bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining HRD Scholar-Practitioners
Authors: Short Darren C. , Shindell Thomas J.
Published: August 2009

What do we mean by the term HRD scholar-practitioner? This article describes the role of HRD scholar-practitioners in closing the gap between research and practice and, in so doing, offers a definition of HRD scholar-practitioners. The definition emphasizes HRD scholar-practitioners as a bridge between HRD research and HRD practice, as grounding their practice in research and theory, as champions of research and theory in the workplace and in professional associations, and as researchers who disseminate findings from their own research and practice.
Perspectives on HRD Scholar-Practitioners: Current Issues, Strategic Possibilities, and Next Steps
Authors: Kormanik Martin B. , Shindell Thomas J.
Published: August 2009

Authored from the perspective of two scholar-practitioners, this article attempts to further explore scholar-practitioners in HRD by presenting and then attempting to answer four questions. First, why should HRD as a field care about scholar-practitioners? Second, what are the current issues and challenges faced by HRD scholar-practitioners? Third, what can the future hold for HRD scholar-practitioners in terms of strategic possibilities? Fourth, what are some concrete, tactical next steps that HRD scholar-practitioners and the field of HRD should consider?
Obesity as a Social Problem in the United States
Authors: Smith Morgan C.
Published: August 2009

Obesity rates in the United States have been rising over the past 35 years, resulting in a subsequent increase in nutrition-related chronic disease morbidity and mortality and significant burdens to families, communities, and health care systems. In working to formulate effective public health policy solutions that address the obesity epidemic, it is important to analyze how obesity has been defined and accepted as a social problem. This article applies Hilgartner and Bosk’s public arenas model to examine how obesity is defined in the public arena, how competition plays a role in “framing” the obesity issue, and how operatives influence the ways in which obesity is viewed and understood. Implications for nurses and policy makers are addressed in the context of using the public arenas model as a tool to analyze the social problem of obesity.
The Politics of Nursing Care
Authors: O'Byrne Patrick , Holmes Dave
Published: August 2009

Despite numerous theories, models, and philosophies describing what nurses are and what they do, nursing care is often presented as an apolitical process which primarily focuses on patient needs and priorities. However, it is our position that nursing practice—in all regards—is political. To support this argument, we have drawn on works describing of soft/hard power, pastoral power, stigma, deviance, and governmentality, in addition to explaining our institutional social contract conceptualization of politics. In using these concepts, our political perspective reframes nursing practice as a means by which an individual’s potential or actual deviance (meaning a deviation from social norms) can be identified and then corrected.
Effectiveness and Safety of a Novel Gel Dressing in the Management of Neuropathic Leg Ulcers in Diabetic Patients: A Prospective Double-Blind Randomized Trial
Authors: Abbruzzese L. , Rizzo L. , Fanelli G. , Tedeschi A. , Scatena A. , Goretti C. , Macchiarini S. , Piaggesi A.
Published: August 2009

Neuropathic leg ulcers (NLUs) affect more than 10% of diabetic patients with peripheral neuropathy and represent the most common cause of ulceration of the leg in these patients. Though their pathogenesis is well known, related to the chronic neuropathic edema, the management of NLUs, mainly based on elastocompression, is still controversial, with lower healing rates than nondiabetic venous leg ulcers. The authors tested if a novel gel formulation, containing amino acids and hyaluronic acid (Vulnamin® gel; Errekappa, Milan, Italy), will improve the outcomes of NLUs when used together with elastocompression. Thirty patients affected by NLU were randomized into 2 groups, both treated with 4-layer elastocompressive bandaging: patients in group A were topically treated with the application of Vulnamin® gel, whereas patients in group B received only the inert gel vehicle. The healing rate at 3 months was evaluated as the primary endpoint, whereas the secondary endpoints were healing time, reduction in ulcer area and ulceration score in 4 weeks, number of infective complications, and overall satisfaction of patients. Healing rate was significantly ( P < .05) higher in patients in group A when compared with those in group B; healing time, patients’ satisfaction, and reduction in ulcer area and ulceration score in 4 weeks were also higher in patients in group A. However, no significant differences were found in the prevalence of infections and other adverse events. The use of Vulnamin ® gel with elastocompression is safe and effective in the management of NLUs of diabetic patients.
Virtual Worlds and Their Discontents
Authors: Kücklich Julian Raul
Published: August 2009

In the following article, author argues that virtual worlds are characterized by a particular mode of governmentality. Rather than seeing virtual worlds as analogous to societies in the real world, he suggests regarding them as ‘‘social factories’’ in which the social fabric is inextricably shot through with economic production. While the governmentalization of the global economy and the concomitant economization of governments are processes that originate in the real world, they also result in a ‘‘naturalization’’ of virtual worlds, a tendency which also becomes obvious in the way virtual worlds are discussed in terms of ‘‘population’’ and ‘‘territory.’’ In virtual worlds, the suffusion of governance with economic production thus leads to the formation of precarious forms of governmentality, which are veiled by a pertinent ideology of play.
Rules of Play
Authors: Lastowka Greg
Published: August 2009

