bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal Bone Density Obtained in the Absence of Insulin Receptor Expression in Bone
Authors: Irwin Regina , Lin Hua V. , Motyl Katherine J. , McCabe Laura R.
Published: September 2006

Type I diabetes is characterized by little or no insulin production and hyperglycemic conditions. It is also associated with significant bone loss and increased bone marrow adiposity. To examine the role of reduced insulin signaling in type I diabetic bone loss without inducing hyperglycemia, we used genetically reconstituted insulin receptor knockout mice (IRKO-L1) that are euglycemic as a result of human insulin receptor transgene expression in the pancreas, liver, and brain. RT-PCR analyses demonstrated undetectable levels of insulin receptor expression in IRKO-L1 bone, yet IRKO-L1 bones exhibit similar (and trend toward greater) bone density compared with wild-type animals as determined by microcomputed tomography. More detailed bone analyses indicated that cortical bone area was increased in tibias of IRKO-L1 mice. Osteoblast markers (osteocalcin and runx2 mRNA levels) and resorption markers (serum pyridinoline levels) were similar in wild-type and IRKO-L1 bones. When marrow adiposity was examined, we noticed a decrease in adipocyte number and fatty-acid-binding protein 2 expression in IRKO-L1 mice compared with wild-type mice. Bone marrow stromal cell cultures obtained from wild-type and IRKO-L1 mice demonstrated similar adipogenic and osteogenic potentials, indicating that systemic factors likely contribute to differences in marrow adiposity in vivo. Interestingly, IGF-I receptor mRNA levels were elevated in IRKO-L1 bones, suggesting (in combination with hyperinsulinemic conditions) that increased IGF-I receptor signaling may represent a compensatory response and contribute to the changes in cortical bone. Taken together, these results suggest that reduced insulin receptor signaling in bone is not a major factor contributing to bone loss in type I diabetes.
Angiotensin II-Mediated Protein Kinase D Activation Stimulates Aldosterone and Cortisol Secretion in H295R Human Adrenocortical Cells
Authors: Romero Damian G. , Welsh Bronwyn L. , Gomez-Sanchez Elise P. , Yanes Licy L. , Rilli Silvia , Gomez-Sanchez Celso E.
Published: September 2006

Protein kinases are important mediators in intracellular signaling. Angiotensin II is the most important modulator of adrenal zona glomerulosa cell physiology. Angiotensin II regulates steroidogenesis and proliferation among many other metabolic processes. H295R human adrenal cells are a widely used experimental model to study adrenal cell physiology and metabolism. We screened for protein kinase expression levels using the Kinetwork system in H295R cells after 3 h angiotensin II treatment. Protein kinase D (PKD) was the protein kinase that suffers the most dramatic changes. PKD is a member of a new class of serine/threonine protein kinases that is activated by phosphorylation. Our studies indicated that angiotensin II time- and dose-dependently increased PKD phosphorylation, which occurred within 2 min of angiotensin II treatment and at concentrations as low as 1 nm. PKD phosphorylation was also dose-dependently increased by the PKC activator phorbol 12-myristate 13-acetate. Angiotensin II-mediated PKD phosphorylation was blocked by several PKC inhibitors. Furthermore, PKCε translocation inhibitor peptide decreased angiotensin II-mediated PKD phosphorylation, and PKCε down-regulation by RNA interference also decreased PKD phosphorylation mediated by angiotensin II. Cotransfection of constitutively active PKD mutant constructs up-regulated aldosterone synthase and 11β-hydroxylase expression in reporter assays. Constitutively active PKD mutants increased aldosterone and cortisol secretion under angiotensin II stimulatory conditions. This study reveals that PKD is an intracellular signaling mediator of angiotensin II regulation of steroidogenesis in human adrenal cells. These data provide new insights into the molecular mechanisms involved in angiotensin II-induced physiological and pathophysiological events in adrenal cells.
Transgenerational Epigenetic Imprinting of the Male Germline by Endocrine Disruptor Exposure during Gonadal Sex Determination
Authors: Chang Hung-Shu , Anway Matthew D. , Rekow Stephen S. , Skinner Michael K.
Published: September 2006

Embryonic exposure to the endocrine disruptor vinclozolin at the time of gonadal sex determination was previously found to promote transgenerational disease states. The actions of vinclozolin appear to be due to epigenetic alterations in the male germline that are transmitted to subsequent generations. Analysis of the transgenerational epigenetic effects on the male germline (i.e. sperm) identified 25 candidate DNA sequences with altered methylation patterns in the vinclozolin generation sperm. These sequences were identified and mapped to specific genes and noncoding DNA regions. Bisulfite sequencing was used to confirm the altered methylation pattern of 15 of the candidate DNA sequences. Alterations in the epigenetic pattern (i.e. methylation) of these genes/DNA sequences were found in the F2 and F3 generation germline. Therefore, the reprogramming of the male germline involves the induction of new imprinted-like genes/DNA sequences that acquire an apparent permanent DNA methylation pattern that is passed at least through the paternal allele. The expression pattern of several of the genes during embryonic development were found to be altered in the vinclozolin F1 and F2 generation testis. A number of the imprinted-like genes/DNA sequences identified are associated with epigenetic linked diseases. In summary, an endocrine disruptor exposure during embryonic gonadal sex determination was found to promote an alteration in the epigenetic (i.e. induction of imprinted-like genes/DNA sequences) programming of the male germline, and this is associated with the development of transgenerational disease states.
Conserved Amino Acid Residues that Are Important for Ligand Binding in the Type I Gonadotropin-Releasing Hormone (GnRH) Receptor Are Required for High Potency of GnRH II at the Type II GnRH Receptor
Authors: Mamputha Sipho , Lu Zhi-liang , Roeske Roger W. , Millar Robert P. , Katz Arieh A. , Flanagan Colleen A.
Published: September 2006

