bluuebunny/crossref_metadata_2025 huggingface dataset:
Facial expressions of emotion are not culturally universal
Authors: Jack Rachael E. , Garrod Oliver G. B. , Yu Hui , Caldara Roberto , Schyns Philippe G.
Published: April 2012

Since Darwin’s seminal works, the universality of facial expressions of emotion has remained one of the longest standing debates in the biological and social sciences. Briefly stated, the
universality hypothesis
claims that all humans communicate six basic internal emotional states (happy, surprise, fear, disgust, anger, and sad) using the same facial movements by virtue of their biological and evolutionary origins [Susskind JM, et al. (2008)
Nat Neurosci
11:843–850]. Here, we refute this assumed universality. Using a unique computer graphics platform that combines generative grammars [Chomsky N (1965) MIT Press, Cambridge, MA] with visual perception, we accessed the mind’s eye of 30 Western and Eastern culture individuals and reconstructed their mental representations of the six basic facial expressions of emotion. Cross-cultural comparisons of the mental representations challenge universality on two separate counts. First, whereas Westerners represent each of the six basic emotions with a distinct set of facial movements common to the group, Easterners do not. Second, Easterners represent emotional intensity with distinctive dynamic eye activity. By refuting the long-standing universality hypothesis, our data highlight the powerful influence of culture on shaping basic behaviors once considered biologically hardwired. Consequently, our data open a unique nature–nurture debate across broad fields from evolutionary psychology and social neuroscience to social networking via digital avatars.
Different agonists recruit different stromal interaction molecule proteins to support cytoplasmic Ca
2+
oscillations and gene expression
Authors: Kar Pulak , Bakowski Daniel , Di Capite Joseph , Nelson Charmaine , Parekh Anant B.
Published: April 2012

Stimulation of cells with physiological concentrations of calcium-mobilizing agonists often results in the generation of repetitive cytoplasmic Ca
2+
oscillations. Although oscillations arise from regenerative Ca
2+
release, they are sustained by store-operated Ca
2+
entry through Ca
2+
release-activated Ca
2+
(CRAC) channels. Here, we show that following stimulation of cysteinyl leukotriene type I receptors in rat basophilic leukemia (RBL)-1 cells, large amplitude Ca
2+
oscillations, CRAC channel activity, and downstream Ca
2+
-dependent nuclear factor of activated T cells (NFAT)-driven gene expression are all exclusively maintained by the endoplasmic reticulum Ca
2+
sensor stromal interaction molecule (STIM) 1. However, stimulation of tyrosine kinase-coupled FCεRI receptors evoked Ca
2+
oscillations and NFAT-dependent gene expression through recruitment of both STIM2 and STIM1. We conclude that different agonists activate different STIM proteins to sustain Ca
2+
signals and downstream responses.
Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation
Authors: Mackay Laura K. , Stock Angus T. , Ma Joel Z. , Jones Claerwen M. , Kent Stephen J. , Mueller Scott N. , Heath William R. , Carbone Francis R. , Gebhardt Thomas
Published: April 2012

Although circulating memory T cells provide enhanced protection against pathogen challenge, they often fail to do so if infection is localized to peripheral or extralymphoid compartments. In those cases, it is T cells already resident at the site of virus challenge that offer superior immune protection. These tissue-resident memory T (TRM) cells are identified by their expression of the α-chain from the integrin αE(CD103)β7, and can exist in disequilibrium with the blood, remaining in the local environment long after peripheral infections subside. In this study, we demonstrate that long-lived intraepithelial CD103+CD8+TRMcells can be generated in the absence of in situ antigen recognition. Local inflammation in skin and mucosa alone resulted in enhanced recruitment of effector populations and their conversion to the TRMphenotype. The CD8+TRMcells lodged in these barrier tissues provided long-lived protection against local challenge with herpes simplex virus in skin and vagina challenge models, and were clearly superior to the circulating memory T-cell cohort. The results demonstrate that peripheral TRMcells can be generated and survive in the absence of local antigen presentation and provide a powerful means of achieving immune protection against peripheral infection.
A role for GPx3 in activity of normal and leukemia stem cells
Authors: Herault Olivier , Hope Kristin J. , Deneault Eric , Mayotte Nadine , Chagraoui Jalila , Wilhelm Brian T. , Cellot Sonia , Sauvageau Martin , Andrade-Navarro Miguel A. , Hébert Josée , Sauvageau Guy
Published: April 2012

The determinants of normal and leukemic stem cell self-renewal remain poorly characterized. We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias. Compared with a leukemia with a low frequency of LSCs, a leukemia with a high frequency of LSCs showed hypomethylation of the Gpx3 promoter region, and expressed high levels of Gpx3 and low levels of ROS. LSCs and normal hematopoietic stem cells (HSCs) engineered to express Gpx3 short hairpin RNA (shRNA) were much less competitive in vivo than control cells. However, progenitor cell proliferation and differentiation was not affected by Gpx3 shRNA. Consistent with this, HSCs overexpressing Gpx3 were significantly more competitive than control cells in long-term repopulation experiments, and overexpression of the self-renewal genes Prdm16 or Hoxb4 boosted Gpx3 expression. In human primary acute myeloid leukemia samples, GPX3 expression level directly correlated with adverse prognostic outcome, revealing a potential novel target for the eradication of LSCs.
Human invariant natural killer T cells acquire transient innate responsiveness via histone H4 acetylation induced by weak TCR stimulation
Authors: Wang Xiaohua , Bishop Kathleen A. , Hegde Subramanya , Rodenkirch Lance A. , Pike J. Wesley , Gumperz Jenny E.
Published: April 2012