Massively multiplayer online role-playing games (MMORPGs) constitute social jurisdictions governed by rules of play. When we consider the work of Johan Huizinga and subsequent theorists of human play activities, we find that ludic rules differ from legal rules in important ways. The goals of play also differ from the goals of law. In applying law to MMORPGs and other virtual worlds, it is important to recognize that jurisdictions of play are structured in ways that are fundamentally different from the ways traditional legal rules are structured.
Virtual Worlds
Authors: Castronova Edward , Falk Matthew
Published: August 2009

This article argues for using virtual worlds as experimental environments for social science questions at the macro level. The authors can foresee two major objections to this approach and will address them as to show why they do not prove to be significant. The first being that virtual worlds are not like the real world; therefore, one cannot generalize from events within them. The second of these foreseeable objections states that human society is too complex to be controlled in the way that controlled experimentation requires. Humans discover things by building environments suited for exploring the questions the authors have a rat maze is a very abstract environment, yet it is useful for exploring very general questions of mammalian cognition. The authors conclude that virtual worlds are no less valuable, on net, than other established experimental tools. The next stage in toolmaking, after Petri dishes, rat mazes, and supercolliders, should be virtual worlds.
Ready-to-Eat Cereal Breakfasts Are Associated with Improved Nutrient Intake and Dietary Adequacy but Not Body Mass Index in Black Adolescents
Authors: Williams Brandy M. , O'Neil Carol E. , Keast Debra R. , Cho Susan , Nicklas Theresa A.
Published: August 2009

The goal of this study was to determine whether nutrient intake, dietary adequacy, and weight status were associated with type of breakfast consumption: skipping breakfast, consuming ready-to-eat cereal (RTEC) at breakfast, or consuming other types of foods at breakfast. Data from black adolescents 13 to 18 years of age (n = 988) participating in the 1999-2002 National Health and Nutrition Examination Survey were used in a secondary data analysis. Thirty-seven percent of black adolescents skipped breakfast, 19% consumed RTEC at breakfast, and 44% consumed other breakfasts. RTEC breakfast and other breakfast consumers had higher mean energy intakes than breakfast skippers (P ≤ .05). After adjusting for gender and energy intake, RTEC breakfast consumers had higher intakes of thiamin, riboflavin, niacin, folate, calcium, phosphorus, magnesium, iron, zinc, potassium, and vitamins A, B6, and B12 than breakfast skippers and other breakfast consumers (P ≤ .05). RTEC breakfast consumers had the highest mean adequacy ratio, followed by other breakfast consumers, then breakfast skippers (P ≤ .05). Those consuming RTEC at breakfast had lower mean body mass index (P ≤ .05) and waist circumference (P ≤ .05) than breakfast skippers; however, there was no difference between those consuming RTEC and other breakfasts. If confirmed in prospective studies, consuming a breakfast meal with RTEC may be a useful strategy to encourage in black adolescents as a way to improve nutrient intake and dietary adequacy without increasing weight.
Chromosome looping at the human α-globin locus is mediated via the major upstream regulatory element (HS −40)
Authors: Vernimmen Douglas , Marques-Kranc Fatima , Sharpe Jacqueline A. , Sloane-Stanley Jacqueline A. , Wood William G. , Wallace Helen A. C. , Smith Andrew J. H. , Higgs Douglas R.
Published: August 2009

Previous studies in the mouse have shown that high levels of α-globin gene expression in late erythropoiesis depend on long-range, physical interactions between remote upstream regulatory elements and the globin promoters. Using quantitative chromosome conformation capture (q3C), we have now analyzed all interactions between 4 such elements lying 10 to 50 kb upstream of the human α cluster and their interactions with the α-globin promoter. All of these elements interact with the α-globin gene in an erythroid-specific manner. These results were confirmed in a mouse model of human α globin expression in which the human cluster replaces the mouse cluster in situ (humanized mouse). We have also shown that expression and all of the long-range interactions depend largely on just one of these elements; removal of the previously characterized major regulatory element (called HS −40) results in loss of all the interactions and α-globin expression. Reinsertion of this element at an ectopic location restores both expression and the intralocus interactions. In contrast to other more complex systems involving multiple upstream elements and promoters, analysis of the human α-globin cluster during erythropoiesis provides a simple and tractable model to understand the mechanisms underlying long-range gene regulation.
Dysfunctional expansion of hematopoietic stem cells and block of myeloid differentiation in lethal sepsis
Authors: Rodriguez Sonia , Chora Angelo , Goumnerov Boyan , Mumaw Christen , Goebel W. Scott , Fernandez Luis , Baydoun Hasan , HogenEsch Harm , Dombkowski David M. , Karlewicz Carol A. , Rice Susan , Rahme Laurence G. , Carlesso Nadia
Published: August 2009

