bluuebunny/crossref_metadata_2025 huggingface dataset:
R5 and X4 HIV envelopes induce distinct gene expression profiles in primary peripheral blood mononuclear cells
Authors: Cicala Claudia , Arthos James , Martinelli Elena , Censoplano Nina , Cruz Catherine C. , Chung Eva , Selig Sara M. , Van Ryk Donald , Yang Jun , Jagannatha Shyla , Chun Tae Wook , Ren Ping , Lempicki Richard A. , Fauci Anthony S.
Published: February 2006

HIV envelope binds to and signals through its primary cellular receptor, CD4, and through a coreceptor, either CC chemokine receptor 5 (CCR5) or CXC chemokine receptor 4 (CXCR4). Here, we evaluate the response of peripheral blood mononuclear cells to a panel of genetically diverse R5 and X4 envelope proteins. Modulation of gene expression was evaluated by using oligonucleotide microarrays. Activation of transcription factors was evaluated by using an array of oligonucleotides encoding transcription factor binding sites. Responses were strongly influenced by coreceptor specificity. Treatment of cells from CCR5Δ32 homozygous donors with glycoprotein (gp)120 derived from an R5 virus demonstrated that the majority of responses elicited by R5 envelopes required engagement of CCR5. R5 envelopes, to a greater extent than X4 envelopes, induced the expression of genes belonging to mitogen-activated protein kinase signal transduction pathways and genes regulating the cell cycle. A number of genes induced by R5, but not X4, envelopes were also up-regulated in the resting CD4+T cell population of HIV-infected individuals. These results suggest that R5 envelope facilitates replication of HIV in the pool of resting CD4+T cells. Additionally, signaling by R5 gp120 may facilitate the transmission of R5 viruses by inducing a permissive environment for HIV replication.
Neuroprotection by pharmacologic blockade of the GAPDH death cascade
Authors: Hara Makoto R. , Thomas Bobby , Cascio Matthew B. , Bae Byoung-Il , Hester Lynda D. , Dawson Valina L. , Dawson Ted M. , Sawa Akira , Snyder Solomon H.
Published: February 2006

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) participates in a cell death cascade wherein a variety of stimuli activate nitric oxide (NO) synthases with NO nitrosylating GAPDH, conferring on it the ability to bind to Siah, an E3-ubiquitin-ligase, whose nuclear localization signal enables the GAPDH/Siah protein complex to translocate to the nucleus where degradation of Siah targets elicits cell death.R-(−)-Deprenyl (deprenyl) ameliorates the progression of disability in early Parkinson’s disease and also has neuroprotective actions. We show that deprenyl and a related agent, TCH346, in subnanomolar concentrations, preventS-nitrosylation of GAPDH, the binding of GAPDH to Siah, and nuclear translocation of GAPDH. In mice treated with the dopamine neuronal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), low doses of deprenyl prevent binding of GAPDH and Siah1 in the dopamine-enriched corpus striatum.
Sodium channel genes and the evolution of diversity in communication signals of electric fishes: Convergent molecular evolution
Authors: Zakon Harold H. , Lu Ying , Zwickl Derrick J. , Hillis David M.
Published: February 2006

We investigated whether the evolution of electric organs and electric signal diversity in two independently evolved lineages of electric fishes was accompanied by convergent changes on the molecular level. We found that a sodium channel gene (Na
v
1.4a) that is expressed in muscle in nonelectric fishes has lost its expression in muscle and is expressed instead in the evolutionarily novel electric organ in both lineages of electric fishes. This gene appears to be evolving under positive selection in both lineages, facilitated by its restricted expression in the electric organ. This view is reinforced by the lack of evidence for selection on this gene in one electric species in which expression of this gene is retained in muscle. Amino acid replacements occur convergently in domains that influence channel inactivation, a key trait for shaping electric communication signals. Some amino acid replacements occur at or adjacent to sites at which disease-causing mutations have been mapped in human sodium channel genes, emphasizing that these replacements occur in functionally important domains. Selection appears to have acted on the final step in channel inactivation, but complementarily on the inactivation “ball” in one lineage, and its receptor site in the other lineage. Thus, changes in the expression and sequence of the same gene are associated with the independent evolution of signal complexity.
Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants
Authors: Sieving Paul A. , Caruso Rafael C. , Tao Weng , Coleman Hanna R. , Thompson Darby J. S. , Fullmer Keri R. , Bush Ronald A.
Published: February 2006

Neurotrophic factors are agents with a promising ability to retard progression of neurodegenerative diseases and are effective in slowing photoreceptor degeneration in animal models of retinitis pigmentosa. Here we report a human clinical trial of a neurotrophic factor for retinal neurodegeneration. In this Phase I safety trial, human ciliary neurotrophic factor (CNTF) was delivered by cells transfected with the human
CNTF
gene and sequestered within capsules that were surgically implanted into the vitreous of the eye. The outer membrane of the encapsulated cell implant is semipermeable to allow CNTF to reach the retina. Ten participants received CNTF implants in one eye. When the implants were removed after 6 months, they contained viable cells with minimal cell loss and gave CNTF output at levels previously shown to be therapeutic for retinal degeneration in
rcd1
dogs. Although the trial was not powered to form a judgment as to clinical efficacy, of seven eyes for which visual acuity could be tracked by conventional reading charts, three eyes reached and maintained improved acuities of 10–15 letters, equivalent to two- to three-line improvement on standard Snellen acuity charts. A surgically related choroidal detachment in one eye resulted in a transient acuity decrease that resolved with conservative management. This Phase I trial indicated that CNTF is safe for the human retina even with severely compromised photoreceptors. The approach to delivering therapeutic proteins to degenerating retinas using encapsulated cell implants may have application beyond disease caused by genetic mutations.
A DEAD-box protein alone promotes group II intron splicing and reverse splicing by acting as an RNA chaperone
Authors: Mohr Sabine , Matsuura Manabu , Perlman Philip S. , Lambowitz Alan M.
Published: February 2006