Invariant NKT cells (iNKT cells) are innate T lymphocytes that are thought to play an important role in producing an early burst of IFN-γ that promotes successful tumor immunosurveillance and antimicrobial immunity. The cellular activation processes underlying innate IFN-γ production remain poorly understood. We show here that weak T cell receptor (TCR) stimulation that does not directly activate iNKT cell IFN-γ messenger RNA transcription nevertheless induces histone H4 acetylation at specific regions near the IFNG gene locus. This renders the iNKT cells able to produce IFN-γ in an innate manner (i.e., not requiring concurrent TCR stimulation) upon exposure to IL-12 and IL-18. The iNKT cells retain the capacity for innate activation for hours to days after the initial weak TCR stimulation, although their innate responsiveness gradually declines as a function of histone deacetylation. These results explain how iNKT cells are able to mediate rapid innate IFN-γ secretion in a manner that does not require them to undergo permanent TH1 differentiation. Moreover, our results also indicate that iNKT cell motility is maintained during activation by IL-12 and IL-18. Therefore, iNKT cells activated through this pathway can continue to migrate and may thus disseminate the IFN-γ that they produce, which may amplify its impact.
We hear you
Authors: Borowski Christine
Published: April 2012

Last year, we came to the realization that online supplemental material had gotten out of control. In our conversations with authors and referees, we heard that the time needed to produce it and thoroughly review it was increasing at an unsustainable pace. In response, we changed our policy on supplemental material. Well, we’re still listening. And we’re hearing author frustration with seemingly endless rounds of external review at high-impact journals. We want to let you know that the editors of The Journal of Experimental Medicine have been working hard to avoid contributing to this problem.
Analysis of high-affinity assembly for AMPA receptor amino-terminal domains
Authors: Zhao Huaying , Berger Anthony J. , Brown Patrick H. , Kumar Janesh , Balbo Andrea , May Carrie A. , Casillas Ernesto , Laue Thomas M. , Patterson George H. , Mayer Mark L. , Schuck Peter
Published: April 2012

Analytical ultracentrifugation (AUC) and steady-state fluorescence anisotropy were used to measure the equilibrium dissociation constant (Kd) for formation of dimers by the amino-terminal domains (ATDs) of the GluA2 and GluA3 subtypes of AMPA receptor. Previous reports on GluA2 dimerization differed in their estimate of the monomer–dimer Kd by a 2,400-fold range, with no consensus on whether the ATD forms tetramers in solution. We find by sedimentation velocity (SV) analysis performed using absorbance detection a narrow range of monomer–dimer Kd values for GluA2, from 5 to 11 nM for six independent experiments, with no detectable formation of tetramers and no effect of glycosylation or the polypeptide linker connecting the ATD and ligand-binding domains; for GluA3, the monomer–dimer Kd was 5.6 µM, again with no detectable tetramer formation. For sedimentation equilibrium (SE) experiments, a wide range of Kd values was obtained for GluA2, from 13 to 284 nM, whereas for GluA3, the Kd of 3.1 µM was less than twofold different from the SV value. Analysis of cell contents after the ∼1-week centrifuge run by silver-stained gels revealed low molecular weight GluA2 breakdown products. Simulated data for SE runs demonstrate that the apparent Kd for GluA2 varies with the extent of proteolysis, leading to artificially high Kd values. SV experiments with fluorescence detection for GluA2 labeled with 5,6-carboxyfluorescein, and fluorescence anisotropy measurements for GluA2 labeled with DyLight405, yielded Kd values of 5 and 11 nM, consistent with those from SV with absorbance detection. However, the sedimentation coefficients measured by AUC using absorbance and fluorescence systems were strikingly different, and for the latter are not consistent with hydrodynamic protein models. Thus, for unknown reasons, the concentration dependence of sedimentation coefficients obtained with fluorescence detection SV may be unreliable, limiting the usefulness of this technique for quantitative analysis.
Sawtooth control using electron cyclotron current drive in ITER demonstration plasmas in DIII-D
Authors: Chapman I.T. , La Haye R.J. , Buttery R.J. , Heidbrink W.W. , Jackson G.L. , Muscatello C.M. , Petty C.C. , Pinsker R.I. , Tobias B.J. , Turco F.
Published: April 2012

Sawtooth control using electron cyclotron current drive (ECCD) has been demonstrated in ITER-like plasmas with a large fast ion fraction, wide q = 1 radius and long uncontrolled sawtooth period in DIII-D. The sawtooth period is minimized when the ECCD resonance is just inside the q = 1 surface. Sawtooth destabilization using driven current inside q = 1 avoids the triggering of performance-degrading neoclassical tearing modes (NTMs), even at much higher pressure than required in the ITER baseline scenario. Operation at βN = 3 without 3/2 or 2/1 NTMs has been achieved in ITER demonstration plasmas when sawtooth control is applied using only modest ECCD power. Numerical modelling qualitatively confirms that the achieved driven current changes the local magnetic shear sufficiently to compensate for the stabilizing influence of the energetic particles in the plasma core.
Nonlinear control for stabilization of small neoclassical tearing modes in ITER
Authors: Hennen B.A. , Lauret M. , Hommen G. , Heemels W.P.M.H. , de Baar M.R. , Westerhof E.
Published: April 2012

