bluuebunny/crossref_metadata_2025 huggingface dataset:
Unrelated donor and HLA‐identical sibling haematopoietic stem cell transplantation cure chronic granulomatous disease with good long‐term outcome and growth
Authors: Soncini Elena , Slatter Mary A. , Jones Laura B. K. R. , Hughes Stephen , Hodges Stephen , Flood Terence J. , Barge Dawn , Spickett Gavin P. , Jackson Graham H. , Collin Matthew P. , Abinun Mario , Cant Andrew J. , Gennery Andrew R.
Published: February 2009

Chronic granulomatous disease (CGD) causes recurrent infection and inflammatory disease. Despite antimicrobial prophylaxis, patients experience frequent hospitalisations and 50% mortality by 30 years. Haematopoietic stem cell transplantation (HSCT) can cure CGD with resolution of infection and colitis. This study reports the survival and long‐term outcome in 20 conditioned patients treated between 1998 and 2007, using 10 matched sibling (MSD) and 10 unrelated donors (URD). Age at HSCT, graft‐versus‐host disease (GvHD), growth, and outcome were analysed. Fourteen had ≥1 invasive infection, 10 had colitis and seven had growth failure before HSCT. Median age at transplantation was 75 months (range 15 months–21 years). Eighteen (90%) were alive 4–117 months (median 61) after HSCT with normal neutrophil function. Two died from disseminated fungal infection. Two experienced significant chronic GvHD, with continuing sequelae in 1. Colitis resolved within 8 weeks of HSCT. Mean weight and height for age Z scores on recovery from HSCT rose significantly (P < 0·001). HSCT with MSD or URD gave excellent engraftment and survival, remission of colitis and catch‐up growth, with low incidence of significant GvHD. Transplant‐associated complications were restricted to those with pre‐existing infection or inflammation, supporting the argument for early HSCT for more CGD patients with a well matched donor.
Spatial and temporal dynamics of habitat selection across canopy gradients generates patterns of species richness and composition in aquatic beetles
Authors: BINCKLEY CHRISTOPHER A. , RESETARITS WILLIAM J.
Published: February 2009

Abstract1. Colonisation is a critical ecological process influencing both population and community level dynamics by connecting spatially discrete habitat patches. How communities respond to both natural and anthropogenic disturbances, furthermore, requires a basic understanding of how any environmental change modifies colonisation rates. For example, disturbance‐induced shifts in the quantity of forest cover surrounding aquatic habitats have been associated with the distribution and abundance of numerous aquatic taxa. However, the mechanisms generating these broad and repeatable field patterns are unclear.

2. Such patterns of diversity could result from differential spatial mortality post colonisation, or from colonisation alone if species select sites non‐randomly along canopy coverage gradients. We examined the colonisation/oviposition dynamics of aquatic beetles in experimental ponds placed under both open and closed forest canopies.

3. Canopy coverage imposed a substantial behavioural filter on the colonisation and reproduction of aquatic beetles representing multiple trophic levels, and resulted in significantly higher abundance, richness, and oviposition activity in open canopy ponds. These patterns strengthened overtime; although early in the experiment, the most abundant beetle had similar abundance in open and closed ponds. However, its abundance subsequently declined and then most other species heavily colonised open canopy ponds.

4. The primary response of many aquatic species to disturbances that generate canopy coverage gradients surrounding aquatic ecosystems is behavioural. The magnitude of the colonisation responses reported here rivals, if not exceeds, those produced by predators, suggesting that aquatic landscapes are behaviourally assessed and partitioned across multiple environmental gradients. The community level structure produced solely by selective colonisation, is predicted to strongly modify how patch area and isolation affect colonisation rates and the degree to which communities are linked by the flux of individuals and species.
Species and site differences in Neotropical army ant emigration behaviour
Authors: O’DONNELL SEAN , LATTKE JOHN , POWELL SCOTT , KASPARI MICHAEL
Published: February 2009

Abstract1. Along with large wingless queens and group foraging raids, periodic colony movements or emigrations are a defining feature of army ant behaviour. Emigrations are important because they regulate spacing among colonies, and provide access to new foraging sites.

2. Raid and emigration activity of army ant communities was measured at four Neotropical sites using a standardised sampling protocol. Sampling of emigration activity was carried out throughout the diel cycle.

3. Both raid and emigration activity occurred throughout the day and night. Emigration activity was highest under cover of darkness, but sites and species differed in the diel timing of emigrations. These site and species differences have implications for the evolution of emigration behaviour, as well as for the community ecology of army ants.
Biodiversity of Belgian groundwater fauna in relation to environmental conditions
Authors: MARTIN PATRICK , DE BROYER CLAUDE , FIERS FRANK , MICHEL GEORGES , SABLON ROSE , WOUTERS KAREL
Published: February 2009

1. The Pleistocene glaciations during the Quaternary appear to have resulted in an impoverished groundwater fauna in northern Europe. Re‐colonisation may have occurred either through long‐distance dispersal from unglaciated southern areas or from local refugia.

2. The Belgian groundwater fauna was sampled at multiple sites, and its habitats characterised, to assess whether the composition of present‐day stygobiotic assemblages can be attributed to either of these mechanisms.

3. A total of 202 sampling sites were selected in four hydrogeographic units of the Meuse River catchment. Sites were equally divided among the saturated and unsaturated zones of fractured aquifers (karst) and within the hyporheic and phreatic zones of porous aquifers. Seventeen environmental parameters were determined in parallel.

