bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection of cervical keratinocytes containing integrated HPV16 associates with episome loss and an endogenous antiviral response
Authors: Pett Mark R. , Herdman M. Trent , Palmer Roger D. , Yeo Giles S. H. , Shivji Mahmud K. , Stanley Margaret A. , Coleman Nicholas
Published: February 2006

Integration of high-risk human papillomavirus (HRHPV) into the host genome is a key event in cervical neoplastic progression. Integration is associated with deregulated expression of the viral oncogenes E6 and E7 and acquisition of a selective growth advantage for cells containing integrants. Overexpression of the viral transcriptional regulator E2 from heterologous promoters has an inhibitory effect on transcription from integrated HRHPV. Therefore, we hypothesized that loss of E2-expressing episomes from cells in which integration had previously occurred would be required for such cells to gain a growth advantage. Using the unique W12 model of cervical squamous carcinogenesis, we show that cells containing integrated HPV16 reproducibly emerged during long-term culture when there had been a rapid fall in episome numbers. During the period of emergence, it is possible to isolate single-cell clones containing an intracellular mixture of the integrant being selected and episomes at reduced load. The lower level of E2 expression seen in such cells is associated with partial inhibition of transcription from the HPV16 integrant. Full deregulation is not observed until complete loss of E2-expressing episomes occurs. Microarray analysis showed that episome loss was closely associated with endogenous activation of antiviral response genes that are also inducible by the type I IFN pathway. Taken together, our results indicate that episome loss, associated with induction of antiviral response genes, is a key event in the spontaneous selection of cervical keratinocytes containing integrated HPV16. We conclude that cervical carcinogenesis requires not only HRHPV integration, but also loss of inhibitory episomes.
Changes produced by bound tryptophan in the ribosome peptidyl transferase center in response to TnaC, a nascent leader peptide
Authors: Cruz-Vera Luis Rogelio , Gong Ming , Yanofsky Charles
Published: February 2006

Studies
in vitro
have established that free tryptophan induces
tna
operon expression by binding to the ribosome that has just completed synthesis of TnaC-tRNA
Pro
, the peptidyl-tRNA precursor of the leader peptide of this operon. Tryptophan acts by inhibiting Release Factor 2-mediated cleavage of this peptidyl-tRNA at the
tnaC
stop codon. Here we analyze the ribosomal location of free tryptophan, the changes it produces in the ribosome, and the role of the nascent TnaC-tRNA
Pro
peptide in facilitating tryptophan binding and induction. The positional changes of 23S rRNA nucleotides that occur during induction were detected by using methylation protection and binding/competition assays. The ribosome-TnaC-tRNA
Pro
complexes analyzed were formed
in vitro
; they contained either wild-type TnaC-tRNA
Pro
or its nonfunctional substitute, TnaC(W12R)-tRNA
Pro
. Upon comparing these two peptidyl-tRNA-ribosome complexes, free tryptophan was found to block methylation of nucleotide A2572 of wild-type ribosome-TnaC-tRNA
Pro
complexes but not of ribosome-TnaC(W12R)-tRNA
Pro
complexes. Nucleotide A2572 is in the ribosomal peptidyl transferase center. Tryptophanol, a noninducing competitor of tryptophan, was ineffective in blocking A2572 methylation; however, it did reverse the protective effect of tryptophan. Free tryptophan inhibited puromycin cleavage of TnaC-tRNA
Pro
; it also inhibited binding of the antibiotic sparsomycin. These effects were not observed with TnaC(W12R)-tRNA
Pro
mutant complexes. These findings establish that Trp-12 of TnaC-tRNA
Pro
is required for introducing specific changes in the peptidyl transferase center of the ribosome that activate free tryptophan binding, resulting in peptidyl transferase inhibition. Free tryptophan appears to act at or near the binding sites of several antibiotics in the peptidyl transferase center.
Selective irradiation of the vascular endothelium has no effect on the survival of murine intestinal crypt stem cells
Authors: Schuller Bradley W. , Binns Peter J. , Riley Kent J. , Ma Ling , Hawthorne M. Frederick , Coderre Jeffrey A.
Published: February 2006