In this paper, the feasibility of feedback stabilization of neoclassical tearing modes at small island sizes, corresponding to otherwise unstable island sizes in ITER scenario 2, is demonstrated. The islands are stabilized by application of electron cyclotron resonance heating and current drive in a regime where the application of current drive in open loop normally results in a complete suppression of the island. By applying current drive in closed loop with feedback of real-time measurements of the island width, complete suppression is avoided and the island is stabilized at a specific reduced size. In contrast to complete suppression, control of islands at a specific size will allow the manipulation of a plasma's current density profile in hybrid scenarios. Three conceptual (non-)linear feedback controllers with varying complexity, performance, robustness and required model knowledge are introduced. Simulations show the theoretical feasibility of small island stabilization at a specific reduced width. The controllers are applied to the generalized Rutherford equation, which governs the island evolution subject to electron cyclotron current drive. A strategy for the gradual implementation of the controllers is suggested. Stabilization of small islands by feedback control will allow the use of system identification to extend the model knowledge on the evolution of small islands, and in addition will extend the operational regime.
Analysis of an Emerging Market: Can Methyl Iodide Substitute for Methyl Bromide?
Authors: Hueth Brent , McWilliams Bruce , Sunding David , Zilberman David
Published: April 2012

Recent amendments to the Montreal Protocol specify a 100% reduction in methyl bromide consumption in all developed countries by the year 2005 (except for “critical uses”). In this paper we consider one possible chemical substitute to methyl bromide, methyl iodide, that until recently has received little attention as a potential alternative. We examine the viability of methyl iodide using information from studies of the economic benefits of methyl bromide to California agricultural producers and of methyl iodide effectiveness in preplant fumigation experiments, and from an assessment of the world market for iodine.
How Unilateral Economic Sanctions Affect the Farm Economy: An Inter‐Industry Analysis
Authors: Wiese Arthur M.
Published: April 2012

This paper examines how unilateral economic sanctions affect the U.S. farm economy. A key result is that the total impact of unilateral sanctions on the U.S. economy is larger than the direct impacts on industries whose exports have been constrained (in some cases more than twice as large). Thus, while the direct burden of sanctions may fall on a narrow set of industries, the analysis reveals the extent to which the impacts spill over into other sectors of the economy, an area to date that has not received adequate attention.
The Management of Gout in Primary Care
Authors: Jordan Robert W. , Khan Saira A.
Published: April 2012

Gout is an inflammatory arthropathy secondary to the deposition of monosodium urate crystals in synovial fluid. There are four well-described stages of the condition: asymptomatic hyperuricemia, acute gout attack, intercritical stage and chronic tophaceous gout. Management of the condition is dependent on the individual patient and the stage of disease. The principles are to terminate the acute event, prevent recurrent attacks and disease progression.
Fourier Transform Infrared (FT‐IR) Microspectroscopic Genetic Expression of the Waxy Trait in Isogenic Durum and Common Wheat
Authors: Brewer Lauren R. , Wetzel David L.
Published: April 2012

The aim of recent breeding activity is to develop new wheat lines that incorporate desirable traits that are advantageous in baking and milling. Waxy wheats differ from wild‐type ones in functionality, end use, and biochemical contents (e.g., amylopectin/amylose ratios and lipid contents). Previous waxy wheat investigations focused only on differences in the carbohydrate and protein fractions. The goals of this work were to apply chemical imaging to discriminate between waxy and wild‐type wheats and to define contrasting lipid profiles that occur in the deliberate alteration of the carbohydrate fraction. Fourier transform infrared (IR) microspectroscopic in situ probing and imaging of kernel sections was applied with the use of high spatial resolution. Mid‐IR provided chemical manifestation of lipid genetic expression in isogenic samples. All waxy wheat specimens contained higher lipid content, mostly in the form of glycolipids. The relative lipid profiles differed among common, durum, and waxy wheats. Isogenic partial waxy cultivars and advanced breeding lines were also examined.
Solubility of Haloether Anesthetics in Human and Animal Blood
Authors: Soares Joao H. N. , Brosnan Robert J. , Fukushima Fabíola B. , Hodges Joanne , Liu Hong
Published: April 2012

Background

Anesthetic blood solubility predicts pharmacokinetics for inhaled agents and is essential for determination of blood anesthetic concentrations from end-tidal gas concentrations using Henry's Law. Though used to model anesthetic effects in humans, there are limited interspecies solubility comparisons that include modern haloethers. This study aimed to measure hematocrit-adjusted blood:gas anesthetic partition coefficients (λ B:G) for desflurane, sevoflurane, isoflurane, and methoxyflurane in humans and animals.

Methods

Whole blood was collected from 20 rats, 8 horses, and 4 each of cats, cattle, humans, dogs, goats, pigs, rabbits, and sheep. Plasma or cell volume was removed to adjust all samples to a packed cell volume of 40%. A single-agent calibration gas headspace was added to blood in a glass syringe and was mixed and equilibrated at 37°C for 2 h. Agent concentrations in the calibration gas and syringe headspace were measured using gas chromatography. Anesthetic solubility in saline, citrate-phosphate-dextrose-adenine, and olive oil were similarly measured.

