bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Fatness, Governing Bodies: The Spatialities of the Body Mass Index (BMI) in Anti‐Obesity Politics
Authors: Evans Bethan , Colls Rachel
Published: October 2009

Abstract:  The Body Mass Index (BMI) is the dominant means of defining and diagnosing obesity in national and international public health policy. This paper draws on geographical engagements with Foucault's work on biopower and governmentality to question the power afforded the BMI in obesity policy. With reference to a UK public health intervention involving the measurement of children's bodies within schools, the paper questions the multiple materialities and spatialities of the BMI with reference to both its role in the construction of geographies of obesity and its (in)ability to capture the fleshy, material, and experiential bodies of those individuals involved in the process of measurement. The paper contributes to poststructuralist health geographies through writing fleshy, active bodies into a Foucauldian reading of health and illness, thus questioning the justifications and implications of an obesity politics focussed on the BMI.
Teaching the Politics of Obesity: Insights into Neoliberal Embodiment and Contemporary Biopolitics
Authors: Guthman Julie
Published: October 2009

Abstract:  This article reflects on the author's experiences teaching an undergraduate lecture course on the politics of obesity. The course involved a critical examination of the construction and representation of the so‐called epidemic of obesity and the major causal explanations for the rise in obesity. Students were unusually discomfited by the course and invoked pedagogical concerns and instructor embodiments in expressing their reactions. Student responses demonstrate how obesity talk reflects and reinforces neoliberal rationalities of self‐governance, particularly those that couple bodily control and deservingness and see fatness as weakening the health of the body politic. The course also animated many students to scrutinize more deeply their own diet and exercise practices. I argue that the intensity of reaction stems from the productive power of the discourse of obesity and considerable investment students had in their bodies as neoliberal subjects. Besides classroom observations, the data in this paper are taken from student journals.
Analysis of four prevalent filaggrin mutations (R501X, 2282del4, R2447X and S3247X) in Austrian and German patients with atopic dermatitis
Authors: Greisenegger EK , Novak N , Maintz L , Bieber T , Zimprich F , Haubenberger D , Gleiss A , Stingl G , Kopp T , Zimprich A
Published: October 2009

Background  Recently, mutations in the filaggrin gene (FLG) have been shown to be a major predisposing factor for atopic dermatitis (AD).

Objective  In this study, we evaluated the influence of four prevalent mutations (R501X, 2282del4, R2447X and S3247X) in a large cohort of 462 Austrian and German AD patients and in 402 control individuals.

Results  We found a strong association of the FLG mutations with AD. Subgroup analysis revealed a significantly higher proportion of patients with an early age of disease onset and significantly higher median serum IgE levels among mutation carriers.

Furthermore, we observed an overrepresentation of null alleles in AD patients with concomitant asthma compared with those without this co‐morbidity.

Conclusion  Our data confirm and extend the knowledge of the influence of FLG mutations in AD.
An Italian shared dermatological and rheumatological proposal for the use of biological agents in psoriatic disease
Authors: Marchesoni A , Altomare G , Matucci‐Cerinic M , Balato N , Olivieri I , Salvarani C , Lotti T , Scarpa R , Vena GA , Valesini G , Giannetti A
Published: October 2009

Background  As psoriatic disease (PD) is a condition characterized by the combination of inflammatory skin (psoriasis) and osteo‐articular manifestations (psoriatic arthritis), its treatment should cover both its clinical components.

Objective  The objective of this study was to propose a flexible framework for the use of biological agents in PD.

Methods  The proposal was drawn up by a group of dermatologists and rheumatologist expert in PD and was based on existing evidence and personal opinion.

Results  The three TNF‐α inhibitors (adalimumab, etanercept, infliximab) are effective in all of the psoriatic manifestations and should be used in the case of moderate/severe disease refractory to systemic treatment with non‐biological drugs. We propose the following definitions of moderate/severe disease: PASI > 10 or BSA > 10 or DLQI > 10 for plaque‐psoriasis; BSA ≥ 10 or DLQI ≥ 10 for the other psoriatic skin lesions; DLQI ≥ 10 or meaningful values of the NAPSI or mNAPSI for psoriatic nail involvement; ≥ 1 inflamed joint + patient global VAS34 + physician's judgement or arthritic joint deformities or radiographic joint damage plus ≥ 5 inflamed small joints or ≥ 1 large joints for peripheral joint involvement; ≥ 1 digit with dactylitis and ≥ 1 enthesitic sites + patient global VAS34 + physician's judgement for dactylitis and enthesitis. BASDAI ≥ 4 + physician's judgement for spondylitis; recurrent flares or risk of developing irreversible damage for uveitis. Other assessment instruments can be used if the physician is more familiar with them and if they have been validated.

Conclusion  We provide a shared dermatological and rheumatological proposal for the use of biological agents in PD.
The evolution of the land plant life cycle
Authors: Niklas Karl J. , Kutschera Ulrich
Published: October 2009

The extant land plants are unique among the monophyletic clade of photosynthetic eukaryotes, which consists of the green algae (chlorophytes), the charophycean algae (charophytes), numerous groups of unicellular algae (prasinophytes) and the embryophytes, by possessing, firstly, a sexual life cycle characterized by an alternation between a haploid, gametophytic and a diploid, sporophytic multicellular generation; secondly, the formation of egg cells within multicellular structures called archegonia; and, thirdly, the retention of the zygote and diploid sporophyte embryo within the archegonium. We review the developmental, paleobotanical and molecular evidence indicating that: the embryophytes descended from a charophyte‐like ancestor; this common ancestor had a life cycle with only a haploid multicellular generation; and the most ancient (c. 410 Myr old) land plants (e.g. Cooksonia, Rhynia and Zosterophyllum) had a dimorphic life cycle (i.e. their haploid and diploid generations were morphologically different). On the basis of these findings, we suggest that the multicellular reproductive structures of extant charophytes and embryophytes are developmentally homologous, and that those of the embryophytes evolved by virtue of the co‐option and re‐deployment of ancient algal homeodomain gene networks.