The possible role of vascular endothelial cell damage in the loss of intestinal crypt stem cells and the subsequent development of the gastrointestinal (GI) syndrome is addressed. Mice received whole-body epithermal neutron irradiation at a dose rate of 0.57 ± 0.04 Gy·min
−1
. An additional dose was selectively targeted to endothelial cells from the short-ranged (5–9 μm) particles released from neutron capture reactions in
10
B confined to the blood by incorporation into liposomes 70–90 nm in diameter. Different liposome formulations produced 45 ± 7 or 118 ± 12 μg/g
10
B in the blood at the time of neutron irradiation, which resulted in total absorbed dose rates in the endothelial cells of 1.08 ± 0.09 or 1.90 ± 0.16 Gy·min
−1
, respectively. At 3.5 d after irradiation, the intestinal crypt microcolony assay showed that the 2- to 3-fold increased doses to the microvasculature, relative to the nonspecific whole-body neutron beam doses, caused no additional crypt stem cell loss beyond that produced by the neutron beam alone. The threshold dose for death from the GI syndrome after neutron-beam-only irradiation was 9.0 ± 0.6 Gy. There were no deaths from the GI syndrome, despite calculated absorbed doses to endothelial cells as high as 27.7 Gy, in the groups that received neutron beam doses of <9.0 Gy with boronated liposomes in the blood. These data indicate that endothelial cell damage is not causative in the loss of intestinal crypt stem cells and the eventual development of the GI syndrome.
Genomic anatomy of the Tyrp1 (brown) deletion complex
Authors: Smyth Ian M. , Wilming Laurens , Lee Angela W. , Taylor Martin S. , Gautier Phillipe , Barlow Karen , Wallis Justine , Martin Sancha , Glithero Rebecca , Phillimore Ben , Pelan Sarah , Andrew Rob , Holt Karen , Taylor Ruth , McLaren Stuart , Burton John , Bailey Jonathon , Sims Sarah , Squares Jan , Plumb Bob , Joy Ann , Gibson Richard , Gilbert James , Hart Elizabeth , Laird Gavin , Loveland Jane , Mudge Jonathan , Steward Charlie , Swarbreck David , Harrow Jennifer , North Philip , Leaves Nicholas , Greystrong John , Coppola Maria , Manjunath Shilpa , Campbell Mark , Smith Mark , Strachan Gregory , Tofts Calli , Boal Esther , Cobley Victoria , Hunter Giselle , Kimberley Christopher , Thomas Daniel , Cave-Berry Lee , Weston Paul , Botcherby Marc R. M. , White Sharon , Edgar Ruth , Cross Sally H. , Irvani Marjan , Hummerich Holger , Simpson Eleanor H. , Johnson Dabney , Hunsicker Patricia R. , Little Peter F. R. , Hubbard Tim , Campbell R. Duncan , Rogers Jane , Jackson Ian J.
Published: February 2006

Chromosome deletions in the mouse have proven invaluable in the dissection of gene function. The
brown
deletion complex comprises >28 independent genome rearrangements, which have been used to identify several functional loci on chromosome 4 required for normal embryonic and postnatal development. We have constructed a 172-bacterial artificial chromosome contig that spans this 22-megabase (Mb) interval and have produced a contiguous, finished, and manually annotated sequence from these clones. The deletion complex is strikingly gene-poor, containing only 52 protein-coding genes (of which only 39 are supported by human homologues) and has several further notable genomic features, including several segments of >1 Mb, apparently devoid of a coding sequence. We have used sequence polymorphisms to finely map the deletion breakpoints and identify strong candidate genes for the known phenotypes that map to this region, including three lethal loci (
l4Rn1
,
l4Rn2
, and
l4Rn3
) and the fitness mutant
brown-associated fitness
(
baf
). We have also characterized misexpression of the basonuclin homologue,
Bnc2
, associated with the inversion-mediated coat color mutant
white-based brown
(
B
w
). This study provides a molecular insight into the basis of several characterized mouse mutants, which will allow further dissection of this region by targeted or chemical mutagenesis.
Induction of tolerance in arthritogenic B cells with receptors of differing affinity for self-antigen
Authors: Huang Haochu , Kearney John F. , Grusby Michael J. , Benoist Christophe , Mathis Diane
Published: February 2006

Multiple mechanisms of tolerance induction limit autoimmunity, but their relative contribution for lymphocytes recognizing self-antigens of differing availability is incompletely understood. The mechanisms applied to arthritogenic B cells expressing antigen-specific B cell receptors (BCRs) with different affinities for glucose-6-phosphate isomerase (GPI) were examined in the corresponding Ig gene knock-in mice. This ubiquitously expressed and blood-borne enzyme is the target autoantigen in the K/BxN model of inflammatory arthritis and perhaps in some humans with arthritis. Negative selection of B cells expressing high-affinity anti-GPI specificities, whose surface receptors were occupied by GPI, operated mainly at the transitional B cell stages in the spleen, preventing their final differentiation and entry into follicular areas. Receptor editing contributed to the purging of cells displaying anti-GPI BCRs, and significant numbers of autoreactive cells escaped through expression of an additional Ig light (L) chain, accumulating gradually in lymphoid organs. In contrast, low-affinity anti-GPI B cells, whose surface receptors did not carry GPI, matured normally. The “escaped” dual-L-chain cells and the “ignored” low-affinity cells are the likely precursors of cells that produce pathogenic autoantibodies once T cell help is provided. These studies portray, in a single system, the range of tolerance mechanisms applied to potentially pathogenic B cells, and serve as a base for dissecting where T cell help intervenes and where therapeutic agents impinge.
Electron trap for DNA-bound repair enzymes: A strategy for DNA-mediated signaling
Authors: Yavin Eylon , Stemp Eric D. A. , O’Shea Valerie L. , David Sheila S. , Barton Jacqueline K.
Published: February 2006

Despite a low copy number within the cell, base excision repair (BER) enzymes readily detect DNA base lesions and mismatches. These enzymes also contain [Fe4S4] clusters, yet a redox role for these iron cofactors had been unclear. Here, we provide evidence that BER proteins may use DNA-mediated redox chemistry as part of a signaling mechanism to detect base lesions. By using chemically modified bases, we show electron trapping on DNA in solution with bound BER enzymes by electron paramagnetic resonance (EPR) spectroscopy. We demonstrate electron transfer from two BER proteins, Endonuclease III (EndoIII) and MutY, to modified bases in DNA containing oxidized nitroxyl radical EPR probes. Electron trapping requires that the modified base is coupled to the DNA π-stack, and trapping efficiency is increased when a noncleavable MutY substrate analogue is located distally to the trap. These results are consistent with DNA binding leading to the activation of the repair proteins toward oxidation. Significantly, these results support a mechanism for DNA repair that involves DNA-mediated charge transport.
Mucosal and systemic adjuvant activity of alphavirus replicon particles
Authors: Thompson Joseph M. , Whitmore Alan C. , Konopka Jennifer L. , Collier Martha L. , Richmond Erin M. B. , Davis Nancy L. , Staats Herman F. , Johnston Robert E.
Published: February 2006

Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon particles (VRP). Moreover, coinoculation of null VRP (not expressing any transgene) with inactivated influenza virions, or ovalbumin, resulted in a significant increase in antigen-specific systemic IgG and fecal IgA antibodies, compared with antigen alone. Pretreatment of VRP with UV light largely abrogated this adjuvant effect. These results demonstrate that alphavirus replicon particles possess intrinsic systemic and mucosal adjuvant activity and suggest that VRP RNA replication is the trigger for this activity. We feel that these observations and the continued experimentation they stimulate will ultimately define the specific components of an alternative pathway for the induction of mucosal immunity, and if the activity is evident in humans, will enable new possibilities for safe and inexpensive subunit and inactivated vaccines.
Brain cholesterol turnover required for geranylgeraniol production and learning in mice
Authors: Kotti Tiina J. , Ramirez Denise M. O. , Pfeiffer Brad E. , Huber Kimberly M. , Russell David W.
Published: February 2006

The mevalonate pathway produces cholesterol and nonsterol isoprenoids, such as geranylgeraniol. In the brain, a fraction of cholesterol is metabolized in neurons by the enzyme cholesterol 24-hydroxylase, and this depletion activates the mevalonate pathway. Brains from mice lacking 24-hydroxylase excrete cholesterol more slowly, and the tissue compensates by suppressing the mevalonate pathway. Here we report that this suppression causes a defect in learning. 24-Hydroxylase knockout mice exhibit severe deficiencies in spatial, associative, and motor learning, and in hippocampal long-term potentiation (LTP). Acute treatment of wild-type hippocampal slices with an inhibitor of the mevalonate pathway (a statin) also impairs LTP. The effects of statin treatment and genetic elimination of 24-hydroxylase on LTP are reversed by a 20-min treatment with geranylgeraniol but not by cholesterol. We conclude that cholesterol turnover in brain activates the mevalonate pathway and that a constant production of geranylgeraniol in a small subset of neurons is required for LTP and learning.
Porcine circovirus diseases
Authors: Segalés Joaquim , Allan Gordon M. , Domingo Mariano
Published: February 2006

Porcine circovirus type 2 (PCV2) is a member of the familyCircoviridae, a recently established virus family composed of small, non-enveloped viruses, with a circular, single-stranded DNA genome. PCV2, which is found all over the world in the domestic pig and probably the wild boar, has been recently associated with a number of disease syndromes, which have been collectively named porcine circovirus diseases (PCVD). Postweaning multisystemic wasting syndrome (PMWS), porcine dermatitis and nephropathy syndrome (PDNS) and reproductive disorders are the most relevant ones. Among them, only PMWS is considered to have a severe impact on domestic swine production. PMWS mainly affects nursery and/or fattening pigs; wasting is considered the most representative clinical sign in this disease. Diagnosis of this disease is confirmed by histopathological examination of lymphoid tissues and detection of a moderate to high amount of PCV2 in damaged tissues. Since PMWS is considered a multifactorial disease in which other factors in addition to PCV2 are needed in most cases to trigger the clinical disease, effective control measures have focused on the understanding of the co-factors involved in individual farms and the control or elimination of these triggers. PDNS, an immuno-complex disease characterized by fibrino-necrotizing glomerulonephritis and systemic necrotizing vasculitis, has been linked to PCV2, but a definitive proof of this association is still lacking. PCV2-associated reproductive disease seems to occur very sporadically under field conditions, but it has been characterized by late-term abortions and stillbirths, extensive fibrosing and/or necrotizing myocarditis in fetuses and the presence of moderate to high amounts of PCV2 in these lesions. Taking into account that scientific information on PCV2 and its associated diseases has been markedly expanded in the last 8 years, the objective of this review is to summarize the current state of knowledge of the most relevant aspects of PCV2 biology and PCVD.
Passive and active components of neonatal innate immune defenses
Authors: Firth Matthew A. , Shewen Patricia E. , Hodgins Douglas C.
Published: February 2006

Innate immune defenses are crucial for survival in the first days and weeks of life. At birth, newborns are confronted with a vast array of potentially pathogenic microorganisms that were not encountered in utero. At this age, cellular components of the adaptive immune system are in a naïve state and are slow to respond. Antibodies received from the dam are essential for defense, but represent a finite and dwindling resource. Innate components of the immune system detect pathogen-associated molecular patterns (PAMPs) on microorganisms (and their products) by means of pattern-recognition receptors (PRRs). Soluble mediators of the innate system such as complement proteins, pentraxins, collectins, ficolins, defensins, lactoferrin, lysozyme etc. can bind to structures on pathogens, leading to agglutination, interference with receptor binding, opsonization, neutralization, direct membrane damage and recruitment of additional soluble and cellular elements through inflammation. Cell-associated receptors such as the Toll-like receptors (TLRs) can activate cells and coordinate responses (both innate and adaptive). In this paper, accumulated knowledge of the receptors, soluble and cellular elements that contribute to innate defenses of young animals is reviewed. Research interest in this area has been intermittent, and the literature varies in quantity and quality. It is hoped that documentation of the limitations of our knowledge base will lead to more extensive and enlightening studies.
Gastrointestinal nematode infection in sheep – a review of the alternatives to anthelmintics in parasite control
Authors: Sayers G. , Sweeney T.
Published: February 2006

