective control of S. frugiperda in Brazil. Nevertheless, the occurrence of Cry1F resistance in S. frugiperda across Brazil, and the cross-resistance to Cry1Ab and Cry1A.105, indicates that current Cry1-based maize hybrids face a challenge in managing S. frugiperda in Brazil and highlights the importance of effective insect resistance management for these technologies. PMID:26473961

Cross-Resistance between Cry1 Proteins in Fall Armyworm (Spodoptera frugiperda) May Affect the Durability of Current Pyramided Bt Maize Hybrids in Brazil.

PubMed

Bernardi, Daniel; Salmeron, Eloisa; Horikoshi, Renato Jun; Bernardi, Oderlei; Dourado, Patrick Marques; Carvalho, Renato Assis; Martinelli, Samuel; Head, Graham P; Omoto, Celso

2015-01-01

Genetically modified plants expressing insecticidal proteins from Bacillus thuringiensis (Bt) offer valuable options for managing insect pests with considerable environmental and economic benefits. Despite the benefits provided by Bt crops, the continuous expression of these insecticidal proteins imposes strong selection for resistance in target pest populations. Bt maize (Zea mays) hybrids have been successful in controlling fall armyworm (Spodoptera frugiperda), the main maize pest in Brazil since 2008; however, field-evolved resistance to the protein Cry1F has recently been reported. Therefore it is important to assess the possibility of cross-resistance between Cry1F and other Cry proteins expressed in Bt maize hybrids. In this study, an F2 screen followed by subsequent selection on MON 89034 maize was used to select an S. frugiperda strain (RR) able to survive on the Bt maize event MON 89034, which expresses the Cry1A.105 and Cry2Ab2 proteins. Field-collected insects from maize expressing the Cry1F protein (event TC1507) represented most of the positive (resistance allele-containing) (iso)families found. The RR strain showed high levels of resistance to Cry1F, which apparently also conferred high levels of cross resistance to Cry1A.105 and Cry1Ab, but had only low-level (10-fold) resistance to Cry2Ab2. Life history studies to investigate fitness costs associated with the resistance in RR strain revealed only small reductions in reproductive rate when compared to susceptible and heterozygous strains, but the RR strain produced 32.2% and 28.4% fewer females from each female relative to the SS and RS (pooled) strains, respectively. Consistent with the lack of significant resistance to Cry2Ab2, MON 89034 maize in combination with appropriate management practices continues to provide effective control of S. frugiperda in Brazil. Nevertheless, the occurrence of Cry1F resistance in S. frugiperda across Brazil, and the cross-resistance to Cry1Ab and Cry1A.105, indicates that current Cry1-based maize hybrids face a challenge in managing S. frugiperda in Brazil and highlights the importance of effective insect resistance management for these technologies.

Enhancing the understanding of earthworm feeding behaviour via the use of fatty acid delta13C values determined by gas chromatography-combustion-isotope ratio mass spectrometry.

PubMed

Dungait, Jennifer A J; Briones, Maria J I; Bol, Roland; Evershed, Richard P

2008-06-01

Litter-dwelling (epigeic) Lumbricus rubellus and soil-dwelling (endogeic) Allolobophora chlorotica earthworms were observed aggregating under C(3) (delta(13)C = -31.3 per thousand; delta(15)N = 10.7 per thousand) and C(4) (delta(13)C = -12.6 per thousand; delta(15)N = 7.5 per thousand) synthetic dung pats applied to a temperate grassland (delta(13)C = -30.3 per thousand; delta(15)N = 5.7 per thousand) in an experiment carried out for 372 days. Bulk delta(13)C values of earthworms collected from beneath either C(3) or C(4) dung after 28, 56, 112 and 372 days demonstrated that (i) L. rubellus beneath C(4) dung were significantly (13)C-enriched after 56 days (delta(13)C = -23.8 per thousand) and 112 days (delta(13)C = -22.4 per thousand) compared with those from C(3) dung treatments (56 days, delta(13)C = -26.5 per thousand; 112 days, delta(13)C = -27.0 per thousand), and (ii) A. chlorotica were 2.1 per thousand (13)C-enriched (delta(13)C = -24.2 per thousand) relative to those from C(3) dung (delta(13)C = -26.3 per thousand) treatments after 372 days. Bulk delta(15)N values did not suggest significant uptake of dung N by either species beneath C(3) or C(4) dung, but showed that the endogeic species (total mean delta(15)N = 3.3 per thousand) had higher delta(15)N values than the epigeic species (total mean delta(15)N = 5.4 per thousand). Although the two species exhibited similar fatty acid profiles, individual fatty acid delta(13)C values revealed extensive routing of dietary C into body tissue of L. rubellus, but minor incorporation into A. chlorotica. In particular, the direct incorporation of microbial biomarker fatty acids (iC(17:0), aC(17:0)) from (13)C-labelled dung in situ, the routing of dung C into de novo synthesised compounds (iC(20:4)(omega)(6),C(20:5)(omega)(3), and the assimilation of essential fatty acids ((C(18:1)(omega)(9), C(18:1)(omega(7), C(18:2)(omega(6), C(18:3)(omega)(3)) derived from dung, were determined. John Wiley & Sons, Ltd

Human oocyte cryopreservation: 5-year experience with a sodium-depleted slow freezing method.

PubMed

Boldt, Jeffrey; Tidswell, Non; Sayers, Amy; Kilani, Rami; Cline, Donald

2006-07-01

A slow freezing/rapid thawing method for the cryopreservation of human oocytes has been employed using a sodium-depleted culture media. In 53 frozen egg-embryo transfer (FEET) cycles, a 60.4% survival rate post-thaw was obtained and a 62.0% fertilization rate following intracytoplasmic sperm injection. Overall pregnancy rates were 26.4% per thaw attempt, 30.4% per patient, and 32.6% per embryo transfer. Pregnancy rates using sodium-depleted phosphate-buffered saline (PBS) as the base medium were 20.0% per thaw, 21.7% per patient, and 26.3% per transfer. With sodium-depleted modified human tubal fluid (mHTF) as the base for the cryopreservation medium, rates were 32.1% per thaw attempt, 39.1% per patient, 37.5% per transfer. The overall implantation rates were 4.2% per thawed oocyte and 13.6% per embryo, (PBS: 3.0% per egg, 10.6% per embryo; mHTF:5.3% per oocyte; 15.9% per embryo). These data indicate that the use of a sodium-depleted media with slow freezing and rapid thawing can yield acceptable pregnancy rates after FEET.

Interspecific variation in SO/sub 2/ flux: leaf surface versus internal flux, and components of leaf conductance. [Pisum sativum L. , Lycopersicon esculentum Mill. Flacca, Geranium carolinianum L. , Diplacus aurantiacus (Curtis) Jeps

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olszyk, D.M.; Tingey, D.T.

The objective of this study was to clarify the relationships among stomatal, residual, and epidermal conductances in determining the flux of SO/sub 2/ air pollution to leaves. Variations in leaf SO/sub 2/ and H/sub 2/O vapor fluxes were determined using four plant species: Pisum sativum L. (garden pea), Lycopersicon esculentum Mill. flacca (mutant of tomato), Geranium carolinianum L. (wild geranium), and Diplacus aurantiacus (Curtis) Jeps. (a native California shrub). Fluxes were measured using the mass-balance approach during exposure to 4.56 micromoles per cubic meter (0.11 microliters per liter) SO/sub 2/ for 2 hours in a controlled environmental chamber. Flux throughmore » adaxial and abaxial leaf surfaces with closed stomata ranged from 1.9 to 9.4 nanomoles per square meter per second for SO/sub 2/, and 0.3 to 1.3 millimoles per square meter per second for H/sub 2/O vapor. Flux of SO/sub 2/ into leaves through stomata ranged from approx.0 to 8.5 (dark) and 3.8 to 16.0 (light) millimoles per square meter per second. Flux of H/sub 2/O vapor from leaves through stomata ranged from approx.0 to 0.6 (dark) to 0.4 to 0.9 (light) millimole per square meter per second. Lycopersicon had internal flux rates for both SO/sub 2/ and H/sub 2/O vapor over twice as high as for the other species. Stomatal conductance based on H/sub 2/O vapor flux averaged from 0.07 to 0.13 mole per square meter per second among the four species. Internal conductance of SO/sub 2/ as calculated from SO/sub 2/ flux was from 0.04 mole per square meter per second lower to 0.06 mole per square meter per second higher than stomatal conductance. For Pisum, Geranium, and Diplacus stomatal conductance was the same or slightly higher than internal conductance, indicating that, in general, SO/sub 2/ flux could be predicted from stomatal conductance for H/sub 2/O vapor.« less

Prevalence and risk factors for diabetic retinopathy in Asian Indians with young onset type 1 and type 2 diabetes.

PubMed

Rajalakshmi, Ramachandran; Amutha, Anandakumar; Ranjani, Harish; Ali, Mohammed K; Unnikrishnan, Ranjit; Anjana, Ranjit Mohan; Narayan, K M Venkat; Mohan, Viswanathan

2014-01-01

To assess the prevalence and risk factors for diabetic retinopathy (DR) in people with young onset type 1 (T1DM-Y) and type 2 diabetes (T2DM-Y). T1DM-Y(n=150) and T2DM-Y(n=150) participants, age between 10 and 25 years at diagnosis, had a complete clinical evaluation, biochemical assessment, and four field digital retinal colour photography. The Early Treatment Diabetic Retinopathy Study grading system was used to grade DR. Proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) were considered as sight threatening DR. The prevalence of any DR was 53.3% [95% CI 45.3-61.3] in T1DM-Y (duration of diabetes: 12.4±7.4 years) and 52.7% [44.7-60.7] in T2DM-Y (11.8±8.3 years). The age and gender adjusted prevalence of DR, DME and PDR was 62.5%, 10% and 7.3% in T1DM-Y, whereas it was 65.8%,12.7% and 9.3% in T2DM-Y respectively. In multivariable logistic regression, diabetes duration [Odds ratio (OR) 1.99 per 5 years; CI 1.42-2.79], waist circumference [1.28 per 5 cm;1.05-1.56] and microalbuminuria [2.39 per 50 μg;1.07-5.31] were associated with DR in T1DM-Y, and diabetes duration [2.21 per 5 years; 1.61-3.02], diastolic blood pressure [1.54 per 5 mmHg;1.18-2.02], Glycated hemoglobin [1.37 per %;1.07-1.75] and lower stimulated C-peptide [1.54 per 0.5 pmol/ml;1.15-2.05;] were associated with DR in T2DM-Y. Over half of the people with young-onset diabetes, regardless of type, have retinopathy within 10-12 years of diabetes duration, emphasizing the need for regular eye screening and aggressive control of glucose and blood pressure to prevent DR. Copyright © 2014 Elsevier Inc. All rights reserved.

Laboratory toxicity studies demonstrate no adverse effects of Cry1Ab and Cry3Bb1 to larvae of Adalia bipunctata (Coleoptera: Coccinellidae): the importance of study design.

PubMed

Alvarez-Alfageme, Fernando; Bigler, Franz; Romeis, Jörg

2011-06-01

Scientific studies are frequently used to support policy decisions related to transgenic crops. Schmidt et al., Arch Environ Contam Toxicol 56:221-228 (2009) recently reported that Cry1Ab and Cry3Bb were toxic to larvae of Adalia bipunctata in direct feeding studies. This study was quoted, among others, to justify the ban of Bt maize (MON 810) in Germany. The study has subsequently been criticized because of methodological shortcomings that make it questionable whether the observed effects were due to direct toxicity of the two Cry proteins. We therefore conducted tritrophic studies assessing whether an effect of the two proteins on A. bipunctata could be detected under more realistic routes of exposure. Spider mites that had fed on Bt maize (events MON810 and MON88017) were used as carriers to expose young A. bipunctata larvae to high doses of biologically active Cry1Ab and Cry3Bb1. Ingestion of the two Cry proteins by A. bipunctata did not affect larval mortality, weight, or development time. These results were confirmed in a subsequent experiment in which A. bipunctata were directly fed with a sucrose solution containing dissolved purified proteins at concentrations approximately 10 times higher than measured in Bt maize-fed spider mites. Hence, our study does not provide any evidence that larvae of A. bipunctata are sensitive to Cry1Ab and Cry3Bb1 or that Bt maize expressing these proteins would adversely affect this predator. The results suggest that the apparent harmful effects of Cry1Ab and Cry3Bb1 reported by Schmidt et al., Arch Environ Contam Toxicol 56:221-228 (2009) were artifacts of poor study design and procedures. It is thus important that decision-makers evaluate the quality of individual scientific studies and do not view all as equally rigorous and relevant.

Hybrid 2D photonic crystal-assisted Lu3Al5O12:Ce ceramic-plate phosphor and free-standing red film phosphor for white LEDs with high color-rendering index.

PubMed

Park, Hoo Keun; Oh, Ji Hye; Kang, Heejoon; Zhang, Jian; Do, Young Rag

2015-03-04

This paper reports the combined optical effects of a two-dimensional (2D) SiNx photonic crystal layer (PCL)-assisted Lu3Al5O12:Ce (LuAG:Ce) green ceramic-plate phosphor (CPP) and a free-standing (Sr,Ca)AlSiN3:Eu red film phosphor to enhance luminous efficacy, color rendering index (CRI), and special CRI (R9) of LuAG:Ce CPP-capped white light-emitting diodes (LEDs) for high-power white LEDs at 350 mA. By introducing the 2D SiNx PCL, the luminous efficacy was improved by a factor of 1.25 and 1.15 compared to that of the conventional flat CPP-capped LED and the thickness-increased CPP-capped LED (with a thickness of 0.15 mm), respectively, while maintaining low color-rendering properties. The combining of the free-standing red film phosphor in the flat CPP-capped, the 2D PCL-assisted CPP-capped, and the thickness-increased CPP-capped LEDs led to enhancement of the CRI and the special CRI (R9); it also led to a decrease of the correlated color temperature (CCT) due to broad wavelength coverage via the addition of red emission. High CRI (94), natural white CCT (4450 K), and acceptable luminous efficacy (71.1 lm/W) were attained from the 2D PCL-assisted LuAG:Ce CPP/free-standing red film phosphor-based LED using a red phosphor concentration of 7.5 wt %. It is expected that the combination of the 2D PCL and the free-standing red film phosphor will be a good candidate for achieving a high-power white CPP-capped LED with excellent CRI.

Cry1Ac and Vip3Aa proteins from Bacillus thuringiensis targeting Cry toxin resistance in Diatraea flavipennella and Elasmopalpus lignosellus from sugarcane

PubMed Central

2017-01-01

The biological potential of Vip and Cry proteins from Bacillus is well known and widely established. Thus, it is important to look for new genes showing different modes of action, selecting those with differentiated entomotoxic activity against Diatraea flavipennella and Elasmopalpus lignosellus, which are secondary pests of sugarcane. Therefore, Cry1 and Vip3 proteins were expressed in Escherichia coli, and their toxicities were evaluated based on bioassays using neonate larvae. Of those, the most toxic were Cry1Ac and Vip3Aa considering the LC50 values. Toxins from E. coli were purified, solubilized, trypsinized, and biotinylated. Brush Border Membrane Vesicles (BBMVs) were prepared from intestines of the two species to perform homologous and heterologous competition assays. The binding assays demonstrated interactions between Cry1Aa, Cry1Ac, and Vip3Aa toxins and proteins from the BBMV of D. flavipennella and E. lignosellus. Homologous competition assays demonstrated that binding to one of the BBMV proteins was specific for each toxin. Heterologous competition assays indicated that Vip3Aa was unable to compete for Cry1Ac toxin binding. Our results suggest that Cry1Ac and Vip3Aa may have potential in future production of transgenic sugarcane for control of D. flavipennella and E. lignosellus, but more research is needed on the potential antagonism or synergism of the toxins in these pests. PMID:28123906

DOE Office of Scientific and Technical Information (OSTI.GOV)

Topkan, Erkan, E-mail: docdretopkan@gmail.com; Yildirim, Berna Akkus; Guler, Ozan Cem

Purpose: To investigate the safety and efficacy of single-dose 8-Gy palliative chest reirradiation (CRI) in metastatic non-small cell lung cancer (M-NSCLC) patients with painful thoracic failures (TF) within the previous radiation portal. Patients and Methods: We retrospectively analyzed the clinical data of 78 M-NSCLC patients who received single-dose 8-Gy CRI for painful TF after concurrent chemoradiation therapy to a total radiation dose of 52 to 66 Gy between 2007 and 2012. Primary endpoints included significant pain relief (SPR) defined as a ≥2 point decrement in the Visual Analogue Scale for Pain inventory (VAS-P), time to pain relief, and duration of painmore » control. Secondary objectives were survival and prognostic factors. Results: Treatment was well tolerated, with only 5.1% grade 3 pneumonitis and 1.3% grade 2 esophagitis. Pre-CRI median and post-CRI minimum VAS-P were 7 and 3 (P<.001), respectively. SPR was noted in 67 (85.9%) patients, and only 3 (3.9%) scored progressive pain. Median time to lowest VAS-P and duration of pain control were 27 days and 6.1 months, respectively. Median overall survival (OS) was 7.7 months, and the 1-year OS rate was 26.5%. On multivariate analyses, lower Eastern Cooperative Oncology group score (1-2; P<.001), absence of anemia (P=.001), and fewer metastatic sites (1-2; P<.001) were found to be associated with longer OS. Conclusions: Single-dose 8-Gy CRI provides safe, effective, and durable pain palliation for TF in radically irradiated M-NSCLC patients. Because of its convenience, lower cost, and higher comfort, the present protocol can be considered an appropriate option for patients with limited life spans.« less

Diurnal rhythmicity of the clock genes Per1 and Per2 in the rat ovary.

PubMed

Fahrenkrug, Jan; Georg, Birgitte; Hannibal, Jens; Hindersson, Peter; Gräs, Søren

2006-08-01

Circadian rhythms are generated by endogenous clocks in the central brain oscillator, the suprachiasmatic nucleus, and peripheral tissues. The molecular basis for the circadian clock consists of a number of genes and proteins that form transcriptional/translational feedback loops. In the mammalian gonads, clock genes have been reported in the testes, but the expression pattern is developmental rather than circadian. Here we investigated the daily expression of the two core clock genes, Per1 and Per2, in the rat ovary using real-time RT-PCR, in situ hybridization histochemistry, and immunohistochemistry. Both Per1 and Per2 mRNA displayed a statistically significant rhythmic oscillation in the ovary with a period of 24 h in: 1) a group of rats during proestrus and estrus under 12-h light,12-h dark cycles; 2) a second group of rats representing a mixture of all 4 d of the estrous cycle under 12-h light,12-h dark conditions; and 3) a third group of rats representing a mixture of all 4 d of estrous cycle during continuous darkness. Per1 mRNA was low at Zeitgeber time 0-2 and peaked at Zeitgeber time 12-14, whereas Per2 mRNA was delayed by approximately 4 h relative to Per1. By in situ hybridization histochemistry, Per mRNAs were localized to steroidogenic cells in preantral, antral, and preovulatory follicles; corpora lutea; and interstitial glandular tissue. With newly developed antisera, we substantiated the expression of Per1 and Per2 in these cells by single/double immunohistochemistry. Furthermore, we visualized the temporal intracellular movements of PER1 and PER2 proteins. These findings suggest the existence of an ovarian circadian clock, which may play a role both locally and in the hypothalamo-pituitary-ovarian axis.

Prevalence of bovine milk pathogens in Azorean pastures: mobile versus fixed milking machines.

PubMed

Azevedo, C; Pacheco, D; Soares, L; Moitoso, M; Maldonado, J; Guix, R; Simões, J

2016-01-01

The aims of the present study were (1) to evaluate the influence of using mobile (n=47) or fixed (n=45) milking machines in Azorean herds on the apparent prevalence of several milk pathogens in bulk tank milk (BTM) and (2) to determine whether separated subclinical mastitic cows can serve, in real time, as predictors of milk pathogen prevalence for the remaining animals at the herd level. The use of a mobile or fixed milking machine influenced (P≤0.05) the prevalence of Staphylococcus aureus (72.3 per cent; n=34 v 51.1 per cent; n=23, respectively) and Klebsiella species (46.8 per cent; n=22 v 26.7 per cent; n=12, respectively). S aureus (95 per cent CI OR 1.1 to 6.0) and Klebsiella species (95 per cent CI OR 1.0 to 5.8) were 2.5 times more likely to increase in the BTM of herds using mobile milking machines. The prevalence of coagulase-negative staphylococci (100 per cent; n=92), Escherichia coli (75.0 per cent), Corynebacterium bovis (57.6 per cent), Enterococcus species (55.4 per cent), Streptococcus dysgalactiae (51.1 per cent), Streptococcus uberis (41.3 per cent), Actinomyces pyogenes or Peptostreptococcus indolicus (41.3 per cent) and Streptococcus agalactiae (32.6 per cent) in BTM remained similar among the herds. κ coefficients were always <0.70, indicating intra-herd disagreement of the prevalence of milk pathogens between BTM and separated milking cows. Milking hygiene should be improved in pastures, focusing specifically on herds that use a mobile milking machine. The segregated cows at milking time are not good predictors of milk pathogens in BTM.

MAPK Signaling Pathway Alters Expression of Midgut ALP and ABCC Genes and Causes Resistance to Bacillus thuringiensis Cry1Ac Toxin in Diamondback Moth

PubMed Central

Wu, Qingjun; Wang, Shaoli; Xie, Wen; Zhu, Xun; Baxter, Simon W.; Zhou, Xuguo; Jurat-Fuentes, Juan Luis; Zhang, Youjun

2015-01-01

Insecticidal crystal toxins derived from the soil bacterium Bacillus thuringiensis (Bt) are widely used as biopesticide sprays or expressed in transgenic crops to control insect pests. However, large-scale use of Bt has led to field-evolved resistance in several lepidopteran pests. Resistance to Bt Cry1Ac toxin in the diamondback moth, Plutella xylostella (L.), was previously mapped to a multigenic resistance locus (BtR-1). Here, we assembled the 3.15 Mb BtR-1 locus and found high-level resistance to Cry1Ac and Bt biopesticide in four independent P. xylostella strains were all associated with differential expression of a midgut membrane-bound alkaline phosphatase (ALP) outside this locus and a suite of ATP-binding cassette transporter subfamily C (ABCC) genes inside this locus. The interplay between these resistance genes is controlled by a previously uncharacterized trans-regulatory mechanism via the mitogen-activated protein kinase (MAPK) signaling pathway. Molecular, biochemical, and functional analyses have established ALP as a functional Cry1Ac receptor. Phenotypic association experiments revealed that the recessive Cry1Ac resistance was tightly linked to down-regulation of ALP, ABCC2 and ABCC3, whereas it was not linked to up-regulation of ABCC1. Silencing of ABCC2 and ABCC3 in susceptible larvae reduced their susceptibility to Cry1Ac but did not affect the expression of ALP, whereas suppression of MAP4K4, a constitutively transcriptionally-activated MAPK upstream gene within the BtR-1 locus, led to a transient recovery of gene expression thereby restoring the susceptibility in resistant larvae. These results highlight a crucial role for ALP and ABCC genes in field-evolved resistance to Cry1Ac and reveal a novel trans-regulatory signaling mechanism responsible for modulating the expression of these pivotal genes in P. xylostella. PMID:25875245

Night workers with circadian misalignment are susceptible to alcohol-induced intestinal hyperpermeability with social drinking.

PubMed

Swanson, Garth R; Gorenz, Annika; Shaikh, Maliha; Desai, Vishal; Kaminsky, Thomas; Van Den Berg, Jolice; Murphy, Terrence; Raeisi, Shohreh; Fogg, Louis; Vitaterna, Martha Hotz; Forsyth, Christopher; Turek, Fred; Burgess, Helen J; Keshavarzian, Ali

2016-07-01

Alcohol-induced intestinal hyperpermeability (AIHP) is a known risk factor for alcoholic liver disease (ALD), but only 20-30% of heavy alcoholics develop AIHP and ALD. The hypothesis of this study is that circadian misalignment would promote AIHP. We studied two groups of healthy subjects on a stable work schedule for 3 mo [day workers (DW) and night workers (NW)]. Subjects underwent two circadian phase assessments with sugar challenge to access intestinal permeability between which they drank 0.5 g/kg alcohol daily for 7 days. Sleep architecture by actigraphy did not differ at baseline or after alcohol between either group. After alcohol, the dim light melatonin onset (DLMO) in the DW group did not change significantly, but in the NW group there was a significant 2-h phase delay. Both the NW and DW groups had no change in small bowel permeability with alcohol, but only in the NW group was there an increase in colonic and whole gut permeability. A lower area under the curve of melatonin inversely correlated with increased colonic permeability. Alcohol also altered peripheral clock gene amplitude of peripheral blood mononuclear cells in CLOCK, BMAL, PER1, CRY1, and CRY2 in both groups, and inflammatory markers lipopolysaccharide-binding protein, LPS, and IL-6 had an elevated mesor at baseline in NW vs. DW and became arrhythmic with alcohol consumption. Together, our data suggest that central circadian misalignment is a previously unappreciated risk factor for AIHP and that night workers may be at increased risk for developing liver injury with alcohol consumption. Copyright © 2016 the American Physiological Society.

Impacts of moonlight on fish reproduction.

PubMed

Ikegami, Taro; Takeuchi, Yuki; Hur, Sung-Pyo; Takemura, Akihiro

2014-04-01

The waxing and waning cycle of the moon is repeated at approximately 1-month intervals, and concomitant changes occur in the levels of moonlight and cueing signals detected by organisms on the earth. In the goldlined spinefoot Siganus guttatus, a spawner lunar-synchronized around the first quarter moon, periodic changes in moonlight are used to cue gonadal development and gamete release. Rearing of mature fish under artificial constant full moon and new moon conditions during the spawning season leads to disruption or delay of synchronous spawning around the predicted moon phase. Melatonin, an endogenous transducer of the environmental light/dark cycle, increases in the blood and in the pineal gland around the new moon period and decreases around the full moon period. In synchrony with melatonin fluctuation, melatonin receptor(s) mRNA abundance is higher during the new moon period than during the full moon. The melatonin/melatonin receptor system is likely affected by moonlight. Measurements of the expression patterns of clock genes in neural tissues demonstrate that Cryptochrome (Cry1 and Cry3) and Period (Per2) fluctuate with lunar periodicity, the former peaking in the medial part of the brain around the first quarter moon period, and the latter peaking in the pineal gland around the full moon. Some clock genes may respond to periodic changes in moon phase and appear to be involved in the generation of lunar-related rhythmicity in lunar spawners. Thus, some fish use moonlight-related periodicities as reliable information for synchronizing the timing of reproductive events. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of seed blends and soil-insecticide on western and northern corn rootworm emergence from mCry3A + eCry3.1Ab Bt maize

USDA-ARS?s Scientific Manuscript database

Blended seed mixtures containing various ratios of transgenic Bt maize expressing the mCry3A + eCry3.1Ab proteins and non-Bt maize (near-isoline maize) were deployed alone and in combination with a soil applied insecticide (Force CS) to evaluate the survivorship of the western corn rootworm, Diabrot...

Inspiratory Phonation in Baby Voice.

PubMed

Wermke, Kathleen; Haschemi, Asin Ahmad; Hesse, Volker; Robb, Michael P

2018-03-01

This study aimed to evaluate the developmental occurrence of inspiratory phonations (IPs) in the spontaneous cries of healthy infants across the first 10 weeks of life. This is a populational retrospective study. The spontaneous crying of 17 healthy infants (10 were male) was retrospectively investigated. Sound files of spontaneously uttered cries that were repeatedly recorded once per week for across the first 10 weeks of life were retrospectively analyzed. Frequency spectra and waveforms were used to identify the occurrence of IPs and to measure the duration and fundamental frequency (fo) of each instance of IP. A consistent number of IPs were identified across the 10-week period. All infants were observed to produce IPs in their spontaneous cries, although the frequency of occurrence was not consistent across infants. A marked sex difference was observed with female infants producing a higher number of IPs compared to males. The duration and fo of IPs did not differ significantly across the 10 weeks or between sexes. The production of IPs is a regularly occurring phenomenon in healthy, normally developing infants' spontaneous crying. The proportional difference in the production of IPs between female and male infants, observed for the first time here, is postulated to be linked to sex-based differences (including steroidal hormones) in respiratory anatomy and physiology. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

DNA Repair and Ethnic Differences in Prostate Cancer Risk

DTIC Science & Technology

2007-03-01

did you drink meal replacement, energy, or high-protein beverages such as Instant Breakfast, Ensure, Slimfast, Sustacal or others? NEVER (GO TO...you eat pasta, spaghetti, or other noodles ? NEVER (GO TO QUESTION 61) 1–6 times per year 2 times per week 7–11 times per year 3–4 times per...ate pasta, spaghetti, or other noodles , how much did you usually eat? Less than 1 cup 1 to 3 cups More than 3 cups 60b. How often did you

Simulation analysis of the unconfined aquifer, Raft River geothermal area, Idaho-Utah

USGS Publications Warehouse

Nichols, William D.

1979-01-01

This study covers about 1,000 mi2 (2,600 km2 ) of the southern Raft River drainage basin in south-central Idaho and northwest Utah. The main area of interest, approximately 200 mi2 (520 km2 ) of semiarid agricultural and rangeland in the southern Raft River Valley that includes the known Geothermal Resource Area near Bridge, Idaho, was modelled numerically to evaluate the hydrodynamics of the unconfined aquifer. Computed and estimated transmissivity values range from 1,200 feet squared per day (110 meters squared per day) to 73,500 feet squared per day (6,830 meters squared per day). Water budgets, including ground-water recharge and discharge for approximate equilibrium conditions, have been computed by several previous investigators; their estimates of available ground-water recharge range from about 46,000 acre-feet per year (57 cubic hectometers per year) to 100,000 acre-feet per year (123 cubic hectometers per year).Simulation modeling of equilibrium conditions represented by 1952 water levels suggests: (1) recharge to the water-table aquifer is about 63,000 acre-feet per year (77 cubic hectometers per year); (2) a significant volume of ground water is discharged through evapotranspiration by phreatophytes growing on the valley bottomlands; (3) the major source of recharge may be from upward leakage of water from a deeper, confined reservoir; and (4) the aquifer transmissivity probably does not exceed about 12,000 feet squared per day (3,100 meters squared per day). Additional analysis carried out by simulating transient conditions from 1952 to 1965 strongly suggests that aquifer transmissivity does not exceed about 7,700 feet squared per day (700 meters squared per day). The model was calibrated using slightly modified published pumpage data; it satisfactorily reproduced the historic water-level decline over the period 1952-65.

Baseline sensitivity of maize borers in India to the Bacillus thuringiensis insecticidal proteins Cry1A.105 and Cry2Ab2.

PubMed

Jalali, Sushil K; Yadavalli, Lalitha; Ojha, Rakshit; Kumar, Pradyumn; Sulaikhabeevi, Suby B; Sharma, Reema; Nair, Rupa; Kadanur, Ravi C; Kamath, Subray P; Komarlingam, Mohan S

2015-08-01

Among the major pests of maize in India are two stem borers, Chilo partellus (Swinhoe) and Sesamia inferens (Walker), and an earworm, Helicoverpa armigera (Hübner). As a pest control strategy, transgenic Bacillus thuringiensis (Bt) maize hybrids are undergoing regulatory trials in India. We have determined the sensitivity of the target lepidopterans to the insecticidal Bt proteins expressed in Bt maize, as this determines product efficacy and the resistance management strategy to be adopted. Maize hybrids with event MON89034 express two insecticidal Bt proteins, Cry1A.105 and Cry2Ab2. Sensitivity profiles of 53 populations of C. partellus, 21 populations of S. inferens and 21 populations of H. armigera, collected between 2008 and 2013 from maize-growing areas in India, to Cry1A.105 and Cry2Ab2 proteins were generated through dose-response assays. Cry1A.105 protein was the most effective to neonates of C. partellus (mean MIC90 range 0.30-1.0 µg mL(-1) ) and H. armigera (mean MIC90 range 0.71-8.22 µg mL(-1) ), whereas Cry2Ab2 (mean MIC90 range 0.65-1.70 µg mL(-1) ) was the most effective to S. inferens. Populations of C. partellus, S. inferens and H. armigera were susceptible to the Bt proteins Cry1A.105 and Cry2Ab2. The Bt sensitivity data will serve as precommercialisation benchmarks for resistance monitoring purposes. © 2014 Society of Chemical Industry.

Clock genes and salt-sensitive hypertension: a new type of aldosterone-synthesizing enzyme controlled by the circadian clock and angiotensin II.

PubMed

Okamura, Hitoshi; Doi, Masao; Goto, Kaoru; Kojima, Rika

2016-10-01

With the current societal norm of shiftwork and long working hours, maintaining a stable daily life is becoming very difficult. An irregular lifestyle disrupts circadian rhythms, resulting in the malfunction of body physiology and ultimately leading to lifestyle-related diseases, including hypertension. By analyzing completely arrhythmic Cry1/Cry2 double-knockout (Cry-null) mice, we found salt-sensitive hypertension accompanied by hyperaldosteronism. On the basis of a DNA microarray analysis of the adrenal gland and subsequent biochemical analyses, we discovered that Hsd3b6/HSD3B1, a subtype of 3β-HSD, is markedly overexpressed in aldosterone-producing cells in the Cry-null adrenal cortex. In addition, we found that Hsd3b6/HSD3B1, which converts pregnenolone to progesterone, is a clock-controlled gene and might also be a key enzyme for the regulation of aldosterone biosynthesis, in addition to the previously established CYP11B2, which synthesizes aldosterone from deoxycorticosterone. Importantly, angiotensin II induces HSD3B1 via the transcription factor NGFIB in human adrenocortical H295R cells, similarly to CYP11B2. As HSD3B1 levels are abnormally high in the adrenal aldosterone-producing cells of idiopathic hyperaldosteronism (IHA), the temporal component of this system in the pathophysiology of IHA is a promising area for future research.

Associations of Sugar and Artificially Sweetened Soda with Albuminuria and Kidney Function Decline in Women

PubMed Central

Curhan, Gary C.

2011-01-01

Summary Background and objectives Sugar-sweetened soda is reported to be associated with increased risk for diabetes and albuminuria, but there are currently limited data on how sugar or artificially sweetened soda may be related to kidney function decline. Design, setting, participants, & measurements This study identified 3318 women participating in the Nurses' Health Study with data on soda intake and albuminuria; of these, 3256 also had data on estimated GFR (eGFR) change between 1989 and 2000. Cumulative average beverage intake was derived from the 1984, 1986, 1990, 1994, and 1998 food frequency questionnaires. Serving categories included <1/mo (referent), 1 to 4/mo, 2 to 6/wk, 1 to 1.9/d, and ≥2/d. Microalbuminuria (MA) was considered a urinary albumin-to-creatinine ratio of 25 to 355 μg/mg. For kidney function change, the primary outcome was a ≥30% decline in eGFR over 11 years; rapid eGFR decline defined as ≥3 ml/min per 1.73 m2 per year was also examined. Results Consumption of ≥2 servings per day of artificially sweetened (diet) soda was independently associated with eGFR decline ≥30% (OR 2.02, 95% CI 1.36 to 3.01) and ≥3 ml/min per 1.73 m2 per year (OR 2.20, 95% CI 1.36 to 3.55). No increased risk for eGFR decline was observed for <2 servings per day of diet soda. No associations were noted between diet soda and MA or sugar soda and MA or eGFR decline. Conclusions Consumption of ≥2 servings per day of artificially sweetened soda is associated with a 2-fold increased odds for kidney function decline in women. PMID:20884773

Associations of sugar and artificially sweetened soda with albuminuria and kidney function decline in women.

PubMed

Lin, Julie; Curhan, Gary C

2011-01-01

Sugar-sweetened soda is reported to be associated with increased risk for diabetes and albuminuria, but there are currently limited data on how sugar or artificially sweetened soda may be related to kidney function decline. This study identified 3318 women participating in the Nurses' Health Study with data on soda intake and albuminuria; of these, 3256 also had data on estimated GFR (eGFR) change between 1989 and 2000. Cumulative average beverage intake was derived from the 1984, 1986, 1990, 1994, and 1998 food frequency questionnaires. Serving categories included <1/mo (referent), 1 to 4/mo, 2 to 6/wk, 1 to 1.9/d, and ≥ 2/d. Microalbuminuria (MA) was considered a urinary albumin-to-creatinine ratio of 25 to 355 μg/mg. For kidney function change, the primary outcome was a ≥ 30% decline in eGFR over 11 years; rapid eGFR decline defined as ≥ 3 ml/min per 1.73 m(2) per year was also examined. Consumption of ≥ 2 servings per day of artificially sweetened (diet) soda was independently associated with eGFR decline ≥ 30% (OR 2.02, 95% CI 1.36 to 3.01) and ≥ 3 ml/min per 1.73 m(2) per year (OR 2.20, 95% CI 1.36 to 3.55). No increased risk for eGFR decline was observed for <2 servings per day of diet soda. No associations were noted between diet soda and MA or sugar soda and MA or eGFR decline. Consumption of ≥ 2 servings per day of artificially sweetened soda is associated with a 2-fold increased odds for kidney function decline in women.

Proteomics-based identification of midgut proteins correlated with Cry1Ac resistance in Plutella xylostella (L.).

PubMed

Xia, Jixing; Guo, Zhaojiang; Yang, Zezhong; Zhu, Xun; Kang, Shi; Yang, Xin; Yang, Fengshan; Wu, Qingjun; Wang, Shaoli; Xie, Wen; Xu, Weijun; Zhang, Youjun

2016-09-01

The diamondback moth, Plutella xylostella (L.), is a worldwide pest of cruciferous crops and can rapidly develop resistance to many chemical insecticides. Although insecticidal crystal proteins (i.e., Cry and Cyt toxins) derived from Bacillus thuringiensis (Bt) have been useful alternatives to chemical insecticides for the control of P. xylostella, resistance to Bt in field populations of P. xylostella has already been reported. A better understanding of the resistance mechanisms to Bt should be valuable in delaying resistance development. In this study, the mechanisms underlying P. xylostella resistance to Bt Cry1Ac toxin were investigated using two-dimensional differential in-gel electrophoresis (2D-DIGE) and ligand blotting for the first time. Comparative analyses of the constitutive expression of midgut proteins in Cry1Ac-susceptible and -resistant P. xylostella larvae revealed 31 differentially expressed proteins, 21 of which were identified by mass spectrometry. Of these identified proteins, the following fell into diverse eukaryotic orthologous group (KOG) subcategories may be involved in Cry1Ac resistance in P. xylostella: ATP-binding cassette (ABC) transporter subfamily G member 4 (ABCG4), trypsin, heat shock protein 70 (HSP70), vacuolar H(+)-ATPase, actin, glycosylphosphatidylinositol anchor attachment 1 protein (GAA1) and solute carrier family 30 member 1 (SLC30A1). Additionally, ligand blotting identified the following midgut proteins as Cry1Ac-binding proteins in Cry1Ac-susceptible P. xylostella larvae: ABC transporter subfamily C member 1 (ABCC1), solute carrier family 36 member 1 (SLC36A1), NADH dehydrogenase iron-sulfur protein 3 (NDUFS3), prohibitin and Rap1 GTPase-activating protein 1. Collectively, these proteomic results increase our understanding of the molecular resistance mechanisms to Bt Cry1Ac toxin in P. xylostella and also demonstrate that resistance to Bt Cry1Ac toxin is complex and multifaceted. Copyright © 2016 Elsevier B.V. All rights reserved.

Multistate Models Reveal Long-Term Trends of Northern Spotted Owls in the Absence of a Novel Competitor.

PubMed

Kroll, Andrew J; Jones, Jay E; Stringer, Angela B; Meekins, Douglas J

2016-01-01

Quantifying spatial and temporal variability in population trends is a critical aspect of successful management of imperiled species. We evaluated territory occupancy dynamics of northern spotted owls (Strix occidentalis caurina), California, USA, 1990-2014. The study area possessed two unique aspects. First, timber management has occurred for over 100 years, resulting in dramatically different forest successional and structural conditions compared to other areas. Second, the barred owl (Strix varia), an exotic congener known to exert significant negative effects on spotted owls, has not colonized the study area. We used a Bayesian dynamic multistate model to evaluate if territory occupancy of reproductive spotted owls has declined as in other study areas. The state-space approach for dynamic multistate modeling imputes the number of territories for each nesting state and allows for the estimation of longer-term trends in occupied or reproductive territories from longitudinal studies. The multistate approach accounts for different detection probabilities by nesting state (to account for either inherent differences in detection or for the use of different survey methods for different occupancy states) and reduces bias in state assignment. Estimated linear trends in the number of reproductive territories suggested an average loss of approximately one half territory per year (-0.55, 90% CRI: -0.76, -0.33), in one management block and a loss of 0.15 per year (-0.15, 90% CRI: -0.24, -0.07), in another management block during the 25 year observation period. Estimated trends in the third management block were also negative, but substantial uncertainty existed in the estimate (-0.09, 90% CRI: -0.35, 0.17). Our results indicate that the number of territories occupied by northern spotted owl pairs remained relatively constant over a 25 year period (-0.07, 90% CRI: -0.20, 0.05; -0.01, 90% CRI: -0.19, 0.16; -0.16, 90% CRI: -0.40, 0.06). However, we cannot exclude small-to-moderate declines or increases in paired territory numbers due to uncertainty in our estimates. Collectively, we conclude spotted owl pair populations on this landscape managed for commercial timber production appear to be more stable and do not show sharp year-over-year declines seen in both managed and unmanaged landscapes with substantial barred owl colonization and persistence. Continued monitoring of reproductive territories can determine whether recent declines continue or whether trends reverse as they have on four previous occasions. Experimental investigations to evaluate changes to spotted owl occupancy dynamics when barred owl populations are reduced or removed entirely can confirm the generality of this conclusion.