Contents

Summary
27

I.
Introduction
28

II.
Developmental constraint or a phyletic legacy?
29

III.
Green plant phylogeny
29

IV.
The ancestral green plant life cycle
31

V.
Haplobiontic or diplobiontic life cycles?
32

VI.
Pseudo‐archegonia, plasmodesmata, and parenchyma
33

VII.
Genomic re‐deployment and embryophyte reproduction
35

VIII.
Developmental homologies?
35

IX.
Isomorphic or dimorphic?
36

X.
Conclusions
38

Acknowledgements
39

References
39
How does moss photosynthesis relate to leaf and canopy structure? Trait relationships for 10 Hawaiian species of contrasting light habitats
Authors: Waite Mashuri , Sack Lawren
Published: October 2009

DOI: 10.1111/j.1469-8137.2009.03111.xCommentary p 1
Angelman syndrome: Current understanding and research prospects
Authors: Dan Bernard
Published: October 2009

Angelman syndrome is a neurogenetic disorder characterized by developmental delay, severe intellectual disability, absent speech, exuberant behavior with happy demeanor, motor impairment, and epilepsy, due to deficientUBE3Agene expression that may be caused by various abnormalities of chromosome 15. Recent findings in animal models demonstrated altered dendritic spine formation as well as both synaptic [including γ‐aminobutyric acid (GABA)AandN‐methyl‐d‐aspartate (NMDA) transmission] and nonsynaptic (including gap junction) influences in various brain regions, including hippocampus and cerebellar cortex. Reversal of selected abnormalities in rescue genetically engineered animal models is encouraging, although it should not be misinterpreted as promising “cure” for affected patients. Much research is still required to fully understand the functional links between lack ofUBE3Aexpression and clinical manifestations of Angelman syndrome. Studies of regulation ofUBE3Aexpression, including imprinting‐related methylation, may point to possibilities of therapeutic upregulation. Understanding relevant roles of the gene product might lead to targeted intervention. Further documentation of brain network dynamics, with particular emphasis on hippocampus, thalamocortical, and cerebellar networks is needed, including in a developmental perspective. There is also a need for further clinical research for improving management of problems such as epilepsy, behavior, communication, learning, motor impairment, and sleep disturbances.
Increased Acid Sphingomyelinase Activity in Peripheral Blood Cells of Acutely Intoxicated Patients With Alcohol Dependence
Authors: Reichel Martin , Greiner Elisabeth , Richter‐Schmidinger Tanja , Yedibela Özlem , Tripal Philipp , Jacobi Andrea , Bleich Stefan , Gulbins Erich , Kornhuber Johannes
Published: October 2009

Background:  Acid sphingomyelinase (ASM; EC 3.1.4.12) hydrolyses membrane sphingomyelin into the bioactive lipid ceramide and is thus involved in different cellular processes such as differentiation, immunity, or cell death. Activation of ASM has been reported in particular in conjunction with the cellular stress response to several external stimuli, and increased ASM activity was observed in a variety of human diseases. Ethanol‐induced activation of ASM has been observed in different cell culture systems, thus raising the question about the effect of alcohol intoxication in human subjects on ASM activity in vivo.

Methods:  We determined ASM activity in peripheral blood mononucleated cells of 27 patients suffering from alcohol dependence. Patients were classified according to their blood alcohol concentration at admission, and ASM activity was determined repeatedly from all patients during alcohol withdrawal.

Results:  Acutely intoxicated patients displayed significantly higher ASM activity than patients in early abstinence (Mann–Whitney U test: Z = − 2.6, p = 0.009). ASM activity declined in acutely intoxicated patients to normal values with the transition from the intoxicated state to early abstinence (Wilcoxon test: Z = −2.7, p = 0.007). At the end of withdrawal, ASM activity was significantly increased again compared to the early phase of abstinence in both patient groups (Wilcoxon test: Z = −2.691, p = 0.007 and Z = −2.275, p = 0.023, respectively).

Conclusions:  Alcohol‐induced activation of ASM occurs in human subjects and might be responsible for deleterious effects of ethanol intoxication. Chronic alcohol abuse may induce deregulation of sphingomyelin metabolism in general, and this impairment may cause side effects during withdrawal from alcohol.
Galanin Knockout Mice Show Disturbances in Ethanol Consumption and Expression of Hypothalamic Peptides That Stimulate Ethanol Intake
Authors: Karatayev Olga , Baylan Jessica , Weed Valerie , Chang Siyi , Wynick David , Leibowitz Sarah F.
Published: October 2009

Background:  There is growing evidence suggesting that hypothalamic galanin (GAL), which is known to stimulate intake of a fat‐rich diet, has a role in promoting the consumption of ethanol. The present study further examined this possibility in GAL knockout (GALKO) mice.