Severe sepsis is one of the leading causes of death worldwide. High mortality rates in sepsis are frequently associated with neutropenia. Despite the central role of neutrophils in innate immunity, the mechanisms causing neutropenia during sepsis remain elusive. Here, we show that neutropenia is caused in part by apoptosis and is sustained by a block of hematopoietic stem cell (HSC) differentiation. Using a sepsis murine model, we found that the human opportunistic bacterial pathogen Pseudomonas aeruginosa caused neutrophil depletion and expansion of the HSC pool in the bone marrow. “Septic” HSCs were significantly impaired in competitive repopulation assays and defective in generating common myeloid progenitors and granulocyte-monocyte progenitors, resulting in lower rates of myeloid differentiation in vitro and in vivo. Delayed myeloid-neutrophil differentiation was further mapped using a lysozyme–green fluorescent protein (GFP) reporter mouse. Pseudomonas's lipopolysaccharide was necessary and sufficient to induce myelosuppresion and required intact TLR4 signaling. Our results establish a previously unrecognized link between HSC regulation and host response in severe sepsis and demonstrate a novel role for TLR4.
Mechanisms underlying neutrophil-mediated monocyte recruitment
Authors: Soehnlein Oliver , Lindbom Lennart , Weber Christian
Published: August 2009

Extravasation of polymorphonuclear leukocytes (PMNs) to the site of inflammation precedes a second wave of emigrating monocytes. That these events are causally connected has been established a long time ago. However, we are now just beginning to understand the molecular mechanisms underlying this cellular switch, which has become even more complex considering the emergence of monocyte subsets, which are affected differently by signals generated from PMNs. PMN granule proteins induce adhesion as well as emigration of inflammatory monocytes to the site of inflammation involving β2-integrins and formyl-peptide receptors. Furthermore, modification of the chemokine network by PMNs and their granule proteins creates a milieu favoring extravasation of inflammatory monocytes. Finally, emigrated PMNs rapidly undergo apoptosis, leading to the discharge of lysophosphatidylcholine, which attracts monocytes via G2A receptors. The net effect of these mechanisms is the accumulation of inflammatory monocytes, thus promoting proinflammatory events, such as release of inflammation-sustaining cytokines and reactive oxygen species. As targeting PMNs without causing serious side effects seems futile, it may be more promising to aim at interfering with subsequent PMN-driven proinflammatory events.
CD43 processing and nuclear translocation of CD43 cytoplasmic tail are required for cell homeostasis
Authors: Seo Wooseok , Ziltener Hermann J.
Published: August 2009

The sialomucin CD43 is highly expressed on most hematopoietic cells. In this study, we show that the CD43 ectodomain is shed from murine granulocytes, mast cells, and T cells, but not from macrophages. To study the significance of CD43 shedding, we constructed 2 CD43/34 chimeras in which the CD43 membrane-proximal or transmembrane domain was swapped with the corresponding domain from CD34 that is not shed from cells. Viability of cells that normally shed CD43 was negatively affected when forced to express either of the 2 CD43/34 chimeras, but toxicity was reduced when cells coexpressed wild-type CD43. The CD43 cytoplasmic tail (CD43ct) was found to translocate into the nucleus, and inhibition of either its nuclear translocation or its release by γ-secretase was proapoptotic. Involvement of CD43 in regulation of apoptosis is consistent with our findings that CD43ct was modified by small ubiquitin-like modifier-1 and was colocalized with promyelocytic nuclear bodies. CD43-deficient cells exhibited reduced levels of promyelocytic nuclear bodies and had increased sensitivity to apoptosis induced by growth factor withdrawal or T-regulatory cell suppression. Taken together, our data indicate an essential function of CD43 processing and nuclear localization of CD43ct in cell homeostasis and apoptosis.
How I treat mycosis fungoides and Sézary syndrome
Authors: Prince H. Miles , Whittaker Sean , Hoppe Richard T.
Published: August 2009

The most common subtypes of primary cutaneous T-cell lymphomas are mycosis fungoides (MF) and Sézary syndrome (SS). The majority of patients have indolent disease; and given the incurable nature of MF/SS, management should focus on improving symptoms and cosmesis while limiting toxicity. Management of MF/SS should use a “stage-based” approach; treatment of early-stage disease (IA-IIA) typically involves skin directed therapies that include topical corticosteroids, phototherapy (psoralen plus ultraviolet A radiation or ultraviolet B radiation), topical chemotherapy, topical or systemic bexarotene, and radiotherapy. Systemic approaches are used for recalcitrant early-stage disease, advanced-stage disease (IIB-IV), and transformed disease and include retinoids, such as bexarotene, interferon-α, histone deacetylase inhibitors, the fusion toxin denileukin diftitox, systemic chemotherapy including transplantation, and extracorporeal photopheresis. Examples of drugs under active investigation include new histone deacetylase inhibitors, forodesine, monoclonal antibodies, proteasome inhibitors, and immunomodulatory agents, such as lenalidomide. It is appropriate to consider patients for novel agents within clinical trials if they have failed front-line therapy and before chemotherapy is used.
The angiogenic factor midkine is regulated by dexamethasone and retinoic acid during alveolarization and in alveolar epithelial cells
Authors: Zhang Huayan , Garber Samuel J , Cui Zheng , Foley Joseph P , Mohan Gopi S , Jobanputra Minesh , Kaplan Feige , Sweezey Neil B , Gonzales Linda W , Savani Rashmin C
Published: August 2009

Background

A precise balance exists between the actions of endogenous glucocorticoids (GC) and retinoids to promote normal lung development, in particular during alveolarization. The mechanisms controlling this balance are largely unknown, but recent evidence suggests that midkine (MK), a retinoic acid-regulated, pro-angiogenic growth factor, may function as a critical regulator. The purpose of this study was to examine regulation of MK by GC and RA during postnatal alveolar formation in rats.