4. More than 140 species were recorded, including representatives of the Amphipoda, Cladocera, Copepoda, Hydrachnidia, Isopoda, Oligochaeta, Ostracoda, Mollusca, Syncarida and Nematoda. Thirty stygobiont species were identified, of which 10 species were new to the Belgian fauna, raising the total number of stygobiotic species in Belgium to 41.

5. The frequency of occurrences of stygobiotic species was always low, with 37% of the sampled sites lacking stygobionts. A few species were exclusive to one hydrological zone, although no statistically significant differences were detected in species richness at any of the four hierarchial levels considered (Meuse catchment = region, hydrogeographic units, aquifer type and hydrological zone).

6. Overall, results suggest that the stygobiotic fauna of Belgium is species‐poor and mostly comprises widely distributed species with broad ecological tolerances. This supports the view that eurytopic species re‐colonised the area by long‐distance dispersal from refugia in southern Europe. The virtual absence of endemic species further suggests that the scenario of an ancient fauna that survived in local refugia is of minor importance.
Abundance and production of bacteria, and relationship to phytoplankton production, in a large tropical lake (Lake Tanganyika)
Authors: STENUITE STEPHANE , PIRLOT SAMUEL , TARBE ANNE‐LAURE , SARMENTO HUGO , LECOMTE MÉLANIE , THILL SOPHIE , LEPORCQ BRUNO , SINYINZA DANNY , DESCY JEAN‐PIERRE , SERVAIS PIERRE
Published: February 2009

1. Abundance and bacterial production (BP) of heterotrophic bacteria (HBact) were measured in the north and south basins of Lake Tanganyika, East Africa, during seasonal sampling series between 2002 and 2007. The major objective of the study was to assess whether BP can supplement phytoplankton particulate primary production (particulate PP) in the pelagic waters, and whether BP and particulate PP are related in this large lake. HBact were enumerated in the 0–100 m surface layer by epifluorescence microscopy and flow cytometry; BP was quantified using3H‐thymidine incorporation, usually in three mixolimnion layers (0–40, 40–60 and 60–100 m).

2. Flow cytometry allowed three subpopulations to be distinguished: low nucleic acid content bacteria (LNA), high nucleic acid content bacteria (HNA) andSynechococcus‐like picocyanobacteria (PCya). The proportion of HNA was on average 67% of total bacterial abundance, and tended to increase with depth. HBact abundance was between 1.2 × 105and 4.8 × 106 cells mL−1, and was maximal in the 0–40 m layer (i.e. roughly, the euphotic layer). Using a single conversion factor of 15 fg C cell−1, estimated from biovolume measurements, average HBact biomass (integrated over a 100‐m water column depth) was 1.89 ± 1.05 g C m−2.

3. Significant differences in BP appeared between seasons, especially in the south basin. The range of BP integrated over the 0–100 m layer was 93–735 mg C m−2 day−1, and overlapped with the range of particulate PP (150–1687 mg C m−2 day−1) measured in the same period of time at the same sites.

4. Depth‐integrated BP was significantly correlated to particulate PP and chlorophyll‐a, and BP in the euphotic layer was on average 25% of PP.

5. These results suggest that HBact contribute substantially to the particulate organic carbon available to consumers in Lake Tanganyika, and that BP may be sustained by phytoplankton‐derived organic carbon in the pelagic waters.
Nitrogen effects on net ecosystem carbon exchange in a temperate steppe
Authors: NIU SHULI , WU MINGYU , HAN YI , XIA JIANGYANG , ZHANG ZHE , YANG HAIJUN , WAN SHIQIANG
Published: February 2009

It has widely been documented that nitrogen (N) enrichment stimulates plant growth and net primary production. However, there is still dispute on how N addition affects net ecosystem CO2 exchange (NEE), which represents the balance between ecosystem carbon (C) uptake and release. We conducted an experimental study to examine effects of N addition on NEE in a temperate steppe in northern China from 2005 to 2008. N was added at a rate of 10 g N m−2 yr−1 with NH4NO3 alone or in combination with phosphorous (P, 5 g P2O5 m−2 yr−1) in both clipped and unclipped plots. Over the 4 years, N addition significantly stimulated growing‐season NEE, on average, by 27%. Neither the main effects of P addition or clipping nor their interactions with N addition were statistically significant on NEE in any of the 4 years. However, the magnitude of N stimulation on NEE declined over time. N addition significantly increased NEE by 60% in 2005 and 21% in 2006, but its effect was not significant in 2007 and 2008. N‐induced shift in species composition was primarily responsible for the declined N stimulation over time. The gradually increasing coverage of the upper canopy species (Stipa krylovii) and standing litter accumulation induced light limitation on the lower canopy species (Artemisia frigida). Thus, N‐induced shifts in plant species composition strongly regulated the direct effects of N addition on C sequestration in the temperate steppe.
Arctic alpine vegetation change over 20 years
Authors: WILSON SCOTT D. , NILSSON CHRISTER
Published: February 2009

Recent arctic warming experiments have recorded significant vegetation responses, typically an increase in shrub cover and a loss of species richness. We report similar changes in vegetation along an arctic mountainside in northern Sweden over 20 years. During this time mean annual temperature increased by 2.0 °C, and growing season temperature by 2.3 °C. Growing season length increased by 28% at the bottom of our study area, in birch forest, and by 175% on the mountaintop. Neither total vegetation cover nor the cover of bare ground changed. One common dwarf shrub, Empetrum hermaphroditum, and two common forbs, Viola biflora and Geranium sylvaticum, increased in abundance over time, but no common species moved up the gradient. Species richness declined significantly over time, with an average loss of two species per 50 cm × 100 cm plot. The richness of herbaceous species at intermediate altitudes decreased significantly with increasing shrub cover. In spite of large changes in temperature, the type and magnitude of vegetation change along this mountainside were relatively modest and consistent with those from wide‐spread warming experiments.
Potential effects of elevated atmospheric carbon dioxide on benthic autotrophs and consumers in stream ecosystems: a test using experimental stream mesocosms
Authors: HARGRAVE CHAD W. , GARY KAITLEN P. , ROSADO SAMIR K.
Published: February 2009

