bluuebunny/crossref_metadata_2025 huggingface dataset:
In the absence of Lgt, lipoproteins are shed from Streptococcus uberis independently of Lsp
Authors: Denham E. L. , Ward P. N. , Leigh J. A.
Published: December 2008

The role of lipoprotein diacylglyceryl transferase (Lgt) and lipoprotein signal peptidase (Lsp) responsible for processing lipoproteins was investigated inStreptococcus uberis, a common cause of bovine mastitis. In the absence of Lgt, three lipoproteins [MtuA (SUB0473), Hap (SUB1625) and an extracellular solute-binding protein (SUB0365)] were detected in extracellular locations. All were shown by Edman degradation analysis to be cleaved on the carboxy side of the LXXC lipobox. Detection of MtuA, a lipoprotein shown previously to be essential for infectivity and virulence, was used as a surrogate lipoprotein marker to locate and assess processing of lipoproteins. The absence of Lgt did not prevent location of MtuA to the cell membrane, its location in the wild-type strain but, in contrast to the situation with wild-type, did result in a widespread location of this protein. In the absence of both Lgt and Lsp, MtuA was similarly released from the bacterial cell. In such strains, however, the cell-associated MtuA represented the full-length gene product, indicating that Lsp was able to cleave non-lipidated (lipo)proteins but was not responsible for their release from this bacterium.
Differential metabolic activity by dental plaque bacteria in association with two preparations of MUC5B mucins in solution and in biofilms
Authors: Wickström Claes , Hamilton Ian R. , Svensäter Gunnel
Published: December 2008

Salivary mucin, MUC5B, is an oligomeric glycoprotein, heterogeneous in size and with a diverse repertoire of oligosaccharides, which differ in composition and charge. Since complex salivary glycoproteins are considered to be the major source of nutrients for the oral supragingival microbiota, the major aim of the current study was to determine whether different preparations of non-denatured MUC5B could be isolated exhibiting different biological properties in relation to the microflora associated with the surfaces of the oral cavity. Two preparations, solMUC5B and gelMUC5B, were isolated by density-gradient centrifugation and were shown to have different buoyant densities, carbohydrate content and surface-adsorbing characteristics. To ascertain differences in biological activity, the two mucin preparations, both in solution and adsorbed to a model surface, were incubated with freshly isolated dental plaque and assayed for metabolic (dehydrogenase) activity with the fluoresecent substrate CTC (5-cyano-2,3-ditolyl tetrazolium chloride). The plaque bacteria exhibited higher metabolism with the solMUC5B preparation in solution, with 79.4 % active plaque cells compared to the controls without mucin (9.6 %), while gelMUC5B showed 48.2 % active cells with the same plaque population. In contrast, the same mucins adhered to a surface elicited a significantly lower metabolic response, with surface-associated plaque cells showing only 12.1 % active cells with solMUC5B and 29.2 % with gelMUC5B. These results suggested that the metabolism by the plaque cells adsorbed to surface-associated mucins was downregulated compared to the same cells suspended in mucin solution. This was confirmed in an experiment where active dispersed plaque/solMUC5B suspensions were shown to lose significant metabolic activity (e.g. 74.9 to 19.3 %) when allowed to interact with gelMUC5B adsorbed to a surface. Clearly, the solMUC5B and gelMUC5B preparations exhibited different biological activity when assayed with freshly plaque bacteria in suspension and in a biofilm.
Role of calcium in acclimation of the cyanobacterium Synechococcus elongatus PCC 7942 to nitrogen starvation
Authors: Leganés Francisco , Forchhammer Karl , Fernández-Piñas Francisca
Published: December 2008

A Ca2+ signal is required for the process of heterocyst differentiation in the filamentous diazotrophic cyanobacterium Anabaena sp. PCC 7120. This paper presents evidence that a transient increase in intracellular free Ca2+ is also involved in acclimation to nitrogen starvation in the unicellular non-diazotrophic cyanobacterium Synechococcus elongatus PCC 7942. The Ca2+ transient was triggered in response to nitrogen step-down or the addition of 2-oxoglutarate (2-OG), or its analogues 2,2-difluoropentanedioic acid (DFPA) and 2-methylenepentanedioic acid (2-MPA), to cells growing with combined nitrogen, suggesting that an increase in intracellular 2-OG levels precedes the Ca2+ transient. The signalling protein PII and the transcriptional regulator NtcA appear to be needed to trigger the signal. Suppression of the Ca2+ transient by the intracellular Ca2+ chelator N,N′-[1,2-ethanediylbis(oxy-2,1-phenylene)]bis[N-[2-[(acetyloxy)methoxy]-2-oxoethyl]]-,bis[(acetyloxy)methyl] ester (BAPTA-AM) inhibited expression of the glnB and glnN genes, which are involved in acclimation to nitrogen starvation and transcriptionally activated by NtcA. BAPTA-AM treatment partially inhibited expression of the nblA gene, which is involved in phycobiliprotein degradation following nutrient starvation and is regulated by NtcA and NblR; in close agreement, BAPTA-AM treatment partially inhibited bleaching following nitrogen starvation. Taken together, the results presented here strongly suggest an involvement of a defined Ca2+ transient in acclimation of S. elongatus to nitrogen starvation through NtcA-dependent regulation.
Experimental determination of translational start sites resolves uncertainties in genomic open reading frame predictions – application to Mycobacterium tuberculosis
Authors: Smollett Katherine L. , Fivian-Hughes Amanda S. , Smith Joanne E. , Chang Anchi , Rao Tara , Davis Elaine O.
Published: December 2008

