bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene expression profiling in lung fibroblasts reveals new players in alveolarization
Authors: Boucherat Olivier , Franco-Montoya Marie-Laure , Thibault Christelle , Incitti Roberto , Chailley-Heu Bernadette , Delacourt Christophe , Bourbon Jacques R.
Published: October 2007

Little is known about the molecular basis of lung alveolarization. We used a microarray profiling strategy to identify novel genes that may regulate the secondary septation process. Rat lung fibroblasts were extemporaneously isolated on postnatal days 2, 7, and 21, i.e., before, during, and after septation, respectively. Total RNA was extracted, and cRNAs were hybridized to Affymetrix rat genome 230 2.0 microarrays. Expression levels of a selection of genes were confirmed by real-time PCR. In addition to genes already known to be upregulated during alveolarization including drebrin, midkine, Fgfr3, and Fgfr4, the study allowed us to identify two remarkable groups of genes with opposite profiles, i.e., gathering genes either transiently up- or downregulated on day 7. The former group includes the transcription factors retinoic acid receptor ( RXR)-γ and homeobox ( Hox) a2, a4, and a5 and genes involved in Wnt signaling ( Wnt5a, Fzd1, and Ndp); the latter group includes the extracellular matrix components Comp and Opn and the signal molecule Slfn4. Profiling in whole lung from fetal life to adulthood confirmed that changes were specific for alveolarization. Two treatments that arrest septation, hyperoxia and dexamethasone, inhibited the expression of genes that are upregulated during alveolarization and conversely enhanced that of genes weakly expressed during alveolarization and upregulated thereafter. The possible roles of these genes in secondary septation are discussed. Gene expression profiling analysis on freshly isolated cells represents a powerful approach to provide new information about differential regulation of genes during alveolarization and pathways potentially involved in the pathogenesis of bronchopulmonary dysplasia.
Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum
Authors: Olsen Christopher M. , Huang Yong , Goodwin Shirlean , Ciobanu Daniel C. , Lu Lu , Sutter Thomas R. , Winder Danny G.
Published: October 2007

To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone ( Crh), the GABA transporter ( Slc6a1), and prodynorphin ( Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G-coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Furthermore, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.
Mapping, Genetic Isolation, and Characterization of Genetic Loci That Determine Resistance to Atherosclerosis in C3H Mice
Authors: Wang Susanna S. , Shi Weibin , Wang Xuping , Velky Leandra , Greenlee Sarah , Wang Min T. , Drake Thomas A. , Lusis Aldons J.
Published: October 2007

Objective—

C3H/HeJ (C3H) mice are extremely resistant to atherosclerosis. To identify the genetic factors involved in lesion initiation, we studied a cross between C3H and the susceptible strain C57BL/6J (B6) on a hyperlipidemic (apolipoprotein E–null) background.

Methods and Results—

Whereas a previous cross in mice fed a Western diet for 16 weeks revealed a very complex inheritance pattern with many significant lesion QTLs, the present cross, on a chow diet, revealed a single major locus on chromosome 9 (lod=5.0,
Ath29
*), and a suggestive locus on chromosome 4 (lod=2.6,
Ath8
). QTLs for plasma HDL, total cholesterol, and triglyceride levels were found on chromosome 1 over the
ApoA2
gene. Neither of the lesion QTLs were associated with differences in plasma lipid levels or other systemic risk factors, consistent with the concept that genetic factors affecting cellular functions of the vessel wall are important determinants of atherosclerosis susceptibility. We generated a congenic strain for
Ath29
and confirmed its contribution to lesion development. Toll-like receptor 4 (
Tlr4
), the lipopolysaccharide (LPS) receptor, is located in the
Ath8
region and is known to be defective in C3H/HeJ mice. We constructed a congenic strain carrying a normal
Tlr4
gene on the C3H
Apoe
-null background and found that the defective
Tlr4
does not contribute significantly to lesion resistance during early lesion development.

Conclusions—

We identified one major QTL on chromosome 9,
Ath29
, for early lesion development in the BXH
ApoE
−/−
cross fed on a chow diet and confirmed its contribution in congenic mice. We have also determined that
Tlr4
on the C3H
ApoE
−/−
background does not contribute to early lesion development. *
Ath29
is referred to as
Ath22
in Su et al 2006.
Intrinsic Pathway of Coagulation and Arterial Thrombosis
Authors: Gailani David , Renné Thomas
Published: October 2007

Formation of a fibrin clot is mediated by a group of tightly regulated plasma proteases and cofactors. While this system is essential for minimizing blood loss from an injured blood vessel (hemostasis), it also contributes to pathologic fibrin formation and platelet activation that may occlude vessels (thrombosis). Many antithrombotic drugs target key elements of the plasma coagulation mechanism such as thrombin and factor Xa, based on the premise that plasma elements contributing to thrombosis are primarily those involved in hemostasis. Recent studies with genetically altered mice raise questions about this paradigm. Deficiencies of the intrinsic pathway proteases factor XII and factor XI are not associated with abnormal hemostasis in mice, but impair formation of occlusive thrombi in arterial injury models, indicating that pathways not essential for hemostasis participate in arterial thrombosis. If factor XII or factor XI make similar contributions to thrombosis in humans, these proteases could be ideal targets for drugs to treat or prevent thromboembolic disease with minimal risk of therapy-associated bleeding.
Development and Validation of a Short Form of the Fugl-Meyer Motor Scale in Patients With Stroke
Authors: Hsieh Yu-Wei , Hsueh I-Ping , Chou Yeh-Tai , Sheu Ching-Fan , Hsieh Ching-Lin , Kwakkel Gert
Published: October 2007

