bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid, efficient functional characterization and recovery of HIV-specific human CD8
+
T cells using microengraving
Authors: Varadarajan Navin , Kwon Douglas S. , Law Kenneth M. , Ogunniyi Adebola O. , Anahtar Melis N. , Richter James M. , Walker Bruce D. , Love J. Christopher
Published: February 2012

The nature of certain clinical samples (tissue biopsies, fluids) or the subjects themselves (pediatric subjects, neonates) often constrain the number of cells available to evaluate the breadth of functional T-cell responses to infections or therapeutic interventions. The methods most commonly used to assess this functional diversity ex vivo and to recover specific cells to expand in vitro usually require more than 10
6
cells. Here we present a process to identify antigen-specific responses efficiently ex vivo from 10
4
–10
5
single cells from blood or mucosal tissues using dense arrays of subnanoliter wells. The approach combines on-chip imaging cytometry with a technique for capturing secreted proteins—called “microengraving”—to enumerate antigen-specific responses by single T cells in a manner comparable to conventional assays such as ELISpot and intracellular cytokine staining. Unlike those assays, however, the individual cells identified can be recovered readily by micromanipulation for further characterization in vitro. Applying this method to assess HIV-specific T-cell responses demonstrates that it is possible to establish clonal CD8
+
T-cell lines that represent the most abundant specificities present in circulation using 100- to 1,000-fold fewer cells than traditional approaches require and without extensive genotypic analysis a priori. This rapid (<24 h), efficient, and inexpensive process should improve the comparative study of human T-cell immunology across ages and anatomic compartments.
Human apurinic/apyrimidinic endonuclease 1 translocalizes to mitochondria after photodynamic therapy and protects cells from apoptosis
Authors: Li Meng‐Xia , Shan Jin‐Lu , Wang Dong , He Yong , Zhou Qian , Xia Lei , Zeng Lin‐Li , Li Zeng‐Peng , Wang Ge , Yang Zhen‐Zhou
Published: February 2012

Photodynamic therapy (PDT) is an effective therapeutic regime for lung cancer. Mitochondrial functional failure is considered to be one of the most important factors causing cell death after PDT. However, the detailed mechanisms that are involved are still unclear. We previously reported that apurinic/apyrimidinic endonuclease (APE1) plays a critical role in regulating sensitivity to PDT in the lung cancer A549 cell line. An important mitochondrial regulatory role for APE1 has recently been reported, so therefore we explored the role of APE1 in cell survival after PDT‐induced oxidative stress through regulation of mitochondrial function. We first observed that photoirradiation induced the mitochondrial translocation of APE1. The ability of APE1 to regulate mitochondrial membrane potential and reactive oxygen species (ROS) production after photoirradiation was tested in APE1 knockdown A549 cells. APE1‐deficient A549 cells were characterized as having a lower mitochondrial membrane potential and higher ROS production, which led to increased apoptosis through the mitochondrial pathway after PDT. Additionally, unexpected activity of APE1 was observed in mitochondria: the control of mitochondrial transcriptional activity by redox regulation of mitochondrial transcription factor A (TFAM). Furthermore, two dominant‐negative mutants of APE1 were overexpressed to enhance their individual activities in mitochondria. The results suggest that both these APE1 activities play a role in the regulation of mitochondrial function but through different mechanisms. The present study not only provides possible mechanisms for APE1 in regulating survival after photoirradiation but also uncovers a new activity of APE1 in mitochondria. (Cancer Sci 2012; 103: 882–888)
Clinicopathological and prognostic impact of human epidermal growth factor receptor type 2 (HER2) and hormone receptor expression in uterine papillary serous carcinoma
Authors: Togami Shinichi , Sasajima Yuko , Oi Takateru , Ishikawa Mitsuya , Onda Takashi , Ikeda Shun‐Ichi , Kato Tomoyasu , Tsuda Hitoshi , Kasamatsu Takahiro
Published: February 2012

Uterine papillary serous carcinoma (UPSC) is a rare and aggressive variant of endometrial carcinoma. Little is known about the pathological and biological features of this tumor. Human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) expression have an important role in tumor behavior and clinical outcome, but their relevance in UPSC is not clear. In the present study, the immunohistochemical expression of HER2 and HR was assessed in 27 patients with Stage I disease, 13 with Stage II disease, 25 with Stage III disease, and 6 with Stage IV disease. Correlations between HER2 and HR expression and the clinicopathological parameters of UPSC were evaluated using Cox's univariate and multivariate analyses. For all patients, the 5‐year recurrence‐free survival (RFS) and overall survival (OS) rates were 51% and 66%, respectively; in patients with Stage I, II, III and IV disease, the RFS and OS were 67%/81%, 59%/77%, 43%/54% and 0%/0%, respectively. Of all 71 patients, 14% (10/71) were positive for HER2 and 52% (37/71) were positive for HR. Overexpression of HER2 was correlated with lower OS (P = 0.01), whereas HR overexpression was correlated with higher OS (P = 0.008). In multivariate models, HER2, HR, and histologic subtype were identified as independent prognostic indicators for RFS (P = 0.022, P = 0.018, and P = 0.01, respectively), but HR was the only independent factor associated with OS (P = 0.044). Thus, HER2 and HR are prognostic variables in UPSC, with HR an independent prognostic factor for OS. (Cancer Sci 2012; 103: 926–932)
LXRβ activation increases intestinal cholesterol absorption, leading to an atherogenic lipoprotein profile
Authors: Hu X. , Steffensen K. R. , Jiang Z.‐Y. , Parini P. , Gustafsson J.‐Å. , Gåfvels M. , Eggertsen G.
Published: February 2012

Abstract.  Hu X, Steffensen KR, Jiang Z‐Y, Parini P, Gustafsson J‐Å, Gåfvels M, Eggertsen G (Karolinska Institutet, Huddinge, Stockholm, Sweden; Karolinska Institutet, Huddinge, Stockholm, Sweden; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; and University of Houston, Houston, TX, USA). LXRβ activation increases intestinal cholesterol absorption, leading to an atherogenic lipoprotein profile. J Intern Med 2012; 272: 452–464.