Elevated atmospheric carbon dioxide (eCO2) has been shown to have a variety of ecosystem‐level effects in terrestrial systems, but few studies have examined how eCO2 might affect aquatic habitats. This limits broad generalizations about the effects of a changing climate across biomes. To broaden this generalization, we used free air CO2 enrichment to compare effects of eCO2 (i.e., double ambient ∼720 ppm) relative to ambient CO2 (aCO2∼360 ppm) on several ecosystem properties and functions in large, outdoor, experimental mesocosms that mimicked shallow sand‐bottom prairie streams. In general, we showed that eCO2 had strong bottom‐up effects on stream autotrophs, which moved through the food web and indirectly affected consumer trophic levels. These general effects were likely mediated by differential CO2 limitation between the eCO2 and aCO2 treatments. For example, we found that eCO2 decreased water‐column pH and increased dissolved CO2 in the mesocosms, reducing CO2‐limitation at times of intense primary production (PP). At these times, PP of benthic algae was about two times greater in the eCO2 treatment than aCO2 treatment. Elevated PP enhanced the rate of carbon assimilation relative to nutrient uptake, which reduced algae quality in the eCO2 treatment. We predicted that reduced algae quality would negatively affect benthic invertebrates. However, density, biomass and average individual size of benthic invertebrates increased in the eCO2 treatment relative to aCO2 treatment. This suggested that total PP was a more important regulator of secondary production than food quality in our experiment. This study broadens generalizations about ecosystem‐level effects of a changing climate by providing some of the first evidence that the global increase in atmospheric CO2 might affect autotrophs and consumers in small stream ecosystems throughout the southern Great Plains and Gulf Coastal slope of North America.
IL‐1β, IL‐6, KC and MCP‐1 are elevated in synovial fluid from haemophilic mice with experimentally induced haemarthrosis
Authors: ØVLISEN K. , KRISTENSEN A. T. , JENSEN A. L. , TRANHOLM M.
Published: February 2009

Summary.  The hallmark of haemophilia is the joint morbidity resulting from haemarthrosis that accounts for the majority of the bleeds. The exact mechanisms underlying changes are not fully elucidated. Cytokines are speculated to be involved in the progression and in vitro studies have confirmed the presence of elevated levels of cytokines in synovial tissue and cartilage from patients with haemophilic synovitis. In this study, the presence of selected cytokines in synovial fluid from haemophilia A mice with experimentally induced haemarthroses treated with rFVIII, rFVIIa and an rFVIIa analogue were investigated. Ten cytokines previously shown to be involved in arthritic syndromes were evaluated. Interleukin (IL)‐1β, IL‐2, IL‐4, IL‐6, IL‐10, IL‐17, Tumor Necrosis Factor‐alpha (TNF‐ α), keratinocyte‐derived chemokine (KC), Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) and monocyte chemotactic protein‐1 (MCP‐1) were included. In this article, we demonstrate, for the first time, that bleeding in knee joints of haemophilia A mice resulted in correlated increased levels of the pro‐inflammatory cytokines: IL‐1β, IL‐6, KC and the MCP‐1 in synovial fluid. These results suggest an important role of MCP‐1 in the recruitment of monocytes and furthermore that the inflamed synovium releases IL‐1β, IL‐6 and KC, which in turn might contribute to further progression of the inflammatory process.
Endosomal processing for antigen presentation mediated by CD1 and Class I major histocompatibility complex: roads to display or destruction
Authors: Boes Marianne , Stoppelenburg Arie J. , Sillé Fenna C. M.
Published: February 2009

The presentation of antigen in a form that can be recognized by T lymphocytes of the immune system requires antigen processing and association of antigen‐derived fragments with molecules encoded by the major histocompatibility complex (MHC) locus or by the CD1 locus. Much emphasis on antigen processing and presentation in the last decades has focused on what we consider ‘conventional routes’ of antigen processing and presentation, whereby extracellular antigens are processed for presentation via Class II MHC complexes and cytosolic antigens are presented as peptide–Class I MHC complexes. We here highlight two other pathways in myeloid dendritic cells, those of lipid antigen presentation in association with CD1 and of peptide cross‐presentation via Class I MHC complexes. Some pathogens evade immune recognition through inhibition of antigen presentation of phagosomal origin. Deviations in endosomal antigen processing and presentation are also seen in individuals suffering from glycosphingolipid lysosomal lipid storage diseases. We summarize recent developments in the endosomal antigen processing and presentation pathway, for display as lipid–CD1 complexes to natural killer T cells and as peptide–Class I MHC complexes to CD8 T cells.
T‐cell reconstitution without T‐cell immunopathology in two models of T‐cell‐mediated tissue destruction
Authors: Penaloza‐MacMaster Pablo , Masopust David , Ahmed Rafi
Published: February 2009