Background and Purpose—

The 50-item Fugl-Meyer motor scale (FM) is commonly used in outcome studies. However, the lengthy administration time of the FM keeps it from being widely accepted for routine clinical use. We aimed to develop a short form of the FM (the S-FM) with sound psychometric properties for stroke patients.

Methods—

The FM was administered to 279 patients. It was then simplified based on expert opinions and the results of Rasch analysis. The psychometric properties (including Rasch reliability, concurrent validity, predictive validity, and responsiveness) of the S-FM were examined and were compared with those of the FM. The concurrent validity and responsiveness of the S-FM were further validated in a sample from the Netherlands.

Results—

We selected 6 items for each subscale to construct a 12-item S-FM. The S-FM demonstrated high Rasch reliability, high concurrent validity with the original scale, moderate responsiveness, and moderate predictive validity with the comprehensive activities of daily living function. The S-FM also showed sufficient concurrent validity and responsiveness on the Dutch sample.

Conclusions—

Our results provide strong evidence that the psychometric properties of the S-FM are comparable with those of the FM. The S-FM contains only 12 items, making it a very efficient measure for assessing the motor function of stroke patients in both clinical and research settings.
Simultanagnosia: When a Rose Is Not Red
Authors: Coslett H. Branch , Lie Grace
Published: October 2007

Information regarding object identity (“what”) and spatial location (“where/how to”) is largely segregated in visual processing. Under most circumstances, however, object identity and location are linked. We report data from a simultanagnosic patient (K.E.) with bilateral posterior parietal infarcts who was unable to “see” more than one object in an array despite relatively preserved object processing and normal preattentive processing. K.E. also demonstrated a finding that has not, to our knowledge, been reported: He was unable to report more than one attribute of a single object. For example, he was unable to name the color of the ink in which words were written despite naming the word correctly. Several experiments demonstrated, however, that perceptual attributes that he was unable to report influenced his performance. We suggest that binding of object identity and location is a limited-capacity operation that is essential for conscious awareness for which the posterior parietal lobe is crucial.
Linking Cortical Spike Pattern Codes to Auditory Perception
Authors: Walker Kerry M. M. , Ahmed Bashir , Schnupp Jan W. H.
Published: October 2007

Neurometric analysis has proven to be a powerful tool for studying links between neural activity and perception, especially in visual and somatosensory cortices, but conventional neurometrics are based on a simplistic rate-coding hypothesis that is clearly at odds with the rich and complex temporal spiking patterns evoked by many natural stimuli. In this study, we investigated the possible relationships between temporal spike pattern codes in the primary auditory cortex (A1) and the perceptual detection of subtle changes in the temporal structure of a natural sound. Using a two-alternative forced-choice oddity task, we measured the ability of human listeners to detect local time reversals in a marmoset twitter call. We also recorded responses of neurons in A1 of anesthetized and awake ferrets to these stimuli, and analyzed these responses using a novel neurometric approach that is sensitive to temporal discharge patterns. We found that although spike count-based neurometrics were inadequate to account for behavioral performance on this auditory task, neurometrics based on the temporal discharge patterns of populations of A1 units closely matched the psychometric performance curve, but only if the spiking patterns were resolved at temporal resolutions of 20 msec or better. These results demonstrate that neurometric discrimination curves can be calculated for temporal spiking patterns, and they suggest that such an extension of previous spike count-based approaches is likely to be essential for understanding the neural correlates of the perception of stimuli with a complex temporal structure.
Neuroimaging Studies of Mental Rotation: A Meta-analysis and Review
Authors: Zacks Jeffrey M.
Published: October 2007

Mental rotation is a hypothesized imagery process that has inspired controversy regarding the substrate of human spatial reasoning. Two central questions about mental rotation remain: Does mental rotation depend on analog spatial representations, and does mental rotation depend on motor simulation? A review and meta-analysis of neuroimaging studies help answer these questions. Mental rotation is accompanied by increased activity in the intraparietal sulcus and adjacent regions. These areas contain spatially mapped representations, and activity in these areas is modulated by parametric manipulations of mental rotation tasks, supporting the view that mental rotation depends on analog representations. Mental rotation also is accompanied by activity in the medial superior precentral cortex, particularly under conditions that favor motor simulation, supporting the view that mental rotation depends on motor simulation in some situations. The relationship between mental rotation and motor simulation can be understood in terms of how these two processes update spatial reference frames.
Comparing State- Versus Facility-Level Effects on Crowding in U.S. Correctional Facilities
Authors: Steiner Benjamin , Wooldredge John
Published: October 2007