Objectives.  Liver X receptors (LXRs) are essential for the regulation of intestinal cholesterol absorption. Because two isoforms exist, LXRα and LXRβ, with overlapping but not identical functions, we investigated whether LXRα and LXRβ exert different effects on intestinal cholesterol absorption.

Design.  Wild‐type (WT), LXRα−/− and LXRβ−/− mice were fed control diet, 0.2% cholesterol‐enriched diet or 0.2% cholesterol‐enriched diet plus the LXR agonist GW3965.

Results.  When fed a control diet, all three genotypes showed similar levels of cholesterol absorption. Of interest, a significant increase in cholesterol absorption was found in the LXRα−/− mice, but not in the WT or LXRβ−/− animals, when fed a diet enriched with 0.2% cholesterol or 0.2% cholesterol + GW3965. Reduced faecal neutral sterol excretion and a hydrophobic bile acid profile were also observed in LXRα−/− mice. Greater increases in the apolipoprotein (apo)B‐containing lipoproteins in serum were seen in the LXRα−/− mice. A 0.2% cholesterol + GW3965 diet suppressed intestinal Npc1l1 protein expression to the same extent for all genotypes, while Abca1 and Abcg5 were elevated to the same degree.

Conclusions.  In the intestine, LXRα and LXRβ seem to exert similar effects on expression of cholesterol‐transporting proteins such as Npc1l1. Selective activation of LXRβ may generate effects such as increased cholesterol absorption and elevated serum levels of apoB‐containing lipoproteins, which seem to be counteracted by LXRα. Therefore, an intestinal LXRβ‐specific pathway might exist in terms of cholesterol transportation in addition to the main pathway.
Anti‐apolipoprotein A‐1 IgG in patients with myocardial infarction promotes inflammation through TLR2/CD14 complex
Authors: Pagano S. , Satta N. , Werling D. , Offord V. , de Moerloose P. , Charbonney E. , Hochstrasser D. , Roux‐Lombard P. , Vuilleumier N.
Published: February 2012

Abstract.  Pagano S, Satta N, Werling D, Offord V, de Moerloose P, Charbonney E, Hochstrasser D, Roux‐Lombard P, Vuilleumier N (Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland; Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland; Royal Veterinary College, Hertfordshire, UK; St. Michael’s Hospital, Toronto, Canada; Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland). Anti‐apolipoprotein A‐1 IgG in patients with myocardial infarction promotes inflammation through TLR2/CD14 complex. J Intern Med 2012; 272: 344–357.

Objectives.  Toll‐like receptor (TLR)‐mediated vascular inflammation, inducible by – amongst other factors – auto‐antibodies, is increasingly recognized as a potential mediator of cardiovascular disease. We investigated whether anti‐apolipoprotein (Apo)A‐1 IgG was associated with a pro‐inflammatory cytokine profile in myocardial infarction (MI) patients and whether anti‐ApoA‐1 IgG elicited a pro‐inflammatory response by activating TLRs.

Methods.  As surrogate markers of atherosclerotic plaque vulnerability, interleukin (IL)‐6, tumour necrosis factor (TNF)‐α, matrix metalloproteinase (MMP)‐9 and MMP‐3 levels were assessed in 221 consecutive MI patients. Using human monocyte‐derived macrophages (HMDMs) we investigated (i) the anti‐ApoA‐1 IgG interaction with TLRs using proximity ligation assay and (ii) anti‐ApoA‐1 IgG‐dependent IL‐6/TNF‐α production. TLR involvement was further confirmed using HEK293‐Blue TLR‐2/‐4 cells and by computational docking simulations.

Results.  In MI patients, anti‐ApoA‐1 IgG positivity was associated with higher levels of IL‐6, TNF‐α and MMP‐9, but lower MMP‐3 levels. In in vitro experiments, anti‐ApoA‐1 antibodies bound to HDMDs in a TLR2‐dependent manner, resulting in nuclear translocation of NFκB and a significant increase in TNF‐α and IL‐6 production. Subsequent functional studies highlighted the importance of CD14 as co‐receptor in the anti‐ApoA‐1 IgG–TLR2‐induced cytokine production. Additional bioinformatic studies identified structural homologies between TLR2 and ApoA‐1, which may explain the observed cross‐reactivity between antibodies against these two molecules.