Group II intron RNAs self-splice
in vitro
but only at high salt and/or Mg
2+
concentrations and have been thought to require proteins to stabilize their active structure for efficient splicing
in vivo
. Here, we show that a DEAD-box protein, CYT-19, can by itself promote the splicing and reverse splicing of the yeast aI5γ and bI1 group II introns under near-physiological conditions by acting as an ATP-dependent RNA chaperone, whose continued presence is not required after RNA folding. Our results suggest that the folding of some group II introns may be limited by kinetic traps and that their active structures, once formed, do not require proteins or high Mg
2+
concentrations for structural stabilization. Thus, during evolution, group II introns could have spliced and transposed by reverse splicing by using ubiquitous RNA chaperones before acquiring more specific protein partners to promote their splicing and mobility. More generally, our results provide additional evidence for the widespread role of RNA chaperones in folding cellular RNAs.
Structures of eukaryotic ribonucleotide reductase I provide insights into dNTP regulation
Authors: Xu Hai , Faber Catherine , Uchiki Tomoaki , Fairman James W. , Racca Joseph , Dealwis Chris
Published: March 2006

Ribonucleotide reductase catalyzes a crucial step in
de novo
DNA synthesis and is allosterically controlled by relative levels of dNTPs to maintain a balanced pool of deoxynucleoside triphosphates in the cell. In eukaryotes, the enzyme comprises a heterooligomer of α
2
and β
2
subunits. The α subunit, Rnr1, contains catalytic and regulatory sites. Here, we report the only x-ray structures of the eukaryotic α subunit of ribonucleotide reductase from
Saccharomyces cerevisiae
. The structures of the apo-, AMPPNP only-, AMPPNP–CDP-, AMPPNP–UDP-, dGTP–ADP- and TTP–GDP-bound complexes give insight into substrate and effector binding and specificity cross-talk. These are Class I structures with the only fully ordered catalytic sites, including loop 2, a stretch of polypeptide that spans specificity and catalytic sites, conferring specificity. Binding of specificity effector rearranges loop 2; in our structures, this rearrangement moves P294, a residue unique to eukaryotes, out of the catalytic site, accommodating substrate binding. Substrate binding further rearranges loop 2. Cross-talk, by which effector binding regulates substrate preference, occurs largely through R293 and Q288 of loop 2, which are analogous to residues in
Thermotoga maritima
that mediate cross-talk. However loop-2 conformations and residue–substrate interactions differ substantially between yeast and
T. maritima
. In most effector–substrate complexes, water molecules help mediate substrate–loop 2 interactions. Finally, the substrate ribose binds with its 3′ hydroxyl closer than its 2′ hydroxyl to C218 of the catalytic redox pair. We also see a conserved water molecule at the catalytic site in all our structures, near the ribose 2′ hydroxyl.
Repair of DNA–polypeptide crosslinks by human excision nuclease
Authors: Reardon Joyce T. , Sancar Aziz
Published: March 2006

DNA–protein crosslinks are relatively common DNA lesions that form during the physiological processing of DNA by replication and recombination proteins, by side reactions of base excision repair enzymes, and by cellular exposure to bifunctional DNA-damaging agents such as platinum compounds. The mechanism by which pathological DNA–protein crosslinks are repaired in humans is not known. In this study, we investigated the mechanism of recognition and repair of protein–DNA and oligopeptide–DNA crosslinks by the human excision nuclease. Under our assay conditions, the human nucleotide excision repair system did not remove a 16-kDa protein crosslinked to DNA at a detectable level. However, 4- and 12-aa-long oligopeptides crosslinked to the DNA backbone were recognized by some of the damage recognition factors of the human excision nuclease with moderate selectivity and were excised from DNA at relatively efficient rates. Our data suggest that, if coupled with proteolytic degradation of the crosslinked protein, the human excision nuclease may be the major enzyme system for eliminating protein–DNA crosslinks from the genome.
Circadian time-keeping during early stages of development
Authors: Ziv Limor , Gothilf Yoav
Published: March 2006

