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Objective— To gain insight into the function of proprotein convertase subtilisin kexin type 9 (PCSK9) in humans by establishing whether circulating levels are influenced by diurnal, dietary, and hormonal changes. Methods and Results— We monitored circulating PCSK9 in a set of dynamic human experiments and could show that serum PCSK9 levels display a diurnal rhythm that closely parallels that of cholesterol synthesis, measured as serum lathosterol. In contrast to these marked diurnal changes in cholesterol metabolism, serum low-density lipoprotein (LDL) cholesterol levels remained stable during the diurnal cycle. Depletion of liver cholesterol by treatment with the bile acid–binding resin, cholestyramine, abolished the diurnal rhythms of both PCSK9 and lathosterol. Fasting (>18 hours) strongly reduced circulating PCSK9 and lathosterol levels, whereas serum LDL levels remained unchanged. Growth hormone, known to be increased during fasting in humans, reduced circulating PCSK9 in parallel to LDL cholesterol levels. Conclusion— Throughout the day, and in response to fasting and cholesterol depletion, circulating PCSK9 displays marked variation, presumably related to oscillations in hepatic cholesterol that modify its activity in parallel with cholesterol synthesis. In addition to this sterol-mediated regulation, additional effects on LDL receptors may be mediated by hormones directly influencing PCSK9.

Phosphorylcholine (PC) may play an important role in the atherogenic and pro-inflammatory effects of oxidized low density lipoproteins. We recently demonstrated that low levels of IgM antibodies against PC (anti-PC) are associated with development of myocardial infarction and stroke. We here evaluate the association between anti-PC and dementia and Alzheimer's disease (AD). We conducted a nested case-control study of 182 incident dementia cases (serum collected before onset of dementia) matched to 366 controls and a case-control study of 97 prevalent dementia cases (serum collected after dementia onset) matched to 205 controls. Controls were matched on gender and age at blood draw (+/- 1 year). Participants were from the Swedish Twin Registry. Anti-PC levels were measured by ELISA. The odds ratio (OR) of dementia was modeled using conditional logistic regression. Patients with dementia had significantly lower mean anti-PC levels than controls (39.1 versus 49.5 U/ml). The likelihood of having dementia or AD was doubled for individuals with the lowest 25% anti-PC levels (OR=2.04 and 2.70, respectively). The results were similar after adjustments for potential confounders. There was no association between anti-PC levels and incident dementia. Low levels of atheroprotective anti-PC could play a role in AD and dementia. Potential mechanisms include decreased anti-inflammatory potential and effects on the vasculature. Further attention is merited to elucidate the role of anti-PC in AD development and the usefulness of anti-PC as a part of risk prediction, prognosis, diagnosis, or treatment.

Chinese tallow tree (TT) seeds are a rich source of lipids and have the potential to be a biodiesel feedstock, but currently, its invasive nature does not favor large scale cultivation. Being a nonfood material, they have many advantages over conventional crops that are used for biodiesel production. The purpose of this study was to determine optimal oil extraction parameters in a batch-type and laboratory scale continuous-flow microwave system to obtain maximum oil recovery from whole TT seeds using ethanol as the extracting solvent. For the batch system, extractions were carried out for different time-temperature combinations ranging from 60 to 120 degrees C for up to 20 min. The batch system was modified for continuous extractions, which were carried out at 50, 60, and 73 degrees C and maintained for various residence times of up to 20 min. Control runs were performed under similar extraction conditions and the results compared well, especially when accounting for extremely short extraction times (minutes vs hours). Maximum yields of 35.32% and 32.51% (by weight of dry mass) were obtained for the continuous and batch process, respectively. The major advantage of microwave assisted solvent extraction is the reduced time of extraction required to obtain total recoverable lipids, with corresponding reduction in energy consumption costs per unit of lipid extracted. This study indicates that microwave extraction using ethanol as a solvent can be used as a viable alternative to conventional lipid extraction techniques for TT seeds.

We describe transgenic mouse lines that express lacZ under the control of the Hox 3.3 Promoter II. The correct anterior boundary can be fixed by 3.6 kb of promoter DNA (plus 1.6 kb of 5′ transcribed sequences), both in tissues of ectodermal and mesodermal origin. The posterior border, however, is not respected, and lacZ expression continues into the tail region. One line has particularly strong graded expression in the anterior proximal limb bud. Other lines, containing a shorter promoter fragment (0.6 kb), have ectopic expression in the head region, including one line that has expression in the anterior half of the retina. Such mouselines make it possible to molecularly distinguish cells in regions of the embryo that look otherwise identical and may be useful in studying the establishment of molecular differences in the mouse embryo.