Results

Except for goats, all animal species had at least one λ B:G measurement that differed significantly from humans. For each agent, λ B:G positively correlated with serum triglyceride concentrations, but this only explained 25% of interspecies variability. Desflurane was significantly less soluble in blood than sevoflurane in some species (e.g., humans) but not in others (e.g., rabbits).

Conclusions

Anesthetic partition coefficients differ significantly between humans and most animals for haloether anesthetics. Because of their similar λ B:G values, goats may be a better animal model for inhaled anesthetic pharmacokinetics in people.
Predictors and Clinical Outcomes from Failed Laryngeal Mask Airway Unique™
Authors: Ramachandran Satya Krishna , Mathis Michael R. , Tremper Kevin K. , Shanks Amy M. , Kheterpal Sachin
Published: April 2012

Background

Although the estimated risk of life-threatening adverse respiratory events during supraglottic airway device use is rare, the reported rate of events leading to failure of the airway device is 0.2-8%. Little is known about the risk-adjusted prediction of Laryngeal Mask Airway failure requiring rescue tracheal intubation and its impact on patient outcomes.

Methods

All adult patients in whom a laryngeal mask airway (LMA Unique™, uLMA™; LMA North America, Inc., San Diego, CA) was used in ambulatory and nonambulatory anesthesia settings were included. The primary outcome was uLMA™ failure, defined as an airway event requiring uLMA™ removal and tracheal intubation. The secondary outcomes were the incidence of difficult mask ventilation and unplanned hospital admissions.

Results

Of the 15,795 cases included in our study, 170 (1.1%) experienced the primary outcome of uLMA™ failure. More than 60% of patients with uLMA™ failure experienced significant hypoxia, hypercapnia, or airway obstruction, whereas 42% presented with inadequate ventilation related to leak. Four independent risk factors for failed uLMA™ were identified: surgical table rotation, male sex, poor dentition, and increased body mass index. A 3-fold increased incidence of difficult mask ventilation was observed in patients with uLMA™ failure. Among outpatients with uLMA™ failure, 13.7% had unplanned hospital admission, 5.6% of whom needed intensive care for persistent hypoxemia.

Conclusions

The study supports the use of the uLMA™ as an effective supraglottic airway device with a relatively low failure rate. However, there are clinically relevant consequences of uLMA™ failure, as evidenced by the high rate of acute respiratory events and need for unplanned hospital admissions.
Differential DNase I hypersensitivity reveals factor-dependent chromatin dynamics
Authors: He Housheng Hansen , Meyer Clifford A. , Chen Mei Wei , Jordan V. Craig , Brown Myles , Liu X. Shirley
Published: April 2012

Transcription factor cistromes are highly cell-type specific. Chromatin accessibility, histone modifications, and nucleosome occupancy have all been found to play a role in defining these binding locations. Here, we show that hormone-induced DNase I hypersensitivity changes (ΔDHS) are highly predictive of androgen receptor (AR) and estrogen receptor 1 (ESR1) binding in prostate cancer and breast cancer cells, respectively. While chromatin structure prior to receptor binding and nucleosome occupancy after binding are strikingly different for ESR1 and AR, ΔDHS is highly predictive for both. AR binding is associated with changes in both local nucleosome occupancy and DNase I hypersensitivity. In contrast, while global ESR1 binding is unrelated to changes in nucleosome occupancy, DNase I hypersensitivity dynamics are also predictive of the ESR1 cistrome. These findings suggest that AR and ESR1 have distinct modes of interaction with chromatin and that DNase I hypersensitivity dynamics provides a general approach for predicting cell-type specific cistromes.
Limited mitochondrial DNA variation within South Africa's black rhino (Diceros bicornis minor) population and implications for management
Authors: Anderson‐Lederer Rosalynn M. , Linklater Wayne L. , Ritchie Peter A.
Published: April 2012

The taxonomy of African black rhinoceros (Diceros bicornis) remains unresolved. Maintaining levels of genetic diversity and species rescue by reintroduction and restocking requires its resolution. We compared the sequences of the mitochondrial DNA (mtDNA) control region for a total of 101 D. bicornis from three subspecies: D. b. minor, D. b. michaeli and D. b. bicornis. A single unique haplotype was found within the 65 D. b. minor samples from KwaZulu‐Natal (KZN) Province, South Africa, 55 of which came from Hluhluwe‐iMfolozi Game Park (HiP) and Mkuzi Game Reserve (MGR) source populations. However, six different haplotypes were represented in eleven D. b. minor samples from Zimbabwe. Similarly, published autosomal microsatellite data indicate low levels of diversity within the KZN D. b. minor populations. The low levels of mtDNA diversity within the KZN metapopulation point to the possible need for genetic supplementation. However, there is a need to determine whether the low levels of genetic variation within KZN D. b. minor are a result of the recent bottleneck or whether KZN historically always had low diversity.
Cannabidiol as potential anticancer drug
Authors: Massi Paola , Solinas Marta , Cinquina Valentina , Parolaro Daniela
Published: April 2012

Over the past years, several lines of evidence support an antitumourigenic effect of cannabinoids including Δ9‐tetrahydrocannabinol (Δ9‐THC), synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti‐proliferative and pro‐apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of Δ9‐THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non‐psychoactive cannabinoid compounds with structural affinity for Δ9‐THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents.
Dysregulated adipokine metabolism in chronic obstructive pulmonary disease
Authors: Breyer Marie‐Kathrin , Rutten Erica P.A. , Locantore Nicholas W. , Watkins Michael L. , Miller Bruce E. , Wouters Emiel F.M. ,   on behalf of the ECLIPSE Investigators (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints)
Published: April 2012

Eur J Clin Invest 2012; 42 (9): 983–991

Background  Research concerning the involvement of body composition and systemic inflammatory markers in adipokine metabolism in chronic obstructive pulmonary disease (COPD) is still limited. Therefore, we primarily aimed to investigate the adipokine metabolism in relation to these systemic inflammatory biomarkers and to evaluate possible gender‐related differences in the adipokine metabolism in patients with COPD.