Efforts to curb production losses caused by nematode parasitism in sheep have led to the development of a number of control methods to complement or replace anthelmintics. The need for alternative control measures stems from the emergence of anthelmintic-resistant parasitic nematodes with reports of multi-class resistance to these drugs now emerging. A number of these control methods such as predacious microfungi, protein supplementation, plant extracts in feed and vaccines have demonstrated potential to control infection but require development and examination under natural conditions. Breeding for natural resistance to nematode infection has already shown success in controlling the disease under natural conditions. Selection for resistance is currently based on fecal egg count measurements but identification of genetic indicators of resistance will provide a more efficient method of selection. Current quantitative trait loci for nematode resistance include the MHC genes, interferon gamma gene, IgE gene and microsatellites on chromosome 1, 5 and 6. This paper reviews the current alternatives to anthelmintics to control infection, with an emphasis on breeding for host resistance and identification of genetic indicators of resistance.
Proliferative enteropathy: a global enteric disease of pigs caused byLawsonia intracellularis
Authors: Kroll Jeremy J. , Roof Michael B. , Hoffman Lorraine J. , Dickson James S. , Hank Harris D. L.
Published: February 2006

Proliferative enteropathy (PE; ileitis) is a common intestinal disease affecting susceptible pigs raised under various management systems around the world. Major developments in the understanding of PE and its causative agent,Lawsonia intracellularis, have occurred that have led to advances in the detection of this disease and methods to control and prevent it. Diagnostic tools that have improved overall detection and early onset of PE in pigs include various serological and molecular-based assays. Histological tests such as immunohistochemistry continue to be the gold standard in confirmingLawsonia-specific lesions in pigspost mortem. Despite extreme difficulties in isolatingL. intracellularis, innovations in the cultivation and the development of pure culture challenge models, have opened doors to better characterization of the pathogenesis of PE throughin vivoandin vitro L. intracellularis–host interactions. Advancements in molecular research such as the genetic sequencing of the entireLawsoniagenome have provided ways to identify various immunogens, metabolic pathways and methods for understanding the epidemiology of this organism. The determinations of immunological responsiveness in pigs to virulent and attenuated isolates ofL. intracellularisand identification of various immunogens have led to progress in vaccine development.
Plant-made vaccines: biotechnology and immunology in animal health
Authors: Rice J. , Ainley W. M. , Shewen P.
Published: February 2006

The use of plants as production systems for vaccine antigens has been actively investigated over the last 15 years. The original research focused on the value of this expression system for oral delivery based on the hypothesis that plant-expressed antigens would be more stable within the digestive tract and would allow for the use of the oral route of administration to stimulate a mucosal immune response. However, while first conceived for utility via the oral route, plant-made antigens have also been studied as classical immunogens delivered via a needle to model animal systems. Antigens have been expressed in a number of whole plant and cell culture systems. Several alternative expression platforms have been developed to increase expression of antigens or to elicit preferred immunological responses. The biotechnological advances in plant expression and the immunological testing of these antigens will be reviewed in this paper focusing primarily on diseases of livestock and companion animals.
Listeria monocytogenes: silage, sandwiches and science
Authors: Czuprynski Charles J.
Published: February 2006

Listeria monocytogenesis amongst the most intriguing and well studied of the pathogenic bacteria. However, the understanding and perspective one has ofL. monocytogenesdepends to a large extent on the microbiological issues with which one is faced as a part of your professional duties. The focus of the veterinary clinician or investigator is likely to be foremost on the neurologic (circling disease) and reproductive diseasesL. monocytogenescauses. To the food microbiologist, the principal concern is to prevent introduction ofL. monocytogenesinto food products, or to identify its presence and prevent its multiplication to numbers of organisms that are likely to pose a substantial risk to humans who ingest the product. To the cellular immunologist, listeriosis represents a robust murine model that helped to elucidate many important concepts in innate and adaptive immunity, andL. monocytogenesis a potential vector for delivery of novel vaccines. To the student of molecular pathogenesis,L. monocytogenesis a powerful and well-characterized model organism for studying the cellular microbiology of an intracellular pathogen. In this brief overview, I will attempt to highlight some of the classical observations, and contemporary insights, onL. monocytogenesand listeriosis, and integrate these perspectives into a common framework. By so doing, I hope to provide those with one perspective on listeriosis with an appreciation of the broad array of problems and issues faced by those who focus on some other aspect ofL. monocytogenesand its pathogenesis.
A reduced protein diet induces stearoyl-CoA desaturase protein expression in pig muscle but not in subcutaneous adipose tissue: relationship with intramuscular lipid formation
Authors: Doran O. , Moule S. K. , Teye G. A. , Whittington F. M. , Hallett K. G. , Wood J. D.
Published: February 2006

