bluuebunny/crossref_metadata_2025 huggingface dataset:
Histopathologic and Ultrastructural Studies on Experimental Caprine Besnoitiosis
Authors: Oryan A. , Namazi F. , Silver I. A.
Published: February 2011

The distribution pattern and associated tissue reactions with progressive changes in Besnoitia caprae cysts were investigated in 6 experimentally infected 16- to 20-month-old male goats. Each goat was subcutaneously inoculated with approximately 13 × 108 B caprae bradyzoites. The animals were examined daily for development of clinical besnoitiosis, and skin biopsies from distal parts of the limbs were taken at weekly intervals. At 15, 30, 60, 120, 180, and 365 days postinfection (DPI), 1 goat was euthanized. Samples were collected at autopsy from various organs for histologic and ultrastructural studies. No cysts were seen in tissue sections on 15, 30, and 365 DPI, but large numbers were present at 60, 120, and 180 DPI in the skin of the distal limbs, scrotum, and ears, with fewer in the tongue, palate, sclera, testicles, and spermatic cord. No cysts were seen in the lungs, liver, kidneys, spleen, central nervous system, or lymph nodes. Cyst numbers peaked at 60 DPI, then declined from 120 to 180 DPI. Degenerated cysts were relatively rare at 60 DPI but more numerous at 180 compared with 120. A granulomatous reaction—predominantly characterized by macrophages, lymphocytes, and plasma cells—surrounded each degenerated cyst. All goats showed testicular tubular degeneration with little or no spermatogenic activity. The sizes of cysts and their wall thickness, with the size of bradyzoites and some of their organelles, exhibited progressive chronologic changes.
Immunohistochemical Expression of E-cadherin Does Not Distinguish Canine Cutaneous Histiocytoma From Other Canine Round Cell Tumors
Authors: Ramos-Vara J. A. , Miller M. A.
Published: February 2011

Immunohistochemistry for E-cadherin (ECAD) has been used to distinguish canine cutaneous histiocytoma from other leukocytic neoplasms (“round cell tumors”). To determine the specificity of this test, 5 types of canine cutaneous round cell tumors were evaluated for immunohistochemical expression of ECAD. Tumors of all 5 types had variable cytoplasmic, plasma membrane, and/or paranuclear ECAD expression: All 13 cutaneous histiocytomas were ECAD+; all but 1 of 14 mast cell tumors expressed ECAD; 10 of 12 epitheliotropic lymphomas reacted with E-cadherin antibody; of 72 plasmacytomas, 54 were ECAD+; and 5 of 5 histiocytic sarcomas were positive. Conclusions based on these results include the following: First, immunoreactivity for ECAD is not limited to leukocytes of cutaneous histiocytoma; second, antibody to ECAD also labels neoplastic cells in most mast cell tumors, plasmacytomas, cutaneous histiocytic sarcomas, and epitheliotropic lymphomas; third, although most histiocytomas have membranous ECAD expression, the immunoreactivity varies among round cell tumors and is frequently concurrent in different cellular compartments; fourth, the distinctively paranuclear ECAD expression pattern in epitheliotropic lymphomas might distinguish them from other round cell tumors; and, fifth, ECAD should be used with other markers (eg, MUM1 for plasmacytomas, KIT for mast cell tumors, CD3 and CD79a for lymphomas) to distinguish among canine round cell tumors.
Feminist Contributions to Understanding Women’s Lives and the Social Environment
Authors: Swigonski Mary E. , Raheim Salome
Published: February 2011

This article traces the tides of three waves of feminism that have flowed within the United States and highlights the critical contributions of theoretical insights from these waves to expand and enhance social workers’ understanding of the lives of women and the social environment. In particular, the article highlights the specific contributions of a set of core concepts (gender, care, power, difference, and diversity) that emerged within feminist theory and analysis during the second and third waves of U.S. feminism to social work’s understanding of women’s lives and the social environment and to assessment of the person—environment interaction.
Providing Context for Social Workers’ Response to Sexual Assault Victims
Authors: Murphy Sharon B. , Potter Sharyn J. , Pierce-Weeks Jennifer , Stapleton Jane G. , Wiesen-Martin Desireé , Phillips Kimberly G.
Published: February 2011

The authors sought to give voice to women victims of sexual assault whose stories otherwise remain muted. The study reported here provided rare insights into victims who sought emergency services at a hospital following a sexual assault. The data (N = 745) were collected by sexual assault nurse examiners in one northeastern state between 1997 and 2007.
Policies and Practices Used by States to Serve Children With Autism Spectrum Disorders
Authors: Henderson Kelly
Published: February 2011

There has been swift growth in the number of children and youth identified with autism and autism spectrum disorders (ASD) and who receive services through U.S. early intervention and special education systems. This growth, coupled with the intensive and unique needs of this population, has prompted many state agencies to implement policies and practices to improve delivery of services to children with ASD. The results of a national survey of Part C and Part B agencies under the Individuals with Disabilities Education Act show that most Part B and many Part C agencies are engaged in initiatives specific to ASD. Professional development, technical assistance, and direct services to children with ASD are the most common approaches used. Case studies of five states’ efforts detail the nature of the ASD initiatives and the use of specific approaches within their state settings.
Prevention of Recurrent Atrial Fibrillation With Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers: A Systematic Review and Meta-Analysis of Randomized Trials
Authors: Bhuriya Rohit , Singh Mukesh , Sethi Ankur , Molnar Janos , Bahekar Amol , Singh Param Puneet , Khosla Sandeep , Arora Rohit
Published: February 2011