Conclusions.  Anti‐ApoA‐1 IgG positivity in MI is associated with a high‐risk cytokine profile. These auto‐antibodies promote inflammation by stimulating the TLR2/CD14 receptor complex, probably because of molecular mimicry, which may contribute to atherosclerosis‐related complications in patients.
A functional variant in the promoter region regulates the C‐reactive protein gene and is a potential candidate for increased risk of atrial fibrillation
Authors: Chang S.‐N. , Tsai C.‐T. , Wu C.‐K. , Lee J.‐K. , Lai L.‐P. , Huang S.‐W. , Huang L.‐Y. , Tseng C.‐D. , Lin J.‐L. , Chiang F.‐T. , Hwang J.‐J.
Published: February 2012

Abstract.  Chang S‐N, Tsai C‐T, Wu C‐K, Lee J‐K, Lai L‐P, Huang S‐W, Huang L‐Y, Tseng C‐D, Lin J‐L, Chiang F‐T, Hwang J‐J (National Taiwan University Hospital Yun‐Lin Branch, Yun‐Lin; National Taiwan University Hospital, Taipei; National Taiwan University Hospital, Taipei; Institute of Pharmacology, Taipei; and Graduate Institute of Biomedical Engineering, Taipei, Taiwan). A functional variant in the promoter region regulates the C‐reactive protein gene and is a potential candidate for increased risk of atrial fibrillation. J Intern Med 2012; 272: 305–315.

Objectives.  In a large population‐based cohort, the level of C‐reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown.

Methods.  A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association.

Results.  Three polymorphisms (T‐861C, A‐821G and C‐390A/C‐390T) were found in the 1‐kb promoter of CRP. A triallelic polymorphism (C‐390A/C‐390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The −390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L‐type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts.

Conclusion.  A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.
Thyroid Transcription Factor 1, a Homeodomain Containing Transcription Factor, Contributes to Regulating Periodic Oscillations in GnRH Gene Expression
Authors: Matagne V. , Kim J. G. , Ryu B. J. , Hur M. K. , Kim M. S. , Kim K. , Park B. S. , Damante G. , Smiley G. , Lee B. J. , Ojeda S. R.
Published: February 2012

Thyroid transcription factor 1 (TTF1), a member of the Nkx family of transcription factors required for basal forebrain morphogenesis, functions in the postnatal hypothalamus as a transcriptional regulator of genes encoding neuromodulators and hypophysiotrophic peptides. One of these peptides is gonadotrophin‐releasing hormone (GnRH). In the present study, we show that Ttf1 mRNA abundance varies in a diurnal and melatonin‐dependent fashion in the preoptic area of the rat, with maximal Ttf1 expression attained during the dark phase of the light/dark cycle, preceding the nocturnal peak in GnRH mRNA content. GnRH promoter activity oscillates in a circadian manner in GT1‐7 cells, and this pattern is enhanced by TTF1 and blunted by small interfering RNA‐mediated Ttf1 gene silencing. TTF1 transactivates GnRH transcription by binding to two sites in the GnRH promoter. Rat GnRH neurones in situ contain key proteins components of the positive (BMAL1, CLOCK) and negative (PER1) limbs of the circadian oscillator, and these proteins repress Ttf1 promoter activity in vitro. By contrast, Ttf1 transcription is activated by CRY1, a clock component required for circadian rhythmicity. In turn, TTF1 represses transcription of Rev‐erbα, a heme receptor that controls circadian transcription within the positive limb of the circadian oscillator. These findings suggest that TTF1 is a component of the molecular machinery controlling circadian oscillations in GnRH gene transcription.
Attraction of Stomoxys sp. to various fruits and flowers in Mali
Authors: MÜLLER G. C. , HOGSETTE J. A. , BEIER J. C. , TRAORE S. F. , TOURE M. B. , TRAORE M. M. , BAH S. , DOUMBIA S. , SCHLEIN Y.
Published: February 2012

The attraction of three Stomoxys species to 26 fruits and 26 flowers of different plant species was investigated in two different sites in Mali during 2008. Stomoxys niger bilineatus Grunberg (Diptera: Muscidae) was attracted to a wider spectrum of species, significantly attracted by four fruits and eight flowers compared with control traps, whereas S. sitiens Rondani (Diptera: Muscidae) was attracted to six fruits and seven flowers of different plants, and S. calcitrans L. (Diptera: Muscidae) was only attracted to one fruit and three flowers. Cold anthrone assays showed a significantly higher prevalence of sugar feeding amongst all three species at the lagoon site than at the site near Mopti. The rhythm of activity study shows temporally separated blood‐ and sugar‐feeding periods for S. niger bilineatus and S. sitiens, but not for S. calcitrans. A comparison between blood and sugar feeding throughout the day shows that sugar feeding activity is as frequent as blood feeding activity. Because not much is known about the preferred sugar sources for Stomoxys species in their natural habitats, the present study provides valuable information regarding the attraction capability of several plants with possible future implication for Stomoxys control strategies.
The role of flotillin FloA and stomatin StoA in the maintenance of apical sterol‐rich membrane domains and polarity in the filamentous fungus Aspergillus nidulans
Authors: Takeshita Norio , Diallinas George , Fischer Reinhard
Published: February 2012