The zebrafish pineal gland is a photoreceptive organ containing an intrinsic central circadian oscillator, which drives daily rhythms of gene expression and the melatonin hormonal signal. Here we investigated the effect of light, given at early developmental stages before pineal gland formation, on the pineal circadian oscillator. Embryos that were exposed to light at 0–6, 10–13, or 10–16 h after fertilization exhibited clock-controlled rhythms of arylalkylamine-
N
-acetyltransferase (
zfaanat2
) mRNA in the pineal gland during the third and fourth day of development. This rhythm was absent in embryos that were placed in continuous dark within 2 h after fertilization (before blastula stage). Differences in the phases of these rhythms indicate that they are determined by the time of illumination. Light treatments at these stages also caused a transient increase in
period2
mRNA levels, and the development of
zfaanat2
mRNA rhythm was abolished by PERIOD2 knock-down. These results indicate that light exposure at early developmental stages, and light-induced expression of period2, are both required for setting the phase of the circadian clock. The 24-h rhythm is then maintained throughout rapid proliferation and, remarkably, differentiation.
A contribution towards simplifying area-wide tsetse surveys using medium resolution meteorological satellite data
Authors: Hendrickx G. , Napala A. , Slingenbergh J.H.W. , De Deken R. , Rogers D.J.
Published: March 2006

A raster or grid-based Geographic Information System with data on tsetse, trypanosomiasis, animal production, agriculture and land use has recently been developed in Togo. The area-wide sampling of tsetse fly, aided by satellite imagery, is the subject of two separate papers. This paper on a first paper, published in this journal, describing the generation of digital tsetse distribution and abundance maps and how these accord with the local climatic and agro-ecological setting. Such maps when combined with data on the disease, the hosts and their owners, should contribute the knowledge of the spatial epidemiology of trypanosomiasis and assist planning of integrated control operations. Here we address the problem of generating tsetse distribution and abundance maps from remotely sensed data, using a restricted amount of field data. Different discriminant models have been applied using contemporary tsetse data and remotely sensed, low resolution data acquired from the National Oceanographic and Atmospheric Administration (NOAA) and Meteosat platforms. The results confirm the potential of satellite data application and multivariate for the prediction of the tsetse distribution and abundance. This opens up new avenues because satellite predictions and field data may be combined to strengthen and/or substitute one another. The analysis shows how the strategic incorporation of satellite imagery may minimize field of data. Field surveys may be modified and conducted in two stages, first concentrating on the expected fly distribution limits and thereafter on fly abundance. The study also shows that when applying satellite data, care should be taken in selecting the optimal number of predictor because this number varies with the amount of training data for predicting abundance and on the homogeneity of the distribution limits for predicting fly presence. Finally, it is suggested that in addition to the use of contemporary training data and predictor variables, training predicted data sets should refer to the same eco-geographic zone.
Descriptions of the Anopheles (Cellia) farauti complex of sibling species (Diptera: Culicidae) in Australia
Authors: Schmidt E.R. , Foley D.H. , Hartel G.F. , Williams G.M. , Bryan J.H.
Published: March 2006

Descriptions of the three sibling species of the Anopheles farauti complex in Australia, A. farauti Laveran (formerly A. farauti No. 1), A. hinesorum Schmidt sp.n. (formerly A. farauti No. 2) and A. torresiensis Schmidt sp.n. (formerly A. farauti No. 3) are provided. These species form a part of the punctulatus group, which contains the major malaria vectors in the southwest Pacific. Morphological markers are described for adult females, fourth instar larvae and pupae which identify most specimens, and are in keys.
Larval diet affects number of femoral ‘brush’ scales in male Helicoverpa punctigera moths (Lepidoptera: Noctuidae)
Authors: Nurindah  , Walter G.H. , Tiongson R.L.
Published: March 2006

Males of Helicoverpa punctigera (Wallengren) show considerable variation in the number of femoral scales on the prothoracic legs. Such intraspecific variation in adult morphology could indicate the presence of undetected sibling species, or it may be related to larval diet. Helicoverpa punctigera is polyphagous, and different host plant species are likely to represent diets of different quality. Femoral lengths and the numbers of femoral scales on the prothoracic legs were therefore determined from: (i) individuals that had been collected as larvae from various host in the field; and (ii) individuals that had been laboratory-reared, in split-family tests, on different diets, namely cotton, lucerne, sowthistle and artificial diet. Host plant species (and therefore presumably diet quality) influenced femoral length of H. punctigera males perhaps in conjunction with this, the number of femoral scales on the fore leg. The rearing experiment indicated, in addition, that the effect of host plant quality varies with larval stage, and that the pattern of this variation across the immature stages is dependent on host plant species. recorded variation in the morphology of field-collected H. punctigera males is therefore most readily explained as a consequence of different individuals developing (at least for most of their larval life) on different host plant species, with diet quality varying significantly species. The relevance of these results for insect developmental studies and evolutionary interpretations of host relationships is outlined.
Effects of added fruits and vegetables on dietary intakes and body weight in Scottish adults
Authors: Whybrow Stephen , Harrison Claire L.S. , Mayer Claus , Stubbs R. James
Published: February 2006