GnRH I regulates reproduction. A second form, designated GnRH II, selectively binds type II GnRH receptors. Amino acids of the type I GnRH receptor required for binding of GnRH I (Asp2.61(98), Asn2.65(102), and Lys3.32(121)) are conserved in the type II GnRH receptor, but their roles in receptor function are unknown. We have delineated their functions using mutagenesis, signaling and binding assays, immunoblotting, and computational modeling. Mutating Asp2.61(97) to Glu or Ala, Asn2.65(101) to Ala, or Lys3.32(120) to Gln decreased potency of GnRH II-stimulated inositol phosphate production. Consistent with proposed roles in ligand recognition, mutations eliminated measurable binding of GnRH II, whereas expression of mutant receptors was not decreased. In detailed analysis of how these residues affect ligand-dependent signaling, [Trp2]-GnRH I showed lesser decreases in potency than GnRH I at the Asp2.61(97)Glu mutant. In contrast, [Trp2]-GnRH II showed the same loss of potency as GnRH II at this mutant. This suggests that Asp2.61(97) contributes to recognition of His2 of GnRH I, but not of GnRH II. GnRH II showed a large decrease in potency at the Asn2.65(101)Ala mutant compared with analogs lacking the C⋕O group of Gly10NH2. This suggests that Asn2.65(101) recognizes Gly10NH2 of GnRH II. GnRH agonists showed large decreases in potency at the Lys3.32(120)Gln mutant, but antagonist activity was unaffected. This suggests that Lys3.32(120) recognizes agonists, but not antagonists, as in the type I receptor. These data indicate that roles of conserved residues are similar, but not identical, in the type I and II GnRH receptors.
Liver X Receptors Regulate Adrenal Steroidogenesis and Hypothalamic-Pituitary-Adrenal Feedback
Authors: Nilsson Maria , Stulnig Thomas M. , Lin Chin-Yo , Yeo Ai Li , Nowotny Peter , Liu Edison T. , Steffensen Knut R.
Published: September 2006

The nuclear hormone receptors liver X receptor α (LXRα) (NR1H3) and LXRβ (NR1H2) are established regulators of cholesterol, lipid, and glucose metabolism and are attractive drug targets for the treatment of diabetes and cardiovascular disease. Adrenal steroid hormones including glucocorticoids and mineralocorticoids are known to interfere with glucose metabolism, insulin signaling, and blood pressure regulation. Here we present genome-wide expression profiles of LXR-responsive genes in both the adrenal and the pituitary gland. LXR activation in cultured adrenal cells inhibited expression of multiple steroidogenic genes and consequently decreased adrenal steroid hormone production. In addition, LXR agonist treatment elevated ACTH mRNA expression and hormone secretion from pituitary cells both in vitro and in vivo. Reduced expression of the glucocortioid-activating enzyme 11β-hydroxysteroid dehydrogenase 1 in pituitary cells upon LXR activation suggests blunting of the negative feedback of glucocorticoids by LXRs. In conclusion, LXRs independently interfere with the hypothalamic-pituitary-adrenal axis regulation at the level of the pituitary and the adrenal gland.
Activation of Pregnane X Receptor Disrupts Glucocorticoid and Mineralocorticoid Homeostasis
Authors: Zhai Yonggong , Pai Harish V. , Zhou Jie , Amico Janet A. , Vollmer Regis R. , Xie Wen
Published: September 2006

The pregnane X receptor (PXR) was isolated as a xenobiotic receptor that regulates responses to various xenobiotic agents. In this study, we show that PXR plays an important endobiotic role in adrenal steroid homeostasis. Activation of PXR by genetic (transgene) or pharmacological (ligand, such as rifampicin) markedly increased plasma concentrations of corticosterone and aldosterone, the respective primary glucocorticoid and mineralocorticoid in rodents. The increased levels of corticosterone and aldosterone were associated with activation of adrenal steroidogenic enzymes, including cytochrome P450 (CYP)11a1, CYP11b1, CYP11b2, and 3β-hydroxysteroid dehydrogenase. The PXR-activating transgenic mice also exhibited hypertrophy of the adrenal cortex, loss of glucocorticoid circadian rhythm, and lack of glucocorticoid responses to psychogenic stress. Interestingly, the transgenic mice had normal pituitary secretion of ACTH and the corticosterone-suppressing effect of dexamethasone was intact, suggesting a functional hypothalamus-pituitary-adrenal axis despite a severe disruption of adrenal steroid homeostasis. The ACTH-independent hypercortisolism in the PXR-activating transgenic mice is reminiscent of the pseudo-Cushing’s syndrome in patients. The glucocorticoid effect appears to be PXR specific, as the activation of constitutive androstane receptor in transgenic mice had little effect. We propose that PXR is a potential endocrine disrupting factor that may have broad implications in steroid homeostasis and drug-hormone interactions.
Restriction for gene insertion within the Lactococcus lactis Ll.LtrB group II intron
Authors: Plante Isabelle , Cousineau Benoit
Published: September 2006