Apical sterol‐rich plasma membrane domains (SRDs), which can be viewed using the sterol‐binding fluorescent dye filipin, are gaining attention for their important roles in polarized growth of filamentous fungi. The microdomain scaffolding protein flotillin/reggie and related stomatin were thought to be good candidates involved in the formation of SRDs. Here, we show that the flotillin/reggie orthologue FloA tagged with GFP localized as stable dots along the plasma membrane except hyphal tips. Deletion of floA reduced the growth rate, often resulted in irregularly shaped hyphae and impaired SRDs. In contrast, the stomatin orthologue StoA, tagged with GFP, localized at the cortex of young branch tips and at the subapical cortex in long hyphal tips, and was transported bi‐directionally along microtubules on endosomes. Deletion of stoA resulted in irregular hyphal morphology and increased branching especially in young hyphae, but did not obviously affect SRDs. Double deletion of floA and stoA enhanced the defects of growth and hyphal morphology. Our data suggest that the plasma membrane of hyphal tips and in subapical regions are distinct and that FloA is involved in membrane compartmentalization and probably indirectly in SRD maintenance.
Importance and regulation of inositol biosynthesis during growth and differentiation of Streptomyces
Authors: Zhang Guohua , Tian Yuqing , Hu Kun , Zhu Yu , Chater Keith F. , Feng Chi , Liu Gang , Tan Huarong
Published: February 2012

Unusually among bacteria, actinobacteria possess myo‐inositol 1‐phosphate synthase (mIPS). In the developmentally complex Streptomyces coelicolor, the mIPS‐encoding gene (inoA) is cotranscribed with a putative regulatory gene (inoR). The inoRA transcript was more abundant in an inoR in‐frame deletion mutant, and InoR formed different complexes in vitro with an extensive region around the inoRA promoter. Binding was relieved by adding glucose 6‐phosphate. Thus, InoR is a metabolite‐sensitive autorepressor that influences inoA expression, and hence the level of inositol, by controlling transcription from PinoRA. Disruption of inoA resulted in inositol‐dependent growth and development, with full phenotypic correction at 0.1 mM inositol: at lower inositol concentrations differentiation was arrested at intermediate stages. This pattern may partly reflect increased demand for membrane phospholipids during sporulation septation. A corresponding sharp upregulation of inoRA transcription coincident with sporulation was dependent on a developmental regulator, WhiI. A truncated form of WhiI could bind two sites downstream of PinoRA, and one of the WhiI‐binding sites overlapped the InoR‐binding site. The combined action of a metabolic regulator and a developmental regulator at the simple PinoRA promoter is a previously undescribed strategy for the differential provision of developmentally appropriate levels of a substance required during the formation of spore chains.
SlrA/SinR/SlrR inhibits motility gene expression upstream of a hypersensitive and hysteretic switch at the level of σD in Bacillus subtilis
Authors: Cozy Loralyn M. , Phillips Andrew M. , Calvo Rebecca A. , Bate Ashley R. , Hsueh Yi‐Huang , Bonneau Richard , Eichenberger Patrick , Kearns Daniel B.
Published: February 2012

Exponentially growing Bacillus subtilis cultures are epigenetically differentiated into two subpopulations in which cells are either ON or OFF for σd‐dependent gene expression: a pattern suggestive of bistability. The gene encoding σD, sigD, is part of the 31‐gene fla/che operon where its location at the 3′ end, 25 kb away from the strong Pfla/che promoter, determines its expression level relative to a threshold. Here we show that addition of a single extra copy of the slrA gene in the chromosome inhibited σd‐dependent gene expression. SlrA together with SinR and SlrR reduced sigD transcript by potentiating a distance‐dependent decrease in fla/che operon transcript abundance that was not mediated by changes in expression from the Pfla/che promoter. Consistent with acting upstream of σD, SlrA/SinR/SlrR was bypassed by artificial ectopic expression of sigD and hysteretically maintained for 20 generations by engaging the sigD gene at the native locus. SlrA/SinR/SlrR was also bypassed by increasing fla/che transcription and resulted in a hypersensitive output in flagellin expression. Thus, flagellin gene expression demonstrated hypersensitivity and hysteresis and we conclude that σd‐dependent gene expression is bistable.
Further evidence for linkage of bipolar disorder to chromosomes 6 and 17 in a new independent pedigree series
Authors: Greenwood Tiffany A , Nievergelt Caroline M , Sadovnick A Dessa , Remick Ronald A , Keck Paul E , McElroy Susan L , Shekhtman Tatyana , McKinney Rebecca , Kelsoe John R
Published: February 2012

Greenwood TA, Nievergelt CM, Sadovnick AD, Remick RA, Keck PE Jr, McElroy SL, Shekhtman T, McKinney R, Kelsoe JR. Further evidence for linkage of bipolar disorder to chromosomes 6 and 17 in a new independent pedigree series. Bipolar Disord 2012: 14: 71–79. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Objectives:  We have previously reported the results of a linkage analysis of bipolar disorder in an initial set of 20 pedigrees ascertained through collaboration among three sites. We now report the results of our genome‐wide linkage analysis in an independent sample of 34 pedigrees segregating bipolar disorder.

Methods:  Families were ascertained through a bipolar I or II disorder proband for the presence of bipolar I disorder, bipolar II disorder, or recurrent major depression in at least two other family members. A total of 440 markers at an average spacing of 8 cM were genotyped in 229 family members using fluorescent methods.

Results:  Initial nonparametric analyses of chromosomes 6 and 17 provided evidence for a modest replication of linkage to these chromosomes previously reported in other studies. Additional analyses using multipoint parametric methods provided further evidence to support the 6q25 region with a heterogeneity logarithm of odds score of 3.28. Evidence from two‐point parametric analyses also provides a modest replication of our previous findings of linkage to the 23 cM region of chromosome 22q13 in our original University of California, San Diego sample of 20 families and 57 families from the National Institute of Mental Health bipolar disorder sample.