Correct identification of translational start sites is important for understanding protein function and transcriptional regulation. The annotated translational start sites contained in genome databases are often predicted using bioinformatics and are rarely verified experimentally, and so are not all accurate. Therefore, we devised a simple approach for determining translational start sites using a combination of epitope tagging and frameshift mutagenesis. This assay was used to determine the start sites of threeMycobacterium tuberculosisproteins: LexA, SigC and Rv1955. We were able to show that proteins may begin before or after the predicted site. We also found that a small, non-annotated open reading frame upstream of Rv1955 was expressed as a protein, which we have designated Rv1954A. This approach is readily applicable to any bacterial species for which plasmid transformation can be achieved.
Citrate-mediated iron uptake in Pseudomonas aeruginosa: involvement of the citrate-inducible FecA receptor and the FeoB ferrous iron transporter
Authors: Marshall Bryan , Stintzi Alain , Gilmour Christie , Meyer Jean-Marie , Poole Keith
Published: December 2008

In an attempt to identify components of a ferric citrate uptake system in Pseudomonas aeruginosa, a mutant library of a siderophore-deficient strain (IA614) was constructed and screened for defects in citrate-promoted growth in an Fe-restricted medium. A mutant disrupted in gene PA3901, encoding a homologue of the outer-membrane ferric citrate receptor, FecA, of Escherichia coli (FecAE.c.), was recovered and shown to be deficient in citrate-promoted growth and citrate-mediated Fe uptake. A mutant disrupted in gene PA4825, encoding a homologue of the MgtA/MgtB Mg2+ transporters in Salmonella enterica, was similarly deficient in citrate-promoted growth, though this was due to a citrate sensitivity of the mutant apparently resulting from citrate-promoted acquisition of Fe2+ and resultant oxidative stress. Consistent with citrate delivering Fe to cells as Fe2+, a P. aeruginosa mutant lacking the FeoB Fe2+ transporter homologue, PA4358, was compromised for citrate-promoted growth in Fe-restricted medium and showed markedly reduced citrate-mediated Fe uptake. Subsequent elimination of two Fe3+ transporter homologues, PA5216 and PA4687, in the feoB mutant failed to further compromise citrate-promoted growth or Fe uptake, though the additional loss of pcoA, encoding a periplasmic ferroxidase implicated in Fe2+ acquisition, completely abrogated citrate-mediated Fe uptake. Fe acquisition mediated by other siderophores (e.g. pyoverdine) was, however, unaffected in the quadruple knockout strain. These data indicate that Fe delivered to P. aeruginosa by citrate is released as Fe2+, probably in the periplasm, prior to its transport into cells via Fe transport components.
Osmoregulated periplasmic glucans of Salmonella enterica serovar Typhimurium are required for optimal virulence in mice
Authors: Bhagwat Arvind A. , Jun Won , Liu Liu , Kannan Porteen , Dharne Mahesh , Pheh Benedict , Tall Ben D. , Kothary Mahendra H. , Gross Kenneth C. , Angle Scott , Meng Jianghong , Smith Allen
Published: December 2008

We purified osmoregulated periplasmic glucans (OPGs) fromSalmonella entericaserovar Typhimurium and found them to be composed of 100 % glucose with 2-linked glucose as the most abundant residue, with terminal glucose, 2,3-linked and 2,6-linked glucose also present in high quantities. The two structural genes for OPG biosynthesis,opgGandopgH, form a bicistronic operon, and insertion of a kanamycin resistance gene cassette into this operon resulted in a strain devoid of OPGs. TheopgGHmutant strain was impaired in motility and growth under low osmolarity conditions. TheopgGHmutation also resulted in a 2 log increase in the LD50in mice compared to the wild-type strain SL1344. Inability to synthesize OPGs had no significant impact on the organism's lipopolysaccharide pattern or its ability to survive antimicrobial peptides-, detergent-, pH- and nutrient-stress conditions. We observed that theopgGH-defective strain respired at a reduced rate under acidic growth conditions (pH 5.0) and had lower ATP levels compared to the wild-type strain. These data indicate that OPGs ofS.Typhimurium contribute towards mouse virulence as well as growth and motility under low osmolarity growth conditions.
Characterization of an NADH oxidase of the flavin-dependent disulfide reductase family from Methanocaldococcus jannaschii
Authors: Case Christopher L. , Rodriguez Jason R. , Mukhopadhyay Biswarup
Published: December 2008

