bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Herpes Simplex Virus by Polyamines
Authors: Yudovin-Farber Ira , Gurt Irina , Hope Ronen , Domb Abraham J , Katz Ehud 
Published: October 2009

Background: Herpes simplex virus (HSV) establishes latent infection in humans with periodic reactivation. Acyclovir, valacyclovir and foscarnet are in medical use today against HSV type-1 (HSV-1) and type-2 (HSV-2), inhibiting the DNA synthesis of the viruses. Additional drugs that will affect the growth of these viruses by other mechanisms and also decrease the frequency of appearance of drug-resistant mutants are required. Methods: Cationic polysaccharides were synthesized by conjugation of various oligoamines to oxidized polysaccharides by reductive amination. Polycations of dextran, pullulan and arabinogalactan were grafted with oligoamines of 2–4 amino groups forming Schiff-base imine-based conjugates followed by reduction with borohydride to obtain the stable amine-based conjugate. Evaluation of toxicity to BS-C-1 cells and antiviral activity against HSV-1 and HSV-2 of the different compounds was performed in vitro by a semiquantitative assay. A quantitative study with a selected compound followed. Results: Structure–activity relationship studies showed that the nature of the grafted oligoamine of the polycation plays an essential role in the antiviral activity against HSV-1 and HSV-2. Dextran-propan-1,3-diamine (DPD) was found to be the most potent of all the compounds examined. DPD did not decrease the infectivity of HSV upon direct exposure to the virions. The growth of HSV was significantly inhibited when DPD was added to the host cells 1 h prior to infection, thus preventing the adsorption and penetration of the virus into the cells. Conclusions: Our in vitro data warrant clinical investigation. DPD could have an advantage as a topical application in combination therapy of HSV lesions.
Early Life Factors and Adult-onset Rheumatoid Arthritis
Authors: SIMARD JULIA F. , COSTENBADER KAREN H. , HERNÁN MIGUEL A. , LIANG MATTHEW H. , MITTLEMAN MURRAY A. , KARLSON ELIZABETH W. 
Published: October 2009

Objective.Early life factors have been associated with risk of developing autoimmune disease in adulthood. We investigated the association of preterm birth and being breastfed with the incidence of rheumatoid arthritis (RA) in 2 large prospective cohorts.Methods.We studied participants from the Nurses’ Health Study (NHS) and the Nurses’ Health Study II (NHSII) who provided information on perinatal factors. The NHS (n = 121,701) and NHSII (n = 116,608) are large prospective cohorts of women followed since 1976 and 1989, respectively. Incident RA was confirmed using the American College of Rheumatology criteria and a medical record review. Cox models were used to estimate the hazard ratio of RA associated with being born preterm and being breastfed and its duration, adjusting for potential confounders. Random effects metaanalytic methods were used to compute combined estimates from the 2 cohorts.Results.We found no statistically significant association between preterm birth and incident RA [relative risk (RR) = 1.1, 95% CI 0.8, 1.5]. Being breastfed was not associated with increased incidence of RA (RR = 1.0, 95% CI 0.7, 1.4), regardless of the duration of breastfeeding.Conclusion.In these cohorts of women, neither being preterm birth nor being breastfed was associated with the onset of RA.
The Specificity of Trimming of MHC Class I-Presented Peptides in the Endoplasmic Reticulum
Authors: Hearn Arron , York Ian A. , Rock Kenneth L. 
Published: October 2009

Abstract
Aminopeptidases in the endoplasmic reticulum (ER) can cleave antigenic peptides and in so doing either create or destroy MHC class I-presented epitopes. However, the specificity of this trimming process overall and of the major ER aminopeptidase ERAP1 in particular is not well understood. This issue is important because peptide trimming influences the magnitude and specificity of CD8 T cell responses. By systematically varying the N-terminal flanking sequences of peptides in a cell-free biochemical system and in intact cells, we elucidated the specificity of ERAP1 and of ER trimming overall. ERAP1 can cleave after many amino acids on the N terminus of epitope precursors but does so at markedly different rates. The specificity seen with purified ERAP1 is similar to that observed for trimming and presentation of epitopes in the ER of intact cells. We define N-terminal sequences that are favorable or unfavorable for Ag presentation in ways that are independent from the epitopes core sequence. When databases of known presented peptides were analyzed, the residues that were preferred for the trimming of model peptide precursors were found to be overrepresented in N-terminal flanking sequences of epitopes generally. These data define key determinants in the specificity of Ag processing.
Targeting of DC-SIGN on Human Dendritic Cells by Minor Fimbriated Porphyromonas gingivalis Strains Elicits a Distinct Effector T Cell Response
Authors: Zeituni Amir E. , Jotwani Ravi , Carrion Julio , Cutler Christopher W. 
Published: October 2009