The literature on prison crowding underscores the potential importance of both state- and facility-level effects on crowding, although empirical research has not assessed these relative effects because of the sole focus on states as units of analysis. This article describes findings from bi-level analyses of crowding across 459 state-operated facilities in 45 states. Findings from cross-sectional models of prison crowding in 1995 and 2000, measured as a ratio of a facility's inmate population to its design capacity, revealed significant differences in levels of crowding based on costs, types of inmates held, and court orders (at the facility level), as well as sentencing policies and the annual number of drug arrests (at the state level). A longitudinal analysis also revealed that differences in crowding levels between 1995 and 2000 coincided with changes in whether facilities increased their design capacity and with rising costs of incarceration. The implications of these findings are discussed.
Psychiatric Disorder in a Juvenile Assessment Center
Authors: McReynolds Larkin S. , Wasserman Gail A. , DeComo Robert E. , John Reni , Keating Joseph M. , Nolen Scott
Published: October 2007

Juvenile assessment centers (JACs) were developed to address service fragmentation and promote the sharing of information among agencies providing services to youth involved with the juvenile justice system. To date, there are no reports that describe the diagnostic profiles of the youth served by such centers. The authors hypothesize that the rates of psychiatric disorder among youth at JAC intake would be lower than rates reported for youth in secure care, that girls would show higher rates of some disorders, and that those with substance disorders would show higher rates of other, co-occurring disorders. Disorder was measured on the Voice Diagnostic Interview Schedule for Children in 1,012 randomly selected youth (248 girls). Rates of disorder for JAC youth are lower than those reported for incarcerated samples and more comparable to other general intake samples; JAC youth's diagnostic profiles remain elevated compared to youth in the general population, and girls report higher rates of disorder in three of four diagnostic clusters examined. Clinical and policy implications are discussed.
Anatomopathological Analysis of Sentinel and Nonsentinel Lymph Nodes in Breast Cancer: Hematoxylin-Eosin Versus Immunohistochemistry
Authors: Teixeira Soares Cleverson , Frederigue-Junior Ulisses , de Luca Laurival Antonio
Published: October 2007

The authors compare the detection of metastases in sentinel lymph nodes (SLNs) and nonsentinel lymph nodes (NSLNs) using hematoxylin-eosin (HE) staining versus immunohistochemistry (IHC). Thirty-six patients with breast carcinoma undergo exeresis of the primary tumor and of 50 SLNs and 491 NSLNs. Sentinel lymph nodes are sectioned into transverse slices of 2- to 3-mm thickness, and a cytologic smear and a frozen section were obtained from each slice. The slices are completely cut into serial sections at 100-µm intervals. Two consecutive 4-µm-thick sections are then obtained from each level and were prepared for HE staining and IHC. Nonsentinel lymph nodes are evaluated similarly to SLNs. The authors obtain 4076 SLN sections and 32 012 NSLN sections, for a total of 36 088 sections. A comparison of HE staining versus IHC based on the total number of sections shows a sensitivity of 93.8%, a negative predictive value of 98.9%, and an accuracy of 99.1%. The values obtained by HE staining are similar to those obtained by IHC.
Esophageal GIST: Case Report of Surgical Enucleation and Update on Current Diagnostic and Therapeutic Options
Authors: Portale Giuseppe , Zaninotto Giovanni , Costantini Mario , Rugge Massimo , Pennelli Gian Maria , Rampado Sabrina , Bocus Paolo , Ancona Ermanno
Published: October 2007

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, but they have been rarely reported in the esophagus. The authors present the case of an esophageal GIST and discuss the diagnostic course and therapeutic options, as currently reported in the literature.
Cecal Adenocarcinoma With Prominent Rhabdoid Feature: Report of a Case With Immunohistochemical, Ultrastructural, and Molecular Analyses
Authors: Kono Tokuyuki , Imai Yasuo , Imura Johji , Ono Yuko , Hagiwara Shingo , Taira Katsuyoshi , Fujita Masanori , Tsubaki Masahiro , Sunagawa Masakatsu , Fujimori Takahiro
Published: October 2007

Colorectal adenocarcinoma with rhabdoid phenotype is extremely rare, and only 1 case of adenocarcinoma showing rhabdoid dedifferentiation has been reported. The authors present another case of cecal adenocarcinoma with prominent rhabdoid feature in a 66-year-old man. The 13-cm sized tumor consisted mainly of rhabdoid cells and partly of adenocarcinoma, and transition from adenocarcinoma to rhabdoid areas was noted. Ultrastructural analysis revealed intracytoplasmic aggregates of intermediate filaments in the rhabdoid cells. Adenocarcinoma cells were diffusely immunoreactive to cytokeratin 7 and AE1/3, but occasionally positive for vimentin. The rhabdoid cells were negative for cytokeratin 7, weakly/focally immunoreactive to AE1/3, and diffusely positive for vimentin. These results suggested that the rhabdoid cells were dedifferentiated adenocarcinoma. Analysis of the rhabdoid cells with molecular techniques is also presented.
Primitive Small Cell Tumor With Epithelial, Gangliocytic, Neuroendocrine, and Mesenchymal Differentiation: Report of 2 Cases
Authors: Michal Michal , Kazakov Dmitry V. , Šima Radek , Vaněček Tomas
Published: October 2007