Conclusions:  Our results suggest replication of some reported linkage peaks, such as 6q25 and 17p12; however, other peaks from our own previous study, such as 5p15, 13q32, and 22q13, were either not replicated or were only modestly replicated in these analyses.
Pollen‐specific immunoglobulin E positivity is associated with worsening of depression scores in bipolar disorder patients during high pollen season
Authors: Manalai Partam , Hamilton Robert G , Langenberg Patricia , Kosisky Susan E , Lapidus Manana , Sleemi Aamar , Scrandis Debra , Cabassa Johanna A , Rogers Christine A , Regenold William T , Dickerson Faith , Vittone Bernard J , Guzman Alvaro , Balis Theodora , Tonelli Leonardo H , Postolache Teodor T
Published: February 2012

Manalai P, Hamilton RG, Langenberg P, Kosisky SE, Lapidus M, Sleemi A, Scrandis D, Cabassa JA, Rogers CA, Regenold WT, Dickerson F, Vittone BJ, Guzman A, Balis T, Tonelli LH, Postolache TT. Pollen‐specific immunoglobulin E positivity is associated with worsening of depression scores in bipolar disorder patients during high pollen season. Bipolar Disord 2012: 14: 90–98. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Objective:  An association between allergic disease and depression has been consistently reported, but whether the key mediating ingredients are predominantly biological, psychological, or mere artifacts remains unknown. In the current study, we examined a hypothesized relationship between allergen‐specific immunoglobulin E (IgE) status and changes in allergy symptoms with worsening in depression scores.

Methods:  In patients with recurrent mood disorders, we individually coupled sensitization to specific seasonal aeroallergens (as assessed by allergen‐specific IgE) with temporal windows of exposure to aeroallergens (low versus high tree or ragweed pollen counts, measured according to the National Allergy Bureau guidelines). We compared Structured Interview Guide for the Hamilton Depression Rating Scale–Seasonal Affective Disorder Version (SIGH‐SAD) depression score changes in 41 patients with mood disorders [25 with major depression and 16 with bipolar I disorder, diagnosed by Structured Clinical Interview for DSM (SCID)] seropositive for tree or ragweed pollen‐specific IgE antibody versus 53 patients with mood disorders (30 with major depression and 23 with bipolar I disorder) seronegative for aeroallergen‐specific IgE.

Results:  Worsening in total depressive scores from low to high pollen exposure was greater in allergen‐specific IgE‐positive patients as compared to allergen‐specific IgE antibody‐negative patients (p = 0.01). When stratified by polarity, the association was significant only in patients with bipolar I disorder (p = 0.004). This relationship was resilient to adjustment for changes in allergy symptom scores.

Conclusion:  To our knowledge, this is the first report of coupling a molecular marker of vulnerability (allergen‐specific IgE) with a specific environmental trigger (airborne allergens) leading to exacerbation of depression in patients with bipolar I disorder.
Relationship between suicidality and impulsivity in bipolar I disorder: a diffusion tensor imaging study
Authors: Mahon Katie , Burdick Katherine E , Wu Jinghui , Ardekani Babak A , Szeszko Philip R
Published: February 2012

Mahon K, Burdick KE, Wu J, Ardekani BA, Szeszko PR. Relationship between suicidality and impulsivity in bipolar I disorder: a diffusion tensor imaging study.  Bipolar Disord 2012: 14: 80–89. © 2012 The Authors.  Journal compilation © 2012 John Wiley & Sons A/S.

Background:  Impulsivity is characteristic of individuals with bipolar disorder and may be a contributing factor to the high rate of suicide in patients with this disorder. Although white matter abnormalities have been implicated in the pathophysiology of bipolar disorder, their relationship to impulsivity and suicidality in this disorder has not been well‐investigated.

Methods:  Diffusion tensor imaging scans were acquired in 14 bipolar disorder patients with a prior suicide attempt, 15 bipolar disorder patients with no prior suicide attempt, and 15 healthy volunteers. Bipolar disorder patients received clinical assessments including measures of impulsivity, depression, mania, and anxiety. Images were processed using the Tract‐Based Spatial Statistics method in the FSL software package.

Results:  Bipolar disorder patients with a prior suicide attempt had lower fractional anisotropy (FA) within the left orbital frontal white matter (p < 0.05, corrected) and higher overall impulsivity compared to patients without a previous suicide attempt. Among patients with a prior suicide attempt, FA in the orbital frontal white matter region correlated inversely with motor impulsivity.

Conclusions:  Abnormal orbital frontal white matter may play a role in impulsive and suicidal behavior among patients with bipolar disorder.
Olfactory acuity is associated with mood and function in a pilot study of stable bipolar disorder patients
Authors: Hardy Caitlin , Rosedale Mary , Messinger Julie W , Kleinhaus Karine , Aujero Nicole , Silva Hanna , Goetz Raymond R , Goetz Deborah , Harkavy‐Friedman Jill , Malaspina Dolores
Published: February 2012

Hardy C, Rosedale M, Messinger JW, Kleinhaus K, Aujero N, Silva H, Goetz RR, Goetz D, Harkavy‐Friedman J, Malaspina D. Olfactory acuity is associated with mood and function in a pilot study of stable bipolar disorder patients.  Bipolar Disord 2012: 14: 109–117. © 2012 The Authors.  Journal compilation © 2012 John Wiley & Sons A/S.

Objectives:  Olfactory dysfunction is described in several neuropsychiatric disorders but there is little research on olfactory processing in bipolar disorder.