The Ll.LtrB intron, from the low G+C gram-positive bacterium Lactococcus lactis, was the first bacterial group II intron shown to splice and mobilize in vivo. The detailed retrohoming and retrotransposition pathways of Ll.LtrB were studied in both L. lactis and Escherichia coli. This bacterial retroelement has many features that would make it a good gene delivery vector. Here we report that the mobility efficiency of Ll.LtrB expressing LtrA in trans is only slightly affected by the insertion of fragments <100 nucleotides within the loop region of domain IV. In contrast, Ll.LtrB mobility efficiency is drastically decreased by the insertion of foreign sequences >1 kb. We demonstrate that the inhibitory effect caused by the addition of expression cassettes on Ll.LtrB mobility efficiency is not sequence specific, and not due to the expression, or the toxicity, of the cargo genes. Using genetic screens, we demonstrate that in order to maintain intron mobility, the loop region of domain IV, more specifically domain IVb, is by far the best region to insert foreign sequences within Ll.LtrB. Poisoned primer extension and Northern blot analyses reveal that Ll.LtrB constructs harboring cargo sequences splice less efficiently, and show a significant reduction in lariat accumulation in L. lactis. This suggests that cargo-containing Ll.LtrB variants are less stable. These results reveal the potential, yet limitations, of the Ll.LtrB group II intron to be used as a gene delivery vector, and validate the random insertion approach described in this study to create cargo-containing Ll.LtrB variants that are mobile.
There is no opposition between Formal and Cognitive Semantics
Authors: Hamm Fritz , Kamp Hans , Lambalgen Michiel van
Published: September 2006

1. Introduction

The history of modern semantics is characterised by two research traditions which are based on radically different views concerning both conceptual motivation and the purpose of semantic research.

Realistic semantics conceives of semantics as characterising the relationsship between linguistic expressions and reality. In most cases this relationship is explicated by means of modeltheoretic concepts. The following quote from one of the founding fathers of realistic semantics clearly rejects a mentalist stance.
Comments on: Fritz Hamm, Hans Kamp, Michiel van Lambalgen, There is no opposition between Formal and Cognitive Semantics
Authors: Bierwisch Manfred
Published: September 2006

Although I am strongly inclined to agree with the headline of the target-paper, it is not clear to me to what extent it contributes to this position. This is primarily due to the unfortunate strategy to defer crucial parts of its demonstration and of the supporting arguments to Lambalgen and Hamm (2004). Either the reader is assumed to be familiar with this reference, but then he doesn't need the paper under discussion, or he is not, and then he is left in doubt about crucial points. My comments are made from of the latter position.
Ontology for human talk and thought (not robotics)
Authors: Bittner Maria
Published: September 2006

1. Introduction

Hamm, Kamp, and van Lambalgen 2006 (hereafter HKL) propose to relate NL discourse to cognitive representations that also deal with world knowledge, planning, belief revision, etc. Their implementation involves translating NL discourse first into DRT, which explicates the linguistic information, and then into an event calculus, which uses world knowledge and non-monotonic reasoning to arrive at the final cognitive representation.
Representing events and discourse; comments on Hamm, Kamp and van Lambalgen
Authors: Fernando Tim
Published: September 2006

In [HKL00] (henceforth HKL), Hamm, Kamp and van Lambalgen declare “there is no opposition between formal and cognitive semantics,” notwithstanding the realist/mentalist divide. That divide separates two sides Jackendoff has (in [Jac96], following Chomsky) labeled E(xternalized)-semantics, relating language to a reality independent of speakers, and I(nternalized)-semantics, revolving around mental representations and thought. Although formal semanticists have (following David Lewis) traditionally leaned towards E-semantics, it is reasonable to apply formal methods also to I-semantics. This point is made clear in HKL via two computational approaches to natural language semantics, Discourse Representation Theory (DRT, [KR93]) and the Event Calculus (EC) presented in [LH05]. In this short note, I wish to raise certain questions about EC that can be traced to the applicability of formal methods to E-semantics and I-semantics alike. These opposing orientations suggest different notions of time, event and representation.
What is an action-based model of interpretation?
Authors: Michaelis Laura A
Published: September 2006

Scholars of linguistic meaning have always talked about sentences in terms of the things that they instruct their interpreters to do, find or check, and so the idea of an action-based model of interpretation is not entirely new. In denotational or ‘realist’ semantics, a sentence tells its interpreter how to determine its truth or falsity. In representational semantics, a sentence tells its interpreter to retrieve an array of semantic frames and make them fit together. When denotational semanticists started paying attention to narratives, they found an ingenious way to combine the representationalist idea of meaning as the integration of knowledge structures with the realist's view of meaning as truth conditions: they proposed that a sentence, rather than merely having a truth value, has a truth interval – the time for which it is true (Herweg 1991) – and that the interpreter can use linguistic and extralinguistic cues to determine whether or not two truth intervals overlap. Sometimes, however, the necessary contextual cues are lacking. For example, the English past tense, unlike its French analog, is aspectually neutral; therefore, the narrative passage in (1) is ambiguous:
Is semantics computational?
Authors: Steedman Mark , Stone Matthew
Published: September 2006