An increased consumption of fruits and vegetables (F&V) has been suggested as a way to limit, or even lower, energy and fat intakes. The present study examined the effects of incorporating F&V supplements into the diets of adults who reported consuming <240g (three portions) of F&V per d on energy and fat intakes, and change in body weight, over 8 weeks using a randomised parallel design. Thirty-four males and twenty-eight females (age 42·6 (sd 11·1) years, BMI 23·7 (sd 2·7) kg/m2) were each provided with supplements of 0, 300 or 600g F&V per d. Food, nutrient and energy intakes were measured before, during and at the end of the supplementation period using 7 d weighed records. Mean daily energy intakes were not different among the three groups before (P=0·151) or during the supplementation periods (P=0·407), although changes in energy intakes over the study period tended to be more positive with increasing amounts of F&V supplements (P=0·078). There was no difference in changes of body weights during the study (P=0·242). Carbohydrate (P<0·001), sugar (P<0·001), fibre (P<0·001) and weight of food consumed (P=0·022) increased in the treatment groups. There were no significant differences, or changes, in fat intakes among the three groups. Consumption of mandatory F&V supplements for 8 weeks produced beneficial changes in diet composition, but did not result in lower reported energy or fat intakes, and did not result in loss of body weight.
Effect of dietary quercetin and sphingomyelin on intestinal nutrient absorption and animal growth
Authors: Barrenetxe J. , Aranguren P. , Grijalba A. , Martínez-Peñuela J.M. , Marzo F. , Urdaneta E.
Published: February 2006

Research on cancer and other conditions has shown flavonoids and sphingolipids to be food components capable of exerting chemoprotective action. Nevertheless, little is known about their effects on healthy individuals and their potential usefulness as therapeutic agents. The present study examined the possible action of a dietary flavonoid, quercetin, and a sphingolipid, sphingomyelin, as functional foods in healthy animals. In particular, the effect on animal growth of supplementing a conventional diet with one or other of these substances (0·5% quercetin and 0·05% sphingomyelin) was considered. Possible action affecting intestinal physiology was also analysed by measuring the uptake of sugar and dipeptide, mediated by the Na+-dependent sugar transporter SGLT1 and the dipeptide Na+/H+exchanger PEPT1 respectively, and the activity of related intestinal enzymes such as sucrase, maltase and aminopeptidase N. Both substances seemed to modify small intestinal activity in healthy mice, altering intestinal enzymatic activity and nutrient uptake. These effects observed in the small intestine did not impair normal development of the animals, as no differences in serum biochemical parameters or in organ and body weights were found. The findings should help in elucidating the mechanisms of action of these food components with a view to their possible use in the prevention of certain pathological conditions.
Health and nutrition education in primary schools in Crete: 10 years' follow-up of serum lipids, physical activity and macronutrient intake
Authors: Manios Yannis , Kafatos Anthony ,   the Preventive Medicine and Nutrition Clinic University of Crete Research Team
Published: February 2006

The current study is a 4-year follow-up after the 6-year-long health and nutrition intervention programme applied in the primary schools of Crete. The aim of the current work was to identify whether the benefits obtained in certain health indices at the end of the intervention period were also present 4 years later. From a representative population of 441 pupils (250 from the intervention schools and 191 from the control schools), biochemical, dietary and physical activity data were obtained at baseline, at the end of the intervention period and after intervention (academic years 1992–1993, 1997–1998 and 2001–2002, respectively). The findings of the current study revealed that the favourable changes in serum lipids observed at the end of the intervention period were maintained from baseline to after intervention for total cholesterol (−24·3 (SE 1·65)V. −9·70 (SE 2·03) mg/dl;P=0·001), LDL-cholesterol (−18·6 (SE 1·41)V. −2·49 (SE 1·75) mg/dl;P<0·001), HDL-cholesterol (−8·34 (SE 0·75)V. −9·60 (SE 1·10) mg/dl;P=0·014) and total cholesterol:HDL-cholestrol ratio (0·31 (SE 0·06)V. 0·04 (SE 0·05);P=0·001). Similar favourable changes for the intervention group were observed in leisure-time physical activities (38·3 (SE 11·7)V. −13·2 (SE 10·9) min/week;P=0·038) and BMI (6·05 (SE 0·18)V. 6·67 (SE 0·21) kg/m2;P=0·014), whereas no changes were observed in the fitness and dietary indices examined. The findings of the current study are encouraging, indicating maintenance of the favourable changes observed in serum lipids, BMI and physical activity 4 years after the programme had ended
The efficacy of ferrous bisglycinate and electrolytic iron as fortificants in bread in iron-deficient school children
Authors: van Stuijvenberg Martha E. , Smuts Cornelius M. , Wolmarans Petronella , Lombard Carl J. , Dhansay Muhammad A.
Published: February 2006

Food fortification is an important long-term strategy for addressing micronutrient deficiencies. Finding the ideal Fe fortification compound, however, remains a challenge. In the present study the effect of ferrous bisglycinate as fortificant in brown bread was compared with that of electrolytic Fe among Fe-deficient school children in a randomised controlled trial. Children (n160), aged 6–11 years, with serum ferritin <20μg/l, were randomly assigned to one of three treatment categories: (i) standard unfortified bread; (ii) bread with electrolytic Fe as fortificant; and (iii) bread with ferrous bisglycinate as fortificant. Each child received four slices of bread (120g) on school days, which supplied an average of 3·66mg elemental Fe per intervention day for 137d (2·52mg/d for 75d and 5·04mg/d for 62d) over a period of 7·5 months. Hb, serum ferritin, serum Fe and transferrin saturation were measured at baseline and at the end of the intervention. Significant treatment effects were observed for Hb (P=0·013), serum Fe (P=0·041) and transferrin saturation (P=0·042) in the ferrous bisglycinate group, but not in the electrolytic Fe group. There were no significant intervention effects for serum ferritin in either treatment group. Overall, ferrous bisglycinate as Fe fortificant in brown bread performed better than electrolytic Fe in a group of Fe-deficient school children over a period of 7·5 months.
Towards the advancement of the Mediterranean food cultures
Authors: Dernini Sandro
Published: February 2006