The authors describe 2 tumors that, to the best of their knowledge, are hitherto undescribed. The predominant cell type was small round to fusiform dark blue cells. The dark blue cells formed distinct epithelial cords with gland-like formations with mucicarmine-positive mucus. Another distinctive component of the tumors was a mesenchymal one. The mesenchymal areas appeared benign and could be likened to a fibroma having a densely collagenous stroma, or they had spindle cells set in the myxoid background, rendering a myxoma-like appearance. Another distinctive feature was ganglion cell differentiation. Mitotic figures, including atypical forms, were found only in the small cell component. All cells were immunohistochemically negative for actin, calponin, desmin, HMB45, neurofilament protein, CD99/MIC2, Melan A, tyrosinase, serotonin, CD56, Melan A, GFAP, and S-100 protein. Cytokeratin, synaptophysin, FLI1 protein, and chromogranin antibodies reacted only in the primitive small round cells, while all the other components were cytokeratin negative. Fluorescence in situ hybridization showed that the tumors are without the EWSR1 gene translocation and gain 12p. Ultrastructurally, the cells were endowed with well-formed intercellular desmosomes membrane-bound secretory in the cytoplasm. Granules were found in the cytoplasm. We suggest the name “primitive small cell tumor with epithelial, gangliocytic, neuroendocrine, and mesenchymal differentiation” for this neoplasm.
Ossifying Fibromyxoid Tumor May Express CD56 and CD99: A Case Report
Authors: Miliaras Dimosthenis , Meditskou Soultana , Ketikidou Maria
Published: October 2007

Ossifying fibromyxoid tumor (OFMT) is an uncommon soft tissue neoplasm characterized by a combination of myxoid and/or fibrous stroma with areas of ossification. Although most authors postulate a neuroectodermal origin for this peculiar tumor, there is no agreement in the literature regarding its histogenesis. In this article, we present the immunohistochemical findings of a case of a 39-year-old white male with an OFMT of the soft tissue in the mandibular region. The tumor was positive to S-100 protein, glial fibrillary acidic protein, CD99, CD56 and negative to smooth muscle actin, cytokeratins AE1/AE3, epithelial membrane antigen, and CD68. To the best of our knowledge, this is the first case reported to be positive to CD56 and CD99. Immunoreactivity to these two antibodies, together with reactivity for S-100 protein and glial fibrillary acidic protein, suggests that OFMT is of a neuroectodermal origin. In our opinion, in the absence of reactivity to at least one neuroectodermal marker one should seriously question a diagnosis of OFMT.
p53 and mdm2 Expression in Colorectal Carcinoma: A Correlative Analysis With Clinical Staging and Histological Parameters
Authors: Das Prasenjit , Vaiphei Kim , Jain Deepali , Jai Dev Wig
Published: October 2007

Colorectal carcinoma (CRC) is rare in the Indian subcontinent. The two-hit carcinogenic theory has been well established from the turn of this century, in which p53 is described as a late marker in colorectal carcinogenesis, and murine double minute 2 (mdm2) has not yet been correlated with colorectal carcinoma. With the recent introduction of anti-mdm2 oligonucleotides, it is apparent that if its role can be established in colorectal carcinogenesis, the DNA conservation of the wild p53 strain would be achieved therapeutically because mdm2 conserves the wild p53 strain. We studied 32 cases with adequate number of controls and found a positive correlation ( P = .001) between these proteins. These proteins were expressed in tumor adjacent to the hyperplastic mucosa, dysplastic mucosa, and aberrant crypt foci, unlike in studies in the West. The expression of these proteins was correlated with aggressive tumor behavior. All these indicate significant diagnostic, therapeutic, and prognostic roles for these proteins.
Association of NET-1 Gene Expression With Human Hepatocellular Carcinoma
Authors: Li Chen  , Zhiwei Wang  , Xi Zhan  , Li De-Chuen , Zhu York-Yuan , Jianwei Zhu
Published: October 2007

NET-1 is a member of the NET- x family. To explore the potential role of NET-1 in hepatocellular carcinoma (HCC), the expression of NET-1 and the relationship with HCC were examined for the first time. We found that NET-1 was frequently expressed in HCC and the peritumor tissue. The relative amounts of NET-1 mRNA in HCC and peritumor tissue were 0.645 ± 0.37 and 0.466 ± 0.30, respectively, indicating a higher expression level in HCC than in the peritumor ( P < .05). NET-1 protein is usually located on the cell membrane and in the cytoplasm of HCC cells. NET-1 immunoreactivity was found in 126 out of 130 samples of HCC tissue (96.92%). An association of NET-1 expression with cytological variants, histopathological grading, and clinical stages of HCC was also found ( P < .05). Detection of NET-1 gene expression in liver biopsy may provide useful information about the biological behavior of HCC.
Amyloid Precursor Protein and Mitochondrial Dysfunction in Alzheimer's Disease
Authors: Anandatheerthavarada Hindupur K. , Devi Latha
Published: October 2007