Methods:  Two groups of female and male GALKO mice, compared to wild‐type (WT) controls, were trained to voluntarily drink increasing concentrations of ethanol, while maintained on lab chow and water. They were examined in terms of their daily ethanol intake and preference, acute consumption of a high‐fat diet, preference for flavored solutions, and expression of different peptides shown to stimulate ethanol intake.

Results:  In the GALKO mice compared to WT, the results revealed: (i) a 35 to 45% decrease in ethanol intake and preference, which was evident only at the highest (15%) ethanol concentration, was stronger in female than in male mice, and was seen with comparisons to littermate as well as nonlittermate WT mice; (ii) a 48% decrease in acute intake of a fat‐rich diet, again stronger in female than male mice; (iii) no difference in consumption of sucrose or quinine solutions in preference tests; (iv) a total loss of GAL mRNA in the hypothalamic paraventricular nucleus (PVN) of female and male mice; and (v) a gender‐specific change in mRNA levels of peptides in the perifornical lateral hypothalamus (PFLH), orexin and melanin‐concentrating hormone, which are known to stimulate ethanol and food intake and were markedly decreased in females while increased in males.

Conclusions:  These results provide strong support for a physiological role of PVN GAL in stimulating the consumption of ethanol, as well as a fat‐rich diet. Ablation of the GAL gene produced a behavioral phenotype, particularly in females, which may reflect the functional relationship of galanin to ovarian steroids. It also altered the peptides in the PFLH, with their reduced expression contributing to the larger behavioral effects observed in females and their increased expression attenuating these effects in males.
Neuropeptide S Receptor Gene Expression in Alcohol Withdrawal and Protracted Abstinence in Postdependent Rats
Authors: Ruggeri Barbara , Braconi Simone , Cannella Nazzareno , Kallupi Marsida , Soverchia Laura , Ciccocioppo Roberto , Ubaldi Massimo
Published: October 2009

Background:  Alcoholism is a chronic disease characterized by frequent intoxications followed by withdrawal episodes and relapse to alcohol use. Neuroplastic changes associated with these intoxication and withdrawal cycles are thought to play a key role in disease progression. Recently, it has been shown that neuropeptide S (NPS), a newly deorphanized neuropeptide receptor system, facilitates relapse to alcohol seeking in laboratory animals. Given that a history of ethanol intoxication may increase vulnerability to alcohol addiction, we sought to determine whether NPS receptor (NPSR) gene expression is altered during withdrawal.

Methods:  Rats were subjected to 1 week of intoxication by oral alcohol administration. NPSR gene expression was analyzed by in situ hybridization in rats 12 hours and 7 days after the last alcohol administration. To investigate the functional significance of NPSR system adaptation following protracted withdrawal 7 days after intoxication, we tested the anxiolytic‐like properties of NPS in nondependent and postdependent rats using the shock probe defensive burying test (DB).

Results:  At both time points, increased NPSR gene expression was observed in several brain areas, including the endopiriform nucleus, the motor cortex, and the medial amygdaloid nucleus. Moderate increases in gene expression were also found in the lateral hypothalamus, paraventricular nucleus, basolateral and central amygdala. Differences from control animals were more pronounced after 7 days of abstinence. The upregulation of the NPSR system at this time point was confirmed by functional data indicating that intracerebroventricular (ICV) NPS administration (0.0, 0.3, and 0.1 nmol/rat) elicits more pronounced anxiolytic effects in postdependent animals than in controls subjected to the electric shock probe DB test.

Conclusions:  Neuropeptide S receptor mRNA expression is increased in different brain areas of postdependent rats; as shown in the DB test, this expression change is functionally relevant.
Linkage Analysis of Alcohol Dependence Symptoms in the Community
Authors: Hansell Narelle K. , Agrawal Arpana , Whitfield John B. , Morley Katherine I. , Gordon Scott D. , Lind Penelope A. , Pergadia Michele L. , Montgomery Grant W. , Madden Pamela A. F. , Todd Richard D. , Heath Andrew C. , Martin Nicholas G.
Published: October 2009

Background:  We have previously identified suggestive linkage for alcohol consumption in a community‐based sample of Australian adults. In this companion paper, we explore the strength of genetic linkage signals for alcohol dependence symptoms.

Methods:  An alcohol dependence symptom score, based on DSM‐IIIR and DSM‐IV criteria, was examined. Twins and their nontwin siblings (1,654 males, 2,518 females), aged 21 to 81 years, were interviewed, with 803 individuals interviewed on 2 occasions, approximately 10 years apart. Linkage analyses were conducted on datasets compiled to maximize data collected at either the younger or the older age. In addition, linkage was compared between full samples and truncated samples that excluded the lightest drinkers (approximately 10% of the sample).

Results:  Suggestive peaks on chromosome 5p (LODs >2.2) were found in a region previously identified in alcohol linkage studies using clinical populations. Linkage signal strength was found to vary between full and truncated samples and when samples differed only on the collection age for a sample subset.

Conclusions:  The results support the finding that large community samples can be informative in the study of alcohol‐related traits.
Red blood cell aging markers during storage in citrate‐phosphate‐dextrose–saline‐adenine‐glucose‐mannitol
Authors: Antonelou Marianna H. , Kriebardis Anastasios G. , Stamoulis Konstantinos E. , Economou‐Petersen Effrosini , Margaritis Lukas H. , Papassideri Issidora S.
Published: October 2009

BACKGROUND: It has been suggested that red blood cell (RBC) senescence is accelerated under blood bank conditions, although neither protein profile of RBC aging nor the impact of additive solutions on it have been studied in detail.