Antigen‐specific T cells play a pivotal role in adaptive immune responses. However, they also contribute to the progression of a variety of diseases including autoimmune disorders, graft rejection and graft‐versus‐host disease (GVHD). Non‐specific immune‐ablation treatments compromise the ability of the host to respond to infection, whereas the selective removal of epitope‐specific T cells could theoretically ameliorate T‐cell‐mediated pathology while preserving the rest of the host immune function. In this study we investigated whether it is possible to destroy specific unwanted antigen‐specific T cells by incubating polyclonal T‐cell populations with major histocompatibility complex (MHC) tetramers that are conjugated to the ribosomal‐inactivating toxin, saporin. This strategy resulted in a dramatic reduction in the number of targeted antigen (Ag)‐specific CD8 T cells with no observable bystander toxicity in vitro. Moreover, in a model of transferable T‐cell‐dependent neurological disease induced by intracerebral (i.c.) lymphocytic choriomeningitis virus (LCMV) infection, the targeted killing of LCMV‐specific CD8 T cells extended the survival of mice or fully prevented their death, depending on the dose of cells transferred. In addition, the tetramer– saporin conjugate also reduced liver damage in a model of donor T‐cell‐mediated hepatic destruction. These data provide a proof of principle that MHC tetramers could be exploited for the elimination or clinical manipulation of T‐cell responses by linking effector molecules (a toxin in this case) to MHC tetramers. Also, the results suggest that it may be feasible to remodel T‐cell responses, especially in immunocompromised hosts who receive adoptive cell transfers with many potential alloreactive cells.
IFN‐γ production in response to Tax 161–233, and frequency of CD4+ Foxp3+ and Lin− HLA‐DRhigh CD123+ cells, discriminate HAM/TSP patients from asymptomatic HTLV‐1‐carriers in a Peruvian population
Authors: Best Ivan , López Giovanni , Verdonck Kristien , González Elsa , Tipismana Martín , Gotuzzo Eduardo , Vanham Guido , Clark Daniel
Published: February 2009

Human T‐lymphotropic virus 1 (HTLV‐1) can cause HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of this study was to gain insight into the pathogenesis of HAM/TSP by focusing on the CD8+ T‐cell response. Twenty‐three HTLV‐1‐seronegative controls (SC), 29 asymptomatic HTLV‐1 carriers (AC) and 48 patients with HAM/TSP were enrolled in the study. We evaluated the production of interferon‐γ (IFN‐γ) in peripheral blood mononuclear cells stimulated with Tax overlapping peptides, the expression of genes related to the CD8+ cytotoxic T‐cell response, the frequency of CD4+ Foxp3+ cells and of dendritic cells, and the HTLV‐1 provirus load (PVL). The frequency of cells producing IFN‐γ in response to Tax 161–233, but not to Tax 11–19, discriminated patients with HAM/TSP from AC. The increased pro‐inflammatory response observed in patients with HAM/TSP was shared by AC with a high PVL, who also exhibited lower levels of granzyme H mRNA in unstimulated CD8+ T cells than AC with a low PVL. Patients with HAM/TSP showed higher frequencies of CD4+ Foxp3+ cells and lower frequencies of plasmacytoid dendritic cells (pDC) than AC. Our findings are consistent with a model in which HTLV‐1, along with the host genetic background, drives quantitative and qualitative changes in pDC and CD4+ Foxp3+ cells that lead to a predominance of inflammatory responses over lytic responses in the CD8+ T‐cell response of individuals predisposed to develop HAM/TSP.
The CTLA‐4 gene polymorphisms are associated with CTLA‐4 protein expression levels in multiple sclerosis patients and with susceptibility to disease
Authors: Karabon Lidia , Kosmaczewska Agata , Bilinska Malgorzata , Pawlak Edyta , Ciszak Lidia , Jedynak Anna , Jonkisz Anna , Noga Leszek , Pokryszko‐Dragan Anna , Koszewicz Magdalena , Frydecka Irena
Published: February 2009

Cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) is an important molecule in the down‐regulation of T‐cell activation. A study was undertaken to evaluate the association of the CTLA‐4 gene polymorphisms −319C/T, +49A/G, (AT)n, CT60A/G and Jo31G/T with the levels of membrane CTLA‐4 (mCTLA‐4) and cytoplasmic CTLA‐4 (cCTLA‐4) in CD4+ T lymphocytes from patients with multiple sclerosis (MS) and with susceptibility to MS, and the course of the disease. It was found that the Jo31GG and CT60GG genotypes were associated with decreased mean fluorescence intensity (MFI) of total CTLA‐4 (mCTLA‐4 + cCTLA‐4) molecules in CD4+ T cells from both relapsing‐remitting (RR) and secondary progressive (SP) MS patients compared with others. Consequently, possessing the Jo31G allele and/or the CT60G allele were associated with susceptibility to MS. The percentages of cells expressing mCTLA‐4 and cCTLA‐4 in RR patients were higher in carriers of the alleles non‐predisposing to MS (namely CT60A and Jo31T), but the percentages of corresponding cells were unexpectedly significantly lower in SP patients than in RR patients. Increased risk of paresthesia and pyramidal signs as a first manifestation of disease, and earlier transition to the SP form in those patients, was also noted. It is hypothesized that the decreasing frequencies of cells expressing immunosuppressive mCTLA‐4 and cCTLA‐4 in carriers of alleles non‐predisposing to MS (i.e. CT60A and Jo31T) may lead to inadequate down‐regulation of ongoing T‐cell responses in these patients and, as a consequence, earlier progression of disease from the RR form to the SP form.
Dental anxiety among survivors of childhood cancer: a cross‐sectional study
Authors: WOGELIUS PIA , ROSTHØJ STEEN , DAHLLÖF GÖRAN , POULSEN SVEN
Published: February 2009

Background.   Childhood cancer survivors may have experienced a high number of invasive medical and dental procedures which are known to be risk factors for dental anxiety.