7 CFR 932.149 - Modified minimum quality requirements for specified styles of canned olives of the ripe type.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Fragments (Pitted Style Only) Not more than 1.3% average by count Major Stems Not more than 3 HEVM Not more... per 300 grams Major Stems Not more than 3 HEVM Not more than 2 units per sample Broken Pieces and End... Fragments Average of not more than 1 by count per 300 grams Major Stems Not more than 3 HEVM Not more than 2...

7 CFR 932.149 - Modified minimum quality requirements for specified styles of canned olives of the ripe type.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Fragments (Pitted Style Only) Not more than 1.3% average by count Major Stems Not more than 3 HEVM Not more... per 300 grams Major Stems Not more than 3 HEVM Not more than 2 units per sample Broken Pieces and End... Fragments Average of not more than 1 by count per 300 grams Major Stems Not more than 3 HEVM Not more than 2...

7 CFR 932.149 - Modified minimum quality requirements for specified styles of canned olives of the ripe type.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Fragments (Pitted Style Only) Not more than 1.3% average by count Major Stems Not more than 3 HEVM Not more... per 300 grams Major Stems Not more than 3 HEVM Not more than 2 units per sample Broken Pieces and End... Fragments Average of not more than 1 by count per 300 grams Major Stems Not more than 3 HEVM Not more than 2...

7 CFR 932.149 - Modified minimum quality requirements for specified styles of canned olives of the ripe type.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Fragments (Pitted Style Only) Not more than 1.3% average by count Major Stems Not more than 3 HEVM Not more... per 300 grams Major Stems Not more than 3 HEVM Not more than 2 units per sample Broken Pieces and End... Fragments Average of not more than 1 by count per 300 grams Major Stems Not more than 3 HEVM Not more than 2...

7 CFR 932.149 - Modified minimum quality requirements for specified styles of canned olives of the ripe type.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Fragments (Pitted Style Only) Not more than 1.3% average by count Major Stems Not more than 3 HEVM Not more... per 300 grams Major Stems Not more than 3 HEVM Not more than 2 units per sample Broken Pieces and End... Fragments Average of not more than 1 by count per 300 grams Major Stems Not more than 3 HEVM Not more than 2...

Safety Assessment of Bacillus thuringiensis Insecticidal Proteins Cry1C and Cry2A with a Zebrafish Embryotoxicity Test.

PubMed

Gao, Yan-Jie; Zhu, Hao-Jun; Chen, Yi; Li, Yun-He; Peng, Yu-Fa; Chen, Xiu-Ping

2018-05-02

As a result of the large-scale planting of transgenic Bacillus thuringiensis (Bt) crops, fish would be exposed to freely soluble Bt insecticidal protein(s) that are released from Bt crop tissues into adjacent bodies of water or by way of direct feeding on deposited plant material. To assess the safety of two Bt proteins Cry1C and Cry2A to fish, we used zebrafish as a representative species and exposed their embryos to 0.1, 1, and 10 mg/L of the two Cry proteins until 132 h post-fertilization and then several developmental, biochemical, and molecular parameters were evaluated. Chlorpyrifos (CPF), a known toxicant to aquatic organisms, was used as a positive control. Although CPF exposure resulted in significant developmental, biochemical, and molecular changes in the zebrafish embryos, there were almost no significant differences after Cry1C or Cry2A exposure. Thus, we conclude that zebrafish embryos are not sensitive to Cry1C and Cry2A insecticidal proteins at test concentrations.

Influence of Roads on the Surrounding Natural Environment - Vegetation, Soil, and Ground Water

DTIC Science & Technology

1980-02-01

0 __________ _______ ___ _ ii _ _ _ _ en 12bm ~11 I.IO .Figuz 9. Observationsomr~ de Gundlatorp (nr 15). 1W 15, - 1~Karlsharnn - Ronrioby, (Study site...0s . . number of’ srscie s - -- ANTAL ATf 1EJPER RUTA 9 10 13 3 Per souare TOTALI AITAL LATER 13 total n- -her of srnecies Table 2. Analyses of...50. It .5 POA ANNUA 2 1 3 5 100. 3. 2.7 POA NERORALIS 2 0 0 1 50. . 8 No.of species per square ANJTAL ARTER PE.R RUTA 7 6 S 6 Total no. Of S ~eciesE

40 CFR Table 2 to Subpart Dddd of... - Model Rule-Emission Limitations That Apply to Incinerators Before [Date to be specified in state...

Code of Federal Regulations, 2014 CFR

2014-07-01

... parts per million by dry volume 3-run average (1 hour minimum sample time per run) Performance test..., appendix A-4). Oxides of nitrogen 388 parts per million by dry volume 3-run average (1 hour minimum sample... (1 hour minimum sample time per run) Performance test (Method 6 or 6c of appendix A of this part) a...

40 CFR Table 2 to Subpart Dddd of... - Model Rule-Emission Limitations That Apply to Incinerators Before [Date to be specified in state...

Code of Federal Regulations, 2013 CFR

2013-07-01

... parts per million by dry volume 3-run average (1 hour minimum sample time per run) Performance test..., appendix A-4). Oxides of nitrogen 388 parts per million by dry volume 3-run average (1 hour minimum sample... (1 hour minimum sample time per run) Performance test (Method 6 or 6c of appendix A of this part) a...

Bt proteins Cry1Ah and Cry2Ab do not affect cotton aphid Aphis gossypii and ladybeetle Propylea japonica

PubMed Central

Zhao, Yao; Zhang, Shuai; Luo, Jun-Yu; Wang, Chun-Yi; Lv, Li-Min; Wang, Xiao-Ping; Cui, Jin-Jie; Lei, Chao-Liang

2016-01-01

Plant varieties expressing the Bt (Bacillus thuringiensis) insecticidal proteins Cry1Ah and Cry2Ab have potential commercialization prospects in China. However, their potential effects on non-target arthropods (NTAs) remain uncharacterized. The cotton aphid Aphis gossypii is a worldwide pest that damages various important crops. The ladybeetle Propylea japonica is a common and abundant natural enemy in many cropping systems in East Asia. In the present study, the effects of Cry1Ah and Cry2Ab proteins on A. gossypii and P. japonica were assessed from three aspects. First, neither of the Cry proteins affected the growth or developmental characteristics of the two test insects. Second, the expression levels of the detoxification-related genes of the two test insects did not change significantly in either Cry protein treatment. Third, neither of the Cry proteins had a favourable effect on the expression of genes associated with the amino acid metabolism of A. gossypii and the nutrition utilization of P. japonica. In conclusion, the Cry1Ah and Cry2Ab proteins do not appear to affect the cotton aphid A. gossypii or the ladybeetle P. japonica. PMID:26829252

Mass balance and isotope effects during nitrogen transport through septic tank systems with packed-bed (sand) filters.

PubMed

Hinkle, Stephen R; Böhlke, J K; Fisher, Lawrence H

2008-12-15

Septic tank systems are an important source of NO3(-) to many aquifers, yet characterization of N mass balance and isotope systematics following septic tank effluent discharge into unsaturated sediments has received limited attention. In this study, samples of septic tank effluent before and after transport through single-pass packed-bed filters (sand filters) were evaluated to elucidate mass balance and isotope effects associated with septic tank effluent discharge to unsaturated sediments. Chemical and isotopic data from five newly installed pairs and ten established pairs of septic tanks and packed-bed filters serving single homes in Oregon indicate that aqueous solute concentrations are affected by variations in recharge (precipitation, evapotranspiration), NH4+ sorption (primarily in immature systems), nitrification, and gaseous N loss via NH3 volatilization and(or) N2 or N2O release during nitrification/denitrification. Substantial NH4+ sorption capacity was also observed in laboratory columns with synthetic effluent. Septic tank effluent delta15N-NH4+ values were almost constant and averaged +4.9 per thousand+/-0.4 per thousand (1 sigma). In contrast, delta15N values of NO3(-) leaving mature packed-bed filters were variable (+0.8 to +14.4 per thousand) and averaged +7.2 per thousand+/-2.6 per thousand. Net N loss in the two networks of packed-bed filters was indicated by average 10-30% decreases in Cl(-)-normalized N concentrations and 2-3 per thousand increases in delta15N, consistent with fractionation accompanying gaseous N losses and corroborating established links between septic tank effluent and NO3(-) in a local, shallow aquifer. Values of delta18O-NO3(-) leaving mature packed-bed filters ranged from -10.2 to -2.3 per thousand (mean -6.4 per thousand+/-1.8 per thousand), and were intermediate between a 2/3 H2O-O+1/3 O2-O conceptualization and a 100% H2O-O conceptualization of delta18O-NO3(-) generation during nitrification.

Viability of Listeria monocytogenes on uncured turkey breast commercially prepared with and without buffered vinegar during extended storage at 4 and 10°C.

PubMed

Porto-Fett, Anna C S; Campano, Stephen G; Shoyer, Bradley A; Wadsworth, Sarah; Luchansky, John B

2014-06-01

We determined the viability of Listeria monocytogenes on uncured turkey breast containing buffered vinegar (BV) and surface treated with a stabilized solution of sodium chlorite in vinegar (VSC). Commercially produced, uncured, deli-style turkey breast was formulated with BV (0.0, 2.0, 2.5, or 3.0%), sliced (ca. 100 g and ca. 1.25 cm thick), and subsequently surface inoculated (ca. 4.3 log CFU per slice) in each of two trials with a five-strain cocktail of L. monocytogenes. Next, 1 ml per side of a 2 or 10% solution of VSC was added to each package before vacuum sealing and storing at 4 or 10°C. Without antimicrobials, L. monocytogenes numbers increased by ca. 6.2 log CFU per slice after 90 and 48 days of storage at 4 or 10°C, respectively. At 4°C, L. monocytogenes numbers increased by ca. 0.4 to 1.9 log CFU per slice on turkey breast formulated with 2.0 or 2.5% BV and treated or not with 2% VSC, whereas when treated with 10% VSC, L. monocytogenes levels remained relatively unchanged over 90 days. However, when turkey breast was formulated with 3.0% BV and treated or not with VSC, pathogen numbers decreased by ca. 0.7 to 1.3 log CFU per slice. At 10°C, L. monocytogenes numbers increased by ca. 1.5 to 5.6 log CFU per slice after 48 days when formulated with 2.0 to 3.0% BV and treated or not with 2% VSC. When formulated with 2.0% BV and treated with 10% VSC, L. monocytogenes numbers increased by ca. 3.3 log CFU per slice, whereas when formulated with 2.5 or 3.0% BV and treated with 10% VSC, L. monocytogenes decreased by ca. 0.3 log CFU per slice. Inclusion of BV as an ingredient in uncured turkey breast, alone or in combination with VSC added to the package, appreciably suppressed outgrowth of L. monocytogenes during an extended refrigerated shelf life.

Exercise training improves endothelial function in resistance arteries of young prehypertensives.

PubMed

Beck, D T; Martin, J S; Casey, D P; Braith, R W

2014-05-01

Prehypertension is associated with reduced conduit artery endothelial function and perturbation of oxidant/antioxidant status. It is unknown whether endothelial dysfunction persists to resistance arteries and whether exercise training affects oxidant/antioxidant balance in young prehypertensives. We examined resistance artery function using venous occlusion plethysmography measurement of forearm (FBF) and calf blood flow (CBF) at rest and during reactive hyperaemia (RH), as well as lipid peroxidation (8-iso-PGF2α) and antioxidant capacity (Trolox-equivalent antioxidant capacity; TEAC) before and after exercise intervention or time control. Forty-three unmedicated prehypertensive and 15 matched normotensive time controls met screening requirements and participated in the study (age: 21.1±0.8 years). Prehypertensive subjects were randomly assigned to resistance exercise training (PHRT; n=15), endurance exercise training (PHET; n=13) or time-control groups (PHTC; n=15). Treatment groups exercised 3 days per week for 8 weeks. Peak and total FBF were lower in prehypertensives than normotensives (12.7±1.2 ml min(-1) per100 ml tissue and 89.1±7.7 ml min(-1) per 100 ml tissue vs 16.3±1.0 ml min(-1) per 100 ml tissue and 123.3±6.4 ml min(-1) per 100 ml tissue, respectively; P<0.05). Peak and total CBF were lower in prehypertensives than normotensives (15.3±1.2 ml min(-1) per 100 ml tissue and 74±8.3 ml min(-1) per 100 ml tissue vs 20.9±1.4 ml min(-1) per 100 ml tissue and 107±9.2 ml min(-1) per 100 ml tissue, respectively; P<0.05). PHRT and PHET improved humoral measures of TEAC (+24 and +30%) and 8-iso-PGF2α (-43 and -40%, respectively; P < or = 0.05). This study provides evidence that young prehypertensives exhibit reduced resistance artery endothelial function and that short-term (8 weeks) resistance or endurance training are effective in improving resistance artery endothelial function and oxidant/antioxidant balance in young prehypertensives.

The Hard X-ray 20-40 keV AGN Luminosity Function

NASA Technical Reports Server (NTRS)

Beckmann, V.; Soldi, S.; Shrader, C. R.; Gehrels, N.; Produit, N.

2006-01-01

We have compiled a complete, significance limited extragalactic sample based on approximately 25,000 deg(sup 2) to a limiting flux of 3 x 10(exp -11) ergs per square centimeter per second. (approximately 7,000 deg(sup 2)) to a flux limit of 10(exp -11) ergs per square centimeter per second)) in the 20 - 40 keV band with INTEGRAL. We have constructed a detailed exposure map to compensate for effects of non-uniform exposure. The flux-number relation is best described by a power-law with a slope of alpha = 1.66 plus or minus 0.11. The integration of the cumulative flux per unit area leads to f(sub 20-40 keV) = 2.6 x 10(exp -10) ergs per square centimeter per second per sr(sup -1) which is about 1% of the known 20-40 keV X-ray background. We present the first luminosity function of AGN in the 20-40 keV energy range, based on 68 extragalactic objects detected by the imager IBIS/ISGRI on-board INTEGRAL. The luminosity function shows a smoothly connected two power-law form, with an index of gamma (sub 1) = 0.9 below, and gamma (sub 2) = 2.2 above the turn-over luminosity of L(sub *), = 4.6 x 10(sup 43) ergs per second. The emissivity of all INTEGRAL AGNs per unit volume is W(sub 20-40keV)(greater than 10(sup 41) ergs per second) = 2.8 x 10(sup 38) ergs per second h(sup 3)(sub 70) Mpc(sup -3). These results are consistent with those derived in the 2-20keV energy band and do not show a significant contribution by Compton-thick objects. Because the sample used in this study is truly local (z(raised bar) = 0.022)), only limited conclusions can be drawn for the evolution of AGNs in this energy band. But the objects explaining the peak in the cosmic X-ray background are likely to be either low luminosity AGN (L(sub x) less than 10(sup 41) ergs per second) or of other type, such as intermediate mass black holes, clusters, and star forming regions.

Meta-analysis of time-series studies of air pollution and mortality: effects of gases and particles and the influence of cause of death, age, and season.

PubMed

Stieb, David M; Judek, Stan; Burnett, Richard T

2002-04-01

A comprehensive, systematic synthesis was conducted of daily time-series studies of air pollution and mortality from around the world. Estimates of effect sizes were extracted from 109 studies, from single- and multipollutant models, and by cause of death, age, and season. Random effects pooled estimates of excess all-cause mortality (single-pollutant models) associated with a change in pollutant concentration equal to the mean value among a representative group of cities were 2.0% (95% CI 1.5-2.4%) per 31.3 microg/m3 particulate matter (PM) of median diameter < or = 10 microm (PM10); 1.7% (1.2-2.2%) per 1.1 ppm CO; 2.8% (2.1-3.5%) per 24.0 ppb NO2; 1.6% (1.1-2.0%) per 31.2 ppb O3; and 0.9% (0.7-1.2%) per 9.4 ppb SO2 (daily maximum concentration for O3, daily average for others). Effect sizes were generally reduced in multipollutant models, but remained significantly different from zero for PM10 and SO2. Larger effect sizes were observed for respiratory mortality for all pollutants except O3. Heterogeneity among studies was partially accounted for by differences in variability of pollutant concentrations, and results were robust to alternative approaches to selecting estimates from the pool of available candidates. This synthesis leaves little doubt that acute air pollution exposure is a significant contributor to mortality.

PER, a Circadian Clock Component, Mediates the Suppression of MMP-1 Expression in HaCaT Keratinocytes by cAMP.

PubMed

Yeom, Miji; Lee, HansongI; Shin, Seoungwoo; Park, Deokhoon; Jung, Eunsun

2018-03-23

Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy. Treatment with siPer3 alleviated the suppression of MMP-1 expression induced by forskolin. Results revealed PER3 suppresses the expression of MMP-1 via cAMP signaling pathway. Additionally, we screened for an activator of PER that could repress the expression of MMP-1 using HaCaT cell line containing PER promoter-luciferase reporter gene. Results showed Lespedeza capitate extract (LCE) increased PER promoter activity. LCE inhibited the expression of MMP-1 and its effect of LCE was abolished in knockdown of PER2 or PER3, demonstrating LCE can repress the expression of MMP-1 through PER. Since circadian clock component PER can regulate MMP-1 expression, it might be a new molecular mechanism to develop therapeutics to alleviate skin aging and skin cancer.

Molecular cloning and functional analysis of a blue light receptor gene MdCRY2 from apple (Malus domestica).

PubMed

Li, Yuan-Yuan; Mao, Ke; Zhao, Cheng; Zhao, Xian-Yan; Zhang, Rui-Fen; Zhang, Hua-Lei; Shu, Huai-Rui; Hao, Yu-Jin

2013-04-01

MdCRY2 was isolated from apple fruit skin, and its function was analyzed in MdCRY2 transgenic Arabidopsis. The interaction between MdCRY2 and AtCOP1 was found by yeast two-hybrid and BiFC assays. Cryptochromes are blue/ultraviolet-A (UV-A) light receptors involved in regulating various aspects of plant growth and development. Investigations of the structure and functions of cryptochromes in plants have largely focused on Arabidopsis (Arabidopsis thaliana), tomato (Solanum lycopersicum), pea (Pisum sativum), and rice (Oryza sativa). However, no data on the function of CRY2 are available in woody plants. In this study, we isolated a cryptochrome gene, MdCRY2, from apple (Malus domestica). The deduced amino acid sequences of MdCRY2 contain the conserved N-terminal photolyase-related domain and the flavin adenine dinucleotide (FAD) binding domain, as well as the C-terminal DQXVP-acidic-STAES (DAS) domain. Relationship analysis indicates that MdCRY2 shows the highest similarity to the strawberry FvCRY protein. The expression of MdCRY2 is induced by blue/UV-A light, which represents a 48-h circadian rhythm. To investigate the function of MdCRY2, we overexpressed the MdCRY2 gene in a cry2 mutant and wild type (WT) Arabidopsis, assessed the phenotypes of the resulting transgenic plants, and found that MdCRY2 functions to regulate hypocotyl elongation, root growth, flower initiation, and anthocyanin accumulation. Furthermore, we examined the interaction between MdCRY2 and AtCOP1 using a yeast two-hybrid assay and a bimolecular fluorescence complementation assay. These data provide functional evidence for a role of blue/UV-A light-induced MdCRY2 in controlling photomorphogenesis in apple.

The epidemiology of plunging ranula in South Auckland.

PubMed

Chin, Seung Joon; Zeng, Irene S L; Morton, Randall P

2016-12-01

Estimate the incidence rate and provide basic descriptive epidemiologic characteristics of plunging ranulas in a multi-ethnic population. Case series with chart review. The study group comprised all Counties Manukau Health (CMH, Manukau City, Auckland, New Zealand) patients presenting to the CMH Department of Otolaryngology with a diagnosis of plunging ranula from January 2001 to December 2013, as recorded in the departmental case register. Non-CMH domicile patients were excluded. South Auckland comprised the base population, as serviced by CMH. The 2006 New Zealand census data was used for population demographics. A total of 134 cases of plunging ranula were identified. The overall annual crude incidence rate was 2.4 per 100,000 person-years. The gender specific incidence rate for males was 3.2 per 100,000 (95% confidence interval [CI]: 2.5. 3.9) and for females was 2.0 per 100,000 (95% CI: 1.5, 2.6). The overall age-adjusted annual incidence rate was 2.6 per 100,000 (95% CI: 2.1, 3.0). The age-adjusted incidence was highest among Maori (6.7 per 100,000, 95% CI 4.9, 8.4), followed by Pacific Island (4.4 per 100,000, 95% CI 3.2, 5.6), Asian (0.7 per 100,000, 95% CI 0.2, 1.2), and European population (0.6 per 100,000, 95% CI 0.3, 0.8). We have quantified for the first time the age-specific and age-adjusted incidence rates for plunging ranula by gender and ethnicity. The results show a likely underlying genetic predisposition for this condition, possibly with a superimposed environmental acquired factor relating to external, minor blunt trauma to the neck. 4. Laryngoscope, 126:2739-2743, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Low osmolar (non-ionic) contrast media versus high osmolar (ionic) contrast media in intravenous urography and enhanced computerized tomography: a cost-effectiveness analysis.

PubMed

Wangsuphachart, S

1991-12-01

The cost-effectiveness of three alternative policies for the use of intravenous contrast media for urography and enhanced computerized tomography (CT) are analyzed. Alternative #1 is to use high osmolar contrast media (HOCM) in all patients, the historical policy. Alternative #2 is to replace it with low osmolar contrast media (LOCM) in all patients. Alternative #3 is to use LOCM only in the high risk patients. Data on the 6,242 patients who underwent intravenous urography and enhanced CT at the Department of Radiology, Chulalongkorn Hospital in 1989 were used. Both societal and hospital viewpoints were analyzed. The incremental cost-effectiveness (ICE) between #2 and #1 was 26,739 Baht (US$1,070) per healthy day saved (HDS), while the ICE between #3 and #1 was 12,057 Baht (US$482) per HDS. For fatal cases only, ICE between #2 and #1 was 35,111 Baht (US$1,404) per HDS, while the ICE between #3 and #1 was 18,266 Baht (US$731) per HDS. The incremental cost (IC) per patient was 2,341 Baht (US$94) and 681 Baht (US$27) respectively. For the hospital viewpoint the ICE between #2 and #1 was 13,744 (US$550) and between #3 and #1 was 6,127 Baht (US$245) per HDS. The IC per patient was 1,203 Baht (US$48) and 346 Baht (US$14), respectively. From the sensitivity analysis, #3 should be used if the LOCM price is reduced more than 75% (equal to 626 Baht or less) and more than 80% of the patients are able to pay for the contrast media.

Frequency Response Evaluation of Multiple Accelerometers Using a Modal Data Acquisition System

DTIC Science & Technology

1988-01-01

Computedi PCB @80 HZ 49mv/g 1@500 HZ 9.3mv/g lImp-sine Ifrom Imp-sine SN (2)V/g figureIV/g figure jV/g l(V/ gpk )xl.414(2)1 857 1 1.17 42 1 1.17 3 1.20 1.20...per g rms, V/ gpk = volts rms per g peak. 15 II Laboratory Transfer Function Procedures - 1. Setup and Power up equipment. a. Setup equipment per

Threshold-based insulin-pump interruption for reduction of hypoglycemia.

PubMed

Bergenstal, Richard M; Klonoff, David C; Garg, Satish K; Bode, Bruce W; Meredith, Melissa; Slover, Robert H; Ahmann, Andrew J; Welsh, John B; Lee, Scott W; Kaufman, Francine R

2013-07-18

The threshold-suspend feature of sensor-augmented insulin pumps is designed to minimize the risk of hypoglycemia by interrupting insulin delivery at a preset sensor glucose value. We evaluated sensor-augmented insulin-pump therapy with and without the threshold-suspend feature in patients with nocturnal hypoglycemia. We randomly assigned patients with type 1 diabetes and documented nocturnal hypoglycemia to receive sensor-augmented insulin-pump therapy with or without the threshold-suspend feature for 3 months. The primary safety outcome was the change in the glycated hemoglobin level. The primary efficacy outcome was the area under the curve (AUC) for nocturnal hypoglycemic events. Two-hour threshold-suspend events were analyzed with respect to subsequent sensor glucose values. A total of 247 patients were randomly assigned to receive sensor-augmented insulin-pump therapy with the threshold-suspend feature (threshold-suspend group, 121 patients) or standard sensor-augmented insulin-pump therapy (control group, 126 patients). The changes in glycated hemoglobin values were similar in the two groups. The mean AUC for nocturnal hypoglycemic events was 37.5% lower in the threshold-suspend group than in the control group (980 ± 1200 mg per deciliter [54.4 ± 66.6 mmol per liter] × minutes vs. 1568 ± 1995 mg per deciliter [87.0 ± 110.7 mmol per liter] × minutes, P<0.001). Nocturnal hypoglycemic events occurred 31.8% less frequently in the threshold-suspend group than in the control group (1.5 ± 1.0 vs. 2.2 ± 1.3 per patient-week, P<0.001). The percentages of nocturnal sensor glucose values of less than 50 mg per deciliter (2.8 mmol per liter), 50 to less than 60 mg per deciliter (3.3 mmol per liter), and 60 to less than 70 mg per deciliter (3.9 mmol per liter) were significantly reduced in the threshold-suspend group (P<0.001 for each range). After 1438 instances at night in which the pump was stopped for 2 hours, the mean sensor glucose value was 92.6 ± 40.7 mg per deciliter (5.1 ± 2.3 mmol per liter). Four patients (all in the control group) had a severe hypoglycemic event; no patients had diabetic ketoacidosis. This study showed that over a 3-month period the use of sensor-augmented insulin-pump therapy with the threshold-suspend feature reduced nocturnal hypoglycemia, without increasing glycated hemoglobin values. (Funded by Medtronic MiniMed; ASPIRE ClinicalTrials.gov number, NCT01497938.).

Bioinformatic analysis for allergenicity assessment of Bacillus thuringiensis Cry proteins expressed in insect-resistant food crops.

PubMed

Randhawa, Gurinder Jit; Singh, Monika; Grover, Monendra

2011-02-01

The novel proteins introduced into the genetically modified (GM) crops need to be evaluated for the potential allergenicity before their introduction into the food chain to address the safety concerns of consumers. At present, there is no single definitive test that can be relied upon to predict allergic response in humans to a new protein; hence a composite approach to allergic response prediction is described in this study. The present study reports on the evaluation of the Cry proteins, encoded by cry1Ac, cry1Ab, cry2Ab, cry1Ca, cry1Fa/cry1Ca hybrid, being expressed in Bt food crops that are under field trials in India, for potential allergenic cross-reactivity using bioinformatics search tools. The sequence identity of amino acids was analyzed using FASTA3 of AllergenOnline version 10.0 and BLASTX of NCBI Entrez to identify any potential sequence matches to allergen proteins. As a step further in the detection of allergens, an independent database of domains in the allergens available in the AllergenOnline database was also developed. The results indicated no significant alignment and similarity of Cry proteins at domain level with any of the known allergens revealing that there is no potential risk of allergenic cross-reactivity. Copyright © 2010 Elsevier Ltd. All rights reserved.

Hospitalization and survival in patients using epoprostenol for injection in the PROSPECT observational study.

PubMed

Frantz, Robert P; Schilz, Robert J; Chakinala, Murali M; Badesch, David B; Frost, Adaani E; McLaughlin, Vallerie V; Barst, Robyn J; Rosenberg, Daniel M; Miller, Dave P; Hartline, Brian K; Benton, Wade W; Farber, Harrison W

2015-02-01

Few studies have prospectively reported outcomes in patients with pulmonary arterial hypertension (PAH) treated with epoprostenol in the modern-day era of oral therapy and combination treatments. The Registry to Prospectively Describe Use of Epoprostenol for Injection (Veletri, prolonged room temperature stable-epoprostenol [RTS-Epo]) in Patients with Pulmonary Arterial Hypertension (PROSPECT) was established to prospectively describe the course of PAH in patients prescribed RTS-Epo. PROSPECT is a multicenter, US-based drug registry of primarily group 1 patients with PAH treated with RTS-Epo who were parenteral-naive or parenteral-transitioned at enrollment. Patients were followed until discontinuation of RTS-Epo, withdrawal, loss to follow-up, death, or end of study (maximum 1 year). One-year freedom from hospitalization (FH) and survival estimates were summarized by prostacyclin history (parenteral-naive or parenteral-transitioned), sex, and chronic renal insufficiency (CRI). A total of 336 patients were included. The overall 1-year FH estimate was 51.0% ± 2.8% and was lower in parenteral-naive patients than parenteral-transitioned patients (42.8% ± 4.3% vs 57.1% ± 3.7%, respectively; P = .002). FH estimates were lower in male patients than female patients (38.3% ± 5.9% vs 54.6% ± 3.2%, respectively; P < .015) and in patients with CRI than patients without CRI (17.0% ± 8.4% vs 53.7% ± 2.9%, respectively; P < .001). The overall 1-year survival estimate was 84.0% ± 2.1%. Survival was poorer in parenteral-naive patients, male patients, and patients with CRI. Risk of hospitalization and mortality remain high in patients with PAH. In particular, patients who are parenteral-naive at initiation of RTS-Epo therapy, male patients, and patients with CRI require close monitoring and aggressive clinical management.

Role of muscarinic receptor subtypes in central antinociception.

PubMed Central

Bartolini, A.; Ghelardini, C.; Fantetti, L.; Malcangio, M.; Malmberg-Aiello, P.; Giotti, A.

1992-01-01

1. The ability to modify the pain threshold by the two M1-muscarinic agonists: McN-A-343 and AF-102B and by the specific M2-agonist arecaidine was examined in mice and rats by using three different noxious stimuli: chemical (writhing test), thermic (hot-plate test) and mechanical (paw pressure test). 2. In the mouse hot-plate test McN-A-343 (20-50 micrograms per mouse i.c.v.) and AF-102B (1-10 mg kg-1 i.p.) produced significant antinociception which was prevented by atropine (1 microgram per mouse i.c.v.) and by the two selective M1 antagonists: pirenzepine (0.01 micrograms per mouse i.c.v.) and dicyclomine (0.08 micrograms per mouse i.c.v. or 10 mg kg-1 i.p.) but not by the specific M2-antagonist AFDX-116 (0.1 micrograms per mouse i.c.v.), naloxone (1 mg kg-1 i.p.) or by the acetylcholine (ACh) depletor hemicholinium-3 (HC-3) (1 micrograms per mouse i.c.v.). McN-A-343 and AF-102B were able to increase the pain threshold also in the mouse acetic acid writhing test and in rat paw pressure test. These antinociceptive effects were completely prevented by dicyclomine (0.08 micrograms per mouse i.c.v. or 10 mg kg-1 i.p.) but not by AFDX-116 (0.1 microgram per mouse or rat i.c.v.). 3. In contrast with the M1-agonists, the M2-agonist arecaidine (0.1-2 micrograms per mouse or rat i.c.v.) did not induce antinociception in all three analgesic tests. However, arecaidine, at the same i.c.v. doses, was able to reduce the pain threshold in the hot-plate and paw pressure tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1375858

Baseline Psychosocial Characteristics Predict Frequency of Continuous Glucose Monitoring in Youth with Type 1 Diabetes.

PubMed

McGill, Dayna E; Volkening, Lisa K; Butler, Deborah A; Harrington, Kara R; Katz, Michelle L; Laffel, Lori M

2018-05-04

Consistent use of continuous glucose monitoring (CGM) has been associated with improved glycemic control in youth with type 1 diabetes (T1D). There are many barriers to device uptake and continued use. There is a need to understand patient-specific characteristics when considering CGM. We evaluated patterns of CGM use and associations between baseline psychosocial measures and frequency of CGM use over 1 year. Youth with T1D (n = 120), ages 8-18 years, completed questionnaires at CGM initiation and after 6 and 12 months assessing depressive symptoms, diabetes burden, and diabetes-specific and generic quality of life (QOL). Youth (51% male and 95% white) had mean age 12.7 ± 2.7 years, diabetes duration 6.1 ± 3.6 years, and glycated hemoglobin (HbA 1c ) 8.0 ± 0.8%. Over 1 year, 35% of youth used CGM 6 to 7 days per week, 45% used CGM 3-5 days per week, and 20% used CGM only 0-2 days per week. Youth who used CGM 3-7 days per week over 12 months had lower HbA 1c at months 9 and 12 than youth who used CGM 0-2 days per week (9 months: 7.9 ± 0.9% vs. 8.5 ± 1.1%, P = 0.006 and 12 months: 8.0 ± 0.9% vs. 8.5 ± 1.1%, P = 0.02). Those using CGM 0-2 days per week had greater endorsement of depressive symptoms and diabetes burden and reported lower QOL at baseline compared with those using CGM 3-7 days per week. CGM use for 3 or more days per week over 12 months had a protective effect on HbA 1c . Providers should consider addressing psychosocial parameters when initiating CGM to maximize uptake and promote continued use in youth with T1D.

Adsorption of transgenic insecticidal Cry1Ab protein to silica particles. Effects on transport and bioactivity.

PubMed

Madliger, Michael; Gasser, Christoph A; Schwarzenbach, René P; Sander, Michael

2011-05-15

Bt crops are genetically modified to be resistant against insect pests by expressing insecticidal Cry proteins. The processes governing the fate and bioavailability of the expressed transgenic Cry proteins in soils are poorly understood. We studied adsorption of Cry1Ab to negatively charged silica (SiO(2)) particles, a major soil constituent and a model for negatively charged mineral surfaces, at pH 5 to 10 and ionic strengths I = 10 mM to 250 mM, both in solution depletion and saturated column transport experiments. Cry1Ab-SiO(2) interactions were dominated by patch-controlled electrostatic attraction (PCEA), as evident from increasing Cry1Ab attraction to SiO(2) with decreasing I at pH at which both Cry1Ab and SiO(2) were net negatively charged. Experimental and modeling evidence is provided that the surface heterogeneity of SiO(2) particles modulated PCEA, leading to a fraction of adsorption sites with slow Cry1Ab desorption kinetics. Desorption rates from these sites increased upon increasing the solution pH. In toxicity bioassays, we demonstrated that Cry1Ab retained insecticidal activity when adsorbed to SiO(2), suggesting high protein conformational stability during adsorption-desorption cycles. Models predicting Cry1A protein adsorption in soils therefore need to account for combined effects of the nonuniform protein surface charge distribution and of sorbent surface heterogeneity.

Establishment of a sandwich enzyme-linked immunosorbent assay for specific detection of Bacillus thuringiensis (Bt) Cry1Ab toxin utilizing a monoclonal antibody produced with a novel hapten designed with molecular model.

PubMed

Dong, Sa; Zhang, Xiao; Liu, Yuan; Zhang, Cunzheng; Xie, Yajing; Zhong, Jianfeng; Xu, Chongxin; Liu, Xianjin

2017-03-01

Cry1Ab toxin is commonly expressed in genetically modified crops in order to control chewing pests. At present, the detection method with enzyme-linked immunosorbent assay (ELISA) based on monoclonal antibody cannot specifically detect Cry1Ab toxin for Cry1Ab's amino acid sequence and spatial structure are highly similar to Cry1Ac toxin. In this study, based on molecular design, a novel hapten polypeptide was synthesized and conjugated to keyhole limpet hemocyanin (KLH). Then, through animal immunization with this antigen, a monoclonal antibody named 2C12, showing high affinity to Cry1Ab and having no cross reaction with Cry1Ac, was produced. The equilibrium dissociation constant (K D ) value of Cry1Ab toxin with MAb 2C12 was 1.947 × 10 -8  M. Based on this specific monoclonal antibody, a sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was developed for the specific determination of Cry1Ab toxin and the LOD and LOQ values were determined as 0.47 ± 0.11 and 2.43 ± 0.19 ng mL -1 , respectively. The average recoveries of Cry1Ab from spiked rice leaf and rice flour samples ranged from 75 to 115%, with coefficient of variation (CV) less than 8.6% within the quantitation range (2.5-100 ng mL -1 ), showing good accuracy for the quantitative detection of Cry1Ab toxin in agricultural samples. In conclusion, this study provides a new approach for the production of high specific antibody and the newly developed DAS-ELISA is a useful method for Cry1Ab monitoring in agriculture products. Graphical Abstract Establishment of a DAS-ELISA for the specific detecting of Bacillus thuringiensis (Bt) Cry1Ab toxin.

Sulfur speciation and stable isotope trends of water-soluble sulfates in mine tailings profiles.

PubMed

Dold, Bernhard; Spangenberg, Jorge E

2005-08-01

Sulfur speciation and the sources of water-soluble sulfate in three oxidizing sulfidic mine tailings impoundments were investigated by selective dissolution and stable isotopes. The studied tailings impoundments--Piuquenes, Cauquenes, and Salvador No. 1--formed from the exploitation of the Rio Blanco/La Andina, El Teniente, and El Salvador Chilean porphyry copper deposits, which are located in Alpine, Mediterranean, and hyperarid climates, respectively. The water-soluble sulfate may originate from dissolution of primary ore sulfates (e.g., gypsum, anhydrite, jarosite) or from oxidation of sulfide minerals exposed to aerobic conditions during mining activity. With increasing aridity and decreasing pyrite content of the tailings, the sulfur speciation in the unsaturated oxidation zones showed a trend from dominantly Fe(III) oxyhydroxide fixed sulfate (e.g., jarosite and schwertmannite) in Piuquenes toward increasing presence of water-soluble sulfate at Cauquenes and Salvador No. 1. In the saturated primary zones, sulfate is predominantly present in water-soluble form (mainly as anhydrite and/or gypsum). In the unsaturated zone at Piuquenes and Cauquenes, the delta34S(SO4)values ranged from +0.5 per thousand to +2.0 per thousand and from -0.4 per thousand to +1.4 per thousand Vienna Canyon Diablo Troilite (V-CDT), respectively, indicating a major sulfate source from pyrite oxidation (delta34S(pyrite) = -1.1 per thousand and -0.9 per thousand). In the saturated zone at Piuquenes and Cauquenes, the values ranged from -0.8 per thousand to +0.3 per thousand and from +2.2 per thousand to +3.9 per thousand, respectively. At Cauquenes the 34S enrichment in the saturated zone toward depth indicates the increasing contribution of isotopically heavy dissolved sulfate from primary anhydrite (approximately +10.9 per thousand). At El Salvador No. 1, the delta34S(SO4) average value is -0.9 per thousand, suggesting dissolution of supergene sulfate minerals (jarosite, alunite, gypsum) with a delta34S approximately -0.7 per thousand as the most probable sulfate source. The gradual decrease of delta18O(SO4) values from the surface to the oxidation front in the tailings impoundments at Piuquenes (from -4.5 per thousand to -8.6 per thousand Vienna Standard Mean Ocean Water, V-SMOW) and at Cauquenes (from -1.3 per thousand to -3.5 per thousand) indicates the increasing importance of ferric iron as the main electron acceptor in the oxidation of pyrite. The different delta18O(SO4) values between the tailings impoundments studied here reflect the local climates.

40 CFR 89.424 - Dilute emission sampling calculations.

Code of Federal Regulations, 2014 CFR

2014-07-01

... emission level (HC, CO, CO2, PM, or NOX) in g/kW-hr. gi = Mass flow in grams per hour, = grams measured...= Hydrocarbon emissions, in grams per test mode. Density HC= Density of hydrocarbons is (.5800 kg/m3) for #1... emissions, in grams per test mode. Density NO 2= Density of oxides of nitrogen is 1.913 kg/m3, assuming they...

40 CFR 89.424 - Dilute emission sampling calculations.

Code of Federal Regulations, 2012 CFR

2012-07-01

... emission level (HC, CO, CO2, PM, or NOX) in g/kW-hr. gi = Mass flow in grams per hour, = grams measured...= Hydrocarbon emissions, in grams per test mode. Density HC= Density of hydrocarbons is (.5800 kg/m3) for #1... emissions, in grams per test mode. Density NO 2= Density of oxides of nitrogen is 1.913 kg/m3, assuming they...

40 CFR 89.424 - Dilute emission sampling calculations.

Code of Federal Regulations, 2013 CFR

2013-07-01

... emission level (HC, CO, CO2, PM, or NOX) in g/kW-hr. gi = Mass flow in grams per hour, = grams measured...= Hydrocarbon emissions, in grams per test mode. Density HC= Density of hydrocarbons is (.5800 kg/m3) for #1... emissions, in grams per test mode. Density NO 2= Density of oxides of nitrogen is 1.913 kg/m3, assuming they...