A permanent transgenic mouse line was generated carrying 40 copies of the human Hox3.3 gene. The resulting mice express large amounts of Hox3.3 protein in posterior regions of the embryo where this homeodomain protein is normally not expressed. The transgene causes homeotic transformations of the skeleton, in particular the appearance of an extra pair of ribs in the lumbar region, transformation of the shape of posterior ribs into that of more anterior ones, and the joining of an additional pair of ribs to the sternum. The phenotype of this line resembles that obtained by the targeted loss-of-function mutation of Hox3.1 (Le Mouellic et al., 1992). In transient assays, the human Hox3.3 transgene leads to the formation of additional ribs in more posterior vertebrae as well.

Homeo box-containing genes (Hox) are expressed in restricted regions of vertebrate embryos and may specify positional information. The organization and expression patterns of these genes are highly conserved among different species, suggesting that their regulation may also have been conserved. We developed a transient expression system, using mosaically transgenic zebrafish, which allows rapid analysis of transgene expression, and examined the activities of two mammalian Hox genes, mouse Hox-1.1 and human HOX-3.3. We found that these Hox promoters are activated in specific regions and tissues of developing zebrafish embryos and that this specificity depends upon the same regulatory elements within the promoters that specify the spatial expression of these genes in mice. Our results suggest that the promoter activities have been remarkably conserved from fish to mammals. To study the regulation of Hox expression in the developing nervous system, we analyzed the promoter activities in spt-1 mutants that have a mesodermal deficiency. Our results suggest that interactions, probably with the paraxial mesoderm, differentially regulate the activities of Hox promoters in the developing nervous system.

This paper details some of the various robotics projects which have been inspired by the natural world, and which the authors believe will have an impact on the future of robotic space exploration. This includes both hardware-centric projects such as RiSE, and projects which concentrate more on software and control such as Swarm-bots. The authors outline two of the biologically inspired planetary explorer robots currently under investigation at the University of Surrey.

The focus of this dissertation has been the biophysical analysis of two related research subjects: a model membrane glycolipid system and glycolipid-rich biomembranes. The objective of the model system study was to provide a biological understanding of the molecular conformation and dynamics at the membrane surface. The biomembrane project is in the first stages of development where the immediate goal is to observe the structure and phase behaviour of cyanobacterial thylakoid membranes. It has been possible to apply a motional model deduced for the glycerol C3$\sp\prime$ position of 1,2-di-O-tetradecyl-3-O-$(\beta$-D-glucopyranosyl)-sn-glycerol $(\beta$-DTGL) in the gel state not only to the more fluid liquid crystalline state, but also to the analysis of the glucose head group ($\{$1-$\rm \sp2H\sb1\})$ motions. The above model, however, did not completely simulate the relaxation data of the $\beta$-DTGL glucose head group. Therefore, conformational energy calculations have been used to assess the flexibility of the head group about its glycosidic bond, in a liquid-crystalline membrane matrix. Algal thylakoid membranes are known for their ability to undergo conformational changes during periods of photosynthetic activity. The ultimate goal of the biomembrane project was to use $\sp2$H NMR to study such conformational changes in thylakoid membranes. However, this project is in the first stages of development; the more modest but attainable short term goal was to observe directly the structure and phase behaviour of two strains of cyanobacterial thylakoid membranes, Anacystis nidulans and A. nidulans R2. In both the previous studies and this study, it was found that the heterogeneous systems undergo broad phase transitions and that acyl chain unsaturation lowers the phase transition temperature of the membranes. Although pure digalactosyldiacyglycerol is known to stabilize lamellar membrane phases, it appears as though phosphatidylglycerol (PG) is more influential in stabilizing the lamellar membrane structure of the cyanobacterial thylakoid membranes. This effect was more noticeable for the spectra of extracted lipids; in the absence of protein and with low PG levels, the lipids formed non-lamellar phases at lower temperatures. (Abstract shortened by UMI.)