Background: Controversy persists regarding the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in the prevention of recurrent atrial fibrillation (AF). We performed a meta-analysis of randomized controlled trials (RCTs), not designed a priori to test this hypothesis, to explore whether ACEs and ARBs reduce recurrent AF. Methods: We performed a systematic literature search for RCTs using ACEIs or ARBs and providing data on the outcome of recurrent AF. Statistical heterogeneity across the trials was tested using the Cochran Q statistic and I2 was computed to quantify heterogeneity. A 2-sided α error of less than .05 was considered statistically significant (P < .05). Results: The analysis was based on 8 RCTs including 2323 patients. The Mantel-Haenszel random-effect model was used to calculate relative risk (RR) for studies using ACEIs or ARBs, and for studies using ARBs. The fixed-effect model was used to calculate RR for studies using ACEIs. Meta-analysis of the studies revealed that ACEIs or ARBs significantly reduced the incidence of recurrent AF (RR, 0.611; 95% CI, 0.441-0.847; P = .003). The RR for recurrent AF was 0.643 (95% CI, 0.439-0.941; P = .023) for studies using ARBs and 0.54 (95% CI, 0.377-0.80; P = .002) for studies using ACEIs. Conclusion: In this meta-analysis of RCTs not designed a priori to test the hypothesis, ACEs and ARBs were associated with a significant reduction in recurrent AF. Large-scale randomized trials designed a priori to test the hypothesis are necessary to complete the totality of evidence.
A Dynamic Approach to Tax Evasion
Authors: Dalamagas Basil
Published: February 2011

Standard models of tax evasion use a static decision-under-uncertainty setting to determine how an individual’s evasion decision is affected by the fiscal instruments. Most of these models fail to create a framework, within which unique relationships between tax evasion and its main determinants (especially tax rates and actual income) could be derived. The purpose of this paper is to establish a new pattern of unambiguous relationships in the evasion theory, by shifting the emphasis from the comparative static analysis of previous studies to a comparative-dynamics framework in the context of a neoclassical growth model, in which time and the average burden from all kinds of taxes also play an important role in affecting the taxpayer’s decision making process.
Review of Meta-Analyses on the Association Between Child Sexual Abuse and Adult Mental Health Difficulties: A Systematic Approach
Authors: Hillberg Tanja , Hamilton-Giachritsis Catherine , Dixon Louise
Published: February 2011

This review evaluates the quality of recent meta-analyses on child sexual abuse and adult psychopathology. Using systematic review methods, seven recently published, English-language meta-analyses met the inclusion criteria of assessing outcome of child sexual abuse. Some methodological weaknesses were identified, such as failure to assess the validity of the primary studies. Child sexual abuse was found to be a nonspecific risk factor in the development of adult mental health difficulties, but the effect sizes varied (partly related to sample type and size). No gender difference was consistently found on adult mental health difficulties but was for victims’ perceived mental health consequence. Future meta-analyses need to consider their methods of assessing primary studies to allow for an evidence-based model of adult psychopathology.
The Relation Between Childhood Maltreatment and Self-Injury: A Review of the Literature on Conceptualization and Intervention
Authors: Lang Colleen M. , Sharma-Patel Komal
Published: February 2011

The following article reviews literature pertaining to the association between child maltreatment and self-injury and the ways it varies according to maltreatment type. Research supporting various mediators of the relations between different maltreatment types and self-injury is summarized. Informing mediator models, dominant theories of functionality, particularly affect regulation theories, are summarized and granted empirical support. Following from explanations of its functionality, three developmental pathways (regulatory, representational/interpersonal, and reactive/neurobiological) leading from child maltreatment to self-injury are presented within an organizational model of psychopathology. Understanding the deviations in these pathways that perpetuate self-injury helps to inform intervention approaches that forge pathways perpetuating resilience instead. Three psychosocial treatments (i.e., Dialectical Behavior Therapy [DBT], Trauma-Focused Cognitive—Behavioral Therapy [TF-CBT], and Acceptance and Commitment Therapy [ACT]) were chosen for review, based upon their accumulating evidence bases, as well as upon the relevance of their core components in correcting or compensating for trauma-related developmental deviations.
Exploring the Role of Cognitive Reserve in Early-Onset Dementia
Authors: Fairjones Sarah E. , Vuletich Elizabeth J. , Pestell Carmela , Panegyres Peter K.
Published: February 2011

Aim: Cognitive reserve (CR) is important in protecting the brain from injury and has not been investigated in people with early-onset dementia (EOD). Methods: A retrospective case control study of 44 patients with dementia onset prior to 65 years of age: Alzheimer’s disease (AD) = 23; frontotemporal dementia (FTD) = 21. Groups were matched for age, education, Mini-Mental State Examination (MMSE), premorbid IQ, sex and APOE ε4 genotype. Years of formal education were used as a marker of CR. Relationships between education and neuropsychological data was examined using linear regression analyses. Results: There were no demographic differences between the AD and FTD groups. Significant associations were found between education and attention, working memory and visuospatial abilities. There was an effect of CR for the EOD group and selective effects in FTD and AD. Conclusion: Our findings suggest CR is operational in patients with FTD and AD.
Allusions in New York Times and Times Supplement news headlines
Authors: Shie Jian-Shiung
Published: February 2011