STUDY DESIGN AND METHODS: RBCs and vesicles derived from RBCs in both citrate‐phosphate‐dextrose (CPD)–saline‐adenine‐glucose‐mannitol (SAGM) and citrate‐phosphate‐dextrose‐adenine (CPDA) were evaluated for the expression of cell senescence markers (vesiculation, protein aggregation, degradation, activation, oxidation, and topology) through immunoblotting technique and immunofluorescence or immunoelectron microscopy study.

RESULTS: A group of cellular stress proteins exhibited storage time– and storage medium–related changes in their membrane association and exocytosis. The extent, the rate, and the expression of protein oxidation, Fas oligomerization, caspase activation, and protein modifications in Band 3, hemoglobin, and immunoglobulin G were less conspicuous and/or exhibited significant time retardation under storage in CPD‐SAGM, compared to the CPDA storage. There was evidence for the localization of activated caspases near to the membrane of both cells and vesicles.

CONCLUSIONS: We provide circumstantial evidence for a lower protein oxidative damage in CPD‐SAGM–stored RBCs compared to the CPDA‐stored cells. The different expression patterns of the senescence markers in the RBCs seem to be accordingly related to the oxidative stress management of the cells. We suggest that the storage of RBCs in CPD‐SAGM might be more alike the in vivo RBC aging process, compared to storage in CPDA, since it is characterized by a slower stimulation of the recognition signaling pathways that are already known to trigger the erythrophagocytosis of senescent RBCs.
Sonochemical Synthesis of Networked Silica Shell with Reduced Microporosity on Titania Nanocores for Photocatalytic Activity Reduction
Authors: El‐Toni Ahmed Mohamed , Yin Shu , Sato Tsugio
Published: October 2009

Silica shells with a high density of networks and reduced microporosity has been formed on titania nanocores via a sonochemical approach in the absence of ammonia as a hydrolyzing catalyst. The TiO2‐silica core‐shell nanoparticles were characterized by transmission electron microscopy, energy‐dispersive X‐ray analysis, Fourier transform infrared spectroscopy (FTIR), and microporosity measurements. The photocatalytic activity of coated titania was also reported. FTIR measurements showed that the silica shell was formed with a high density of networks through the formation of asymmetric Si–O–Si vibration and asymmetric Si–O–Si stretching vibration bonds. Moreover, the thickness and microporosity of the silica shell could be altered by controlling the sonochemical power and time parameters.
Oxygen Diffusivities and Surface Exchange Coefficients in Porous Mullite/Zirconia Composites Measured by the Conductivity Relaxation Method
Authors: Ko Hong‐Da , Lin Chien‐Cheng
Published: October 2009

Oxygen diffusivities and surface exchange coefficients in various porous mullite/zirconia composites were measured at oxygen partial pressures ranging from 20.2 to 2.02 kPa using the conductivity relaxation method. However, the oxygen diffusivities in porous high‐zirconia composites could not be determined because of the predominant surface exchange reaction. Oxygen diffusivities and surface exchange coefficients in low‐zirconia composites increased with the zirconia content, while the surface exchange coefficients in high‐zirconia composites were approximately constant. A percolation threshold of the surface exchange coefficients occured at ∼40 vol% zirconia for porous zirconia/mullite composites. The oxygen diffusivities in porous low‐zirconia composites were independent of the oxygen partial pressure, implying that oxygen diffusion in these composites was related to the migration of oxygen vacancies, whose concentration was independent of the oxygen partial pressure. The surface exchange coefficients of high‐zirconia composites decreased with increasing oxygen partial pressure. Finally, it was inferred that the rate‐limiting step for oxygen surface exchange could be the charge‐transfer process.
Low‐Temperature Sputtering Deposition of Aligned Polycrystalline CaCu3Ti4O12 Nanorods
Authors: Joanni Ednan , Savu Raluca , Jančar Bostjan , Bueno Paulo R. , Varela José A.
Published: October 2009

Vertically aligned polycrystalline CaCu3Ti4O12 nanorods were obtained by rf sputtering at low substrate temperatures. The rods grow by electrostatic attraction and aggregation of charged clusters, independently of the substrate used. These nanostructures exhibit a strong nonlinear current × voltage behavior and high losses during cyclic testing, indicating a combination of Schottky's barrier and Joule's heating effects.
Body Height Measurements in Images
Authors: Hoogeboom Bart , Alberink Ivo , Goos Mirelle
Published: October 2009

Abstract:  For any measurement of a person’s height in an image, a difference exists between the actual height of the person and the image measurement. In order to gain knowledge about statistical behavior of differences between actual and measured heights it is necessary to make reference recordings, e.g., of test persons under the same recording conditions. To test whether the differences are dependent on camera and further circumstances, an experiment was set up which involved the measurement of 22 test persons using three cameras of varying quality. Reproducibility of measurements per image appears to be strongly dependent on the camera (quality), whereas systematic bias differs with the view point of the camera. Operator dependency of the measurement process is found, so its repetition by different operators is recommended.
Maternal thyroid hormones are transcriptionally active during embryo–foetal development: results from a novel transgenic mouse model
Authors: Nucera Carmelo , Muzzi Patrizia , Tiveron Cecilia , Farsetti Antonella , Regina Federico La , Foglio Benedetta , Shih Shou‐Ching , Moretti Fabiola , Pietra Linda Della , Mancini Francesca , Sacchi Ada , Trimarchi Francesco , Vercelli Alessandro , Pontecorvi Alfredo
Published: October 2009