Chinese Tallow Tree (TT) has been widely considered as a noxious invader in the U.S. without any potential benefits. Recent research has revealed that TT seeds contain large percentage of oil that primarily consists of palmitic fatty acid, along with some oleic, linoleic and linolinic fatty acids. These fatty acids make TT seed oil a good candidate to be transesterified into biodiesel. In general, literature on TT seed is scarce and the effect of storage conditions on the oil quality of the seeds in particular has not been published to our knowledge. This study aims to address the issue of oil quality of TT seeds during different storage conditions. The TT seeds were stored for 3 months at various combinations of storage temperatures (0°C, 4°C, 10°C, room temperature), and controlled atmosphere storage conditions (3% CO2, 6% CO2, vacuum, normal headspace). On a weekly basis, extracted oil from the seeds was analyzed for its oxidative stability and FFA content to obtain information on the oil quality. Results of the study reveal optimum storage conditions of TT seeds to extract maximum benefit in terms of oil quality at a minimum cost.

The purpose of this research was to design, test, and optimize a continuous microwave extraction method using temperature and residence time during and after microwave exposure as optimizing parameters for extraction of major isoflavones (genistin, genistein, daidzin, and daidzein) from soy flour. The extraction yield of four isoflavones at different heating temperatures (55 and 73 degrees C) and extraction times (0, 4, 8, 12, and 16 min) were investigated and compared with yields provided by a conventional solvent extraction method. The microwave prototype consisted of multiple, commercially available, batch-type, house-hold microwave units placed on top of each other in series to impart a continuous operation. The optimum parameters for microwave-assisted extraction of isoflavones were 73 degrees C for 8 min using a 3:1 ethanol-to soy flour ratio. At these parameters, the total yield of isoflavones extracted doubled, while the amount of oil extracted was 12%. Continuous microwave-assisted solvent extraction is a viable method for extraction of soybean isoflavones at relatively short residence times and high throughput.

Microwaves can be a more efficient method than traditional thermal treatment to deliver the energy required for heating in solvent-oil extraction due to its volumetric, direct coupling with the material. An understanding of the behavior of dielectric properties of solvent–feedstock mixtures is important for designing and optimizing any microwave-based extraction process. In this study rice bran and soybean flour were mixed separately with four different solvents (methanol, ethanol, hexane and isopropanol) at different ratios (1:2, 1:1, 2:1 w/w). For the samples mixed with ethanol, the dielectric properties were measured at 23, 30, 40 and 50 °C, while for all other sample-solvent mixtures experiments were performed at room temperature. Dielectric properties were determined using a vector network analyzer and dielectric probe kit using the open-ended coaxial probe method in the frequency range of 300 MHz to 3 GHz. Results from the study indicate that dielectric constants were dependent on frequency and were strongly influenced by temperature, mix ratio and solvent type. The dielectric loss of all mixtures except those with hexane (which were virtually zero) varied with frequency and temperature, solvent type, and mix ratio. Most of the results presented are emphasized at 433, 915 and 2450 MHz, frequencies allocated by the Federal Communication Commission (F.C.C.) for microwave applications. The results of the study, presented here for the first time to our knowledge, will help in selection of appropriate solvent, mixing ratio and frequency for designing microwave-assisted oil extraction systems.

Chinese Tallow Tree (CTT) has been widely considered as an invasive species that does not have potential benefits. Recent research has revealed that CTT has a very high yield of seeds containing large percentage of oil. The oil that is produced from the CTT has been found to contain high amounts of palmitic fatty acid, along with some oleic, linoleic and linolinic fatty acids. These acids can be base transesterified to form biodiesel. In general literature on CTT seed is scarce and the effect of storage conditions on the oil quality of the seeds in particular has not been published to our knowledge. This study aims to address the issue of oil quality of CTT seeds during different storage conditions. Different storage temperatures (0°C, 4°C, 10°C, room temperature), and controlled atmosphere storage conditions (3% CO, 6% CO, vacuum, normal headspace) were investigated for their effect on the oil quality of CTT seeds. The seeds were stored for a total period of three months with the oil quality being analyzed at regular intervals on a weekly basis. Extracted oil from the seeds was analyzed by titratable acidity and peroxide value methods to obtain information on the oil quality. Results of the study revealed optimum conditions for storage of CTT seeds to extract maximum benefit in terms of oil quality at a minimum cost.