The Forum on Mediterranean Food Cultures has the purpose to foster an interdisciplinary dialogue to acknowledge the underestimated role of the Mediterranean diet and of the Mediterranean food cultures for an effective sustainable development in the Mediterranean. It is addressed towards the achievement of food security and a broader nutritional well-being in the entire Mediterranean area. The Forum uses a creative approach for the development of community-based programmes to manage the emerging trend of childhood overweight and obesity, as well as to reduce the increasing erosion of the Mediterranean food cultural heritage.
The Mediterranean diet in a world context
Authors: Alexandratos Nikos
Published: February 2006

Objective

To put the debate on the Mediterranean diet in context by highlighting historical and prospective changes in the level and composition of food consumption in the world and key Mediterranean countries.

Design

Data from FAO's food balance sheets are used to illustrate historical evolution. Projections to 2030 are presented from FAO's recent and ongoing work on exploring world food and agriculture futures.

Setting

International.

Results and conclusions

Many developing countries are undergoing diet transitions bringing them closer to the diets prevalent in the richer countries, i.e. with more energy-dense foods. There follows an increase in the incidence of diet-related non-communicable diseases, which are superimposed on the health problems related to undernutrition that still afflict them. In parallel, many low-income countries are making little progress towards raising food consumption levels necessary for good nutrition and food security. Wider adoption of food consumption patterns akin to those of the Mediterranean diet hold promise of contributing to mitigate adverse effects of such diet transitions. However, the evolution of food consumption in the Mediterranean countries themselves is not encouraging, as these countries have also followed the trend towards higher shares of energy-dense foods. Possible policy responses to these problems include measures to raise awareness of the benefits of healthier diets and/or to change relative food prices in favour of such diets (by taxing fattening foods) or, at the extreme, making individuals who follow ‘bad’ diets, and thus are prone to associated diseases, bear a higher part of the consequent costs borne by the public health systems (tax fat people).
Qualitative methods to evaluate Mediterranean diet in adults
Authors: Gerber Mariette
Published: February 2006

Objective

To fulfil a comprehensive approach to consumption, which is necessary to characterise food habits and their relationship to diseases, using a diet quality index (DQI) developed for a Mediterranean region (Med-DQI).

Setting

A cross-sectional nutritional survey provided the data for the construction of the DQI.

Subjects

A representative sample made up of 964 subjects from a French Mediterranean area, Hérault département.

Methods

Foods such as olive oil, fish and cereals were used instead of nutrients to build up scores which constructed the Med-DQI. Biochemical analysis identified biomarkers used to validate the Med-DQI. Correspondence factorial analysis illustrated the characteristics of subjects with different scores given by the Med-DQI.

Results

The subjects could be satisfactorily classified by the Med-DQI. The oldest age, less educated, overweight, manual workers, living in a rural area and male classes showed a better Med-DQI. For women, they were also from the oldest age class, but some of them were from the upper social class, with an ideal BMI and lived by the Mediterranean shore. A composite biomarker index, based on plasma carotene and vitamin E levels and the percentage of EPA and DHA in erythrocytes membranes, can identify subjects with good and poor Med-DQI.

Conclusion

Med-DQI G is a good instrument to identify groups at risk with regard to nutritional quality. Subjects with α+β-carotene levels > 1 mg/l, vitamin E > 30 mg/l, EPA > 0.65% and DHA > 4% of fatty acids in erythrocytes are likely to have a good diet.
Evaluating adherence to recommended diets in adults: the Alternate Healthy Eating Index
Authors: McCullough Marjorie L , Willett Walter C
Published: February 2006

Objective

The Healthy Eating Index (HEI), designed to assess adherence to the Dietary Guidelines for Americans and the Food Guide Pyramid, was previously associated with only a small reduction in major chronic disease risk in US adult men and women. We assessed whether an alternate index would better predict risk.

Design

Dietary intake reported by men and women from two prospective cohorts was scored according to an a priori designed Alternate Healthy Eating Index (AHEI). In contrast with the original HEI, the AHEI distinguished quality within food groups and acknowledged health benefits of unsaturated oils. The score was then used to predict development of CVD, cancer or other causes of death in the same population previously tested.

Subjects

67 271 women from the Nurses' Health Study and 38 615 men from the Health Professionals' Follow-up Study.

Results

Men and women with AHEI scores in the top vs. bottom quintile had a significant 20% and 11% reduction in overall major chronic disease, respectively. Reductions were stronger for CVD risk in men (RR = 0.61, 95% CI 0.49–0.75) and women (RR = 0.72, 95% CI 0.60–0.86). The score did not predict cancer risk.