Even though several studies highlighted the role of maternal thyroid hormones (THs) during embryo–foetal development, direct evidence of their interaction with embryonic thyroid receptors (TRs) is still lacking. We generated a transgenic mouse model ubiquitously expressing a reporter gene tracing TH action during development. We engineered a construct (TRE2×) containing two TH‐responsive elements controlling the expression of the LacZ reporter gene, which encodes β‐galactosidase (β‐gal). The specificity of the TRE2× activation by TH was evaluated in NIH3T3 cells by cotransfecting TRE2× along with TRs, retinoic or oestrogen receptors in the presence of their specific ligands. TRE2× transgene was microinjected into the zygotes, implanted in pseudopregnant BDF1 (a first‐generation (F1) hybrid from a cross of C57BL/6 female and a DBA/2 male) mice and transgenic mouse models were developed. β‐gal expression was assayed in tissue sections of transgenic mouse embryos at different stages of development. In vitro, TRE2× transactivation was observed only following physiological T3 stimulation, mediated exclusively by TRs. In vivo, β‐gal staining, absent until embryonic day 9.5–10.5 (E9.5–E10.5), was observed as early as E11.5–E12.5 in different primordia (i.e. central nervous system, sense organs, intestine, etc.) of the TRE2× transgenic embryos, while the foetal thyroid function (FTF) was still inactive. Immunohistochemistry for TRs essentially colocalized with β‐gal staining. No β‐gal staining was detected in embryos of hypothyroid transgenic mice. Importantly, treatment with T3 in hypothyroid TRE2× transgenic mice rescued β‐gal expression. Our results provide in vivo direct evidence that during embryonic life and before the onset of FTF, maternal THs are transcriptionally active through the action of embryonic TRs. This model may have clinical relevance and may be employed to design end‐point assays for new molecules affecting THs action.
Importance and mechanism of ‘switch’ function of SAP family adapters
Authors: Veillette André , Dong Zhongjun , Pérez‐Quintero Luis‐Alberto , Zhong Ming‐Chao , Cruz‐Munoz Mario‐Ernesto
Published: October 2009

Summary:  The signaling lymphocytic activation molecule (SLAM)‐associated protein (SAP) family of adapters includes SAP, Ewing’s sarcoma‐associated transcript‐2 (EAT‐2), and EAT‐2‐related transducer (ERT). These Src homology‐2 (SH2) domain‐only molecules play critical roles in immune regulation. The prototype of the SAP family, SAP, is mutated in X‐linked lymphoproliferative disease in humans. Moreover, genetically engineered mice lacking one or more SAP family members have defects in multiple immune cell types including T cells, natural killer (NK) cells, NKT cells, and B cells. Accumulating data show that SAP family adapters regulate immunity by influencing the functions of SLAM family receptors, through two distinct but cooperative mechanisms. First, SAP family adapters couple SLAM family receptors to active biochemical signals, which promote immune cell functions. Second, SAP family adapters interfere with the intrinsic ability of SLAM family receptors to trigger inhibitory signals, which could be mediated via molecules such as SH2 domain‐containing 5′‐inositol phosphatase‐1. The latter effect of SAP family adapters does not seem to be because of direct blocking of inhibitory effector binding to SLAM family receptors. Rather, it appears to implicate alternative mechanisms such as functional competition, trans‐regulation, or steric hindrance. In the absence of SAP family adapters, the inhibitory signals mediated by SLAM family receptors suppress critical activating receptors, explaining in part the pronounced phenotypes seen in SAP family adapter‐deficient humans and mice. Thus, SAP family adapters are molecular switches that regulate immunity as a result of their capacity to control the type of signals and functions emanating from SLAM family receptors.
Regulation of lymphocyte development and activation by the LAT family of adapter proteins
Authors: Fuller Deirdre M. , Zhang Weiguo
Published: October 2009

Summary:  Transmembrane adapter proteins (TRAPs) are critical components of signaling pathways in lymphocytes, linking antigen receptor engagement to downstream cellular processes. While these proteins lack intrinsic enzymatic activity, their phosphorylation following receptor ligation allows them to function as scaffolds for the assembly of multi‐molecular signaling complexes. Many TRAPs have recently been discovered, and numerous studies demonstrate their roles in the positive and negative regulation of lymphocyte maturation, activation, and differentiation. One such example is the linker for activation of T cells (LAT) family of adapter proteins. While LAT has been shown to play an indispensable role in T‐cell and mast cell function, the other family members, linker for activation of B cells (LAB) and linker for activation of X cells (LAX), are necessary to fine‐tune immune responses. In addition to its well‐established role in the positive regulation of lymphocyte activation, LAT exerts an inhibitory effect on T‐cell receptor‐mediated signaling. Furthermore, LAT, along with LAB and LAX, plays a crucial role in establishing and maintaining tolerance. Here, we review recent data concerning the regulation of lymphocyte development and activation by the LAT family of proteins.
Adapter and enzymatic functions of proteases in T‐cell activation
Authors: Hailfinger Stephan , Rebeaud Fabien , Thome Margot
Published: October 2009

Summary:  Proteases control many vital aspects of humoral and cellular immune responses, including the maturation of cytokines and the killing of target cells. Recently, it has become evident that triggering of the T‐cell receptor controls T‐cell proliferation through proteases such as mucosa‐associated lymphoid tissue 1 (MALT1) and Caspase‐8 that act both as adapters and enzymes. Here, we discuss the role of these and other proteases that are relevant to the control of the T‐cell response and represent interesting targets of therapeutic immunomodulation.
The molecular assembly and organization of signaling active B‐cell receptor oligomers
Authors: Tolar Pavel , Sohn Hae Won , Liu Wanli , Pierce Susan K.
Published: October 2009