Materials and methods  One hundred and eighty‐six subjects with COPD [mean (SD) FEV1%pred: 50 (±16)] and 113 controls, matched for age, gender and body composition were selected from the ECLIPSE cohort. The following serological data were collected: serum levels of leptin, adiponectin and systemic inflammatory biomarkers such as C‐reactive protein (CRP), Interleukin‐6 (IL‐6) and fibrinogen.

Results  Compared with controls, patients with COPD had higher levels of CRP, IL‐6, fibrinogen and adiponectin. After stratification for gender, men with COPD had higher CRP, IL6 and fibrinogen levels compared with male controls, while women with COPD had higher levels of CRP and fibrinogen compared with the female controls. Moreover, in both female controls and patients with COPD, leptin correlated with CRP and fibrinogen, while leptin only correlated with CRP in male controls. Adiponectin correlated negatively with CRP, only in patients with COPD. Body mass index and gender were the strongest determinants for both leptin and adiponectin.

Conclusions  This study shows a gender‐dependent dysregulation of adipokine metabolism in patients with COPD compared with BMI‐matched controls. Furthermore, results from this study suggest a more prominent role of adiponectin in the systemic response to COPD.
The relative importance of deforestation, precipitation change, and temperature sensitivity in determining the future distributions and diversity of Amazonian plant species
Authors: Feeley Kenneth J. , Malhi Yadvinder , Zelazowski Przemyslaw , Silman Miles R.
Published: April 2012

Tropical forests are threatened by many human disturbances – two of the most important of which are deforestation and climate change. To mitigate the impacts of these disturbances, it is important to understand their potential effects on the distributions of species. In the tropics, such understanding has been hindered by poor knowledge of the current distributions and range limits of most species. Here, we use herbarium collection records to model the current and future distributions of ca. 3000 Amazonian plant species. We project these distributions into the future under a range of different scenarios related to the magnitude of climate change and extent of deforestation as well as the response of species to changes in temperature, precipitation, and atmospheric concentrations of
CO2

. We find that the future of Amazonian diversity will be dependant primarily on the ability of species to tolerate or adapt to rising temperatures. If the thermal niches of tropical plant species are fixed and incapable of expanding under rapid warming, then the negative effects of climate change will overshadow the effects of deforestation, greatly reducing the area of suitable habitat available to most species and potentially leading to massive losses of biodiversity throughout the Amazon. If tropical species are generally capable of tolerating warmer temperatures, rates of habitat loss will be greatly reduced but many parts of Amazonia may still experience rapid losses of diversity, with the effects of enhanced seasonal water stress being similar in magnitude to the effects of deforestation.
Haemophilia prophylaxis: how can we justify the costs?
Authors: FELDMAN B. M. , BERGER K. , BOHN R. , CARCAO M. , FISCHER K. , GRINGERI A. , HOOTS K. , MANTOVANI L. , WILLAN A. R. , SCHRAMM W.
Published: April 2012

Summary. Severe haemophilia results in increased mortality and poorer quality of life. Factor prophylaxis leads to a more normal life, but is very costly; most of the cost is due to the high cost of replacement factor. Despite its high cost, factor prophylaxis has been adopted throughout the developed world – even in different health care systems. We argue that there are at least five possible reasons why societies may value factor prophylaxis despite its cost: (i) it is directed towards an inherited disease, (ii) the treatment is largely directed towards children, (iii) the disease is rare and the overall cost to society is small, (iv) the treatment is preventative, and v) the high cost is largely the result of providing safe products. In an era of rising health care costs, there is a strong research agenda to establish the factors that determine the value of expensive therapies for rare diseases like haemophilia.
Intrafamilial transmission of hepatitis C virus in patients with severe haemophilia A
Authors: CULASSO A. C. A. , ALOISI N. , CANDELA M. , CAMPOS R. H. , BARÉ P.
Published: April 2012

Summary.  The history behind the production of clotting factor concentrates produced differences in the prevalence of Hepatitis C Virus (HCV) and other blood‐borne infections in haemophilic patients. Prevalence rates of HCV infection up to 100% were reported in patients treated with concentrates before 1985. Conversely, nowadays, viral inactivation and recombinant technologies have effectively prevented transfusion‐transmitted viral pathogens. Recently, new HCV infections in three young brothers were observed. In the absence of any other risk of transmission, their HIV/HCV coinfected uncle, who was living in the same house, was subject to study. Plasma samples of the four relatives were investigated in order to test whether the infections have a common source. A phylogenetic approach using the most variable (E2) viral sequences was carried out using samples from the four family members. The HCV sequences from the study resulted highly related, being those obtained from the uncle the most ancestral ones. Because of the chronological order in which the infections occurred and the relatedness of the sequences, an infection from the uncle to his nephews is the most likely explanation. Special cares must be applied in the case of household contact among members of a family with inherited bleeding disorders.
Comparison of stem cell properties of cells isolated from normal and inflamed dental pulps
Authors: Pereira L. O. , Rubini M. R. , Silva J. R. , Oliveira D. M. , Silva I. C. R. , Poças‐Fonseca M. J. , Azevedo R. B.
Published: April 2012

Pereira LO, Rubini MR, Silva JR, Oliveira DM, Silva ICR, Poças‐Fonseca MJ, Azevedo RB. Comparison of stem cell properties of cells isolated from normal and inflamed dental pulps. International Endodontic Journal00, 000–000, 2012.