Growing evidence suggests that mitochondrial dysfunction is one of the key intracellular lesions associated with the pathogenesis of Alzheimer's disease (AD). Mitochondria, the powerhouses of the cell, participate in a number of physiological functions that include calcium homeostasis, signal transduction, and apoptosis. However, the pathophysiological mechanisms underlying the decline of mitochondrial vital functions leading to the dysfunction of mitochondria during AD are not well understood. Recent literature has observed the accumulation of Alzheimer's amyloid precursor protein (APP) and its C-terminal—cleaved product β-amyloid (Aβ) in the mitochondrial compartment. Furthermore, evidence also implicates that the accumulation of full-length APP and Aβ in the mitochondrial compartment has a causative role in impairing mitochondrial physiological functions. Here, we review the mode of mitochondrial transport of full-length APP and Aβ and its pathological implications in bringing about mitochondrial dysfunction as seen in AD. NEUROSCIENTIST 13(6):626—638, 2007. DOI: 10.1177/1073858407303536
Neuron—Glial Communication at Synapses: Insights From Vertebrates and Invertebrates
Authors: Murai Keith K. , Van Meyel Donald J.
Published: October 2007

Glial cells are instrumental for many aspects of nervous-system function. Interestingly, complex neuron—glial interactions at synapses are commonly found in both invertebrates and vertebrates. Although these interactions are known to be important for synaptic physiology, the cellular processes and molecular mechanisms involved have not been fully uncovered. Identifying the common and unique features of neuron—glial interactions between invertebrates and vertebrates may provide valuable insights into the relationship of neuron—glial cross-talk to nervous-system function. This review highlights selected studies that have revealed structural and functional insights into neuron—glial interactions at synapses in invertebrate and vertebrate model systems. NEUROSCIENTIST 13(6): 657—666, 2007. DOI: 10.1177/1073858407304393
TNF α: A Trigger of Autonomic Dysfunction
Authors: Hermann Gerlinda E. , Rogers Richard C.
Published: October 2007

During disease, infection, or trauma, the cytokine tumor necrosis factorα (TNF α) causes fever, fatigue, malaise, allodynia, anorexia, gastric stasis associated with nausea, and emesis via interactions with the central nervous system. Our studies have focused on how TNFα produces a profound gastric stasis by acting on vago-vagal reflex circuits in the brainstem. Sensory elements of this circuit (i.e., nucleus of the solitary tract [NST] and area postrema) are activated by TNFα. In response, the efferent elements (i.e., dorsal motor neurons of the vagus) cause gastroinhibition via their action on the gastric enteric plexus. We find that TNFα presynaptically modulates the release of glutamate from primary vagal afferents to the NST and can amplify vagal afferent responsiveness by sensitizing presynaptic intracellular calcium-release mechanisms. The constitutive presence of TNFα receptors on these afferents and their ability to amplify afferent signals may explain how TNF α can completely disrupt autonomic control of the gut. NEUROSCIENTIST 14(1):53—67, 2008. DOI: 10.1177/1073858407305725
Defining the Group
Authors: Masuoka Natalie
Published: October 2007

Latinos can opt for many different forms of ethnic group identity, ranging from that based on national origin to that based on a racialized non-White status. Unclear, however, is which of these forms of group identity is the most relevant to politics. The purpose of this study is twofold: to examine the different forms of Latino group consciousness and to uncover the relationship of each with political participation. This article outlines the three major forms of Latino group consciousness: national origin, panethnic, and racial. Ordered logistic and logistic models are used to determine the factors that predict strong identification with each form of group consciousness and the impact of those forms of consciousness on political participation. Although Latinos are more likely to evoke national origin or panethnic identities, racial identities are those that most strongly encourage political participation.
The Influence of Hand Dominance on the Response to a Constraint-Induced Therapy Program Following Stroke
Authors: Langan Jeanne , van Donkelaar Paul
Published: October 2007

Background. Following stroke it is common to exhibit deficits in mobility of the upper extremity. Constraint-induced therapy (CIT) is a rehabilitation technique used to promote use of the more affected hand via constraint of the less affected hand. One factor that could impact the outcome following CIT is hand dominance. Years of preferred use of one hand may give individuals with the dominant hand affected by stroke an advantage in improving the mobility of the more affected hand compared to those individuals with the nondominant hand affected by stroke. In addition, the diminished use of the less affected hand during CIT may also create changes. Objective. Our goal was to better understand how hand dominance may influence the response to a CIT program both cortically and behaviorally in both the more affected hand and less affected constrained hand. Methods. A repeated measures design with a double baseline was used to assess changes in clinical tests and functional magnetic resonance imaging (fMRI) in individuals with their dominant or nondominant hand affected by stroke involved in a CIT program. Results. No significant differences were found between groups in their responses to CIT. Overall subjects demonstrated behavioral and cortical changes with the more affected hand and the less affected constrained hand did not significantly change. Conclusion. CIT promotes improvement of the more affected hand particularly on complex tests without decrements to the less affected constrained hand. Cortically, statistically significant changes in activation were noted after the intervention for the more affected hand; no changes were noted with the less affected constrained hand.
Frequency of Uterine Malformations Among Women in a Restricted Gene Pool Community
Authors: Ismail Saad Ramzi
Published: October 2007