Methods:  We assessed odor detection threshold (sensitivity) and smell identification test scores, along with symptoms, cognition, and social function in 20 DSM‐IV bipolar disorder patients and 44 control subjects.

Results:  The patient and control groups had similar demographic measures, intelligence, and mean olfaction scores, but significantly differed in social domains, including adjustment, function, and anxiety. Odor detection sensitivity showed significantly opposite correlations for the depressive and manic mood domains in bipolar disorder (r to z = 2.83, p = 0.005). Depressive symptoms were related to increased sensitivity (the ability to detect odors at a lower concentration) and mania symptoms were related to decreased sensitivity for odor detection. Increased sensitivity for odor detection also predicted significantly better employment (r = −0.642, p = 0.024), whereas less sensitivity was associated with social avoidance (r = 0.702, p = 0.024) and social fear (r = 0.610, p = 0.046).

Conclusions:  Diminished odor detection sensitivity predicted mania and social avoidance, whereas more sensitive odor detection predicted more depressive symptoms but better employment functioning in bipolar disorder patients. Odor acuity may be an illness state marker of mood syndromes in bipolar disorder. Alternatively, differences in odor acuity may identify heterogeneous subgroups within the bipolar spectrum. Longitudinal assessments in a large, sex‐stratified sample are needed to understand the implications of odor sensitivity in patients with bipolar disorder.
Predator Detection is Limited in Microhabitats with High Light Intensity: An Experiment with Brown‐Headed Cowbirds
Authors: Fernández‐Juricic Esteban , Deisher Marcella , Stark Amy C. , Randolet Jacquelyn
Published: February 2012

Variations in ambient light conditions across different microhabitats can modify the detectability of predators and prey. Prey have been shown to be more visible in sunlit than in shaded patches, leading to higher predation risk and more investment in vigilance (predation risk hypothesis). Additionally, prey have been hypothesized to take longer to detect predators in sunlit compared to shaded patches because of the excess of sunlight causing glare effects (disability glare hypothesis). We tested the predictions of these two non‐mutually exclusive hypotheses in a seminatural experiment with brown‐headed cowbirds by measuring vigilance behavior and detection of a ground predator in patches under the shade of vegetation and in the open. Light intensity and achromatic contrast were higher in the sunlit patches, which could enhance glare effects, but chromatic contrast was higher in the shaded patches. Brown‐headed cowbirds took longer to show alert reactions to and flee from a ground predator in sunlit compared to shaded patches. However, the two parameters associated with perceived predation risk (vigilance prior to the predator exposure and time to resume foraging after the attack) did not differ between sunlit and shaded patches. Our findings support to a greater extent the disability glare hypothesis than the predation risk hypothesis. Overall, ambient light conditions can affect two critical components of behavioral predator–prey interactions in terrestrial habitats: detection of and escape from predators. The effects of disability glare are expected to be more pronounced in bird species with wider visual fields or without sun‐shading structures; however, species may compensate through various behaviors (e.g. avoidance of sunlit patches and changes in head orientation).
A Behavioral Biology for the Future
Authors: Burghardt Gordon M.
Published: February 2012

Some comments are appended to Patrick Bateson’s reflections on the future of behavioral biology that were triggered by remembering the contributions of Günter Tembrock to ethology. While the suggestions made are valid and insightful, a few specific areas where exciting research possibilities may reside are added including those involving communication and language, culture and ritual, brain imaging, genetics, animal tracking, and aesthetics. The need for the historical grounding of graduate education in behavior studies is also emphasized as an important possible factor if the future will effectively fulfill its mission and recognize its legacy.
Effect of gastric acid suppression with pantoprazole on the efficacy of sevelamer hydrochloride as a phosphate binder in haemodialysis patients: A pilot study
Authors: LAI BERYL , CERVELLI MATTHEW J
Published: February 2012

Sevelamer hydrochloride (HCL) is thought to require an appropriately acidic environment in order to bind gastrointestinal phosphate. Changes in gastric acidity with acid suppressants may therefore alter the efficacy of sevelamer HCL. Given the widespread use of acid suppression therapy in chronic kidney disease patients, there is potential for a common significant drug interaction to occur. This pilot study evaluated the in vivo effect of gastric acid suppression with pantoprazole on the efficacy of sevelamer HCL as a phosphate binder in maintenance haemodialysis patients. The study protocol was a cross‐over, double‐blinded, randomized, placebo‐controlled trial in 10 haemodialysis patients randomly assigned to pantoprazole 40 mg daily or placebo for two consecutive 6‐week periods. Serum phosphate was not significantly altered during pantoprazole compared with placebo treatment (1.61 ± 0.45 mmol/L vs 1.76 ± 0.42 mmol/L, P = 0.204). There were no differences in serum calcium, parathyroid hormone and bicarbonate. This pilot study demonstrates preliminary in vivo evidence for no effect of gastric acid suppression on the effectiveness of sevelamer HCL. Our results are limited by small sample size and therefore, larger experimental studies should be conducted. Although our study did not find a significant drug interaction, given the high prevalence of acid suppressant use in dialysis patients, physicians should be aware of the potential influence of acid suppression on the efficacy of phosphate binders and regularly assess the clinical need for acid suppression therapy.
Polypharmacy – we make it worse! A cross‐sectional study from an acute admissions unit
Authors: Betteridge T. M. , Frampton C. M. , Jardine D. L.
Published: February 2012