Abstract
The oral mucosal pathogen Porphyromonas gingivalis expresses at least two adhesins: the 67-kDa mfa-1 (minor) fimbriae and the 41-kDa fimA (major) fimbriae. In periodontal disease, P. gingivalis associates in situ with dermal dendritic cells (DCs), many of which express DC-SIGN (DC-specific ICAM-3 grabbing nonintegrin; CD209). The cellular receptors present on DCs that are involved in the uptake of minor/major fimbriated P. gingivalis, along with the effector immune response induced, are presently unclear. In this study, stably transfected human DC-SIGN+/− Raji cell lines and monocyte-derived DCs (MoDCs) were pulsed with whole, live, wild-type Pg381 or isogenic major (DPG-3)-, minor (MFI)-, or double fimbriae (MFB)-deficient mutant P. gingivalis strains. The influence of blocking Abs, carbohydrates, full-length glycosylated HIV-1 gp120 envelope protein, and cytochalasin D on the uptake of strains and on the immune responses was determined in vitro. We show that the binding of minor fimbriated P. gingivalis strains to Raji cells and MoDCs is dependent on DC-SIGN, whereas the double fimbriae mutant strain does not bind. Binding to DC-SIGN on MoDCs is followed by the internalization of P. gingivalis into DC-SIGN-rich intracellular compartments, and MoDCs secrete low levels of inflammatory cytokines and remain relatively immature. Blocking DC-SIGN with HIV-1 gp120 prevents the uptake of minor fimbriated strains and deregulates the expression of inflammatory cytokines. Moreover, MoDCs promote a Th2 or Th1 effector response, depending on whether they are pulsed with minor or major fimbriated P. gingivalis strains, respectively, suggesting distinct immunomodulatory roles for the two adhesins of P. gingivalis.
PU.1 Regulates Positive Regulatory Domain I-Binding Factor 1/Blimp-1 Transcription in Lymphoma Cells
Authors: Desai Shruti , Bolick Sophia C. E. , Maurin Michelle , Wright Kenneth L. 
Published: October 2009

Abstract
The human positive regulatory domain I-binding factor 1 (PRDI-BF1) and its murine homolog Blimp-1 promote differentiation of mature B cells into Ab-secreting plasma cells. In contrast, ectopic expression of PRDI-BF1 in lymphoma cells can lead to inhibition of proliferation or apoptosis. However, little is currently known about the regulation of PRDM1, the gene encoding PRDI-BF1. This report establishes that in lymphoma cells stimulation through the BCR rapidly induces endogenous PRDM1 at the level of transcription with minor changes in mRNA stability. The induced PRDM1-encoded protein localizes to its target genes in vivo and suppresses their expression. In vivo genomic footprinting of the PRDM1 promoter in unstimulated lymphoma and myeloma cells reveals multiple common in vivo occupied elements throughout the promoter. Further functional and structural analysis of the promoter reveals that the promoter is preloaded and poised for activation in the B cell lines. The transcription factor PU.1 is shown to be required for the BCR-induced expression of PRDM1 in lymphoma cells and in PU.1-positive myeloma cells. Activation of PRDM1 is associated with loss of the corepressor transducin-like enhancer of split 4 from the PU.1 complex. These findings indicate that PRDM1 is poised for activation in lymphoma cells and therefore may be a potential therapeutic target to inhibit lymphoma cell proliferation and survival.
Ikaros Is a Regulator of Il10 Expression in CD4+ T Cells
Authors: Umetsu Sarah E. , Winandy Susan 
Published: October 2009