Methanocaldococcus jannaschii, a deeply rooted hyperthermophilic anaerobic methanarchaeon from a deep-sea hydrothermal vent, carries an NADH oxidase (Nox) homologue (MJ0649). According to the characteristics described here, MJ0649 represents an unusual member within group 3 of the flavin-dependent disulfide reductase (FDR) family. This FDR group comprises Nox, NADH peroxidases (Npx) and coenzyme A disulfide reductases (CoADRs); each carries a Cys residue that forms Cys-sulfenic acid during catalysis. A sequence analysis identified MJ0649 as a CoADR homologue. However, recombinant MJ0649 (rMJNox), expressed inEscherichia coliand purified to homogeneity an 86 kDa homodimer with 0.27 mol FAD (mol subunit)−1, showed Nox but not CoADR activity. Incubation with FAD increased FAD content to 1 mol (mol subunit)−1and improved NADH oxidase activity 3.4-fold. The FAD-incubated enzyme was characterized further. The optimum pH and temperature were ≥10 and ≥95 °C, respectively. At pH 7 and 83 °C, apparentKmvalues for NADH and O2were 3 μM and 1.9 mM, respectively, and the specific activity at 1.4 mM O2was 60 μmol min−1 mg−1; 62 % of NADH-derived reducing equivalents were recovered as H2O2and the rest probably generated H2O. rMjNox had poor NADPH oxidase, NADH peroxidase and superoxide formation activities. It reduced ferricyanide, plumbagin and 5,5′-dithiobis(2-nitrobenzoic acid), but not disulfide coenzyme A and disulfide coenzyme M. Due to a highKm, O2is not a physiologically relevant substrate for MJ0649; its true substrate remains unknown.
Influence of Poly(L-Lactic Acid) Nanofibers and BMP-2–Containing Poly(L-Lactic Acid) Nanofibers on Growth and Osteogenic Differentiation of Human Mesenchymal Stem Cells
Authors: Schofer Markus D. , Fuchs-Winkelmann Susanne , Gräbedünkel Christian , Wack Christina , Dersch Roland , Rudisile Markus , Wendorff Joachim H. , Greiner Andreas , Paletta Jürgen R. J. , Boudriot Ulrich
Published: December 2008

The aim of this study was to characterize synthetic poly-(L-lactic acid) (PLLA) nanofibers concerning their ability to promote growth and osteogenic differentiation of stem cells in vitro, as well as to test their suitability as a carrier system for growth factors. Fiber matrices composed of PLLA or BMP-2–incorporated PLLA were seeded with human mesenchymal stem cells and cultivated over a period of 22 days under growth and osteoinductive conditions, and analyzed during the course of culture, with respect to gene expression of alkaline phosphatase (ALP), osteocalcin (OC), and collagen I (COL-I). Furthermore, COL-I and OC deposition, as well as cell densities and proliferation, were analyzed using fluorescence microscopy. Although the presence of nanofibers diminished the dexamethasone-induced proliferation, there were no differences in cell densities or deposition of either COL-I or OC after 22 days of culture. The gene expression of ALP, OC, and COL-I decreased in the initial phase of cell cultivation on PLLA nanofibers as compared to cover slip control, but normalized during the course of cultivation. The initial down-regulation was not observed when BMP-2 was directly incorporated into PLLA nanofibers by electrospinning, indicating that growth factors like BMP-2 might survive the spinning process in a bioactive form.
Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts
Authors: Sanford Jeremy R. , Wang Xin , Mort Matthew , VanDuyn Natalia , Cooper David N. , Mooney Sean D. , Edenberg Howard J. , Liu Yunlong
Published: December 2008

Metazoan genes are encrypted with at least two superimposed codes: the genetic code to specify the primary structure of proteins and the splicing code to expand their proteomic output via alternative splicing. Here, we define the specificity of a central regulator of pre-mRNA splicing, the conserved, essential splicing factor SFRS1. Cross-linking immunoprecipitation and high-throughput sequencing (CLIP-seq) identified 23,632 binding sites for SFRS1 in the transcriptome of cultured human embryonic kidney cells. SFRS1 was found to engage many different classes of functionally distinct transcripts including mRNA, miRNA, snoRNAs, ncRNAs, and conserved intergenic transcripts of unknown function. The majority of these diverse transcripts share a purine-rich consensus motif corresponding to the canonical SFRS1 binding site. The consensus site was not only enriched in exons cross-linked to SFRS1 in vivo, but was also enriched in close proximity to splice sites. mRNAs encoding RNA processing factors were significantly overrepresented, suggesting that SFRS1 may broadly influence the post-transcriptional control of gene expression in vivo. Finally, a search for the SFRS1 consensus motif within the Human Gene Mutation Database identified 181 mutations in 82 different genes that disrupt predicted SFRS1 binding sites. This comprehensive analysis substantially expands the known roles of human SR proteins in the regulation of a diverse array of RNA transcripts.
Trichilemmal carcinoma arising in seborrheic keratosis: A case report and published work review
Authors: OYAMA Noritaka , KANEKO Fumio
Published: December 2008

The secondary skin malignancies arising in seborrheic keratosis (SK) are uncommon, and the causal association between the pre‐existing lesion and subsequent malignant transformation remains uncertain. Among these enigmatic conditions, trichilemmal differentiation and/or neoplasms in SK have rarely been reported thus far. Herein, we describe a case of invasive trichilemmal carcinoma arising in a long‐standing SK of the abdominal skin, and clinicopathologically review this rare complication with a computerized medical published work search (PubMed) and citations from earlier reports. To our knowledge, only four cases of trichilemmal tumors arising in SK have been observed, and, interestingly, all cases, including ours, were Japanese. Four of five cases (80%) developed the tumors in non‐sun‐exposed SK, and indeed had no apparent actinic damage in the histology. The pre‐existing SK itself is more likely to act as the primary pathogenic event for developing the secondary trichilemmal tumors than a coincidental phenomenon and a consequence of skin damage by cumulative sun exposure.
Identification of Xanthomonas citri ssp. citri host specificity genes in a heterologous expression host
Authors: RYBAK MYRIAN , MINSAVAGE GERALD V. , STALL ROBERT E. , JONES JEFFREY B.
Published: December 2008