This random, retrospective cross-sectional study was performed to determine the frequency of uterine malformation in restricted gene pool communities. During 2003—2006, 800 women from the community of LaCrete in northern Alberta, Canada (known restricted gene pool for over 500 years), participated. Of the participants, 156 (19.5% of the study population) showed some form of structural uterine malformation. This is 5.5 times higher than what is reported in the general population. All 156 subjects were further investigated with magnetic resonance imaging, 3D sonography, hysterosalpingiography, hysteroscopy, and laparoscopy. These tests revealed that 30 of these women had no previous pregnancies or live births, 40 had one or more previous pregnancies and live births and more than two miscarriages, and 55 had recurrent miscarriages. This study has provided new insights into the increasing number of uterine malformations in the LaCrete population. The significantly higher prevalence of uterine malformations in a restricted gene pool community compared to the reported prevalence in the general population might indicate a direct link between a lack of genetic diversity and the development of uterine malformations in women.
Neither DNA hypomethylation nor changes in the kinetics of erythroid differentiation explain 5-azacytidine's ability to induce human fetal hemoglobin
Authors: Mabaera Rodwell , Greene Michael R. , Richardson Christine A. , Conine Sarah J. , Kozul Courtney D. , Lowrey Christopher H.
Published: October 2007

5-azacytidine (5-Aza) is a potent inducer of fetal hemoglobin (HbF) in people with β-thalassemia and sickle cell disease. Two models have been proposed to explain this activity. The first is based on the drug's ability to inhibit global DNA methylation, including the fetal globin genes, resulting in their activation. The second is based on 5-Aza's cytotoxicity and observations that HbF production is enhanced during marrow recovery. We tested these models using human primary cells in an in vitro erythroid differentiation system. We found that doses of 5-Aza that produce near maximal induction of γ-globin mRNA and HbF do not alter cell growth, differentiation kinetics, or cell cycle, but do cause a localized demethylation of the γ promoter. However, when we reduced γ promoter methylation to levels equivalent to those seen with 5-Aza or to the lower levels seen in primary fetal erythroid cells using DNMT1 siRNA and shRNA, we observed no induction of γ-globin mRNA or HbF. These results suggest that 5-Aza induction of HbF is not the result of global DNA demethylation or of changes in differentiation kinetics, but involves an alternative, previously unrecognized mechanism. Other results suggest that posttranscriptional regulation plays an important role in the 5-Aza response.
Increased risk of breast cancer among survivors of allogeneic hematopoietic cell transplantation: a report from the FHCRC and the EBMT-Late Effect Working Party
Authors: Friedman Debra L. , Rovo Alicia , Leisenring Wendy , Locasciulli Anna , Flowers Mary E. D. , Tichelli Andre , Sanders Jean E. , Deeg H. Joachim , Socie Gerard
Published: October 2007

As risk for secondary breast cancer is elevated among cancer survivors treated with conventional therapy, we sought to determine the risk among 3337 female 5-year survivors who underwent an allogeneic hematopoietic cell transplantation (HCT) at the Fred Hutchinson Cancer Research Center or at one of 82 centers reporting to the European Bone Marrow Transplant Registry. Risk was calculated using standardized incidence ratios (SIRs), and risk factors were evaluated with a multivariable Cox proportional hazards model. Fifty-two survivors developed breast cancer at a median of 12.5 (range: 5.7-24.8) years following HCT (SIR = 2.2). Twenty-five–year cumulative incidence was 11.0%, higher among survivors who received total body irradiation (TBI) (17%) than those who did not receive TBI (3%). In multivariable analysis, increased risk was associated with longer time since transplantation (hazard ratio [HR] for 20+ years after transplantation = 10.8), use of TBI (HR = 4.0), and younger age at transplantation (HR = 9.5 for HCT < 18 years). Hazard for death associated with breast cancer was 2.5 (95% CI: 1.1-5.8). We conclude that female survivors of allogeneic HCT are at increased risk of breast cancer and should be educated about the need for regular screening.
qPIPSA: Relating enzymatic kinetic parameters and interaction fields
Authors: Gabdoulline Razif R , Stein Matthias , Wade Rebecca C
Published: October 2007

Background

The simulation of metabolic networks in quantitative systems biology requires the assignment of enzymatic kinetic parameters. Experimentally determined values are often not available and therefore computational methods to estimate these parameters are needed. It is possible to use the three-dimensional structure of an enzyme to perform simulations of a reaction and derive kinetic parameters. However, this is computationally demanding and requires detailed knowledge of the enzyme mechanism. We have therefore sought to develop a general, simple and computationally efficient procedure to relate protein structural information to enzymatic kinetic parameters that allows consistency between the kinetic and structural information to be checked and estimation of kinetic constants for structurally and mechanistically similar enzymes.