Although polypharmacy is a major problem in the elderly, very few data have been published from Australasia. We retrospectively audited 68% of elderly patients admitted acutely to our medical unit (n= 424, mean age 80.3 ± 8 years) during a 30‐day period (September, 2008). We found that long‐term medications increased during hospital stay from 6.6 ± 4 to 7.7 ± 4 (P < 0.001). Adverse drug reactions were responsible for 24 admissions (5.7%). Polypharmacy is made worse by acute admission to hospital.
Advanced extragonadal yolk sac tumor serially followed up with 18F‐fluorodexyglucose‐positoron emission tomography and computerized tomography and serum alpha‐fetoprotein
Authors: Baba Tsukasa , Su Saori , Umeoka Shigeaki , Abiko Kaoru , Nakamoto Yuji , Mandai Masaki , Matsumura Noriomi , Konishi Ikuo
Published: February 2012

Although yolk sac tumors (YSTs) are the second most common malignant germ cell tumor of the ovary, those arising from the omentum or pelvic peritoneum are extremely rare and have no established treatment guidelines. We report a case of a primary YST disseminated throughout the abdomen and associated with a high serum alpha‐fetoprotein (AFP) elevation (441 611 ng/ml). Optimal cytoreduction was not achieved in order to preserve the patient's fertility and avoid adjacent organ injury. Residual tumor responded to adjuvant chemotherapy with a sharp decline in AFP levels, and confirmed remission was documented by serial 18F‐fluorodexyglucose‐positoron emission tomography and computerized tomography (FDG‐PET/CT). In cases of advanced YST with unresectable residual disease, AFP levels combined with FDG‐PET/CT scans may be a helpful way to monitor treatment response and assist in treatment planning for a disease that primarily affects young women who may desire to preserve fertility.
Measurement of the fetal isovolumetric contraction time in the fetus with a left ventricular aneurysm
Authors: Fujita Yasuyuki , Hidaka Nobuhiro , Yumoto Yasuo , Morihana Eiji , Fukushima Kotaro , Wake Norio
Published: February 2012

We present a case of an antenatally diagnosed congenital aneurysm of the left ventricle in which fetal cardiac contractility was evaluated by measuring the fetal isovolumetric contraction time (ICT). The workup of the fetus at 26 weeks' gestation led to the identification of a left ventricle aneurysm. Initially, the value of ICT of the left ventricle indicated adequate cardiac function. However, the fetal ICT was gradually prolonged, suspecting deteriorated cardiac contractility. Following an uncomplicated term delivery, a postnatal echocardiogram showed normal cardiac function. It is considered that because of the hypokinesis of the wall of the left ventricular aneurysm, the ICT did not fully predict cardiac function in this setting.
Cyanobacterial construction of hot spring siliceous stromatolites in Yellowstone National Park
Authors: Pepe‐Ranney Charles , Berelson William M. , Corsetti Frank A. , Treants Merika , Spear John R.
Published: February 2012

Living stromatolites growing in a hot spring in Yellowstone National Park are composed of silica‐encrusted cyanobacterial mats. Two cyanobacterial mat types grow on the stromatolite surfaces and are preserved as two distinct lithofacies. One mat is present when the stromatolites are submerged or at the water–atmosphere interface and the other when stromatolites protrude from the hot spring. The lithofacies created by the encrustation of submerged mats constitutes the bulk of the stromatolites, is comprised of silica‐encrusted filaments, and is distinctly laminated. To better understand the cyanobacterial membership and community structure differences between the mats, we collected mat samples from each type. Molecular methods revealed that submerged mat cyanobacteria were predominantly one novel phylotype while the exposed mats were predominantly heterocystous phylotypes (Chlorogloeopsis HTF and Fischerella). The cyanobacterium dominating the submerged mat type does not belong in any of the subphylum groups of cyanobacteria recognized by the Ribosomal Database Project and has also been found in association with travertine stromatolites in a Southwest Japan hot spring. Cyanobacterial membership profiles indicate that the heterocystous phylotypes are ‘rare biosphere’ members of the submerged mats. The heterocystous phylotypes likely emerge when the water level of the hot spring drops. Environmental pressures tied to water level such as sulfide exposure and possibly oxygen tension may inhibit the heterocystous types in submerged mats. These living stromatolites are finely laminated and therefore, in texture, may better represent similarly laminated ancient forms compared with more coarsely laminated living marine examples.
A third mode of surface‐associated growth: immobilization of Salmonella enterica serovar Typhimurium modulates the RpoS‐directed transcriptional programme
Authors: Knudsen Gitte M. , Nielsen Maj‐Britt , Grassby Terri , Danino‐Appleton Vittoria , Thomsen Line E. , Colquhoun Ian J. , Brocklehurst Tim F. , Olsen John E. , Hinton Jay C. D.
Published: February 2012