We provide the first conclusive evidence that Xanthomonas axonopodis pv. citri Asiatic strain (Xac‐A) and, in particular, Xac‐Aw, a unique citrus canker A strain isolated from Key lime in Wellington, Florida, induces a hypersensitive reaction (HR) in grapefruit leaves. Using the heterologous tomato pathogen X. perforans, as a recipient of the Xac‐Aw genomic library, we identified a 1599‐bp open reading frame responsible for HR in grapefruit, but not Key lime, and designated it avrGf1. Xac‐AwΔavrGf1 produced typical, although visibly reduced, citrus canker symptoms (i.e. raised pustules) in grapefruit and typical canker symptoms in Key lime. We also determined that the X. perforans transconjugant carrying an Xac‐Aw hrpG elicited HR in grapefruit and Key lime leaves, and that xopA in X. perforans was partly responsible for HR. Xac‐A transconjugants carrying the X. perforans xopA were reduced in ability to grow in grapefruit leaves relative to wild‐type Xac‐A. The X. perforans xopA appears to be a host‐limiting factor. An avrBs3 homologue, which contained 18.5 repeats and induced HR in tomato, was designated avrTaw. This gene, when expressed in a pustule‐minus Xac‐Aw, did not complement pustule formation; however, pthAw, a functional pthA homologue, complemented the mutant strain to produce typical pustules in Key lime, but markedly reduced pustules in grapefruit. Both avrBs3 homologues, when expressed in a typical Xac‐A strain, resulted in typical citrus canker pustules in grapefruit, indicating that neither homologue suppressed pustule size in grapefruit. Xac‐Aw contains other unidentified factors that suppress development in grapefruit.
Mapping and expression analyses during porcine foetal muscle development of 12 genes involved in histone modifications
Authors: Peng Y. B. , Yerle M. , Liu B.
Published: December 2008

Histone modifications (methylation and demethylation) regulate gene expression and play a role in cell proliferation and differentiation by their actions on chromatin structure. In this context, we studied the temporal expression profiles of genes acting on histone methylation and demethylation during skeletal muscle proliferation and differentiation. Quantitative real‐time PCR was used to quantify the mRNA levels of CARM1, JARID1A, JMJD2A, LSD1, PRMT2, PRMT5, SMYD1, SMYD2, SMYD3, SETDB1, Suv39h2 and SUZ12 in foetal skeletal muscle. Our results showed that CARM1, JARID1A, JMJD2A, SMYD1 and SMYD2 were differentially expressed in embryonic muscles of 33 days post‐conception (dpc), 65 dpc and 90 dpc. These 12 genes were mapped to porcine chromosomes (SSC) 2q21–24, 5q25, 6q35, 6q12–21, 6p15, 7q21, 3q21–27, 9q26, 10p16, 4q15–16, 10q14–16 and 12p12 respectively. Taking into account the reported QTL mapping results, gene expression analysis and radiation hybrid mapping results, these results suggest that five genes (CARM1, JARID1A, JMJD2A, SMYD1 and SMYD2) could be good candidate genes for growth and backfat thickness traits.
Expression and role of Notch signalling in the regeneration of rat tracheal epithelium
Authors: Ma X.‐B. , Jia X.‐S. , Liu Y.‐L. , Wang L.‐L. , Sun S.‐L. , Song N. , Wang E.‐H. , Li F.
Published: December 2008

Objectives:  This study is to explore the role of Notch signalling during the regeneration of rat tracheal epithelium after injury induced by 5‐fluorouracil (5‐FU).

Materials and methods:  We developed an ex vivo model of rat tracheal epithelial regeneration using 5‐FU to induce injury. Expression levels of members of the Notch signalling pathway, ABCG2, CK19, and proliferating cell nuclear antigen (PCNA) were examined by reverse transcription–polymerase chain reaction, Western blot, and immunofluorescence. One group of tracheas were cultured in the medium with a γ‐secretase inhibitor or Jag‐1 peptide after 5‐FU treatment and another group were pre‐treated with the γ‐secretase inhibitor or Jag‐1 peptide before 5‐FU treatment. The expression changes of ABCG2, CK19, and PCNA were examined by Western blot or immunofluorescence and the morphologic changes were observed by haematoxylin and eosin stain during the recovery process.

Results:  Expression levels of Notch3, Jagged1, and Hey1 were increased in rat tracheal epithelial cells after treatment with 5‐FU. During injury recovery, disruption of Notch signalling by treatment with the γ‐secretase inhibitor reduced expression of ABCG2 and PCNA, but promoted expression of CK19, while persistent activation of Notch signalling promoted expression of ABCG2 and PCNA, but reduced expression of CK19. Under both conditions, recovery from injury was reduced. However, blocking Notch signalling prior to 5‐FU treatment led to the complete blockage of recovery, while activating Notch signalling before 5‐FU treatment promoted recovery.

Conclusions:  During tracheal epithelial regeneration, Notch signalling maintains an undifferentiated state and promotes proliferation among a population of tracheal epithelial cells.
Continuous hypoxic culturing maintains activation of Notch and allows long‐term propagation of human embryonic stem cells without spontaneous differentiation
Authors: Prasad S. M. , Czepiel M. , Cetinkaya C. , Smigielska K. , Weli S. C. , Lysdahl H. , Gabrielsen A. , Petersen K. , Ehlers N. , Fink T. , Minger S. L. , Zachar V.
Published: December 2008

Objective:  The maintenance of pluripotency of human embryonic stem cells (hESCs) requires a high efficiency of self‐renewal. During in vitro propagation, however, hESCs have a propensity to differentiate spontaneously. In this study, we assessed the nature of hESC responses to hypoxic conditions.