Probing resistivity and doping concentration of semiconductors at the nanoscale using scanning microwave microscopy

NASA Astrophysics Data System (ADS)

Brinciotti, Enrico; Gramse, Georg; Hommel, Soeren; Schweinboeck, Thomas; Altes, Andreas; Fenner, Matthias A.; Smoliner, Juergen; Kasper, Manuel; Badino, Giorgio; Tuca, Silviu-Sorin; Kienberger, Ferry

2015-08-01

We present a new method to extract resistivity and doping concentration of semiconductor materials from Scanning Microwave Microscopy (SMM) S11 reflection measurements. Using a three error parameters de-embedding workflow, the S11 raw data are converted into calibrated capacitance and resistance images where no calibration sample is required. The SMM capacitance and resistance values were measured at 18 GHz and ranged from 0 to 100 aF and from 0 to 1 MΩ, respectively. A tip-sample analytical model that includes tip radius, microwave penetration skin depth, and semiconductor depletion layer width has been applied to extract resistivity and doping concentration from the calibrated SMM resistance. The method has been tested on two doped silicon samples and in both cases the resistivity and doping concentration are in quantitative agreement with the data-sheet values over a range of 10-3 Ω cm to 101 Ω cm, and 1014 atoms per cm3 to 1020 atoms per cm3, respectively. The measured dopant density values, with related uncertainties, are [1.1 +/- 0.6] × 1018 atoms per cm3, [2.2 +/- 0.4] × 1017 atoms per cm3, [4.5 +/- 0.2] × 1016 atoms per cm3, [4.5 +/- 1.3] × 1015 atoms per cm3, [4.5 +/- 1.7] × 1014 atoms per cm3. The method does not require sample treatment like cleavage and cross-sectioning, and high contact imaging forces are not necessary, thus it is easily applicable to various semiconductor and materials science investigations.

Bt rice harbouring cry genes controlled by a constitutive or wound-inducible promoter: protection and transgene expression under Mediterranean field conditions.

PubMed

Breitler, Jean Christophe; Vassal, Jean Michel; del Mar Catala, Maria; Meynard, Donaldo; Marfà, Victoria; Melé, Enric; Royer, Monique; Murillo, Isabel; San Segundo, Blanca; Guiderdoni, Emmanuel; Messeguer, Joaquima

2004-09-01

Seven homozygous transgenic lines of two European commercial cultivars of rice (Ariete (A) and Senia (S)), harbouring the cry1B or cry1Aa Bacillus thuringiensis (Bt) delta-endotoxin genes, were field evaluated for protection from striped stem borer (SSB) (Chilo suppressalis) damage during the 2001 and 2002 summer crop seasons in the Delta de l'Ebre region, Spain. The plant codon-optimized toxin gene was placed under the control of the promoter of either the constitutive ubi1 gene or the wound-inducible mpi gene from maize. Stable, high-level, insecticidal protein accumulation was observed throughout root, leaf and seed tissues of field-grown plants harbouring the cry1B (lines A64.1, A33.1, A3.4 and S98.9) or cry1Aa (lines S05.1 and A19.14) genes under the control of the ubi1 promoter. Conversely, no toxin was detected in unwounded vegetative tissues of the A9.1 line harbouring the cry1B gene controlled by the mpi promoter, indicating that natural environmental stresses did not trigger the activity of the wound-inducible promoter. However, the toxin accumulated at 0.2% total soluble proteins in A9.1 sheath tissue exhibiting brown lesions resulting from SSB damage. The agronomical traits and performance of the transgenic lines were generally comparable with parental controls, except in the two lines accumulating Cry1Aa, which exhibited a high frequency of plants non-true to type. Natural infestation was assisted with manual infestations of L2/L3 SSB larvae in border control plants surrounding the experimental plots, which served as a reservoir for the second-cycle SSB population. The observation of damage (brown lesions and dead hearts) during the crop season and dissection of plants at harvest stage revealed a range of protection amongst the transgenic lines, which was highly consistent with the level of toxin accumulation and with previous experience in greenhouse assays. Lines A3.4 and S05.1 were found to exhibit stable and full protection against SSB attacks, mediated by the accumulation of Cry1B and Cry1Aa toxin, respectively, which was comparable with that afforded by the spraying of chemical insecticides on control plants. The wound-induced A9.1 line exhibited a satisfactory level of protection, with a notably low level of penetration of SSB larvae in the stems, but higher external symptoms than constitutive lines, probably due to the time lag to benefit from the protective effect of Cry1B.

Total Sulfur Amino Acid Requirements Are Not Altered in Children with Chronic Renal Insufficiency, but Minimum Methionine Needs Are Increased.

PubMed

Elango, Rajavel; Humayun, Mohammad A; Turner, Justine M; Rafii, Mahroukh; Langos, Veronika; Ball, Ronald O; Pencharz, Paul B

2017-10-01

Background: The total sulfur amino acid (TSAA) and minimum Met requirements have been previously determined in healthy children. TSAA metabolism is altered in kidney disease. Whether TSAA requirements are altered in children with chronic renal insufficiency (CRI) is unknown. Objective: We sought to determine the TSAA (Met in the absence of Cys) requirements and minimum Met (in the presence of excess Cys) requirements in children with CRI. Methods: Five children (4 boys, 1 girl) aged 10 ± 2.6 y with CRI were randomly assigned to receive graded intakes of Met (0, 5, 10, 15, 25, and 35 mg · kg -1 · d -1 ) with no Cys in the diet. Four of the children (3 boys, 1 girl) were then randomly assigned to receive graded dietary intakes of Met (0, 2.5, 5, 7.5, 10, and 15 mg · kg -1 · d -1 ) with 21 mg · kg -1 · d -1 Cys. The mean TSAA and minimum Met requirements were determined by measuring the oxidation of l-[1- 13 C]Phe to 13 CO 2 (F 13 CO 2 ). A 2-phase linear-regression crossover analysis of the F 13 CO 2 data identified a breakpoint at minimal F 13 CO 2 Urine samples collected from all study days and from previous studies of healthy children were measured for sulfur metabolites. Results: The mean and population-safe (upper 95% CI) intakes of TSAA and minimum Met in children with CRI were determined to be 12.6 and 15.9 mg · kg -1 · d -1 and 7.3 and 10.9 mg · kg -1 · d -1 , respectively. In healthy school-aged children the mean and upper 95% CI intakes of TSAA and minimum Met were determined to be 12.9 and 17.2 mg · kg -1 · d -1 and 5.8 and 7.3 mg · kg -1 · d -1 , respectively. A comparison of the minimum Met requirements between healthy children and children with CRI indicated significant ( P < 0.05) differences. Conclusion: These results suggest that children with CRI have a similar mean and population-safe TSAA to that of healthy children, suggesting adequate Cys synthesis via transsulfuration, but higher minimum Met requirement, suggesting reduced remethylation rates. © 2017 American Society for Nutrition.

Duane's retraction syndrome: a retrospective review from Kathmandu, Nepal.

PubMed

Shrestha, Gauri Shankar; Sharma, Ananda Kumar

2012-01-01

  The aim was to study the clinical characteristics of Duane's retraction syndrome (DRS) in Nepalese patients.   Medical records from 52 cases of DRS from May 2003 to April 2010 were retrospectively reviewed for age, gender, laterality and clinical characteristics. Forty-one case records (78.8 per cent) that had complete clinical findings were considered for further evaluation. Examination included visual acuity by Snellen chart, refraction, associated horizontal and vertical strabismus in primary gaze, upshoot and downshoot on attempted adduction, binocular vision assessed with the Worth four-dot test on adopted gaze and stereopsis examined with the Titmus stereo test.   DRS type I was the most common type observed in 73.2 per cent of cases, followed by DRS type II (14.6 per cent) and DRS type III (12.2 per cent). It was more common in female patients (58.5 per cent) than male patients (χ(2) = 4.6, df = 1, p = 0.03). DRS was more common in the left eye (68.3 per cent) than the right eye and unilaterally present in 95.1 per cent of subjects. In primary gaze, orthotropia (41.5 per cent) was more common than exotropia (34.1 per cent) and esotropia (24.4 per cent) and vertical strabismus was present in 24.4 per cent of subjects. Upshoot and downshoot on attempted adduction was seen in 14.6 and 9.8 per cent, respectively. Binocular single vision was present in 68.3 per cent of subjects by Worth four-dot test at near. Stereopsis of 3,000 seconds of arc was present in 9.8 per cent, 100 to 200 seconds of arc in 14.6 per cent and 40 to 60 seconds of arc in 43.9 per cent with the Titmus stereo test.   DRS is more common in female patients and the left eye. DRS type I is the most common type. © 2011 The Authors. Clinical and Experimental Optometry © 2011 Optometrists Association Australia.

Effects of exposure to ambient ultrafine particles on respiratory health and systemic inflammation in children.

PubMed

Clifford, Sam; Mazaheri, Mandana; Salimi, Farhad; Ezz, Wafaa Nabil; Yeganeh, Bijan; Low-Choy, Samantha; Walker, Katy; Mengersen, Kerrie; Marks, Guy B; Morawska, Lidia

2018-05-01

It is known that ultrafine particles (UFP, particles smaller than 0.1 μm) can penetrate deep into the lungs and potentially have adverse health effects. However, epidemiological data on the health effects of UFP is limited. Therefore, our objective was to test the hypothesis that exposure to UFPs is associated with respiratory health status and systemic inflammation among children aged 8 to 11 years. We conducted a cross-sectional study among 655 children (43.3% male) attending 25 primary (elementary) schools in the Brisbane Metropolitan Area, Australia. Ultrafine particle number concentration (PNC) was measured at each school and modelled at homes using Land Use Regression to derive exposure estimates. Health outcomes were respiratory symptoms and diagnoses, measured by parent-completed questionnaire, spirometric lung function, exhaled nitric oxide (FeNO), and serum C reactive protein (CRP). Exposure-response models, adjusted for potential personal and environmental confounders measured at the individual, home and school level, were fitted using Bayesian methods. PNC was not independently associated with respiratory symptoms, asthma diagnosis or spirometric lung function. However, PNC was positively associated with an increase in CRP (1.188-fold change per 1000 UFP cm -3 day/day (95% credible interval 1.077 to 1.299)) and an increase in FeNO among atopic participants (1.054 fold change per 1000 UFP cm -3 day/day (95% CrI 1.005 to 1.106)). UFPs do not affect respiratory health outcomes in children but do have systemic effects, detected here in the form of a positive association with a biomarker for systemic inflammation. This is consistent with the known propensity of UFPs to penetrate deep into the lung and circulatory system. Copyright © 2018 Elsevier Ltd. All rights reserved.

Highly permeable artificial water channels that can self-assemble into two-dimensional arrays

PubMed Central

Shen, Yue-xiao; Si, Wen; Erbakan, Mustafa; Decker, Karl; De Zorzi, Rita; Saboe, Patrick O.; Kang, You Jung; Majd, Sheereen; Butler, Peter J.; Walz, Thomas; Aksimentiev, Aleksei; Hou, Jun-li; Kumar, Manish

2015-01-01

Bioinspired artificial water channels aim to combine the high permeability and selectivity of biological aquaporin (AQP) water channels with chemical stability. Here, we carefully characterized a class of artificial water channels, peptide-appended pillar[5]arenes (PAPs). The average single-channel osmotic water permeability for PAPs is 1.0(±0.3) × 10−14 cm3/s or 3.5(±1.0) × 108 water molecules per s, which is in the range of AQPs (3.4∼40.3 × 108 water molecules per s) and their current synthetic analogs, carbon nanotubes (CNTs, 9.0 × 108 water molecules per s). This permeability is an order of magnitude higher than first-generation artificial water channels (20 to ∼107 water molecules per s). Furthermore, within lipid bilayers, PAP channels can self-assemble into 2D arrays. Relevant to permeable membrane design, the pore density of PAP channel arrays (∼2.6 × 105 pores per μm2) is two orders of magnitude higher than that of CNT membranes (0.1∼2.5 × 103 pores per μm2). PAP channels thus combine the advantages of biological channels and CNTs and improve upon them through their relatively simple synthesis, chemical stability, and propensity to form arrays. PMID:26216964

Transgenic cotton coexpressing Vip3A and Cry1Ac has a broad insecticidal spectrum against lepidopteran pests.

PubMed

Chen, Wen-Bo; Lu, Guo-Qing; Cheng, Hong-Mei; Liu, Chen-Xi; Xiao, Yu-Tao; Xu, Chao; Shen, Zhi-Cheng; Wu, Kong-Ming

2017-10-01

Although farmers in China have grown transgenic Bt-Cry1Ac cotton to resist the major pest Helicoverpa armigera since 1997 with great success, many secondary lepidopteran pests that are tolerant to Cry1Ac are now reported to cause considerable economic damage. Vip3AcAa, a chimeric protein with the N-terminal part of Vip3Ac and the C-terminal part of Vip3Aa, has a broad insecticidal spectrum against lepidopteran pests and has no cross resistance to Cry1Ac. In the present study, we tested insecticidal activities of Vip3AcAa against Spodoptera litura, Spodoptera exigua, and Agrotis ipsilon, which are relatively tolerant to Cry1Ac proteins. The bioassay results showed that insecticidal activities of Vip3AcAa against these three pests are superior to Cry1Ac, and after an activation pretreatment, Vip3AcAa retained insecticidal activity against S. litura, S. exigua and A. ipsilon that was similar to the unprocessed protein. The putative receptor for this chimeric protein in the brush border membrane vesicle (BBMV) in the three pests was also identified using biotinylated Vip3AcAa toxin. To broaden Bt cotton activity against a wider spectrum of pests, we introduced the vip3AcAa and cry1Ac genes into cotton. Larval mortality rates for S. litura, A. ipsilon and S. exigua that had fed on this new cotton increased significantly compared with larvae fed on non-Bt cotton and Bt-Cry1Ac cotton in a laboratory experiment. These results suggested that the Vip3AcAa protein is an excellent option for a "pyramid" strategy for integrated pest management in China. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009.

PubMed

Dabelea, Dana; Mayer-Davis, Elizabeth J; Saydah, Sharon; Imperatore, Giuseppina; Linder, Barbara; Divers, Jasmin; Bell, Ronny; Badaru, Angela; Talton, Jennifer W; Crume, Tessa; Liese, Angela D; Merchant, Anwar T; Lawrence, Jean M; Reynolds, Kristi; Dolan, Lawrence; Liu, Lenna L; Hamman, Richard F

2014-05-07

Despite concern about an "epidemic," there are limited data on trends in prevalence of either type 1 or type 2 diabetes across US race and ethnic groups. To estimate changes in the prevalence of type 1 and type 2 diabetes in US youth, by sex, age, and race/ethnicity between 2001 and 2009. Case patients were ascertained in 4 geographic areas and 1 managed health care plan. The study population was determined by the 2001 and 2009 bridged-race intercensal population estimates for geographic sites and membership counts for the health plan. Prevalence (per 1000) of physician-diagnosed type 1 diabetes in youth aged 0 through 19 years and type 2 diabetes in youth aged 10 through 19 years. In 2001, 4958 of 3.3 million youth were diagnosed with type 1 diabetes for a prevalence of 1.48 per 1000 (95% CI, 1.44-1.52). In 2009, 6666 of 3.4 million youth were diagnosed with type 1 diabetes for a prevalence of 1.93 per 1000 (95% CI, 1.88-1.97). In 2009, the highest prevalence of type 1 diabetes was 2.55 per 1000 among white youth (95% CI, 2.48-2.62) and the lowest was 0.35 per 1000 in American Indian youth (95% CI, 0.26-0.47) and type 1 diabetes increased between 2001 and 2009 in all sex, age, and race/ethnic subgroups except for those with the lowest prevalence (age 0-4 years and American Indians). Adjusted for completeness of ascertainment, there was a 21.1% (95% CI, 15.6%-27.0%) increase in type 1 diabetes over 8 years. In 2001, 588 of 1.7 million youth were diagnosed with type 2 diabetes for a prevalence of 0.34 per 1000 (95% CI, 0.31-0.37). In 2009, 819 of 1.8 million were diagnosed with type 2 diabetes for a prevalence of 0.46 per 1000 (95% CI, 0.43-0.49). In 2009, the prevalence of type 2 diabetes was 1.20 per 1000 among American Indian youth (95% CI, 0.96-1.51); 1.06 per 1000 among black youth (95% CI, 0.93-1.22); 0.79 per 1000 among Hispanic youth (95% CI, 0.70-0.88); and 0.17 per 1000 among white youth (95% CI, 0.15-0.20). Significant increases occurred between 2001 and 2009 in both sexes, all age-groups, and in white, Hispanic, and black youth, with no significant changes for Asian Pacific Islanders and American Indians. Adjusted for completeness of ascertainment, there was a 30.5% (95% CI, 17.3%-45.1%) overall increase in type 2 diabetes. Between 2001 and 2009 in 5 areas of the United States, the prevalence of both type 1 and type 2 diabetes among children and adolescents increased. Further studies are required to determine the causes of these increases.

Comparative performance of modified full-length and truncated Bacillus thuringiensis-cry1Ac genes in transgenic tomato.

PubMed

Koul, Bhupendra; Yadav, Reena; Sanyal, Indraneel; Amla, Devindra Vijay

2015-01-01

Bt-cry1Ac gene has been reputedly effective against Helicoverpa armigera a notorious lepidopteran pest. Reports on the expression of full-length and truncated cry1Ac genes in plants for effective resistance against Helicoverpa sp. have been documented however, their performance is still ambiguous. Moreover, the question remains to be addressed that truncation of 3' end of the native gene was documented and suggested for active insecticidal toxin production while the most successful transgenic event(s) of commercialized-cotton are based on full-length of the cry gene. Therefore, we performed a comparative study on the efficacy of the two versions of cry1Ac genes (full-length: 3,510 bp and truncated: 1,845 bp) in T0 and T1 transgenic tomato plants and analyzed the extent of protection against H. armigera and also compared the results with our previous findings related to a successful transgenic tomato line Ab25E, expressing cry1Ab gene. The integration of cry1Ac gene(s) in T0 transgenic plants and its inheritance in T1 progeny was observed by PCR, RT-PCR and Southern blot hybridization analysis while, the toxin integrity, expression and toxicity was monitored by Western immunoassay, DAS-ELISA and insect bioassay respectively. An average transformation frequency and Bt-Cry protein content of 16.93 ± 2.10 and 0.0020-0.0128% of total soluble protein (TSP) was obtained with pRD400 vector (Trcry1Ac) while, a much lower value of 9.30 ± 2.041 and 0.0001 - 0.0026% of TSP was observed with pNBRI-1 vector (Flcry1Ac), respectively. The promising Trcry1Ac T0 transgenic plants and their T1 progeny gave full protection from H. armigera. Although Flcry1Ac gene showed lower transformation frequency and lower expression, it showed higher toxicity to H. armigera when compared with truncated Trcry1Ac gene. The full-length cry1Ac gene can be redesigned for higher expression and performance in dicots or a hybrid gene could be designed having a blend of strong receptor binding and stable expression characteristics for enhanced efficacy and toxicity to the susceptible insects.

Strong magnetization and Chern insulators in compressed graphene/CrI 3 van der Waals heterostructures

NASA Astrophysics Data System (ADS)

Zhang, Jiayong; Zhao, Bao; Zhou, Tong; Xue, Yang; Ma, Chunlan; Yang, Zhongqin

2018-02-01

Graphene-based heterostructures are a promising material system for designing the topologically nontrivial Chern insulating devices. Recently, a two-dimensional monolayer ferromagnetic insulator CrI3 was successfully synthesized in experiments [B. Huang et al., Nature (London) 546, 270 (2017), 10.1038/nature22391]. Here, these two interesting materials are proposed to build a heterostructure (Gr /CrI3). Our first-principles calculations show that the system forms a van der Waals (vdW) heterostructure, which is relatively facilely fabricated in experiments. A Chern insulating state is acquired in the Gr /CrI3 heterostructure if the vdW gap is compressed to a distance between about 3.3 and 2.4 Å, corresponding to a required external pressure between about 1.4 and 18.3 GPa. Amazingly, very strong magnetization (about 150 meV) is found in graphene, induced by the substrate CrI3, despite the vdW interactions between them. A low-energy effective model is employed to understand the mechanism. The work functions, contact types, and band alignments of the Gr /CrI3 heterostructure system are also studied. Our work demonstrates that the Gr /CrI3 heterostructure is a promising system to observe the quantum anomalous Hall effect at high temperatures (up to 45 K) in experiments.

An integrated microbial electrolysis-anaerobic digestion process combined with pretreatment of wastewater solids to improve hydrogen production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beegle, Jeff R.; Borole, Abhijeet P.

A combined anaerobic digestion (AD) and microbial electrolysis cell (MEC) system, named here as ADMEC, was investigated in this paper to evaluate the energy recovery from pretreated wastewater solids. Alkaline and thermal hydrolysis pretreatment methods increased the solubility of organic compounds present in the raw solids by 25% and 20%, respectively. The soluble phase from pretreatment was separated and used for microbial electrolysis, whereas the insoluble fraction was fed into semi-continuous digesters. The digester effluent was later utilized as a second MEC substrate. The pretreatment had variable effects on AD and MEC performance. The methane content in AD biogas wasmore » higher in pretreated groups, 78.29 ± 2.89% and 73.2 ± 1.79%, for alkaline and thermal, than the control, 50.26 ± 0.53%, but the overall biogas production rates were lower than the control, 20 and 30 mL CH 4 gCOD -1 d -1 for alkaline and thermal compared to 80 mL CH 4 gCOD -1 d -1. The effluent streams from thermally pretreated digesters were the best substrate for microbial electrolysis, in terms of hydrogen production and efficiency. The MECs produced 1.7 ± 0.2 L-H 2 per L per day, 0.3 ± 0.1 L-H 2 per L per day, and 0.29 ± 0.1 L-H 2 per L per day, for thermal, alkaline, and control reactors. The productivity was lower compared to acetate and propionate controls, which yielded 5.79 ± 0.03 L-H 2 per L per day and 3.49 ± 0.10 L-H 2 per L per day, respectively. The pretreatment solubilized fractions were not ideal substrates for microbial electrolysis. Finally, a chemical oxygen demand (COD) mass balance showed that pretreatment shifts the electron flux away from methane and biomass sinks towards hydrogen production.« less

An integrated microbial electrolysis-anaerobic digestion process combined with pretreatment of wastewater solids to improve hydrogen production

DOE PAGES

Beegle, Jeff R.; Borole, Abhijeet P.

2017-08-17

A combined anaerobic digestion (AD) and microbial electrolysis cell (MEC) system, named here as ADMEC, was investigated in this paper to evaluate the energy recovery from pretreated wastewater solids. Alkaline and thermal hydrolysis pretreatment methods increased the solubility of organic compounds present in the raw solids by 25% and 20%, respectively. The soluble phase from pretreatment was separated and used for microbial electrolysis, whereas the insoluble fraction was fed into semi-continuous digesters. The digester effluent was later utilized as a second MEC substrate. The pretreatment had variable effects on AD and MEC performance. The methane content in AD biogas wasmore » higher in pretreated groups, 78.29 ± 2.89% and 73.2 ± 1.79%, for alkaline and thermal, than the control, 50.26 ± 0.53%, but the overall biogas production rates were lower than the control, 20 and 30 mL CH 4 gCOD -1 d -1 for alkaline and thermal compared to 80 mL CH 4 gCOD -1 d -1. The effluent streams from thermally pretreated digesters were the best substrate for microbial electrolysis, in terms of hydrogen production and efficiency. The MECs produced 1.7 ± 0.2 L-H 2 per L per day, 0.3 ± 0.1 L-H 2 per L per day, and 0.29 ± 0.1 L-H 2 per L per day, for thermal, alkaline, and control reactors. The productivity was lower compared to acetate and propionate controls, which yielded 5.79 ± 0.03 L-H 2 per L per day and 3.49 ± 0.10 L-H 2 per L per day, respectively. The pretreatment solubilized fractions were not ideal substrates for microbial electrolysis. Finally, a chemical oxygen demand (COD) mass balance showed that pretreatment shifts the electron flux away from methane and biomass sinks towards hydrogen production.« less

Transgenic Bt cotton driven by the green tissue-specific promoter shows strong toxicity to lepidopteran pests and lower Bt toxin accumulation in seeds.

PubMed

Wang, Qing; Zhu, Yi; Sun, Lin; Li, Lebin; Jin, Shuangxia; Zhang, Xianlong

2016-02-01

A promoter of the PNZIP (Pharbitis nil leucine zipper) gene (1.459 kb) was cloned from Pharbitis nil and fused to the GUS (β-glucuronidase) and Bacillus thuringiensis endotoxin (Cry9C) genes. Several transgenic PNZIP::GUS and PNZIP::Cry9C cotton lines were developed by Agrobacterium-mediated transformation. Strong GUS staining was detected in the green tissues of the transgenic PNZIP::GUS cotton plants. In contrast, GUS staining in the reproductive structures such as petals, anther, and immature seeds of PNZIP::GUS cotton was very faint. Two transgenic PNZIP::Cry9C lines and one transgenic cauliflower mosaic virus (CaMV) 35S::Cry9C line were selected for enzyme-linked immunosorbent assay (ELISA) and insect bioassays. Expression of the Cry9C protein in the 35S::Cry9C line maintained a high level in most tissues ranging from 24.6 to 45.5 μg g(-1) fresh weight. In green tissues such as the leaves, boll rinds, and bracts of the PNZIP::Cry9C line, the Cry9C protein accumulated up to 50.2, 39.7, and 48.3 μg g(-1) fresh weight respectively. In contrast, seeds of the PNZIP::Cry9C line (PZ1.3) accumulated only 0.26 μg g(-1) fresh weight of the Cry9C protein, which was 100 times lower than that recorded for the seeds of the CaMV 35S::Cry9C line. The insect bioassay showed that the transgenic PNZIP::Cry9C cotton plant exhibited strong resistance to both the cotton bollworm and the pink bollworm. The PNZIP promoter could effectively drive Bt toxin expression in green tissues of cotton and lower accumulated levels of the Bt protein in seeds. These features should allay public concerns about the safety of transgenic foods. We propose the future utility of PNZIP as an economical, environmentally friendly promoter in cotton biotechnology.

Molecular characterization of Cry1D-133 toxin from Bacillus thuringiensis strain HD133 and its toxicity against Spodoptera littoralis.

PubMed

BenFarhat-Touzri, Dalel; Driss, Fatma; Jemli, Sonia; Tounsi, Slim

2018-06-01

Bacillus thuringiensis subsp. aizawai strain HD133, known by its effectiveness against Spodoptera species, produces bipyramidal crystals encompassing the insecticidal proteins Cry1Ab, Cry1Ca and Cry1D-133 in the proportions 60:37:3, respectively. In this study, we dealt with the relevance of the low rate of Cry1D-133. The cry1D-133 gene from HD133 was cloned and sequenced. Both nucleotide and amino acid sequence similarity analyses with the cry1D genes available in the GenBank database revealed that cry1D-133 is a new variant of cry1Da-type genes with 99% identity with cry1Da1. Molecular modeling of the Cry1D-133 toxin showed that its higher toxicity is correlated to a higher number of toxin-receptor interactions. Optimal culture conditions of 4 h post-induction time, 160 rpm agitation and 37 °C post-induction temperature were determined and adopted to overproduce Cry1D-133 toxin at adequate amounts to carryout bioassays. A gradual increase of the proportion of Cry1D-133 to the HD133 insecticidal proteins forming the crystal (Cry1D-133, Cry1Ca and Cry1Ab) showed an improvement of the toxicity against Spodoptera littoralis larvae. Therefore, the potential of Cry1D-133 to enhance HD133 toxicity could promote its combination with other B. thuringiensis insecticidal proteins toxins in order to increase target range or to delay the emergence of resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

White Paper Powering Sustainable Low-Carbon Economies: Some Fact and Figures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilles J. Youinou

2015-04-01

In 2011, the world production of electricity was about 22.1 trillion kilowatt-hour1 (kWhe): 9.1 from coal, 4.8 from gas, 2.6 from nuclear, 1.1 from oil, 3.5 from hydropower and 1.0 from other sources (geothermal, solar, wind, biofuels). With a world population of about 7 billion in 2011, it corresponds to an average of 3,160 kWhe/year/capita. While most industrialized countries enjoy a high standard of living with, at least, 8,000 kWhe per year and per person, most developing countries live with less than 3,000 kWhe per year per person. The need for electricity is growing fast, especially in developing countries, andmore » by 2040 the world production of electricity is projected to reach about 40 trillion kWhe.2 Assuming a world population of 10 billion and an average consumption of 6,000 kWhe per year per person in 2100 the world annual production of electricity could reach 60 trillion kWhe.« less

Analysis of cross-resistance to Vip3 proteins in eight insect colonies selected for resistance to Bacillus thuringiensis insecticidal proteins

USDA-ARS?s Scientific Manuscript database

Bacillus thuringiensis Vip3 proteins are synthesized and secreted during the vegetative growth phase. They are activated by gut proteases, recognize and bind to midgut receptors, form pores and lyse cells. We tested the susceptibility to Vip3Aa and Vip3Ca of Cry1A-, Cry2A-, Dipel- and Vip3-resistant...

Infectious reactivation of cytomegalovirus explaining age- and sex-specific patterns of seroprevalence.

PubMed

van Boven, Michiel; van de Kassteele, Jan; Korndewal, Marjolein J; van Dorp, Christiaan H; Kretzschmar, Mirjam; van der Klis, Fiona; de Melker, Hester E; Vossen, Ann C; van Baarle, Debbie

2017-09-01

Human cytomegalovirus (CMV) is a herpes virus with poorly understood transmission dynamics. Person-to-person transmission is thought to occur primarily through transfer of saliva or urine, but no quantitative estimates are available for the contribution of different infection routes. Using data from a large population-based serological study (n = 5,179), we provide quantitative estimates of key epidemiological parameters, including the transmissibility of primary infection, reactivation, and re-infection. Mixture models are fitted to age- and sex-specific antibody response data from the Netherlands, showing that the data can be described by a model with three distributions of antibody measurements, i.e. uninfected, infected, and infected with increased antibody concentration. Estimates of seroprevalence increase gradually with age, such that at 80 years 73% (95%CrI: 64%-78%) of females and 62% (95%CrI: 55%-68%) of males are infected, while 57% (95%CrI: 47%-67%) of females and 37% (95%CrI: 28%-46%) of males have increased antibody concentration. Merging the statistical analyses with transmission models, we find that models with infectious reactivation (i.e. reactivation that can lead to the virus being transmitted to a novel host) fit the data significantly better than models without infectious reactivation. Estimated reactivation rates increase from low values in children to 2%-4% per year in women older than 50 years. The results advance a hypothesis in which transmission from adults after infectious reactivation is a key driver of transmission. We discuss the implications for control strategies aimed at reducing CMV infection in vulnerable groups.

40 CFR Table 2 to Subpart Dddd of... - Model Rule-Emission Limitations

Code of Federal Regulations, 2012 CFR

2012-07-01

... part) Hydrogen chloride 62 parts per million by dry volume 3-run average (1 hour minimum sample time...) Sulfur dioxide 20 parts per million by dry volume 3-run average (1 hour minimum sample time per run...-8) or ASTM D6784-02 (Reapproved 2008).c Opacity 10 percent Three 1-hour blocks consisting of ten 6...

2D and 3D numerical simulations of morphodynamics structures in a large-amplitude meanders

USDA-ARS?s Scientific Manuscript database

In the pioneering study of the Ishikari River, Japan, Kinoshita (Kinoshita 1957, 1961) described two types of meandering channels: (1) channel with two bars per meander wavelength (one bar per bend), and (2) channel with three or more bars per meander wavelength (multiple bars per bend). Based on th...

Identification of Bacillus thuringiensis Cry1AbMod binding-proteins from Spodoptera frugiperda.

PubMed

Martínez de Castro, Diana L; García-Gómez, Blanca I; Gómez, Isabel; Bravo, Alejandra; Soberón, Mario

2017-12-01

Bacillus thuringiensis Cry toxins are currently used for pest control in transgenic crops but evolution of resistance by the insect pests threatens the use of this technology. The Cry1AbMod toxin was engineered to lack the alpha helix-1 of the parental Cry1Ab toxin and was shown to counter resistance to Cry1Ab and Cry1Ac toxins in different insect species including the fall armyworm Spodoptera frugiperda. In addition, Cry1AbMod showed enhanced toxicity to Cry1Ab-susceptible S. frugiperda populations. To gain insights into the mechanisms of this Cry1AbMod-enhanced toxicity, we isolated the Cry1AbMod toxin binding proteins from S. frugiperda brush border membrane vesicles (BBMV), which were identified by pull-down assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LC-MS/MS results indicated that Cry1AbMod toxin could bind to four classes of aminopeptidase (N1, N3, N4 y N5) and actin, with the highest amino acid sequence coverage acquired for APN 1 and APN4. In addition to these proteins, we found other proteins not previously described as Cry toxin binding proteins. This is the first report that suggests the interaction between Cry1AbMod and APN in S. frugiperda. Copyright © 2017 Elsevier Inc. All rights reserved.

Ingestion of Bt corn pollen containing Cry1Ab/2Aj or Cry1Ac does not harm Propylea japonica larvae

PubMed Central

Liu, Yanmin; Liu, Qingsong; Wang, Yanan; Chen, Xiuping; Song, Xinyuan; Romeis, Jörg; Li, Yunhe; Peng, Yufa

2016-01-01

Propylea japonica (Thunberg) (Coleoptera: Coccinellidae) is a prevalent pollen consumer in corn fields and is therefore exposed to insecticidal proteins contained in the pollen of insect-resistant transgenic corn cultivars expressing Cry proteins derived from Bacillus thuringiensis (Bt). In the present study, the potential effect of Cry1Ab/2Aj- or Cry1Ac-containing transgenic Bt corn pollen on the fitness of P. japonica larvae was evaluated. The results show that the larval developmental time was significantly shorter when P. japonica larvae were fed pollen from Bt corn cultivars rather than control pollen but that pupation rate, eclosion rate, and adult fresh weight were not significantly affected. In the feeding experiments, the stability of the Cry proteins in the food sources was confirmed. When Bt corn pollen passed through the gut of P. japonica, 23% of Cry1Ab/2Aj was digested. The results demonstrate that consumption of Bt corn pollen containing Cry1Ab/2Aj or Cry1Ac has no detrimental effect on P. japonica larvae; the shortened developmental time of larvae that consumed these proteins was likely attributable to unknown differences in the nutritional composition between the Bt-transgenic and control corn pollen. PMID:27005950

Advancing circadian rhythms before eastward flight: a strategy to prevent or reduce jet lag.

PubMed

Eastman, Charmane I; Gazda, Clifford J; Burgess, Helen J; Crowley, Stephanie J; Fogg, Louis F

2005-01-01

To develop a practical pre-eastward flight treatment to advance circadian rhythms as much as possible but not misalign them with sleep. One group had their sleep schedule advanced by 1 hour per day and another by 2 hours per day. Baseline at home, treatment in lab. Young healthy adults (11 men, 15 women) between the ages of 22 and 36 years. Three days of a gradually advancing sleep schedule (1 or 2 hours per day) plus intermittent morning bright light (one-half hour approximately 5000 lux, one-half hour of <60 lux) for 3.5 hours. The dim light melatonin onset was assessed before and after the 3-day treatment. Subjects completed daily sleep logs and symptom questionnaires and wore wrist activity monitors. The dim light melatonin onset advanced more in the 2-hours-per-day group than in the 1-hour-per-day group (median phase advances of 1.9 and 1.4 hours), but the difference between the means (1.8 and 1.5 hours) was not statistically significant. By the third treatment day, circadian rhythms were misaligned relative to the sleep schedule, and subjects had difficulty falling asleep in the 2-hours-per-day group, but this was not the case in the 1-hour-per-day group. Nevertheless, the 2-hours-per-day group did slightly better on the symptom questionnaires. In general, sleep disturbance and other side effects were small. A gradually advancing sleep schedule with intermittent morning bright light can be used to advance circadian rhythms before eastward flight and, thus, theoretically, prevent or reduce subsequent jet lag. Given the morning light treatment used here, advancing the sleep schedule 2 hours per day is not better than advancing it 1 hour per day because it was too fast for the advance in circadian rhythms. A diagram is provided to help the traveler plan a preflight schedule.

[Trend analysis on the death rate of ischemic heart disease and cerebrovascular disease among Xuzhou residents from 2011 to 2015].

PubMed

Chen, P P; Lou, P A; Zhang, P; Qiao, C; Li, T; Dong, Z M

2017-07-24

Objective: To analyze the epidemiological characteristics and trend of ischemic heart disease and cerebrovascular disease mortality among Xuzhou residents from 2011 to 2015. Methods: The mortality data of the ischemic heart disease and cerebrovascular disease were obtained from the registration disease surveillance system covering the residents of the city from 2011 to 2015. Ischemic heart disease and cerebrovascular disease were identified according to the international classification of diseases (ICD-10), Ischemic heart diseases include I20 to I25 (angina pectoris, acute myocardial infarction, certain current complications following acute myocardial infarction, other acute ischemic heart diseases chronic ischemic heart disease); cerebrovascular diseases include I60 to I69 (subarachnoid hemorrhage, intracerebral hemorrhage, other non-traumatic hemorrhage, cerebral infarction, stroke not specified as hemorrhage or infarction, other cerebrovascular diseases, sequelae of cerebrovascular disease). Results: (1)From 2011 to 2015, the chronic ischemia Cardio-Cerebrovascular disease mortality of residents in Xuzhou was 261.2 per one hundred thousand (129 950/49 748 321), 269.9 per one hundred thousand(69 562/25 775 930)for male residents, 252.0 per one hundred thousand(60 388/23 972 391)for female residents, the mortality rate in men was significantly higher than that in women ( P <0.05). The chronic ischemic Cardio-Cerebrovascular disease mortality rate of urban residents was 243.8 per one hundred thousand(17 049/6 993 787), which was lower than the rate of rural residents (264.0 per one hundred thousand(112 901/42 754 534), P <0.05). (2)From 2011 to 2015, the mortality rate of ischemic heart disease in Xuzhou city remained unchanged: 117.1 per one hundred thousand(11 416/9 747 768), 126.8 per one hundred thousand(12 177/9 600 745), 112.0 per one hundred thousand(11 184/9 986 877), 115.2 per one hundred thousand(11 697/10 151 842), 117.1 per one hundred thousand(12 019/10 261 089, P >0.05). The mortality rate of cerebrovascular disease were 154.0 per one hundred thousand(15 014/9 747 768), 155.9 per one hundred thousand(14 964/9 600 745), 143.5 per one hundred thousand(14 330/9 986 877), 135.5 per one hundred thousand(13 752/10 151 842), 130.6 per one hundred thousand(13 397/10 261 089)respectively, presented with a downward trend( P <0.05). The mortality rate of ischemic cerebrovascular disease were 62.7 per one hundred thousand(6 108/9 747 768), 74.7 per one hundred thousand(7 176/9 600 745), 72.3 per one hundred thousand(7 221/9 986 877), 70.9 per one hundred thousand(7 200/10 151 842)and 72.4 per one hundred thousand(7 431/10 261 089)respectively( P >0.05). The mortality rate of hemorrhagic cerebrovascular disease were 77.6 per one hundred thousand(7 562/9 747 768), 71.6 per one hundred thousand(6 873/9 600 745), 61.2 per one hundred thousand(6 115/9 986 877), 55.3 per one hundred thousand(5 613/10 151 842)and 46.4 per one hundred thousand(4 763/10 261 089)respectively, presented with a downward trend( P <0.05). (3)The average death age due to ischemic heart diseases of all residents was (77.0±13.1)years old, (76.4±13.2) years old among urban residents, (77.1±7.1 )years old among rural residents, (74.3±13.5)years old for male residents, (80.0±12.0) years old for female residents. The average death age due to ischemic cerebrovascular diseases of all residents was (76.4±11.9)years old, (76.5±12.3) years old among urban residents, (76.4±11.9 )years old among rural residents, (74.3±12.2)years old among male residents, (79.0±11.1) years old among female residents. From 2011 to 2015, the death age due to ischemic heart diseases were (76.3±13.5), (77.2±13.0), (76.6±13.3), (77.1±12.9)and(77.8±12.9)years old respectively; the death age due to cerebrovascular disease were (75.8±12.1), (76.3±11.8), (76.6±11.8), (76.6±12.0)and(77.1±11.9)years old respectively. The Spearman rank correlation analysis showed that the death age due to ischemic heart disease and cerebrovascular disease increased year by year in the past 5 years. ( r value was 0.033 and 0.038, respectively, all P <0.01). Conclusion: From 2011 to 2015, the mortality of hemorrhagic cerebrovascular disease decreased, while the mortality of ischemic cardiovascular and cerebrovascular diseases remained unchanged among Xuzhou residents.

Nutritional habits in Italian university students.