1. Introduction

Both formal semantics and cognitive semantics are the source of important insights about language. By developing precise statements of the rules of meaning in fragmentary, abstract languages, formalists have been able to offer perspicuous accounts of how we might come to know such rules and use them to communicate with others. Conversely, by charting the overall landscape of interpretations, cognitivists have documented how closely interpretations draw on the commonsense knowledge that lets us make our way in the world. There is no opposition between these insights. Sooner or later we will have a semantics that responds to both.
The future of semantics?
Authors: Stokhof Martin
Published: September 2006

The paper by Fritz Hamm, Hans Kamp and Michiel van Lambalgen (in what follows abbreviated as ‘hkl’) is a very rich one. Not only does it contain a wealth of empirical and formal insights concerning the analysis of tense and aspect, planning and causality, and other phenomena, it also contains some penetrating remarks concerning the scope and method of semantic theory. It is the latter aspect of the paper that I want to make a few comments on in what follows.
Replies to comments
Authors: Hamm Fritz , Kamp Hans , Lambalgen Michiel van
Published: September 2006

1. Bierwisch

Manfred Bierwisch starts his comment with the complaint that crucial parts of our paper rely on van Lambalgen and Hamm (2005). This is of course true, and it points to a predicament of which we have been aware: In order that we could say, within the space allotted to us, that which we wanted to say in this paper almost all the technical details of van Lambalgen and Hamm (2005) had to be left out. We do not agree, however, with Bierwisch' contention that someone familiar with the book could just as well have done without the paper. For one thing, the book, while acknowledging DRT as an important motivation for the ‘Proper Treatment of Events’ approach it presents, has no explicit discussion of the formal relations between the two theories, let alone any hints of how they could be put together. And precisely this is a central message of the paper: that there is a way of combining the two and that a combination of DRT and PTE techniques can help to bridge the gap between formal and cognitive aspects of linguistic structure and meaning.
Sooner Versus Later: Factors Associated with Temporal Sequencing of Suicide
Authors: Kaplan Mark S. , McFarland Bentson H. , Huguet Nathalie , Newsom Jason T.
Published: September 2006

There are few (if any) population‐based prospective studies that provide information on factors associated with temporal sequencing of suicide. In this prospective population‐based study, the National Health Interview Survey (NHIS), 1986–1994, was linked to the National Death Index (NDI), 1986–1997, to assess factors that predict recent (within 12 months of interview, termed sooner) suicide versus suicide further in the future (more than 12 months after interview, termed later). Of the 653 completed suicides in the NHIS cohort, 13.4 percent completed suicide within a year of interview, and 86.6 percent did so after a year. Sooner decedents were more likely to be White, less educated, unemployed, and to use firearms than any other method compared with later decedents. Surprisingly, sooner decedents had higher levels of self‐rated health at baseline. These results have substantial implications for clinicians and other professionals who interact with people at highest risk of suicide. Unfortunately, it may be unrealistic to expect that health care providers can modify the behavior of individuals at highest risk of suicide.
The Social Context of Adolescent Suicide Attempts: Interactive Effects of Parent, Peer, and School Social Relations
Authors: Kidd Sean , Henrich Christopher C. , Brookmeyer Kathryn A. , Davidson Larry , King Robert A. , Shahar Golan
Published: September 2006

An ecological developmental model of adolescent suicidality was used to inform a hierarchical logistic regression analysis of longitudinal interactions between parent, peer, and school relations and suicide attempts. Reanalyzing data from the National Longitudinal Study of Adolescent Health, it was found that parent relations were the most consistent protective factor, and among boys with prior suicide attempts, school relations augmented the effects of parent relations when peer relations were low. Results indicated the need to understand suicidal behavior as a component of interactive social processes in the design of clinical interventions.
Examining the Relationship Between At‐Risk Gambling and Suicidality in a National Representative Sample of Young Adults
Authors: Feigelman William , Gorman Bernard S. , Lesieur Henry
Published: September 2006

Although many clinical studies document a relationship between gambling and suicidality, evidence of this association in general population surveys has been mixed. Probing this association in a nationally representative sample of young adults with data from the National Longitudinal Survey of Adolescent Health, we made same gender comparisons of depression and suicidality between 298 at‐risk gamblers and 13,000 others. Although gamblers of both genders showed higher depression, only females reported significantly higher suicide thoughts and attempts. Males with gambling problems were no more likely than nongamblers to have suicide thoughts or to make prior suicide attempts on three separate measurement occasions.
Does Availability of Mental Health Resources Prevent Recurrent Suicidal Behavior? An Ecological Analysis
Authors: Cooper Sara L. , Lezotte Dennis , Jacobellis Jillian , DiGuiseppi Carolyn
Published: September 2006

This study examines whether availability of mental health resources in the county of residence is associated with subsequent suicidal behavior after a previous suicide attempt. Among 10,922 individuals who attempted suicide in Colorado between 1998 and 2002, residence in a county that offered a minimum safety‐net of mental health services significantly reduced the risk of suicidal behavior for at least 1 year after the index attempt. Safety‐net services included mental health treatment, crisis treatment, and case management. These results suggest one strategy for prevention of suicidal behavior that could inform state‐level health policy development and resource allocation.
Grief Shortly After Suicide And Natural Death: A Comparative Study Among Spouses and First‐Degree Relatives
Authors: de Groot M.H. , de Keijser J. , Neeleman J.
Published: September 2006