A reduced protein diet (RPD) is known to increase the level of intramuscular lipid in pig meat with a smaller effect on the amount of subcutaneous adipose tissue. This might be due to tissue-specific activation of the expression of lipogenic enzymes by the RPD. The present study investigated the effect of a RPD, containing palm kernel oil, soyabean oil or palm oil on the activity and expression of one of the major lipogenic enzymes, stearoyl-CoA desaturase (SCD) and on the level of total lipids and the fatty acid composition of muscle and subcutaneous adipose tissue in pigs. The RPD significantly increased SCD protein expression and activity in muscle but not in subcutaneous adipose tissue. The level of MUFA and total fatty acids in muscle was also elevated when the RPD was fed, with only small changes in subcutaneous adipose tissue. A positive significant correlation between SCD protein expression and total fatty acids in muscle was found. The results suggest that an increase in intramuscular but not subcutaneous adipose tissue fatty acids under the influence of a RPD is related to tissue-specific activation of SCD expression. It is suggested that the SCD isoform spectra in pig subcutaneous adipose tissue and muscle might be different.
Accelerometry combined with heart rate telemetry in the assessment of total energy expenditure
Authors: Johansson H. Patrik , Rossander-Hulthén Lena , Slinde Frode , Ekblom Björn
Published: February 2006

The aim of the present study was: (1) to develop a new method for total energy expenditure (TEE) assessment, using accelerometry (ACC) and heart rate (HR) telemetry in combination; (2) to validate the new method against the criterion measure (DLW) and to compare with two of the most common methods, FLEX-HR and ACC alone. In the first part of the study VO2, HR and ACC counts were measured in twenty-seven subjects during walking and running on a treadmill. Considering the advantages and disadvantages of the HR and ACC methods an analysis model was developed, using ACC at intensities of low and medium levels and HR at higher intensities. During periods of inactivity, RMR is used. A formula for determining TEE from ACC, HR and RMR was developed: TEE =1·1×(EQHR×TTHR+EQACC1×TTACC1+EQACC2×TTACC2+RMR×TTRMR). In the validation part of the study a sub-sample of eight subjects wore an accelerometer, HR was logged and TEE was measured for 14d with the DLW method. Analysis of the Bland–Altman plots with 95% CI indicates that there are no significant differences in TEE estimated with HR–ACC and ACC alone compared with TEE measured with DLW. It is concluded that the HR–ACC combination as well as ACC alone has potential as a method for assessment of TEE during free-living activities as compared with DLW
Vegetable lipid sourcesin vitrobiosyntheis of triacylglycerols and phospholipids in the intestine of sea bream(Sparus aurata)
Authors: Caballero Maria José , Gallardo Germ´an , Robaina Lidia , Montero Daniel , Fernández Antonio , Izquierdo Marisol
Published: February 2006

Despite the good growth performance of several fish species when dietary fish oil is partly replaced by vegetable oils, recent studies have reported several types of intestinal morphological alterations in cultured fish fed high contents of vegetable lipid sources. However, the physiological process implied in these morphological changes have not been clarified yet, since alterations in the physiological mechanisms involved in the different processes of lipid absorption could be responsible for such gut morphological features. The objective of the present study was to investigate the activities of reacylation pathways in fish, the glycerol-3-phosphate and the monoacylglycerol pathways, in order to clarify the intestinal triacylglycerol (TAG) and phospholipid biosynthesis to better understand the morphological alterations observed in the intestine of fish fed vegetable oils. Intestinal microsomes of sea bream fed different lipid sources (fish, soyabean and rapeseed oils) at three different inclusion levels were isolated and incubated with l-[14C(U)]glycerol-3-phosphate and [1-14C]palmitoyl CoA. The results showed that in this fish species the glycerol-3-phosphate pathway is mainly involved in phospholipid synthesis, whereas TAG synthesis is mainly mediated by the monoacylglycerol pathway. Feeding with rapeseed oil reduced the reacylation activity in both pathways, explaining the high accumulation of lipid droplets in the supranuclear portion of the intestinal epithelium, whereas soyabean oil enhanced phosphatidylcholine synthesis, being associated with the increase in VLDL found in previous studies.
The influence of birth weight and genetic factors on lipid levels: a study in adult twins
Authors: Tuya Chuluuntulga , Mutch William J. , Haggarty Paul , Campbell Doris M. , Cumming Alastair , Kelly Kevin , Broom Iain , McNeill Geraldine
Published: February 2006

Twins can be used to investigate the biological basis for observed associations between birth weight and later disease risk, as they experiencein uterogrowth restriction compared with singletons, which can differ in magnitude within twin pairs despite partial or total genetic identity. In the present study, sixty monozygotic and seventy-one dizygotic same-sex twin pairs aged 19–50 years and eighty-nine singleton controls matched for age, gestational age, sex, maternal age and parity were recruited from an obstetric database. Associations between fasting lipid levels and birth weight were assessed by linear regression with adjustment for possible confounding factors. Twins were significantly lighter at birth but were not significantly different in adult height, weight or lipid levels from the singleton controls. There was a significant inverse association between birth weight and both total and LDL-cholesterol levels among singleton controls (−0·53mmol/l per kg (95% CI −0·97, −0·09),P=0·02 and −0·39mmol/l per kg (95% CI −0·76, −0·02),P=0·04, respectively), but there was no significant association between birth weight and lipid levels in either unpaired or within-pair analysis of twins. The results suggest that thein uterogrowth restriction and early catch-up growth experienced by twins does not increase the risk of an atherogenic lipid profile in adult life.
Low folic acid status and its association with anaemia in urban adolescent girls and women of childbearing age in Sri Lanka
Authors: Thoradeniya Tharanga , Wickremasinghe Rajitha , Ramanayake Ramani , Atukorala Sunethra
Published: February 2006