PubMed

Teleman, Adele Anna; de Waure, Chiara; Soffiani, Valentina; Poscia, Andrea; Di Pietro, Maria Luisa

2015-01-01

Dietary habits have been indicated by research as key elements in both disease pathogenesis and prevention and health promotion. We analyzed data collected from Italian university students regarding consumption of fruits, vegetables, fast-foods, sweets, energizing drinks, and coffee, average number of eating episodes per day and regularity of breakfast habits. 44% of the university student population eats in average at least 1 portion of fruit per day. 22.5% eats at least 2 portions of vegetables per day. 8.5% eats in average 5 times per day with 48.6% declaring an average of 3 eating episodes per day. 11.3% consumes eccessive amounts of caffeine. 49.1% of the females reaches the recommended consumption of fruit, compared to only 33.8% of males (p < 0.05). 27.7% of females eats at least 2 portions of vegetables per day, compared to 12.0% of males (p < 0.05). Eccessive coffee drinkers pass from 8.9% in the 18-21 age group to 16% in the 25-30 year old age group (p < 0.05). This study showed that the eating habits of young adults do not follow national recommendations. Less than 50% of university students eats at least 1 portion of fruit per day and less than 1 out of 4 eats at least 2 portions of vegetables per day. Less than 10% of the students eats in average 5 times per day and more than 1 out of 3 does not have breakfast regularly every morning. Interventions targeting university students are required in order to increase their knowledge on healthy eating habits and to ameliorate their dietary behaviours.

Efficacy of genetically modified Bt toxins alone and in combinations against pink bollworm resistant to Cry1Ac and Cry2Ab

USDA-ARS?s Scientific Manuscript database

Evolution of resistance in pests threatens the long-term success of transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt). Previous work showed that genetically modified Bt toxins Cry1AbMod and Cry1AcMod effectively countered resistance to native Bt toxins Cry1Ab and ...

42 CFR Appendix - Tables to Subpart H of Part 84

Code of Federal Regulations, 2012 CFR

2012-10-01

... at 9.7 km. (6 miles) per hour 1 1 1 1 1 1 1 Pulls 20 kg. (45 pound) weight to 5 feet 15 times in 1... km. (3 miles) per hour 1 1 1 2 2 2 Pulls 20 kg. (45 pound) weight to 5 feet 30 times in 2 minutes 30... Sampling and readings 2 2 2 2 Perform 1 hour test 2, 3, or 4 times respectively. Walks at 4.8 km. (3 miles...

42 CFR Appendix - Tables to Subpart H of Part 84

Code of Federal Regulations, 2014 CFR

2014-10-01

... at 9.7 km. (6 miles) per hour 1 1 1 1 1 1 1 Pulls 20 kg. (45 pound) weight to 5 feet 15 times in 1... km. (3 miles) per hour 1 1 1 2 2 2 Pulls 20 kg. (45 pound) weight to 5 feet 30 times in 2 minutes 30... Sampling and readings 2 2 2 2 Perform 1 hour test 2, 3, or 4 times respectively. Walks at 4.8 km. (3 miles...

42 CFR Appendix - Tables to Subpart H of Part 84

Code of Federal Regulations, 2013 CFR

2013-10-01

... at 9.7 km. (6 miles) per hour 1 1 1 1 1 1 1 Pulls 20 kg. (45 pound) weight to 5 feet 15 times in 1... km. (3 miles) per hour 1 1 1 2 2 2 Pulls 20 kg. (45 pound) weight to 5 feet 30 times in 2 minutes 30... Sampling and readings 2 2 2 2 Perform 1 hour test 2, 3, or 4 times respectively. Walks at 4.8 km. (3 miles...

Pain-relieving agents for infantile colic.

PubMed

Biagioli, Elena; Tarasco, Valentina; Lingua, Carla; Moja, Lorenzo; Savino, Francesco

2016-09-16

Infantile colic is a common disorder in the first months of life, affecting somewhere between 4% and 28% of infants worldwide, depending on geography and definitions used. Although it is self limiting and resolves by four months of age, colic is perceived by parents as a problem that requires action. Pain-relieving agents, such as drugs, sugars and herbal remedies, have been suggested as interventions to reduce crying episodes and severity of symptoms. To assess the effectiveness and safety of pain-relieving agents for reducing colic in infants younger than four months of age. We searched the following databases in March 2015 and again in May 2016: CENTRAL, Ovid MEDLINE, Embase and PsycINFO, along with 11 other databases. We also searched two trial registers, four thesis repositories and the reference lists of relevant studies to identify unpublished and ongoing studies. We included randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of pain-relieving agents given to infants with colic. We used the standard methodological procedures of The Cochrane Collaboration. We included 18 RCTs involving 1014 infants. All studies were small and at high risk of bias, often presenting major shortcomings across multiple design factors (e.g. selection, performance, attrition, lack of washout period).Three studies compared simethicone with placebo, and one with Mentha piperita; four studies compared herbal agents with placebo; two compared sucrose or glucose with placebo; five compared dicyclomine with placebo; and two compared cimetropium - one against placebo and the other at two different dosages. One multiple-arm study compared sucrose and herbal tea versus no treatment. Simethicone. Comparison with placebo revealed no difference in daily hours of crying reported for simethicone at the end of treatment in one small, low-quality study involving 27 infants. A meta-analysis of data from two cross-over studies comparing simethicone with placebo showed no difference in the number of of infants who responded positively to treatment (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.73 to 1.23; 110 infants, low-quality evidence).One small study (30 participants) compared simethicone with Mentha piperita and found no difference in crying duration, number of crying episodes or number of responders. Herbal agents. We found low-quality evidence suggesting that herbal agents reduce the duration of crying compared with placebo (mean difference (MD) 1.33, 95% CI 0.71 to 1.96; three studies, 279 infants), with different magnitude of benefit noted across studies (I² = 96%). We found moderate-quality evidence indicating that herbal agents increase response over placebo (RR 2.05, 95% CI 1.56 to 2.70; three studies, 277 infants). Sucrose. One very low-quality study involving 35 infants reported that sucrose reduced hours spent crying compared with placebo (MD 1.72, 95% CI 1.38 to 2.06). Dicyclomine. We could consider only one of the five studies of dicyclomine (48 infants) for the primary comparison. In this study, more of the infants given dicyclomine responded than than those given placebo (RR 2.50, 95% CI 1.17 to 5.34). Cimetropium bromide. Data from one very low-quality study comparing cimetropium bromide with placebo showed reduced crying duration among infants treated with cimetropium bromide (MD -30.20 minutes per crisis, 95% CI -39.51 to -20.89; 86 infants). The same study reported that cimetropium increased the number of responders (RR 2.29, 95% CI 1.44 to 3.64).No serious adverse events were reported for all of the agents considered, with the exception of dicyclomine, for which two of five studies reported relevant adverse effects (longer sleep 4%, wide-eyed state 4%, drowsiness 13%). At the present time, evidence of the effectiveness of pain-relieving agents for the treatment of infantile colic is sparse and prone to bias. The few available studies included small sample sizes, and most had serious limitations. Benefits, when reported, were inconsistent.We found no evidence to support the use of simethicone as a pain-relieving agent for infantile colic.Available evidence shows that herbal agents, sugar, dicyclomine and cimetropium bromide cannot be recommended for infants with colic.Investigators must conduct RCTs using standardised measures that allow comparisons among pain-relieving agents and pooling of results across studies. Parents, who most often provide the intervention and assess the outcome, should always be blinded.

Oral rehydration therapy in a rural area, northern Thailand.

PubMed

Varavithya, W; Sangshaisirisak, S; Ramaboot, S; Ruangkanchanasetr, S; Vivatwongkasem, C

1989-01-01

A cross-sectional sampling survey of mothers' practice of ORT in Amphoe Bunpotphesai in the northern part of Thailand included 1,619 children under five. Two hundred and six children were reported to have 223 diarrheal episodes. The incidence of diarrhea in children under five was 3.4 episodes per child per year. When children had diarrhea 65.5 per cent of mothers sought help from health providers, 25.2 per cent treated their children with drugs bought from stores, 2.3 per cent used herbal medicine and 6.1 per cent did not treat their children. 50.7 per cent of diarrheal episodes mother gave ORT, using ORS 19.7, commercial electrolytes mixture 16.6 and home available fluid 14.4 per cent. The accuracy of dilution of electrolytes powder from the packets was checked in 80 incidences. 31.8 and 27.8 per cent of mothers made correct dilution of ORS and commercial electrolytes products respectively. Health providers carried both ORS and commercial electrolytes packets. ORS added to a glass of water was found in 13.6 per cent which was 3 times concentrated. Commercial electrolytes products were too dilute in 72.2 per cent. 17.5 per cent of mothers divided electrolytes powder to add in one spoon of water to treat their children as one drug dose. Data showed that the ORT use rate was 50.7 per cent. Home available fluid was used by 14.4 per cent. ORT should be further promoted to control diarrheal diseases and health providers should give instructions to every mother or child minder on how to dispense ORS or electrolytes packets for appropriate dilution and use.

Cardiorespiratory instability in monitored step-down unit patients: using cluster analysis to identify patterns of change

PubMed Central

Clermont, Gilles; Chen, Lujie; Dubrawski, Artur W.; Ren, Dianxu; Hoffman, Leslie A.; Pinsky, Michael R.; Hravnak, Marilyn

2018-01-01

Cardiorespiratory instability (CRI) in monitored step-down unit (SDU) patients has a variety of etiologies, and likely manifests in patterns of vital signs (VS) changes. We explored use of clustering techniques to identify patterns in the initial CRI epoch (CRI1; first exceedances of VS beyond stability thresholds after SDU admission) of unstable patients, and inter-cluster differences in admission characteristics and outcomes. Continuous noninvasive monitoring of heart rate (HR), respiratory rate (RR), and pulse oximetry (SpO2) were sampled at 1/20 Hz. We identified CRI1 in 165 patients, employed hierarchical and k-means clustering, tested several clustering solutions, used 10-fold cross validation to establish the best solution and assessed inter-cluster differences in admission characteristics and outcomes. Three clusters (C) were derived: C1) normal/high HR and RR, normal SpO2 (n = 30); C2) normal HR and RR, low SpO2 (n = 103); and C3) low/normal HR, low RR and normal SpO2 (n = 32). Clusters were significantly different based on age (p < 0.001; older patients in C2), number of comorbidities (p = 0.008; more C2 patients had ≥ 2) and hospital length of stay (p = 0.006; C1 patients stayed longer). There were no between-cluster differences in SDU length of stay, or mortality. Three different clusters of VS presentations for CRI1 were identified. Clusters varied on age, number of comorbidities and hospital length of stay. Future study is needed to determine if there are common physiologic underpinnings of VS clusters which might inform clinical decision-making when CRI first manifests. PMID:28229353

Voyager Observations of Magnetic Fields and Cosmic Rays in the Heliosheath

NASA Technical Reports Server (NTRS)

Burlaga, L. F.; Ness, N. F.; Stone, E.; McDonald, F. B.

2011-01-01

The major features of the profile of >70 MeV/nuc cosmic ray intensity (CRI) observed by Voyager 1 (V1) in the heliosheath from 2005.8 - 2010.24 are described by the empirical "CR-B" relation as the cumulative effect of variations of the magnetic field strength B. The CRI profile observed by Voyager 2 (V2) from 2008.60 to 2010.28 in the heliosheath is also described by the CR-B relation. On a smaller scale, of the order of a hundred days, a sequence of 3 CRI decreases observed by V1 during 2006 was interpreted as the effect of a propagating interplanetary shock first interacting with the termination shock, then moving past V1, and finally reflecting from the heliopause and propagating back to V1. Our observations show that the second CRI decrease in this sequence began during the passage of a "Global Merged Interaction Region" (GMIR), approx. 40 days after the arrival of the GMIR and its possible shock. The first and third CRI decreases in the sequence were associated with local enhancements of B. The magnetic field observations associated with the second sequence of 3 cosmic ray intensity decreases observed by V1 in 2007/2008 are more difficult to reconcile with the scenario of Webber et al. and the CR-B relation. The discrepancy might indicate the importance of latitudinal effects.

Cost-effectiveness of supervised exercise therapy compared with endovascular revascularization for intermittent claudication.

PubMed

van den Houten, M M L; Lauret, G J; Fakhry, F; Fokkenrood, H J P; van Asselt, A D I; Hunink, M G M; Teijink, J A W

2016-11-01

Current guidelines recommend supervised exercise therapy (SET) as the preferred initial treatment for patients with intermittent claudication. The availability of SET programmes is, however, limited and such programmes are often not reimbursed. Evidence for the long-term cost-effectiveness of SET compared with endovascular revascularization (ER) as primary treatment for intermittent claudication might aid widespread adoption in clinical practice. A Markov model was constructed to determine the incremental costs, incremental quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio of SET versus ER for a hypothetical cohort of patients with newly diagnosed intermittent claudication, from the Dutch healthcare payer's perspective. In the event of primary treatment failure, possible secondary interventions were repeat ER, open revascularization or major amputation. Data sources for model parameters included original data from two RCTs, as well as evidence from the medical literature. The robustness of the results was tested with probabilistic and one-way sensitivity analysis. Considering a 5-year time horizon, probabilistic sensitivity analysis revealed that SET was associated with cost savings compared with ER (-€6412, 95 per cent credibility interval (CrI) -€11 874 to -€1939). The mean difference in effectiveness was -0·07 (95 per cent CrI -0·27 to 0·16) QALYs. ER was associated with an additional €91 600 per QALY gained compared with SET. One-way sensitivity analysis indicated more favourable cost-effectiveness for ER in subsets of patients with low quality-of-life scores at baseline. SET is a more cost-effective primary treatment for intermittent claudication than ER. These results support implementation of supervised exercise programmes in clinical practice. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

A decision analytic model to investigate the cost-effectiveness of poisoning prevention practices in households with young children.

PubMed

Achana, Felix; Sutton, Alex J; Kendrick, Denise; Hayes, Mike; Jones, David R; Hubbard, Stephanie J; Cooper, Nicola J

2016-08-03

Systematic reviews and a network meta-analysis show home safety education with or without the provision of safety equipment is effective in promoting poison prevention behaviours in households with children. This paper compares the cost-effectiveness of home safety interventions to promote poison prevention practices. A probabilistic decision-analytic model simulates healthcare costs and benefits for a hypothetical cohort of under 5 year olds. The model compares the cost-effectiveness of home safety education, home safety inspections, provision of free or low cost safety equipment and fitting of equipment. Analyses are conducted from a UK National Health Service and Personal Social Services perspective and expressed in 2012 prices. Education without safety inspection, provision or fitting of equipment was the most cost-effective strategy for promoting safe storage of medicines with an incremental cost-effectiveness ratio of £2888 (95 % credible interval (CrI) £1990-£5774) per poison case avoided or £41,330 (95%CrI £20,007-£91,534) per QALY gained compared with usual care. Compared to usual care, home safety interventions were not cost-effective in promoting safe storage of other household products. Education offers better value for money than more intensive but expensive strategies for preventing medicinal poisonings, but is only likely to be cost-effective at £30,000 per QALY gained for families in disadvantaged areas and for those with more than one child. There was considerable uncertainty in cost-effectiveness estimates due to paucity of evidence on model parameters. Policy makers should consider both costs and effectiveness of competing interventions to ensure efficient use of resources.

Molecular genetic analysis of circadian timekeeping in Drosophila

PubMed Central

Hardin, Paul E.

2014-01-01

A genetic screen for mutants that alter circadian rhythms in Drosophila identified the first clock gene - the period (per) gene. The per gene is a central player within a transcriptional feedback loop that represents the core mechanism for keeping circadian time in Drosophila and other animals. The per feedback loop, or core loop, is interlocked with the Clock (Clk) feedback loop, but whether the Clk feedback loop contributes to circadian timekeeping is not known. A series of distinct molecular events are thought to control transcriptional feedback in the core loop. The time it takes to complete these events should take much less than 24h, thus delays must be imposed at different steps within the core loop. As new clock genes are identified, the molecular mechanisms responsible for these delays have been revealed in ever-increasing detail, and provide an in depth accounting of how transcriptional feedback loops keep circadian time. The phase of these feedback loops shift to maintain synchrony with environmental cycles, the most reliable of which is light. Although a great deal is known about cell-autonomous mechanisms of light-induced phase shifting by CRYPTOCHROME (CRY), much less is known about non-cell autonomous mechanisms. CRY mediates phase shifts through an uncharacterized mechanism in certain brain oscillator neurons, and carries out a dual role as a photoreceptor and transcription factor in other tissues. Here I will review how transcriptional feedback loops function to keep time in Drosophila, how they impose delays to maintain a 24h cycle, and how they maintain synchrony with environmental light:dark cycles. The transcriptional feedback loops that keep time in Drosophila are well conserved in other animals, thus what we learn about these loops in Drosophila should continue to provide insight into the operation of analogous transcriptional feedback loops in other animals. PMID:21924977

Screening for single-chain variable fragment antibodies against multiple Cry1 toxins from an immunized mouse phage display antibody library.

PubMed

Dong, Sa; Bo, Zongyi; Zhang, Cunzheng; Feng, Jianguo; Liu, Xianjin

2018-04-01

Single-chain variable fragment (scFv) is a kind of antibody that possess only one chain of the complete antibody while maintaining the antigen-specific binding abilities and can be expressed in prokaryotic system. In this study, scFvs against Cry1 toxins were screened out from an immunized mouse phage displayed antibody library, which was successfully constructed with capacity of 6.25 × 10 7  CFU/mL. Using the mixed and alternative antigen coating strategy and after four rounds of affinity screening, seven positive phage-scFvs against Cry1 toxins were selected and characterized. Among them, clone scFv-3H9 (MG214869) showing relative stable and high binding abilities to six Cry1 toxins was selected for expression and purification. SDS-PAGE indicated that the scFv-3H9 fragments approximately 27 kDa were successfully expressed in Escherichia coli HB2151 strain. The purified scFv-3H9 was used to establish the double antibody sandwich enzyme-linked immunosorbent assay method (DAS-ELISA) for detecting six Cry1 toxins, of which the lowest detectable limits (LOD) and the lowest quantitative limits (LOQ) were 3.14-11.07 and 8.22-39.44 ng mL -1 , respectively, with the correlation coefficient higher than 0.997. The average recoveries of Cry1 toxins from spiked rice leaf samples were ranged from 84 to 95%, with coefficient of variation (CV) less than 8.2%, showing good accuracy for the multi-residue determination of six Cry1 toxins in agricultural samples. This research suggested that the constructed phage display antibody library based on the animal which was immunized with the mixture of several antigens under the same category can be used for the quick and effective screening of generic antibodies.

Comparative safety of anti-epileptic drugs during pregnancy: a systematic review and network meta-analysis of congenital malformations and prenatal outcomes.

PubMed

Veroniki, Areti Angeliki; Cogo, Elise; Rios, Patricia; Straus, Sharon E; Finkelstein, Yaron; Kealey, Ryan; Reynen, Emily; Soobiah, Charlene; Thavorn, Kednapa; Hutton, Brian; Hemmelgarn, Brenda R; Yazdi, Fatemeh; D'Souza, Jennifer; MacDonald, Heather; Tricco, Andrea C

2017-05-05

Pregnant women with epilepsy frequently experience seizures related to pregnancy complications and are often prescribed anti-epileptic drugs (AEDs) to manage their symptoms. However, less is known about the comparative safety of AED exposure in utero. We aimed to compare the risk of congenital malformations (CMs) and prenatal outcomes of AEDs in infants/children who were exposed to AEDs in utero through a systematic review and Bayesian random-effects network meta-analysis. MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to December 15, 2015. Two reviewers independently screened titles/abstracts and full-text papers for experimental and observational studies comparing mono- or poly-therapy AEDs versus control (no AED exposure) or other AEDs, then abstracted data and appraised the risk of bias. The primary outcome was incidence of major CMs, overall and by specific type (cardiac malformations, hypospadias, cleft lip and/or palate, club foot, inguinal hernia, and undescended testes). After screening 5305 titles and abstracts, 642 potentially relevant full-text articles, and 17 studies from scanning reference lists, 96 studies were eligible (n = 58,461 patients). Across all major CMs, many AEDs were associated with higher risk compared to control. For major CMs, ethosuximide (OR, 3.04; 95% CrI, 1.23-7.07), valproate (OR, 2.93; 95% CrI, 2.36-3.69), topiramate (OR, 1.90; 95% CrI, 1.17-2.97), phenobarbital (OR, 1.83; 95% CrI, 1.35-2.47), phenytoin (OR, 1.67; 95% CrI, 1.30-2.17), carbamazepine (OR, 1.37; 95% CrI, 1.10-1.71), and 11 polytherapies were significantly more harmful than control, but lamotrigine (OR, 0.96; 95% CrI, 0.72-1.25) and levetiracetam (OR, 0.72; 95% CrI, 0.43-1.16) were not. The newer generation AEDs, lamotrigine and levetiracetam, were not associated with significant increased risks of CMs compared to control, and were significantly less likely to be associated with children experiencing cardiac malformations than control. However, this does not mean that these agents are not harmful to infants/children exposed in utero. Counselling is advised concerning teratogenic risks when the prescription is written for a woman of childbearing age and before women continue with these agents when considering pregnancy, such as switching from polytherapy to monotherapy with evidence of lower risk and avoiding AEDs, such as valproate, that are consistently associated with CMs. These decisions must be balanced against the need for seizure control. PROSPERO CRD42014008925.

49 CFR 229.117 - Speed indicators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... locomotive at speeds in excess of 20 miles per hour shall be equipped with a speed indicator which is— (1) Accurate within ±3 miles per hour of actual speed at speeds of 10 to 30 miles per hour and accurate within ±5 miles per hour at speeds above 30 miles per hour; and (2) Clearly readable from the engineer's...

49 CFR 229.117 - Speed indicators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... locomotive at speeds in excess of 20 miles per hour shall be equipped with a speed indicator which is— (1) Accurate within ±3 miles per hour of actual speed at speeds of 10 to 30 miles per hour and accurate within ±5 miles per hour at speeds above 30 miles per hour; and (2) Clearly readable from the engineer's...

49 CFR 229.117 - Speed indicators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... locomotive at speeds in excess of 20 miles per hour shall be equipped with a speed indicator which is— (1) Accurate within ±3 miles per hour of actual speed at speeds of 10 to 30 miles per hour and accurate within ±5 miles per hour at speeds above 30 miles per hour; and (2) Clearly readable from the engineer's...

Three-dimensional magnetic critical behavior in CrI 3

DOE PAGES

Liu, Yu; Petrovic, C.

2018-01-18

CrI 3 is a promising candidate for the van der Waals bonded ferromagnetic devices since its ferromagnetism can be maintained upon exfoliating of bulk crystals down to single layer. In this work we studied critical properties of bulk CrI 3 single crystals around the paramagnetic to ferromagnetic phase transition. Critical exponents β= 0.260(4) with a critical temperature T c= 60.05(13) K and γ= 1.136(6) with T c= 60.43(4) K are obtained by the Kouvel-Fisher method, whereas δ= 5.32(2) is obtained by a critical isotherm analysis at T c= 60 K. In conclusion, the critical exponents determined in bulk CrI 3more » single crystals suggest a three-dimensional long-range magnetic coupling with the exchange distance decaying as J(r)≈r -4:69« less

Domain III of Cry1Ac Is Critical to Binding and Toxicity against Soybean Looper (Chrysodeixis includens) but Not to Velvetbean Caterpillar (Anticarsia gemmatalis).

PubMed

Mushtaq, Rubina; Shakoori, Abdul Rauf; Jurat-Fuentes, Juan Luis

2018-02-27

Insecticidal proteins Cry1Ac and Cry2Ac7 from the bacterium Bacillus thuringiensis (Bt) belong to the three-domain family of Bt toxins. Commercial transgenic soybean hybrids produce Cry1Ac to control the larvae of the soybean looper ( Chrysodeixis includens ) and the velvet bean caterpillar ( Anticarsia gemmatalis ). The specificity of Cry1Ac is determined by loops extending from domain II and regions of domain III in the three-dimensional structure of the toxin. In this study, we constructed a hybrid toxin (H1.2Ac) containing domains I and II of Cry1Ac and domain III of Cry2Ac7, in an attempt to obtain a protein with enhanced toxicity compared to parental toxins. Bioassays with H1.2Ac revealed toxicity against the larvae of A. gemmatalis but not against C. includens . Saturation binding assays with radiolabeled toxins and midgut brush border membrane vesicles demonstrated no specific H1.2Ac binding to C. includens , while binding in A. gemmatalis was specific and saturable. Results from competition binding assays supported the finding that Cry1Ac specificity against A. gemmatalis is mainly dictated by domain II. Taken together, these distinct interactions with binding sites may help explain the differential susceptibility to Cry1Ac in C. includens and A. gemmatalis , and guide the design of improved toxins against soybean pests.

Mutational disruption of the ABCC2 gene in fall armyworm, Spodoptera frugiperda, confers resistance to the Cry1Fa and Cry1A.105 insecticidal proteins.

PubMed

Flagel, Lex; Lee, Young Wha; Wanjugi, Humphrey; Swarup, Shilpa; Brown, Alana; Wang, Jinling; Kraft, Edward; Greenplate, John; Simmons, Jeni; Adams, Nancy; Wang, Yanfei; Martinelli, Samuel; Haas, Jeffrey A; Gowda, Anilkumar; Head, Graham

2018-05-08

The use of Bt proteins in crops has revolutionized insect pest management by offering effective season-long control. However, field-evolved resistance to Bt proteins threatens their utility and durability. A recent example is field-evolved resistance to Cry1Fa and Cry1A.105 in fall armyworm (Spodoptera frugiperda). This resistance has been detected in Puerto Rico, mainland USA, and Brazil. A S. frugiperda population with suspected resistance to Cry1Fa was sampled from a maize field in Puerto Rico and used to develop a resistant lab colony. The colony demonstrated resistance to Cry1Fa and partial cross-resistance to Cry1A.105 in diet bioassays. Using genetic crosses and proteomics, we show that this resistance is due to loss-of-function mutations in the ABCC2 gene. We characterize two novel mutant alleles from Puerto Rico. We also find that these alleles are absent in a broad screen of partially resistant Brazilian populations. These findings confirm that ABCC2 is a receptor for Cry1Fa and Cry1A.105 in S. frugiperda, and lay the groundwork for genetically enabled resistance management in this species, with the caution that there may be several distinct ABCC2 resistances alleles in nature.

Long-term results of heart valve replacement with the Edwards Duromedics bileaflet prosthesis: a prospective ten-year clinical follow-up.

PubMed

Podesser, B K; Khuenl-Brady, G; Eigenbauer, E; Roedler, S; Schmiedberger, A; Wolner, E; Moritz, A

1998-05-01

The Edwards Duromedics valve (Baxter Healthcare Corp., Edwards Division, Santa Ana, Calif.) was designed with a self-irrigating hinge mechanism to reduce thromboembolic complications. After good initial clinical results, distribution was suspended in 1988 after reports of valve fracture after 20,000 valves had been implanted. The manufacturer conducted extensive studies to improve the Edwards Duromedics and reintroduced a modified version, which is available as Edwards Tekna. The purpose of the study was the evaluation of long-term results of the original Edwards Duromedics that might be important for the current version, the Edwards Tekna valve. A prospective clinical 10-year follow-up was performed of 508 patients who underwent valve replacement with the Edwards Duromedics valve in the aortic (n = 268), mitral (n = 183), and aortic and mitral (n = 56) position. The perioperative mortality rate was 6.9%; follow-up was 98% complete, comprising 3648 patient-years for a mean follow-up of 86 months (range: 33 to 144 months). The actuarial freedom from complications at the 10-year follow-up and the incidence rate (percent per patient-year) were as follows: late mortality rate, 69.2% +/- 2.4% (3.5% per patient-year); thromboembolism, 90.7% +/- 1.6% (0.96% per patient-year); anticoagulation-related hemorrhage, 87.7% +/- 1.7% (1.34% per patient-year); prosthetic valve endocarditis, 96.7% +/- 0.09% (0.38% per patient-year); valve-related mortality rate, 89.3% +/- 1.6% (1.21% per patient-year); valve failure, 86.2% +/- 1.85% (1.54% per patient-year); and valve-related morbidity and mortality rate, 71.1% +/- 2.3% (3.2% per patient-year). Three leaflet escapes were observed (one lethal, two successful reoperations; 99.1% +/- 0.05% freedom, 0.08% per patient-year). All patients functionally improved (86% in New York Heart Association classes I and II), and incidence of anemia was insignificant. These results confirm that the Edwards Duromedics valve shows excellent performance concerning thromboembolism, hemolysis, and functional improvement and will serve as a reference for the last version, the Edwards Tekna valve, where comparable long-term data are currently not available.

21 CFR 558.485 - Pyrantel.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., or 80 grams per pound pyrantel tartrate. (b) Approvals. See sponsors in § 510.600(c) of this chapter for uses as in paragraph (e) of this section: (1) No. 066104: 9.6, 19.2, 48, and 80 grams per pound for use as in paragraph (e)(1) of this section. (2) [Reserved] (3) No. 017790: 9.6 and 19.2 grams per...

Systematic Motorcycle Management and Health Care Delivery: A Field Trial.

PubMed

Mehta, Kala M; Rerolle, Francois; Rammohan, Sonali V; Albohm, Davis C; Muwowo, George; Moseson, Heidi; Sept, Lesley; Lee, Hau L; Bendavid, Eran

2016-01-01

We investigated whether managed transportation improves outreach-based health service delivery to rural village populations. We examined systematic transportation management in a small-cluster interrupted time series field trial. In 8 districts in Southern Zambia, we followed health workers at 116 health facilities from September 2011 to March 2014. The primary outcome was the average number of outreach trips per health worker per week. Secondary outcomes were health worker productivity, motorcycle performance, and geographical coverage. Systematic fleet management resulted in an increase of 0.9 (SD = 1.0) trips to rural villages per health worker per week (P < .001), village-level health worker productivity by 20.5 (SD = 5.9) patient visits, 10.2 (SD = 1.5) measles immunizations, and 5.2 (SD = 5.4) child growth assessments per health worker per week. Motorcycle uptime increased by 3.5 days per week (P < .001), use by 1.5 days per week (P < .001), and mean distance by 9.3 kilometers per trip (P < .001). Geographical coverage of health outreach increased in experimental (P < .001) but not control districts. Systematic motorcycle management improves basic health care delivery to rural villages in resource-poor environments through increased health worker productivity and greater geographical coverage.

Evaluation of potential fitness costs associated with eCry3.1Ab resistance in Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae)

USDA-ARS?s Scientific Manuscript database

Both an eCry3.1Ab resistant and paired control western corn rootworm, Diabrotica virgifera virgifera colony were tested for adult longevity, egg oviposition, egg viability, and larval development in order to evaluate the potential fitness costs associated with eCry3.1Ab resistance in the western cor...

Bacterial Vegetative Insecticidal Proteins (Vip) from Entomopathogenic Bacteria

PubMed Central

Chakroun, Maissa; Banyuls, Núria; Bel, Yolanda; Escriche, Baltasar

2016-01-01

SUMMARY Entomopathogenic bacteria produce insecticidal proteins that accumulate in inclusion bodies or parasporal crystals (such as the Cry and Cyt proteins) as well as insecticidal proteins that are secreted into the culture medium. Among the latter are the Vip proteins, which are divided into four families according to their amino acid identity. The Vip1 and Vip2 proteins act as binary toxins and are toxic to some members of the Coleoptera and Hemiptera. The Vip1 component is thought to bind to receptors in the membrane of the insect midgut, and the Vip2 component enters the cell, where it displays its ADP-ribosyltransferase activity against actin, preventing microfilament formation. Vip3 has no sequence similarity to Vip1 or Vip2 and is toxic to a wide variety of members of the Lepidoptera. Its mode of action has been shown to resemble that of the Cry proteins in terms of proteolytic activation, binding to the midgut epithelial membrane, and pore formation, although Vip3A proteins do not share binding sites with Cry proteins. The latter property makes them good candidates to be combined with Cry proteins in transgenic plants (Bacillus thuringiensis-treated crops [Bt crops]) to prevent or delay insect resistance and to broaden the insecticidal spectrum. There are commercially grown varieties of Bt cotton and Bt maize that express the Vip3Aa protein in combination with Cry proteins. For the most recently reported Vip4 family, no target insects have been found yet. PMID:26935135

Qualified measurement setup of polarization extinction ratio for Panda PMF with LC/UPC connector

NASA Astrophysics Data System (ADS)

Thongdaeng, Rutsuda; Worasucheep, Duang-rudee; Ngiwprom, Adisak

2018-03-01

Polarization Extinction Ratio (PER) is one of the key parameters for Polarization Maintaining Fiber (PMF) connector. Based on our previous studies, the bending radius of fiber greater than 1.5 cm will not affect the insertion loss of PMF [1]. Moreover, the measured PER of Panda PMF with LC/UPC connectors is more stable when that PMF is coiled around a hot rod with a minimum of 3-cm in diameter at 75°C temperature [2]. Hence, the hot rod with less constrained 6-cm in diameter at constant 75°C was selected for this PER measurement. Two PER setups were verified and compared for measuring LC/UPC PMF connectors. The Polarized Laser Source (PLS) at 1550 nm wavelength and PER meter from OZ Optics were used in both setups, in which the measured connector was connected to PLS at 0° angle while the other end was connected to PER meter. In order to qualify our setups, the percentage of Repeatability and Reproducibility (%R&R) were tested and calculated. In each setup, the PER measurement was repeated 3 trials by 3 appraisers using 10 LC/UPC PMF connectors (5 LC/UPC PMF patchcords with 3.5+/-0.5 meters in length) in random order. The 1st setup, PMF was coiled at a larger 20-cm diameter for 3 to 5 loops and left in room temperature during the test. The 2nd setup, PMF was coiled around a hot rod at constant 75°C with 6-cm diameter for 8 to 10 loops for at least 5 minutes before testing. There are 3 ranges of %R&R acceptation guide line: <10% is acceptable, between 10% - 30% is marginal, and <30% is unacceptable. According to our results, the %R&R of the 1st PER test setup was 16.2% as marginality, and the 2nd PER test setup was 8.9% as acceptance. Thus, providing the better repeatability and reproducibility, this 2nd PER test setup having PMF coiled around a hot rod at constant 75°C with 6-cm diameter was selected for our next study of the impact of hot temperature on PER in LC/UPC PMF connector.

Residual Associations of Inflammatory Markers with eGFR after Accounting for Measured GFR in a Community-Based Cohort without CKD.

PubMed

Schei, Jørgen; Stefansson, Vidar T N; Mathisen, Ulla Dorte; Eriksen, Bjørn O; Solbu, Marit D; Jenssen, Trond G; Melsom, Toralf

2016-02-05

eGFR on the basis of creatinine (eGFRcre) associates differently with cardiovascular disease and mortality than eGFR on the basis of cystatin C (eGFRcys). This may be related to risk factors affecting the level of creatinine and cystatin C along non-GFR pathways, which may confound the association between eGFR and outcome. Nontraditional risk factors are usually not measured in epidemiologic studies of eGFR and cannot be adjusted for to reduce confounding. We examined whether the inflammatory markers soluble TNF receptor type 2 (sTNFR2), C-reactive protein (CRP), and fibrinogen associated differently with eGFR than with measured GFR (mGFR). GFR was measured by iohexol clearance in 1627 middle-aged participants without kidney disease, diabetes, or cardiovascular disease enrolled in the Renal Iohexol Clearance Survey Study from the Sixth Tromsø Study between 2007 and 2009. Generalized estimating equations were used to assess the residual associations between eGFR (eGFRcre, eGFRcys, and eGFR on the basis of creatinine and cystatin C) and the inflammatory markers relative to mGFR. sTNFR2, CRP, and fibrinogen were associated with a higher eGFRcre after accounting for mGFR in multivariable-adjusted models (2.63 ml/min per 1.73 m(2); 95% confidence interval [95% CI], 2.1 to 3.2 per SD increase in sTNFR2, 0.93 ml/min per 1.73 m(2); 95% CI, 0.3 to 1.5 per SD increase in log CRP, and 1.19 ml/min per 1.73 m(2); 95% CI, 0.6 to 1.8 per SD increase in fibrinogen). sTNFR2 and CRP were inversely associated with eGFRcys (-1.4 ml/min per 1.73 m(2); 95% CI, -2.1 to -0.6 per SD increase in sTNFR2, and -0.76 ml/min per 1.73 m(2); 95% CI, -1.4 to -0.1 per SD increase in log CRP). eGFRcre and eGFRcys are associated with inflammatory factors after accounting for mGFR but in opposite directions. These non-GFR-related associations may bias risk estimates by eGFR and, in part, explain the different risks predicted by eGFRcre and eGFRcys in longitudinal studies. Copyright © 2016 by the American Society of Nephrology.

Bt Crops Producing Cry1Ac, Cry2Ab and Cry1F Do Not Harm the Green Lacewing, Chrysoperla rufilabris

PubMed Central

Tian, Jun-Ce; Wang, Xiang-Ping; Long, Li-Ping; Romeis, Jörg; Naranjo, Steven E.; Hellmich, Richard L.; Wang, Ping; Earle, Elizabeth D.; Shelton, Anthony M.

2013-01-01

The biological control function provided by natural enemies is regarded as a protection goal that should not be harmed by the application of any new pest management tool. Plants producing Cry proteins from the bacterium, Bacillus thuringiensis (Bt), have become a major tactic for controlling pest Lepidoptera on cotton and maize and risk assessment studies are needed to ensure they do not harm important natural enemies. However, using Cry protein susceptible hosts as prey often compromises such studies. To avoid this problem we utilized pest Lepidoptera, cabbage looper (Trichoplusia ni) and fall armyworm (Spodoptera frugiperda), that were resistant to Cry1Ac produced in Bt broccoli (T. ni), Cry1Ac/Cry2Ab produced in Bt cotton (T. ni), and Cry1F produced in Bt maize (S. frugiperda). Larvae of these species were fed Bt plants or non-Bt plants and then exposed to predaceous larvae of the green lacewing Chrysoperla rufilabris. Fitness parameters (larval survival, development time, fecundity and egg hatch) of C. rufilabris were assessed over two generations. There were no differences in any of the fitness parameters regardless if C. rufilabris consumed prey (T. ni or S. frugiperda) that had consumed Bt or non-Bt plants. Additional studies confirmed that the prey contained bioactive Cry proteins when they were consumed by the predator. These studies confirm that Cry1Ac, Cry2Ab and Cry1F do not pose a hazard to the important predator C. rufilabris. This study also demonstrates the power of using resistant hosts when assessing the risk of genetically modified plants on non-target organisms. PMID:23544126

Enhanced toxicity of Bacillus thuringiensis Cry3A 8-endotoxin in coleopterans by mutagenesis in recetor binding loop

Treesearch

Sheng-Jiun Wu; Noah C. Koller; Deborah L. Miller; Leah S. Bauer; Donald H. Dean

2000-01-01

We used site-directed mutagenesis to modify the Bacillus cry3A gene in amino acid residues 350-354. Two mutant toxins, A1 (R345A, Y350F, Y351F) and A2 (R345A,DeltaY350, DeltaY351, showed significantly improved...

Ground-water contamination in East Bay Township, Michigan

USGS Publications Warehouse

Twenter, F.R.; Cummings, T.R.; Grannemann, N.G.

1985-01-01

Glacial deposits, as much as 360 feet thick, underlie the study area. The upper 29 to 118 feet, a sand and gravel unit, is the aquifer tapped for water by all wells in the area. This unit is underlain by impermeable clay that is at least 100 feet thick. Ground-water flow is northeastward at an estimated rate of 3 to 6 feet per day. Hydraulic conductivities in the aquifer range from 85 to 150 feet per day; 120 feet per day provided the best match of field data in a ground-water flow model. The depth to water ranged from 1 to 20 feet. Chemical anlayses indicate that ground water is contaminated with organic chemicals from near the Hangar/Administration building at the U.S. Coast Guard Air Station to East Bay, about 4,300 feet northeast. The plume, which follows ground-water flow lines, ranges from 180 to 400 feet wide. In the upper reach of the plume, hydrocarbons less dense than water occur at the surface of the water table; they move downward in the aquifer as they move toward East Bay. Maximum concentrations of the major organic compounds include: benzene, 3,390 micrograms per liter; toluene, 55,500 micrograms per liter; xylene, 3,900 micrograms per liter; tetrachloroethylene, 3,410 micrograms per liter; and bis (2-ethyl hexyl) phthalate, 2,100 micrograms per liter. Soils are generally free of these hydrocarbons; however, in the vicinity of past drum storage, aircraft maintenance operations, and fuel storage and dispensing, as much as 1,100 micrograms per kilogram of tetrachloroethylene and 1,500 micrograms per kilogram of bis (2-ethyl hexyl) phthalate were detected. At a few locations higher molecular weight hydrocarbons, characteristic of petroleum distillates, were found.

High rates of sexually transmissible infections in HIV-positive patients in the Australian HIV Observational Database: a prospective cohort study.