Chronic dysfunction after complicated grief is not rare and emphasizes the need to identify bereaved individuals at risk. Three months following bereavement, self‐reported psychiatric and general health of 153 relatives of 74 suicides was worse than of 70 relatives of 39 natural deaths. Moreover, the felt need for professional help was higher among the former, even after adjustment for expectedness of death, sociodemographic differences, and relatives'/spouses' neuroticism. This suggests that suicide‐bereaved individuals may constitute a high‐risk group of mourners in need of targeted postvention.
Cognitive Vulnerability to Depression, Rumination, Hopelessness, and Suicidal Ideation: Multiple Pathways to Self‐Injurious Thinking
Authors: Smith Jeannette M. , Alloy Lauren B. , Abramson Lyn Y.
Published: September 2006

In order to advance the detection and prevention of suicide, recent research has focused on predictors of suicidal ideation and behavior such as negative cognitive styles, dysfunctional attitudes, hopelessness, and rumination. In this study the relationships among these risk factors in the context of the Attention Mediated Hopelessness (AMH) theory of depression are examined. One hundred and twenty‐seven undergraduates in the Cognitive Vulnerability to Depression (CVD) project were followed for 2.5 years. The CVD project followed initially nondepressed freshmen, at either high or low cognitive risk for depression, in order to predict onsets and recurrences of depressive disorders. The presence and duration of suicidal ideation were predicted prospectively by rumination and hopelessness, and hopelessness partially mediated the relationship between rumination and ideation and fully mediated the association between rumination and duration of suicidality. Further, rumination mediated the relationship between cognitive vulnerability and suicidal ideation.
Social Work Education in Suicide Intervention and Prevention: An Unmet Need?
Authors: Feldman Barry N. , Freedenthal Stacey
Published: September 2006

Research shows that social work graduate programs offer little education in suicide prevention and intervention, yet social workers' experiences and attitudes regarding suicide education are unknown. This Web‐based survey of 598 social workers found that almost all respondents had worked with at least one suicidal client, but most received little, if any, training in suicide prevention or intervention while in graduate school. Respondents largely viewed their social work program's training in suicide prevention and intervention as inadequate. Implications for social work education and practice are discussed.
Suicide Risk Among Persons with Foreign Background in Denmark
Authors: Sundaram Vanita , Qin Ping , Zøllner Lilian
Published: September 2006

There is a dearth of knowledge about factors correlated with suicide risk among minority groups in Western societies. In the present study we compared suicide risk among persons with foreign background with that of the majority population to determine whether certain minority groups are at a particular risk for suicide, as well as to illuminate gender differences herein. Suicide risk was generally higher among persons with foreign background compared with the majority population and the risk was highest among Nordic‐born persons. Overall, suicide risk was significantly lower among Asian‐born persons; however, there were gender differences in correlations between ethnicity and suicide risk.
Force Measurements of Human Embryonic Stem Cell-Derived Cardiomyocytes in an In Vitro Transplantation Model
Authors: Pillekamp Frank , Reppel Michael , Rubenchyk Olga , Pfannkuche Kurt , Matzkies Matthias , Bloch Wilhelm , Sreeram Narayanswami , Brockmeier Konrad , Hescheler Jürgen
Published: September 2006

Human embryonic stem cell (hESC)-derived cardiomyocytes have been suggested for cardiac cell replacement therapy. However, there are no data on loaded contractions developed by these cells and the regulation thereof. We developed a novel in vitro transplantation model in which beating cardiomyocytes derived from hESCs (line H1) were isolated and transplanted onto noncontractile, ischemically damaged ventricular slices of murine hearts. After 2–3 days, transplanted cells started to integrate mechanically into the existing matrix, resulting in spontaneous movements of the whole preparation. Preparations showed a length-dependent increase of active tension. In transplanted early beating hESC-derived cardiomyocytes, frequency modulation by field stimulation was limited to a small range around their spontaneous beating rate. Our data demonstrate that this novel in vitro transplantation model is well suited to assess the mechanical properties and functional integration of cells suggested for cardiac replacement strategies.
In Vitro Expanded Cells Contributing to Rapid Severe Combined Immunodeficient Repopulation Activity Are CD34+38−33+90+45RA−
Authors: Vanheusden Katrien , Van Coppernolle Stefanie , De Smedt Magda , Plum Jean , Vandekerckhove Bart
Published: September 2006

Expansion of hematopoietic stem cells could be used clinically to shorten the prolonged aplastic phase after umbilical cord blood (UCB) transplantation. In this report, we investigated rapid severe combined immunodeficient (SCID) repopulating activity (rSRA) 2 weeks after transplantation of CD34+ UCB cells cultured with serum on MS5 stromal cells and in serum- and stroma-free cultures. Various subpopulations obtained after culture were studied for rSRA. CD34+ expansion cultures resulted in vast expansion of CD45+ and CD34+ cells. Independent of the culture method, only the CD34+33+38− fraction of the cultured cells contained rSRA. Subsequently, we subfractionated the CD34+38− fraction using stem cell markers CD45RA and CD90. In vitro differentiation cultures showed CD34+ expansion in both CD45RA− and CD90+ cultures, whereas little increase in CD34+ cells was observed in both CD45RA+ and CD90− cultures. By four-color flow cytometry, we could demonstrate that CD34+38−45RA− and CD34+38−90+ cell populations were largely overlapping. Both populations were able to reconstitute SCID/nonobese diabetic mice at 2 weeks, indicating that these cells contained rSRA activity. In contrast, CD34+38−45RA+ or CD34+38−90− cells contributed only marginally to rSRA. Similar results were obtained when cells were injected intrafemorally, suggesting that the lack of reconstitution was not due to homing defects. In conclusion, we show that after in vitro expansion, rSRA is mediated by CD34+38−90+45RA− cells. All other cell fractions have limited reconstitutive potential, mainly because the cells have lost stem cell activity rather than because of homing defects. These findings can be used clinically to assess the rSRA of cultured stem cells.
Higher Expression of Transcription Targets and Components of the Nuclear Factor-κB Pathway Is a Distinctive Feature of Umbilical Cord Blood CD34+ Precursors
Authors: Panepucci Rodrigo Alexandre , Calado Rodrigo Tocantins , Rocha Vanderson , Proto-Siqueira Rodrigo , Silva Wilson Araujo , Zago Marco Antonio
Published: September 2006