Methods

Newborn rats were treated with dexamethasone (DEX) and/or all-trans-retinoic acid (RA) during the first two weeks of life. Lung morphology was assessed by light microscopy and radial alveolar counts. MK mRNA and protein expression in response to different treatment were determined by Northern and Western blots. In addition, MK protein expression in cultured human alveolar type 2-like cells treated with DEX and RA was also determined.

Results

Lung histology confirmed that DEX treatment inhibited and RA treatment stimulated alveolar formation, whereas concurrent administration of RA with DEX prevented the DEX effects. During normal development, MK expression was maximal during the period of alveolarization from postnatal day 5 (PN5) to PN15. DEX treatment of rat pups decreased, and RA treatment increased lung MK expression, whereas concurrent DEX+RA treatment prevented the DEX-induced decrease in MK expression. Using human alveolar type 2 (AT2)-like cells differentiated in culture, we confirmed that DEX and cAMP decreased, and RA increased MK expression.

Conclusion

We conclude that MK is expressed by AT2 cells, and is differentially regulated by corticosteroid and retinoid treatment in a manner consistent with hormonal effects on alveolarization during postnatal lung development.
The ordering of expression among a few genes can provide simple cancer biomarkers and signal BRCA1 mutations
Authors: Lin Xue , Afsari Bahman , Marchionni Luigi , Cope Leslie , Parmigiani Giovanni , Naiman Daniel , Geman Donald
Published: August 2009

Background

A major challenge in computational biology is to extract knowledge about the genetic nature of disease from high-throughput data. However, an important obstacle to both biological understanding and clinical applications is the "black box" nature of the decision rules provided by most machine learning approaches, which usually involve many genes combined in a highly complex fashion. Achieving biologically relevant results argues for a different strategy. A promising alternative is to base prediction entirely upon the relative expression ordering of a small number of genes.

Results

We present a three-gene version of "relative expression analysis" (RXA), a rigorous and systematic comparison with earlier approaches in a variety of cancer studies, a clinically relevant application to predicting germline BRCA1 mutations in breast cancer and a cross-study validation for predicting ER status. In the BRCA1 study,RXAyields high accuracy with a simple decision rule: in tumors carrying mutations, the expression of a "reference gene" falls between the expression of two differentially expressed genes,PPP1CBandRNF14. An analysis of the protein-protein interactions among the triplet of genes andBRCA1 suggests that the classifier has a biological foundation.

Conclusion

RXAhas the potential to identify genomic "marker interactions" with plausible biological interpretation and direct clinical applicability. It provides a general framework for understanding the roles of the genes involved in decision rules, as illustrated for the difficult and clinically relevant problem of identifyingBRCA1 mutation carriers.
Structure-based substrate screening for an enzyme
Authors: Xu Tao , Zhang Lujia , Wang Xuedong , Wei Dongzhi , Li Tianbi
Published: August 2009

Background

Nowadays, more and more novel enzymes can be easily found in the whole enzyme pool with the rapid development of genetic operation. However, experimental work for substrate screening of a new enzyme is laborious, time consuming and costly. On the other hand, many computational methods have been widely used in lead screening of drug design. Seeing that the ligand-target protein system in drug design and the substrate-enzyme system in enzyme applications share the similar molecular recognition mechanism, we aim to fulfill the goal of substrate screening by in silico means in the present study.

Results

A computer-aided substrate screening (CASS) system which was based on the enzyme structure was designed and employed successfully to help screen substrates of Candida antarctica lipase B (CALB). In this system, restricted molecular docking which was derived from the mechanism of the enzyme was applied to predict the energetically favorable poses of substrate-enzyme complexes. Thereafter, substrate conformation, distance between the oxygen atom of the alcohol part of the ester (in some compounds, this oxygen atom was replaced by nitrogen atom of the amine part of acid amine or sulfur atom of the thioester) and the hydrogen atom of imidazole of His224, distance between the carbon atom of the carbonyl group of the compound and the oxygen atom of hydroxyl group of Ser105 were used sequentially as the criteria to screen the binding poses. 223 out of 233 compounds were identified correctly for the enzyme by this screening system. Such high accuracy guaranteed the feasibility and reliability of the CASS system.

Conclusion

The idea of computer-aided substrate screening is a creative combination of computational skills and enzymology. Although the case studied in this paper is tentative, high accuracy of the CASS system sheds light on the field of computer-aided substrate screening.
The innate immune and systemic response in honey bees to a bacterial pathogen, Paenibacillus larvae
Authors: Chan Queenie WT , Melathopoulos Andony P , Pernal Stephen F , Foster Leonard J
Published: August 2009

Background

There is a major paradox in our understanding of honey bee immunity: the high population density in a bee colony implies a high rate of disease transmission among individuals, yet bees are predicted to express only two-thirds as many immunity genes as solitary insects, e.g., mosquito or fruit fly. This suggests that the immune response in bees is subdued in favor of social immunity, yet some specific immune factors are up-regulated in response to infection. To explore the response to infection more broadly, we employ mass spectrometry-based proteomics in a quantitative analysis of honey bee larvae infected with the bacterium Paenibacillus larvae. Newly-eclosed bee larvae, in the second stage of their life cycle, are susceptible to this infection, but become progressively more resistant with age. We used this host-pathogen system to probe not only the role of the immune system in responding to a highly evolved infection, but also what other mechanisms might be employed in response to infection.