In 2004 The New York Times (NYT) launched a weekly Times Supplement (TS) with Taiwan’s United Daily News. This article aims to explore non-lexicalized allusion variation between TS headlines and NYT headlines as a discourse strategy. A textual survey was conducted on a corpus comprising 605 TS news articles and their corresponding NYT articles. Non-lexicalized allusions were identified and explored within a reader-oriented approach. And a stylistic analysis was performed to explore cognitive, pragmatic, and rhetorical roles of non-lexicalized allusions in the corpus. The results show that non-lexicalized allusions occur in far fewer TS than NYT headlines. The allusion downsizing increases the accessibility of TS headlines to general TS readers at the cost of cultural diverseness and stylistic expressiveness in the headline language, making the language of TS headlines stylistically more restricted and culturally less Western. NYT headline language exemplifies English as a native language (ENL), whereas TS headline language is a specific genre of English as an international language (EIL). This article also discusses cultural implications of non-lexicalized allusions for EIL learning. It is pointed out that EIL is an integration of elements of all varieties of English involved in international or intercultural discourse. The cultural knowledge behind non-lexicalized allusions dealt with in this article represents one such element of EIL.
Role expansion as a persuasion process
Authors: M. Grant Adam , A. Hofmann David
Published: February 2011

Evidence establishes that employees often expand their roles to take on broader responsibilities in response to direct requests from others. However, surprisingly little research has investigated the interpersonal influence processes through which individuals convince others to expand their roles. We develop a conceptual framework to explain how senders persuade receivers to accept role expansion requests. Our framework describes why senders often fail to tailor their requests to receivers’ values, identifies the conditions under which this systematic bias is eliminated, and suggests strategies for senders to tailor their requests more effectively. Our perspective highlights how role expansion is often a reactive—rather than proactive—process in which interpersonal influence is a key building block.
The ability to influence others via emotion displays
Authors: Côté Stéphane , Hideg Ivona
Published: February 2011

We propose a new dimension of emotional intelligence (EI) that is particularly relevant in organizational settings: the ability to influence others via emotion displays. In this article, we first describe social functional accounts of emotions and the evidence supporting social effects of emotions. Then, we propose that individuals differ in the degree to which they can influence the behaviors, attitudes, and emotions of others via their emotion displays, and we demonstrate that this individual variation meets the criteria for an emotional ability. We articulate the mechanisms by which the ability to influence others via emotion displays is related to competence in organizational settings. In addition, we develop propositions about factors that moderate the effect of this ability on competence. We describe the research implications of our model.
Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies
Authors: Tiu Ramon V. , Gondek Lukasz P. , O'Keefe Christine L. , Elson Paul , Huh Jungwon , Mohamedali Azim , Kulasekararaj Austin , Advani Anjali S. , Paquette Ronald , List Alan F. , Sekeres Mikkael A. , McDevitt Michael A. , Mufti Ghulam J. , Maciejewski Jaroslaw P.
Published: February 2011

Single nucleotide polymorphism arrays (SNP-As) have emerged as an important tool in the identification of chromosomal defects undetected by metaphase cytogenetics (MC) in hematologic cancers, offering superior resolution of unbalanced chromosomal defects and acquired copy-neutral loss of heterozygosity. Myelodysplastic syndromes (MDSs) and related cancers share recurrent chromosomal defects and molecular lesions that predict outcomes. We hypothesized that combining SNP-A and MC could improve diagnosis/prognosis and further the molecular characterization of myeloid malignancies. We analyzed MC/SNP-A results from 430 patients (MDS = 250, MDS/myeloproliferative overlap neoplasm = 95, acute myeloid leukemia from MDS = 85). The frequency and clinical significance of genomic aberrations was compared between MC and MC plus SNP-A. Combined MC/SNP-A karyotyping lead to higher diagnostic yield of chromosomal defects (74% vs 44%, P < .0001), compared with MC alone, often through detection of novel lesions in patients with normal/noninformative (54%) and abnormal (62%) MC results. Newly detected SNP-A defects contributed to poorer prognosis for patients stratified by current morphologic and clinical risk schemes. The presence and number of new SNP-A detected lesions are independent predictors of overall and event-free survival. The significant diagnostic and prognostic contributions of SNP-A–detected defects in MDS and related diseases underscore the utility of SNP-A when combined with MC in hematologic malignancies.
Alternatively spliced variants of interleukin-4 promote inflammation differentially
Authors: Luzina Irina G , Lockatell Virginia , Todd Nevins W , Highsmith Kendrick , Keegan Achsah D , Hasday Jeffrey D , Atamas Sergei P
Published: February 2011