Summary:  In B cells, antigen drives the formation of B‐cell receptor (BCR) clusters that initiate the formation of signaling complexes associated with the cytoplasmic domains of the BCRs. These signaling active complexes contain a number of protein and lipid kinases and phosphatases and adapter and scaffolding proteins that together function to trigger downstream signaling cascades leading to the activation of a variety of genes associated with B‐cell activation. Although we are learning a considerable amount about the molecular details of the assembly of immune receptor signaling complexes, as reviewed in this volume, a fundamental question remains, namely how does antigen binding outside the cell initiate the assembly of signaling complexes inside the cell. For B cells, we do not yet understand how the information that the ectodomain of the BCR has bound to an antigen is translated across the membrane to induce changes in the cytoplasmic domains that trigger the assembly of signaling complexes. Here we describe what is known about the initiation of the antigen‐driven BCR signal transduction in the newly emerging context of B‐cell recognition of antigens presented by antigen‐presenting cells in lymphoid tissues. We also discuss a recently proposed model for the initiation of BCR signaling termed the ‘conformation‐induced oligomerization model’ and address the implications of this model for the mechanisms by which BCR signaling may be modulated by adapters and coreceptors.
Hierarchical role of CD3 chains in thymocyte development
Authors: Dave Vibhuti P.
Published: October 2009

Summary:  Assembly, expression, and signal transduction by the pre‐T‐cell receptor (pre‐TCR) and TCR complexes are critical for normal thymocyte development. How environmental cues sensed by these two receptor complexes are translated into biological responses that result in the generation of functionally mature T cells is increasingly better understood. Invariant CD3γ, δ, ε, and ζ polypeptides are central to the function of these two receptor complexes. CD3 chains ensure correct intracellular assembly, surface expression, and signal transduction via the receptors in ligand‐independent and ‐dependent manners. In the present review, the roles of the CD3 chains, particularly CD3γ, δ, and ε, in thymocyte differentiation in mice and humans are reviewed.
Phosphoinositide 3‐kinase‐regulated adapters in lymphocyte activation
Authors: Zhang Ting‐ting , Li Hongzhao , Cheung Samuel M. , Costantini Jennifer L. , Hou Sen , Al‐Alwan Monther , Marshall Aaron J.
Published: October 2009

Summary:  Signaling via phosphoinositide 3‐kinases (PI3Ks) has emerged as a central component of lymphocyte activation via immunoreceptors, costimulatory receptors, cytokine receptors, and chemokine receptors. The discovery of phosphoinositide‐binding pleckstrin homology (PH) domains has substantially increased understanding of how PI3Ks activate cellular responses. Accumulating evidence indicates that PH‐domain containing adapter molecules provide important links between PI3K and lymphocyte function. Here, we review data on PI3K‐regulated adapter proteins of the Grb‐associated binder (GAB), Src kinase‐associated phosphoprotein (SKAP), and B‐lymphocyte adapter molecule of 32 kDa (Bam32)/ dual‐adapter for phosphotyrosine and 3‐phosphoinositides (DAPP)/TAPP families, with a focus on the latter group. Current data support the model that recruitment of these adapters to the plasma membrane of activated lymphocytes is driven by the phosphoinositides phosphatidylinositol‐3,4,5‐tris‐phosphate and phosphatidylinositol‐3,4‐bisphosphate, generated through the action of PI3Ks and under the regulatory control of lipid phosphatases Src homology 2 domain‐containing inositol phosphatase (SHIP), phosphatase and tensin homolog, and inositol polyphosphate 4‐phosphatase. At the plasma membrane, these adapters serve to assemble distinct protein complexes. Bam32/DAPP1 and SKAPs function to promote activation of monomeric guanosine triphosphatases, including Rac and Rap, and promote integrin activation, lymphocyte adhesion to matrix proteins, and cell:cell interactions between B and T lymphocytes. GABs can provide feedforward amplification or feedback inhibition of PI3K signaling. Current work is further defining the molecular interactions driven by these molecules and identifying the functions of TAPP adapters, which also appear to be involved in lymphocyte adhesion and are specific effectors downstream of the SHIP product phosphatidylinositol‐3,4‐bisphosphate.
Endocytic events in TCR signaling: focus on adapters in microclusters
Authors: Balagopalan Lakshmi , Barr Valarie A. , Samelson Lawrence E.
Published: October 2009

Summary:  Although the critical role of T‐cell receptor (TCR) microclusters in T‐cell activation is now widely accepted, the mechanisms of regulation of these TCR‐rich structures, which also contain enzymes, adapters, and effectors, remain poorly defined. Soon after microcluster formation, several signaling proteins rapidly dissociate from the TCR. Recent studies from our laboratory demonstrated that the movement of the adapters linker for activation of T cells (LAT) and Src homology 2 domain‐containing leukocyte protein of 76 kDa (SLP‐76) away from initial microcluster formation sites represents endocytic events. Ubiquitylation, Cbl proteins, and multiple endocytic pathways are involved in the internalization events that disassemble signaling microclusters. Several recent studies have indicated that microcluster movement and centralization plays an important role in signal termination. We suggest that microcluster movement is directly linked to endocytic events, thus implicating endocytosis of microclusters as a means to regulate signaling output of the T cell.
The expanding roles of ITAM adapters FcRγ and DAP12 in myeloid cells
Authors: Hamerman Jessica A. , Ni Minjian , Killebrew Justin R. , Chu Ching‐Liang , Lowell Clifford A.
Published: October 2009