Results

Using quantitative proteomics, we compared the hemolymph (insect blood) of five-day old healthy and infected honey bee larvae and found a strong up-regulation of some metabolic enzymes and chaperones, while royal jelly (food) and energy storage proteins were down-regulated. We also observed increased levels of the immune factors prophenoloxidase (proPO), lysozyme and the antimicrobial peptide hymenoptaecin. Furthermore, mass spectrometry evidence suggests that healthy larvae have significant levels of catalytically inactive proPO in the hemolymph that is proteolytically activated upon infection. Phenoloxidase (PO) enzyme activity was undetectable in one or two-day-old larvae and increased dramatically thereafter, paralleling very closely the age-related ability of larvae to resist infection.

Conclusion

We propose a model for the host response to infection where energy stores and metabolic enzymes are regulated in concert with direct defensive measures, such as the massive enhancement of PO activity.
Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease
Authors: Granata Simona , Zaza Gianluigi , Simone Simona , Villani Gaetano , Latorre Dominga , Pontrelli Paola , Carella Massimo , Schena Francesco Paolo , Grandaliano Giuseppe , Pertosa Giovanni
Published: August 2009

Background

Chronic renal disease (CKD) is characterized by complex changes in cell metabolism leading to an increased production of oxygen radicals, that, in turn has been suggested to play a key role in numerous clinical complications of this pathological condition. Several reports have focused on the identification of biological elements involved in the development of systemic biochemical alterations in CKD, but this abundant literature results fragmented and not exhaustive.

Results

To better define the cellular machinery associated to this condition, we employed a high-throughput genomic approach based on a whole transcriptomic analysis associated with classical molecular methodologies. The genomic screening of peripheral blood mononuclear cells revealed that 44 genes were up-regulated in both CKD patients in conservative treatment (CKD, n = 9) and hemodialysis (HD, n = 17) compared to healthy subjects (HS, n = 8) (p < 0.001, FDR = 1%). Functional analysis demonstrated that 11/44 genes were involved in the oxidative phosphorylation system. Western blotting for COXI and COXIV, key constituents of the complex IV of oxidative phosphorylation system, performed on an independent testing-group (12 healthy subjects, 10 CKD and 14 HD) confirmed an higher synthesis of these subunits in CKD/HD patients compared to the control group. Only for COXI, the comparison between CKD and healthy subjects reached the statistical significance. However, complex IV activity was significantly reduced in CKD/HD patients compared to healthy subjects (p < 0.01). Finally, CKD/HD patients presented higher reactive oxygen species and 8-hydroxydeoxyguanosine levels compared to controls.

Conclusion

Taken together these results suggest, for the first time, that CKD/HD patients may have an impaired mitochondrial respiratory system and this condition may be both the consequence and the cause of an enhanced oxidative stress.
The Lactamase Engineering Database: a critical survey of TEM sequences in public databases
Authors: Thai Quan Ke , Bös Fabian , Pleiss Jürgen
Published: August 2009

Background

TEM β-lactamases are the main cause for resistance against β-lactam antibiotics. Sequence information about TEM β-lactamases is mainly found in the NCBI peptide database and TEM mutation table at http://www.lahey.org/Studies/temtable.asp. While the TEM mutation table is manually curated by experts in the lactamase field, who guarantee reliable and consistent information, the rapidly growing sequence and annotation information from the NCBI peptide database is sometimes inconsistent. Therefore, the Lactamase Engineering Database has been developed to collect the TEM β-lactamase sequences from the NCBI peptide database and the TEM mutation table, systematically compare sequence information and naming, identify inconsistencies, and thus provide a versatile tool for reconciliation of data and for an investigation of the sequence-function relationship.

Description

The LacED currently provides 2399 sequence entries and 37 structure entries. Sequence information on 150 different TEM β-lactamases was derived from the TEM mutation table which provides a unique number to each protein classified as TEM β-lactamase. 293 TEM-like proteins were found in the NCBI protein database, but only 113 TEM β-lactamase were common to both data sets. The 180 TEM β-lactamases from the NCBI protein database which have not yet been assigned to a TEM number fall in three classes: (1) 89 proteins from microbial organisms and 35 proteins from cloning or expression vectors had a new mutation profile; (2) 55 proteins had inconsistent annotation in terms of TEM assignment or reported mutation profile; (3) 39 proteins are fragments. The LacED is web accessible at http://www.LacED.uni-stuttgart.de and contains multisequence alignments, structure information and reconciled annotation of TEM β-lactamases. The LacED is weekly updated and supplies all data for download.