Folic acid deficiency is implicated in the aetiology of nutritional anaemia and adverse pregnancy outcomes for the fetus. Data on folic acid status among adolescent girls and non-pregnant, non-lactating young women are limited. We assessed folic acid status in a random sample of 552 subjects (277 adolescent girls aged 15–18·9 years and 275 women aged 19–30 years) living in Colombo, Sri Lanka. The association of low folic acid status with anaemia was evaluated. Socio-economic, food intake and anthropometric data were obtained. Hb, serum folic acid, vitamin B12 and ferritin and plasma homocysteine concentrations were measured. Forty-three per cent of subjects studied had low serum folic acid concentrations (<3ng/ml) and 47/ had low Fe stores (serum ferritin <20μg/l). Overall prevalence of anaemia was 12·9%, and 43·9% of anaemic subjects had both low folic acid status and depleted Fe stores (serum ferritin <12μg/l). Both low folate status and depleted Fe stores were significantly associated with anaemia (odds ratio=2·32; 95% CI 1·34, 4·01 and odds ratio=5·98; 95% CI 3·36, 10·63, respectively). Serum folic acid concentration was associated (r=0·108, P=0·015) with folate intake as indicated by a computed folate index. Folate index was associated inversely with household size and positively with economic status and education level. In this study population low folic acid status, besides depleted Fe stores, was associated with anaemia. The high prevalence of low folic acid status observed highlights the need for nutrition education to improve intakes of folate, Fe and other micronutrients among adolescent girls and young women.
Sources of saturated fatty acids in Belgian adolescents' diet: implications for the development of food-based dietary guidelines
Authors: Matthys C. , De Henauw S. , Bellemans M. , De Maeyer M. , De Backer G.
Published: February 2006

The objectives of the present study are to describe the dietary sources of total fat and of saturated fatty acids (SFA) and to formulate food-based dietary guidelines for SFA in Belgian adolescents. A random sample of 13–18-year-old adolescents was drawn from secondary schools in the region of Ghent. A 7d estimated food record method was used to quantify nutrient and food intake. The average daily SFA intake is 4% above the recommended 10% of the total energy contribution. The most important contributors of SFA on food group level were ‘fats, oils and savoury sauces’, ‘meat and meat products’, ‘sugar, confectionery, sweet fillings and sauces’, ‘cheese’, ‘milk and milk products’ and ‘bread, rusk and breakfast rolls’. On food subgroup level ‘fresh meat’, ‘high-fat margarine’ and ‘high-fat cheese’ had the highest contribution to SFA intake in all adolescents. Adolescents with a low SFA intake (lowest tertile) were compared with adolescents with a high intake (highest tertile). In the lowest tertile the intake of total fat and MUFA was significantly lower than in the highest tertile, while the intake of total carbohydrates, mono- and disaccharides and complex carbohydrates was significantly higher. Overall, the high-fat cheese intake is significantly lower in the lowest tertile, while the fruit intake is higher. The present analysis shows that the nutritional profile of Belgian adolescents could be potentially improved by decreasing the portion sizes of fresh meat (in boys), high-fat margarine, high-fat cheese and reducing intake of commercially prepared baked goods and processed foods, including fast foods.
Polyunsaturated fatty acids and conjugated linoleic acid isomers in breast milk are associated with plasma non-esterified and erythrocyte membrane fatty acid composition in lactating women
Authors: Torres Alexandre G. , Ney Jacqueline G. , Meneses Flávia , Trugo Nádia M. F.
Published: February 2006

Maternal adipose tissue is a major contributor to breast milk long-chain fatty acids, probably through the pool of plasma NEFA. The fatty acid composition of the erythrocyte membrane (EM) is a biochemical index of the intake of fatty acids not synthesized endogenously and of PUFA and long-chain PUFA fatty acid status. The present study investigated the associations between breast milk fatty acid composition and the composition of plasma NEFA and of EM fatty acids with special reference to PUFA, long-chain PUFA and conjugated linoleic acid (CLA). The detailed fatty acid composition of mature breast milk was also reported. Thirty-three healthy, lactating Brazilian women donated milk samples; of these, twenty-four also donated blood samples in an observational cross-sectional study. Breast milk fatty acid composition presented several associations with NEFA and EM composition, which explained most (≥50%) of the variability of selected milk PUFA, long-chain PUFA and CLA. Milk CLA was associated with fatty acids that are markers of dairy fat intake in the diet, NEFA and EM. In general, breast milkn-3 fatty acids and CLA, but notn-6 fatty acids, were associated with EM composition, whereas both then-6 andn-3 fatty acids and CLA in milk were associated with NEFA composition, possibly owing to its role as a direct source of fatty acids for breast milk. These findings emphasize the contribution of the NEFA pool derived from the adipose tissue to the long-chain fatty acid composition of breast milk.
Asparagus adscendens(Shweta musali) stimulates insulin secretion, insulin action and inhibits starch digestion
Authors: Mathews Jacqueline N. , Flatt Peter R. , Abdel-Wahab Yasser H.
Published: February 2006