HIPOLIDE, D. C., L. L. LOBO, R. DE MEDEIROS, B. NEUMANN, AND S. TUFIK. Treatment with dexamethasone alters yawning behavior induced by cholinergic but not dopaminergic agonist. PHYSIOL BEHAV 65 (4/5) 829–832, 1999.—Because stressful manipulations have been reported to modify drug-induced yawning, the present study investigated the effects of single and repeated treatment with a synthetic glucocorticoid, dexamethasone (DEXA) on apomorphine- and pilocarpine-induced yawning in male rats. Neither single nor repeated treatment with DEXA altered apomorphine-induced yawning. Single administration of DEXA, however, resulted in an increased number of yawns induced by pilocarpine. Conversely, repeated administration of DEXA led to a decreased number of yawns induced by pilocarpine. In conclusion, the present findings show that dopaminergic and cholinergic are distinctly altered by DEXA, in terms of yawning behavior when animals received DEXA.

Effects of stress on drug-induced yawning: Constant vs. intermittent stress. PHYSIOL BEHAV 58(1) 181-184, 1995.--Experiment 1 tested whether chronic exposure to immobilization, foot shock or forced swimming would result in suppression of apomorphine-, pilocarpine-, and physostigmine-induced yawning. Immobilization caused suppression of yawning, whereas foot shock and swimming resulted in increased number of yawns. Since interstressor interval was long in the two latter stressors, animals could have recovered and the increase in yawning could be due to the last (acute) exposure to stress. In Experiment 2 we recorded the number of yawns induced by pilocarpine in animals exposed to 1 h of swimming or foot shock. No differences between control and acutely stressed animals were detected. These results suggest that yawning is differently altered by constant and intermittent stressors (i.e., diminished by constant and increased by intermittent stress).

The soliton-lattice algorithm, an exact algebraic method of inverting the Bloch equation to obtain frequency-selective radio-frequency pulses is described. Some general properties of pulses are described that were obtained with the help of this algorithm. It is used to obtain two new pulses. A highly prefocused pulse is shown that can be used in short-echo-timein vivo31P spectroscopic imaging, and an adiabatic selective inversion pulse is obtained.

Introduction The purpose of this study was to investigate the effects of vegan diet in patients with rheumatoid arthritis (RA) on blood lipids oxidized low-density lipoprotein (oxLDL) and natural atheroprotective antibodies against phosphorylcholine (anti-PCs). Methods Sixty-six patients with active RA were randomly assigned to either a vegan diet free of gluten (38 patients) or a well-balanced non-vegan diet (28 patients) for 1 year. Thirty patients in the vegan group completed more than 3 months on the diet regimen. Blood lipids were analyzed by routine methods, and oxLDL and anti-PCs were analyzed by enzyme-linked immunosorbent assay. Data and serum samples were obtained at baseline and after 3 and 12 months. Results Mean ages were 50.0 years for the vegan group and 50.8 years for controls. Gluten-free vegan diet induced lower body mass index (BMI) and low-density lipoprotein (LDL) and higher anti-PC IgM than control diet (p < 0.005). In the vegan group, BMI, LDL, and cholesterol decreased after both 3 and 12 months (p < 0.01) and oxLDL after 3 months (p = 0.021) and trendwise after 12 months (p = 0.090). Triglycerides and high-density lipoprotein did not change. IgA anti-PC levels increased after 3 months (p = 0.027) and IgM anti-PC levels increased trendwise after 12 months (p = 0.057). There was no difference in IgG anti-PC levels. In the control diet group, IgM anti-PC levels decreased both after 3 and 12 months (p < 0.01). When separating vegan patients into clinical responders and non-responders at 12 months, the effects on oxLDL and anti-PC IgA were seen only in responders (p < 0.05). Conclusion A gluten-free vegan diet in RA induces changes that are potentially atheroprotective and anti-inflammatory, including decreased LDL and oxLDL levels and raised anti-PC IgM and IgA levels.

Central administration of ACTH in rats induces yawning and stretching. In order to study the effects of REM sleep deprivation on ACTH-induced yawning, the peptide was injected immediately after the REM sleep deprivation period or 24 h later. REM sleep deprivation impaired ACTH-induced yawning, but after a 24-hour recovery period, rats displayed a number of yawns similar to those in control animals. Implications for an involvement of dopaminergic and mainly cholinergic systems are discussed.