Materials and methods:  Human embryonic stem cells were grown in normoxic and hypoxic conditions, and the cells expressing Oct4 and stage‐specific embryonic antigen‐1 were identified by indirect immunofluorescence. The transcriptional expression of Nanog, Notch1, and Oct4 was determined by a real‐time reverse transcription–polymerase chain reaction, and the inhibition of Notch‐mediated signalling was achieved with a γ‐secretase inhibitor.

Results:  In contrast to culture at 21% oxygen, where the colonies displayed a marked degree of differentiation, we found that during exposure to 5% oxygen, the hESC colonies displayed a homogenous and flat morphology that was consistent with the presence of Oct4‐positive phenotype, indicating no spontaneous differentiation. When cultured at 5% oxygen for either 4 weeks or up to 18 months, high levels of Nanog and Notch1 transcriptional expression were detected, albeit the expression was significantly lower during longer exposure. The suppression of differentiation was rapidly reversed on transfer of the hypoxic cultures to normoxic conditions. Looking into the molecular mechanisms of the maintenance of self‐renewal at low oxygen tensions, we found that inhibition of Notch signalling fully abrogated the hypoxic induction of undifferentiated phenotype.

Conclusion:  Our data, thus, indicate that hypoxic exposure has the capacity to sustain long‐term self‐renewal of hESCs and that this effect is mediated through activation of Notch.
Cluster randomized trial of a parent‐based intervention to support early development of children in a low‐income country
Authors: Rahman A. , Iqbal Z. , Roberts C. , Husain N.
Published: December 2008

Background  Programmes that promote early psychological development of children in the developed world have been found to be beneficial. However, such programmes are rare in underprivileged parts of the developing world. We adapted one such parent‐based programme (Learning Through Play) for a rural Pakistani population and aimed to study if: (1) it was acceptable to community health workers; (2) the programme led to an improvement, after a period of 6 months, in mothers' knowledge and attitudes about early infant development; (3) it led to a reduction in the levels of maternal mental distress in the post‐natal period.

Methods  Using a cluster randomized design with villages as unit of randomization, 163 mothers from 24 villages in a rural sub‐district of Rawalpindi, Pakistan, received the ‘Learning Through Play’ programme, whereas 146 mothers from 24 villages acted as controls. Twenty‐four community health workers were trained to carry out the programme. Assessments were conducted using a specially developed 15‐item Infant Development Questionnaire and the 20‐item Self‐Reporting Questionnaire (SRQ).

Results  Over 80% of the community health workers trained found the programme to be relevant and were able to integrate it into their routine work. There was a significant increase in mothers' knowledge and positive attitudes about infant development in the intervention group, compared with the control group. Women in the intervention group answered correctly 4.3 (95% CI 3.7–14.9, P < 0.001) more questions than the control group. There was no difference in levels of mental distress measured by the SRQ.

Conclusions  The ‘Learning Through Play’ programme was successfully integrated into the existing health system and accepted by community health workers. The programme succeeded in improving the knowledge and attitudes of mothers about infant development.
Exploring synergies between human rights and public health ethics: A whole greater than the sum of its parts
Authors: Reading Richard
Published: December 2008

.
 
Nixon S. &
Forman L.
(
2008
)

,
8
,
2
.
 
DOI: 10.1186/1472‐698X‐8‐2
.

Background  The fields of human rights and public health ethics are each concerned with promoting health and elucidating norms for action. To date, however, little has been written about the contribution that these two justificatory frameworks can make together. This paper explores how a combined approach may make a more comprehensive contribution to resolving normative health issues and to advancing a normative framework for global health action than either approach made alone. We explore this synergy by first providing overviews of public health ethics and of international human rights law relevant to health and, second, by articulating complementarities between human rights and public health ethics.

Discussion  We argue that public health ethics can contribute to human rights by: (i) reinforcing the normative claims of international human rights law; (ii) strengthening advocacy for human rights; and (iii) bridging the divide between public health practitioners and human rights advocates in certain contemporary health domains. We then discuss how human rights can contribute to public health ethics by contributing to discourses on the determinants of health through: (i) definitions of the right to health and the notion of the indivisibility of rights; (ii) emphasis on the duties of states to progressively realize the health of citizens; and (iii) recognition of the protection of human rights as itself a determinant of health. We also discuss the role that human rights can play for the emergent field of public health ethics by refocusing attention on the health and illness on marginalized individuals and populations.

Summary  Actors within the fields of public health, ethics and human rights can gain analytic tools by embracing the untapped potential for collaboration inherent in such a combined approach.
Cohort differences in the progression of developmental pathways: evidence for period effects on secular trends of violence in males
Authors: Reading Richard
Published: December 2008

.
 
Fabio A.,
Yuan Z.,
Wisniewski S. R.,
Henry D. B.,
Farrington D. P.,
Bridge J. A. &
Loeber R.
(
2008
)

,
14
,
311
–
318
.
 
DOI: 10.1136/ip.2007.017814
.