Aim  To compare cells from normal and inflamed human dental pulps regarding the presence of stem cells, their proliferation and differentiation potential.

Methodology  Human dental pulp stem cells (hDPSCs) were isolated from normal (DPSC‐N) and inflamed dental pulps (DPSC‐I). They were compared in respect to proliferation (MTT assay), morphology and STRO‐1 expression. STRO‐1‐positive cells were subject to proliferation (MTT and CFU counting) and morphological analyses and then submitted to odonto‐osteogenic, adipogenic and condrogenic differentiation. Differentiated cells were evaluated concerning morphology and the expression, by qRT‐PCR, of BSP, LPL and SOX‐9 genes. The amount of mineralized matrix produced after odonto‐osteogenic differentiation was compared with quantitative Alizarin Red staining.

Results  No difference was observed in the morphology and in the proliferation rate of DPSC‐N and DPSC‐I either before or after separation of STRO‐1‐positive cells. These cells represented 0.46% (±0.14) and 0.43% (±0.19) of the cell population from normal and inflamed dental pulps, respectively. Both DPSC‐N and DPSC‐I were capable of differentiating under the three assayed conditions and presented similar patterns for BSP, LPL and SOX‐9 expression. Mineralized matrix production was also compatible. In all the quantitative experiments, differences were found between cells from each patient, either from normal or from inflamed pulps. Nonetheless, there was no statistical difference between these two groups.

Conclusion  The morphology, proliferation rate and differentiation potential of DPSC‐I were similar to the observed in DPSC‐N, thus demonstrating that the inflammatory process did not affect the stem cell properties that were assessed.
Patterns of beta diversity in Europe: the role of climate, land cover and distance across scales
Authors: Keil Petr , Schweiger Oliver , Kühn Ingolf , Kunin William E. , Kuussaari Mikko , Settele Josef , Henle Klaus , Brotons Lluís , Pe’er Guy , Lengyel Szabolcs , Moustakas Aristides , Steinicke Henning , Storch David
Published: April 2012

Aim We test the prediction that beta diversity (species turnover) and the decay of community similarity with distance depend on spatial resolution (grain). We also study whether patterns of beta diversity are related to variability in climate, land cover or geographic distance and how the independent effects of these variables depend on the spatial grain of the data.

Location Europe, Great Britain, Finland and Catalonia.

Methods We used data on European birds, plants, butterflies, amphibians and reptiles, and data on British plants, Catalonian birds and Finnish butterflies. We fitted two or three nested grids of varying resolutions to each of these datasets. For each grid we calculated differences in climate, differences in land‐cover composition (CORINE) and beta diversity (βsim, βJaccard) between all pairs of grid cells. In a separate analysis we looked specifically at pairs of adjacent grid cells (the first distance class). We then used variation partitioning to identify the magnitude of independent statistical associations (i.e. independent effects in the statistical sense) of climate, land cover and geographic distance with spatial patterns of beta diversity.

Results Beta diversity between grid cells at any given distance decreased with increasing grain. Geographic distance was always the most important predictor of beta diversity for all pairwise comparisons at the extent of Europe. Climate and land cover had weaker but distinct and grain‐dependent effects. Climate was more important at relatively coarse grains, whereas land‐cover effects were stronger at finer grains. In the country‐wide analyses, climate and land cover were more important than geographic distance. Climatic and land‐cover models performed poorly and showed no systematic grain dependence for beta diversity between adjacent grid cells.

Main conclusions We found that relationships between geographic distance and beta diversity, as well as the environmental correlates of beta diversity, are systematically grain dependent. The strong independent effect of distance indicates that, contrary to the current belief, a substantial fraction of species are missing from areas with a suitable environment. Moreover, the effects of geographic distance (at continental extents) and land cover (at fine grains) indicate that any species distribution modelling should take both environment and dispersal limitation into account.
The mandarin Chinese shortened version of Oral Health Impact Profile for partially edentate patients with implant‐supported prostheses
Authors: LIU J. Y. , POW E. H. N. , CHEN Z. F. , ZHENG J. , ZHANG X. C. , CHEN J.
Published: April 2012