Aim.  The aim of this study was to examine the prevalence of dental anxiety among children who have survived cancer.

Design.  In a cross‐sectional study, we examined 51 6‐ to 14‐year‐old children who had been treated for cancer at Aalborg Hospital, and 192 children without cancer. All children answered the Dental Subscale of the Children's Fear Survey Schedule. Dental anxiety was defined as a dental anxiety score exceeding the mean dental anxiety score + 1 standard deviation for the children without cancer.

Results.  Children with cancer did not have an increased prevalence of dental anxiety compared with children without cancer: the prevalence ratio was 0.41 [95% confidence interval (CI): 0.10–1.24]. The mean dental anxiety score was 23.1 (95% CI: 21.2–25.0) among children who had been treated for cancer, and 24.7 (95% CI: 23.4–26.0) among children without cancer (mean difference: 1.6; 95% CI: 1.1–4.3).

Conclusion.  Cancer and cancer treatment during childhood were not associated with an increased risk of dental anxiety in this population.
Erosive tooth wear among children in the United States: relationship to race/ethnicity and obesity
Authors: MCGUIRE JESSE , SZABO ANIKO , JACKSON SCOTT , BRADLEY T. GERARD , OKUNSERI CHRISTOPHER
Published: February 2009

Objective.  The study aims were to estimate the prevalence of erosive tooth wear (ETW) in children and to specifically examine its association with race/ethnicity and obesity in the United States.

Design.  We analysed data from the National Health and Nutrition Examination Survey (NHANES), 2003–2004. ETW was measured using the modified Smith and Knight Tooth Wear Index derived from the 1998 United Kingdom Adult Health Survey.

Results.  This study shows that 45.9% of children aged 13–19 years had evidence of ETW in at least one tooth. The prevalence of ETW was bilaterally symmetrical in all teeth examined and was most prevalent in maxillary teeth. Females had significantly lower rates of ETW of any tooth compared to males. African Americans had significantly lower rates of ETW (except in the canines), and Hispanics had similar rates compared to whites. Compared to ‘healthy weight’ children, those ‘at risk for overweight’ had lower rates of ETW and the ‘overweight’ groups had higher rates, but results were not significant.

Conclusions.  Substantial proportions of children in the US are affected by ETW. Compared to whites, African American children had significantly lower rates of ETW. Although not significant, ‘overweight’ (obese) children had increased odds of having ETW and those at ‘risk for overweight’ had lower odds compared to ‘healthy weight’ children.
Effects of early breastfeeding on neonatal glucose levels of term infants born to women with gestational diabetes
Authors: Chertok I. R. A. , Raz I. , Shoham I. , Haddad H. , Wiznitzer A.
Published: February 2009

Background:  Infants born to diabetic women are at higher risk for hypoglycaemia related to hyperinsulinism in response to maternal hyperglycaemia during pregnancy. As such, recommendations to prevent neonatal hypoglycaemia include infant feeding in the early postpartum period. The present study aimed to examine the effect of early breastfeeding and type of nutrition used for the first feed (human milk or formula) on glucose levels in infants born to women with gestational diabetes.

Methods:  The prospective pilot study of 84 infants born to gestational diabetic women examined the glycaemic levels of infants who were breastfed in the delivery room compared to glycaemic levels of those who were not. The study also compared the glycaemic levels of infants who breastfed with those who received formula for their first feed.

Results:  Infants who were breastfed in the delivery room had a significantly lower rate of borderline hypoglycaemia than those who were not breastfed in the early postpartum period (10% versus 28%; Fisher’s exact test., P = 0.05,). Likewise, infants breastfed in the delivery room had significantly higher mean blood glucose level compared to infants who were not breastfed in the delivery room (3.17 versus 2.86 mmol L−1, P = 0.03). Additionally, breastfed infants had a significantly higher mean blood glucose level compared to those who were formula fed for their first feed (3.20 versus 2.68 mmol L−1, P = 0.002).

Conclusions:  Early breastfeeding may facilitate glycaemic stability in infants born to women with gestational diabetes.
Nutrient density and variation in nutrient intake with changing energy intake in multimorbid nursing home residents
Authors: Lammes E. , Törner A. , Akner G.
Published: February 2009

Background:  The low energy intake seen in some institutionalised elderly has led to a focus on energy dense diets. The present study aimed to investigate nutrient density in the diet of nursing home residents, and calculate how changes in energy intake affect nutrient intake.

Methods:  The investigation comprised a longitudinal observational study analysing the relation between energy and nutrient intake in a general nursing home in Sweden. Food intake was weighed for 5 days every sixth month over 1.5 years and nutrient density was calculated. The 52 multimorbid residents [mean (range) age 84 (67–102) years] with three complete 5‐day weighed food records were included in the study. A mixed linear model was used to calculate changes in nutrient intake with changing energy intake.

Results:  Nutrient density was adequate for vitamins A, B12, thiamine, riboflavin and niacin, and low for vitamins D and E, folate, potassium, magnesium and iron. The mixed linear model showed that the fat‐soluble vitamins, as well as folate and vitamin B12, increased the most with increasing energy intake, whereas sodium, potassium, thiamine and selenium had the smallest increase.