Abstract
IL-10 is a regulatory cytokine critical for controlling inflammatory responses. Here we show that Ikaros, a zinc finger DNA-binding protein, plays an important role in the regulation of Il10 in murine CD4+ T cells. Upon initial stimulation of the TCR, T cells deficient in Ikaros express significantly lower levels of IL-10 compared with wild-type T cells. In addition, under Th2 skewing conditions, which induce IL-10 production by wild-type T cells, Ikaros null T cells are unable to properly differentiate, producing only low levels of IL-10. Expression of a dominant-negative isoform of Ikaros in wild-type Th2 cells represses IL-10 production but does not significantly alter expression levels of the genes encoding the transcription factors GATA-3 and T-bet. Furthermore, expression of Ikaros in Ikaros null T cells restores expression of the Th2 cytokines IL-10 and IL-4 while reducing production of the Th1 cytokine, IFN-γ. Coexpression of Ikaros and GATA-3 further increases IL-10 production, showing that these two factors have an additive effect on activating Il10 expression. Finally, we show that Ikaros binds to conserved regulatory regions of the Il10 gene locus in Th2 cells, supporting a direct role for Ikaros in Il10 expression. Thus, we provide evidence for Ikaros as a regulator of Il10 and Ifng gene expression and suggest a role for Ikaros in directing lineage-specific cytokine gene activation and repression.
Ly49H Engagement Compensates for the Absence of Type I Interferon Signaling in Stimulating NK Cell Proliferation During Murine Cytomegalovirus Infection
Authors: Geurs Theresa L. , Zhao Yun M. , Hill Elaise B. , French Anthony R. 
Published: October 2009

Abstract
NK cells vigorously proliferate during viral infections, resulting in an expanded pool of innate lymphocytes that are able to participate in early host defense. The relative contributions of cytokines and activation receptors in stimulating NK cell proliferation during viral infections are not well characterized. In this study, we demonstrated that signaling through the NK cell activation receptor Ly49H was able to compensate for the absence of cytokine stimulation in the preferential phase of viral-induced proliferation during murine cytomegalovirus infection. In the absence of type I IFN stimulation, NK cell proliferation was strongly biased toward cells expressing the Ly49H receptor, even at early time points when minimal preferential Ly49H-mediated proliferation was observed in wild-type mice. In the absence of effective Ly49H signaling or following infection with virus that did not express the ligand for Ly49H, no difference was observed in the proliferation of subsets of NK cells that either express or lack expression of Ly49H, although the overall proliferation of NK cells in IFNαβR−/− mice was substantially reduced. These results highlight the contribution of NK cell activation receptors in stimulating proliferation and subsequent expansion of NK cells that are able to recognize virally infected cells.
HOXB4-Transduced Embryonic Stem Cell-Derived Lin−c-kit+ and Lin−Sca-1+ Hematopoietic Progenitors Express H60 and Are Targeted by NK Cells
Authors: Tabayoyong William B. , Salas Juan G. , Bonde Sabrina , Zavazava Nicholas 
Published: October 2009

Abstract
Embryonic stem (ES) cells are a novel source of cells, especially hematopoietic progenitor cells that can be used to treat degenerative diseases in humans. However, there is a need to determine how ES cell-derived progenitors are regulated by both the adaptive and innate immune systems post transplantation. In this study, we demonstrate that hematopoietic progenitor cells (HPCs) derived from mouse ES cells ectopically expressing HOXB4 fail to engraft long-term in the presence of NK cells. In particular, the H60-expressing Lin−c-kit+ and Lin−Sca-1+ subpopulations were preferentially deleted in Rag2−/−, but not in Rag2−/−γc−/− mice. Up-regulation of class I expression on HPCs prevented their lysis by NK cells, and Ab-mediated depletion of NK cells restored long-term HPC engraftment. In contrast to the notion that ES-derived cells are immune-privileged, we show in this study that NK cells form a formidable barrier to the long-term engraftment of ES cell-derived hematopoietic progenitors.
The Adaptor Protein Shc Plays a Key Role during Early B Cell Development
Authors: Giles Amber J. , Bender Timothy P. , Ravichandran Kodi S. 
Published: October 2009