Summary  This study was to validate a mandarin Chinese version of Oral Health Impact Profile (OHIP‐49) in China and to develop a shortened version of OHIP appropriate for use in partially dentate patients with implant‐supported prostheses. The original 49 items of OHIP were translated into mandarin Chinese using a forward–backward method and administered to 580 subjects selected by stratified random sampling. Self‐perceived oral health status and treatment need were also collected. Reliability and validity of the Chinese version of OHIP (OHIP‐C49) were validated. A shortened version (OHIP‐I) was derived from the OHIP‐C49 by exploratory factor analysis (EFA) as well as expert‐based approach in partially dentate patients (n = 102) with implant‐supported prostheses. For validation of the new modified shortened version, another independent sample of 97 partially dentate patients completed OHIP‐I and their self‐perceived oral health status at baseline and at least 3 months after dental implant rehabilitation. Five hundred and thirty‐seven effectual questionnaires were reclaimed from the 580 subjects interviewed. Cronbach’s alpha ranged from 0·78 to 0·96 and test–retest correlation coefficients ranged from 0·84 to 0·97 for subscale and summary scores. Construct validity was demonstrated by priori hypothesised associations between the OHIP‐C49 scores and self‐perceived oral health (P < 0·001). The reliability and validity of OHIP‐I were similar to which of the OHIP‐C49, and the responsiveness appeared able to measure the effect of dental implant therapy effectively. The mandarin version of OHIP‐49 showed sufficient psychometric properties for Chinese. The modified shortened version (OHIP‐I) may be appropriate for the evaluation of implant therapy outcomes in partially dentate Chinese patients.
Determining the direction of tooth grinding: an in vitro study
Authors: Ten BERGE F. , Te POEL J. , RANJITKAR S. , KAIDONIS J. A. , LOBBEZOO F. , HUGHES T. E. , TOWNSEND G. C.
Published: April 2012

Summary  The analysis of microwear patterns, including scratch types and widths, has enabled reconstruction of the dietary habits and lifestyles of prehistoric and modern humans. The aim of this in vitro study was to determine whether an assessment of microwear features of experimental scratches placed on enamel, perpendicularly to the direction of grinding, could predict the grinding direction. Experimental scratches were placed using a scalpel blade on standardised wear facets that had been prepared by wearing opposing enamel surfaces in an electromechanical tooth wear machine. These control ‘baseline’ facets (with unworn experimental scratches) were subjected to 50 wear cycles, so that differential microwear could be observed on the leading and trailing edges of the ‘final’ facets. In Group 1 (n = 28), the ‘footprint’ microwear patterns corresponding to the known grinding direction of specimens in the tooth wear machine were identified. Then, they were used to predict the direction of tooth grinding blindly in the same sample after a 2‐week intermission period. To avoid overfitting the predictive model, its sensitivity was also cross‐validated in a new sample (Group 2, n = 14). A crescent‐shaped characteristic observed in most experimental scratches matched the grinding direction on all occasions. The best predictor of the direction of grinding was a combined assessment of the leading edge microwear pattern and the crescent characteristic (82·1% in Group 1 and 92·9% in Group 2). In conclusion, a simple scratch test can determine the direction of tooth grinding with high reliability, although further improvement in sensitivity is desirable.
Recent colonization of the Galápagos by the tree Geoffroea spinosa Jacq. (Leguminosae)
Authors: CAETANO S. , CURRAT M. , PENNINGTON R. T. , PRADO D. , EXCOFFIER L. , NACIRI Y.
Published: April 2012

This study puts together genetic data and an approximate bayesian computation (ABC) approach to infer the time at which the tree Geoffroea spinosa colonized the Galápagos Islands. The genetic diversity and differentiation between Peru and Galápagos population samples, estimated using three chloroplast spacers and six microsatellite loci, reveal significant differences between two mainland regions separated by the Andes mountains (Inter Andean vs. Pacific Coast) as well as a significant genetic differentiation of island populations. Microsatellites identify two distinct geographical clusters, the Galápagos and the mainland, and chloroplast markers show a private haplotype in the Galápagos. The nuclear distinctiveness of the Inter Andean populations suggests current restricted pollen flow, but chloroplast points to cross‐Andean dispersals via seeds, indicating that the Andes might not be an effective biogeographical barrier. The ABC analyses clearly point to the colonization of the Galápagos within the last 160 000 years and possibly as recently as 4750 years ago (475 generations). Founder events associated with colonization of the two islands where the species occurs are detected, with Española having been colonized after Floreana. We discuss two nonmutually exclusive possibilities for the colonization of the Galápagos, recent natural dispersal vs. human introduction.
Detailed analysis of Helicobacter pylori Fur‐regulated promoters reveals a Fur box core sequence and novel Fur‐regulated genes
Authors: Pich Oscar Q. , Carpenter Beth M. , Gilbreath Jeremy J. , Merrell D. Scott
Published: April 2012

In Helicobacter pylori, iron balance is controlled by the Ferric uptake regulator (Fur), an iron‐sensing repressor protein that typically regulates expression of genes implicated in iron transport and storage. Herein, we carried out extensive analysis of Fur‐regulated promoters and identified a 7‐1‐7 motif with dyad symmetry (5′‐TAATAATnATTATTA‐3′), which functions as the Fur box core sequence of H. pylori. Addition of this sequence to the promoter region of a typically non‐Fur regulated gene was sufficient to impose Fur‐dependent regulation in vivo. Moreover, mutation of this sequence within Fur‐controlled promoters negated regulation. Analysis of the H. pylori chromosome for the occurrence of the Fur box established the existence of well‐conserved Fur boxes in the promoters of numerous known Fur‐regulated genes, and revealed novel putative Fur targets. Transcriptional analysis of the new candidate genes demonstrated Fur‐dependent repression of HPG27_51, HPG27_52, HPG27_199, HPG27_445, HPG27_825 and HPG27_1063, as well as Fur‐mediated activation of the cytotoxin associated gene A, cagA (HPG27_507). Furthermore, electrophoretic mobility shift assays confirmed specific binding of Fur to the promoters of each of these genes. Future experiments will determine whether loss of Fur regulation of any of these particular genes contributes to the defects in colonization exhibited by the H. pylori fur mutant.
Combined transcriptomic and physiological approaches reveal strong differences between short‐ and long‐term response of rice (Oryza sativa) to iron toxicity
Authors: QUINET MURIEL , VROMMAN DELPHINE , CLIPPE ANDRÉ , BERTIN PIERRE , LEQUEUX HÉLÈNE , DUFEY INÈS , LUTTS STANLEY , LEFÈVRE ISABELLE
Published: April 2012