Conclusions:  Nutritional density of the food should be considered when planning diets for elderly patients with poor appetite.
Social and ethnic differences in folic acid use preconception and during early pregnancy in the UK: effect on maternal folate status
Authors: Brough L. , Rees G. A. , Crawford M. A. , Dorman E. K.
Published: February 2009

Background:  The role of folate supplementation in preventing neural tube defects is well known; however, preconception supplement use continues to be low, especially amongst the socially disadvantaged. The present study explored periconception folic acid supplement use in a socially deprived, ethnically diverse population.

Methods:  Pregnant women (n = 402) in the first trimester of pregnancy were recruited in East London. Using a researcher led questionnaire, details were obtained regarding social class, ethnicity and folic acid use. Red cell folate levels were determined for 367 participants during the first trimester.

Results:  Although 76% of participants reported using folic acid supplements during the first trimester, only 12% started preconception and a further 17% started before neural tube closure. Mothers from higher social groups or with higher levels of education were more likely to use folic acid and started taking it earlier. Ethnic differences were also seen in preconception usage (Africans, 5%; West Indians, 8%; Asians, 12%; Caucasians, 19%; P = 0.038). Participants who took folic acid supplements had significantly higher mean (SD) red cell folate concentrations than those who took none [936 (*\1.6) and 579 (*\1.6) nmol L−1, respectively; P < 0.001].

Conclusions:  Folic acid supplement use preconception and prior to neural tube closure continues to be low, exhibiting both social and ethnic disparities.
Influence of gum‐chewing on the haemodynamics in female masseter muscle
Authors: ABE N. , YASHIRO K. , HIDAKA O. , TAKADA K.
Published: February 2009

Summary  Blood flow in active skeletal muscles provides energy substrate, oxygen and reduction of excessive heat and metabolic by‐products. Although cyclic jaw motions such as those during mastication and speech articulation are the primitive oro‐facial functions, possible effects of the cyclic muscle contractions on the intramuscular haemodynamics of the jaw muscles remains scarcely known. We investigated the masseteric haemodynamics during and after gum‐chewing. Ten healthy female adults participated in the study. Electromyography, kinetics of masseter muscle oxygenation, electrocardiogram and blood pressure were recorded simultaneously. The subjects were asked to perform gum‐chewing and cyclic jaw motion without gum bolus (empty‐chewing task). The haemodynamics parameters were compared between the two experimental conditions. During gum‐chewing task, deoxygenated haemoglobin and sympathetic nerve activity increased, while tissue blood oxygen saturation decreased. Blood pressure and parasympathetic nerve activity did not change. The overall behaviour of haemodynamic parameters during empty‐chewing task was similar to that observed during gum‐chewing task. However, the latency periods from the end of chewing until significant changes in the haemodynamic parameters were notably shorter (P < 0·05) in gum‐chewing task as compared with those associated with empty‐chewing task. The duration of the changes was shorter with empty‐chewing than with gum‐chewing. Fluctuations in masseter muscle haemodynamics associated with chewing jaw movement differed depending on the level of muscle contraction during movement. The differences became statistically significant immediately after the commencement of chewing and after the cessation movement. During the chewing movement, automatic nerve activities increased in response to the level of muscle contraction during movement.
Plasma buprenorphine concentrations after the application of a 70 μg/h transdermal patch in dogs. Preliminary report
Authors: ANDALUZ A. , MOLL X. , VENTURA R. , ABELLÁN R. , FRESNO L. , GARCÍA F.
Published: February 2009

The objective of the present study was to evaluate the plasma concentrations and pharmacokinetics of buprenorphine after transdermal application in dogs (n = 4). A 70 μg/h transdermal buprenorphine patch was applied to the ventral abdomen of four healthy beagles. Blood samples were collected through a preplaced jugular catheter before and at 1, 2, 4, 8, 12, 24, 36, 48 and every 6 h until 108 h after the patch application. Plasma buprenorphine concentrations were measured using a125I‐labelled radioimmunoassay (RIA) assay. No adverse effects were observed in any of the dogs. Concentrations of buprenorphine were detected in plasma after the application of the transdermal buprenorphine patch on the four experimental animals. Buprenorphine plasma concentrations increased during the first 36 h and then remained in the 0.7–1.0 ng/mL range during the study period. A decrease in plasma buprenorphine concentration was not observed during the study. Although analgesia could not be demonstrated the present study shows the ability of buprenorphine transdermal delivery systems developed for human use to deliver measurable concetrations of buprenorphine in dogs.
Low uptake of treatment for hepatitis C virus infection in a large community‐based study of inner city residents
Authors: Grebely J. , Raffa J. D. , Lai C. , Krajden M. , Kerr T. , Fischer B. , Tyndall M. W.
Published: February 2009

Summary. Despite the availability of effective therapy for hepatitis C virus (HCV) infection, there are little data on the uptake of treatment. We evaluated factors associated with HCV infection and the uptake of HCV treatment in a large community‐based inner city cohort in Vancouver, Canada. The Community Health and Safety Evaluation is a cohort study of inner city residents recruited from January 2003 to June 2004. HIV and HCV status and information on prescriptions for HCV treatment were determined through linkage with provincial databases. HCV prevalence was calculated and factors associated with HCV infection were identified. HCV treatment uptake and incidence of HCV infection from January 2000 to December 2004 were expressed in terms of person‐years of observation. Among 2913 individuals, HCV antibody testing was performed in 2118 and the HCV seroprevalence was 64.2% (1360 of 2118). In total, 1.1% of HCV antibody‐positive individuals (15 of 1360) initiated treatment for HCV infection from January 2000 to December 2004 [0.28 cases per 100 person‐years (95% CI, 0.15–0.46)]. Three of 15 (20.0%) treated individuals achieved a sustained virological response. During the same period, the incidence of HCV infection was 7.26 cases (95% CI, 5.72–8.80) per 100 person‐years. Overall, the rate of new HCV seroconversions in this cohort in the study period was about 25 times the rate of HCV treatment uptake. There are extremely low rates of HCV treatment initiation and very limited effectiveness, despite a high prevalence of HCV infection in this large community‐based cohort of inner city residents with access to universal healthcare.
First DNA sequences from Asian cave bear fossils reveal deep divergences and complex phylogeographic patterns
Authors: KNAPP MICHAEL , ROHLAND NADIN , WEINSTOCK JACOBO , BARYSHNIKOV GENNADY , SHER ANDREI , NAGEL DORIS , RABEDER GERNOT , PINHASI RON , SCHMIDT HEIKO A. , HOFREITER MICHAEL
Published: February 2009