IL-4δ2 is a natural splice variant of IL-4 that lacks the region encoded by the second exon. Numerous reports have suggested that the expression levels of IL-4δ2 change in various diseases, especially those with pulmonary involvement, but the in vivo effects of this splice variant have never been studied. Replication-deficient, AdV-mediated gene delivery of mIL-4δ2 to mouse lungs in vivo was used, and the effects compared with similar adenoviral delivery of mIL-4 or with infection with a noncoding NULL viral construct. Overexpression of IL-4δ2 or IL-4 caused pulmonary infiltration by T and B lymphocytes, whereas in contrast to IL-4, IL-4δ2 did not induce eosinophilia or goblet cell hyperplasia. Microarray analysis of global gene expression revealed that IL-4δ2 and IL-4 had differential effects on gene expression. These splice variants also differentially regulated pulmonary levels of the cytokines TNF-α, eotaxin, IL-1α, IFN-γ, and MCP-1, whereas both tended to increase total lung collagen modestly. Pulmonary infiltration by lymphocytes in response to overexpression of IL-4δ2 was attenuated but not abrogated completely by germline deficiency of IL-4Rα or STAT6, whereas deficiency of endogenous IL-4 had no effect. Thus, IL-4δ2 promotes lymphocytic inflammation in vivo (although differentially from IL-4, in part), and the effects of IL-4δ2 are not mediated by endogenous IL-4. Differential targeting of IL-4δ2 and IL-4 may therefore be considered in developing future therapeutic agents.
Plasma Distribution and Signaling Activities of IGF-II Precursors
Authors: Marks Alicia G. , Carroll Julie M. , Purnell Jonathan Q. , Roberts Charles T.
Published: February 2011

IGF-II is thought to function through activation of the IGF-I receptor (IGF-IR) and the A isoform of the IR, with the IGF-IR being relevant to tumorigenesis and the IR to both tumorigenesis and metabolic control. In the paraneoplastic syndrome of nonislet cell tumor hypoglycemia, tumor-derived IGF-II has been proposed to exert both proliferative and metabolic effects, exemplifying this dual mode of action. Increased levels of IGF-II precursors (“big” and pro–IGF-II) have been reported in the circulation of nonislet cell tumor patients and have been proposed to exert greater or different effects than mature IGF-II. However, most studies have not defined which version is being investigated, and the relative activation of the IR and IGF-IR by IGF-II precursors has not been delineated. In this study, we determined the distribution of IGF-II isoforms in normal human plasma and their ability to activate the alternative versions of the IR. The majority (71%) of total IGF-II in human plasma was the mature form, while “big” and pro–IGF-II comprised 16% and 13%, respectively, with more variation seen in the levels of mature IGF-II. In IGF-IR–deficient cells expressing similar levels of human IR-A or IR-B, mature and “big” IGF-II exhibited similar activation of IR signaling, while pro–IGF-II exhibited significantly less activation. Downstream activation of Akt by mature and “big” IGF-II was greater in IR-A cells, consistent with previous reports of the greater affinity of IR-A for IGF-II. Thus, both IGF-II precursor forms are present in human plasma but do not preferentially activate the IR.
Rapid Effects of Estrogen Receptor α and β Selective Agonists on Learning and Dendritic Spines in Female Mice
Authors: Phan Anna , Lancaster Karla E. , Armstrong John N. , MacLusky Neil J. , Choleris Elena
Published: February 2011

Estrogen receptor (ER) agonists rapidly affect neural plasticity within 1 h, suggesting they play a functional role in learning and memory. However, behavioral learning experiments on such a rapid time scale are lacking. Therefore we investigated whether the ERα agonist propyl pyrazole triol (PPT) and ERβ agonist diarylpropionitrile (DPN) could affect social recognition, object recognition, or object placement learning within 40 min of drug administration. At the same time, we examined their effects on CA1 hippocampal dendritic spines. Ovariectomized female CD1 mice were administered a range of PPT or DPN doses (0, 30, 50, 75, or 150 μg/mouse). PPT at the middle doses improved social recognition, facilitated object recognition and placement at a dose of 75 μg, and increased dendritic spine density in the stratum radiatum and lacunosum-moleculare. In contrast, DPN impaired social recognition at higher doses, did not affect object recognition, but slightly facilitated object placement learning at the 75-μg dose. DPN did not affect spines in the stratum radiatum but decreased spine density and increased spine length in the lacunosum-moleculare. This suggests that rapid estrogen-mediated learning enhancements may predominantly be mediated through ERα, while the effects of DPN are weaker and may depend on the learning paradigm. The role of ERα and ERβ in learning and memory may vary depending on the timing of drug administration, as genomic studies often implicate ERβ in enhancing effects on learning and memory. To our knowledge, this is the first report of estrogens' effects on learning within such a short time frame.
The Adapter Protein APPL1 Links FSH Receptor to Inositol 1,4,5-Trisphosphate Production and Is Implicated in Intracellular Ca2+ Mobilization
Authors: Thomas Richard M. , Nechamen Cheryl A. , Mazurkiewicz Joseph E. , Ulloa-Aguirre Alfredo , Dias James A.
Published: February 2011