Abstract
The adaptor protein Shc is phosphorylated downstream of many cell surface receptors, including Ag and cytokine receptors. However, the role of Shc in B cell development has not been addressed. Here, through conditional expression of a dominant negative Shc mutant and conditional loss of Shc protein expression, we tested a role for Shc during early B lymphopoiesis. We identified a requirement for Shc beginning at the transition from the pre-pro-B to pro-B stage, with a strong reduction in the number of pre-B cells. This developmental defect is due to increased cell death rather than impaired proliferation or commitment to the B lineage. Additional studies suggest a role for Shc in IL-7-dependent signaling in pro-B cells. Shc is phosphorylated in response to IL-7 stimulation in pro-B cells, and pro-B cells from mice with impaired Shc signaling display increased apoptosis. Together, these data demonstrate a critical role for Shc in early B lymphopoiesis with a requirement in early B cell survival. In addition, we also identify Shc as a required player in signaling downstream of the IL-7R in early B cells.
Adventitious Organogenesis
Authors: De Klerk Geert‐Jan 
Published: October 2009

AbstractIn plants, differentiated somatic cells may dedifferentiate and subsequently redifferentiate into (adventitious) shoots, roots, or embryos. The formation of adventitious shoots (caulogenesis) and roots (rhizogenesis) is specified with the term adventitious organogenesis, whereas somatic embryogenesis refers to the formation of adventitious (somatic) embryos. Adventitious organogenesis occurs frequently during natural life but may be achieved at very high frequencies in tissue culture. It is one of the basic tools in vegetative plant propagation and plant breeding. In propagation, adventitious formation of shoots is important in micropropagation of many crops and adventitious formation of roots from (micro)cuttings is required to obtain complete plants from excised shoots. In breeding, adventitious organogenesis is essential among others in transformation and haploid production. This article reviews adventitious organogenesis from the point of view of developmental biology and deals with physiological, biochemical, molecular, and genetic aspects. It covers both practical and fundamental aspects.
Antibody Engineering
Authors: Yoo Esther M. , Morrison Sherie L. 
Published: October 2009

AbstractThere is great potential for the use of antibodies for various applications in biotechnology, immunity and human health. In this article, we will describe the structure and function of immunoglobulins and the advances, as well as challenges in engineering antibodies. Many factors need to be considered to produce the most effective and relevant antibody for a given purpose. The five different immunoglobulin isotypes that differ in their role in the immune system are described. The various receptors and ligands that bind antibodies and engage in effector functions are also discussed. Using genetic modifications and manipulation, it is now possible to engineer antibodies, antibody fragments, and fusion proteins. In addition, the advantages and limitations in the use of various expression systems such as cell lines and transgenic animals are outlined. Antibodies have been studied extensively for decades and much is known about them. The many years of exploring the antibody molecule should be brought to fruition as we move our scientific knowledge from the laboratory to develop innovative tools for biology as well as treatments and prophylactics against pathogens and human diseases.
Apoptosis
Authors: Al‐Rubeai Mohamed , Khoo Soo Hean Gary , Singh Rabinder P. 
Published: October 2009

AbstractApoptosis is now acknowledged as a fundamentally important process that plays an essential role in embryogenesis and in the maintenance and functionality of the highly ordered cell populations that constitute higher organisms. In this article, we describe the biochemical basis of apoptosis, the morphological changes that accompany it, and some of the techniques that have been used to identify apoptotic cells. This is followed by a general discussion of the regulation and induction of apoptosis. We then describe studies that have investigated this phenomenon from a biotechnological perspective. Particular reference is made to the conditions that elicit an apoptotic response, the cell lines that are susceptible, and the cellular engineering approaches to enhance cell survival and productivity in the bioreactor environment.
Bioreactor Scale‐Up
Authors: Palomares Laura A. , Ramírez Octavio T. 
Published: October 2009

Abstract
Scaling‐up is a determinant step during process development. Successful scale‐up requires careful calculation of the geometric relations of the large‐scale bioreactor to avoid heterogeneities. In this article, the work done by various engineers in bioreactor design and prediction of possible environmental gradients in bioreactors is presented and discussed, with emphasis on reactors for cell culture. Several bioreactor configurations are discussed. Other issues such as heat transfer are also presented. The theoretical framework for predicting the behavior of large‐scale cultures is presented.
Microbial Primary Metabolites: Biosynthesis and Perspectives
Authors: Sanchez Sergio , Demain Arnold L. 
Published: October 2009