Ferrous iron toxicity is a mineral disorder frequently occurring under waterlogged soils where rice is cultivated. To decipher the main metabolic pathways involved in rice response to iron excess, seedlings have been exposed to 125 mg L−1 FeSO4 for 3 weeks. A combined transcriptomic, biochemical and physiological study has been performed after short‐term (3 d) or long‐term (3 weeks) exposure to iron in order to elucidate the strategy of stress adaptation with time. Our results showed that short‐ and long‐term exposure involved a very different response in gene expression regarding both the number and function. A larger number of genes were up‐ or down‐regulated after 3 d than after 3 weeks of iron treatment; these changes also occurred in shoot even though no significant difference in iron concentration was recorded. Those modifications in gene expression after 3 d affected not only genes involved in hormonal signalling but also genes involved in C‐compound and carbohydrate metabolism, oxygen and electron transfer, oxidative stress, and iron homeostasis and transport. Modification in some gene expression can be followed by modification in corresponding metabolic products and physiological properties, or differed in time for some others, underlying the importance of an integrated study.
COMT Val158Met modulates the effect of childhood adverse experiences on the risk of alcohol dependence
Authors: Schellekens Arnt F. A. , Franke Barbara , Ellenbroek Bart , Cools Alexander , de Jong Cor A. J. , Buitelaar Jan K. , Verkes Robbert‐Jan
Published: April 2012

Genetic factors and childhood adverse experiences contribute to the vulnerability to alcohol dependence. However, empirical data on the interplay between specific genes and adverse experiences are few. The COMT Val158Met and DRD2/ANKK1 Taq1A genotypes have been suggested to affect both stress sensitivity and the risk for alcohol dependence. This study tested the hypothesis that genetic variation in COMT Val158Met and DRD2/ANKK1 Taq1A interacts with childhood adverse experiences to predict alcohol dependence. Male abstinent alcohol‐dependent patients (n = 110) and age‐matched healthy male controls (n = 99) were genotyped for the COMT Val158Met and the DRD2/ANKK1 Taq1A genotypes. Childhood adverse events were measured using three self‐report questionnaires. Alcohol dependence severity, age of onset and duration of alcohol dependence were analyzed as secondary outcome measures. Statistical analysis involved logistic regression analysis and analysis of variance. Alcohol‐dependent patients reported increased childhood adversity. The interaction between childhood adversity and the COMT Val158Met genotype added significantly to the prediction model. This gene–environment interaction was confirmed in the analysis of the secondary outcome measures, i.e. alcohol dependence severity, age of onset and duration of alcohol dependence. The DRD2/ANKK1 Taq1A genotype was not related to alcohol dependence, nor did it interact with childhood adversity in predicting alcohol dependence. This study provides evidence for a gene–environment interaction in alcohol dependence, in which an individual's sensitivity to childhood adverse experience is moderated by the COMT genotype. Exposed carriers of a low‐activity Met allele have a higher risk to develop severe alcohol dependence than individuals homozygous for the Val allele.
Homozygous and compound heterozygous mutations in the ATP6V1B1 gene in patients with renal tubular acidosis and sensorineural hearing loss
Authors: Mohebbi N , Vargas‐Poussou R , Hegemann SCA , Schuknecht B , Kistler AD , Wüthrich RP , Wagner CA
Published: April 2012

Mohebbi N, Vargas‐Poussou R, Hegemann SCA, Schuknecht B, Kistler AD, Wüthrich RP, Wagner CA. Homozygous and compound heterozygous mutations in the ATP6V1B1 gene in patients with renal tubular acidosis and sensorineural hearing loss.

Distal renal tubular acidosis (dRTA) is characterized by the inability to excrete acid in the renal collecting ducts resulting in inappropriately alkaline urine and hyperchloremic (normal anion gap) metabolic acidosis in the context of a normal (or near‐normal) glomerular filtration rate. Inborn dRTA can be due to autosomal dominant or recessive gene defects. Clinical symptoms vary from mild acidosis, incidental detection of kidney stones or renal tract calcification to severe findings such as failure to thrive, severe metabolic acidosis, and nephrocalcinosis. The majority of patients with recessive dRTA present with sensorineural hearing loss (SNHL). Few cases with abnormal widening of the vestibular aqueduct have been described with dRTA. Mutations in three different genes have been identified, namely SLC4A1, ATP6V1B1, and ATP6V0A4. Patients with mutations in the ATP6V1B1 proton pump subunit develop dRTA and in most of the cases sensorineural hearing loss early in childhood. We present two patients from two different and non‐consanguineous families with dRTA and SNHL. Direct sequencing of the ATP6V1B1 gene revealed that one patient harbors two homozygous mutations and the other one is a compound heterozygous. To our knowledge, this is the first case in the literature describing homozygosity in the same dRTA gene on both alleles.