Phospholipid composition of reconstituted high density lipoproteins influences their ability to inhibit endothelial cell adhesion molecule expression

Manuscript received 3 September 1999 and in revised form 9 March 2000.The ability of different phosphatidylcholine (PC) species to inhibit cytokine-induced expression of vascular cell adhesion molecule 1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) was investigated. PC species containing palmitoyl- in the sn -1 position and palmitoyl- (DPPC), arachidonyl- (PAPC), linoleoyl- (PLPC) or oleoyl- (POPC) in the sn -2 position were compared. These PC species were studied as components of reconstituted high density lipoproteins (rHDL) (containing apolipoprotein A-I [apoA-I] as the sole protein) or as small unilamellar vesicles (SUVs). The rHDL containing PLPC and PAPC inhibited VCAM-1 expression in activated HUVECs by 95 and 70%, respectively, at an apoA-I concentration of 16 m M . At this concentration of apoA-I, POPC rHDL inhibited by only 16% and DPPC rHDL did not inhibit at all. These differences could not be explained by differential binding of the rHDL to HUVECs. The same hierarchy of inhibitory activity was observed when these PC species were presented to the cells as SUVs but only when the SUVs also contained an antioxidant. It was concluded that rHDL PC is responsible for their inhibitory activity and that this varies widely with different PC species. —Baker, P. W., K-A. Rye, J. R. Gable, M. A. Vadas, and P. J. Barter. Phospholipid composition of reconstituted high density lipoproteins influences their ability to inhibit endothelial cell adhesion molecule expression. J. Lipid Res. 2000. 41: 1261–1267.Paul W. Baker, Kerry-Anne Rye, Jennifer R. Gamble, Mathew A. Vadas, and Philip J. Barte

Preparation of facilities for fundamental research with ultracold neutrons at PNPI

The WWR-M reactor of PNPI offers a unique opportunity to prepare a source for ultracold neutrons (UCN) in an environment of high neutron flux (about 3*10^12 n/cm^2/s) at still acceptable radiation heat release (about 4*10^-3 W/g). It can be realized within the reactor thermal column situated close to the reactor core. With its large diameter of 1 m, this channel allows to install a 15 cm thick bismuth shielding, a graphite premoderator (300 dm^3 at 20 K), and a superfluid helium converter (35 dm^3). At a temperature of 1.2 K it is possible to remove the heat release power of about 20 W. Using the 4pi flux of cold neutrons within the reactor column can bring more than a factor 100 of cold neutron flux incident on the superfluid helium with respect to the present cold neutron beam conditions at the ILL reactor. The storage lifetime for UCN in superfluid He at 1.2 K is about 30 s, which is sufficient when feeding experiments requiring a similar filling time. The calculated density of UCN with energy between 50 neV and 250 neV in an experimental volume of 40 liters is about 10^4 n/cm^3. Technical solutions for realization of the project are discussed.Comment: 10 pages, more detail

The UK risk assessment scheme for all non-native species

1. A pest risk assessment scheme, adapted from the EPPO (European and Mediterranean Plant Protection Organisation) scheme, was developed to assess the risks posed to UK species, habitats and ecosystems by non-native taxa. 2. The scheme provides a structured framework for evaluating the potential for non-native organisms, whether intentional or unintentional introductions, to enter, establish, spread and cause significant impacts in all or part of the UK. Specialist modules permit the relative importance of entry pathways, the vulnerability of receptors and the consequences of policies to be assessed and appropriate risk management options to be selected. Spreadsheets for summarising the level of risk and uncertainty, invasive attributes and economic impact were created. In addition, new methods for quantifying economic impact and summarising risk and uncertainty were explored. 3. Although designed for the UK, the scheme can readily be applied elsewhere

Antigiardial activity of novel guanidine compounds

From four focused compound libraries based on the known anticoccidial agent robenidine, 44 compounds total were synthesised and screened for antigiardial activity. All active compounds were counter-screened for antibiotic and cytotoxic action. Of the analogues examined, 21 displayed IC50<5 μM, seven with IC50<1.0 μM. Most active were 2,2′-bis{[4-(trifluoromethoxy)phenyl]methylene}carbonimidic dihydrazide hydrochloride (30), 2,2′-bis{[4-(trifluoromethylsulfanyl)phenyl]methylene}carbonimidic dihydrazide hydrochloride (32), and 2,2′-bis[(2-bromo-4,5-dimethoxyphenyl)methylene]carbonimidic dihydrazide hydrochloride (41) with IC50=0.2 μM. The maximal observed activity was a 5 h IC50 value of 0.2 μM for 41. The clinically used metronidazole was inactive at this timepoint at a concentration of 25 μM. Robenidine off-target effects at bacteria and cell line toxicity were removed. Analogue 41 was well tolerated in mice treated orally (100 mg/kg). Following 5 h treatment with 41, no Giardia regrowth was noted after 48 h

Protein sequence and structure: Is one more fundamental than the other?