Delayed engraftment, better reconstitution of progenitors, higher thymic function, and a lower incidence of the graft-versus-host disease are characteristics associated with umbilical cord blood (UCB) transplants, compared with bone marrow (BM). To understand the molecular mechanisms causing these intrinsic differences, we analyzed the differentially expressed genes between BM and UCB hematopoietic stem and progenitor cells (HSPCs). The expressions of approximately 10,000 genes were compared by serial analysis of gene expression of magnetically sorted CD34+ cells from BM and UCB. Differential expression of selected genes was evaluated by real-time polymerase chain reaction on additional CD34+ samples from BM (n = 22), UCB (n = 9), and granulocyte colony stimulating factor-mobilized peripheral blood (n = 6). The overrepresentation of nuclear factor-κB (NF-κB) pathway components and targets was found to be a major characteristic of UCB HSPCs. Additional promoter analysis of 41 UCB-overrepresented genes revealed a significantly higher number of NF-κB cis-regulatory elements (present in 22 genes) than would be expected by chance. Our results point to an important role of the NF-κB pathway on the molecular and functional differences observed between BM and UCB HSPCs. Our study forms the basis for future studies and potentially for new strategies to stem cell graft manipulation, by specific NF-κB pathway modulation on stem cells, prior to transplant.
Concise Review: Multipotent Mesenchymal Stromal Cells in Blood
Authors: He Qiling , Wan Chao , Li Gang
Published: September 2006

Peripheral blood-derived multipotent mesenchymal stromal cells circulate in low number. They share, most although not all, of the surface markers with bone marrow-derived multipotent mesenchymal stromal cells, possess diverse and complicated gene expression characteristics, and are capable of differentiating along and even beyond mesenchymal lineages. Although their origin and physio-pathological function are still unclear, their presence in the adult peripheral blood might relate to some interesting but controversial subjects in the field of adult stem cell biology, such as systemic migration of bone marrow-derived multipotent mesenchymal stromal cells and the existence of common hematopoietic-mesenchymal precursors. In this review, current studies/knowledge about peripheral blood-derived multipotent mesenchymal stromal cells is summarized, and the above-mentioned topics are discussed.
Concise Review: Bone Morphogenetic Protein Pleiotropism in Neural Stem Cells and Their Derivatives—Alternative Pathways, Convergent Signals
Authors: Chen Hui-Ling , Panchision David M.
Published: September 2006

Bone morphogenetic proteins (BMPs) are a class of morphogens that are critical regulators of the central nervous system (CNS), peripheral nervous system, and craniofacial development. Modulation of BMP signaling also appears to be an important component of the postnatal stem cell niche. However, describing a comprehensive model of BMP actions is complicated by their paradoxical effects in precursor cells, which include dorsal specification, promoting proliferation or mitotic arrest, cell survival or death, and neuronal or glial fate. In addition, in postmitotic neurons BMPs can promote dendritic growth, act as axonal chemorepellants, and stabilize synapses. Although many of these responses depend on interactions with other incoming signals, some reflect the recruitment of distinct BMP signal transduction pathways. In this review, we classify the diverse effects of BMPs on neural cells, focus on the known mechanisms that specify distinct responses, and discuss the remaining challenges in identifying the cellular basis of BMP pleiotropism. Addressing these issues may have importance for stem cell mobilization, differentiation, and cell integration/survival in reparative therapies.
Cellular Cardiomyoplasty: Improvement of Left Ventricular Function Correlates with the Release of Cardioactive Cytokines
Authors: Ebelt Henning , Jungblut Mirco , Zhang Ying , Kubin Thomas , Kostin Sawa , Technau Antje , Oustanina Svetlana , Niebrügge Sylvia , Lehmann Jürgen , Werdan Karl , Braun Thomas
Published: September 2006

A growing number of studies are reporting beneficial effects of the transplantation of alleged cardiac stem cells into diseased hearts after myocardial infarction. However, the mechanisms by which transplanted cells might help to promote repair of cardiac tissue are not understood and might involve processes different from the differentiation of transplanted cells into cardiomyocytes. We have compared the effects exerted by skeletal myoblasts (which are not able to form new cardiomyocytes) and ESC-derived cardiomyocytes after implantation into infarcted mouse hearts by echocardiographic follow-up and histological analysis and related these effects to the release of cardioactive cytokines. We found that both cell types led to a long-lasting improvement of left ventricle function and to an improvement of tissue architecture. Since no relevant amounts of myoblast-derived cells were present in infarcted hearts 28 days after transplantation, we investigated the release of cytokines from implanted cells both before and after transplantation into infarcted hearts. ESC-derived cardiomyocytes and myoblasts secreted substantial amounts of interleukin (IL)-1α, IL-6, tumor necrosis factor-β, and oncostatin M, which strongly supported survival and protein synthesis of cultured cardiomyocytes. We postulate that the beneficial effects of the transplantation of myoblasts and cardiomyocytes on heart function and morphology only partially (if at all) depend on the integration of transplanted cells into the myocardium but do depend on the release of a complex blend of cardioactive cytokines.
Evaluation of the ADAPT Model for Simulating Nitrogen Dynamics in a Tile‐Drained Agricultural Watershed in Central Illinois
Authors: Sogbedji Jean M. , McIsaac Gregory F.
Published: September 2006