Summary:  The adapter proteins DAP12 and FcRγ associate with a wide spectrum of receptors in a variety of innate immune cells to mediate intracellular signaling pathways when their cognate receptor is engaged. These adapter proteins are coupled to their receptors through charged residues within the transmembrane regions of the adapter and receptor. DAP12 and FcRγ contain specific protein domains (referred to as immunoreceptor tyrosine‐based activation motifs) that serve as the substrates and docking sites for kinases, allowing amplification of intracellular signaling reactions. Recent research has broadened the repertoire of receptors that utilize these adapters for signaling to include not only novel immunoglobulin superfamily members but also cytokine receptors, integrins, and other adhesion molecules. There is abundant evidence that these multifunctional signaling adapters also mediate inhibitory activity, downmodulating signaling from Toll‐like receptors and other heterologous receptors. In this review, we discuss the newly described receptors that utilize DAP12 and/or FcRγ adapters to modulate innate immune responses.
Grb2, a simple adapter with complex roles in lymphocyte development, function, and signaling
Authors: Jang Ihn Kyung , Zhang Jinping , Gu Hua
Published: October 2009

Summary:  Lymphocyte development, activation, and tolerance depend on antigen receptor signaling transduced via multiple intracellular signalosomes. These signalosomes are assembled by different adapters. Given that signaling molecules can be either positive or negative regulators for a biochemical target, the complex of a target with different regulator may dictate the final signaling outcome. Grb2 is a simple adapter known to be involved in a variety of growth factor receptor signaling. However, its role in antigen receptor signaling as well as lymphocyte development and function has emerged only recently. Despite its simple molecular structure, recent experiments show that Grb2 may play a complex role in T and B‐cell antigen receptor signaling. In this article, we review recent findings about the physiological role of Grb2 in T and B‐cell development and activation and summarize the current mechanistic understanding of how Grb2 exerts its function following T and B‐cell antigen receptor stimulation.
The roles of Dok family adapters in immunoreceptor signaling
Authors: Mashima Ryuichi , Hishida Yukihiro , Tezuka Tohru , Yamanashi Yuji
Published: October 2009

Summary:  The mammalian Dok protein family has seven members (Dok‐1–Dok‐7). The Dok proteins share structural similarities characterized by the NH2‐terminal pleckstrin homology and phosphotyrosine‐binding domains followed by SH2 target motifs in the COOH‐terminal moiety, indicating an adapter function. Indeed, Dok‐1 was originally identified as a 62 kDa protein that binds with p120 rasGAP, a potent inhibitor of Ras, upon tyrosine phosphorylation by a variety of protein tyrosine kinases. Among the Dok family, only Dok‐1, Dok‐2, and Dok‐3 are preferentially expressed in hematopoietic/immune cells. Dok‐1 and its closest relative Dok‐2 act as negative regulators of the Ras–Erk pathway downstream of many immunoreceptor‐mediated signaling systems, and it is believed that recruitment of p120 rasGAP by Dok‐1 and Dok‐2 is critical to their negative regulation. By contrast, Dok‐3 does not bind with p120 rasGAP. However, accumulating evidence has demonstrated that Dok‐3 is a negative regulator of the activation of JNK and mobilization of Ca2+ in B‐cell receptor‐mediated signaling, where the interaction of Dok‐3 with SHIP‐1 and Grb2 appears to be important. Here, we review the physiological roles and underlying mechanisms of Dok family proteins.
Contributions of Wiskott–Aldrich syndrome family cytoskeletal regulatory adapters to immune regulation
Authors: Zhang Jinyi , Dong Baoxia , Siminovitch Katherine A.
Published: October 2009

Summary:  Cytoskeletal structure and dynamic rearrangement are integrally involved in coupling external stimuli to the orchestrated network of molecular interactions and cellular responses required for T‐cell effector function. Members of the Wiskott––Aldrich syndrome protein (WASp) family are now widely recognized as cytoskeletal scaffolding adapters that coordinate the transmission of stimulatory signals to downstream induction of actin remodeling and cytoskeletal‐dependent T‐cell responses. In this review, we discuss the structural and functional properties of the WASp family members, with an emphasis on the roles of these proteins in the molecular pathways underpinning T‐cell activation. The contributions of WASp family proteins and the cytoskeletal reorganization they evoke to expression of specific T‐cell effector functions and the implications of such activity to normal immune responses and to the immunologic deficits manifested by Wiskott–Aldrich syndrome patients are also described.
PKA‐Mediated Golgi Remodeling During cAMP Signal Transmission
Authors: Mavillard Fabiola , Hidalgo Josefina , Megias Diego , Levitsky Kostantin L. , Velasco Angel
Published: October 2009