Although the growth of bacteria has been studied for more than a century, it is only in recent decades that surface‐associated growth has received attention. In addition to the well‐characterized biofilm and swarming lifestyles, bacteria can also develop as micro‐colonies supported by structured environments in both food products and the GI tract. This immobilized mode of growth has not been widely studied. To develop our understanding of the effects of immobilization upon a food‐borne bacterial pathogen, we used the IFR Gel Cassette model. The transcriptional programme and metabolomic profile of Salmonella enterica serovar Typhimurium ST4/74 were compared during planktonic and immobilized growth, and a number of immobilization‐specific characteristics were identified. Immobilized S. Typhimurium did not express motility and chemotaxis genes, and electron microscopy revealed the absence of flagella. The expression of RpoS‐dependent genes and the level of RpoS protein were increased in immobilized bacteria, compared with planktonic growth. Immobilized growth prevented the induction of SPI1, SPI4 and SPI5 gene expression, likely mediated by the FliZ transcriptional regulator. Using an epithelial cell‐based assay, we showed that immobilized S. Typhimurium was significantly less invasive than planktonic bacteria, and we suggest that S. Typhimurium grown in immobilized environments are less virulent than planktonic bacteria. Our findings identify immobilization as a third type of surface‐associated growth that is distinct from the biofilm and swarming lifestyles of Salmonella.
The island biogeography of languages
Authors: Gavin Michael C. , Sibanda Nokuthaba
Published: February 2012

Aim To examine the degree to which area, isolation, environmental conditions and time since first settlement explain variation in language richness among islands.

Location Pacific islands ranging east–west from Rapa Nui to Indonesia and north–south from Hawaii to New Zealand.

Methods We constructed a dataset of 264 Pacific islands that support 1640 languages (c. 24% of the world's languages). We examined possible predictors of language richness using three different types of models: linear regression models, linear mixed models that included random effects for language phylogeny and simultaneous autoregressive models. We tested whether the following variables, alone or in combination, predict language richness: island area and isolation, climate (rainfall, temperature), mean growing season, soil fertility, habitat heterogeneity (elevation, number of ecoregions), time since first human settlement.

Results We identified two optimal models (delta Akaike information criterion < 2). One (R2= 0.52) included area, with 86% of remaining variation accounted for by random effects for phylogeny. The other (R2= 0.56) included a spatial component, area and a suite of other variables (of which isolation and settlement scale were significant). Of the hypotheses tested (mean growing season, ecological risk, habitat heterogeneity, climate, time since settlement, area–isolation theory), area–isolation performed best, alone explaining 44% of variation in language richness.

Main conclusions Language diversity relates strongly to island area, and, after controlling for area, with variables linked to isolation (e.g. distance to continent, time since settlement). The influence of environmental productivity may be scale and context dependent. Although environmental productivity may shape language diversity patterns at a global scale, it plays little role on Pacific islands. Approximately half the variance in language richness remains unexplained. Unlike other taxa, for which area, isolation and environmental conditions explain up to 90% of variation in richness, human diversity patterns appear to also be influenced by other variables (e.g. economic, political and social factors).
Phylogenetic ecology of foliar N and P concentrations and N:P ratios across mediterranean‐type ecosystems
Authors: Stock William D. , Verboom G. Anthony
Published: February 2012

Aim  Interpretations of global‐scale patterns in foliar N and P concentrations and N:P ratios across climatic gradients and biomes often ignore complications imposed by taxonomic and phylogenetic structure in the nutrient concentrations of the constituent taxa. We analysed foliar N and P concentrations and N:P ratios of species from similar climate zones, but with contrasting soil fertility, to determine the relative importance of phylogeny and geographic region in driving foliar nutrient concentrations.

Location  Mediterranean climate regions.

Methods  Mean foliar N and P concentrations of 564 species from five mediterranean climate regions were compiled. Regional comparisons of foliar N and P concentrations and N:P ratios were performed using a phylogenetically independent contrasts (PIC) procedure. We also evaluated phylogenetic structuring in these variables, determining for each clade whether (1) the mean trait value and (2) the variance in trait values deviate significantly from chance expectation.

Results  Foliar N and P concentrations were found to vary between regions, a result confirmed using PIC. Tests of phylogenetic structure identified lineages having unusually high or low N and P concentrations, these being largely consistent amongst two of the regions. There was a general pattern of conservatism in foliar N and P concentrations and N:P ratios with localized instances of overdispersion.

Main conclusions  Our findings identify soil fertility as a strong environmental filter which has led to the dominance of low‐nutrient adapted lineages in the South African Cape and Western Australia. There is also a pronounced clade‐specific ‘stoichiometric homeostasis’ in foliar N and P concentrations and N:P ratios and this strong phylogenetic conservatism, together with the narrow range of foliar concentrations, is an evolutionary outcome of factors associated with developmental and physiological nutrient requirements specific to each lineage. Our results reinforce the need to include phylogenetic considerations in discussions of the biological stoichiometry of plants if we are to expand our current knowledge of foliar N and P concentrations and N:P patterns from an ecological to a biogeographic scale.
Dignity and the right of internally displaced adolescents in Colombia to sexual and reproductive health
Authors: Bosmans Marleen , Gonzalez Fernando , Brems Eva , Temmerman Marleen
Published: February 2012

In Colombia, national policies and laws on the protection of vulnerable populations pay specific attention to the sexual and reproductive health needs and rights of internally displaced adolescents. This paper describes how a United Nations Population Fund (UNFPA)‐supported programme (September 2000–August 2004) on the sexual and reproductive health of internally displaced adolescents contributed to restoring their dignity as a precursor to promoting their sexual and reproductive health rights. Different forms of the arts were used as basic techniques to discover their body and to provide sexual and reproductive health information and education. The arts were found to play a key role in restoring their dignity. Although dignity appeared to be a determinant of greater awareness of rights, it did not lead to increased empowerment with regard to rights. The availability of and access to sexual and reproductive health services remains a problem and displaced populations continue to have little or no power to hold their authorities accountable.