PubMed

Mulhall, Brian P; Wright, Stephen; Allen, Debbie; Brown, Katherine; Dickson, Bridget; Grotowski, Miriam; Jackson, Eva; Petoumenos, Kathy; Read, Phillip; Read, Timothy; Russell, Darren; Smith, David J; Templeton, David J; Fairley, Christopher K; Law, Matthew G

2014-09-01

Background In HIV-positive people, sexually transmissible infections (STIs) probably increase the infectiousness of HIV. In 2010, we established a cohort of individuals (n=554) from clinics in the Australian HIV Observational Database (AHOD). We calculated retrospective rates for four STIs for 2005-10 and prospective incidence rates for 2010-11. At baseline (2010), patient characteristics were similar to the rest of AHOD. Overall incidence was 12.5 per 100 person-years. Chlamydial infections increased from 3.4 per 100 person-years (95% confidence interval (CI): 1.9-5.7) in 2005 to 6.7 per 100 person-years (95% CI: 4.5-9.5) in 2011, peaking in 2010 (8.1 per 100 person-years; 95% CI: 5.6-11.2). Cases were distributed among rectal (61.9%), urethral (34%) and pharyngeal (6.3%) sites. Gonococcal infections increased, peaking in 2010 (4.7 per 100 person-years; 95% CI: 5.6-11.2; Ptrend=0.0099), distributed among rectal (63.9%), urethral (27.9%) and pharyngeal (14.8%) sites. Syphilis showed several peaks, the largest in 2008 (5.3 per 100 person-years; 95% CI: 3.3-8.0); the overall trend was not significant (P=0.113). Genital warts declined from 7.5 per 100 person-years (95% CI: 4.8-11.3) in 2005 to 2.4 per 100 person-years (95% CI: 1.1-4.5) in 2011 (Ptrend=0.0016). For chlamydial and gonococcal infections, incidence was higher than previous Australian estimates among HIV-infected men who have sex with men, increasing during 2005-2011. Rectal infections outnumbered infections at other sites. Syphilis incidence remained high but did not increase; that of genital warts was lower and decreased.

Estimation of Freely-Dissolved Concentrations of Polychlorinated Biphenyls, 2,3,7,8-Substituted Congeners and Homologs of Polychlorinated dibenzo-p-dioxins and Dibenzofurans in Water for Development of Total Maximum Daily Loadings for the Bluestone River Watershed, Virginia and West Virginia

USGS Publications Warehouse

Gale, Robert W.

2007-01-01

The Commonwealth of Virginia Department of Environmental Quality, working closely with the State of West Virginia Department of Environmental Protection and the U.S. Environmental Protection Agency is undertaking a polychlorinated biphenyl source assessment study for the Bluestone River watershed. The study area extends from the Bluefield area of Virginia and West Virginia, targets the Bluestone River and tributaries suspected of contributing to polychlorinated biphenyl, polychlorinated dibenzo-p-dioxin and dibenzofuran contamination, and includes sites near confluences of Big Branch, Brush Fork, and Beaver Pond Creek. The objectives of this study were to gather information about the concentrations, patterns, and distribution of these contaminants at specific study sites to expand current knowledge about polychlorinated biphenyl impacts and to identify potential new sources of contamination. Semipermeable membrane devices were used to integratively accumulate the dissolved fraction of the contaminants at each site. Performance reference compounds were added prior to deployment and used to determine site-specific sampling rates, enabling estimations of time-weighted average water concentrations during the deployed period. Minimum estimated concentrations of polychlorinated biphenyl congeners in water were about 1 picogram per liter per congener, and total concentrations at study sites ranged from 130 to 18,000 picograms per liter. The lowest concentration was 130 picograms per liter, about threefold greater than total hypothetical concentrations from background levels in field blanks. Polychlorinated biphenyl concentrations in water fell into three groups of sites: low (130-350 picogram per liter); medium (640-3,500 picogram per liter; and high (11,000-18,000 picogram per liter). Concentrations at the high sites, Beacon Cave and Beaverpond Branch at the Resurgence, were about four- to sixfold higher than concentrations estimated for the medium group of sites. Minimum estimated concentrations of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in water were about 0.2 to 1 femtograms per liter. Estimated total concentrations of 2,3,7,8-substituted congeners in water at study sites ranged from less than 1 to 22,000 femtograms per liter and less than 1 to 2,300 femtograms per liter for polychlorinated dibenzo-p-dioxin and dibenzofuran congeners, respectively. Total concentrations of 2,3,7,8-substituted congeners in water were comprised largely of octachlorodibenzo-p-dioxin and dibenzofuran, with less than 10 percent of the total contributed by concentrations of other congeners, mainly 2,3,7,8-heptachlorodibenzo-p-dioxin and dibenzofuran. Of special interest for this study was 2,3,7,8-tetrachlorodibenzo-p-dioxin with a regulatory surface water-quality criterion of 1,200 femtograms per liter. Estimated concentrations in water ranged from 0.5 to 41 femtograms per liter. Concentrations in water were less than 5 femtograms per liter at all study sites, except the Bluefield Westside Sewage Treatment Plan, with an estimated concentration of 41 femtograms per liter. Estimated total concentrations of homologs of polychlorinated dibenzo-p-dioxins and dibenzofurans in water at the study sites ranged from 3,200 to 36,000 femtograms per liter and 210-4,800 femtograms per liter, respectively. Again, homologs of polychlorinated dibenzo-p-dioxins and dibenzofurans in water were comprised largely of octachlorodibenzo-p-dioxin and dibenzofuran.

The effects of the number of rubber bands placed at each endoscopic session upon variceal outcomes: a prospective, randomized study.

PubMed

Ramirez, Francisco C; Colon, Victor J; Landan, Derek; Grade, Andrew J; Evanich, Elizabeth

2007-07-01

To determine the role of the number of bands placed per session upon patient-related and procedural-related outcomes. Patients were assigned to receive as many bands as could be possibly placed (group 1) or up to a maximum of six bands (group 2) per session. The primary outcome measured was the number of sessions to achieve obliteration. Other outcomes measured included: rebleeding, variceal recurrence, mortality (within 6 wk and within 1 yr), complications, banding and total procedure times, and number of bands misfired. A total of 86 patients were enrolled: 45 in group 1 and 41 in group 2. The two groups had similar age, Child-Pugh scores, grade of varices at entry. The overall proportion of patients achieving obliteration was 56% (53% and 59% for groups 1 and 2, respectively). Despite receiving significantly more mean bands per session, patients in group 1 required similar (mean +/- SEM) number of sessions to obliteration (2.9 +/- 0.3 vs 3.3 +/- 0.3) and total number of bands (20.0 +/- 2.4 vs 16.6 +/- 1.8) to achieve this goal compared with group 2. The overall proportion of patients with variceal rebleeding was 25%, the 1-yr variceal recurrence 31.3%, and the overall early- and 1-yr mortality were 18.6% and 33.7%, respectively. These proportions were similar in the two groups. Banding and total procedure times were significantly longer and associated with significantly more misfired bands per session in group 1. Compared with a maximum of six bands per session, the placement of >6 bands per session was not associated with better patient outcomes but with significantly more prolonged banding and total procedure times and significantly more misfired bands.

Feeding, oviposition and survival of Liriomyza trifolii (Diptera: Agromyzidae) on Bt and non-Bt cottons

USDA-ARS?s Scientific Manuscript database

The effects of Bt transgenic cottons (Bt-I expressing cry1Ac and Bt-H expressing cry1Ab and cry2Ab or cry1Ab and cry1Fa) and non-Bt cottons on feeding, oviposition and longevity of adults, and development and survival of Liriomyza trifolii larvae were studies under laboratory conditions, and infesta...

In situ surface transfer process of Cry1Ac protein on SiO2： The effect of biosurfactants for desorption.

PubMed

Miao, Shuzhou; Yuan, Xingzhong; Liang, Yunshan; Wang, Hou; Leng, Lijian; Wu, Zhibin; Jiang, Longbo; Li, Yifu; Mo, Dan; Zeng, Guangming

2018-01-05

Genetically modified Bacillus thuringiensis (Bt) crops, which have been widely used in agricultural transgenic plants, express insecticidal Cry proteins and release the toxin into soils. Taking into consideration the environmental risk of Cry proteins, biosurfactant-rhamnolipids were applied to desorb Cry proteins from soil environment, which has not been elucidated before. Quartz crystal microbalance with dissipation (QCM-D) was used in this article to investigate the adsorption and desorption behaviors of Cry1Ac on SiO 2 surface (model soil). Results showed that patch-controlled electrostatic attraction (PCEA) governed Cry1Ac adsorption to SiO 2, and the solution pH or ionic strength can affect PCEA. The adsorption kinetics could be fitted by the pseudo-second-order model, and the adsorption isotherm was fitted to Langmuir model with correlation coefficients higher than 0.999. The desorption characteristics of Cry1Ac from SiO 2 were assessed in the presence of mono-rhamnolipid, di-rhamnolipid or complex-rhamnolipid. Mono-rhamnolipid exhibited the most significant positive effect on desorption performance. With a complete removal of Cry1Ac reached when mono-rhamnolipid concentration was up to 50mgL -1 . Additionally, the desorption was enhanced at alkaline pH range, and Cry1Ac can be completely and rapidly desorbed by rhamnolipids from SiO 2 at ionic strength of 5×10 -2 M. Copyright © 2017 Elsevier B.V. All rights reserved.

Race, APOL1 Risk, and eGFR Decline in the General Population

PubMed Central

Rebholz, Casey M.; Chen, Yuan; Rawlings, Andreea M.; Estrella, Michelle M.; Selvin, Elizabeth; Appel, Lawrence J.; Tin, Adrienne; Coresh, Josef

2016-01-01

The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987–1989 (baseline) to 2011–2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th–90th percentile) unadjusted eGFR decline was 1.5 (1.0–2.2) ml/min per 1.73 m2 per year for whites, 2.1 (1.4–3.1) ml/min per 1.73 m2 per year for blacks with APOL1 low-risk status, and 2.3 (1.5–3.5) ml/min per 1.73 m2 per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified. PMID:26966015

Race, APOL1 Risk, and eGFR Decline in the General Population.

PubMed

Grams, Morgan E; Rebholz, Casey M; Chen, Yuan; Rawlings, Andreea M; Estrella, Michelle M; Selvin, Elizabeth; Appel, Lawrence J; Tin, Adrienne; Coresh, Josef

2016-09-01

The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987-1989 (baseline) to 2011-2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th-90th percentile) unadjusted eGFR decline was 1.5 (1.0-2.2) ml/min per 1.73 m(2) per year for whites, 2.1 (1.4-3.1) ml/min per 1.73 m(2) per year for blacks with APOL1 low-risk status, and 2.3 (1.5-3.5) ml/min per 1.73 m(2) per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified. Copyright © 2016 by the American Society of Nephrology.

7 CFR 58.938 - Physical requirements and microbiological limits for sweetened condensed milk.

Code of Federal Regulations, 2013 CFR

2013-01-01

... retain a definite form. (e) Microbiological limits. (1) Coliforms, less than 10 per gram; (2) yeasts, less than 5 per gram; (3) molds, less than 5 per gram; (4) total plate count, less than 1,000 per gram... amount of sediment retained on a lintine disc after a sample composed of 225 grams of product dissolved...

Abnormal circadian locomotor rhythms and Per gene expression in six-month-old triple transgenic mice model of Alzheimer's disease.

PubMed

Wu, Meina; Zhou, Fang; Cao, Xiuli; Yang, Junting; Bai, Yu; Yan, Xudong; Cao, Jimin; Qi, Jinshun

2018-05-29

Circadian rhythm disturbance (CRD) is one of the iconic manifestations in Alzheimer's disease (AD), a disease tightly associated with age, but the characteristics and gender difference of CRD occurred in AD have not been well demonstrated. Using 6-month-old triple transgenic AD mouse model (3xTg-AD) without obvious brain pathological changes, we demonstrated the gender difference of CRD at this age. We further showed abnormal Per gene expression in the central clock suprachiasmatic nucleus (SCN) of the 3xTg-AD mice. Specifically, compared with the wide type (WT) mice, the 3xTg-AD mice showed disrupted circadian locomotor rhythms both at LD (light-dark 12 h:12 h) and DD (constant dark) conditions, such as increased activities in the resting phase, decreased and scattered activities in the active phase, decreased overall activity intensities, amplitude, robustness, and increased intradaily variability. We further observed that 3xTg-AD female mice showed obviously less CRD compared with the 3xTg-AD male mice, and female mice of both WT and 3xTg-AD were more active in locomotor activity. Accordingly, 3xTg-AD mice showed a phase delay in the expression of Per1 and Per2 mRNA in the SCN, with the levels of Per1 and Per2 mRNA were significantly lower than that of WT mice at specific time points. We conclude that 3xTg-AD mice exhibit behavioral CRD at the age of six months with male gender preference, and these phenomena are at least partly associated with the alteration of Per1 and Per2 transcription patterns in the SCN. Copyright © 2018 Elsevier B.V. All rights reserved.

A serosurvey for selected pathogens in Greek European wild boar

PubMed Central

Touloudi, A.; Valiakos, G.; Athanasiou, L. V.; Birtsas, P.; Giannakopoulos, A.; Papaspyropoulos, K.; Kalaitzis, C.; Sokos, C.; Tsokana, C. N.; Spyrou, V.; Petrovska, L.; Billinis, C.

2015-01-01

Objectives Serum samples, collected from 94 European wild boar (Sus scrofa) during the hunting seasons 2006 -2010 from different regions of Greece, were examined in order to estimate the role of these wildlife species as reservoir of pathogens important for livestock and/or public health. Materials and Methods The assays used for this purpose were commercial indirect ELISA for the detection of antibodies against porcine circovirus type 2 (PCV-2), porcine reproductive and respiratory syndrome (virus) (PRRSV), Aujeszky's disease virus (ADV), influenza A (IA) virus, Actinobacillus pleuropneumoniae, Mycoplasma hyopneumoniae, Salmonella species, Trichinella species and indirect immunofluorescence antibody test for the detection of antibodies against Toxoplasma gondii and Neospora caninum. Results Antibodies against PCV-2, PRRSV, ADV, IA virus,A. pleuropneumoniae, M. hyopneumoniae,Salmonella species, Trichinella species, T. gondii and N. caninum were detected in 19.1 per cent, 12.8 per cent, 35.1 per cent, 1.1 per cent, 57.4 per cent, 0 per cent, 4.3 per cent, 6.4 per cent, 5.2 per cent and 1.1 per cent of the samples, respectively. Cluster analysis revealed a hot spot of seropositivity near Bulgarian border; seropositivity to ADV was more common among female animals. Conclusions These results indicate exposure of wild boar to most of the above-mentioned pathogens, raising concern about the possibility that these species may pose a significant health risk for livestock and/or humans. PMID:26392908

Cryptochrome and Phytochrome Cooperatively but Independently Reduce Active Gibberellin Content in Rice Seedlings under Light Irradiation

PubMed Central

Hirose, Fumiaki; Inagaki, Noritoshi; Hanada, Atsushi; Yamaguchi, Shinjiro; Kamiya, Yuji; Miyao, Akio; Hirochika, Hirohiko; Takano, Makoto

2012-01-01

In contrast to a wealth of knowledge about the photoregulation of gibberellin metabolism in dicots, that in monocots remains largely unclear. In this study, we found that a blue light signal triggers reduction of active gibberellin content in rice seedlings with simultaneous repression of two gibberellin 20-oxidase genes (OsGA20ox2 and OsGA20ox4) and acute induction of four gibberellin 2-oxidase genes (OsGA2ox4–OsGA2ox7). For further examination of the regulation of these genes, we established a series of cryptochrome-deficient lines through reverse genetic screening from a Tos17 mutant population and construction of knockdown lines based on an RNA interference technique. By using these lines and phytochrome mutants, we elucidated that cryptochrome 1 (cry1), consisting of two species in rice plants (cry1a and cry1b), is indispensable for robust induction of the GA2ox genes. On the other hand, repression of the GA20ox genes is mediated by phytochromes. In addition, we found that the phytochromes also mediate the repression of a gibberellin 3-oxidase gene (OsGA3ox2) in the light. These results imply that, in rice seedlings, phytochromes mediate the repression of gibberellin biosynthesis capacity, while cry1 mediates the induction of gibberellin inactivation capacity. The cry1 action was demonstrated to be dominant in the reduction of active gibberellin content, but, in rice seedlings, the cumulative effects of these independent actions reduced active gibberellin content in the light. This pathway design in which different types of photoreceptors independently but cooperatively regulate active gibberellin content is unique from the viewpoint of dicot research. This redundancy should provide robustness to the response in rice plants. PMID:22764280

Cryptochrome and phytochrome cooperatively but independently reduce active gibberellin content in rice seedlings under light irradiation.

PubMed

Hirose, Fumiaki; Inagaki, Noritoshi; Hanada, Atsushi; Yamaguchi, Shinjiro; Kamiya, Yuji; Miyao, Akio; Hirochika, Hirohiko; Takano, Makoto

2012-09-01

In contrast to a wealth of knowledge about the photoregulation of gibberellin metabolism in dicots, that in monocots remains largely unclear. In this study, we found that a blue light signal triggers reduction of active gibberellin content in rice seedlings with simultaneous repression of two gibberellin 20-oxidase genes (OsGA20ox2 and OsGA20ox4) and acute induction of four gibberellin 2-oxidase genes (OsGA2ox4-OsGA2ox7). For further examination of the regulation of these genes, we established a series of cryptochrome-deficient lines through reverse genetic screening from a Tos17 mutant population and construction of knockdown lines based on an RNA interference technique. By using these lines and phytochrome mutants, we elucidated that cryptochrome 1 (cry1), consisting of two species in rice plants (cry1a and cry1b), is indispensable for robust induction of the GA2ox genes. On the other hand, repression of the GA20ox genes is mediated by phytochromes. In addition, we found that the phytochromes also mediate the repression of a gibberellin 3-oxidase gene (OsGA3ox2) in the light. These results imply that, in rice seedlings, phytochromes mediate the repression of gibberellin biosynthesis capacity, while cry1 mediates the induction of gibberellin inactivation capacity. The cry1 action was demonstrated to be dominant in the reduction of active gibberellin content, but, in rice seedlings, the cumulative effects of these independent actions reduced active gibberellin content in the light. This pathway design in which different types of photoreceptors independently but cooperatively regulate active gibberellin content is unique from the viewpoint of dicot research. This redundancy should provide robustness to the response in rice plants.

Unconditional cash transfers for clinical and economic outcomes among HIV-affected Ugandan households: a bayesian randomised trial.

PubMed

Mills, Edward J; Adhvaryu, Achyuta; Jakiela, Pamela; Birungi, Josephine; Okoboi, Stephen; Chimulwa, Teddy; Wangisi, Jonathan; Achilla, Tina; Popoff, Evan; Golchi, Shirin; Karlan, Dean

2018-05-28

HIV infection has profound clinical and economic costs at the household level. This is particularly important in low-income settings, where access to additional sources of income or loans may be limited. While several microfinance interventions have been proposed, unconditional cash grants, a strategy to allow participants to choose how to use finances that may improve household security and health, has not previously been evaluated. We examined the effect of an unconditional cash transfer to HIV-infected individuals using a 2 x 2 factorial randomised trial in two rural districts in Uganda. Our primary outcomes were changes in CD4 cell count, sexual behaviors, and adherence to ART. Secondary outcomes were changes in household food security and adult mental health. We applied a Bayesian approach for our primary analysis. We randomized 2170 patients as participatants, with 1081 receiving a cash grant. We found no important intervention effects on CD4 t-cell counts between groups (mean difference [MD] 35.48, 95% Credible Interval [CrI] -59.9-1131.6), food security (odds ratio [OR] 1.22, 95% CrI: 0.47, 3.02), medication adherence (OR 3.15, 95% CrI: 0.58, 18.15), or sexual behavior (OR 0.45 95% CrI: 0.12, 1.55), or health expenditure in the previous 3 weeks (Mean Difference $2.65, 95% CrI: -9.30, 15.69). In secondary analysis, we detected an effect of mental planning on CD4 change between groups (104.2 cells, 9% CrI: 5.99, 202.16). We did not have data on viral load outcomes. Although all outcomes were associated with favorable point estimates, our trial did not demonstrate important effects of unconditional cash grants on health outcomes.

Television Viewing and Risk of Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality A Meta-analysis

PubMed Central

Grøntved, Anders; Hu, Frank B.

2015-01-01

Context Prolonged television (TV) viewing is the most prevalent and pervasive sedentary behavior in industrialized countries and has been associated with morbidity and mortality. However, a systematic and quantitative assessment of published studies is not available. Objective To perform a meta-analysis of all prospective cohort studies to determine the association between TV viewing and risk of type 2 diabetes, fatal or nonfatal cardiovascular disease, and all-cause mortality. Data Sources and Study Selection Relevant studies were identified by searches of the MEDLINE database from 1970 to March 2011 and the EMBASE database from 1974 to March 2011 without restrictions and by reviewing reference lists from retrieved articles. Cohort studies that reported relative risk estimates with 95% confidence intervals (CIs) for the associations of interest were included. Data Extraction Data were extracted independently by each author and summary estimates of association were obtained using a random-effects model. Data Synthesis Of the 8 studies included, 4 reported results on type 2 diabetes (175 938 individuals; 6428 incident cases during 1.1 million person-years of follow-up), 4 reported on fatal or nonfatal cardiovascular disease (34 253 individuals; 1052 incident cases), and 3 reported on all-cause mortality (26 509 individuals; 1879 deaths during 202 353 person-years of follow-up). The pooled relative risks per 2 hours of TV viewing per day were 1.20 (95% CI, 1.14-1.27) for type 2 diabetes, 1.15 (95% CI, 1.06-1.23) for fatal or nonfatal cardiovascular disease, and 1.13 (95% CI, 1.07-1.18) for all-cause mortality. While the associations between time spent viewing TV and risk of type 2 diabetes and cardiovascular disease were linear, the risk of all-cause mortality appeared to increase with TV viewing duration of greater than 3 hours per day. The estimated absolute risk differences per every 2 hours of TV viewing per day were 176 cases of type 2 diabetes per 100 000 individuals per year, 38 cases of fatal cardiovascular disease per 100 000 individuals per year, and 104 deaths for all-cause mortality per 100 000 individuals per year. Conclusion Prolonged TV viewing was associated with increased risk of type 2 diabetes, cardiovascular disease, and all-cause mortality. PMID:21673296

Prevalence of Type 1 and Type 2 Diabetes Among Children and Adolescents From 2001 to 2009

PubMed Central

Dabelea, Dana; Mayer-Davis, Elizabeth J.; Saydah, Sharon; Imperatore, Giuseppina; Linder, Barbara; Divers, Jasmin; Bell, Ronny; Badaru, Angela; Talton, Jennifer W.; Crume, Tessa; Liese, Angela D.; Merchant, Anwar T.; Lawrence, Jean M.; Reynolds, Kristi; Dolan, Lawrence; Liu, Lenna L.; Hamman, Richard F.

2015-01-01

IMPORTANCE Despite concern about an “epidemic,” there are limited data on trends in prevalence of either type 1 or type 2 diabetes across US race and ethnic groups. OBJECTIVE To estimate changes in the prevalence of type 1 and type 2 diabetes in US youth, by sex, age, and race/ethnicity between 2001 and 2009. DESIGN, SETTING, AND PARTICIPANTS Case patients were ascertained in 4 geographic areas and 1 managed health care plan. The study population was determined by the 2001 and 2009 bridged-race intercensal population estimates for geographic sites and membership counts for the health plan. MAIN OUTCOMES AND MEASURES Prevalence (per 1000) of physician-diagnosed type 1 diabetes in youth aged 0 through 19 years and type 2 diabetes in youth aged 10 through 19 years. RESULTS In 2001, 4958 of 3.3 million youth were diagnosed with type 1 diabetes for a prevalence of 1.48 per 1000 (95% CI, 1.44–1.52). In 2009, 6666 of 3.4 million youth were diagnosed with type 1 diabetes for a prevalence of 1.93 per 1000 (95% CI, 1.88–1.97). In 2009, the highest prevalence of type 1 diabetes was 2.55 per 1000 among white youth (95% CI, 2.48–2.62) and the lowest was 0.35 per 1000 in American Indian youth (95% CI, 0.26–0.47) and type 1 diabetes increased between 2001 and 2009 in all sex, age, and race/ethnic subgroups except for those with the lowest prevalence (age 0–4 years and American Indians). Adjusted for completeness of ascertainment, there was a 21.1% (95% CI, 15.6%–27.0%) increase in type 1 diabetes over 8 years. In 2001, 588 of 1.7 million youth were diagnosed with type 2 diabetes for a prevalence of 0.34 per 1000 (95% CI, 0.31–0.37). In 2009, 819 of 1.8 million were diagnosed with type 2 diabetes for a prevalence of 0.46 per 1000 (95% CI, 0.43–0.49). In 2009, the prevalence of type 2 diabetes was 1.20 per 1000 among American Indian youth (95% CI, 0.96–1.51); 1.06 per 1000 among black youth (95% CI, 0.93–1.22); 0.79 per 1000 among Hispanic youth (95% CI, 0.70–0.88); and 0.17 per 1000 among white youth (95% CI, 0.15–0.20). Significant increases occurred between 2001 and 2009 in both sexes, all age-groups, and in white, Hispanic, and black youth, with no significant changes for Asian Pacific Islanders and American Indians. Adjusted for completeness of ascertainment, there was a 30.5% (95% CI, 17.3%–45.1%) overall increase in type 2 diabetes. CONCLUSIONS AND RELEVANCE Between 2001 and 2009 in 5 areas of the United States, the prevalence of both type 1 and type 2 diabetes among children and adolescents increased. Further studies are required to determine the causes of these increases. PMID:24794371

Structure of Full-length Drosophila Cryptochrome

PubMed Central

Zoltowski, Brian D.; Vaidya, Anand T.; Top, Deniz; Widom, Joanne; Young, Michael W.; Crane, Brian R.

2011-01-01

The Cryptochrome/Photolyase (CRY/PL) family of photoreceptors mediates adaptive responses to UV and blue light exposure in all kingdoms of life 1; 2; 3; 4; 5. Whereas PLs function predominantly in DNA repair of cyclobutane pyrimidine dimers (CPDs)and 6-4 photolesions caused by UV radiation, CRYs transduce signals important for growth, development, magnetosensitivity and circadian clocks1; 2; 3; 4; 5. Despite these diverse functions, PLs/CRYs preserve a common structural fold, a dependence on flavin adenine dinucleotide (FAD) and an internal photoactivation mechanism3; 6. However, members of the CRY/PL family differ in the substrates recognized (protein or DNA), photochemical reactions catalyzed and involvement of an antenna cofactor. It is largely unknown how the animal CRYs that regulate circadian rhythms act on their substrates. CRYs contain a variable C-terminal tail that appends the conserved PL homology domain (PHD) and is important for function 7; 8; 9; 10; 11; 12. Herein, we report a 2.3 Å resolution crystal structure of Drosophila CRY with an intact C-terminus. The C-terminal helix docks in the analogous groove that binds DNA substrates in PLs. Conserved Trp536 juts into the CRY catalytic center to mimic PL recognition of DNA photolesions. The FAD anionic semiquinone found in the crystals assumes a conformation to facilitate restructuring of the tail helix. These results help reconcile the diverse functions of the CRY/PL family by demonstrating how conserved protein architecture, and photochemistry can be elaborated into a range of light-driven functions. PMID:22080955

Field-evolved resistance to Cry1Ab maize by Spodoptera frugiperda in Brazil.

PubMed

Omoto, Celso; Bernardi, Oderlei; Salmeron, Eloisa; Sorgatto, Rodrigo J; Dourado, Patrick M; Crivellari, Augusto; Carvalho, Renato A; Willse, Alan; Martinelli, Samuel; Head, Graham P

2016-09-01

The first Bt maize in Brazil was launched in 2008 and contained the MON 810 event, which expresses Cry1Ab protein. Although the Cry1Ab dose in MON 810 is not high against fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith), MON 810 provided commercial levels of control. To support insect resistance management in Brazil, the baseline and ongoing susceptibility of FAW was examined using protein bioassays, and the level of control and life history parameters of FAW were evaluated on MON 810 maize. Baseline diet overlay assays with Cry1Ab (16 µg cm(-2) ) caused 76.3% mortality to field FAW populations sampled in 2009. Moderate mortality (48.8%) and significant growth inhibition (88.4%) were verified in leaf-disc bioassays. In greenhouse trials, MON 810 had significantly less damage than non-Bt maize. The surviving FAW larvae on MON 810 (22.4%) had a 5.5 day increase in life cycle time and a 24% reduction in population growth rate. Resistance monitoring (2010-2015) showed a significant reduction in Cry1Ab susceptibility of FAW over time. Additionally, a significant reduction in the field efficacy of MON 810 maize against FAW was observed in different regions from crop season 2009 to 2013. The decrease in susceptibility to Cry1Ab was expected, but the specific contributions to this resistance by MON 810 maize cannot be distinguished from cross-resistance to Cry1Ab caused by exposure to Cry1F maize. Technologies combining multiple novel insecticidal traits with no cross-resistance to the current Cry1 proteins and high activity against the same target pests should be pursued in Brazil and similar environments. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

[Leisure-time physical activity and sedentary behaviors among Chinese adults in 2010].

PubMed

Chen, Xiao-rong; Jiang, Yong; Wang, Li-min; Li, Yi-chong; Zhang, Mei; Hu, Nan; Zhao, Wen-hua

2012-05-01

To understand the prevalence of participation in leisure-time physical activity, and sedentary behaviors among Chinese adults. Data from Chinese Chronic Disease Surveillance (2010) was used. Among adults aged 18 years old and over, the information on frequency and duration of occupational activity, house chores, commuting and leisure time activity was collected by an interview with Global Physical Activity Questionnaire (GPAQ). The time spent on watching TV, reading, using computers or playing games after work was also surveyed. This present study only analyzed the percentage of participating in leisure time moderate or vigorous intensity physical activity at least 10 minutes three days per week and the time spent on TV, reading, using computer and playing games during after hours among Chinese adults of 98 649 subjects. 11.9% (95%CI: 10.5% - 13.3%) of all adults took part in leisure time moderate or vigorous intensity physical activity at least 10 minutes for three days per week, with-group the percentage highest among age-group 18 - 24 (15.6%, 95%CI: 10.5% - 13.3%) and lowest among age 25 - 34 (9.9%, 95%CI: 8.0% - 11.7%) and 75 years old and over (9.9%, 95%CI: 8.2% - 11.6%) (P < 0.01). The age related change showed a double-peak curve. The percentage was higher in male (13.1%, 95%CI: 11.6% - 14.6%) than in female (10.6%, 95%CI: 9.3% - 12.0%) (P < 0.01). Among the populations engaged in diverse occupations, the lowest percentage was detected among those in farming, forestry, husbandry and fishing (4.2%, 95%CI: 3.4% - 4.9%). Higher percentage was found among the residents lived in urban areas (19.9%, 95%CI: 17.4% - 22.5%) than in rural areas (8.2%, 95%CI: 6.7% - 9.8%) (P < 0.01), and higher in the east area (14.8%, 95%CI: 11.9% - 17.6%) compared to that in central (9.7%, 95%CI: 8.1% - 11.3%) or in west areas (10.3%, 95%CI: 8.4% - 12.3%) in China (P < 0.01). Furthermore, (2.7 ± 2.0) hours per day was spent in sedentary behaviors, such as watching TV, reading, using computers or playing games during after hours. Those aged 18 - 24 years-old spent most time (3.8 ± 2.6) hours per day in sedentary behaviors and the time reduced with age (P < 0.01). More time on Sedentary behaviors were taken by male (2.9 ± 2.1 hours per day) than by female ((2.6 ± 1.9) hours per day) (P < 0.01), with more hours spent in urban ((3.3 ± 2.2) hours per day) than that in rural ((2.5 ± 1.9) hours per day) (P < 0.01). No difference was detected among the residents lived in east ((2.9 ± 2.1) hours per day), central ((2.7 ± 2.0) hours per day) and west area ((2.6 ± 2.0) hours per day) (P > 0.05). The percentage of taking part in moderate and vigorous activity during leisure time was generally low. Average time spent in after hours sedentary behaviors was long.

The organization of human epidermis: functional epidermal units and phi proportionality.

PubMed

Hoath, Steven B; Leahy, D G

2003-12-01

The concept that mammalian epidermis is structurally organized into functional epidermal units has been proposed on the basis of stratum corneum (SC) architecture, proliferation kinetics, melanocyte:keratinocyte ratios (1:36), and, more recently, Langerhans cell: epidermal cell ratios (1:53). This article examines the concept of functional epidermal units in human skin in which the maintenance of phi (1.618034) proportionality provides a central organizing principle. The following empirical measurements were used: 75,346 nucleated epidermal cells per mm2, 1394 Langerhans cells per mm2, 1999 melanocytes per mm2, 16 (SC) layers, 900-microm2 corneocyte surface area, 17,778 corneocytes per mm2, 14-d (SC) turnover time, and 93,124 per mm2 total epidermal cells. Given these empirical data: (1) the number of corneocytes is a mean proportional between the sum of the Langerhans cell + melanocyte populations and the number of epidermal cells, 3393/17,778-17,778/93,124; (2) the ratio of nucleated epidermal cells over corneocytes is phi proportional, 75,346/17,778 approximately phi3; (3) assuming similar 14-d turnover times for the (SC) and Malpighian epidermis, the number of corneocytes results from subtraction of a cellular fraction equal to approximately 2/phi2 x the number of living cells, 75,436 - (2/phi2 x 75,346) approximately 17,778; and (4) if total epidermal turnover time equals (SC) turnover time x the ratio of living/dead cells, then compartmental turnover times are unequal (14 d for (SC) to 45.3 d for nucleated epidermis approximately 1/2phi) and cellular replacement rates are 52.9 corneocytes/69.3 keratinocytes per mm2 per h approximately 2/phi2. These empirically derived equivalences provide logicomathematical support for the presence of functional epidermal units in human skin. Validation of a phi proportional unit architecture in human epidermis will be important for tissue engineering of skin and the design of instruments for skin measurement.

Ketoanalogue-Supplemented Vegetarian Very Low-Protein Diet and CKD Progression.

PubMed

Garneata, Liliana; Stancu, Alexandra; Dragomir, Diana; Stefan, Gabriel; Mircescu, Gabriel

2016-07-01

Dietary protein restriction may improve determinants of CKD progression. However, the extent of improvement and effect of ketoanalogue supplementation are unclear. We conducted a prospective, randomized, controlled trial of safety and efficacy of ketoanalogue-supplemented vegetarian very low-protein diet (KD) compared with conventional low-protein diet (LPD). Primary end point was RRT initiation or >50% reduction in initial eGFR. Nondiabetic adults with stable eGFR<30 ml/min per 1.73 m(2), proteinuria <1 g/g urinary creatinine, good nutritional status, and good diet compliance entered a run-in phase on LPD. After 3 months, compliant patients were randomized to KD (0.3 g/kg vegetable proteins and 1 cps/5 kg ketoanalogues per day) or continue LPD (0.6 g/kg per day) for 15 months. Only 14% of screened patients patients were randomized, with no differences between groups. Adjusted numbers needed to treat (NNTs; 95% confidence interval) to avoid composite primary end point in intention to treat and per-protocol analyses in one patient were 4.4 (4.2 to 5.1) and 4.0 (3.9 to 4.4), respectively, for patients with eGFR<30 ml/min per 1.73 m(2) Adjusted NNT (95% confidence interval) to avoid dialysis was 22.4 (21.5 to 25.1) for patients with eGFR<30 ml/min per 1.73 m(2) but decreased to 2.7 (2.6 to 3.1) for patients with eGFR<20 ml/min per 1.73 m(2) in intention to treat analysis. Correction of metabolic abnormalities occurred only with KD. Compliance to diet was good, with no changes in nutritional parameters and no adverse reactions. Thus, this KD seems nutritionally safe and could defer dialysis initiation in some patients with CKD. Copyright © 2016 by the American Society of Nephrology.

[Dabigatran versus warfarin for the prevention of stroke in Chinese patients with nonvalvular atrial fibrillation: Chinese subpopulation analysis of RE-LY].

PubMed

Gao, X; Yang, Y M; Zhu, J; Dai, Y; Tan, H Q

2016-11-24

Objective: This analysis was performed to evaluate the efficacy in stroke prevention and safety of dabigatran in Chinese nonvalvular atrial fibrillation(NVAF) patients enrolled in RE-LY trial. Methods: RE-LY was an prospective, open-label, randomized, multicenter study. From March 2006 to March 2009, 541 atrial fibrillation patients at risk of stroke were recruited from 13 medical centers in China. Patients randomly received, in a blinded fashion, fixed doses of dabigatran-110 mg or 150 mg twice daily or, in an unblinded fashion, adjusted-dose warfarin. The primary efficacy endpoint was stroke or systemic embolism. The primary safety endpoint was major bleeding. Results: The incidence of stroke in the Chinese subpopulation was 1.94% per year(7 cases) in the group that received 110 mg of dabigatran (dabigatran 110) and 1.10% per year(4 cases) in the group that received 150 mg of dabigatran (dabigatran 150), as compared with 2.87% per year (10 cases) in warfarin group . Incidence of ischemic stroke was 1.11% per year(4 patients) in dabigatran 110 group, 0.82% per year(3 cases) in dabigatran 150 group and 2.01% per year(7 patients) in warfarin group. Incidence of hemorrhagic stroke was 0.28% per year(1 case) in dabigatran 110 group, 0.27% per year(1 case) in dabigatran 150 group and 0.57% per year(2 cases) in warfarin group. All-cause mortality was similar among the three treatment groups: 3.33% per year(12 cases) in dabigatran 110, 2.19% per year(8 cases) in dabigatran 150 and 2.58% per year(9 cases) in warfarin group. Incidence of major bleeding event was 0.56% per year(2 cases) in both dabigatran groups, as compared with 1.43% per year(5 cases) in warfarin group. Gastrointestinal disorders such as dyspepsia occurred in 12.8% patients of both dabigatran groups, and in 5.6% patients of warfarin group. Conclusions: Despite the descriptive statistical analysis in nature of present study due to the limited number of subjects, our subgroup analysis implies that like warfarin, dabigatran is efficacious and safe for thromboembolism prevention in Chinese patients with atrial fibrillation at risk of stroke. Clinical Trail Registry National Institutes of Health(http: //www.clinicaltrials.gov), CT00262600.

Biphasic Activation of Ribulose Bisphosphate Carboxylase in Spinach Leaves as Determined from Nonsteady-State CO2 Exchange 1

PubMed Central

Woodrow, Ian E.; Mott, Keith A.

1992-01-01

The activation kinetics of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) following an increase in photon flux density (PFD) were studied by analyzing CO2 assimilation time courses in spinach leaves (Spinacia oleracea). When leaves were exposed to 45 minutes of darkness before illumination at 690 micromoles per square meter per second, Rubisco activation followed apparent first-order kinetics with a relaxation time of about 3.8 minutes. But when leaves were illuminated for 45 minutes at 160 micromoles per square meter per second prior to illumination at 690 micromoles per square meter per second the relaxation time for Rubisco activation was only 2.1 minutes. The kinetics of this change in relaxation times were investigated by exposing dark-adapted leaves to 160 micromoles per square meter per second for different periods before increasing the PFD to 690 micromoles per square meter per second. It was found that the apparent relaxation time for Rubisco activation changed from 3.8 to 2.1 minutes slowly, requiring at least 8 minutes for completion. This result indicates that at least two sequential, slow processes are involved in light-mediated activation of Rubisco in spinach leaves and that the relaxation times characterizing these two processes are about 4 and 2 minutes, respectively. The kinetics of the first process in the reverse direction and the dependence of the relaxation time for the second process on the magnitude of the increase in PFD were also determined. Evidence that the first slow process is activation of the enzyme Rubisco activase and that the second slow process is the catalytic activation of Rubisco by activase is discussed. PMID:16668865

Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity

PubMed Central

Zhang, Ying; Markert, Matthew J.; Groves, Shayna C.; Hardin, Paul E.; Merlin, Christine

2017-01-01

Circadian repression of CLOCK-BMAL1 by PERIOD and CRYPTOCHROME (CRY) in mammals lies at the core of the circadian timekeeping mechanism. CRY repression of CLOCK-BMAL1 and regulation of circadian period are proposed to rely primarily on competition for binding with coactivators on an α-helix located within the transactivation domain (TAD) of the BMAL1 C terminus. This model has, however, not been tested in vivo. Here, we applied CRISPR/Cas9-mediated mutagenesis in the monarch butterfly (Danaus plexippus), which possesses a vertebrate-like CRY (dpCRY2) and an ortholog of BMAL1, to show that insect CRY2 regulates circadian repression through TAD α-helix–dependent and –independent mechanisms. Monarch mutants lacking the BMAL1 C terminus including the TAD exhibited arrhythmic eclosion behavior. In contrast, mutants lacking the TAD α-helix but retaining the most distal C-terminal residues exhibited robust rhythms during the first day of constant darkness (DD1), albeit with a delayed peak of eclosion. Phase delay in this mutant on DD1 was exacerbated in the presence of a single functional allele of dpCry2, and rhythmicity was abolished in the absence of dpCRY2. Reporter assays in Drosophila S2 cells further revealed that dpCRY2 represses through two distinct mechanisms: a TAD-dependent mechanism that involves the dpBMAL1 TAD α-helix and dpCLK W328 and a TAD-independent mechanism involving dpCLK E333. Together, our results provide evidence for independent mechanisms of vertebrate-like CRY circadian regulation on the BMAL1 C terminus and the CLK PAS-B domain and demonstrate the importance of a BMAL1 TAD-independent mechanism for generating circadian rhythms in vivo. PMID:28831003

Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity.