FSH binds to its receptor (FSHR) on target cells in the ovary and testis, to regulate oogenesis and spermatogenesis, respectively. The signaling cascades activated after ligand binding are extremely complex and have been shown to include protein kinase A, mitogen-activated protein kinase, phosphatidylinositol 3-kinase/protein kinase B, and inositol 1,4,5-trisphosphate–mediated calcium signaling pathways. The adapter protein APPL1 (Adapter protein containing Pleckstrin homology domain, Phosphotyrosine binding domain and Leucine zipper motif), which has been linked to an assortment of other signaling proteins, was previously identified as an interacting protein with FSHR. Thus, alanine substitution mutations in the first intracellular loop of FSHR were generated to determine which residues are essential for FSHR-APPL1 interaction. Three amino acids were essential; when any one of them was altered, APPL1 association with FSHR mutants was abrogated. Two of the mutants (L377A and F382A) that displayed poor cell-surface expression were not studied further. Substitution of FSHR-K376A did not affect FSH binding or agonist-stimulated cAMP production in either transiently transfected human embryonic kidney cells or virally transduced human granulosa cells (KGN). In the KGN line, as well as primary cultures of rat granulosa cells transduced with wild type or mutant receptor, FSH-mediated progesterone or estradiol production was not affected by the mutation. However, in human embryonic kidney cells inositol 1,4,5-trisphosphate production was curtailed and KGN cells transduced with FSHR-K376A evidenced reduced Ca2+ mobilization from intracellular stores after FSH treatment.
Localization of retinitis pigmentosa 2 to cilia is regulated by Importin β2
Authors: Hurd Toby W. , Fan Shuling , Margolis Ben L.
Published: February 2011

Ciliopathies represent a newly emerging group of human diseases that share a common etiology resulting from dysfunction of the cilium or centrosome. The gene encoding the retinitis pigmentosa 2 protein (RP2) is mutated in X-linked retinitis pigmentosa. RP2 localizes to the ciliary base and this requires the dual acylation of the N-terminus, but the precise mechanism by which RP2 is trafficked to the cilia is unknown. Here we have characterized an interaction between RP2 and Importin β2 (transportin-1), a member of the Importin-β family that regulates nuclear–cytoplasmic shuttling. We demonstrate that Importin β2 is necessary for localization of RP2 to the primary cilium because ablation of Importin β2 by shRNA blocks entry both of endogenous and exogenous RP2 to the cilium. Furthermore, we identify two distinct binding sites of RP2, which interact independently with Importin β2. One binding site is a nuclear localization signal (NLS)-like sequence that is located at the N-terminus of RP2 and the other is an M9-like sequence within the tubulin folding cofactor C (TBCC) domain. Mutation of the NLS-like consensus sequence did not abolish localization of RP2 to cilia, suggesting that the sequence is not essential for RP2 ciliary targeting. Interestingly, we found that several missense mutations that cause human disease fall within the M9-like sequence of RP2 and these mutations block entry of RP2 into the cilium, as well as its interaction with Importin β2. Together, this work further highlights a role of Importin β2 in regulation of the entry of RP2 and other proteins into the ciliary compartment.
Phenotypic analysis of misato function reveals roles of noncentrosomal microtubules in Drosophila spindle formation
Authors: Mottier-Pavie Violaine , Cenci Giovanni , Vernì Fiammetta , Gatti Maurizio , Bonaccorsi Silvia
Published: February 2011

Mitotic spindle assembly in centrosome-containing cells relies on two main microtubule (MT) nucleation pathways, one based on centrosomes and the other on chromosomes. However, the relative role of these pathways is not well defined. In Drosophila, mutants without centrosomes can form functional anastral spindles and survive to adulthood. Here we show that mutations in the Drosophila misato (mst) gene inhibit kinetochore-driven MT growth, lead to the formation of monopolar spindles and cause larval lethality. In most prophase cells of mst mutant brains, asters are well separated, but collapse with progression of mitosis, suggesting that k-fibers are essential for maintenance of aster separation and spindle bipolarity. Analysis of mst; Sas-4 double mutants showed that mitotic cells lacking both the centrosomes and the mst function form polarized MT arrays that resemble monopolar spindles. MT regrowth experiments after cold exposure revealed that in mst; Sas-4 metaphase cells MTs regrow from several sites, which eventually coalesce to form a single polarized MT array. By contrast, in Sas-4 single mutants, chromosome-driven MT regrowth mostly produced robust bipolar spindles. Collectively, these results indicate that kinetochore-driven MT formation is an essential process for proper spindle assembly in Drosophila somatic cells.
PERP regulates enamel formation via effects on cell–cell adhesion and gene expression
Authors: Jheon Andrew H. , Mostowfi Pasha , Snead Malcolm L. , Ihrie Rebecca A. , Sone Eli , Pramparo Tiziano , Attardi Laura D. , Klein Ophir D.
Published: February 2011

Little is known about the role of cell–cell adhesion in the development of mineralized tissues. Here we report that PERP, a tetraspan membrane protein essential for epithelial integrity, regulates enamel formation. PERP is necessary for proper cell attachment and gene expression during tooth development, and its expression is controlled by P63, a master regulator of stratified epithelial development. During enamel formation, PERP is localized to the interface between the enamel-producing ameloblasts and the stratum intermedium (SI), a layer of cells subjacent to the ameloblasts. Perp-null mice display dramatic enamel defects, which are caused, in part, by the detachment of ameloblasts from the SI. Microarray analysis comparing gene expression in teeth of wild-type and Perp-null mice identified several differentially expressed genes during enamel formation. Analysis of these genes in ameloblast-derived LS8 cells upon knockdown of PERP confirmed the role for PERP in the regulation of gene expression. Together, our data show that PERP is necessary for the integrity of the ameloblast–SI interface and that a lack of Perp causes downregulation of genes that are required for proper enamel formation.
Expression of Sorting Nexin 18 (SNX18) Is Dynamically Regulated in Developing Spinal Motor Neurons
Authors: Nakazawa Shiori , Gotoh Naoya , Matsumoto Hirotaka , Murayama Chiaki , Suzuki Toshiharu , Yamamoto Tohru
Published: February 2011