Background  Rates of violence in the USA have fluctuated widely over the past few decades. Theorists have examined period and cohort effects, but there appear to be no studies examining these effects on progression in developmental pathways towards violence.

Objective  To assess whether differences in progression among individuals in the Pittsburgh Youth Study are consistent with period or cohort effects.

Design  Multivariate logistic regression was conducted to examine differences between cohorts in the odds of progressing through the developmental pathway towards violence. Adjusted and unadjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) are reported.

Setting  Pittsburgh Pennsylvania, from 1987 to 2000.

Subjects  Two cohorts of male adolescents from the Pittsburgh Youth Study. The youngest cohort (n = 503) was followed from median ages 7 to 20, and the oldest cohort (n = 506) was followed up from median ages 13 to 25.

Main outcome measure  The odds of progression along a developmental pathway towards violence.

Results  There was no statistically significant difference between the cohorts in progression from minor aggression to physical fighting (OR = 1.13, 95% CI 0.77–1.65). However, after adjustment for major risk factors, the oldest cohort was significantly more likely to progress from physical fighting to violence (OR = 2.34, 95% CI 1.39–3.92).

Conclusions  These results provide initial evidence that cohort effects, which would be present early in development, do not contribute significantly to later differences in reported violence and raise the possibility of whether period effects can explain these differences.
First evidence of a possible association between gastric acid suppression during pregnancy and childhood asthma: a population‐based register study
Authors: Dehlink E. , Yen E. , Leichtner A. M. , Hait E. J. , Fiebiger E.
Published: December 2008

Background
Recent data in mice suggest that acid suppression during pregnancy yields offspring with type 2 T helper‐dominant immunity, suggesting a predisposition for allergy.

Objective
To determine the association of in utero exposure to acid‐suppressive medications and the subsequent development of allergic diseases in children.

Methods
We studied a population‐based observational cohort formed by linking data from three Swedish national healthcare registers: the Medical Birth Register, the Hospital Discharge Register, and the Swedish Prescribed Drug Register. Main outcome measures included a hospital discharge diagnosis of an allergic disease or prescription for asthma medications, epinephrine auto‐injectors, antihistamines or steroid ointments in children. Data were analysed using the Mantel–Haenszel procedure.

Results
Twenty‐nine thousand four hundred and ninety (5.03%) children had a discharge diagnosis of allergy or prescriptions for allergy medications. Five thousand six hundred and forty‐five (0.96%) children had been exposed to acid suppression therapy during pregnancy; of these, 405 (0.07%) were treated for allergic diseases. Exposure to acid‐suppressive medications in utero was associated with an increased odds ratio (OR) for developing allergy (OR 1.43, 95% confidence interval (95% CI) 1.29–1.59). We observed this association irrespective of the type of drug, time of exposure during pregnancy, and maternal history of allergy. The use of maternal acid‐suppressive medication was associated with an increased OR for the development of childhood asthma (3.7% in the population at large vs. 5.6% in exposed children, OR 1.51, 95% CI 1.35–1.69), but not for other allergic diseases.

Conclusion
These data provide first evidence of a significant association between in utero exposure to acid‐suppressive drugs and the risk of developing childhood asthma.
Detection of allergen composition and in vivo immunogenicity of depigmented allergoids of Betula alba
Authors: Carnés J. , Himly M. , Gallego M. , Iraola V. , Robinson D. S. , Fernández‐Caldas E. , Briza P.
Published: December 2008

Background
Chemical modification of allergen vaccines to reduce IgE binding improves safety while maintaining clinical efficacy. However, this also complicates the characterization of allergoids using techniques as for native allergen extracts.

Objectives
The objective of this study was to analyse the molecular size of Betula alba depigmented allergoids, conservation of major allergens in the allergoids and in vivo antibody response to immunization.

Methods
The molecular size of depigmented allergoids was evaluated by high performance‐size exclusion chromatography and light scattering techniques. Protein composition was compared with native extracts by capillary liquid chromatography–tandem mass spectrometry based peptide mapping. Rabbits were immunized with depigmented allergoid of Betula pollen adsorbed onto aluminium hydroxide (Depigoid®). IgG antibodies against individual allergens were determined by ELISA and immunoblot.

Results
Depigmented allergoids contained a range of high molecular weight particles, approximately 60% of which had a molecular weight of 1–3 MDa. Peptide sequencing confirmed the preservation of five isoforms of Bet v 1, as well as Bet v 2, Bet v 6 and Bet v 7. Sera from immunized rabbits showed high levels of specific IgG to rBet v 1.0101 and rBet v 2.

Conclusions
The mean protein content was 544±106 μg per mg of freeze‐dried material for depigmented allergoids and 434±71 for native extracts. They retain the capacity to induce specific IgG antibodies against individual allergens present in the native extract. These findings confirm the immunogenicity of depigmented allergoids and may explain why patients treated with these vaccines are protected against the native allergens. Analysis of molecular size and allergen content may be useful techniques for characterization and standardization of allergoid products.
Probiotic supplementation in the first 6 months of life in at risk Asian infants – effects on eczema and atopic sensitization at the age of 1 year
Authors: Soh S. E. , Aw M. , Gerez I. , Chong Y. S. , Rauff M. , Ng Y. P. M. , Wong H. B. , Pai N. , Lee B. W. , Shek L. P.‐C.
Published: December 2008

Background
The role of probiotics in allergy prevention remains uncertain but has been shown in some studies to have a possible protective effect on eczema.