Diabetes mellitus is a complex metabolic disease characterised by glucose overproduction and under-utilisation. As the incidence of diabetes expands rapidly across the globe there is an urgent need to expand the range of effective treatments. Higher plants such asAsparagus adscendensprovide therapeutic opportunities and a rich source of potential antidiabetic agents. In the present study an aqueous extract ofAsparagus adscendenswas shown to induce a significant non-toxic 19–248% increase in glucose-dependent insulinotropic actions (P<0·001) in the clonal pancreatic β cell line, BRIN-BD11. In addition, the extract produced an 81% (P<0·0001) increase in glucose uptake in 3T3-L1 adipocytes.Asparagus adscendensalso produced a 21% (P<0·001) decrease in starch digestionin vitro. The present study has revealed the presence of insulinotropic, insulin-enhancing activity and inhibitory effects on starch digestion inAsparagus adscendens. The former actions are dependent on the active principle(s) in the plant being absorbed intact. Future work assessing its use as a dietary adjunct or as a source of active components may provide new opportunities for the treatment of diabetes
Calcium deficiency-induced secondary hyperparathyroidism and osteopenia are rapidly reversible with calcium supplementation in growing rabbit pups
Authors: Mehrotra Meenal , Gupta Sushil K. , Kumar Krishan , Awasthi Pradeep K. , Dubey Manoj , Pandey Chandra M. , Godbole Madan M.
Published: February 2006

The reversibility of osteopenia secondary to isolated Ca deficiency (CaDef) is still not clear. We studied the effect of severe CaDef on Ca homeostasis and bone accrual in a ‘hypercalcaemic’ animal, the rabbit, during the post-weaning period and its reversibility on Ca supplementation. Male Belgian 5-week-old rabbit pups were fed CaDef diet (0·026% Ca) for 10 weeks. As compared with those fed with a normal chow diet (0·45% Ca), CaDef pups developed significant hypocalcaemia (P<0·05), hypocalciuria (urinary Ca 76 (sem 12) V 17 (sem 1) mg/l;P<0·005), hypophosphataemia (serum inorganic P 100 (sem 6) V. 65 (sem 4) mg/l; P<0·005), secondary hyperparathyroidism (SHPT) (serum intact parathyroid hormone human equivalent 18·2 (sem 1·4) V. 125·0 (sem 4·5) pg/ml; P<0·001) and elevated serum calcitriol levels (34·0 (sem 3·9) V. 91·0 (sem 1·0) pg/ml; v<0·005). Elevated urinary C-terminal telopeptide of class I collagen (P<0·005) and total serum alkaline phosphatase (P<0·005) suggested increased bone turnover. There was a significantly lower gain in bone mineral density (BMD) and bone mineral content (BMC) in the whole body and lumbar spine in vivo, and various sub-regions of the femur and tibia in vitro.Supplementation of adequate Ca (0·45% Ca) after 15 weeks on the normal diet resulted in rapid catch-up growth, and resolution of SHPT. Rapid gain in various BMD and BMC parameters continued at 30 weeks of age, and both were comparable with those in rabbits on a normal diet. We conclude that Ca deficiency-induced SHPT and poor bone accrual in growing rabbit pups are rapidly reversible with Ca supplementation. The present study indicates that early intervention may be a more appropriate window period for human nutritional corrective measures.
Influence of an algal triacylglycerol containing docosahexaenoic acid (22:6n-3) and docosapentaenoic acid (22:5n-6) on cardiovascular risk factors in healthy men and women
Authors: Sanders Thomas A.B. , Gleason Kelly , Griffin Bruce , Miller George J.
Published: February 2006

The intake of long-chainn-3 PUFA, including DHA (22:6n-3), is associated with a reduced risk of CVD.Schizochytrium sp.are an important primary source of DHA in the marine food chain but they also provide substantial quantities of then-6 PUFA docosapentaenoic acidn-6; DPA). The effect of this oil on cardiovascular risk factors was evaluated using a double-blind randomised placebo-controlled parallel-design trial in thirty-nine men and forty women. Subjects received 4g oil/d for 4 weeks; the active treatment provided 1·5g DHA and 0·6g DPA. Active treatment increased plasma concentrations of arachidonic acid, adrenic acid, DPA and DHA by 21, 11, 11 and 88mg/l respectively and the proportions of DPA and DHA in erythrocyte phospholipids by 78 and 27% respectively. Serum total, LDL- and HDL-cholesterol increased by 0·33mmol/l (7·3%), 0·26mmol/l (10·4%) and 0·14mmol/l (9·0%) compared with placebo (allp≤0·001). Factor VII (FVII) coagulant activity increased by 12% following active treatment (P=0·006). There were no significant differences between treatments in LDL size, blood pressure, plasma glucose, serum C-reactive protein, plasma FVII antigen, FVII activated, fibrinogen, von Willebrand factor, tocopherol or carotenoid concentrations, plasminogen activator inhibitor-1, creatine kinase or troponin-I activities, haematology or liver function tests or self-reported adverse effects. Overall, the oil was well tolerated and did not adversely affect cardiovascular risk.
Phytosterol-mediated inhibition of intestinal cholesterol absorption is independent of ATP-binding cassette transporter A1
Authors: Calpe-Berdiel Laura , Escolà-Gil Joan Carles , Blanco-Vaca Francisco
Published: February 2006

An increased activity of ATP-binding cassette transporter (ABC) A1 has been proposed as a mechanism underlying the hypocholesterolaemic effect of phytosterols. In the present study, ABCA1-deficient mice (ABCA1−/− mice) were used to examine the involvement of the ABCA1 in the reduction of intestinal cholesterol absorption in response to a phytosterol-enriched diet. A decrease in intestinal cholesterol absorption of 39 and 35% was observed after phytosterol treatment in ABCA1+/+ mice and in ABCA1−/− mice, respectively. No statistically significant changes in plasma lipoprotein profile or in intestinal ABCG5, ABCG8 and Niemann-Pick C1-Like 1 gene expression levels were found when phytosterol-treated ABCA1−/− mice and untreated ABCA1−/− mice were compared. We conclude that phytosterol inhibition of cholesterol absorption in mice is independent of ABCA1
Yoghurt accelerates the recovery of defence mechanisms againstStreptococcus pneumoniaein protein-malnourished mice
Authors: Villena Julio , Racedo Silvia , Agüero Graciela , Alvarez Susana
Published: February 2006