Assessing the accuracy of agronomic and water quality simulation models in different soils, land‐use systems, and environments provides a basis for using and improving these models. We evaluated the performance of the ADAPT model for simulating riverine nitrate‐nitrogen (NO3‐N) export from a 1500‐km2 watershed in central Illinois, where approximately 85% of the land is used for maize‐soybean production and tile drainage is common. Soil chemical properties, crop nitrogen (N) uptake coefficient, dry matter ratio, and a denitrification reduction coefficient were used as calibration parameters to optimize the fit between measured and simulated NO3‐N load from the watershed for the 1989 to 1993 period. The applicability of the calibrated parameter values was tested by using these values for simulating the 1994 to 1997 period on the same watershed. Willmott's index of agreement ranged from 0.91 to 0.97 for daily, weekly, monthly, and annual comparisons of riverine nitrate N loads. Simulation accuracy generally decreased as the time interval decreased. Willmott's index for simulated crop yields ranged from 0.91 to 0.99; however, observed crop yields were used as input to the model. The partial N budget results suggested that 52 to 72 kg N ha−1 yr−1 accumulated in the soil, but simulated biological N fixation associated with soybeans was considerably greater than literature values for the region. Improvement of the N fixation algorithms and incorporation of mechanisms that describe soybean yield in response to environmental conditions appear to be needed to improve the performance of the model.
Bioconversion of Selenate in Methanogenic Anaerobic Granular Sludge
Authors: Astratinei Violeta , van Hullebusch Eric , Lens Piet
Published: September 2006

The capacity of anaerobic granular sludge to remove selenate from contaminated wastewater was investigated. The potential of different types of granular sludge to remove selenate from the liquid phase was compared to that of suspended sludge and contaminated soil and sediment samples. The selenate removal rates ranged from 400 to 1500 μg g VSS−1 h−1, depending on the source of biomass, electron donor, and the initial selenate concentration. The granular structure protects the microorganisms when exposed to high selenate concentrations (0.1 to 1 mM). Anaerobic granular sludge “Eerbeek,” originating from a UASB reactor treating paper mill wastewater, removed about 90, 50, and 36% of 0.1, 0.5, and 1 mM of Se, respectively, from the liquid phase when incubated with 20 mM lactate at 30°C and pH 7.5. Selenite, elemental Se (Seo), and metal selenide precipitates were the conversion products. Enrichments from the anaerobic granular sludge “Eerbeek” were able to convert 90% of the 10‐mM selenate to Seo at a rate of 1505 μg Se(VI) g cells−1 h−1, a specific growth rate of 0.0125 g cells h−1, and a yield of 0.083 g cells mg Se−1 Both microbial metabolic processes (e.g dissimilatory reduction) as well as microbially mediated physicochemical mechanisms (adsorption and precipitation) contribute to the removal of selenate from the Se‐containing medium.
Combined Effects of Constant versus Variable Intensity Simulated Rainfall and Reduced Tillage Management on Cotton Preemergence Herbicide Runoff
Authors: Potter Thomas L. , Truman Clint C. , Strickland Timothy C. , Bosch David D. , Webster Theodore M. , Franklin Dorcas H. , Bednarz Craig W.
Published: September 2006

Pesticide runoff research relies heavily on rainfall simulation experiments. Most are conducted at a constant intensity, i.e., at a fixed rainfall rate; however, large differences in natural rainfall intensity is common. To assess implications we quantified runoff of two herbicides, fluometuron and pendimethalin, and applied preemergence after planting cotton on Tifton loamy sand. Rainfall at constant and variable intensity patterns representative of late spring thunderstorms in the Atlantic Coastal Plain region of Georgia (USA) were simulated on 6‐m2 plots under strip‐ (ST) and conventional‐tillage (CT) management. The variable pattern produced significantly higher runoff rates of both compounds from CT but not ST plots. However, on an event‐basis, runoff totals (% applied) were not significantly different, with one exception: fluometuron runoff from CT plots. There was about 25% more fluometuron runoff with the variable versus the constant intensity pattern (P = 0.10). Study results suggest that conduct of simulations using variable intensity storm patterns may provide more representative rainfall simulation‐based estimates of pesticide runoff and that the greatest impacts will be observed with CT. The study also found significantly more fluometuron in runoff from ST than CT plots. Further work is needed to determine whether this behavior may be generalized to other active ingredients with similar properties [low Koc (organic carbon partition coefficient) ∼100 mL g−1; high water solubility ∼100 mg L−1]. If so, it should be considered when making tillage‐specific herbicide recommendations to reduce runoff potential.
Stream Buffer Effectiveness in an Agriculturally Influenced Area, Southwestern Georgia
Authors: Muenz Tara K. , Golladay Stephen W. , Vellidis George , Smith Lora L.
Published: September 2006