Conclusion

The Lactamase Engineering Database enables a systematic analysis of TEM β-lactamase sequence and annotation data from different data sources, and thus provides a valuable tool to identify inconsistencies in sequences from the NCBI peptide database, to detect TEM β-lactamases with a novel mutation profile, and to identify new amino acid positions at which mutations can occur.
CgOpt1, a putative oligopeptide transporter from Colletotrichum gloeosporioides that is involved in responses to auxin and pathogenicity
Authors: Chagué Véronique , Maor Rudy , Sharon Amir
Published: August 2009

Background

The fungus Colletotrichum gloeosporioides f. sp. aeschynomene produces high levels of indole-3-acetic acid (IAA) in axenic cultures and during plant infection. We generated a suppression subtractive hybridization library enriched for IAA-induced genes and identified a clone, which was highly expressed in IAA-containing medium.

Results

The corresponding gene showed similarity to oligopeptide transporters of the OPT family and was therefore named CgOPT1. Expression of CgOPT1 in mycelia was low, and was enhanced by external application of IAA. cgopt1-silenced mutants produced less spores, had reduced pigmentation, and were less pathogenic to plants than the wild-type strain. IAA enhanced spore formation and caused changes in colony morphology in the wild-type strain, but had no effect on spore formation or colony morphology of the cgopt1-silenced mutants.

Conclusion

Our results show that IAA induces developmental changes in C. gloeosporioides. These changes are blocked in cgopt1-silenced mutants, suggesting that this protein is involved in regulation of fungal response to IAA. CgOPT1 is also necessary for full virulence, but it is unclear whether this phenotype is related to auxin.
The mRNA expression of SETD2 in human breast cancer: correlation with clinico-pathological parameters
Authors: Al Sarakbi W , Sasi W , Jiang WG , Roberts T , Newbold RF , Mokbel K
Published: August 2009

Background

SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation.

There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings.

Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer.

Methods

A total of 153 samples were analysed.

The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19).

Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period.

Results

The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage.

SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041).

Conclusion

This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer.
Manipulating insulin signaling to enhance mosquito reproduction
Authors: Arik Anam J , Rasgon Jason L , Quicke Kendra M , Riehle Michael A
Published: August 2009

Backgrond

In the mosquito Aedes aegypti the insulin/insulin growth factor I signaling (IIS) cascade is a key regulator of many physiological processes, including reproduction. Two important reproductive events, steroidogenesis in the ovary and yolk synthesis in the fat body, are regulated by the IIS cascade in mosquitoes. The signaling molecule phosphatase and tensin homolog (PTEN) is a key inhibitor of the IIS cascade that helps modulate the activity of the IIS cascade. In Ae. aegypti, six unique splice variants of AaegPTEN were previously identified, but the role of these splice variants, particularly AaegPTEN3 and 6, were unknown.

Results

Knockdown of AaegPTEN or its specific splice variant AaegPTEN6 (the splice variant thought to regulate reproduction in the ovary and fat body) using RNAi led to a 15–63% increase in egg production with no adverse effects on egg viability during the first reproductive cycle. Knockdown of AaegPTEN3, expressed predominantly in the head, had no effect on reproduction. We also characterized the protein expression patterns of these two splice variants during development and in various tissues during a reproductive cycle.

Conclusion

Previous studies in a range of organisms, including Drosophila melanogaster and Caenorhabditis elegans, have demonstrated that disruption of the IIS cascade leads to decreased reproduction or sterility. In this study we demonstrate that knockdown of the IIS inhibitor PTEN can actually increase reproduction in the mosquito, at least during the first reproductive cycle.
The human placenta releases substances that drive lung cancer into apoptosis
Authors: Marwitz Sebastian , Zeiser Tobias , Schultz Holger , Kähler Daniel , Abdullah Mahdi , Hauber Hans-Peter , Zabel Peter , Vollmer Ekkehard , Goldmann Torsten
Published: August 2009

Background

As there is no optimal treatment of non small cell lung cancer due to its resistance to common chemotherapeutics, we investigated the effect of human placenta-conditioned medium on tumor tissue. The human placenta constitutes a mixture of maternal and fetal origin and displays a variety of immunomodulatory aspects.

Methods

Freshly resected non small cell lung cancer tissues were incubated with placenta-conditioned medium in a short-term tissue culture model and A549 cells were challenged, respectively. Term placenta was used for producing conditioned medium and HOPE-fixed stimulated tumor tissue was analyzed for expression of caspase-3 and Ki67 via immunohistochemistry. The effects of conditioned medium on squamous cell carcinoma were further compared to physiological concentrations of Carboplat/Gemzar.

Results

Conditioned medium caused in 2 of 3 cases elevated expression of caspase-3 and reduced expression of Ki67 in 3 out of 3 cases, while the chemotherapeutic agents caused no comparable expression of caspase-3 or reduction of Ki67. In cell culture up to 50% of karyopyknosis was investigated and even sterile-filtrated medium caused widespread reduction of Ki67 on protein level.