PubMed

Zhang, Ying; Markert, Matthew J; Groves, Shayna C; Hardin, Paul E; Merlin, Christine

2017-09-05

Circadian repression of CLOCK-BMAL1 by PERIOD and CRYPTOCHROME (CRY) in mammals lies at the core of the circadian timekeeping mechanism. CRY repression of CLOCK-BMAL1 and regulation of circadian period are proposed to rely primarily on competition for binding with coactivators on an α-helix located within the transactivation domain (TAD) of the BMAL1 C terminus. This model has, however, not been tested in vivo. Here, we applied CRISPR/Cas9-mediated mutagenesis in the monarch butterfly ( Danaus plexippus ), which possesses a vertebrate-like CRY (dpCRY2) and an ortholog of BMAL1, to show that insect CRY2 regulates circadian repression through TAD α-helix-dependent and -independent mechanisms. Monarch mutants lacking the BMAL1 C terminus including the TAD exhibited arrhythmic eclosion behavior. In contrast, mutants lacking the TAD α-helix but retaining the most distal C-terminal residues exhibited robust rhythms during the first day of constant darkness (DD1), albeit with a delayed peak of eclosion. Phase delay in this mutant on DD1 was exacerbated in the presence of a single functional allele of dpCry2 , and rhythmicity was abolished in the absence of dpCRY2. Reporter assays in Drosophila S2 cells further revealed that dpCRY2 represses through two distinct mechanisms: a TAD-dependent mechanism that involves the dpBMAL1 TAD α-helix and dpCLK W328 and a TAD-independent mechanism involving dpCLK E333. Together, our results provide evidence for independent mechanisms of vertebrate-like CRY circadian regulation on the BMAL1 C terminus and the CLK PAS-B domain and demonstrate the importance of a BMAL1 TAD-independent mechanism for generating circadian rhythms in vivo.

Application of Box-Behnken experimental design to optimize the extraction of insecticidal Cry1Ac from soil.

PubMed

Li, Yan-Liang; Fang, Zhi-Xiang; You, Jing

2013-02-20

A validated method for analyzing Cry proteins is a premise to study the fate and ecological effects of contaminants associated with genetically engineered Bacillus thuringiensis crops. The current study has optimized the extraction method to analyze Cry1Ac protein in soil using a response surface methodology with a three-level-three-factor Box-Behnken experimental design (BBD). The optimum extraction conditions were at 21 °C and 630 rpm for 2 h. Regression analysis showed a good fit of the experimental data to the second-order polynomial model with a coefficient of determination of 0.96. The method was sensitive and precise with a method detection limit of 0.8 ng/g dry weight and relative standard deviations at 7.3%. Finally, the established method was applied for analyzing Cry1Ac protein residues in field-collected soil samples. Trace amounts of Cry1Ac protein were detected in the soils where transgenic crops have been planted for 8 and 12 years.

A phase II, open-label study of the efficacy and safety of imiquimod in the treatment of superficial and mixed infantile hemangioma.

PubMed

McCuaig, Catherine C; Dubois, Josée; Powell, Julie; Belleville, Claude; David, Michèle; Rousseau, Elisabeth; Gendron, Roxanne; Jafarian, Fatemeh; Auger, Isabelle

2009-01-01

To explore the efficacy and safety of imiquimod 5% cream as a treatment for infantile hemangioma. Phase II, open-label, noncomparative study of imiquimod applied during 16 weeks, with posttherapy follow-up 16 weeks later (8 months total). Outpatient pediatric tertiary care referral center in Quebec, Canada. Healthy infants up to 8.8 months of age with previously untreated, nonulcerated, proliferative superficial or mixed infantile hemangioma, excluding periorbital, or perineal localization, > or =100 cm2 in size. Topical imiquimod applied three to seven times per week for 16 weeks to infantile hemangioma. Lesion area, volume, depth (Doppler ultrasound), and color (erythema), serum drug, and interferon-alpha levels. Sixteen infants (11 girls, 5 boys) with a mean age at entry of 4.1 months and mean lesion area of 32.89 cm2, and volume of 39.98 cm3 were enrolled. Two participants discontinued treatment early, one for an adverse event (crying upon application), the other because of the lack of compliance. Local skin reactions were consistent with those reported in adults. Two cases had a decrease and three had an increase in lesion parameters; otherwise no meaningful changes in lesion area, volume, or depth were observed. At the 4-month posttreatment visit, 11 of 14 subjects had improvement in erythema (marginal homogeneity test = 2.668, p = 0.008). Measured serum drug and interferon-alpha levels were low or undetectable. Treatment of infants with infantile hemangioma with imiquimod up to seven times per week for 16 weeks was generally well tolerated with low systemic exposure. Improvement was observed in hemangioma coloration, but not lesion size, suggesting effects were limited to the superficial component.

40 CFR Table 2 to Subpart Dddd of... - Model Rule-Emission Limitations

Code of Federal Regulations, 2010 CFR

2010-07-01

... meter 3-run average (1 hour minimum sample time per run) Performance test (Method 29 of appendix A of this part) Carbon monoxide 157 parts per million by dry volume 3-run average (1 hour minimum sample time per run) Performance test (Method 10, 10A, or 10B, of appendix A of this part) Dioxins/furans...

Updates on the Epidemiology of Age-Related Macular Degeneration.

PubMed

Jonas, Jost B; Cheung, Chui Ming Gemmy; Panda-Jonas, Songhomitra

2017-01-01

This meta-analysis reports on current estimates of the prevalence of age-related macular degeneration (AMD) based on a review of recent meta-analyses and literature research. Within an age of 45-85 years, global prevalences of any AMD, early AMD, and late AMD were 8.7% [95% credible interval (CrI), 4.3‒17.4], 8.0% (95% CrI, 4.0‒15.5), and 0.4% (95% CrI, 0.2-0.8). Early AMD was more common in individuals of European ancestry (11.2%) than in Asians (6.8%), whereas prevalence of late AMD did not differ significantly. AMD of any type was less common in individuals of African ancestry. The number of individuals with AMD was estimated to be 196 million (95% CrI, 140‒261) in 2020 and 288 million (95% CrI, 205‒399) in 2040. The worldwide number of persons blind (presenting visual acuity < 3/60) or with moderate to severe vision impairment (MSVI; presenting visual acuity < 6/18 to 3/60 inclusive) due to macular disease in 2010 was 2.1 million [95% uncertainty interval (UI), 1.9‒2.7] individuals out of 32.4 million individuals blind and 6.0 million (95% UI, 5.2‒8.1) persons out of 191 million people with MSVI. Age-standardized prevalence of macular diseases as cause of blindness in adults aged 50+ years worldwide decreased from 0.2% (95% UI, 0.2‒0.2) in 1990 to 0.1% (95% UI, 0.1‒0.2) in 2010; as cause for MSVI, it remained mostly unchanged (1990: 0.4%; 95% UI, 0.3‒0.5; 2010: 0.4%; 95% UI, 0.4‒0.6), with no significant sex difference. In 2015, AMD was the fourth most common cause of blindness globally (in approximately 5.8% of blind individuals) and third most common cause for MSVI (3.9%). These data show the globally increasing importance of AMD. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

Multistate Models Reveal Long-Term Trends of Northern Spotted Owls in the Absence of a Novel Competitor

PubMed Central

Kroll, Andrew J.; Jones, Jay E.; Stringer, Angela B.; Meekins, Douglas J.

2016-01-01

Quantifying spatial and temporal variability in population trends is a critical aspect of successful management of imperiled species. We evaluated territory occupancy dynamics of northern spotted owls (Strix occidentalis caurina), California, USA, 1990–2014. The study area possessed two unique aspects. First, timber management has occurred for over 100 years, resulting in dramatically different forest successional and structural conditions compared to other areas. Second, the barred owl (Strix varia), an exotic congener known to exert significant negative effects on spotted owls, has not colonized the study area. We used a Bayesian dynamic multistate model to evaluate if territory occupancy of reproductive spotted owls has declined as in other study areas. The state-space approach for dynamic multistate modeling imputes the number of territories for each nesting state and allows for the estimation of longer-term trends in occupied or reproductive territories from longitudinal studies. The multistate approach accounts for different detection probabilities by nesting state (to account for either inherent differences in detection or for the use of different survey methods for different occupancy states) and reduces bias in state assignment. Estimated linear trends in the number of reproductive territories suggested an average loss of approximately one half territory per year (-0.55, 90% CRI: -0.76, -0.33), in one management block and a loss of 0.15 per year (-0.15, 90% CRI: -0.24, -0.07), in another management block during the 25 year observation period. Estimated trends in the third management block were also negative, but substantial uncertainty existed in the estimate (-0.09, 90% CRI: -0.35, 0.17). Our results indicate that the number of territories occupied by northern spotted owl pairs remained relatively constant over a 25 year period (-0.07, 90% CRI: -0.20, 0.05; -0.01, 90% CRI: -0.19, 0.16; -0.16, 90% CRI: -0.40, 0.06). However, we cannot exclude small-to-moderate declines or increases in paired territory numbers due to uncertainty in our estimates. Collectively, we conclude spotted owl pair populations on this landscape managed for commercial timber production appear to be more stable and do not show sharp year-over-year declines seen in both managed and unmanaged landscapes with substantial barred owl colonization and persistence. Continued monitoring of reproductive territories can determine whether recent declines continue or whether trends reverse as they have on four previous occasions. Experimental investigations to evaluate changes to spotted owl occupancy dynamics when barred owl populations are reduced or removed entirely can confirm the generality of this conclusion. PMID:27065016

Simulation of tree shade impacts on residential energy use for space conditioning in Sacramento

NASA Astrophysics Data System (ADS)

Simpson, J. R.; McPherson, E. G.

Tree shade reduces summer air conditioning demand and increases winter heating load by intercepting solar energy that would otherwise heat the shaded structure. We evaluate the magnitude of these effects here for 254 residential properties participating in a utility sponsored tree planting program in Sacramento, California. Tree and building characteristics and typical weather data are used to model hourly shading and energy used for space conditioning for each building for a period of one year. There were an average of 3.1 program trees per property which reduced annual and peak (8 h average from 1 to 9 p.m. Pacific Daylight Time) cooling energy use 153 kWh (7.1%) and 0.08 kW (2.3%) per tree, respectively. Annual heating load increased 0.85 GJ (0.80 MBtu, 1.9%) per tree. Changes in cooling load were smaller, but percentage changes larger, for newer buildings. Averaged over all homes, annual cooling savings of 15.25 per tree were reduced by a heating penalty of 5.25 per tree, for net savings of 10.00 per tree from shade. We estimate an annual cooling penalty of 2.80 per tree and heating savings of 6.80 per tree from reduced wind speed, for a net savings of 4.00 per tree, and total annual savings of 14.00 per tree (43.00 per property). Results are found to be consistent with previous simulations and the limited measurements available.

Risks and benefits of combining aspirin with anticoagulant therapy in patients with atrial fibrillation: an exploratory analysis of stroke prevention using an oral thrombin inhibitor in atrial fibrillation (SPORTIF) trials.

PubMed

Flaker, Greg C; Gruber, Michael; Connolly, Stuart J; Goldman, Steven; Chaparro, Sandra; Vahanian, Alec; Halinen, Matti O; Horrow, Jay; Halperin, Jonathan L

2006-11-01

Aspirin is used in combination with anticoagulant therapy in patients with atrial fibrillation (AF), but evidence of additional efficacy is not available. We compared ischemic events and bleeding in the SPORTIF III and IV randomized trials of anticoagulation with warfarin (international normalized ratio 2-3) or fixed-dose ximelagatran. Low-dose aspirin (<100 mg/d) was allowed based on prevailing guidelines. The 14% of patients receiving aspirin more often had diabetes (27.5% vs 23%, P < .01), coronary artery disease (69% vs 41%, P < .01), previous stroke or transient ischemic attack (26% vs 20%, P < .01), and left ventricular dysfunction (41% vs 36%, P < .01). Addition of aspirin to either warfarin or ximelagatran was associated with no reduction in stroke or systemic embolism. Major bleeding occurred significantly more often with aspirin plus warfarin (3.9% per year) than with warfarin alone (2.3% per year, P < .01), aspirin plus ximelagatran (2.0% per year), or ximelagatran alone (1.9% per year). The rate of myocardial infarction with aspirin and warfarin (0.6% per year) was not significantly different from that with ximelagatran alone (1.0% per year), warfarin alone (1.0% per year), or aspirin and ximelagatran (1.4% per year). Aspirin combined with anticoagulant therapy was associated with no reduction in stroke, systemic embolism, or myocardial infarction in patients with AF. Aspirin combined with warfarin was associated with an incremental rate of major bleeding of 1.6% per year. No increased major bleeding occurred with aspirin and ximelagatran. These results suggest that the risks associated with addition of aspirin to anticoagulation in patients with AF outweigh the benefit.

Galactic foreground contributions to the 5-year Wilkinson Microwave Anisotropy Probe maps

NASA Astrophysics Data System (ADS)

Macellari, N.; Pierpaoli, E.; Dickinson, C.; Vaillancourt, J. E.

2011-12-01

We compute the cross-correlation between intensity and polarization from the 5-year Wilkinson Microwave Anisotropy Probe (WMAP5) data in different sky regions with respect to template maps for synchrotron, dust and free-free emission. We derive the frequency dependence and polarization fraction for all three components in 48 different sky regions of HEALPIX (Nside= 2) pixelization. The anomalous emission associated with dust is clearly detected in intensity over the entire sky at the K (23-GHz) and Ka (33-GHz) WMAP bands, and is found to be the dominant foreground at low Galactic latitudes, between b =-40° and +10°. The synchrotron spectral index obtained from the K and Ka WMAP bands from an all-sky analysis is βs=-3.32 ± 0.12 for intensity and βs=-3.01 ± 0.03 for polarized intensity. The polarization fraction of the synchrotron emission is constant in frequency and increases with latitude from ≈5 per cent near the Galactic plane up to ≈40 per cent in some regions at high latitudes; the average value for |b| < 20° is 8.6 ± 1.7 (stat) ± 0.5 (sys) per cent, while for |b| > 20°, it is 19.3 ± 0.8 (stat) ± 0.5 (sys) per cent. Anomalous dust and free-free emissions appear to be relatively unpolarized. Monte Carlo simulations showed that there were biases of the method due to cross-talk between the components, at up to ≈5 per cent in any given pixel, and ≈1.5 per cent on average, when the true polarization fraction is low (a few per cent or less). Nevertheless, the average polarization fraction of dust-correlated emission at the K band is 3.2 ± 0.9 (stat) ± 1.5 (sys) per cent or less than 5 per cent at 95 per cent confidence. When comparing real data with simulations, eight regions show a detected polarization above the 99th percentile of the distribution from simulations with no input foreground polarization, six of which are detected at above 2σ and display polarization fractions between 2.6 and 7.2 per cent, except for one anomalous region, which has 32 ± 12 per cent. The dust polarization values are consistent with the expectation from spinning dust emission, but polarized dust emission from magnetic-dipole radiation cannot be ruled out. Free-free emission was found to be unpolarized with an upper limit of 3.4 per cent at 95 per cent confidence.

ThinPrep Pap-smear and cervical intraepithelial neoplasia in reproductive-aged Thai women.

PubMed

Rugpao, S; Koonlertkit, S; Ruengkrist, T; Lamlertkittikul, S; Pinjaroen, S; Limtrakul, A; Werawatakul, Y; Sinchai, W

2009-06-01

To estimate the incidence of abnormal cervical cytology by ThinPrep Pap-tests and cervical intraepithelial neoplasia (CIN) in young adult reproductive-aged Thai women. A total of 1254 women distributed in all regions of Thailand were monitored from 2002 through 2004. Women were screened for abnormal cervical cytology using the ThinPrep method every 6 months. Interpretation of cervical cytology was based on the Bethesda system, version 2001. Women who had the ThinPrep Pap results as atypical squamous cells of undetermined significance or worse underwent colposcopic examination. The ThinPrep and all cervical tissue samples obtained from diagnostic or therapeutic procedures were analyzed and reviewed by Covance Central Laboratory Service, Inc., Indianapolis, USA. The cumulative incidence of abnormal ThinPrep Pap-tests was as follows: 15.3 per 100 woman years (WY) (95% confidence interval [CI] 12.3, 18.9) at 6 months; 12.3 per 100 WY (95% CI 10.3, 14.6) at 12 months; and 11.6 per 100 WY (95% CI 10.0, 13.5) at 18 months. Of 1448.6 woman years of follow up, the incidence of CIN1 was 4.1 per 100 WY (95% CI 3.2, 5.3); CIN2 0.8 per 100 WY (95% CI 0.4, 1.4); and CIN3 0.6 per 100 WY (95% CI 0.3, 1.2). The incidence of abnormal ThinPrep Pap-test and CIN in young adult Thai women had been reported. No comparable data is available.

Comparative Effectiveness of Mesalamine, Sulfasalazine, Corticosteroids, and Budesonide for the Induction of Remission in Crohn's Disease: A Bayesian Network Meta-analysis.

PubMed

Coward, Stephanie; Kuenzig, M Ellen; Hazlewood, Glen; Clement, Fiona; McBrien, Kerry; Holmes, Rebecca; Panaccione, Remo; Ghosh, Subrata; Seow, Cynthia H; Rezaie, Ali; Kaplan, Gilaad G

2017-03-01

Induction treatment of mild-to-moderate Crohn's disease is controversial. To compare the induction of remission between different doses of mesalamine, sulfasalazine, corticosteroids, and budesonide for active Crohn's disease. We identified randomized controlled trials from existing Cochrane reviews and an updated literature search in Medline, EMBASE, and CENTRAL to November 2015. We included randomized controlled trials (n = 22) in adult patients with Crohn's disease that compared budesonide, sulfasalazine, mesalamine, or corticosteroids with placebo or each other, for the induction of remission (8-17 wks). Mesalamine (above and below 2.4 g/d) and budesonide (above and below 6 mg/d) were stratified into low and high doses. Our primary outcome was remission, defined as a Crohn's Disease Activity Index score <150. A Bayesian random-effects network meta-analysis was performed on the proportion in remission. Corticosteroids (odds ratio [OR] = 3.80; 95% credible interval [CrI]: 2.48-5.66), high-dose budesonide (OR = 2.96; 95% CrI: 2.06-4.30), and high-dose mesalamine (OR = 2.29; 95% CrI: 1.58-3.33) were superior to placebo. Corticosteroids were similar to high-dose budesonide (OR = 1.21; 95% CrI: 0.84-1.76), but more effective than high-dose mesalamine (OR = 1.83; 95% CrI: 1.16-2.88). Sulfasalazine was not significantly superior to any therapy including placebo. Randomized controlled trials that use a strict definition of induction of remission and disease severity at enrollment to assess effectiveness in treating mild-to-moderate Crohn's disease are limited. Corticosteroids and high-dose budesonide were effective treatments for inducing remission in mild-to-moderate Crohn's disease. High-dose mesalamine is an option among patients preferring to avoid steroids.

Hyperspectral Imagery Throughput and Fusion Evaluation over Compression and Interpolation

DTIC Science & Technology

2008-07-01

MSE ⎛ ⎞ = ⎜ ⎟ ⎝ ⎠ (17) The PSNR values and compression ratios are shown in Table 1 and a plot of PSNR against the bits per pixel ( bpp ) is shown...Ratio bpp 59.3 2.9:1 2.76 46.0 9.2:1 0.87 43.2 14.5:1 0.55 40.8 25.0:1 0.32 38.7 34.6:1 0.23 35.5 62.1:1 0.13 Figure 11. PSNR vs. bits per...and a plot of PSNR against the bits per pixel ( bpp ) is shown in Figure 13. The 3D DCT compression yielded better results than the baseline JPEG

Oxygen exchange profile in rat muscles of contrasting fibre types.

PubMed

Behnke, Brad J; McDonough, Paul; Padilla, Danielle J; Musch, Timothy I; Poole, David C

2003-06-01

To determine whether fibre type affects the O2 exchange characteristics of skeletal muscle at the microcirculatory level we tested the hypothesis that, following the onset of contractions, muscle comprising predominately type I fibres (soleus, Sol, 86 % type I) would, based on demonstrated blood flow responses, exhibit a blunted microvascular PO2 (PO2,m, which is determined by the O2 delivery (QO2) to O2 uptake (VO2) ratio) profile (assessed via phosphorescence quenching) compared to muscle of primarily type II fibres (peroneal, Per, 84 % type II). PO2,m was measured at rest, and following the rest-contractions (twitch, 1 Hz, 2-4 V for 120 s) transition in Sol (n = 6) and Per (n = 6) muscles of Sprague-Dawley rats. Both muscles exhibited a delay followed by a mono-exponential decrease in PO2,m to the steady state. However, compared with Sol, Per demonstrated (1) a larger change in baseline minus steady state contracting PO2,m (DeltaPO2,m) (Per, 13.4 +/- 1.7 mmHg; Sol, 8.6 +/- 0.9 mmHg, P < 0.05); (2) a faster mean response time (i.e. time delay (TD) plus time constant (tau); Per, 23.8 +/- 1.5 s; Sol, 39.6 +/- 4.3 s, P < 0.05); and therefore (3) a greater rate of PO2,m decline (DeltaPO2,m/tau; Per, 0.92 +/- 0.08 mmHg s-1; Sol, 0.42 +/- 0.05 mmHg s-1, P < 0.05). These data demonstrate an increased microvascular pressure head of O2 at any given point after the initial time delay for Sol versus Per following the onset of contractions that is probably due to faster QO2 dynamics relative to those of VO2.

The influence of insulin-dependent diabetes mellitus (IDDM) duration on superoxide anion and hydrogen peroxide production by polymorphonuclear neutrophils.

PubMed

Zozulińska, D A; Wierusz-Wysocka, B; Wysocki, H; Majchrzak, A E; Wykretowicz, A

1996-08-01

We address the question whether oxygen metabolism of polymorphonuclear neutrophils (PMN) is influenced by disease duration in patients with insulin-dependent diabetes mellitus (IDDM). PMN were isolated from patients with IDDM of various durations and from healthy controls. We measured PMN production of superoxide anions (O2-) by cytochrome c reduction (see Babior, B.M. et al. (1973) J. Clin. Invest. 52, 741-746) and PMN production of hydrogen peroxide (H2O2) by phenol red oxygenation (see Pick, E. (1980) J. Immunol. Methods 38, 161-169) in three groups of IDDM patients subdivided according to disease duration (group A: IDDM less that 10 years; group B: IDDM of 10-15 years; group C: IDDM of more than 15 years) and in control healthy subjects (group H). Unstimulated O2- production in all IDDM patients was not statistically different from control values (A: 4.3 +/- 0.4 nmol/10(6) PMN per 30 min, nmol/10(6) PMN per 30 min; C: 4.9 +/- 0.9 nmol/10(6) PMN per 30 min; and H: 3.5 +/- 0.2 nmol/10(6) PMN per 30 min, respectively). In contrast, stimulated O2- production was significantly lower in both patients with 10-15 years, and patients with more than 15 years, duration of IDDM than in controls (B: 25.7 +/- 2.5 nmol/10(6) PMN per 30 min; C: 21.1 +/- 3.4 nmol/10(6) PMN per 30 min and H: 42.2 +/- 1.1 nmol/10(6) PMN per 30 min, respectively) correlating with disease duration (r = -0.44, P < 0.033). The stimulated O2- production in patients with less than 10 years duration of IDDM (A: 35.7 +/- 1.9 nmol/10(6) PMN per 30 min) was slightly lower than in controls. H2O2 production of unstimulated PMN (A: 4.0 +/- 0.5 nmol/10(6) PMN per 30 min; B: 4.4 +/- 0.8 nmol/10(6) PMN per 30 min and C: 4.4 +/-1.0 nmol/10(6) PMN per 30 min, respectively) was much higher than those in controls. In contrast, stimulated H2O2 production did not differ statistically from the value noticed in healthy subjects. The results obtained might indicate that production of H2O2 by unstimulated cells is increased in diabetic patients while generation of O2- by stimulated neutrophils is markedly impaired, suggesting that toxic oxygen species production might be influenced by disease duration.

Hospitalization and Survival in Patients Using Epoprostenol for Injection in the PROSPECT Observational Study

PubMed Central

Frantz, Robert P.; Schilz, Robert J.; Chakinala, Murali M.; Badesch, David B.; Frost, Adaani E.; McLaughlin, Vallerie V.; Barst, Robyn J.; Rosenberg, Daniel M.; Miller, Dave P.; Hartline, Brian K.; Benton, Wade W.

2015-01-01

BACKGROUND: Few studies have prospectively reported outcomes in patients with pulmonary arterial hypertension (PAH) treated with epoprostenol in the modern-day era of oral therapy and combination treatments. The Registry to Prospectively Describe Use of Epoprostenol for Injection (Veletri, prolonged room temperature stable-epoprostenol [RTS-Epo]) in Patients with Pulmonary Arterial Hypertension (PROSPECT) was established to prospectively describe the course of PAH in patients prescribed RTS-Epo. METHODS: PROSPECT is a multicenter, US-based drug registry of primarily group 1 patients with PAH treated with RTS-Epo who were parenteral-naive or parenteral-transitioned at enrollment. Patients were followed until discontinuation of RTS-Epo, withdrawal, loss to follow-up, death, or end of study (maximum 1 year). One-year freedom from hospitalization (FH) and survival estimates were summarized by prostacyclin history (parenteral-naive or parenteral-transitioned), sex, and chronic renal insufficiency (CRI). RESULTS: A total of 336 patients were included. The overall 1-year FH estimate was 51.0% ± 2.8% and was lower in parenteral-naive patients than parenteral-transitioned patients (42.8% ± 4.3% vs 57.1% ± 3.7%, respectively; P = .002). FH estimates were lower in male patients than female patients (38.3% ± 5.9% vs 54.6% ± 3.2%, respectively; P < .015) and in patients with CRI than patients without CRI (17.0% ± 8.4% vs 53.7% ± 2.9%, respectively; P < .001). The overall 1-year survival estimate was 84.0% ± 2.1%. Survival was poorer in parenteral-naive patients, male patients, and patients with CRI. CONCLUSIONS: Risk of hospitalization and mortality remain high in patients with PAH. In particular, patients who are parenteral-naive at initiation of RTS-Epo therapy, male patients, and patients with CRI require close monitoring and aggressive clinical management. PMID:25320967

Effect of Surgical Intervention for Removal of Mandibular Third Molar on Periodontal Healing of Adjacent Mandibular Second Molar: A Systematic Review and Bayesian Network Meta-Analysis.

PubMed

Barbato, Luigi; Kalemaj, Zamira; Buti, Jacopo; Baccini, Michela; La Marca, Michele; Duvina, Marco; Tonelli, Paolo

2016-03-01

The aim of this systematic review is to evaluate and synthesize scientific evidence on the effect of surgical interventions for removal of mandibular third molar (M3M) on periodontal healing of adjacent mandibular second molar (M2M). The protocol was registered at PROSPERO (International Prospective Register of Systematic Reviews) as CRD42012003059. Medline, Cochrane, and EMBASE databases were interrogated to identify randomized controlled trials (RCTs) up to December 22, 2014. Patients with M3Ms fully developed, unilaterally or bilaterally impacted, were considered. Outcomes were clinical attachment level gain (CALg) and probing depth reduction (PDr) with a follow-up ≥ 6 months. Patient-subjective outcomes, such as pain, discomfort, and complications, and financial aspects and chair time, were also explored. A Bayesian network meta-analysis model was used to estimate direct and indirect effects and to establish a ranking of treatments. Sixteen RCTs were included and categorized into four groups investigating the following: 1) regenerative/grafting procedures (10 RCTs); 2) flap design (three RCTs); 3) type of suturing (one RCT); and 4) periodontal care of M2M (two RCTs). Guided tissue regeneration (GTR) with resorbable (GTRr) and non-resorbable (GTRnr) membrane and GTRr with anorganic xenograft (GTRr + AX) showed the highest mean ranking for CALg (2.99, 90% credible interval [CrI] = 1 to 5; 2.80, 90% CrI = 1 to 6; and 2.29, 90% CrI = 1 to 6, respectively) and PDr (2.83, 90% CrI = 1 to 5; 2.52, 90% CrI = 1 to 5; and 2.77, 90% CrI = 1 to 6, respectively). GTRr + AX showed the highest probability (Pr) of being the best treatment for CALg (Pr = 45%) and PDr (Pr = 32%). Direct and network quality of evidence were rated from very low to moderate. To the best of the authors' knowledge, the present review is the first one to evaluate quantitatively and qualitatively the effect of different interventions on periodontal healing distal to the second molar after extraction of the third molar. GTR-based procedures with or without combined grafting therapies provide some adjunctive clinical benefit compared to standard non-regenerative/non-grafting procedures. However, the overall low quality of evidence suggests a low degree of confidence and certainty in treatment effects. Evidence on variations of surgical M3M removal techniques based on flap design, type of suturing, and periodontal care of M2M is limited both qualitatively and quantitatively.

Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients.

PubMed

Yang, Zhiliang; Matsumoto, Ayumi; Nakayama, Kazuhiro; Jimbo, Eriko F; Kojima, Karin; Nagata, Koh-ichi; Iwamoto, Sadahiko; Yamagata, Takanori

2016-01-01

The genetic background of autism spectrum disorder (ASD) is considered a multi-genetic disorder with high heritability. Autistic children present with a higher prevalence of sleep disorders than has been observed in children with normal development. Some circadian-relevant genes have been associated with ASD (e.g., PER1, PER2, NPAS2, MTNR1A, and MTNR1B). We analyzed 28 ASD patients (14 with sleep disorders and 14 without) and 23 control subjects of Japanese descent. The coding regions of 18 canonical clock genes and clock-controlled genes were sequenced. Detected mutations were verified by direct sequencing analysis, and additional control individuals were screened. Thirty-six base changes with amino acid changes were detected in 11 genes. Six missense changes were detected only in individuals with ASD with sleep disturbance: p.F498S in TIMELESS, p.S20R in NR1D1, p.R493C in PER3, p.H542R in CLOCK, p.L473S in ARNTL2, and p.A325V in MTNR1B. Six missense changes were detected only in individuals with ASD without sleep disturbance: p.S1241N in PER1, p.A325T in TIMELESS, p.S13T in ARNTL, p.G24E in MTNR1B, p.G24E in PER2, and p.T1177A in PER3. The p.R493C mutation in PER3 was detected in both groups. One missense change, p.P932L in PER2, was detected only in the control group. Mutations in NR1D1, CLOCK, and ARNTL2 were detected only in individuals with ASD with sleep disorder. The prevalence of the mutations detected only single time differed significantly among all ASD patients and controls (p=0.003). Two kinds of mutations detected only in individuals with ASD with sleep disorder, p.F498S in TIMELESS and p.R366Q in PER3, were considered to affect gene function by three different methods: PolyPhen-2, scale-invariant feature transform (SIFT) prediction, and Mutation Taster (www.mutationtaster.org). The mutations p.S20R in NR1D1, p.H542R in CLOCK, p.L473S in ARNTL2, p.A325T in TIMELESS, p.S13T in ARNTL, and p.G24E in PER2 were diagnosed to negatively affect gene function by more than one of these methods. Mutations in circadian-relevant genes affecting gene function are more frequent in patients with ASD than in controls. Circadian-relevant genes may be involved in the psychopathology of ASD. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

The immune response of Taiwan abalone Haliotis diversicolor supertexta and its susceptibility to Vibrio parahaemolyticus at different salinity levels.

PubMed

Cheng, Winton; Juang, Feng-Ming; Chen, Jiann-Chu

2004-03-01

Addition of NaCl at 2.5% to 3.5% to tryptic soy broth (TSB) significantly increased the growth of Vibrio parahaemolyticus. Taiwan abalone Haliotis diversicolor supertexta held in 30 per thousand seawater were injected with V. parahaemolyticus grown in TSB containing NaCl at 0.5, 1.5, 2.5, 3.5 and 4.5% at a dose of 1.6 x 10(5)colony-forming units (cfu) abalone(-1). After 48 h, the cumulative mortality was significantly higher for the abalone challenged with V. parahaemolyticus grown in 2.5% than those grown in 0.5 and 1.5% NaCl. In other experiments, abalones held in 30 per thousand seawater were injected with TSB-grown V. parahaemolyticus (1.6 x 10(5)cfu abalone(-1)), and then transferred to 20, 25, 30 and 35 per thousand seawater. All abalones held in 20 per thousand were killed in 48 h. The mortality of V. parahaemolyticus-injected abalone held in 30 per thousand was significantly lower over 24-120 h. Abalone held in 30 per thousand seawater and then transferred to 20, 25, 30 and 35 per thousand were examined for THC (total haemocyte count), phenoloxidase activity, respiratory burst, phagocytic activity and clearance efficiency of V. parahemolyticus after 24 and 72 h. The THC increased directly related with salinity levels. Phenoloxidase activity, respiratory burst, phagocytic activity and clearance efficiency of V. parahaemolyticus decreased significantly for the abalone in 20, 25 and 35 per thousand. It is concluded that the abalone transferred from 30 per thousand to 20, 25 and 35 per thousand had reduced immune ability and decreased resistance against V. parahaemolyticus infection.

Efficacy and safety of 1alpha-hydroxyvitamin D3 for prevention of parturient paresis.

PubMed

Gast, D R; Marquardt, J P; Jorgensen, N A; Deluca, H F

1977-12-01

Four trials involved intravenous or intramuscular injections of 1alpha-hydroxyvitavin D3 to test efficacy in preventing parturient paresis. Use of .1 mg intravenously afforded total protection compared with an incidence of 33% (2/6) in controls. Intramuscular injections of .1 mg in 2 ml propylene glycol and .3, .5, and 1.0 mg in 5 ml corn oil resulted in 0, 15.7, 20, and 0% incidence of parturient paresis compared with 33, 16.7, 37.5, and 37.5% incidence of parturient paresis in the controls. There was a rapid increase in serum calcium (12 to 24 h) in response to intravenous treatment, whereas the response to intramuscular injections was gradual but was maintained longer. To evaluate the safety of 1alpha-hydroxyvitamin D3, eight cows, two per treatment, were given intramuscular doses of .5, 1.0, 1.5, or 3.0 mg (three 1.0 mg injections) in 5 ml corn oil. No clinical or pathological evidence of hypervitaminosis C or soft tissue calcification was found. Tissue taken from the injection site 15 days after last injection contained 3 to 38 IU vitamin D activity per 100 g wet tissue compared with control of 8 to 15 IU per 100 g. Total vitamin D activity of milk taken the 11th milking postpartum from cows receiving .5 or 1.0 mg had a mean of 13.4 and 22.6 IU vitamin D activity per liter compared to 19 IU per liter for control milk. Milk from the 5th milking postpartum in the cows receiving .5 mg had a mean activity of 14.5 IU per liter. Milk from animals slaughtered for retention studies had a mean activity of 22 IU per liter.

Thermochemistry of paddle wheel MOFs: Cu-HKUST-1 and Zn-HKUST-1.

PubMed

Bhunia, Manas K; Hughes, James T; Fettinger, James C; Navrotsky, Alexandra

2013-06-25

Metal-organic framework (MOF) porosity relies upon robust metal-organic bonds to retain structural rigidity upon solvent removal. Both the as-synthesized and activated Cu and Zn polymorphs of HKUST-1 were studied by room temperature acid solution calorimetry. Their enthalpies of formation from dense assemblages (metal oxide (ZnO or CuO), trimesic acid (TMA), and N,N-dimethylformamide (DMF)) were calculated from the calorimetric data. The enthalpy of formation (ΔHf) of the as-synthesized Cu-HKUST-H2O ([Cu3TMA2·3H2O]·5DMF) is -52.70 ± 0.34 kJ per mole of Cu. The ΔHf for Zn-HKUST-DMF ([Zn3TMA2·3DMF]·2DMF) is -54.22 ± 0.57 kJ per mole of Zn. The desolvated Cu-HKUST-dg [Cu3TMA2] has a ΔHf of 16.66 ± 0.51 kJ/mol per mole Cu. The ΔHf for Zn-HKUST-amorph [Zn3TMA2·2DMF] is -3.57 ± 0.21 kJ per mole of Zn. Solvent stabilizes the Cu-HKUST-H2O by -69.4 kJ per mole of Cu and Zn-HKUST-DMF by at least -50.7 kJ per mole of Zn. Such strong chemisorption of solvent is similar in magnitude to the strongly exothermic binding at low coverage for chemisorbed H2O on transition metal oxide nanoparticle surfaces. The strongly exothermic solvent-framework interaction suggests that solvent can play a critical role in obtaining a specific secondary building unit (SBU) topology.

The impact of pesticide suicide on the geographic distribution of suicide in Taiwan: a spatial analysis

PubMed Central

2012-01-01

Background Pesticide self-poisoning is the most commonly used suicide method worldwide, but few studies have investigated the national epidemiology of pesticide suicide in countries where it is a major public health problem. This study aims to investigate geographic variations in pesticide suicide and their impact on the spatial distribution of suicide in Taiwan. Methods Smoothed standardized mortality ratios for pesticide suicide (2002-2009) were mapped across Taiwan's 358 districts (median population aged 15 or above = 27 000), and their associations with the size of agricultural workforce were investigated using Bayesian hierarchical models. Results In 2002-2009 pesticide poisoning was the third most common suicide method in Taiwan, accounting for 13.6% (4913/36 110) of all suicides. Rates were higher in agricultural East and Central Taiwan and lower in major cities. Almost half (47%) of all pesticide suicides occurred in areas where only 13% of Taiwan's population lived. The geographic distribution of overall suicides was more similar to that of pesticide suicides than non-pesticide suicides. Rural-urban differences in suicide were mostly due to pesticide suicide. Areas where a higher proportion of people worked in agriculture showed higher pesticide suicide rates (adjusted rate ratio [ARR] per standard deviation increase in the proportion of agricultural workers = 1.58, 95% Credible Interval [CrI] 1.44-1.74) and overall suicide rates (ARR = 1.06, 95% CrI 1.03-1.10) but lower non-pesticide suicide rates (ARR = 0.91, 95% CrI 0.87-0.95). Conclusion Easy access to pesticides appears to influence the geographic distribution of suicide in Taiwan, highlighting the potential benefits of targeted prevention strategies such as restricting access to highly toxic pesticides. PMID:22471759

The impact of pesticide suicide on the geographic distribution of suicide in Taiwan: a spatial analysis.

PubMed

Chang, Shu-Sen; Lu, Tsung-Hsueh; Sterne, Jonathan Ac; Eddleston, Michael; Lin, Jin-Jia; Gunnell, David

2012-04-02

Pesticide self-poisoning is the most commonly used suicide method worldwide, but few studies have investigated the national epidemiology of pesticide suicide in countries where it is a major public health problem. This study aims to investigate geographic variations in pesticide suicide and their impact on the spatial distribution of suicide in Taiwan. Smoothed standardized mortality ratios for pesticide suicide (2002-2009) were mapped across Taiwan's 358 districts (median population aged 15 or above = 27 000), and their associations with the size of agricultural workforce were investigated using Bayesian hierarchical models. In 2002-2009 pesticide poisoning was the third most common suicide method in Taiwan, accounting for 13.6% (4913/36 110) of all suicides. Rates were higher in agricultural East and Central Taiwan and lower in major cities. Almost half (47%) of all pesticide suicides occurred in areas where only 13% of Taiwan's population lived. The geographic distribution of overall suicides was more similar to that of pesticide suicides than non-pesticide suicides. Rural-urban differences in suicide were mostly due to pesticide suicide. Areas where a higher proportion of people worked in agriculture showed higher pesticide suicide rates (adjusted rate ratio [ARR] per standard deviation increase in the proportion of agricultural workers = 1.58, 95% Credible Interval [CrI] 1.44-1.74) and overall suicide rates (ARR = 1.06, 95% CrI 1.03-1.10) but lower non-pesticide suicide rates (ARR = 0.91, 95% CrI 0.87-0.95). Easy access to pesticides appears to influence the geographic distribution of suicide in Taiwan, highlighting the potential benefits of targeted prevention strategies such as restricting access to highly toxic pesticides.

40 CFR Table 13 to Subpart Ddddd... - Alternative Emission Limits for New or Reconstructed Boilers and Process Heaters That Commenced...

Code of Federal Regulations, 2013 CFR

2013-07-01

... oxygen 1 hr minimum sampling time. b. Filterable PM (or TSM) 3.2E-01 lb per MMBtu of heat input; or (4.0E... per run. 13. Units designed to burn liquid fuel a. HCl 1.2E-03 lb per MMBtu of heat input For M26A...