Results

We describe qPIPSA: quantitative Protein Interaction Property Similarity Analysis. In this analysis, molecular interaction fields, for example, electrostatic potentials, are computed from the enzyme structures. Differences in molecular interaction fields between enzymes are then related to the ratios of their kinetic parameters. This procedure can be used to estimate unknown kinetic parameters when enzyme structural information is available and kinetic parameters have been measured for related enzymes or were obtained under different conditions. The detailed interaction of the enzyme with substrate or cofactors is not modeled and is assumed to be similar for all the proteins compared. The protein structure modeling protocol employed ensures that differences between models reflect genuine differences between the protein sequences, rather than random fluctuations in protein structure.

Conclusion

Provided that the experimental conditions and the protein structural models refer to the same protein state or conformation, correlations between interaction fields and kinetic parameters can be established for sets of related enzymes. Outliers may arise due to variation in the importance of different contributions to the kinetic parameters, such as protein stability and conformational changes. The qPIPSA approach can assist in the validation as well as estimation of kinetic parameters, and provide insights into enzyme mechanism.
Family expansion and gene rearrangements contributed to the functional specialization of PRDM genes in vertebrates
Authors: Fumasoni Irene , Meani Natalia , Rambaldi Davide , Scafetta Gaia , Alcalay Myriam , Ciccarelli Francesca D
Published: October 2007

Background

Progressive diversification of paralogs after gene expansion is essential to increase their functional specialization. However, mode and tempo of this divergence remain mostly unclear. Here we report the comparative analysis of PRDM genes, a family of putative transcriptional regulators involved in human tumorigenesis.

Results

Our analysis assessed that the PRDM genes originated in metazoans, expanded in vertebrates and further duplicated in primates. We experimentally showed that fast-evolving paralogs are poorly expressed, and that the most recent duplicates, such as primate-specific PRDM7, acquire tissue-specificity. PRDM7 underwent major structural rearrangements that decreased the number of encoded Zn-Fingers and modified gene splicing. Through internal duplication and activation of a non-canonical splice site (GC-AG), PRDM7 can acquire a novel intron. We also detected an alternative isoform that can retain the intron in the mature transcript and that is predominantly expressed in human melanocytes.

Conclusion

Our findings show that (a) molecular evolution of paralogs correlates with their expression pattern; (b) gene diversification is obtained through massive genomic rearrangements; and (c) splicing modification contributes to the functional specialization of novel genes.
Androgen-induced masculinization in rainbow trout results in a marked dysregulation of early gonadal gene expression profiles
Authors: Baron Daniel , Montfort Jérôme , Houlgatte Rémi , Fostier Alexis , Guiguen Yann
Published: October 2007

Background

Fish gonadal sex differentiation is affected by sex steroids treatments providing an efficient strategy to control the sexual phenotype of fish for aquaculture purposes. However, the biological effects of such treatments are poorly understood. The aim of this study was to identify the main effects of an androgen masculinizing treatment (11β-hydroxyandrostenedione, 11βOHΔ4, 10 mg/kg of food for 3 months) on gonadal gene expression profiles of an all-female genetic population of trout. To characterize the most important molecular features of this process, we used a large scale gene expression profiling approach using rainbow trout DNA microarrays combined with a detailed gene ontology (GO) analysis.

Results

2,474 genes were characterized as up-regulated or down-regulated in trout female gonads masculinized by androgen in comparison with control male or female gonads from untreated all-male and all-female genetic populations. These genes were classified in 13 k-means clusters of temporally correlated expression profiles. Gene ontology (GO) data mining revealed that androgen treatment triggers a marked down-regulation of genes potentially involved in early oogenesis processes (GO 'mitotic cell cycle', 'nucleolus'), an up-regulation of the translation machinery (GO 'ribosome') along with a down-regulation of proteolysis (GO 'proteolysis', 'peptidase' and 'metallopeptidase activity'). Genes considered as muscle fibres markers (GO 'muscle contraction') and genes annotated as structural constituents of the extracellular matrix (GO 'extracellular matrix') or related to meiosis (GO 'chromosome' and 'meiosis') were found significantly enriched in the two clusters of genes specifically up-regulated in androgen-treated female gonads. GO annotations 'Sex differentiation' and 'steroid biosynthesis' were enriched in a cluster of genes with high expression levels only in control males. Interestingly none of these genes were stimulated by the masculinizing androgen treatment.

Conclusion

This study provides evidence that androgen masculinization results in a marked dysregulation of early gene expression profiles when compared to natural testicular or ovarian differentiation. Based on these results we suggest that, in our experimental conditions, androgen masculinization proceeds mainly through an early inhibition of female development.
The 2G allele of promoter region of Matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma
Authors: Nishizawa Rishiho , Nagata Masaki , Noman Arhab A , Kitamura Nobutaka , Fujita Hajime , Hoshina Hideyuki , Kubota Takehiko , Itagaki Manami , Shingaki Susumu , Ohnishi Makoto , Kurita Hiroshi , Katsura Kouji , Saito Chikara , Yoshie Hiromasa , Takagi Ritsuo
Published: October 2007

Background

Matrix metalloproteinase (MMP) is known to be involved in the initial and progressive stages of cancer development, and in the aggressive phenotypes of cancer. This study examines the association of single nucleotide polymorphisms in promoter regions of MMP-1 and MMP-3 with susceptibility to oral squamous cell carcinoma (OSCC).