Conclusion

Human placenta releases substances that mediate apoptosis and reduce proliferation in tumor tissue and cell culture. As even sterile-filtrated medium caused the mentioned effects we hypothesize one or more soluble mediators. The detailed way of promoting apoptosis and nature of these mediators need to be elucidated in further studies.
Synorth: exploring the evolution of synteny and long-range regulatory interactions in vertebrate genomes
Authors: Dong Xianjun , Fredman David , Lenhard Boris
Published: August 2009

Genomic regulatory blocks are chromosomal regions spanned by long clusters of highly conserved noncoding elements devoted to long-range regulation of developmental genes, often immobilizing other, unrelated genes into long-lasting syntenic arrangements. Synorth http://synorth.genereg.net/ is a web resource for exploring and categorizing the syntenic relationships in genomic regulatory blocks across multiple genomes, tracing their evolutionary fate after teleost whole genome duplication at the level of genomic regulatory block loci, individual genes, and their phylogenetic context.
Pivotal Advance: Kaposi’s sarcoma-associated herpesvirus (KSHV)-encoded microRNA specifically induce IL-6 and IL-10 secretion by macrophages and monocytes
Authors: Qin Zhiqiang , Kearney Patricia , Plaisance Karlie , Parsons Chris H
Published: August 2009

MicroRNA encoded by KSHV, a common tumor virus, induces macrophage secretion of tumor-promoting cytokines by down-regulating the transcription factor C/EBPβ p20 isoform (LIP).

Macrophages are an important source of inflammatory cytokines generated during the innate immune response, but in the microenvironment of certain tumors, macrophages promote tumor progression through their preferential secretion of cytokines that support tumor cell growth and suppress antitumoral immune responses. KSHV is the causative agent of KS and lymphomas preferentially arising in immunocompromised patients, and specific cytokines, including IL-6 and IL-10, have been implicated in KSHV-associated cancer pathogenesis. However, the contribution of KSHV-infected macrophages to the cytokine milieu within KSHV-related tumors is unclear. We found that individual KSHV-encoded miRNA induce IL-6 and IL-10 secretion independently and additively by murine macrophages and human myelomonocytic cells. Bioinformatics analysis identified KSHV miRNA binding sites for miR-K12-3 and miR-K12-7 within the 3′UTR of the basic region/leucine zipper motif transcription factor C/EBPβ, a known regulator of IL-6 and IL-10 transcriptional activation. Subsequent immunoblot analyses revealed that miR-K12-3 and miR-K12-7 preferentially reduce expression of C/EBPβ p20 (LIP), an isoform of C/EBPβ known to function as a negative transcription regulator. In addition, RNA interference specifically targeting LIP induced basal secretion of IL-6 and IL-10 by macrophages. Taken together, these data support a role for KSHV miRNA in the programming of macrophage cytokine responses in favor of KSHV-related tumor progression.
Peripheral blood CD4+ T lymphocytes from multiple sclerosis patients are characterized by higher PSGL-1 expression and transmigration capacity across a human blood-brain barrier-derived endothelial cell line
Authors: Bahbouhi Bouchaib , Berthelot Laureline , Pettré Ségolène , Michel Laure , Wiertlewski Sandrine , Weksler Babette , Romero Ignacio-Andres , Miller Florence , Couraud Pierre-Olivier , Brouard Sophie , Laplaud David-Axel , Soulillou Jean-Paul
Published: August 2009

Significant alterations in the transmigration capacity of peripheral blood T-lymphocytes found as a feature in multiple sclerosis.

Mechanisms of T lymphocyte trafficking in the brain remain unclear in MS. We hypothesized that MS is associated with increased CD4+ and CD8+ T lymphocyte trafficking across the BBB. To test this hypothesis, we calculated the frequency of PSGL-1+/CD4+ and PSGL-1+CD8+ or LFA-1+/CD4+/CD8+ T cells in the PBMC of 27 patients with a RR-MS (21 untreated and six IFN-β-treated) and 18 HI. Next, we measured their ex vivo TR across resting and TNF-α-activated human BBB-derived hCMEC/D3 endothelial layers under static conditions. The frequency of PSGL-1+CD4+ T lymphocytes was significantly higher in treated or untreated MS patients than HI. Furthermore, resting hCMEC/D3 TR of CD4+ lymphocytes (purified or in PBMC) from treated or untreated MS patients were significantly higher than those of HI and associated with significant enrichments of CD4+PSGL+ or CD4+PSGL-1+CD45RO+ T cells in their transmigrating fractions. The TR of CD4+ and CD8+ from MS patients across TNF-α-activated hCMEC/D3 were also significantly higher than that observed in HI. Resting hCMEC/D3 transmigration was blocked significantly by anti-PSGL-1/anti-LFA-1 in all groups, and anti-VLA-4 inhibited transmigration of MS T cells specifically. Purified PSGL-1-negative CD4+ lymphocytes transmigrated resting hCMEC/D3 with <10% of transmigrating cells re-expressing PSGL-1, suggesting PSGL-1-independent transmigration mechanisms. The frequency of PSGL-1 was unchanged in CD8+ cells from MS patients, whereas CD8+LFA-1high were reduced significantly in IFN-β-treated patients specifically. Collectively, MS is associated with an expanding pool of PSGL-1+CD4+ T lymphocytes able to transmigrate the BBB endothelium in vitro and possibly contributing to brain pathology.
LOOKING FOR M—
Authors: Keeling Kara
Published: August 2009