Until recently, cave bears were believed to have only inhabited Europe. However, recent morphological evidence suggests that cave bears’ geographic range extended as far east as Transbaikalia, Eastern Siberia. These Asian cave bears were morphologically distinct from European cave bears. However, how they related to European lineages remains unclear, stressing the need to assess the phylogenetic and phylogeographic relationship between Asian cave bears and their European relatives. In this work, we address this issue using a 227 base‐pair fragment of the mitochondrial control region obtained from nine fossil bone samples from eight sites from the Urals, Caucasus, Altai Mountains, Ukraine and Yana River region in Eastern Siberia. Results of the phylogenetic analyses indicate that (i) the cave bear from the Yana River is most closely related to cave bears from the Caucasus region; (ii) the Caucasus/Yana group of bears is genetically very distinct from both European cave bears and brown bears, suggesting that these bears could represent an independent species; and (iii) the Western European cave bear lineage reached at least temporarily to the Altai Mountains, 7000 km east of their known centre of distribution. These results suggest that the diversity of cave bears was greater than previously believed, and that they could survive in a much wider range of ecological conditions than previously assumed. They also agree with recent studies on other extinct and extant species, such as wolves, hyenas and steppe bison, which have also revealed higher genetic and ecological diversity in Pleistocene populations than previously known.
Parallel changes in genetic diversity and species diversity following a natural disturbance
Authors: EVANNO GUILLAUME , CASTELLA EMMANUEL , ANTOINE CÉLINE , PAILLAT GABRIELLE , GOUDET JÉRÔME
Published: February 2009

We examined the spatial and temporal variation of species diversity and genetic diversity in a metacommunity comprising 16 species of freshwater gastropods. We monitored species abundance at five localities of the Ain river floodplain in southeastern France, over a period of four years. Using 190 AFLP loci, we monitored the genetic diversity of Radix balthica, one of the most abundant gastropod species of the metacommunity, twice during that period. An exceptionally intense drought occurred during the last two years and differentially affected the study sites. This allowed us to test the effect of natural disturbances on changes in both genetic and species diversity. Overall, local (alpha) diversity declined as reflected by lower values of gene diversity HS and evenness. In parallel, the among‐sites (beta) diversity increased at both the genetic (FST) and species (FSTC) levels. These results suggest that disturbances can lead to similar changes in genetic and community structure through the combined effects of selective and neutral processes.
McsA and B mediate the delocalization of competence proteins from the cell poles of Bacillus subtilis
Authors: Hahn Jeanette , Kramer Naomi , Briley Kenneth , Dubnau David
Published: February 2009

During the development of transformability (competence), Bacillus subtilis synthesizes a set of proteins that mediate both the uptake of DNA at the cell poles and the recombination of this DNA with the resident chromosome. Most, if not all, of these Com proteins localize to the poles of the cell, where they associate with one another, and are then seen to delocalize as transformability declines. In this study, we use fluorescence microscopy to analyse the localization and delocalization processes. We show that localization most likely occurs by a diffusion‐capture mechanism, not requiring metabolic energy, whereas delocalization is prevented in the presence of sodium azide. The kinetics of localization suggest that this process requires the synthesis of a critical protein or set of proteins, which are needed to anchor the Com protein complex to the poles. We further show that the protein kinase proteins McsA and McsB are needed for delocalization, as are ClpP and either of the AAA+ (ATPases associated with a variety of cellular activities) proteins ClpC or ClpE. Of these proteins, at least McsB, ClpC and ClpP localize to the cell poles of competent cells. Our evidence strongly suggests that delocalization depends on the degradation of the postulated anchor protein(s) by the McsA‐McsB‐(ClpC or ClpE)‐ClpP protease in an ATP‐dependent process that involves the autophosphorylation of McsB. The extent of cell–pole association at any given time reflects the relative rates of localization and delocalization. The kinetics of this dynamic process differs for individual Com proteins, with the DNA‐binding proteins SsbB and DprA exhibiting less net localization.
Genetics and visceral leishmaniasis: of mice and man
Authors: BLACKWELL J. M. , FAKIOLA M. , IBRAHIM M. E. , JAMIESON S. E. , JERONIMO S. B. , MILLER E. N. , MISHRA A. , MOHAMED H. S. , PEACOCK C. S. , RAJU M. , SUNDAR S. , WILSON M. E.
Published: February 2009