Conclusions

The AHEI was twice as strong at predicting major chronic disease and CVD risk compared to the original HEI, suggesting that major chronic disease risk can be further reduced with more comprehensive and detailed dietary guidance.
Food and nutrition policies: what's being done in Turkey
Authors: Pekcan Gülden
Published: February 2006

Objective

The aim of the present paper is to describe the development of the National Plan of Action for Food and Nutrition (NPAFN) for Turkey.

Design

Access to a safe and healthy variety of food, a fundamental human right, was stressed by the International Conference on Nutrition and by the World Food Summit. In the International Conference on Nutrition in December 1992, one major commitment was the preparation of NPAFN. The NPAFN for Turkey was designed according to this commitment.

Setting

Turkey.

Results

To this end, under the coordination of the State Planning Organization, a Working Committee Report for National Food and Nutrition Strategy of Turkey was prepared and published, with the participation of different sectors. The goal of the prepared National Food and Nutrition Strategy for Turkey is to protect and promote health through and healthy nutrition and reduce the burden of diseases, while contributing to socio-economic development and a sustainable food security.

Conclusion

In Turkey the NPAFN was developed and implementation has initiated. Nearly for all the actions, related projects are being developed.
Olive oil consumption and risk of breast cancer in the Canary Islands: a population-based case–control study
Authors: García-Segovia Purificación , Sánchez-Villegas Almudena , Doreste Jorge , Santana Francisco , Serra-Majem Lluís
Published: February 2006

Back ground

Breast cancer mortality and incidence rates in the Canary Islands, and particularly in Gran Canaria, are higher than those in the rest of Spain.

Objectives and design

A case–control study was designed to assess the role of differential fatty acid intakes and olive oil consumption on breast cancer risk in the Canary Islands. The study was conducted between 1999 and 2001, including a total of 755 women: 291 incident cases with confirmed breast cancer and 464 controls randomly selected from the Canary Island Nutrition Survey (ENCA). A semi-quantitative food-frequency questionnaire was completed and potential confounders were adjusted using unconditional logistic regression.

Results

Compared to the first quintile of intake, the highest quintile of monounsaturated fat intake was significantly related to a lower risk of breast cancer (odds ratio = 0.52; 95% CI 0.30–0.92). Regarding olive oil, the odds ratio for women in the three upper quintiles of consumption (≥8.8 g/day) was 0.27 (95% CI 0.17–0.42).

Conclusion

Our results support the protective role of olive oil consumption on breast cancer among Canaries women.
A core approach to practice‐based evidence: A brief history of the origins and applications of the CORE‐OM and CORE System
Authors: Barkham Michael , Mellor-Clark John , Connell Janice , Cahill Jane
Published: March 2006

This article reviews the development of the CORE‐OM and CORE System from 1995 to 2005 in the context of the need to measure, monitor, and manage the delivery of counselling and the psychological therapies in service of providing best quality care for clients. The origins and philosophy of these tools are summarised and practical aspects of how to use them in routine service settings are set out, including an easy to use look‐up table of differing ways of presenting CORE‐OM scores and their associated meaning. The wider family of CORE outcome measures is briefly outlined to show the relationship between the various versions and how each is designed for a specific purpose. These outcome tools are set within the broader context of the CORE System. In turn, the CORE‐OM and CORE System are placed within the paradigm of practice‐based evidence and examples are provided of how these tools have been applied in routine as well as more traditional evaluative settings.

The aim of the present article is two‐fold. The first aim is to provide a background to the origins and development of the CORE‐OM and its role as part of the broader‐based CORE System during the period 1995 to 2005. The second aim is to consider the applications of both the CORE‐OM and CORE System within the context of the developing paradigm of practice‐based evidence up to 2005.
Resourcing a CORE Network to develop a National Research Database to help enhance psychological therapy and counselling service provision
Authors: Mellor-Clark John , Curtis Jenkins Alex , Evans Richard , Mothersole Geoff , McInnes Barry
Published: March 2006

This article profiles the development of an evolving common CORE methodology related to the paradigm of quality evaluation. It profiles the five defining characteristics that currently help to inform that common methodology. The first of these characteristics is the use of CORE‐PC to help store, organise, filter, report and undertake performance appraisals using CORE System data. The second is the role of preparatory training to help overcome the common experience of service performance anxiety in services adopting CORE‐PC. The third characteristic is the use of a common reporting framework that generates internal performance indicators by which relative service and individual practitioner performance can be contrasted. Fourth is the co‐development and use of national service performance indicators created by the voluntary donation of anonymised, aggregated data. The fifth and final characteristic informing the shared methodology is the development of CORE Networks to support the interpretation and utilisation of benchmarks for enhancing service quality. The conclusions acknowledge the relative youth of both the activity and learning, but suggests that the common methodology used by the CORE Network has considerable potential to help identify, share and develop excellence in psychological therapy and counselling services.
Recovery and improvement benchmarks for counselling and the psychological therapies in routine primary care
Authors: Mullin Tracy , Barkham Michael , Mothersole Geoff , Bewick Bridgette M. , Kinder Andrew
Published: March 2006