Lidocaine, Dexmedetomidine and Their Combination Reduce Isoflurane Minimum Alveolar Concentration in Dogs

PubMed Central

Acevedo-Arcique, Carlos M.; Ibancovichi, José A.; Chavez, Julio R.; Gutierrez-Blanco, Eduardo; Moran-Muñoz, Rafael; Victoria-Mora, José M.; Tendillo-Cortijo, Francisco; Santos-González, Martín; Sanchez-Aparicio, Pedro

2014-01-01

The effects of intravenous (IV) lidocaine, dexmedetomidine and their combination delivered as a bolus followed by a constant rate infusion (CRI) on the minimum alveolar concentration of isoflurane (MACISO) in dogs were evaluated. Seven healthy adult dogs were included. Anaesthesia was induced with propofol and maintained with isoflurane. For each dog, baseline MAC (MACISO/BASAL) was determined after a 90-minute equilibration period. Thereafter, each dog received one of the following treatments (loading dose, CRI): lidocaine 2 mg kg−1, 100 µg kg−1 minute−1; dexmedetomidine 2 µg kg−1, 2 µg kg−1 hour−1; or their combination. MAC was then determined again after 45- minutes of treatment by CRI. At the doses administered, lidocaine, dexmedetomidine and their combination significantly reduced MACISO by 27.3% (range: 12.5–39.2%), 43.4% (33.3–53.3%) and 60.9% (46.1–78.1%), respectively, when compared to MACISO/BASAL. The combination resulted in a greater MACISO reduction than the two drugs alone. Their use, at the doses studied, provides a clinically important reduction in the concentration of ISO during anaesthesia in dogs. PMID:25232737

40 CFR 174.532 - Bacillus thuringiensis eCry3.1Ab protein in corn; temporary exemption from the requirement of a...

Code of Federal Regulations, 2010 CFR

2010-07-01

... protein in corn; temporary exemption from the requirement of a tolerance. 174.532 Section 174.532... thuringiensis eCry3.1Ab protein in corn; temporary exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis eCry3.1Ab protein in corn, in or on the food and feed commodities of corn; corn...

40 CFR 174.532 - Bacillus thuringiensis eCry3.1Ab protein in corn; temporary exemption from the requirement of a...

Code of Federal Regulations, 2011 CFR

2011-07-01

... protein in corn; temporary exemption from the requirement of a tolerance. 174.532 Section 174.532... thuringiensis eCry3.1Ab protein in corn; temporary exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis eCry3.1Ab protein in corn, in or on the food and feed commodities of corn; corn...

40 CFR 174.532 - Bacillus thuringiensis eCry3.1Ab protein in corn; temporary exemption from the requirement of a...

Code of Federal Regulations, 2012 CFR

2012-07-01

... protein in corn; temporary exemption from the requirement of a tolerance. 174.532 Section 174.532... thuringiensis eCry3.1Ab protein in corn; temporary exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis eCry3.1Ab protein in corn, in or on the food and feed commodities of corn; corn...

40 CFR 174.532 - Bacillus thuringiensis eCry3.1Ab protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2014 CFR

2014-07-01

... protein in corn; exemption from the requirement of a tolerance. 174.532 Section 174.532 Protection of...Cry3.1Ab protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis eCry3.1Ab protein in corn, in or on the food and feed commodities of corn; corn, field; corn...

40 CFR 174.532 - Bacillus thuringiensis eCry3.1Ab protein in corn; exemption from the requirement of a tolerance.

Code of Federal Regulations, 2013 CFR

2013-07-01

... protein in corn; exemption from the requirement of a tolerance. 174.532 Section 174.532 Protection of...Cry3.1Ab protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis eCry3.1Ab protein in corn, in or on the food and feed commodities of corn; corn, field; corn...

Meta‐analysis of antibiotics versus appendicectomy for non‐perforated acute appendicitis

PubMed Central

Sallinen, V.; Akl, E. A.; You, J. J.; Agarwal, A.; Shoucair, S.; Vandvik, P. O.; Agoritsas, T.; Heels‐Ansdell, D.; Guyatt, G. H.

2016-01-01

Abstract Background For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non‐perforated appendicitis. Methods A comprehensive search was conducted for randomized trials comparing antibiotic therapy with appendicectomy in patients with non‐perforated appendicitis. Key outcomes were analysed using random‐effects meta‐analysis, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Five studies including 1116 patients reported major complications in 25 (4·9 per cent) of 510 patients in the antibiotic and 41 (8·4 per cent) of 489 in the appendicectomy group: risk difference −2·6 (95 per cent c.i. –6·3 to 1·1) per cent (low‐quality evidence). Minor complications occurred in 11 (2·2 per cent) of 510 and 61 (12·5 per cent) of 489 patients respectively: risk difference −7·2 (−18·1 to 3·8) per cent (very low‐quality evidence). Of 550 patients in the antibiotic group, 47 underwent appendicectomy within 1 month: pooled estimate 8·2 (95 per cent c.i. 5·2 to 11·8) per cent (high‐quality evidence). Within 1 year, appendicitis recurred in 114 of 510 patients in the antibiotic group: pooled estimate 22·6 (15·6 to 30·4) per cent (high‐quality evidence). For every 100 patients with non‐perforated appendicitis, initial antibiotic therapy compared with prompt appendicectomy may result in 92 fewer patients receiving surgery within the first month, and 23 more experiencing recurrent appendicitis within the first year. Conclusion The choice of medical versus surgical management in patients with clearly uncomplicated appendicitis is value‐ and preference‐dependent, suggesting a change in practice towards shared decision‐making is necessary. PMID:26990957

Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis.

PubMed

Sallinen, V; Akl, E A; You, J J; Agarwal, A; Shoucair, S; Vandvik, P O; Agoritsas, T; Heels-Ansdell, D; Guyatt, G H; Tikkinen, K A O

2016-05-01

For more than a century, appendicectomy has been the treatment of choice for appendicitis. Recent trials have challenged this view. This study assessed the benefits and harms of antibiotic therapy compared with appendicectomy in patients with non-perforated appendicitis. A comprehensive search was conducted for randomized trials comparing antibiotic therapy with appendicectomy in patients with non-perforated appendicitis. Key outcomes were analysed using random-effects meta-analysis, and the quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Five studies including 1116 patients reported major complications in 25 (4·9 per cent) of 510 patients in the antibiotic and 41 (8·4 per cent) of 489 in the appendicectomy group: risk difference -2·6 (95 per cent c.i. -6·3 to 1·1) per cent (low-quality evidence). Minor complications occurred in 11 (2·2 per cent) of 510 and 61 (12·5 per cent) of 489 patients respectively: risk difference -7·2 (-18·1 to 3·8) per cent (very low-quality evidence). Of 550 patients in the antibiotic group, 47 underwent appendicectomy within 1 month: pooled estimate 8·2 (95 per cent c.i. 5·2 to 11·8) per cent (high-quality evidence). Within 1 year, appendicitis recurred in 114 of 510 patients in the antibiotic group: pooled estimate 22·6 (15·6 to 30·4) per cent (high-quality evidence). For every 100 patients with non-perforated appendicitis, initial antibiotic therapy compared with prompt appendicectomy may result in 92 fewer patients receiving surgery within the first month, and 23 more experiencing recurrent appendicitis within the first year. The choice of medical versus surgical management in patients with clearly uncomplicated appendicitis is value- and preference-dependent, suggesting a change in practice towards shared decision-making is necessary. © 2016 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

Collagen matrix as an inlay in endoscopic skull base reconstruction.

PubMed

Oakley, G M; Christensen, J M; Winder, M; Jonker, B P; Davidson, A; Steel, T; Teo, C; Harvey, R J

2018-03-01

Multi-layer reconstruction has become standard in endoscopic skull base surgery. The inlay component used can vary among autografts, allografts, xenografts and synthetics, primarily based on surgeon preference. The short- and long-term outcomes of collagen matrix in skull base reconstruction are described. A case series of patients who underwent endoscopic skull base reconstruction with collagen matrix inlay were assessed. Immediate peri-operative outcomes (cerebrospinal fluid leak, meningitis, ventriculitis, intracranial bleeding, epistaxis, seizures) and delayed complications (delayed healing, meningoencephalocele, prolapse of reconstruction, delayed cerebrospinal fluid leak, ascending meningitis) were examined. Of 120 patients (51.0 ± 17.5 years, 41.7 per cent female), peri-operative complications totalled 12.7 per cent (cerebrospinal fluid leak, 3.3 per cent; meningitis, 3.3 per cent; other intracranial infections, 2.5 per cent; intracranial bleeding, 1.7 per cent; epistaxis, 1.7 per cent; and seizures, 0 per cent). Delayed complications did not occur in any patients. Collagen matrix is an effective inlay material. It provides robust long-term separation between sinus and cranial cavities, and avoids donor site morbidity, but carries additional cost.

An Open-Label Study of the Long-Term Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (RECAP).

PubMed

Costabel, Ulrich; Albera, Carlo; Lancaster, Lisa H; Lin, Chin-Yu; Hormel, Philip; Hulter, Henry N; Noble, Paul W

2017-01-01

RECAP (NCT00662038) was an open-label extension study in patients with idiopathic pulmonary fibrosis (IPF) who completed either the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) 016 phase 3 trial or the Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY) 004/006 phase 3 trials. To obtain long-term safety data for pirfenidone in patients with IPF in RECAP. Of the 1,334 patients who participated in the phase 3 trials, 1,058 entered RECAP. The final analysis from enrollment (September 2008) to June 2015 is presented. Mean (SD) and median (range) pirfenidone exposures in RECAP were 122 (98) weeks and 88 (>0 to 349) weeks, respectively, with a mean daily dose of 2,091.1 mg. Cumulative total exposure was 2,482 patient exposure years (PEY). The treatment-emergent adverse event (TEAE) rate was 701.9 per 100 PEY. The serious TEAE rate was 53.5 per 100 PEY, with the most common serious TEAE being IPF (11.1 per 100 PEY). Of the 231 deaths (9.3 per 100 PEY), the most common cause was IPF (5.4 per 100 PEY). The treatment discontinuation rate due to a TEAE was 17.9 per 100 PEY; discontinuations were due to IPF (7.2 per 100 PEY), pneumonia, respiratory failure, acute respiratory failure, rash (0.5 per 100 PEY each), and nausea (0.4 per 100 PEY). For patients from CAPACITY 004/006 who entered RECAP, the mean change in percent predicted forced vital capacity from RECAP baseline at 180 weeks was -9.6%. Median on-treatment survival from the first pirfenidone dose in RECAP was 77.2 months. RECAP provides long-term follow-up and safety data for pirfenidone that were consistent with the known profile, with no new safety signals observed. © 2017 The Author(s) Published by S. Karger AG, Basel.

Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota.

PubMed

Zhao, Kai; Ren, Fangfang; Han, Fangting; Liu, Qiwen; Wu, Guogan; Xu, Yan; Zhang, Jian; Wu, Xiao; Wang, Jinbin; Li, Peng; Shi, Wei; Zhu, Hong; Lv, Jianjun; Zhao, Xiao; Tang, Xueming

2016-01-01

In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C was carried out by: (1) studying horizontal gene transfer (HGT) in Sprague Dawley rats fed transgenic rice for 90 d; (2) examining the effect of Cry1C protein in vitro on digestibility and allergenicity; and (3) studying the changes of intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either 60% GM Bacillus thuringiensis (Bt) rice T1C-1 expressing Cry1C protein, the parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed no evidence of HGT between rats and transgenic rice. Sequence searching of the Cry1C protein showed no homology with known allergens or toxins. Cry1C protein was rapidly degraded in vitro with simulated gastric and intestinal fluids. The expressed Cry1C protein did not induce high levels of specific IgG and IgE antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles revealed significant individual differences in the rats' intestinal microbiota.

Systematic Motorcycle Management and Health Care Delivery: A Field Trial

PubMed Central

Rerolle, Francois; Rammohan, Sonali V.; Albohm, Davis C.; Muwowo, George; Moseson, Heidi; Sept, Lesley; Lee, Hau L.; Bendavid, Eran

2016-01-01

Objectives. We investigated whether managed transportation improves outreach-based health service delivery to rural village populations. Methods. We examined systematic transportation management in a small-cluster interrupted time series field trial. In 8 districts in Southern Zambia, we followed health workers at 116 health facilities from September 2011 to March 2014. The primary outcome was the average number of outreach trips per health worker per week. Secondary outcomes were health worker productivity, motorcycle performance, and geographical coverage. Results. Systematic fleet management resulted in an increase of 0.9 (SD = 1.0) trips to rural villages per health worker per week (P < .001), village-level health worker productivity by 20.5 (SD = 5.9) patient visits, 10.2 (SD = 1.5) measles immunizations, and 5.2 (SD = 5.4) child growth assessments per health worker per week. Motorcycle uptime increased by 3.5 days per week (P < .001), use by 1.5 days per week (P < .001), and mean distance by 9.3 kilometers per trip (P < .001). Geographical coverage of health outreach increased in experimental (P < .001) but not control districts. Conclusions. Systematic motorcycle management improves basic health care delivery to rural villages in resource-poor environments through increased health worker productivity and greater geographical coverage. PMID:26562131

Transgenic rice plants expressing a fused protein of Cry1Ab/Vip3H has resistance to rice stem borers under laboratory and field conditions.

PubMed

Chen, Yang; Tian, Jun-Ce; Shen, Zhi-Chen; Peng, Yu-Fa; Hu, Cui; Guo, Yu-Yuan; Ye, Gong-Yin

2010-08-01

Six transgenic rice, Oryza sativa L., lines (G6H1, G6H2, G6H3, G6H4, G6H5, and G6H6) expressing a fused Cry1Ab/Vip3H protein, were evaluated for resistance against the Asiatic rice borer, Chilo suppressalis (Walker) (Lepidoptera: Crambidae), and the stem borer Sesamia inferens (Walker) (Lepidoptera: Noctuidae) in the laboratory and field. The bioassay results indicated that the mortality of Asiatic rice borer and S. inferens neonate larvae on six transgenic lines from seedling to filling stage was up to 100% at 168 h after infestation. The cumulative feeding area by Asiatic rice borer neonate larvae on all transgenic lines was significantly reduced compared with the untransformed parental 'Xiushui 110' rice. A 2-yr field evaluation showed that damage during the vegetative stage (deadheart) or during the reproductive stage (whitehead) caused by Asiatic rice borer and S. inferens for transgenic lines was much lower than the control. For three lines (G6H1, G6H2, and G6H6), no damage was found during the entire growing period. Estimation of fused Cry1Ab/Vip3H protein concentrations using PathoScreen kit for Bt-Cry1Ab/1Ac protein indicated that the expression levels of Cry1Ab protein both in main stems (within the average range of 0.006-0.073% of total soluble protein) and their flag leaves (within the average range of 0.001-0.038% of total soluble protein) were significantly different among six transgenic lines at different developmental stages. Both laboratory and field researches suggested that the transgenic rice lines have considerable potential for protecting rice from attack by both stem borers.

Quantitative analysis of the text and graphic content in ophthalmic slide presentations.

PubMed

Ing, Edsel; Celo, Erdit; Ing, Royce; Weisbrod, Lawrence; Ing, Mercedes

2017-04-01

To determine the characteristics of ophthalmic digital slide presentations. Retrospective quantitative analysis. Slide presentations from a 2015 Canadian primary eye care conference were analyzed for their duration, character and word count, font size, words per minute (wpm), lines per slide, words per slide, slides per minute (spm), text density product (wpm × spm), proportion of graphic content, and Flesch Reading Ease (FRE) score using Microsoft PowerPoint and Word. The median audience evaluation score for the lectures was used to dichotomize the higher scoring lectures (HSL) from the lower scoring lectures (LSL). A priori we hypothesized that there would be a difference in the wpm, spm, text density product, and FRE score between HSL and LSL. Wilcoxon rank-sum tests with Bonferroni correction were utilized. The 17 lectures had medians of 2.5 spm, 20.3 words per slide, 5.0 lines per slide, 28-point sans serif font, 36% graphic content, and text density product of 136.4 words × slides/minute 2 . Although not statistically significant, the HSL had more wpm, fewer words per slide, more graphics per slide, greater text density, and higher FRE score than LSL. There was a statistically significant difference in the spm of the HSL (3.1 ± 1.0) versus the LSL (2.2 ± 1.0) at p = 0.0124. All presenters showed more than 1 slide per minute. The HSL showed more spm than the LSL. The descriptive statistics from this study may aid in the preparation of slides used for teaching and conferences. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Influence of Per3 genotypes on circadian rhythmicity in flight cadets after militarized management.

PubMed

An, Huai-Jie; Zhou, Chang-Xi; Geng, Peiliang; Xu, Hong-Tao; Shi, Chenghe; Zhao, Xiao-Hang; Qian, Yang-Ming

2014-01-01

The purpose of this study was to explore the effect of PERIOD3 (PER3) genotypes on circadian rhythmicity in flight cadets after militarized management. We performed a preliminary study in 146 newly enrolled male flight cadets. Venous blood samples were collected, and genotyping of PER3 (4/5) was determined by using PCR. The morningness-eveningness questionnaire (MEQ) survey was given to flight cadets upon enrollment and after militarized management for 24 months respectively. Comparison of frequency distribution of PER3 genotypes between cases and controls (120 well-matched civilians) was performed using the X(2) test. We also compared the circadian rhythmicity upon enrollment and 24 months after enrollment in flight cadets, and analyzed the connection of changes in circadian clock with PER3 genotypes. The frequency distribution of PER3 genotypes in flight cadets was not significantly different from that in controls subjects. MEQ survey results showed chronotype within flight cadet group varied widely at the two time-points: the moderately morning type (50%) and the neither type (41.1%) upon enrollment; the neither type (76.7%) and the moderately morning type (21.2%) 24 months after enrollment. The circadian rhythm of individuals with the PER3 (5/5) genotype showed no significant difference before and after 24 months of militarized management, whereas notable changes were found in individuals with the PER3 (4/4) genotype (n=116, X(2) =37.26, P < 0.001). In conclusion, we provide some evidence that circadian rhythm of flight cadets with the PER3 (5) allele are less likely to be affected compared to those with the PER3 (4) allele.

Multi-Toxin Resistance Enables Pink Bollworm Survival on Pyramided Bt Cotton

PubMed Central

Fabrick, Jeffrey A.; Unnithan, Gopalan C.; Yelich, Alex J.; DeGain, Ben; Masson, Luke; Zhang, Jie; Carrière, Yves; Tabashnik, Bruce E.

2015-01-01

Transgenic crops producing Bacillus thuringiensis (Bt) proteins kill key insect pests, providing economic and environmental benefits. However, the evolution of pest resistance threatens the continued success of such Bt crops. To delay or counter resistance, transgenic plant “pyramids” producing two or more Bt proteins that kill the same pest have been adopted extensively. Field populations of the pink bollworm (Pectinophora gossypiella) in the United States have remained susceptible to Bt toxins Cry1Ac and Cry2Ab, but field-evolved practical resistance to Bt cotton producing Cry1Ac has occurred widely in India. Here we used two rounds of laboratory selection to achieve 18,000- to 150,000-fold resistance to Cry2Ab in pink bollworm. Inheritance of resistance to Cry2Ab was recessive, autosomal, conferred primarily by one locus, and independent of Cry1Ac resistance. We created a strain with high resistance to both toxins by crossing the Cry2Ab-resistant strain with a Cry1Ac-resistant strain, followed by one selection with Cry2Ab. This multi-toxin resistant strain survived on field-collected Bt cotton bolls producing both toxins. The results here demonstrate the risk of evolution of resistance to pyramided Bt plants, particularly when toxins are deployed sequentially and refuges are scarce, as seen with Bt cotton and pink bollworm in India. PMID:26559899

Single versus multiple sets of resistance exercise: a meta-regression.

PubMed

Krieger, James W

2009-09-01

There has been considerable debate over the optimal number of sets per exercise to improve musculoskeletal strength during a resistance exercise program. The purpose of this study was to use hierarchical, random-effects meta-regression to compare the effects of single and multiple sets per exercise on dynamic strength. English-language studies comparing single with multiple sets per exercise, while controlling for other variables, were considered eligible for inclusion. The analysis comprised 92 effect sizes (ESs) nested within 30 treatment groups and 14 studies. Multiple sets were associated with a larger ES than a single set (difference = 0.26 +/- 0.05; confidence interval [CI]: 0.15, 0.37; p < 0.0001). In a dose-response model, 2 to 3 sets per exercise were associated with a significantly greater ES than 1 set (difference = 0.25 +/- 0.06; CI: 0.14, 0.37; p = 0.0001). There was no significant difference between 1 set per exercise and 4 to 6 sets per exercise (difference = 0.35 +/- 0.25; CI: -0.05, 0.74; p = 0.17) or between 2 to 3 sets per exercise and 4 to 6 sets per exercise (difference = 0.09 +/- 0.20; CI: -0.31, 0.50; p = 0.64). There were no interactions between set volume and training program duration, subject training status, or whether the upper or lower body was trained. Sensitivity analysis revealed no highly influential studies, and no evidence of publication bias was observed. In conclusion, 2 to 3 sets per exercise are associated with 46% greater strength gains than 1 set, in both trained and untrained subjects.

Association of treponeme species with atypical foot lesions in goats.

PubMed

Groenevelt, M; Anzuino, K; Langton, D A; Grogono-Thomas, R

2015-06-13

Five UK goat farms with high levels of lameness (prevalence 14-67 per cent) were investigated. On two farms (farms 1 and 2), the animals presented with typical footrot lesions. The remaining three farms (farms 3, 4 and 5) presented with infected lesions on the foot that did not resemble footrot. These lesions were observed to start from the white line or sole but the interdigital space was rarely affected. Swabs were processed by PCR to assess the presence of Dichelobacter nodosus and three specific treponeme groups (group 1: Treponema medium/Treponema vincentii-like, group 2: Treponema phagedenis-like and group 3: Treponema denticola/Treponema putidum-like) that are reported to be associated with bovine digital dermatitis and contagious ovine digital dermatitis. On farms 1 and 2, 85.7 per cent of samples were found to be positive for D nodosus while only 9.5 per cent were positive for treponeme groups 1, 2 and 3. In contrast, 5.3 per cent of samples from farms 3, 4 and 5 were positive for D nodosus, while 34.2, 68.4 and 36.8 per cent of samples from these farms tested positive for treponeme groups 1, 2 and 3, respectively. T medium/T vincentii-like, T phagedenis-like and T denticola/T putidum-like treponemes were detected on foot lesions of lame goats suggesting that they have a role in the aetiology of this lameness, which has not previously been described in dairy goats. British Veterinary Association.

Road safety analysis on Achmad Yani frontage road Surabaya

NASA Astrophysics Data System (ADS)

Machsus; Prayogo, I.; Chomaedhi; Hayati, D. W.; Utanaka, A.

2017-11-01

This research discusses road safety analysis on the operation of frontage road on the west side of Achmad Yani Road Surabaya. This research began by conducting survey on secondary data of traffic accidents. In addition, primary data survey was conducted to obtain traffic data, geometric road data, and other supporting data at the study site along the west side frontage of Ahmad Yani Road Surabaya. Devices used in this research include camera, handy cam, speed gun, counters of vehicles, rolling meter, computer and others. In outline, the stages to conduct this research are divided into 4 stages, namely 1.the preparation stage, 2.data collection and processing, 3. analysis and discussion, and 4. conclusion. The results of this study showed that the accident characteristics of the frontage road are (i) 3 accidents occured per month, (ii) motorcycles was accounted for the largest proportion of accidents which amounted to 74.6 percent, (iii) there were 3 accident victims per month, and (iv) material losses per month worths 1.2 million. The accident rate in 2016 was 0.04 crashes per one million vehicle travels per kilometer, while during 2 months in 2017 it was 0.15 accidents per one million vehicle travels per kilometer. Black spot area of accident is located on Sta 2 + 800 to 2 + 900 which is in front of Graha Pena building and DBL Arena. The high rate of accidents is influenced by the speed of the vehicle which 85 percentile exceeds the speed limit of 40km per hour.

[Relationship between drinking, smoking, and dietary habits and the body mass index of Japanese alcoholic men].

PubMed

Hosokawa, Yuko; Yokoyama, Akira; Yokoyama, Tetsuji; Wada, Norihito; Mori, Shuka; Matsui, Toshifumi; Mizukami, Yuki; Maesato, Hitoshi; Maruyama, Katsuya

2010-02-01

Malnutrition and emaciation in alcoholics is associated with various alcoholism-related diseases, including Wernicke's encephalopathy, aero-digestive tract cancer, and serious metabolic disorders. We used a self-administered questionnaire survey for structured dietary habit screening to evaluate the dietary profiles of 467 Japanese alcoholic men aged 40 years or over and their relationship to body mass index (BMI). Their average daily ethanol consumption was 119 +/- 65 g (845 +/- 463 kcal). The survey showed that 50.5% of the subjects consumed three meals a day; 32.8%, two meals; 12.2%, one meal; and 4.5% rarely ate. The meals mainly consisted of carbohydrates and protein, with few vegetables. Daily alcohol consumption was inversely correlated with the frequency of meals, drinking milk, and consuming confectionery. The subjects who lived with their family (72.8%) consumed more meals than the subjects liv- ing alone. After excluding 22 subjects with leg edema or ascites, the average BMI was 21.3 +/- 3.2. The group with the lowest BMI values (<18.5) accounted for 19.3% of the subjects, and those with the highest BMI values (> or = 25) accounted for 11.5%. A multivariate stepwise logistic analysis showed that BMI increased 0.15 per 22 g ethanol consumed daily and decreased 0.03 per + 10 cigarettes smoked daily, 0.43 per decrease by one in daily frequency of meals, and 0.54 per category (daily, occasionally, rarely, seldom) of milk consumption. The likelihood of a low BMI <18.5 was significantly and independently associated with smoking [OR (95%CI) =1.24 (1.02-1.51) per +10 cigarettes] and with intake of seafood [0.62 (0.41-0.94) per +1 category], milk [1.52 (1.16-2.00) per +1 category] and green and yellow vegetables [1.52 (1.05-2.21) per +1 category]. Intervention in regard to diet as well as drinking is important to preventing malnutrition and emaciation in alcoholics.

Cost-Effectiveness of Initiating Antiretroviral Therapy at Different Points in TB Treatment in HIV-TB Coinfected Ambulatory Patients in South Africa.

PubMed

Naidoo, Kogieleum; Grobler, Anneke C; Deghaye, Nicola; Reddy, Tarylee; Gengiah, Santhanalakshmi; Gray, Andrew; Abdool Karim, Salim

2015-08-15

Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment improves survival in TB-HIV coinfected patients. In patients with CD4 counts <50 cells per cubic millimeter, there is a substantial clinical and survival benefit of early ART initiation. The purpose of this study was to assess the costs and cost-effectiveness of starting ART at various time points during TB treatment in patients with CD4 counts ≥50 cells per cubic millimeter. In the SAPiT trial, 642 HIV-TB coinfected patients were randomized to 3 arms: receiving ART within 4 weeks of starting TB treatment (early treatment arm; Arm-1), after the intensive phase of TB treatment (late treatment arm; Arm-2), or after completing TB treatment (sequential arm; Arm-3). Direct health care costs were measured from a provider perspective using a micro-costing approach. The incremental cost per death averted was calculated using the trial outcomes. For patients with CD4 count ≥50 cells per cubic millimeter, median monthly variable costs per patient were US $116, US $113, and US $102 in Arm-1, Arm-2 and Arm-3, respectively. There were 12 deaths in 177 patients in Arm-1, 8 deaths in 180 patients in the Arm-2, and 19 deaths in 172 patients in Arm-3. Although the costs were lower in Arm-3, it had a substantially higher mortality rate. The incremental cost per death averted associated with moving from Arm-3 to Arm-2 was US $4199. There was no difference in mortality between Arm-1 and Arm-2, but Arm-1 was slightly more expensive. Initiation of ART after the completion of the intensive phase of TB treatment is cost-effective for patients with CD4 counts ≥50 cells per cubic millimeter.

Pharmacokinetics and anesthetic and cardiopulmonary effects of propofol in red-tailed hawks (Buteo jamaicensis) and great horned owls (Bubo virginianus).

PubMed

Hawkins, Michelle G; Wright, Bonnie D; Pascoe, Peter J; Kass, Philip H; Maxwell, Lara K; Tell, Lisa A

2003-06-01

To determine induction doses, anesthetic constant rate infusions (CRI), and cardiopulmonary effects of propofol in red-tailed hawks and great horned owls and propofol pharmacokinetics in the owls during CRI. 6 red-tailed hawks and 6 great horned owls. The CRI dose necessary for a loss of withdrawal reflex was determined via specific stimuli. Anesthesia was induced by IV administration of propofol (1 mg/kg/min) and maintained by CRI at the predetermined dose for 30 minutes. Heart and respiratory rates, arterial blood pressures, and blood gas tensions were obtained in awake birds and at various times after induction. End-tidal CO2 (ETCO2) concentration and esophageal temperature were obtained after induction. Propofol plasma concentrations were obtained after induction and after completion of the CRI in the owls. Recovery times were recorded. Mean +/- SD doses for induction and CRI were 4.48 +/- 1.09 mg/kg and 0.48 +/- 0.06 mg/kg/min, respectively, for hawks and 3.36 +/- 0.71 mg/kg and 0.56 +/- 0.15 mg/kg/min, respectively, for owls. Significant increases in PaCO2, HCO3, and ETCO2 in hawks and owls and significant decreases in arterial pH in hawks were detected. A 2-compartment model best described the owl pharmacodynamic data. Recovery times after infusion were prolonged and varied widely. Central nervous system excitatory signs were observed during recovery. Effects on blood pressure were minimal, but effective ventilation was reduced, suggesting the need for careful monitoring during anesthesia. Prolonged recovery periods with moderate-to-severe excitatory CNS signs may occur in these species at these doses.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeng, Xiaofei; Borole, Abhijeet P.; Pavlostathis, Spyros G.

Furanic and phenolic compounds, formed during the pretreatment of lignocellulosic biomass, are problematic byproducts in down-stream biofuel processes. A microbial electrolysis cell (MEC) is an alternative technology to handle furanic and phenolic compounds and produce renewable hydrogen (H 2). In this study, we evaluated the performance of a continuous-flow bioanode MEC fed with furanic and phenolic compounds at different operating conditions. All hydraulic retention times (HRTs) tested (6-24 h) resulted in complete transformation of the parent compounds at an organic loading rate (OLR) of 0.2g L -1 per d and applied voltage of 0.6 V. Increasing the OLR to 0.8more » g L -1 per d at an HRT of 6h resulted in an increased H 2 production rate from 0.07 to 0.14 L L anode 1 per d, but an OLR of 3.2 g L -1 per d did not lead to a higher H 2 production rate. Significant methane production was observed at an OLR of 3.2 g L -1 per d. The lack of increased H 2 production at the highest OLR tested was due to a limited rate of exoelectrogenesis but not fermentation, evidenced by the accumulation of high acetate levels and higher growth of fermenters and methanogens over exoelectrogens. Increasing applied voltage from 0.6 to 1.0V at an OLR of 3.2 g L -1 per d and HRT of 6h enhanced exoelectrogenesis and resulted in a 1.7-fold increase of H 2 production. Under all operating conditions, more than 90% of the biomass was biofilm-associated. Lastly, the present study provides new insights into the performance of continuous-flow bioelectrochemical systems fed with complex waste streams resulting from the pretreatment of lignocellulosic biomass.« less

Comparison of deuterated leucine, valine, and lysine in the measurement of human apolipoprotein A-I and B-100 kinetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lichtenstein, A.H.; Cohn, J.S.; Hachey, D.L.

1990-09-01

The production rates of apolipoprotein (apo)B-100 in very low density lipoprotein and in low density lipoprotein and apolipoprotein A-I in high density lipoprotein were determined using a primed-constant infusion of (5,5,5,-2H3)leucine, (4,4,4,-2H3)valine, and (6,6-2H2,1,2-13C2)lysine. The three stable isotope-labeled amino acids were administered simultaneously to determine whether absolute production rates calculated using a stochastic model were independent of the tracer species utilized. Three normolipidemic adult males were studied in the constantly fed state over a 15-h period. The absolute production rates of very low density lipoprotein apoB-100 were 11.4 +/- 5.8 (leucine), 11.2 +/- 6.8 (valine), and 11.1 +/- 5.4 (lysine)more » mg per kg per day (mean +/- SDM). The absolute production rates for low density lipoprotein apoB-100 were 8.0 +/- 4.7 (leucine), 7.5 +/- 3.8 (valine), and 7.5 +/- 4.2 (lysine) mg per kg per day. The absolute production rates for high density lipoprotein apoA-I were 9.7 +/- 0.2 (leucine), 9.4 +/- 1.7 (valine), and 9.1 +/- 1.3 (lysine) mg per kg per day. There were no statistically significant differences in absolute synthetic rates of the three apolipoproteins when the plateau isotopic enrichment values of very low density lipoprotein apoB-100 were used to define the isotopic enrichment of the intracellular precursor pool. Our data indicate that deuterated leucine, valine, or lysine provided similar results when used for the determination of apoA-I and apoB-100 absolute production rates within plasma lipoproteins as part of a primed-constant infusion protocol.« less

Infant and toddler crying, sleeping and feeding problems and trajectories of dysregulated behavior across childhood.

PubMed

Winsper, Catherine; Wolke, Dieter

2014-01-01

Infant and toddler regulatory problems (RPs) including crying, sleeping and feeding, are a frequent concern for parents and have been associated with negative behavioral outcomes in early and middle childhood. Uncertain is whether infant and toddler RPs predict stable, trait-like dysregulated behavior across childhood. We addressed this gap in the literature using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). RPs at 6, 15-18, & 24-30 months and childhood dysregulated behavior at 4, 7, 8, & 9.5 years were assessed using mother report. Latent Class Growth Analysis (LCGA) indicated that trajectories of childhood dysregulated behavior were stable over time. All single RPs (i.e., crying, sleeping & feeding problems) were significantly associated with childhood dysregulated behavior. For example, crying problems at 6 months after controlling for confounders (Odds Ratios; 95% Confidence Intervals): Moderate dysregulated behavior: OR = 1.50, 95% CI [1.09 to 2.06], high dysregulated behavior: OR = 2.13, 95% CI [1.49 to 3.05] and very high dysregulated behavior: OR = 2.85, 95% CI [1.64 to 4.94]. Multiple RPs were especially strongly associated with dysregulated behavior. For example, the RP composite at 15-18 months: 1 RP, very high dysregulated behavior: OR = 2.79, 95% CI [2.17 to 3.57], 2 RPs, very high dysregulated behavior: OR = 3.46, 95% CI [2.38 to 5.01], 3 RPs, very high dysregulated behavior: OR = 12.57, 95% CI [6.38 to 24.74]. These findings suggest that RPs in infants and toddlers predict stable dysregulated behavior trajectories across childhood. Interventions for early RPs could help prevent the development of chronic, highly dysregulated behavior.

Feline hyperthyroidism reported in primary-care veterinary practices in England: prevalence, associated factors and spatial distribution.

PubMed

Stephens, M J; O'Neill, D G; Church, D B; McGreevy, P D; Thomson, P C; Brodbelt, D C

2014-11-08

Feline hyperthyroidism is a commonly diagnosed endocrinopathy that can have a substantial deleterious impact on the welfare of affected cats. This study aimed to estimate the prevalence, associated factors and geographical distribution for feline hyperthyroidism in England, using primary-care veterinary practice clinical data from the VetCompass Animal Surveillance Project. Prevalence was estimated from the overall cat cohort. Associated factor analysis used an age-matched, nested, case-control design with multivariable logistic regression. There were 2,276 cases of feline hyperthyroidism identified from 95,629 cats attending 84 practices from September 2009 to December 2011. Cases were aged 6-25 years. 3.7 per cent of cases and 9.9 per cent of controls were purebred, 56.4 per cent of cases and 56.5 per cent of controls were female, and 88.1 per cent of cases and 86.0 per cent of controls were neutered. The apparent prevalence was 2.4 per cent (95% CI 2.3 to 2.5 per cent) overall, and 8.7 per cent (95% CI 8.3 to 9.0 per cent) in cats aged 10 years or above. Burmese (OR 0.15, 95% CI 0.07 to 0.32, P<0.0001), Persian (OR 0.17, 95% CI 0.08 to 0.33, P<0.0001), Siamese (OR 0.4, 95% CI 0.21 to 0.75, P=0.004) and purebred cats overall (OR 0.33, 95% CI 0.25 to 0.42, P< 0.0001) had lower odds of feline hyperthyroidism than non-purebred cats. Insured cats had increased odds (OR 1.78, 95% CI 1.56 to 2.03, P< 0.001). There was little evidence of spatial variation. This study highlights feline hyperthyroidism as a high-prevalence disease in England, and reports reduced odds of diagnosis in certain breeds and purebred cats overall. British Veterinary Association.

Titanium biomaterials with complex surfaces induced aberrant peripheral circadian rhythms in bone marrow mesenchymal stromal cells.

PubMed

Hassan, Nathaniel; McCarville, Kirstin; Morinaga, Kenzo; Mengatto, Cristiane M; Langfelder, Peter; Hokugo, Akishige; Tahara, Yu; Colwell, Christopher S; Nishimura, Ichiro

2017-01-01

Circadian rhythms maintain a high level of homeostasis through internal feed-forward and -backward regulation by core molecules. In this study, we report the highly unusual peripheral circadian rhythm of bone marrow mesenchymal stromal cells (BMSCs) induced by titanium-based biomaterials with complex surface modifications (Ti biomaterial) commonly used for dental and orthopedic implants. When cultured on Ti biomaterials, human BMSCs suppressed circadian PER1 expression patterns, while NPAS2 was uniquely upregulated. The Ti biomaterials, which reduced Per1 expression and upregulated Npas2, were further examined with BMSCs harvested from Per1::luc transgenic rats. Next, we addressed the regulatory relationship between Per1 and Npas2 using BMSCs from Npas2 knockout mice. The Npas2 knockout mutation did not rescue the Ti biomaterial-induced Per1 suppression and did not affect Per2, Per3, Bmal1 and Clock expression, suggesting that the Ti biomaterial-induced Npas2 overexpression was likely an independent phenomenon. Previously, vitamin D deficiency was reported to interfere with Ti biomaterial osseointegration. The present study demonstrated that vitamin D supplementation significantly increased Per1::luc expression in BMSCs, though the presence of Ti biomaterials only moderately affected the suppressed Per1::luc expression. Available in vivo microarray data from femurs exposed to Ti biomaterials in vitamin D-deficient rats were evaluated by weighted gene co-expression network analysis. A large co-expression network containing Npas2, Bmal1, and Vdr was observed to form with the Ti biomaterials, which was disintegrated by vitamin D deficiency. Thus, the aberrant BMSC peripheral circadian rhythm may be essential for the integration of Ti biomaterials into bone.

Proliferative capability of parietal and zymogen cells.

PubMed Central

Chen, K Y; Withers, H R

1975-01-01

Six to eight week old male mice of C3Hf/Bu strain were killed and studied at various times from 30 minutes to 30 days after tritiated thymidine (3H-TdR) injection. Labelling of parietal and zymogen cells was observed in autoradiographic histological specimens. There were 590 +/- 22 gastric glands per circumference at the body of the stomach. Parietal cells were counted as 16-2 (14-0-18-4) per gland or 9600 per circumference. There were 11-4 (9-4-13-7) zymogen cells per gland or 6700 per circumference. Two labelled immature parietal cells per circumference were seen 30 minutes after 3H-TdR injection, equivalent to a ratio of 1:5000; more mature labelled parietal cells were seen at later times up to 30 days. There was evidence for proliferation during maturation and downward migration of cells toward the body and the lower part of the gastric gland. Our data support earlier evidence that immature parietal cells constantly supply mature parietal cells through migration from a proliferative zone. Whether the parietal cells are derived from the same stem cell compartment as surface epithelium cells is unclear at the present time. An average of 2-6 zymogen cells per circumference, or 1:2500, was found to be labelled. While most zymogen cells were not proliferating, cells entered the proliferating cycle at random. Based on the findings reported in this paper and the radiation responses of both parietal and zymogen cells, it is postulated that they form part of a slow renewal system. Images Fig. 1 (cont.) Fig. 1 (cont.) Fig. 1 (cont.) Fig. 1 Fig. 2 (cont.) Fig. 2 (cont.) Fig. 2 PMID:1213947

The characterization of electroplex generated from the interface between 2-(4-trifluoromethyl-2-hydroxyphenyl)benzothiazole] zinc and N,N'-diphenyl-N,N'- bis(1-naphthyl)-(1,1'-biphenyl)-4,4'-diamine

NASA Astrophysics Data System (ADS)

Zhang, Ye; Hao, Yuying; Meng, Weixin; Xu, Huixia; Wang, Hua; Xu, Bingshe

2012-03-01

The electroplex between (2-(4-trifluoromethyl-2-hydroxyphenyl)benzothiazole) zinc [Zn(4-TfmBTZ)2] as an electron-acceptor and N,N'-diphenyl-N,N'-bis(1-naphthyl)-(1,1'-biphenyl)-4,4'-diamine (NPB) as an electron-donor was characterized by bilayer, blend, and multilayer quantum-well (MQW) device, respectively. The blend composition and quantum-well number are effective parameters for tuning electroluminescence color. White light with high color purity and color rendering index (CRI) was observed from these devices based on Zn(4-TfmBTZ)2/NPB. Moreover, the blend and MQW devices all exhibit high operation stability, hence excellent color stability. For the device with 5 mol% NPB in blend layer, its Commission International Del'Eclairage (CIE) coordinate region is x=0.28-0.31, y=0.33-0.35 and CRI is 83.3-91.2 at 5-9 V. For MQW structure device with NPB of 60 nm thickness, its CIE coordinate region is x=0.29-0.32, y=0.31-0.34 and CRI=87.9-92.5 at 10-15 V. Such high color stability and purity and CRI, being close to ideal white light, are of current important for white OLED.