Ninety per cent of the 500 000 annual new cases of visceral leishmaniasis (VL) occur in India/Bangladesh/Nepal, Sudan and Brazil. Importantly, 80–90% of human infections are sub‐clinical or asymptomatic, usually associated with strong cell‐mediated immunity. Understanding the environmental and genetic risk factors that determine why two people with the same exposure to infection differ in susceptibility could provide important leads for improved therapies. Recent research using candidate gene association analysis and genome‐wide linkage studies (GWLS) in collections of families from Sudan, Brazil and India have identified a number of genes/regions related both to environmental risk factors (e.g. iron), as well as genes that determine type 1 vs. type 2 cellular immune responses. However, until now all of the allelic association studies carried out have been underpowered to find genes of small effect sizes (odds ratios or OR < 2), and GWLS using multicase pedigrees have only been powered to find single major genes, or at best oligogenic control. The accumulation of large DNA banks from India and Brazil now makes it possible to undertake genome‐wide association studies (GWAS), which are ongoing as part of phase 2 of the Wellcome Trust Case Control Consortium. Data from this analysis should seed research into novel genes and mechanisms that influence susceptibility to VL.
Gene expression profiling of ovine keratinocytes stimulated withPsoroptes ovismite antigen – a preliminary study
Authors: WATKINS C. A. , MACKELLAR A. , FREW D. , MACKIE C. , GEORGE A. , HOPKINS J. , BURGESS S. T. G. , MCNEILLY T. N. , HUNTLEY J. F.
Published: February 2009

Sheep scab is caused by the noninvasive mite,Psoroptes ovis, which initiates a profound pro‐inflammatory skin response leading to lesion development. To investigate these early events between the skin and the parasite, primary ovine epidermal keratinocyte cultures were generated and challenged with mite derived antigens. The kinetics of the mRNA response of these cells were monitored by microarray. The results indicated that the cells responded within 1 h of challenge, with a significant increase in the pro‐inflammatory cytokine IL‐8. This result was confirmed by real‐time RT‐PCR, and showed that IL‐8 up‐regulation was maximal at 1 h but declined to pre‐stimulation levels at 24 and 48 h. The IL‐8 mRNA response to mite wash antigens containing secretory and/or excretory proteins was also investigated and compared to the response to whole mite antigen. These studies revealed that the mite wash antigen, at a challenge dose of 10 µg/mL, was markedly more potent and induced significantly higher levels of IL‐8 mRNA than the same concentration of whole mite antigen. These results are discussed in relation to mite establishment and survival on the ovine host.
Genetics of susceptibility to Plasmodium falciparum: from classical malaria resistance genes towards genome‐wide association studies
Authors: VERRA F. , MANGANO V.D. , MODIANO D.
Published: February 2009

Plasmodium falciparum represents one of the strongest selective forces on the human genome. This stable and perennial pressure has contributed to the progressive accumulation in the exposed populations of genetic adaptations to malaria. Descriptive genetic epidemiology provides the initial step of a logical procedure of consequential phases spanning from the identification of genes involved in the resistance/susceptibility to diseases, to the determination of the underlying mechanisms and finally to the possible translation of the acquired knowledge in new control tools. In malaria, the rational development of this strategy is traditionally based on complementary interactions of heterogeneous disciplines going from epidemiology to vaccinology passing through genetics, pathogenesis and immunology. New tools including expression profile analysis and genome‐wide association studies are recently available to explore the complex interactions of host–parasite co‐evolution. Particularly, the combination of genome‐wide association studies with large multi‐centre initiatives can overcome the limits of previous results due to local population dynamics. Thus, we anticipate substantial advances in the interpretation and validation of the effects of genetic variation on malaria susceptibility, and thereby on molecular mechanisms of protective immune responses and pathogenesis.
Combined effect of IL‐10 and TGF‐β1 promoter polymorphisms as a risk factor for aspirin‐intolerant asthma and rhinosinusitis
Authors: Kim S.‐H. , Yang E.‐M. , Lee H.‐N. , Cho B.‐Y. , Ye Y.‐M. , Park H.‐S.
Published: February 2009

Background:  It has been known that interleukin (IL)‐10 promoter polymorphisms at −1082A/G, −819T/C and −592A/C, may influence IL‐10 expression and associate with asthma. Interleukin‐10 facilitates the regulatory function of transforming growth factor (TGF)‐β. The goal of this study was to investigate a gene–gene interaction between IL‐10 and TGF‐β1 polymorphisms in Korean asthmatics with aspirin hypersensitivity.

Methods:  Single‐nucleotide polymorphism genotyping of IL‐10 and TGF‐β1 genes was performed and the functional effect of the IL‐10 polymorphisms was analysed applying a luciferase reporter assay and an electrophoretic mobility shift assay.

Results:  Among the patients with asthma, polymorphism at −1082A/G was significantly associated with the phenotype of aspirin‐intolerant asthma, AIA (P = 0.007, Pc = 0.021). Moreover, a synergistic effect between the TGF‐β1−509C/T and IL‐10−1082A/G polymorphisms on the phenotype of AIA was noted; when stratified by the presence of rhinosinusitis, the frequency of rare alleles (the CT or TT genotype of TGF‐β1−509C/T and AG or GG genotype of IL‐10−1082A/G) was significantly higher in the patients with AIA (15.2%) when compared with those with ATA (6.3%, P = 0.031; odds ratio 4.111; 95% confidence interval 1.504–11.235). In an in vitro functional assay, the −1082G reporter plasmid exhibited significantly greater promoter activity when compared with the −1082A construct in Jurkat T cells (P = 0.011). Moreover, we found that the transcription factor Myc‐associated zinc‐finger protein preferentially bound the −1082G allele.

Conclusion:  Our results suggest that IL‐10 promoter polymorphisms contribute to the development of AIA and that rhinosinusitis may interact genetically with TGF‐β1.