Measuring the outcomes of counselling and the psychological therapies has become an increasingly important component in managing individual services within routine primary care settings. Outcome data collected from multiple settings can be combined to establish benchmarks against which services and practitioners can make comparisons. To achieve this, we used a large data set comprising >11,000 clients from 32 primary care NHS services who completed the CORE‐OM at both intake and end of counselling or therapy. We used four categories relating to components of reliable and clinically significant change (recovery, improvement, no reliable change, and reliable deterioration) to establish service benchmarks. However, we focussed primarily on those relating to recovery and improvement. Importantly, in addition to service benchmarks, we calculated benchmarks for individual practitioners taking into account a simple adjustment for case mix. The resulting benchmarks and their meaning are discussed.
Reflections on benchmarking NHS primary care psychological therapies and counselling
Authors: Mellor-Clark John , Barkham Michael , Mothersole Geoff , McInnes Barry , Evans Richard
Published: March 2006

The concluding paper in this series provides brief reflections from a range of key individuals involved in the development and interpretation of CORE benchmarks for NHS primary care psychological therapy and counselling services. Michael Barkham firstly reflects on some of the research challenges facing the use of benchmarks derived from practice‐based evidence, before acknowledging the potential for such data to help bridge the research‐practice gap as we learn the best use of it. Geoff Mothersole considers similar challenges in using real world data, and explores some of the challenges that managers face in using benchmarks for improved service management practice. Barry McInnes increases the magnification in his reflective focus and looks at the juxtaposition of national guideline recommendations from evidence‐based practice in contrast to those introduced by the growing practice evidence‐base suggesting differential therapist effectiveness. The first of two final strategic reflective perspectives includes Richard Evans's summary of some of the hidden lessons from the benchmarking endeavour to‐date, before my own personal concluding summary looking at lessons learned for the on‐going strategic development of enhanced support for routine quality evaluation.
Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks
Authors: Kruhlak Michael J. , Celeste Arkady , Dellaire Graham , Fernandez-Capetillo Oscar , Müller Waltraud G. , McNally James G. , Bazett-Jones David P. , Nussenzweig André
Published: March 2006

The repair of DNA double-strand breaks (DSBs) is facilitated by the phosphorylation of H2AX, which organizes DNA damage signaling and chromatin remodeling complexes in the vicinity of the lesion (Pilch, D.R., O.A. Sedelnikova, C. Redon, A. Celeste, A. Nussenzweig, and W.M. Bonner. 2003. Biochem. Cell Biol. 81:123–129; Morrison, A.J., and X. Shen. 2005. Cell Cycle. 4:568–571; van Attikum, H., and S.M. Gasser. 2005. Nat. Rev. Mol. Cell. Biol. 6:757–765). The disruption of DNA integrity induces an alteration of chromatin architecture that has been proposed to activate the DNA damage transducing kinase ataxia telangiectasia mutated (ATM; Bakkenist, C.J., and M.B. Kastan. 2003. Nature. 421:499–506). However, little is known about the physical properties of damaged chromatin. In this study, we use a photoactivatable version of GFP-tagged histone H2B to examine the mobility and structure of chromatin containing DSBs in living cells. We find that chromatin containing DSBs exhibits limited mobility but undergoes an energy-dependent local expansion immediately after DNA damage. The localized expansion observed in real time corresponds to a 30–40% reduction in the density of chromatin fibers in the vicinity of DSBs, as measured by energy-filtering transmission electron microscopy. The observed opening of chromatin occurs independently of H2AX and ATM. We propose that localized adenosine triphosphate–dependent decondensation of chromatin at DSBs establishes an accessible subnuclear environment that facilitates DNA damage signaling and repair.
Loss of the proapoptotic protein, Bim, breaks B cell anergy
Authors: Oliver Paula M. , Vass Tibor , Kappler John , Marrack Philippa
Published: March 2006

Although B cells that respond with high avidity to self-antigen are eliminated early in their development, many autoreactive B cells escape elimination and are tolerized later in their lives via anergy. Anergic B cells are unresponsive to antigen and die prematurely. It has been suggested that the proapoptotic protein, Bim, controls the fate of anergic B cells. To test this idea, mice lacking Bim were crossed with mice that express soluble hen egg lysozyme and whose B cells bear receptors specific for the protein. In Bim+/+ mice these B cells are anergic and die rapidly. If the mice lack Bim, however, the B cells live longer, are more mature, respond to antigen, and secrete anti–hen egg lysozyme antibodies. This break of tolerance is not due to expression of endogenous B cell receptors, nor is it dependent on T cells. Rather, it appears to be due to a reduced requirement for the cytokine BAFF. Normal B cells require BAFF both for differentiation and survival. Bim−/− B cells, on the other hand, require BAFF only for differentiation. Therefore, autoreactive B cells are allowed to survive if they lack Bim and thus accumulate sufficient signals from differentiating factors to drive their maturation and production of autoantibodies.
Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors
Authors: Kaneko Yoshikatsu , Nimmerjahn Falk , Madaio Michael P. , Ravetch Jeffrey V.
Published: March 2006