To determine useful metrics for assessing stream water quality in the Southeastern Coastal Plain, we examined differences among two buffered and three unbuffered streams in an agricultural landscape in southwestern Georgia. Potential indicators included amphibian diversity and abundance, aquatic macroinvertebrate populations, riparian vegetative structure, water quality, and stream physical parameters. Variability among sites and treatments (buffered vs. unbuffered) existed, with sites in the same treatment as most similar, and disturbances from a nearby eroding gully strongly affecting one unbuffered site. Of the invertebrate metrics examined, percentages of clingers, Ephemeroptera‐Plecoptera‐Trichoptera (EPT), Elmidae (Coleoptera), Crustacea (Decapoda and Amphipoda), and dipterans were found to be possible indicators of stream health for perennial streams within this region. Overall, buffered sites showed higher percentages of sensitive invertebrate groups and showed lower and more stable concentrations of nitrate N, suspended solids, and fecal coliforms (FCs). Percent canopy cover was similar among sites; however, riparian vegetative coverage and percent leaf litter were greatest at buffered sites. No differences in amphibian abundance, presence, and absence within the riparian area were apparent between sites; however, instream larval salamanders were more abundant at buffered streams. In this study, stream buffers appeared to decrease nutrient and sediment loads to adjacent streams, enhancing overall water quality. Selected benthic macroinvertebrate metrics and amphibian abundance also appeared sensitive to agricultural influences. Amphibians show potential as indicator candidates, however further information is needed on their responses and tolerances to disturbances from the microhabitat to landscape levels.
DEPENDENCY, SELF-CRITICISM, AND THE SYMPTOM SPECIFICITY HYPOTHESIS IN A DEPRESSED CLINICAL SAMPLE
Authors: Desmet Mattias , Vanheule Stijn , Verhaeghe Paul
Published: September 2006

Several theorists have suggested that interpersonal dependency and excessive self-criticism are characteristics of personalities prone to depression. Here the results of a study are presented in which the hypothesis that these personality styles are connected to specific depressive
symptoms in a sample of depressed outpatients (N = 163) was evaluated. Hypotheses were that dependency is specifically associated with the somatic symptom cluster of the Beck Depression Inventory-II (Beck, Steer, & Brown, 1996) and that self-criticism is specifically associated
with the cognitive symptom cluster. In measuring the personality styles, the Depressive Experiences Questionnaire (Blatt, D'Affliti, & Quinlan, 1976) was used. No evidence suggesting that dependency is specifically connected to somatic depressive symptoms was found. Self-criticism
was specifically associated with cognitive depressive symptoms. However, the results suggest that content overlap might explain the relationship between self-criticism and cognitive depressive symptoms.
THE NEED FOR CONTINUING EDUCATION IN MANAGEMENT DEVELOPMENT: CASE OF KUWAIT UNIVERSITY
Authors: Alansari Eissa M. , Al-Shehab Ali J.
Published: September 2006

The need for continuing education in management development was investigated with special reference to Kuwait University, and the nature and practice of continuing education, its purposes, problems and its evaluation in relation to management development were reviewed. It was concluded
that education supports the creation of new social relationships and that continuing education must remedy the failures of formal education, and the existing distortion of socioeconomic and cultural aspects of society. Recommendations are made to facilitate achievement of these goals.
THERAPEUTIC AND NONTHERAPEUTIC REACTIONS IN A GROUP OF NURSES AND DOCTORS IN TURKEY TO PATIENTS WHO HAVE ATTEMPTED SUICIDE
Authors: Demirkiran Fatma , Eskin Mehmet
Published: September 2006

In this study a questionnaire was used to investigate the predictors of therapeutic versus nontherapeutic reactions to patients hospitalized for attempting suicide in a group of doctors (n= 158) and in a group of nurses (n= 206) working in the health care system of a small city in the Western part of Turkey. Doctors said that they would react therapeutically towards patients hospitalized for attempting suicide to a greater extent than did nurses, while nurses said that they would engage in nontherapeutic reactions to a greater extent than doctors did. Believing that suicidal problems should be communicated, feeling sympathy for a suicidal patient and not feeling anxiety/fear for a suicidal patient were found to be the independent predictors of therapeutic reactions, while feeling anger about a suicidal patient emerged as an independent predictor of nontherapeutic reactions in both doctors and nurses. The attitudes of nurses towards suicide were more traditional than the attitudes of doctors. Nurses believed to a greater extent than doctors that suicidal people would be punished after death and that suicide in one's family was to be hidden. Doctors, on the other hand, believed to a greater extent than nurses that suicide attempts resulted from illness/biological reasons. Men were found to be more prejudiced about suicide and suicidal individuals than were women.
PERSONAL AND FAMILY PATHS TO PUPIL ACHIEVEMENT
Authors: Alomar Bader O.
Published: September 2006

Personal and family factors impacting directly and/or indirectly on academic achievement of a total of 751 eighth grade pupils were assessed. Six achievement tests, as well as pupil and parent questionnaires were used for generating empirical data. A structural equation model was
used to test the model's applicability. Path analysis yielded a comparative fit index of .97. Prior achievement, gender, and academic self-concept were found to have highly significant direct impacts on achievement, while academic self-concept, family size, parent education, and family
cultural context exhibited indirect effects on achievement. The overall effect of academic self-concept increased significantly over and above the direct and indirect effects. The intervariables effects provided additional insights into existing correlations.