The sorting nexin (SNX) family proteins, which contain a Phox homology (PX) domain, play crucial roles in regulating the intracellular membrane trafficking of the endocytic pathway. The proper coordination of this pathway is important for axonal elongation; however, little is known about the expression and intracellular dynamics of the SNX members during the formation of the nervous system. Here the authors found that SNX18, which belongs to the Src-homology-3-PX-Bin/Amphiphysin/Rvs domain-containing SNX subfamily, was specifically expressed in differentiating motor neurons in the chick and mouse embryonic spinal cord. The expression of SNX18 in embryonic spinal motor neurons was transient and was downregulated as the neurons matured. The authors further demonstrated that the localization of EGFP-SNX18 in growth cones was dynamically regulated and accumulated especially at areas in contact with permissive substrates. These findings collectively suggest that SNX18 may play an active role in axonal elongation.
Expression of C4.4A, a Structural uPAR Homolog, Reflects Squamous Epithelial Differentiation in the Adult Mouse and during Embryogenesis
Authors: Kriegbaum Mette C. , Jacobsen Benedikte , Hald Andreas , Ploug Michael
Published: February 2011

The glycosylphosphatidylinositol (GPI)–anchored C4.4A was originally identified as a metastasis-associated protein by differential screening of rat pancreatic carcinoma cell lines. C4.4A is accordingly expressed in various human carcinoma lesions. Although C4.4A is a structural homolog of the urokinase receptor (uPAR), which is implicated in cancer invasion and metastasis, no function has so far been assigned to C4.4A. To assist future studies on its function in both physiological and pathophysiological conditions, the present study provide a global survey on C4.4A expression in the normal mouse by a comprehensive immunohistochemical mapping. This task was accomplished by staining paraffin-embedded tissues with a specific rabbit polyclonal anti-C4.4A antibody. In the adult mouse, C4.4A was predominantly expressed in the suprabasal layers of the squamous epithelia of the oral cavity, esophagus, non-glandular portion of the rodent stomach, anus, vagina, cornea, and skin. This epithelial confinement was particularly evident from the abrupt termination of C4.4A expression at the squamo-columnar transition zones found at the ano-rectal and utero-vaginal junctions, for example. During mouse embryogenesis, C4.4A expression first appears in the developing squamous epithelium at embryonic day 13.5. This anatomical location of C4.4A is thus concordant with a possible functional role in early differentiation of stratified squamous epithelia.
Consensus Statement on the Standardization and Evaluation of Growth Hormone and Insulin-like Growth Factor Assays
Authors: Clemmons David R
Published: February 2011

Growth hormone (GH) and insulin-like growth factor I (IGF-I) measurements are widely used in the diagnosis of disorders of GH secretion, evaluation of children with short stature from multiple causes, management of disorders that lead to nutritional insufficiency or catabolism, and monitoring both GH and IGF-I replacement therapy. Therefore, there is an ongoing need for accurate and precise measurements of these 2 peptide hormones. Representatives of the Growth Hormone Research Society, the IGF Society, and the IFCC convened an international workshop to review assay standardization, requirements for improving assay comparability, variables that affect assay interpretation, technical factors affecting assay performance, assay validation criteria, and the development and use of normative data. Special attention was given to preanalytical conditions, the use of international commutable reference standards, antibody specificity, matrix requirements, QC analysis, and interference by binding proteins. Recommendations for each of these variables were made for measurements of each peptide. Additionally, specific criteria for IGF-I were recommended for age ranges of normative data, consideration of Tanner staging, and consideration of the effect of body mass index. The consensus statement concludes that major improvements are necessary in the areas of assay performance and comparability. This group recommends that a commutable standard for each assay be implemented for worldwide use and that its recommendations be applied to accomplish the task of providing reliable and clinically useful results.
Age and sex determination of gaur Bos gaurus (Bovidae)
Authors: Ahrestani Farshid S. , Prins Herbert H.T.
Published: February 2011

One reason why the gaur Bos gaurus is a poorly understood species is because there are no reliable data to age and sex individuals. We studied captive gaur for two years in Mysore Zoo, India and Omaha Zoo, USA, and determined age-specific differences in morphological features and physical growth, by measuring shoulder height, of male and female gaur. We fitted von Bertalanffy growth functions to the shoulder height data and found maximum shoulder heights of 175 cm and 147 cm for males and females, respectively. This study ascertained for the first time that the greater the amount of white on the horns of a gaur, the older it is, and that the sexes can be distinguished based on horn shape and size differences. We found that gaur aged 15 months and below can be classified into three age classes, but are difficult to sex. The sex of gaur aged 15–36 months is best determined by a study of their horns. Adult gaur, greater than three years, are easy to sex, but are difficult to classify into single-year age classes and are reliably classified only into two age classes for females and three for males.
Forced Convective Boiling of Ethylene Glycol/Water Mixtures Inside a Small Tube
Authors: Yu Wenhua , France David M. , Routbort Jules L.
Published: February 2011