Daniel Peddle's film The Aggressives makes perceptible an intolerable yet quotidian violence, as the index of our time. Putting queer theories of temporality into proximity with anticolonial ones, this essay seeks to remain aware of what in The Aggressives escapes attempts to contain it yet nonetheless can be felt and perceived even though—or especially if—it remains unrecognizable or unintelligible to our current common senses. We can think of what escapes these operations as the content that exceeds its expression, that through which poetry from the future might be perceived yet not recognized. Poetry from the future interrupts the habitual formation of bodies, and it is an index of a time to come in which what exists potently, even if not (yet) effectively, today but escapes us will find its time.
Tbx1 controls cardiac neural crest cell migration during arch artery development by regulatingGbx2expression in the pharyngeal ectoderm
Authors: Calmont Amélie , Ivins Sarah , Van Bueren Kelly Lammerts , Papangeli Irinna , Kyriakopoulou Vanessa , Andrews William D. , Martin James F. , Moon Anne M. , Illingworth Elizabeth A. , Basson M. Albert , Scambler Peter J.
Published: August 2009

Elucidating the gene regulatory networks that govern pharyngeal arch artery(PAA) development is an important goal, as such knowledge can help to identify new genes involved in cardiovascular disease. The transcription factor Tbx1 plays a vital role in PAA development and is a major contributor to cardiovascular disease associated with DiGeorge syndrome. In this report, we used various genetic approaches to reveal part of a signalling network by which Tbx1 controls PAA development in mice. We investigated the crucial role played by the homeobox-containing transcription factor Gbx2 downstream of Tbx1. We found that PAA formation requires the pharyngeal surface ectoderm as a key signalling centre from which Gbx2, in response to Tbx1, triggers essential directional cues to the adjacent cardiac neural crest cells (cNCCs)en route to the caudal PAAs. Abrogation of this signal generates cNCC patterning defects leading to PAA abnormalities. Finally, we showed that the Slit/Robo signalling pathway is activated during cNCC migration and that components of this pathway are affected in Gbx2 and Tbx1mutant embryos at the time of PAA development. We propose that the spatiotemporal control of this tightly orchestrated network of genes participates in crucial aspects of PAA development.
Age-dependent changes in the gut environment restrict the invasion of the hindgut by enteric neural progenitors
Authors: Druckenbrod Noah R. , Epstein Miles L.
Published: August 2009

The enteric nervous system (ENS) develops from neural crest cells (NCCs)that enter the foregut and hindgut to become enteric neural-crest-derived cells (ENCCs). When these cells of neural crest origin fail to colonize the terminal hindgut, this aganglionic region becomes non-functional and results in a condition in humans known as Hirschsprung's disease (HSCR). One of the genes associated with HSCR is endothelin receptor type B (Ednrb). To study the development of colonic aganglionosis we have utilized a novel knockout mouse (Ednrbflex3/flex3), in which the expression of a null Ednrb allele and YFP is confined to NCCs. We have identified two primary cellular defects related to defective EDNRB signaling. First, ENCC advance in Ednrbflex3/flex3 embryos is delayed shortly after NCCs enter the gut. Apart from this early delay, Ednrbflex3/flex3 ENCCs advance normally until reaching the proximal colon. Second, as Ednrbflex3/flex3 ENCCs reach the colon at E14.5, they display migratory defects, including altered trajectories and reduced speed, that are not dependent on proliferation or differentiation. We constructed grafts to test the ability of donor ENCCs to invade a recipient piece of aganglionic colon. Our results indicate that the age of the recipient, and not the age or genotype of donor ENCCs, determines whether the colon is invaded. We identify changes in laminin expression that are associated with the failure of ENCCs to invade recipient tissue. Together,our data suggest that a defect in pre-enteric Ednrbflex3/flex3 NCCs results in delayed colonic arrival,which, due to environment changes in the colon, is sufficient to cause aganglionosis.
Extra-embryonic syndecan 2 regulates organ primordia migration and fibrillogenesis throughout the zebrafish embryo
Authors: Arrington Cammon B. , Yost H. Joseph
Published: August 2009

One of the first steps in zebrafish heart and gut organogenesis is the migration of bilateral primordia to the midline to form cardiac and gut tubes. The mechanisms that regulate this process are poorly understood. Here we show that the proteoglycan syndecan 2 (Sdc2) expressed in the extra-embryonic yolk syncytial layer (YSL) acts locally at the YSL-embryo interface to direct organ primordia migration, and is required for fibronectin and laminin matrix assembly throughout the embryo. Surprisingly, neither endogenous nor exogenous sdc2 expressed in embryonic cells can compensate for knockdown of sdc2 in the YSL, indicating that Sdc2 expressed in extra-embryonic tissues is functionally distinct from Sdc2 in embryonic cells. The effects of sdc2 knockdown in the YSL can be rescued by extra-embryonic Sdc2 lacking an extracellular proteolytic cleavage (shedding) site, but not by extra-embryonic Sdc2 lacking extracellular glycosaminoglycan (GAG) addition sites, suggesting that distinct GAG chains on extra-embryonic Sdc2 regulate extracellular matrix assembly, cell migration and epithelial morphogenesis of multiple organ systems throughout the embryo.