We argue that protein native state structures reside in a novel "phase" of matter which confers on proteins their many amazing characteristics. This phase arises from the common features of all globular proteins and is characterized by a sequence-independent free energy landscape with relatively few low energy minima with funnel-like character. The choice of a sequence that fits well into one of these predetermined structures facilitates rapid and cooperative folding. Our model calculations show that this novel phase facilitates the formation of an efficient route for sequence design starting from random peptides.Comment: 7 pages, 4 figures, to appear in J. Stat. Phy

A mechanism for morphogen-controlled domain growth

Many developmental systems are organised via the action of graded distributions of morphogens. In the Drosophila wing disc, for example, recent experimental evidence has shown that graded expression of the morphogen Dpp controls cell proliferation and hence disc growth. Our goal is to explore a simple model for regulation of wing growth via the Dpp gradient: we use a system of reaction-diffusion equations to model the dynamics of Dpp and its receptor Tkv, with advection arising as a result of the flow generated by cell proliferation. We analyse the model both numerically and analytically, showing that uniform domain growth across the disc produces an exponentially growing wing disc

Model-Based Security Testing

Security testing aims at validating software system requirements related to security properties like confidentiality, integrity, authentication, authorization, availability, and non-repudiation. Although security testing techniques are available for many years, there has been little approaches that allow for specification of test cases at a higher level of abstraction, for enabling guidance on test identification and specification as well as for automated test generation. Model-based security testing (MBST) is a relatively new field and especially dedicated to the systematic and efficient specification and documentation of security test objectives, security test cases and test suites, as well as to their automated or semi-automated generation. In particular, the combination of security modelling and test generation approaches is still a challenge in research and of high interest for industrial applications. MBST includes e.g. security functional testing, model-based fuzzing, risk- and threat-oriented testing, and the usage of security test patterns. This paper provides a survey on MBST techniques and the related models as well as samples of new methods and tools that are under development in the European ITEA2-project DIAMONDS.Comment: In Proceedings MBT 2012, arXiv:1202.582

Sweet taste preference in binge-eating disorder: A preliminary investigation

Research suggests that individuals with high liking for sweets are at increased risk for binge eating, which has been minimally investigated in individuals with binge-eating disorder (BED). Forty-one adults (85% female, 83% white) with binge eating concerns completed a sweet taste test and measures of eating disorder behaviors and food cravings. A subset of participants with BED completed an oral glucose tolerance test (OGTT; N = 21) and a 24-hour dietary recall (N = 26). Regression models were used to compare highest sweet preferers (HSP [N = 18]) to other sweet preferers (OSP [N = 23]) and were used to assess associations between sweet taste preference and outcome variables. Effect sizes (ηp2) for differences between HSP and OSP ranged from small (≤ 0.01) to large (≥ 0.24); group differences were statistically nonsignificant except for 24-hour caloric intake (ηp2 = 0.16, p = 0.04), protein intake (ηp2 = 0.16, p = 0.04), and insulin sensitivity index (ηp2 = 0.24, p = 0.04), which were higher in HSP, and postprandial insulin, which was smaller in HSP (ηp2 = 0.27, p = 0.03). Continuous analyses replicated postprandial insulin response. Compared with OSP, HSP reported numerically higher binge-eating frequency (ηp2 = 0.04), over-eating frequency (ηp2 = 0.06), and carbohydrate intake (ηp2 = 0.14), and they exhibited numerically smaller postprandial glucose AUC (ηp2 = 0.16). Sweet taste preference may have implications for glucose regulation, binge-eating frequency, and nutrient intake in BED

PAM50 molecular intrinsic subtypes in the nurses' health Study cohorts

Background: Modified median and subgroup-specific gene subtypes by PAM50 and IHC surrogates improved to fair centering are two essential preprocessing methods to assign when Luminal subtypes were grouped together. Using the breast cancer molecular subtypes by PAM50. We evaluated the modified median method, our study consisted of 46% PAM50 subtypes derived from both methods in a subset of Luminal A, 18% Luminal B, 14% HER2-enriched, 15% Nurses' Health Study (NHS) and NHSII participants; correlat-Basal-like, and 8% Normal-like subtypes; 53% of tumor-ed tumor subtypes by PAM50 with IHC surrogates; and adjacent tissues were Normal-like. Women with the Basal-characterized the PAM50 subtype distribution, proliferation like subtype had a higher rate of relapse within 5 years. scores, and risk of relapse with proliferation and tumor size HER2-enriched subtypes had poorer outcomes prior to weighted (ROR-PT) scores in the NHS/NHSII. 1999. Methods: PAM50 subtypes, proliferation scores, and Conclusions: Either preprocessing method may be uti-ROR-PT scores were calculated for 882 invasive breast tumors lized to derive PAM50 subtypes for future studies. The and 695 histologically normal tumor-adjacent tissues. Cox majority of NHS/NHSII tumor and tumor-adjacent tissues proportional hazards models evaluated the relationship were classified as Luminal A and Normal-like, respectively. between PAM50 subtypes or ROR-PT scores/groups with Impact: Preprocessing methods are important for the recurrence-free survival (RFS) or distant RFS. accurate assignment of PAM50 subtypes. These data provide Results: PAM50 subtypes were highly comparable evidence that either preprocessing method can be used in between the two methods. The agreement between tumor epidemiologic studies

Reproductive and Appetite Hormones and Bulimic Symptoms during Midlife

Eating disorders and related symptoms occur during midlife; however, little is known about their aetiology. It has been hypothesised that perimenopause represents a window of vulnerability for the development or exacerbation of eating disorder symptomatology because, like puberty, perimenopause is a period of reproductive hormone change. We compared symptoms of bulimia nervosa (bulimic symptomatology) assessed via mean scores on a self-report questionnaire in premenopausal and perimenopausal women. We also examined the association between hormone concentrations (reproductive/appetite) and bulimic symptomatology. No mean differences in bulimic symptomatology were observed between premenopause and perimenopause. However, there was a significant positive association between leptin and binge eating. Although no significant associations between reproductive hormones and bulimic symptomatology were observed, additional research is needed to provide definitive information. It is essential to learn more about the aetiology of eating disorders and related symptomatology across the lifespan in order to develop age-relevant treatment and prevention programs