Forced convective boiling heat transfer of water and ethylene glycol/water mixtures with volume concentration ratios of 40/60, 50/50, and 60/40 in a 2.98-mm inner-diameter circular tube has been investigated for both horizontal and vertical upward flows. Boiling heat transfer rates of the test fluids were determined experimentally over a range of mass flux, vapor mass quality, and inlet subcooling through a boiling data reduction procedure that allowed analytical calculation of the fluid boiling temperatures along the experimental test section by applying ideal mixture and equilibrium assumptions along with Raoult’s law. Based on the experimental findings that the heat flux in the nucleation-dominant-boiling region was dependent strongly on the wall superheat but almost independent of the mass flux and the inlet subcooling, prediction equations were developed for boiling heat transfer coefficients of water and ethylene glycol/water mixtures in small channels. The equations predict the experimental data well, and most of the predicted values are within ±30 % of the experimental data.
Influence of GABAAR Monoliganded States on GABAergic Responses
Authors: Petrini Enrica Maria , Nieus Thierry , Ravasenga Tiziana , Succol Francesca , Guazzi Stefania , Benfenati Fabio , Barberis Andrea
Published: February 2011

To reach the open state, the GABAAreceptor (GABAAR) is assumed to bind two agonist molecules. Although it is currently believed that GABAAR could also operate in the monoliganded state, the gating properties of singly bound GABAAR are poorly understood and their physiological role is still obscure. In the present study, we characterize for the first time the gating properties of singly bound GABAARs by using a mutagenesis approach and we propose that monoliganded GABAAR contribute in shaping synaptic responses. At saturating GABA concentrations, currents mediated by recombinant GABAARs with a single functional binding site display slow onset, fast deactivation kinetics, and slow rate of desensitization-resensitization. GABAARs with two binding sites activated by brief pulses of subsaturating GABA concentrations (in the range of the GABA concentration profile in the synaptic cleft) could also mediate fast deactivating currents, displaying deactivation kinetics similar to those mediated by GABAARs with a single functional binding site. Model simulations of receptors activated by realistic synaptic GABA waves revealed that a considerable proportion of GABAAreceptors open in the monoliganded state during synaptic transmission, therefore contributing in shaping IPSCs.
Suppressor of Fused Controls Mid-Hindbrain Patterning and Cerebellar Morphogenesis via GLI3 Repressor
Authors: Kim Jinny J. , Gill Paul S. , Rotin Lianne , van Eede Matthijs , Henkelman R. Mark , Hui Chi-Chung , Rosenblum Norman D.
Published: February 2011

Sonic Hedgehog and its GLI transcriptional effectors control foliation complexity during cerebellar morphogenesis by promoting granule cell precursor proliferation. Here, we reveal a novel contribution of Sonic Hedgehog-GLI signaling to cerebellar patterning and cell differentiation by generating mice with targeted deletion ofSuppressor of Fused(SuFu), a regulator of Sonic Hedgehog signaling, in the mid-hindbrain. PostnatalSuFu-deficient mice exhibit impaired motor coordination and severe cerebellar mispatterning.SuFuconditional knock-out embryos display abnormal mid-hindbrain morphology associated with misexpression ofFgf8, and delayed differentiation and abnormal migration of major cerebellar cell types. Sonic Hedgehog is ectopically expressed in the external granule layer and Hedgehog signaling is upregulated. While expression of full-length GLI transcriptional activators downstream of Hedgehogs is markedly reduced, a processed form of GLI3, a transcriptional repressor, is essentially lost. Genetic expression of aGli3allele encoding GLI3 repressor inSuFu-deficient mice largely rescues abnormal cerebellar patterning and cell differentiation observed in mice withSuFudeficiency alone. Together, our data demonstrate thatSuFucontrols cerebellar patterning and cell differentiation in a GLI3 repressor-dependent manner.
Tau Protein Is Required for Amyloid β-Induced Impairment of Hippocampal Long-Term Potentiation
Authors: Shipton Olivia A. , Leitz Julie R. , Dworzak Jenny , Acton Christine E. J. , Tunbridge Elizabeth M. , Denk Franziska , Dawson Hana N. , Vitek Michael P. , Wade-Martins Richard , Paulsen Ole , Vargas-Caballero Mariana
Published: February 2011

Amyloid β (Aβ) and tau protein are both implicated in memory impairment, mild cognitive impairment (MCI), and early Alzheimer's disease (AD), but whether and how they interact is unknown. Consequently, we asked whether tau protein is required for the robust phenomenon of Aβ-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. We used wild-type mice and mice with a genetic knock-out of tau protein and recorded field potentials in an acute slice preparation. We demonstrate that the absence of tau protein prevents Aβ-induced impairment of LTP. Moreover, we show that Aβ increases tau phosphorylation and that a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks the increased tau phosphorylation induced by Aβ and prevents Aβ-induced impairment of LTP in wild-type mice. Together, these findings show that tau protein is required for Aβ to impair synaptic plasticity in the hippocampus and suggest that the Aβ-induced impairment of LTP is mediated by tau phosphorylation. We conclude that preventing the interaction between Aβ and tau could be a promising strategy for treating cognitive impairment in MCI and early AD.
μ-Opioid Receptor Activation in the Basolateral Amygdala Mediates the Learning of Increases But Not Decreases in the Incentive Value of a Food Reward
Authors: Wassum Kate M. , Cely Ingrid C. , Balleine Bernard W. , Maidment Nigel T.
Published: February 2011