Cyclic AMP (cAMP)‐dependent protein kinase A (PKA) is part of the set of signaling proteins that are stably associated to the cytosolic surface of Golgi membranes in mammalian cells. In principle, Golgi‐associated PKA could participate in either signal transduction events and/or the coordination of Golgi transport activities. Here, we show data indicating that although Golgi‐associated PKA is activated fast and efficiently during cell stimulation by an extracellular ligand it does not contribute significantly to cAMP signal transmission to the nucleus. Instead, most of the PKA catalytic subunits Cαderived from the Golgi complex remain localized in the perinuclear cytoplasm where they induce changes in Golgi structural organization. Thus, in stimulated cells the Golgi complex appears collapsed, showing increased colocalization of previously segregated markers and exhibiting merging of different proximal cisternae within a single stack. In contrast, the trans‐Golgi network remains as a separate compartment. Consequently, the rate of protein transport is increased whereas glycan processing is not severely affected. This remodeling process requires the presence of PKA activity associated to the Golgi membranes. Together these data indicate that Golgi‐associated PKA activity is involved in the adaptation of Golgi dynamic organization to extracellular signaling events.
COMT but not serotonin‐related genes modulates the influence of childhood abuse on anger traits
Authors: Perroud N. , Jaussent I. , Guillaume S. , Bellivier F. , Baud P. , Jollant F. , Leboyer M. , Lewis C. M. , Malafosse A. , Courtet P.
Published: October 2009

Anger‐related traits are regulated by genes as well as early environmental factors. Both childhood maltreatment and genes underlie vulnerability to suicidal behaviors, possibly by affecting the constitution of intermediate phenotypes such as anger traits. The aim of this study was to test the interaction between nine candidate genes and childhood maltreatment in modulating anger‐related traits in 875 adult suicide attempters. The State‐Trait Anger Expression Inventory and the Childhood Trauma Questionnaire were used to examine anger traits and traumatic childhood experiences, respectively. The functional polymorphism of the catecholamine‐O‐methyl‐transferase (COMT) gene Val158Met significantly modulated the association between sexual abuse and anger‐trait level (P = 0.001). In the presence of sexual abuse, individuals carrying the Val high‐activity allele displayed greater disposition toward anger than individuals homozygous for the Met allele (P = 0.0003). Notably, none of the serotonin‐related genes influenced the effect of childhood abuse on anger traits. The results of the present study suggest that anger‐trait level is influenced by the interaction between childhood abuse and functional polymorphism in the COMT gene. This study was carried out in a population with a high frequency of childhood abuse and a high disposition toward anger, and replication in healthy subjects is needed.
Three‐dimensional visualization of renal artery stenosis by 64‐channel multiple detector‐row computed tomographical angiography: review of two paediatric cases
Authors: Ueda N , Iwayama H , Funahashi Y , Suzuki K
Published: October 2009

Three‐dimensional visualization of renal arteries has recently been established by helical contrast‐enhanced multiple detector‐row computed tomographical angiography (MDCTA) in adults. So far, no information is available on its use in children. We reported two children with renal artery stenosis detected by 64‐channel MDCTA. The first patient probably had fibromuscular dysplasia and the other neurofibromatosis type1. The technique showed a left renal artery stenosis with a small left kidney in the first patient and a right renal artery stenosis in the second.

Conclusion:  MDCTA is an accurate and noninvasive imaging technique, easily performed in children, and can be used as an alternative diagnostic modality in children with suspected renovascular hypertension.
Unpacking Racial Socialization: Considering Female African American Primary Caregivers' Racial Identity
Authors: Scottham Krista Maywalt , Smalls Ciara P.
Published: October 2009

The relationship between female African American primary caregivers' racial identity and their racial socialization emphases was examined. Three components of racial identity were evaluated: (1) the importance of race to the self‐concept (centrality), (2) affective feelings toward group membership (private regard), and (3) perceptions of how group members are perceived by nonmembers (public regard). Latent class cluster analysis was used to identify racial identity profiles, or dominant combinations of racial centrality, private regard, and public regard among a sample of 208 female African American primary caregivers. Mean differences in the content of caregivers' socialization emphases by profile group were then assessed. Findings indicated that caregivers with different identity profiles emphasized different messages. These findings and their implications are discussed.
Communicative Correlates of Satisfaction, Family Identity, and Group Salience in Multiracial/Ethnic Families
Authors: Soliz Jordan , Thorson Allison R. , Rittenour Christine E.
Published: October 2009

Guided by the Common Ingroup Identity Model (S. L. Gaertner & J. F. Dovidio, 2000) and Communication Accommodation Theory (C. Shepard, H. Giles, & B. A. LePoire, 2001), we examined the role of identity accommodation, supportive communication, and self‐disclosure in predicting relational satisfaction, shared family identity, and group salience in multiracial/ethnic families. Additionally, we analyzed the association between group salience and relational outcomes as well as the moderating roles of multiracial/ethnic identity and marital status. Individuals who have parents from different racial/ethnic groups were invited to complete questionnaires on their family experiences. Participants (N = 139) answered questions about relationships with mothers, fathers, and grandparents. The results of the multilevel modeling analyses are discussed in terms of implications for understanding multiracial/ethnic families and family functioning.
Parenting and Adolescents' Sexual Initiation
Authors: Longmore Monica A. , Eng Abbey L. , Giordano Peggy C. , Manning Wendy D.
Published: October 2009

This study draws on social control and social learning theories to examine the role of dating‐specific attitudes and practices as predictors of adolescents' sexual initiation. We include attention to the adolescent's reaction to control attempts as a further means of assessing family dynamics (i.e., frequency of dating disagreements). The study uses longitudinal data from 697 adolescents who were not sexually active at the first interview as well as separate interviews with parents. In models that include all parenting variables, parental caring, parents' preferences that the child should delay sex, and the frequency of dating disagreements were significant predictors of initiation of teen sexual activity.