Objective
We aimed to assess the effect of probiotic supplementation in the first 6 months of life on eczema and allergic sensitization at 1 year of age in Asian infants at risk of allergic disease.

Methods
A double‐blind, placebo‐controlled randomized clinical trial involving 253 infants with a family history of allergic disease was carried out. Infants received at least 60 mL of commercially available cow's milk formula with or without probiotic supplementation [Bifidobacterium longum (BL999) 1 × 107 colony forming unit (CFU)/g and Lactobacillus rhamnosus (LPR) 2 × 107 CFU/g] daily for the first 6 months. Clinical evaluation was performed at 1, 3, 6 and 12 months of age, with serum total IgE measurement and skin prick tests conducted at the 12‐month visit. The primary and secondary end‐points were eczema and allergen sensitization, respectively.

Results
The incidence of eczema in the probiotic (22%) group was similar to that in the placebo group (25%) (P=0.53). The median Scoring Atopic Dermatitis score at 12 months was 17.10 (9.74) in the probiotic group and 11.60 (8.40) in the placebo group (P=0.17). The prevalence of allergen sensitization showed no difference (probiotic=24% vs. placebo=19%, P=0.26). The total IgE geometric mean (95% confidence interval) was 18.76 (12.54–24.98) kU/L in the probiotic group and 23.13 (16.01–30.24) kU/L in the placebo group (P=0.15). Atopic eczema (with sensitization) in the probiotic (7.3%) group was comparable to the placebo group (5.8%) (P=0.86).

Conclusion
Early life administration of a cow's milk formula supplemented with probiotics showed no effect on prevention of eczema or allergen sensitization in the first year of life in Asian infants at risk of allergic disease. Further work is needed to determine whether timing of supplementation, dose and probiotic strain are important considerations.
Do helminth parasites protect against atopy and allergic disease?
Authors: Flohr C. , Quinnell R. J. , Britton J.
Published: December 2008

Allergic diseases are rare in areas with high helminth parasite exposure and common where helminth exposure is lacking or significantly reduced, such as urban areas of developing countries and industrialized nations. Studies suggest that helminths induce a systemic immuno‐modulatory network, including regulatory T cells and anti‐inflammatory IL‐10, which might play a key role in the protection against the allergic phenotype. Here, we review the current cross‐sectional, birth cohort, and intervention study evidence for a protective effect of helminth infection on allergy. There is increasing evidence for a causal relationship between helminth infection and reduced skin prick test responsiveness to allergens. Cross‐sectional studies have shown a consistent negative relationship, and these results have been confirmed in several, although not all, intervention studies. The immunological basis for this protective effect is less clear. Recent studies do not support the mast‐cell IgE saturation hypothesis, but suggest that protection is associated with IL‐10 production. As for allergic disease, cross‐sectional studies support a negative relationship between clinical asthma and infection with some helminth species, particularly hookworm, but more studies are required to draw conclusions for eczema and rhinitis. In addition, none of the few intervention studies to date have demonstrated an increase in clinical allergy after helminth treatment, and further studies are needed. Furthermore, we are only beginning to understand the host genetic factors that are potentially involved. A genetically predetermined T‐helper type 2 cell‐dominated cytokine milieu reduces parasite burden and may enhance host survival in an environment where helminth parasites are prevalent. Lack of parasite exposure in such hosts might lead to hypersensitivity to seemingly minor environmental allergen stimuli. Large birth cohort studies in helminth‐endemic areas that use epidemiological, genetic, and immunological tools are required to further examine how helminth parasites affect the development of atopy and allergic disease. Intervention studies with hookworm in parasite‐naïve allergic individuals are currently ongoing in the United Kingdom to test the above hypotheses further.
Acute hyperinsulinaemia and hyperlipidaemia modify circulating adiponectin and its oligomers
Authors: Bobbert Thomas , Weicht Jessica , Mai Knut , Möhlig Matthias , Pfeiffer Andreas F. H. , Spranger Joachim
Published: December 2008

Objective  Obesity and insulin resistance are associated with low adiponectin levels, although adiponectin is exclusively expressed in white adipose tissue. The mechanism beyond that paradox is not entirely clear, although insulin itself may reduce circulating adiponectin levels. However, obesity is also associated with hyperlipidaemia and the effects of free fatty acids (FFAs) and triglycerides (TG) on circulating adiponectin levels have not yet been investigated.

Materials and methods  We analysed the effect of an acute and euglycaemic elevation of insulin on adiponectin oligomers in 23 healthy individuals. In a subgroup including 11 healthy men, FFAs and TG were acutely elevated by infusion of heparin/lipids over 120 min. Again the effect on circulating adiponectin and its oligomers was investigated. Adiponectin was determined by ELISA, oligomers were detected by nondenaturating Western blot.

Results  Acute hyperinsulinaemia resulted in a significant reduction of total adiponectin to 7·74 ± 0·98 µg/ml (P = 0·004). High molecular weight (HMW) adiponectin did not change (0·80 ± 0·12 to 0·81 ± 0·14 µg/ml; P = 0·887), whereas MMW adiponectin decreased from 4·30 ± 0·51 to 3·78 ± 0·48 µg/ml (P = 0·005) and LMW adiponectin from 3·63 ± 0·42 to 3·15 ± 0·46 µg/ml (P = 0·048). Interestingly, heparin/lipid infusion also reduced circulating adiponectin levels (P = 0·001), which was primarily the result of reduced MMW adiponectin (P = 0·004), whereas LMW and HMW were not significantly affected.