Experiments studied the effect of yoghurt on the recovery of defence mechanisms againstStreptococcus pneumoniaerespiratory infection in malnourished mice. Weaned mice were malnourished with a protein-free diet (PFD) for 21d. Malnourished mice were made replete with a balanced diet (BD), yoghurt, or the BD with supplemental yoghurt (BD+Y) for 7, 14 or 21d. The normal control (NC) group was fed the BD whereas malnourished control (MC) mice consumed only the PFD. Mice were challenged with pneumococci at the end of each dietary treatment. MC mice showed increased susceptibility to pneumococcal infection. Blood leucocytes, phagocyte activity and serum and bronco-alveolar anti-pneumococcal IgG and IgA were significantly lower in the MC than in the NC group. Repletion of malnourished mice with the BD for 21d was necessary to obtain a response to infection similar to that of NC mice; however, administration of the BD+Y for 14d was enough to normalise the immune defence mechanisms. Histological examination of MC lungs showed progressive loss of alveolar architecture. Lung injuries were significantly less pronounced in NC mice. Mice treated with the BD+Y for 14d showed histological signs similar to the NC group. The present study showed that administration of yoghurt to malnourished mice induced an early recovery of the immunological parameters studied. Despite the uncertainties about the mechanisms involved and about the human relevance of the effects observed in animal models, the present study provides a strong rationale for the hypothesis that yoghurt consumption by malnourished hosts will accelerate the recovery of the immune mechanisms involved in the protection against respiratory infections
Protective effect of dietary long-chainn-3 polyunsaturated fatty acids on bone loss in gonad-intact middle-aged male rats
Authors: Shen Chwan-Li , Yeh James K. , Rasty Jahan , Li Yong , Watkins Bruce A.
Published: February 2006

This study evaluated the effect of a fat blend containing long-chain (LC)n-3 PUFA on bone mineral density (BMD) and bone metabolism in gonad-intact middle-aged male rats (12 months old,n28). Seven rats were killed on day 0 of dietary intervention to determine the baseline BMD. The remaining rats (seven per group) were fed a diet with one of the following dietary lipid treatments (g/kg diet): 167g safflower oil+33g menhaden oil (N6+N3 diet, control), 200g safflower oil (N6 diet, almost devoid of LCn-3 PUFA), or 190g menhaden oil+10g corn oil (N3 diet, rich in LCn-3 PUFA) for 20 weeks. After 20 weeks, all dietary treatment groups had a lower BMD compared with the baseline reference. However, rats fed the N3 diet had the highest bone mineral content and cortical+subcortical BMD compared with those fed the N6 and control N6+N3 diet. Compared with the control (N6+N3) group, rats fed the N3 diet had higher values for serum insulin-like growth factor-I, parathyroid hormone, 1, 25-(OH)2vitamin D3and bone-specific alkaline phosphatase activity, but lower bone NO production and urinary Ca, whereas rats fed the N6 diet had higher bone prostaglandin E2production and serum pyridinoline. These findings indicate a protective action of LCn-3 PUFA on ageing-induced bone loss in gonad-intact middle-aged male rats through a modulation of local factors and systemic calcitrophic hormones.
Duodenal flow and digestibility in fauna-free sheep and in sheep monofaunated with Entodinium caudatum or Polyplastron multivesiculatum
Authors: Ivan M. , Koenig K.M. , Morgavi D.P. , Rode L.M. , Newbold C.J. , Entz T.
Published: February 2006

Three groups of five rumen and duodenum cannulated fauna-free sheep were used in a 28d experiment. One group remained fauna-free, whereas the second (EN) and third (PP) groups, respectively, were inoculated intraruminally with the protozoan species Entodinium caudatum and Polyplastron multivesiculatum. Rumen fluid, duodenal digesta and faecal samples were collected during the last 12d. The flow of digesta to the duodenum was determined using Yb and Co as dual-phase markers. 15Nitrogen and phosphatidylcholine were used as markers to calculate the duodenal flow of bacterial and protozoal N, respectively. Results showed an increase (P<0·1) in the rumen concentration of NH3-N and total volatile fatty acids, and a decrease (P<0·05) in the duodenal flow of non-NH3-N and bacterial N in sheep with EN and PP monofaunas, compared with fauna-free sheep. There were no differences (P>0·05) in these variables between the two monofauna groups. Protozoal N accounted for 8% of the duodenal non-NH3-N flow in the EN-monofaunated sheep, whereas no such flow was detected in the PP-monofaunated sheep. Apparent rumen digestibility of organic matter, neutral detergent fibre and acid detergent fibre were similar (P>0·05) in the monofaunated groups of sheep, but rumen acid detergent fibre digestibility was higher (P<0·05) in the monofaunated than in the fauna-free groups. Experimental results suggested that, unlike EN, the PP monofauna might not contribute to the duodenal flow of microbial protein, whereas both monofaunas showed a virtually equal degree of predation on rumen bacteria.