Introduction of heterologous anti–glomerular basement membrane antiserum (nephrotoxic serum, NTS) into presensitized mice triggers the production of IgG anti-NTS antibodies that are predominantly IgG2b and the glomerular deposition of pathogenic immune complexes, leading to accelerated renal disease. The pathology observed in this model is determined by the effector cell activation threshold that is established by the coexpression on infiltrating macrophages of the IgG2a/2b restricted activation receptor FcγRIV and its inhibitory receptor counterpart, FcγRIIB. Blocking FcγRIV with a specific monoclonal antibody thereby preventing IgG2b engagement or treatment with high dose intravenous γ-globulin (IVIG) to down-regulate FcγRIV while up-regulating FcγRIIB, protects mice from fatal disease. In the absence of FcγRIIB, IVIG is not protective; this indicates that reduced FcγRIV expression alone is insufficient to protect animals from pathogenic IgG2b immune complexes. These results establish the significance of specific IgG subclasses and their cognate FcγRs in renal disease.
Antibody isotype-specific engagement of Fcγ receptors regulates B lymphocyte depletion during CD20 immunotherapy
Authors: Hamaguchi Yasuhito , Xiu Yan , Komura Kazuhiro , Nimmerjahn Falk , Tedder Thomas F.
Published: March 2006

CD20 monoclonal antibody (mAb) immunotherapy is effective for lymphoma and autoimmune disease. In a mouse model of immunotherapy using mouse anti–mouse CD20 mAbs, the innate monocyte network depletes B cells through immunoglobulin (Ig)G Fc receptor (FcγR)-dependent pathways with a hierarchy of IgG2a/c>IgG1/IgG2b>IgG3. To understand the molecular basis for these CD20 mAb subclass differences, B cell depletion was assessed in mice deficient or blocked for stimulatory FcγRI, FcγRIII, FcγRIV, or FcR common γ chain, or inhibitory FcγRIIB. IgG1 CD20 mAbs induced B cell depletion through preferential, if not exclusive, interactions with low-affinity FcγRIII. IgG2b CD20 mAbs interacted preferentially with intermediate affinity FcγRIV. The potency of IgG2a/c CD20 mAbs resulted from FcγRIV interactions, with potential contributions from high-affinity FcγRI. Regardless, FcγRIV could mediate IgG2a/b/c CD20 mAb–induced depletion in the absence of FcγRI and FcγRIII. In contrast, inhibitory FcγRIIB deficiency significantly increased CD20 mAb–induced B cell depletion by enhancing monocyte function. Although FcγR-dependent pathways regulated B cell depletion from lymphoid tissues, both FcγR-dependent and -independent pathways contributed to mature bone marrow and circulating B cell clearance by CD20 mAbs. Thus, isotype-specific mAb interactions with distinct FcγRs contribute significantly to the effectiveness of CD20 mAbs in vivo, which may have important clinical implications for CD20 and other mAb-based therapies.
Structure and binding kinetics of three different human CD1d–α-galactosylceramide–specific T cell receptors
Authors: Gadola Stephan D. , Koch Michael , Marles-Wright Jon , Lissin Nikolai M. , Shepherd Dawn , Matulis Gediminas , Harlos Karl , Villiger Peter M. , Stuart David I. , Jakobsen Bent K. , Cerundolo Vincenzo , Jones E. Yvonne
Published: March 2006

Invariant human TCR Vα24-Jα18+/Vβ11+ NKT cells (iNKT) are restricted by CD1d–α-glycosylceramides. We analyzed crystal structures and binding characteristics for an iNKT TCR plus two CD1d–α-GalCer–specific Vβ11+ TCRs that use different TCR Vα chains. The results were similar to those previously reported for MHC–peptide-specific TCRs, illustrating the versatility of the TCR platform. Docking TCR and CD1d–α-GalCer structures provided plausible insights into their interaction. The model supports a diagonal orientation of TCR on CD1d and suggests that complementarity determining region (CDR)3α, CDR3β, and CDR1β interact with ligands presented by CD1d, whereas CDR2β binds to the CD1d α1 helix. This docking provides an explanation for the dominant usage of Vβ11 and Vβ8.2 chains by human and mouse iNKT cells, respectively, for recognition of CD1d–α-GalCer.
Lineage specification and plasticity in CD19− early B cell precursors
Authors: Rumfelt Lynn L. , Zhou Yan , Rowley Benjamin M. , Shinton Susan A. , Hardy Richard R.
Published: February 2006

We describe here three CD19− B cell precursor populations in mouse bone marrow identified using 12-color flow cytometry. Cell transfer experiments indicate lineage potentials consistent with multilineage progenitor (MLP), common lymphoid progenitor (CLP), and B lineage–restricted pre-pro–B (Fr. A), respectively. However, single cell in vitro assays reveal lineage plasticity: lymphoid/myeloid lineage potential for CLP and B/T lineage potential for Fr. A. Despite myeloid potential, recombination activating gene 2 reporter activation is first detected at low levels in most MLP cells, with 95% of CLPs showing 10-fold increased levels. Furthermore, single cell analysis shows that half of CLP and 90% of Fr. A cells contain heavy chain DJ rearrangements. These data, together with expression profiles of lineage-specific genes, demonstrate progressive acquisition of B lineage potential and support an asynchronous view of early B cell development, in which B lineage specification initiates in the MLP/CLP stage, whereas myeloid potential is not lost until the pre-pro–B (Fr. A) stage, and B/T lymphoid plasticity persists until the CD19+ pro–B stage. Thus, MLP, CLP, and Fr. A represent progressively B lineage–specified stages in development, before the CD19+ B lineage–committed pro–B stage.