Conclusions  The presented data suggest that both, hyperinsulinaemia and hyperlipidaemia, may contribute to low adiponectin levels in states of obesity.
Epidemiology of primary hyperparathyroidism in Tayside, Scotland, UK
Authors: Yu Ning , Donnan Peter T. , Murphy Michael J. , Leese Graham P.
Published: December 2008

Objective  To evaluate prevalence and incidence of diagnosed primary hyperparathyroidism (PHPT) in adults between 1997 and 2006 in Tayside, Scotland, UK.

Design  Population‐based incidence and prevalence study.

Patients  All Tayside residents aged 20 years and over with an increased serum calcium level (> 2·55 mmol/l) between 1997 and 2006 were included as potential participants. Using a unique patient identifier, data‐linkage enabled a data set of PHPT patients to be created from an algorithm of biochemistry records, nuclear scan records, histology records, hospital clinic letters and community based prescription records. Persons having tertiary hyperparathyroidism (14·0%) were also identified and were excluded.

Outcome measures  Age and sex adjusted incidence density and period prevalence were calculated for each year.

Results  We identified 2709 patients (70·8% female) diagnosed with PHPT by the end of 2006. The mean age of women (68 years SD = 14) was older than that of men (64 years SD = 15) at baseline. The prevalence of diagnosed PHPT in Tayside increased from 1·82 per 1000 population in 1997 to 6·72 per 1000 population in 2006 (P < 0·001). Prevalence of PHPT is higher in females, and the female preponderance increases with age; the annual prevalence ratio between women and men is stable at around 2·5 each year. There was a 3–4‐year cyclical incidence rate varying from 4·13 to 11·30 per 10 000 person‐years.

Conclusion  We observed a general increase in the prevalence of diagnosed PHPT in Tayside, Scotland. The incidence of diagnosis is greater in females than in males and increases with age. The annual incidence followed an apparent cyclic curve during the study period.
A paradoxical difference in relationship between anxiety, depression and thyroid function in subjects on and not on T4: findings from the HUNT study
Authors: Panicker Vijay , Evans Jonathan , Bjøro Trine , Åsvold Bjorn O. , Dayan Colin M. , Bjerkeset Ottar
Published: December 2008

Objective  There have been conflicting reports on the relationship between thyroid function and mood between studies in subjects on T4 and the general population not on T4. We investigated this relationship in a large catchment area‐based study.

Design  We analysed data on serum TSH levels and Hospital Anxiety and Depression Scale (HADS) scores from the HUNT 2 study (age ≥ 40 years). Following a test for interaction, analyses were performed separately in females on T4 (n = 1265) and in people not on T4 (males n = 9319 and females n = 17 694).

Results  More females on T4 had high depression and anxiety scores than females not on T4 (depression 18·4%vs. 13·0%, P < 0·001, anxiety 23·4%vs. 18·7%, P < 0·001). In those not on T4, there was an inverse association between serum TSH and depression score in males (B coefficient = –0·61, 95% CI –0·91 to –0·24, P = 0·001) though not in females (B coefficient = –0·07, –0·33 to 0·19), and an inverse association between TSH and anxiety score in both genders (B coefficient for males = 0·68, 95% CI –1·04 to –0·32, P < 0·001; females –0·37, 95% CI –0·67 to –0·08, P = 0·01). In contrast, in females on T4, TSH was positively associated with both depression (B coefficient = +0·27, 95% CI 0·02 to 0·51, P < 0·05) and anxiety (B coefficient = +0·29, 95% CI 0·01 to 0·56, P < 0·05).

Conclusions  There is a different relationship between thyroid function and depression and anxiety in females on T4 compared with individuals with no thyroid disease. This group also has a higher prevalence of depression and anxiety.
Conservation genetics and management implications for European grayling, Thymallus thymallus: synthesis of phylogeography and population genetics
Authors: GUM B. , GROSS R. , GEIST J.
Published: December 2008

Abstract  European grayling, Thymallus thymallus (L.), populations have steadily declined since the mid‐1980s, mostly because of habitat degradation and increased predation pressure. To provide guidelines for conservation strategies and future management programmes, delineation of conservation and management units is warranted. Over the last decade, several studies have investigated the phylogeography and population genetic structure of T. thymallus using mitochondrial and nuclear microsatellite DNA markers. However, no study has covered the distribution range of T. thymallus across Europe; thus, a comprehensive survey of the evolutionary history of the species is lacking. This paper synthesises the major findings of the molecular studies and provides guidelines for the conservation and management of genetic resources of T. thymallus. At least five major mtDNA lineages have evolved in geographical isolation during the Pleistocene and these lineages should be recognised as the basic evolutionary significant units for T. thymallus in northern, central and southern Europe. There is also evidence for a high level of admixture among major lineages and sublineages, especially in the contact zones of drainages (e.g. in mainland Sweden and Norway and in central Germany), most probably resulting from a complex process of post‐glacial and inter‐glacial colonisation and re‐colonisation events from different refugia during the Pleistocene ice ages. Based on the microsatellite data, T. thymallus shows a substantial level of inter‐population genetic differentiation and, compared with other freshwater fish species, a relatively low level of within‐population genetic diversity. The species develops discrete population structure, both within hydrologically connected rivers or lakes on comparatively small scales as well as in large river systems.