Methods

We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of MMP-1 and MMP-3.

Results

The frequency of the MMP-1 2G allele was higher and that of the 1G homozygote was lower in the OSCC cases (p = 0.034). A multivariate logistic regression analysis revealed that subjects who were 45 years old or older had a significantly increased (2.47-fold) risk of OSCC (95%CI 1.47–4.14, p = 0.0006), and those carrying the MMP-1 2G allele had a 2.30-fold risk (95%CI 1.15–4.58, p = 0.018), indicating independent involvement of these factors in OSCC. One of the key discoveries of this research is the apparent reduction of the MMP-1 1G/1G and 1G/2G genotype distributions among the early onset OSCC cases under the ages of 45 years. It should be noted that the tongue was the primary site in 86.2% of these early onset cases. This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue.

Conclusion

Since the 2G allele is a majority of the MMP-1 genotype in the general population, it seems to act as a genetic pre-condition in OSCC development. However this report suggests a crucial impact of the MMP-1 2G allele in the early onset OSCC.
Prevalence of self-reported diagnosis of diabetes mellitus and associated risk factors in a national survey in the US population: SHIELD (Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes)
Authors: Bays Harold E , Bazata Debbra D , Clark Nathaniel G , Gavin James R , Green Andrew J , Lewis Sandra J , Reed Michael L , Stewart Walter , Chapman Richard H , Fox Kathleen M , Grandy Susan
Published: October 2007

Background

Studies derived from continuous national surveys have shown that the prevalence of diagnosed diabetes mellitus in the US is increasing. This study estimated the prevalence in 2004 of self-reported diagnosis of diabetes and other conditions in a community-based population, using data from the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD).

Methods

The initial screening questionnaire was mailed in 2004 to a stratified random sample of 200,000 households in the US, to identify individuals, age ≥ 18 years of age, with diabetes or risk factors associated with diabetes. Follow-up disease impact questionnaires were then mailed to a representative, stratified random sample of individuals (n = 22,001) in each subgroup of interest (those with diabetes or different numbers of risk factors for diabetes). Estimated national prevalence of diabetes and other conditions was calculated, and compared to prevalence estimates from the National Health and Nutrition Examination Survey (NHANES) 1999–2002.

Results

Response rates were 63.7% for the screening, and 71.8% for the follow-up baseline survey. The SHIELD screening survey found overall prevalence of self-reported diagnosis of diabetes (either type 1 or type 2) was 8.2%, with increased prevalence with increasing age and decreasing income. In logistic regression modeling, individuals were more likely to be diagnosed with type 2 diabetes if they had abdominal obesity (odds ratio [OR] = 3.50; p < 0.0001), BMI ≥28 kg/m2 (OR = 4.04; p < 0.0001), or had been diagnosed with dyslipidemia (OR = 3.95; p < 0.0001), hypertension (OR = 4.82; p < 0.0001), or with cardiovascular disease (OR = 3.38; p < 0.0001).

Conclusion

The SHIELD design allowed for a very large, community-based sample with broad demographic representation of the population of interest. When comparing results from the SHIELD screening survey (self-report only) to those from NHANES 1999–2002 (self-report, clinical and laboratory evaluations), the prevalence of diabetes was similar. SHIELD allows the identification of respondents with and without a current diagnosis of the illness of interest, and potential longitudinal evaluation of risk factors for future diagnosis of that illness.
Mitochondrial DNA mutations in oxyphilic and chief cell parathyroid adenomas
Authors: Costa-Guda Jessica , Tokura Takehiko , Roth Sanford I , Arnold Andrew
Published: October 2007

Background

The potential pathogenetic significance of mitochondrial DNA (mtDNA) mutations in tumorigenesis is controversial. We hypothesized that benign tumorigenesis of a slowly replicating tissue like the human parathyroid might constitute an especially fertile ground on which a selective advantage conferred by mtDNA mutation could be manifested and might contribute to the oxyphilic phenotype observed in a subset of parathyroid tumors.

Methods

We sought acquired mitochondrial DNA mutations by sequencing the entire 16.6 kb mitochondrial genome of each of thirty sporadic parathyroid adenomas (18 chief cell and 12 oxyphil cell), eight independent, polyclonal, parathyroid primary chief cell hyperplasias plus corresponding normal control samples, five normal parathyroid glands, and one normal thyroid gland.

Results

Twenty-seven somatic mutations were identified in 15 of 30 (9 of 12 oxyphil adenomas, 6 of 18 chief cell) parathyroid adenomas studied. No somatic mutations were observed in the hyperplastic parathyroid glands.

Conclusion

Features of the somatic mutations suggest that they may confer a selective advantage and contribute to the molecular pathogenesis of parathyroid adenomas. Importantly, the statistically significant differences in mutation prevalence in oxyphil vs. chief cell adenomas also suggest that mtDNA mutations may contribute to the oxyphil phenotype.