The decision to perform, or not perform, actions known to lead to a rewarding outcome is strongly influenced by the current incentive value of the reward. Incentive value is largely determined by the affective experience derived during previous consumption of the reward—the process of incentive learning. We trained rats on a two-lever, seeking–taking chain paradigm for sucrose reward, in which responding on the initial seeking lever of the chain was demonstrably controlled by the incentive value of the reward. We found that infusion of the μ-opioid receptor antagonist, CTOP (d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2), into the basolateral amygdala (BLA) during posttraining, noncontingent consumption of sucrose in a novel elevated-hunger state (a positive incentive learning opportunity) blocked the encoding of incentive value information normally used to increase subsequent sucrose-seeking responses. Similar treatment with δ [N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864)] or κ [5′-guanidinonaltrindole (GNTI)] antagonists was without effect. Interestingly, none of these drugs affected the ability of the rats to encode a decrease in incentive value resulting from experiencing the sucrose in a novel reduced-hunger state. However, the μ agonist, DAMGO ([d-Ala2, NMe-Phe4, Gly5-ol]-enkephalin), appeared to attenuate this negative incentive learning. These data suggest that upshifts and downshifts in endogenous opioid transmission in the BLA mediate the encoding of positive and negative shifts in incentive value, respectively, through actions at μ-opioid receptors, and provide insight into a mechanism through which opiates may elicit inappropriate desire resulting in their continued intake in the face of diminishing affective experience.
SDF1 Regulates Leading Process Branching and Speed of Migrating Interneurons
Authors: Lysko Daniel E. , Putt Mary , Golden Jeffrey A.
Published: February 2011

Cell migration is required for normal embryonic development, yet how cells navigate complex paths while integrating multiple guidance cues remains poorly understood. During brain development, interneurons migrate from the ventral ganglionic eminence to the cerebral cortex within several migratory streams. They must exit these streams to invade the cortical plate. While SDF1 (stromal cell-derived factor-1) signaling is necessary for normal interneuron stream migration, how they switch from tangential stream migration to invade the cortical plate is unknown. Here, we demonstrate that SDF1 signaling reduces interneuron branching frequency by reducing cAMP levels via a Gisignaling pathway using anin vitromouse explant system, resulting in the maintenance of stream migration. Blocking SDF1 signaling or increasing branching frequency results in stream exit and cortical plate invasion in mouse brain slices. These data support a novel model to understand how migrating interneurons switch from tangential migration to invade the cortical plate in which reducing SDF signaling increases leading process branching and slows the migration rate, permitting migrating interneurons to sense cortically directed guidance cues.
Mechanism of Spontaneous Activity in Afferent Neurons of the Zebrafish Lateral-Line Organ
Authors: Trapani Josef G. , Nicolson Teresa
Published: February 2011

Many auditory, vestibular, and lateral-line afferent neurons display spontaneous action potentials. This spontaneous spiking is thought to result from hair-cell glutamate release in the absence of stimuli. Spontaneous release at hair-cell resting potentials presumably results from CaV1.3 L-type calcium channel activity. Here, using intact zebrafish larvae, we recorded robust spontaneous spiking from lateral-line afferent neurons in the absence of external stimuli. Consistent with the above assumptions, spiking was absent in mutants that lacked either Vesicular glutamate transporter 3 (Vglut3) or CaV1.3. We then tested the hypothesis that spontaneous spiking resulted from sustained CaV1.3 activity due to depolarizing currents that are active at rest. Mechanotransduction currents (IMET) provide a depolarizing influence to the resting potential. However, following block ofIMET, spontaneous spiking persisted and was characterized by longer interspike intervals and increased periods of inactivity. These results suggest that an additional depolarizing influence maintains the resting potential within the activation range of CaV1.3. To test whether the hyperpolarization-activated cation current,Ihparticipates in setting the resting potential, we appliedIhantagonists. Both ZD7288 and DK-AH 269 reduced spontaneous activity. Finally, concomitant block ofIMETandIhessentially abolished spontaneous activity, ostensibly by hyperpolarization outside of the activation range for CaV1.3. Together, our data support a mechanism for spontaneous spiking that results from Ca2+-dependent neurotransmitter release at hair-cell resting potentials that are maintained within the activation range of CaV1.3 channels through activeIMETandIh.
Dopamine-Mediated Reinforcement Learning Signals in the Striatum and Ventromedial Prefrontal Cortex Underlie Value-Based Choices
Authors: Jocham Gerhard , Klein Tilmann A. , Ullsperger Markus
Published: February 2011

A large body of evidence exists on the role of dopamine in reinforcement learning. Less is known about how dopamine shapes the relative impact of positive and negative outcomes to guide value-based choices. We combined administration of the dopamine D2receptor antagonist amisulpride with functional magnetic resonance imaging in healthy human volunteers. Amisulpride did not affect initial reinforcement learning. However, in a later transfer phase that involved novel choice situations requiring decisions between two symbols based on their previously learned values, amisulpride improved participants' ability to select the better of two highly rewarding options, while it had no effect on choices between two very poor options. During the learning phase, activity in the striatum encoded a reward prediction error. In the transfer phase, in the absence of any outcome, ventromedial prefrontal cortex (vmPFC) continually tracked the learned value of the available options on each trial. Both striatal prediction error coding and tracking of learned value in the vmPFC were predictive of subjects' choice performance in the transfer phase, and both were enhanced under amisulpride. These findings show that dopamine-dependent mechanisms enhance reinforcement learning signals in the striatum and sharpen representations of associative values in prefrontal cortex that are used to guide reinforcement-based decisions.