40 CFR Table 7 to Subpart Dddd of... - Model Rule-Emission Limitations That Apply to Energy Recovery Units After May 20, 2011

Code of Federal Regulations, 2011 CFR

2011-07-01

... volume Biomass—490 parts per million dry volumeCoal—59 parts per million dry volume 3-run average (1 hour... with a concentration of 1000 ppm or less for biomass-fed boilers. Dioxins/furans (total mass basis) 2.9... million dry volume Biomass—290 parts per million dry volumeCoal—340 parts per million dry volume 3-run...

21 CFR 558.485 - Pyrantel tartrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... containing 9.6, 19.2, 48, or 80 grams per pound pyrantel tartrate. (b) Approvals. See sponsors in § 510.600(c... grams per pound for use as in paragraph (e)(1) of this section. (2) [Reserved] (3) Nos. 010439, 011490, 011749, 012286, 016968, 017790, 043733, and 049685: 9.6 and 19.2 grams per pound for use as in paragraphs...

Determination of the thermal rate coefficient, products, and branching ratios for the reaction of O/+/ /D-2/ with N2

NASA Technical Reports Server (NTRS)

Torr, D. G.; Torr, M. R.

1980-01-01

Atmosphere Explorer-C satellite measurements are used to determine rate coefficients (RCs) for the following reactions: O(+)(D-2) + N2 yields N2(+) + O (reaction 1), O(+)(D-2) + N2 yields O(+)(S-4) + N2 (reaction 2), and O(+)(D-2) + N2 yields NO(+) + N (reaction 3). Results show the RC for reaction 1 to be 1 (plus 1 or minus 0.5) x 10 to the -10th cu cm per sec, for reaction 2 to be 3 (plus 1 or minus 2) x 10 to the -11th cu cm per sec, and 3 to be less than 5.5 x 10 to the -11th cu cm per sec. It is also found that the reaction of O(+)(D-2) with N2 does not constitute a detectable source of NO(+) ions in the thermosphere.

21 CFR 558.363 - Narasin.

Code of Federal Regulations, 2011 CFR

2011-04-01

... this section are as follows: (1) To 000986: 36, 45, 54, 72, and 90 grams per pound, paragraph (d)(1)(i) of this section. (2) To 000986: 36, 45, 54, 72, and 90 grams per pound, with 10, 20, 50, and 80 percent roxarsone, paragraph (d)(1)(ii) of this section. (3) To 000986: 36 grams per pound, with 36 grams...

21 CFR 558.363 - Narasin.

Code of Federal Regulations, 2012 CFR

2012-04-01

... this section are as follows: (1) To 000986: 36, 45, 54, 72, and 90 grams per pound, paragraph (d)(1)(i) of this section. (2) To 000986: 36, 45, 54, 72, and 90 grams per pound, with 10, 20, 50, and 80 percent roxarsone, paragraph (d)(1)(ii) of this section. (3) To 000986: 36 grams per pound, with 36 grams...

21 CFR 558.363 - Narasin.

Code of Federal Regulations, 2013 CFR

2013-04-01

... this section are as follows: (1) To 000986: 36, 45, 54, 72, and 90 grams per pound, paragraph (d)(1)(i) of this section. (2) To 000986: 36, 45, 54, 72, and 90 grams per pound, with 10, 20, 50, and 80 percent roxarsone, paragraph (d)(1)(ii) of this section. (3) To 000986: 36 grams per pound, with 36 grams...

21 CFR 558.363 - Narasin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... this section are as follows: (1) To 000986: 36, 45, 54, 72, and 90 grams per pound, paragraph (d)(1)(i) of this section. (2) To 000986: 36, 45, 54, 72, and 90 grams per pound, with 10, 20, 50, and 80 percent roxarsone, paragraph (d)(1)(ii) of this section. (3) To 000986: 36 grams per pound, with 36 grams...

Detection of the frequency of PER-1 type extended-spectrum β-lactamase-producing Acinetobacter baumannii clinical isolates in Turkey: a multicenter study.

PubMed

Aşik, Gülşah; Özdemir, Mehmet; Kurtoğlu, Muhammet Güzel; Yağci, Server; Öksüz, Lütfiye; Gül, Mustafa; Koçoğlu, Mücahide Esra; Sesli Çetin, Emel; Seyrek, Adnan; Berktaş, Mustafa; Ayyildiz, Ahmet; Çiftci, İhsan Hakkı

2014-01-01

β-Lactamases are an important resistance mechanism in Acinetobacter baumannii. Pseudomonas extended-resistance (PER-1) type β-lactamase-producing strains have been reported from various geographic locations; however, PER-1 type β-lactamases from Turkish hospitals have not been investigated extensively. The aim of this study was to determine the prevalence of PER-1 type β-lactamases in A. baumannii isolates in various regions of Turkey. A total of 763 clinical A. baumannii isolates were collected from 9 university hospitals and 2 state hospitals between 2008 and 2011. Molecular amplification of the OXA-51 gene from the A. baumannii genome was performed in order to verify identification of the species. Real-time polymerase chain reaction was used to detect blaPER-1 genes. PER-1 was detected in 24.6% of the isolates. The annual frequencies of the PER-1 enzyme were detected as 52.2%, 35.9%, and 8.3% in 2008, 2009, and 2010, respectively. PER-1 prevalence decreased gradually over time. The differences observed in PER-1 prevalence among the regions of Turkey were statistically significant (chi-square test; P < 0.001). These data demonstrate that the frequency of detection of PER-1 type β-lactamases in A. baumannii species has decreased in Turkey. However, the increased carbapenem resistance, together with multidrug resistance, has created a worrisome situation regarding this pathogen.

[Study on the disabilities in aged 0-7 years children in Shenzhen, China].

PubMed

Sun, Xi-bin; Qu, Cheng-yi; Yang, Lei; Yan, Jia-mu; Xie, Jian-wen; Chen, Yi-qing; Long, Mo; Liang, Wei; Li, Su-pei; Gao, Shou-yan; Yin, Dong-yi; Zhou, Wen-pei; Shi, Shuai; Hua, Fang; Zhou, Ben-li; Zhu, Shao-ming; Wang, Li; Feng, Dai-hao; Zhou, Lin

2003-11-01

To explore the prevalence of vision, mental, audibility, language, psychiatry, extremity, and influence factors in the 0 - 7 year olds. A total number of 77,727 0 - 7 year old children living in Shenzhen city were tested with tree phase screening under the Chinese standard of evaluation in disabilities. The prevalence of all disabilities was 5.59 per thousand (adjusted rate was 8.49 per thousand with a false negative of 3.1 per thousand ). The prevalence of mental disease was the highest (1.88 per thousand, with adjusted rate 3.43 per thousand ), the prevalence of language disability was 1.88 per thousand (including retarded language development, with adjusted rate 3.43 per thousand ). The prevalence rates of psychiatry, extremity and audibility disability were 1.59 per thousand, 1.56 per thousand, 1.11 per thousand respectively with of vision the lowest (0.37 per thousand ). The prevalence of all disabilities, audibility, language and mental was on the increase with age. The difference was statistically significant. Among all different age groups regarding psychiatric disease, the highest fell in the 2 - 4 year olds. The prevalence of extremity was not statistically different among age groups. The suspected agents of disease which occurred before or during pregnancy took up 45.7%. The prevalence of six kinds disabilities in Shenzhen was about 10 per thousand lower than that of the samples of the nation in 1989, but two times higher than that of similar studies in Japan. The prevalence rates of language and psychiatric disease were higher than that of the nation in 1989. The causation should be further studied.

Abdominopelvic 1.5-T and 3.0-T MR Imaging in Healthy Volunteers: Relationship to Formation of DNA Double-Strand Breaks.

PubMed

Suntharalingam, Saravanabavaan; Mladenov, Emil; Sarabhai, Theresia; Wetter, Axel; Kraff, Oliver; Quick, Harald H; Forsting, Michael; Iliakis, Georg; Nassenstein, Kai

2018-05-01

Purpose To investigate the relationship between abdominopelvic magnetic resonance (MR) imaging and formation of DNA double-strand breaks (DSBs) in peripheral blood lymphocytes among a cohort of healthy volunteers. Materials and Methods Blood samples were obtained from 40 healthy volunteers (23 women and 17 men; mean age, 27.2 years [range, 21-37 years]) directly before and 5 and 30 minutes after abdominopelvic MR imaging performed at 1.5 T (n = 20) or 3.0 T (n = 20). The number of DNA DSBs in isolated blood lymphocytes was quantified after indirect immunofluorescent staining of a generally accepted DSB marker, γ-H2AX, by means of high-throughput automated microscopy. As a positive control of DSB induction, blood lymphocytes from six volunteers were irradiated in vitro with x-rays at a dose of 1 Gy (70-90 keV). Statistical analysis was performed by using a Friedman test. Results No significant alteration in the frequency of DNA DSB induction was observed after MR imaging (before imaging: 0.22 foci per cell, interquartile range [IQR] = 0.54 foci per cell; 5 minutes after MR imaging: 0.08 foci per cell, IQR = 0.39 foci per cell; 30 minutes after MR imaging: 0.09 foci per cell, IQR = 0.63 foci per cell; P = .057). In vitro radiation of lymphocytes with 1 Gy led to a significant increase in DSBs (0.22 vs 3.43 foci per cell; P = .0312). The frequency of DSBs did not differ between imaging at 1.5 T and at 3.0 T (5 minutes after MR imaging: 0.23 vs 0.06 foci per cell, respectively [P = .57]; 30 minutes after MR imaging: 0.12 vs 0.08 foci per cell [P = .76]). Conclusion Abdominopelvic MR imaging performed at 1.5 T or 3.0 T does not affect the formation of DNA DSBs in peripheral blood lymphocytes. © RSNA, 2018.

The present and future use of physician extenders in general surgery training programs: one response to the 80-hour work week.

PubMed

Pezzi, Christopher; Leibrandt, Thomas; Suryadevara, Sree; Heller, Janice K; Hurley-Martonik, Donna; Kukora, John S

2009-04-01

The aim of this study was to assess the use of physician extenders (PEs) in general surgery residency programs. We surveyed the program directors in surgery for the number of chief residents, PEs on general surgery services, PE duties, whether PEs were hired in response to Accreditation Council for Graduate Medical Education work-hour restrictions, plans to hire additional PEs, and program type. Data were analyzed using the Student's t-test; p values are two-tailed and considered significant if <0.05. There were 163 programs (65%) that responded, (87 university, 70 nonuniversity, and 6 military programs), with a total of 689 graduating chief residents per year. One hundred sixty programs use 840 PEs (median, 3.5 PEs per program; mean, 5.3 PEs per program, 2 PEs per chief resident). One hundred twenty-seven programs (79%) use at least 1 PE (range 1 to 50 PEs); 93 programs (57%) hired 513 (61%) PEs in response to work-hour restrictions. Before 2003, the mean number of PEs per program was 2.0; after 2003, there were 5.3 per program (p=0.0001). Most common uses of PEs included taking histories and physicals (84%), seeing consults (58%), first-assisting (52%), and seeing patients in the emergency department (47%). Forty-seven of 162 (29%) programs plan to hire more PEs in the next 3 years, 76 programs (47%) would like to, but are unsure of funding; 23 programs (14%) are not planning to increase the total, and 16 programs (10%) are unsure. With available funding, 431 additional PEs may be hired in the next 3 years, for a total of 1,271 PEs in 163 programs, or an average of 7.8 PEs per program and 1.8 PEs per chief resident. PEs have been hired in large numbers to assist on general surgery teaching services, with most hired in response to Accreditation Council for Graduate Medical Education work-hour restrictions, and most of their duties are intended to aid resident education. Almost 80% of programs currently use PEs; 76% would like to hire more. Currently 1.2 PEs are used per graduating chief resident; this could increase to 1.8 PEs per chief resident in the next 3 years.

Studies on MUST (Medical Unit, Self-Contained, Transportable) Field Hospital Wastewater Treatment

DTIC Science & Technology

1974-12-01

developer I’henol Sulfate (FJon) Hexachlorophene 6 Disinfectant (4) Miscellaneous Solvents cciA 154 i 4 cs2 76 si 3 Acetone 58 oo 3 33 Tablt...disinfectant, floor cleaner (i-sorliilal (70%) 182 8 Hand lotion CrlvLfrsol 92 oo 1 Shampoo IjEgend Toxicily; Solubility: 1-6(6 being hlglily toxit...Hair Oil 51.0 grams 816 grains 8.44 per 72 <>/ 3.38 Hair Gel 12.1 grams 194 grain> 4.54 per 18 ()/. 1.72 Shampoo 1.6 grams 26.3 grams 5.00 per 192

Tuberculosis in Poland in 2014

PubMed

Korzeniewska-Koseła, Maria

To evaluate the main features of TB epidemiology in 2014 in Poland and to compare with the data on the same phenomena in EU/EEA countries. Analysis of case- based data on TB patients from National TB Register, data on anti-TB drugsusceptibility testing results in cases notified in 2014, data from National Institute of Public Health- NationalInstitute of Hygiene on cases of tuberculosis as AIDS-defining disease, data from Central Statistical Office ondeaths from tuberculosis based on death certificates, data from ECDC report „ European Centre for DiseasePrevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2016. Stockholm: European Centre for Disease Prevention and Control, 2016”. 6 698 TB cases were reported in Poland in 2014. The incidence rate was 17.4 cases per 100 000, withlarge variability between voivodeships from 9.3 to 26.5 per 100 000. The mean annual decrease of TB incidence in 2010- 2014 was 2.1%. 6 066 cases had no history of previous treatment i.e. 15.8 per 100 000. 632 cases i.e. 1.6 per 100 000 – 9.4% of all registered subjects were relapses. The number of all notified pulmonary tuberculosis cases in 2014 was 6311 i.e. 16.4 per 100 000. Pulmonary cases represented 94.2% of all TB cases. In the presented year 387 extrapulmonary TB cases were reported. Children with TB (70 cases) accounted for 1.0% of all cases notified in Poland. The incidence of tuberculosis increases with age from 1.2 per 100 000 among children to 30.4 per 100 000 among patients 65 years old and older. The incidence among men i.e. 24.6 per 100 000 was 2.3 times higher than among women i.e. 10.7 per 100 000. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 45 to 49 years – 40.4 vs. 9.3. The TB incidence in rural population was lower than in urban, respectively 17.0 per 100 000 and 17.7 per 100 000. The number of all registered culture positive TB cases, including relapses, was 4 781. Culture-confirmed cases constituted 71.4% of all TB cases and 72.9% of all pulmonary TB cases. The number of smear-positive pulmonary TB cases reported in 2014 was 2800 i.e. 7.3 per 100 000 respectively what constituted 44.4% of all pulmonary TB cases. TB was initial AIDS indicative disease in 13 persons. In Poland in 2014 there were 35 cases with MDR-TB (including 7 patients of foreign origin) and 97 patients with resistance to isoniazid only, constituting respectively 0.8% and 2.2% of cases with known DST results (DSTs were done in 93.3% of all culture-confirmed TB cases). In 2014, there were 49 foreign-origin TB cases reported in Poland. There were 532 deaths due to tuberculosis reported in 2013 – 1.4 per 100 000; 518 and 14 from extrapulmonary tuberculosis. Mortality among males – 2.2 per 100.000 – was 3.6 X higher than among females – 0.6. 38,5% of all TB deaths were cases 65 years old and older – 3.7 per 100 000. There were no deaths from tuberculosis in children. TB was cause of death in one adolescent. TB mortality in 2013 constituted 0.14% of total mortality in Poland and 27.1% of mortality from infectious diseases. In Poland in 2014 the incidence of tuberculosis was higher than the average in EU/EEA countries. The highest incidence rates occurred in older age groups. The incidence in men was more than 2 times higher than in women. In Poland, unfavorable phenomena as tuberculosis in children, tuberculosis in persons infected with HIV and MDR-TB are less common than in EU/EEA countries.

Detection and characterization of cry1Ac transgene construct in Bt cotton: multiple polymerase chain reaction approach.

PubMed

Singh, Chandra K; Ojha, Abhishek; Kachru, Devendra N

2007-01-01

To comply with international labeling regulations for genetically modified (GM) crops and food, and to enable proper identification of GM organisms (GMOs), effective methodologies and reliable approaches are needed. The spurious and unapproved GM planting has contributed to crop failures and commercial losses. To ensure effective and genuine GM cultivation, a methodology is needed to detect and identify the trait of interest and concurrently evaluate the structural and functional stability of the transgene insert. A multiple polymerase chain reaction (PCR) approach was developed for detection, identification, and gene stability confirmation of cry1Ac transgene construct in Bt cotton. As many as 9 samples of Bt cotton hybrid seeds comprising 3 approved Bt hybrids, MECH-12Bt, MECH-162Bt, MECH-184Bt, and a batch of 6 nonapproved Bt hybrids were tested. Initially, single standard PCR assays were run to amplify predominant GM DNA sequences (CaMV 35S promoter, nos terminator, and npt-II marker gene); a housekeeping gene, Gossypium hirsutum fiber-specific acyl carrier protein gene (acp1); a trait-specific transgene (cry1Ac); and a sequence of 7S 3' transcription terminator which specifically borders with 3' region of cry1Ac transgene cassette. The concurrent amplification of all sequences of the entire cassette was performed by 3 assays, duplex, triplex, and quadruplex multiplex PCR assays, under common assay conditions. The identity of amplicons was reconfirmed by restriction endonuclease digestion profile. The 2 distinct transgene cassettes, cry1Ac and npt-II, of the Bt cotton were amplified using the respective forward primer of promoter and reverse primer of terminator. The resultant amplicons were excised, eluted, and purified. The purified amplicons served as template for nested PCR assays. The nested PCR runs confirmed the transgene construct orientation and identity. The limit of detection as established by our assay for GM trait (cry1Ac) was 0.1%. This approach can be adopted as a standard procedure for complete molecular characterization of Bt cotton. These assays will be of interest and use to importers, breeders, research laboratories, safety regulators, and food processors for detection of cry1Ac bearing GMOs.

Violet Laser Diode Enables Lighting Communication.

PubMed

Chi, Yu-Chieh; Huang, Yu-Fang; Wu, Tsai-Chen; Tsai, Cheng-Ting; Chen, Li-Yin; Kuo, Hao-Chung; Lin, Gong-Ru

2017-09-05

Violet laser diode (VLD) based white-light source with high color rendering index (CRI) for lighting communication is implemented by covering with Y 3 Al 5 O 12 :Ce 3+ (YAG:Ce) or Lu 3 Al 5 O 12 :Ce 3+ /CaAlSiN 3 :Eu 2+ (LuAG:Ce/CASN:Eu) phosphorous diffuser plates. After passing the beam of VLD biased at 70 mA (~2I th ) through the YAG:Ce phosphorous diffuser, a daylight with a correlated color temperature (CCT) of 5068 K and a CRI of 65 is acquired to provide a forward error correction (FEC) certified data rate of 4.4 Gbit/s. By using the VLD biased at 122 mA (~3.5I th ) to excite the LuAG:Ce/CASN:Eu phosphorous diffuser with 0.85-mm thickness, a warm white-light source with a CCT of 2700 K and a CRI of 87.9 is obtained at a cost of decreasing transmission capacity to 2.4 Gbit/s. Thinning the phosphor thickness to 0.75 mm effectively reduces the required bias current by 32 mA to achieve the same CCT for the delivered white light, which offers an enlarged CRI of 89.1 and an increased data rate of 4.4 Gbit/s. Further enlarging the bias current to 105 mA remains the white-light transmission capacity at 4.4 Gbit/s but reveals an increased CCT of 3023 K and an upgraded CRI of 91.5.

42 CFR Appendix - Tables to Subpart H of Part 84

Code of Federal Regulations, 2010 CFR

2010-10-01

... HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND... Sampling and readings 2 2 2 2 Perform 1 hour test 2, 3, or 4 times respectively. Walks at 4.8 km. (3 miles) per hour 3 5 3 4 8 12 18 Sampling and readings 2 2 2 2 2 Walks at 4.8 km. (3 miles) per hour 3 5 8 12...

Multitrophic Cry-protein flow in Bt-cotton

USDA-ARS?s Scientific Manuscript database

Although most genetically engineered cotton plants grown today produce the insecticidal Cry-proteins Cry1Ac and Cry2Ab, studies are lacking on multitrophic Cry-protein acquisition in dual-gene cotton fields. Such field data are important for the design and interpretation of laboratory risk assessmen...

A Cryptochrome 2 mutation yields advanced sleep phase in humans.

PubMed

Hirano, Arisa; Shi, Guangsen; Jones, Christopher R; Lipzen, Anna; Pennacchio, Len A; Xu, Ying; Hallows, William C; McMahon, Thomas; Yamazaki, Maya; Ptáček, Louis J; Fu, Ying-Hui

2016-08-16

Familial Advanced Sleep Phase (FASP) is a heritable human sleep phenotype characterized by very early sleep and wake times. We identified a missense mutation in the human Cryptochrome 2 (CRY2) gene that co-segregates with FASP in one family. The mutation leads to replacement of an alanine residue at position 260 with a threonine (A260T). In mice, the CRY2 mutation causes a shortened circadian period and reduced phase-shift to early-night light pulse associated with phase-advanced behavioral rhythms in the light-dark cycle. The A260T mutation is located in the phosphate loop of the flavin adenine dinucleotide (FAD) binding domain of CRY2. The mutation alters the conformation of CRY2, increasing its accessibility and affinity for FBXL3 (an E3 ubiquitin ligase), thus promoting its degradation. These results demonstrate that CRY2 stability controlled by FBXL3 plays a key role in the regulation of human sleep wake behavior.

Evaluating Drug Cost per Response with SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus.

PubMed

Lopez, Janice M S; Macomson, Brian; Ektare, Varun; Patel, Dipen; Botteman, Marc

2015-09-01

The sodium-glucose cotransporter 2 (SGLT2) inhibitors, which include canagliflozin, dapagliflozin, and empagliflozin, represent a new class of antihyperglycemic agents. Few studies have assessed their cost per response, with "cost per response" being the total cost of a select drug, divided by the resulting change in glycated hemoglobin (HbA1c) levels. To examine the drug cost of SGLT2 inhibitors per a reduction in placebo-adjusted 1% HbA1c in patients with type 2 diabetes mellitus who received treatment during 26 weeks with canagliflozin, dapagliflozin, or empagliflozin. The drug cost per response for each of the 3 agents individually was assessed based on data from a subset of clinical trials discussed in the prescribing information for each drug that were all placebo-controlled studies evaluating each drug as monotherapy, dual therapy (combined with metformin), and triple therapy (combined with metformin and a sulfonylurea) in patients with uncontrolled, type 2 diabetes mellitus. The US 2015 wholesale acquisition cost for each drug was used to calculate each drug's treatment costs over 26 weeks. The average cost per response for each drug was defined as the prescription drug cost of each SGLT2 inhibitor, divided by the average, placebo-adjusted HbA1c reduction at 26 weeks. The drug cost per unit dose was the same for canagliflozin (100 mg or 300 mg), dapagliflozin (5 mg or 10 mg), and empagliflozin (10 mg or 25 mg), at $11.43. The drug cost per placebo-adjusted 1% HbA1c reduction varied by agent and by dose, as a result of the differences in the treatment responses for each of the 3 drugs. The costs per response for canagliflozin 100 mg as monotherapy, dual therapy, and triple therapy regimens ranged from $2286 to $3355, and for canagliflozin 300 mg, from $1793 to $2702. The costs per response for dapagliflozin 5 mg as monotherapy and dual therapy (triple therapy was not available at the time of the study) ranged from $4161 to $5201; the cost for dapagliflozin 10 mg ranged from $2972 to $4161. The costs per response for empagliflozin 10 mg ranged from $2972 to $3467 across the monotherapy, dual therapy, and triple therapy regimens; the cost for empagliflozin 25 mg ranged from $2311 to $3467. Simple analyses, such as the drug cost per placebo-adjusted 1% reduction in HbA1c, may be useful when considering the addition of antihyperglycemic agents to the health plan's formulary.

Summary of geology and ground-water resources of Passaic County, New Jersey

USGS Publications Warehouse

Carswell, L.D.; Rooney, J.G.

1976-01-01

Ground water in Passaic County occurs in intergranular openings of unconsolidated stratified deposits of Quaternary age and in joints and fractures in consolidated rocks of Precambrian, Paleozoic, and Triassic age.The Brunswick Formation of Triassic age is the most important aquifer in the southeastern one-third of Passaic County. Reported yields of public supply and industrial wells range from 50 to 510 gallons per minute (3 to 32 litres per second) and the median yield is 130 gallons per minute (8 litres per second). Most of these wells are 200 to 400 feet (61 to 122 metres) deep. The median yield of all public supply and industrial wells over 300 feet (91 metres) deep and 8 inches (203 millimetres) or larger in diameter is 230 gallons per minute (15 litres per second). Crystalline rocks of Precambrian age are the major source of ground water for domestic use in the northwestern two-thirds of Passaic County. Reported well yields range from 1 to 200 gallons per minute (.06 to 13 litres per second). The median reported yield of domestic wells is 5 gallons per minute (.31 litres per second) and that of public supply wells is 30 gallons per minute (2 litres per second).Other consolidated rocks--rocks of Paleozoic age and the Watchung Basalt of Traissic age--are utilized primarily for domestic water supplies in Passaic County. Reported yields of wells tapping the Paleozoic rocks range from less than 1 to 35 gallons per minute (.06 to 2 litres per second) and the median yield is 10 gallons per minute (.63 litres per second). Reported yields of domestic wells tapping the Watchung Basalt range from less than 1 to 40 gallons per minute (.06 to 3 litres per second) and the median yield is 12 gallons per minute (.76 litres per second). However, reported yields of nine industrial and commercial wells range from 50 to 180 gallons per minute (3 to 11 litres per second).Unconsolidated stratified deposits of Quaternary age are locally an important source of ground water for public supply and industrial use in parts of Passaic County. These deposits have not been extensively explored but are potentially an important source of ground water for future development. Reported yields of wells tapping the stratified deposits range from 4 to 920 gallons per minute (.25 to 58 litres per second). The median reported yield of domestic wells is 16 gallons per minute (1 litre per second) and that of public supply and industrial wells is 130 gallons per minute (8 litres per second. Depths of wells depend upon the thickness of the deposits. Reported depths range from 22 to 170 feet (7 to 52 metres).The quality of ground water in Passaic County varies from one aquifer to another. Water from the Precambrian rocks is soft to moderately hard (34 to 104 milligrams per litre) and is low in dissolved solids (66 to 159 milligrams per litre). Water from the Brunswick Formation is moderately hard to very hard (89 to 540 milligrams per litre). The dissolved solids content ranges from 129 to 563 milligrams per litre). The occurrence of more highly mineralized water at depth in the Brunswick Formation is indicated by an analysis, made in 1885, of 16,000 milligrams per litre of dissolved solids at a depth of 2,050 feet (625 metres) in a well in Paterson. Water from two wells tapping the Quaternary deposits is moderately hard (65 and 83 milligrams per litre) and has dissolved solids contents of 122 and 133 milligrams per litre).Water use from both surface and ground-water supplies in Passaic County averaged about 106 million gallons per day (4.6 cubic metres per second) in 1965. Ground water probably accounts for 5 to 10 percent of this total. Ground-water pumpage by the major public supply companies in the county has increased from 2.1 million gallons per day (.09 cubic metres per second) in 1951 to 4.39 million gallons per day (.19 cubic metres per second) in 1968. About 80 percent of the 4.39 million gallons per day (.19 cubic metres per second) was from wells tapping the Brunswick Formation in the southern part of the county.

21 CFR 522.2670 - Yohimbine injectable.

Code of Federal Regulations, 2011 CFR

2011-04-01

... pregnant dogs or in dogs intended for breeding has not been established. Federal law restricts this drug to... of 2 milligrams per milliliter solution in dogs. (1) Amount. 0.05 milligram per pound (0.11 milligram per kilogram) of body weight. (2) Indications for use. To reverse the effects of xylazine in dogs. (3...

21 CFR 522.2670 - Yohimbine injectable.

Code of Federal Regulations, 2013 CFR

2013-04-01

... pregnant dogs or in dogs intended for breeding has not been established. Federal law restricts this drug to... of 2 milligrams per milliliter solution in dogs. (1) Amount. 0.05 milligram per pound (0.11 milligram per kilogram) of body weight. (2) Indications for use. To reverse the effects of xylazine in dogs. (3...

21 CFR 522.2670 - Yohimbine injectable.

Code of Federal Regulations, 2012 CFR

2012-04-01

... pregnant dogs or in dogs intended for breeding has not been established. Federal law restricts this drug to... of 2 milligrams per milliliter solution in dogs. (1) Amount. 0.05 milligram per pound (0.11 milligram per kilogram) of body weight. (2) Indications for use. To reverse the effects of xylazine in dogs. (3...

21 CFR 522.2670 - Yohimbine injectable.

Code of Federal Regulations, 2010 CFR

2010-04-01

... pregnant dogs or in dogs intended for breeding has not been established. Federal law restricts this drug to... of 2 milligrams per milliliter solution in dogs. (1) Amount. 0.05 milligram per pound (0.11 milligram per kilogram) of body weight. (2) Indications for use. To reverse the effects of xylazine in dogs. (3...

Diagnostic yield and optimal duration of continuous-loop event monitoring for the diagnosis of palpitations. A cost-effectiveness analysis

NASA Technical Reports Server (NTRS)

Zimetbaum, P. J.; Kim, K. Y.; Josephson, M. E.; Goldberger, A. L.; Cohen, D. J.

1998-01-01

BACKGROUND: Continuous-loop event recorders are widely used for the evaluation of palpitations, but the optimal duration of monitoring is unknown. OBJECTIVE: To determine the yield, timing, and incremental cost-effectiveness of each week of event monitoring for palpitations. DESIGN: Prospective cohort study. PATIENTS: 105 consecutive outpatients referred for the placement of a continuous-loop event recorder for the evaluation of palpitations. MEASUREMENTS: Diagnostic yield, incremental cost, and cost-effectiveness for each week of monitoring. RESULTS: The diagnostic yield of continuous-loop event recorders was 1.04 diagnoses per patient in week 1, 0.15 diagnoses per patient in week 2, and 0.01 diagnoses per patient in week 3 and beyond. Over time, the cost-effectiveness ratio increased from $98 per new diagnosis in week 1 to $576 per new diagnosis in week 2 and $5832 per new diagnosis in week 3. CONCLUSIONS: In patients referred for evaluation of palpitations, the diagnostic yield of continuous-loop event recording decreases rapidly after 2 weeks of monitoring. A 2-week monitoring period is reasonably cost-effective for most patients and should be the standard period for continuous-loop event recording for the evaluation of palpitations.

Effectiveness of educational materials designed to change knowledge and behaviors regarding crying and shaken-baby syndrome in mothers of newborns: a randomized, controlled trial.

PubMed

Barr, Ronald G; Rivara, Frederick P; Barr, Marilyn; Cummings, Peter; Taylor, James; Lengua, Liliana J; Meredith-Benitz, Emily

2009-03-01

Infant crying is an important precipitant for shaken-infant syndrome. OBJECTIVE. To determine if parent education materials (The Period of PURPLE Crying [PURPLE]) change maternal knowledge and behavior relevant to infant shaking. This study was a randomized, controlled trial conducted in prenatal classes, maternity wards, and pediatric practices. There were 1374 mothers of newborns randomly assigned to the PURPLE intervention and 1364 mothers to the control group. Primary outcomes were measured by telephone 2 months after delivery. These included 2 knowledge scales about crying and the dangers of shaking; 3 scales about behavioral responses to crying generally and to unsoothable crying, and caregiver self-talk in response to unsoothable crying; and 3 questions concerning the behaviors of sharing of information with others about crying, walking away if frustrated, and the dangers of shaking. The mean infant crying knowledge score was greater in the intervention group (69.5) compared with controls (63.3). Mean shaking knowledge was greater for intervention subjects (84.8) compared with controls (83.5). For reported maternal behavioral responses to crying generally, responses to unsoothable crying, and for self-talk responses, mean scores for intervention mothers were similar to those for controls. For the behaviors of information sharing, more intervention mothers reported sharing information about walking away if frustrated and the dangers of shaking, but there was little difference in sharing information about infant crying. Intervention mothers also reported increased infant distress. Use of the PURPLE education materials seem to lead to higher scores in knowledge about early infant crying and the dangers of shaking, and in sharing of information behaviors considered to be important for the prevention of shaking.

Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice.

PubMed

Liu, Hui; Xu, Hong-Wei; Zhang, Yu-Zhen; Huang, Ya; Han, Guo-Qing; Liang, Tie-Jun; Wei, Li-Li; Qin, Cheng-Yong; Qin, Cheng-Kun

2015-09-28

To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which is an inhibitor of apoptosis, following administration of UDCA. UDCA suppresses growth of BEL7402 hepatocellular carcinoma cells in vivo, in part through apoptosis induction, and is thus a candidate for therapeutic treatment of HCC.

Recombinant Cry1Ia protein is highly toxic to cotton boll weevil (Anthonomus grandis Boheman) and fall armyworm (Spodoptera frugiperda).

PubMed

Martins, E S; Aguiar, R W D S; Martins, N F; Melatti, V M; Falcão, R; Gomes, A C M M; Ribeiro, B M; Monnerat, R G

2008-05-01

To evaluate the activity of cry1Ia gene against cotton pests, Spodoptera frugiperda and Anthonomus grandis. Had isolated and characterized a toxin gene from the Bacillus thuringiensis S1451 strain which have been previously shown to be toxic to S. frugiperda and A. grandis. The toxin gene (cry1Ia) was amplified by PCR, sequenced, and cloned into the genome of a baculovirus. The Cry1Ia protein was expressed in baculovirus infected insect cells, producing protein inclusions in infected cells. The Cry1Ia protein has used in bioassays against to S. frugiperda and A. grandis. Bioassays using the purified recombinant protein showed high toxicity to S. frugiperda and A. grandis larvae. Molecular modelling of the Cry1Ia protein translated from the DNA sequence obtained in this work, showed that this protein possibly posses a similar structure to the Cry3A protein. Ultrastructural analysis of midgut cells from A. grandis incubated with the Cry1Ia toxin, showed loss of microvilli integrity. The results indicate that the cry1Ia is a good candidate for the construction of transgenic plants resistant to these important cotton pests.

Development and production of a flame retardant, general purpose, pressure sensitive adhesive tape

NASA Technical Reports Server (NTRS)

Monaghan, P. B.; Doggett, R. H.

1977-01-01

The specification results for the finished tape properties were as follows: (1) adhesive strength (180 deg peel) on aluminum from 107 to 143 grams per centimeter (0.6 to 0.8 pounds per inch); (2) adhesive strength (180 deg peel) on stainless steel from 71 to 107 grams per centimeter (0.4 to 0.6 pounds per inch); (3) unwind resistance of 536 to 714 grams per centimeter (3 to 4 pounds per inch); (4) tensile strength minimum of 7143 grams per centimeter (40 pounds per inch); (5) elongation from 5 to 10% at break; (6) tear strength, Elmendorf from 200 to 350 grams (0.44 to 0.77 pounds); and (7) tear strength, tongue from 363 to 408 grams (0.8 to 0.9) pounds).

Evaluation of rapid progressors in HIV infection as an extreme phenotype.

PubMed

Olson, Ashley D; Guiguet, Marguerite; Zangerle, Robert; Gill, John; Perez-Hoyos, Santiago; Lodi, Sara; Ghosn, Jade; Dorrucci, Maria; Johnson, Anne; Sannes, Mette; Moreno, Santiago; Porter, Kholoud

2014-09-01

Rapid CD4 cell loss represents an HIV phenotype used to identify causal variants of accelerated disease progression. The optimal rate and threshold for identifying this extreme phenotype in recently infected individuals is unclear. Using a cohort of patients with known dates of HIV-1 seroconversion (SC), CASCADE (Concerted Action on SeroConversion on AIDS and Death in Europe), we identified proportions experiencing nadir CD4 cell levels within 1 year of SC, and assessed their mean AIDS-free survival time at 10-year follow-up and hazard of AIDS/death, compared with those whose CD4 remained >500 cells per cubic millimeter. Follow-up was censored at December 31, 1996 to avoid bias due to combination antiretroviral therapy initiation. Of 4876 individuals, 2.8%, 7.3%, and 24.9% experienced ≥1 CD4 <100, 200, and 350 cells per cubic millimeter, respectively, within 1 year of SC. Minimum CD4 levels of 30, 166, 231, and 506 cells per cubic millimeter were experienced during this period by 1%, 5%, 10%, and 50% of individuals, respectively. Mean (95% confidence interval) AIDS-free survival at 10 years follow-up was 2.9 (2.3 to 3.6), 5.5 (5.0 to 6.1), 6.7 (6.5 to 7.0), 7.4 (7.2 to 7.6), and 8.1 (7.9 to 8.3), for those with minimum counts ≤100, 100-200, 200-350, 350-500, >500 cells per cubic millimeter, respectively. Using counts of >500 cells per cubic millimeter as reference, the hazard ratios (95% confidence interval) of AIDS/death were 15.0 (11.9 to 18.9), 3.6 (2.9 to 4.5), 2.1 (1.8 to 2.4), and 1.5 (1.3 to 1.7), respectively. The hazard ratio increased to 37.5 (26.5 to 53.1) when a minimum CD4 count <100 was confirmed within 1 year of SC. At least 1 CD4 ≤100 cells per cubic millimeter within the first year of SC identifies a rare group of individuals at high risk of disease progression and could form the basis for defining the rapid progressor phenotype.

Seasonal variations of NO and O3 at altitudes of 18.3 and 21.3 km

NASA Technical Reports Server (NTRS)

Loewenstein, M.; Savage, H. F.; Whitten, R. C.

1975-01-01

Nitric oxide and ozone concentrations have been measured in situ from a high-altitude research aircraft. Data which show the variations of NO and O3 with the time of year are presented for altitudes of 18.3 and 21.3 km. The extreme values of the observed NO concentrations at 21.3 km are 1.2 billion per cu cm in summer and 0.2 billion per cu cm in winter. At 18.3 km the extreme values are 1.6 billion per cu cm in summer and 0.1 billion per cu cm in winter. The smoothed NO seasonal data show a variation of about a factor of 2.5 at 21.3 km and a factor of 4 at 18.3 km. The ozone data show the generally expected magnitude and seasonal variation. We have used a photochemical model employing the measured ozone concentrations, the mean solar zenith angle, and seasonal HNO3 data reported by others to predict the seasonal NO variation at 20 km. The result is a summer-to-winter NO ratio of 2.5 which is in fair agreement with the observed ratios.

Salt content in canteen and fast food meals in Denmark.

PubMed

Rasmussen, Lone Banke; Lassen, Anne Dahl; Hansen, Kirsten; Knuthsen, Pia; Saxholt, Erling; Fagt, Sisse

2010-03-16

A high salt (=NaCl) intake is associated with high blood pressure, and knowledge of salt content in food and meals is important, if the salt intake has to be decreased in the general population. To determine the salt content in worksite canteen meals and fast food. For the first part of this study, 180 canteen meals were collected from a total of 15 worksites with in-house catering facilities. Duplicate portions of a lunch meal were collected from 12 randomly selected employees at each canteen on two non-consecutive days. For the second part of the study, a total of 250 fast food samples were collected from 52 retail places representing both city (Aarhus) and provincial towns. The canteen meals and fast food samples were analyzed for chloride by potentiometric titration with silver nitrate solution, and the salt content was estimated. The salt content in lunch meals in worksite canteens were 3.8+/-1.8 g per meal and 14.7+/-5.1 g per 10 MJ for men (n=109), and 2.8+/-1.2 g per meal and 14.4+/-6.2 g per 10 MJ for women (n=71). Salt content in fast food ranged from 11.8+/-2.5 g per 10 MJ (burgers) to 16.3+/-4.4 g per 10 MJ (sausages) with a mean content of 13.8+/-3.8 g per 10 MJ. Salt content in both fast food and in worksite canteen meals is high and should be decreased.