AbstractThe microbial production of primary metabolites contributes significantly to the quality of life. Fermentative production of these compounds is still an important goal of modern biotechnology. Through fermentation, microorganisms growing on inexpensive carbon and nitrogen sources produce valuable products such as amino acids, nucleotides, organic acids, and vitamins, which can be added to food to enhance its flavor, or increase its nutritive values. The contribution of microorganisms goes well beyond the food and health industries with the renewed interest in solvent fermentations. Microorganisms have the potential to provide many petroleum‐derived products as well as the ethanol necessary for liquid fuel. Additional applications of primary metabolites lie in their impact as precursors of many pharmaceutical compounds. The roles of primary metabolites and the microbes which produce them will certainly increase in importance as time goes on.Overproduction of microbial metabolites is related to developmental phases of microorganisms. Inducers, effectors, inhibitors, and various signal molecules play a role in different types of overproduction. Biosynthesis of enzymes catalyzing metabolic reactions in microbial cells is controlled by well‐known positive and negative mechanisms, for example, induction, nutritional regulation (carbon or nitrogen source regulation), and feedback regulation.In the early years of fermentation processes, development of producing strains initially depended on classical strain breeding involving repeated random mutations, each followed by screening or selection. More recently, methods of molecular genetics have been used for the overproduction of primary metabolic products. The development of modern tools of molecular biology enabled more rational approaches for strain improvement. Techniques of transcriptome, proteome, and metabolome analysis, as well as metabolic flux analysis, have recently been introduced in order to identify new and important target genes and to quantify metabolic activities necessary for further strain improvement.
Carotenoids, Microbial Processes
Authors: Schmidt‐Dannert Claudia , Lee Pyung Cheon 
Published: October 2009

AbstractCarotenoids are used commercially as food colorants, feed supplements, nutraceuticals, and for cosmetic and pharmaceutical purposes. However, only a handful of the more than several hundred different carotenoids identified in nature can be obtained in useful quantities by chemical synthesis, extraction from their natural sources or microbial fermentation. The current global market for all commercially used carotenoids is expected to rise at an average annual growth rate of 2.9% reaching over $1 billion in 2009. The over‐the‐counter and pharmaceutical sector has become a new market for carotenoids and, together with an increasing demand for carotenoids in traditional feed and food applications, pushes efforts for the production of diverse carotenoid structures in useful quantities. As an alternative to chemical synthesis and extraction from natural sources, microbial processes are being currently developed for the production of carotenoids. In this article we will discuss the recent progress made in the development of microbial processes for carotenoid production.
Cell Wall Disruption and Lysis
Authors: Garcia F. A. P. 
Published: October 2009

Abstract
The microbial world has been increasingly exploited for the production of useful materials. The disruption of the cell wall is a necessary step in the separation and purification of intracellular products. A general review of the chemical composition and structure of the cell wall is given for different kinds of microorganisms. The effects of cell growth conditions on the resistance of the cell wall to disruption are analysed and quantitative data of the cell wall strength is presented. Different methods of quantifying the efficiency of the disintegration process are commented. A review is made of the main technologies used for the disintegration of the cell wall, which have gained large acceptance for either analytical or preparative and large scale applications. The implications of the disruption process for further separation operations are also reviewed. New trends for process intensification by coupling the disruption/permeabilization step with primary capture techniques to yield pure target proteins in fewer process steps are also reviewed.
Chromatography, Industrial Scale, Validation: Checklists for Systems Compliance
Authors: Weinberg Sandy , Rockburne Carl A. 
Published: October 2009

AbstractThe US Food and Drug Administration provides a series of regulatory guidelines and directives definiing the required validation for chromotography systems. This validation process is critical to the demonstration of managerial control of the system, and provides the necessary credibility for the output of a chromatographic analysis. This article provides a checklist for that validation process, referencing the key points in that list to appropriate sections of the Good Manufacturing Practices, Code of Federal Requirements, and other significant guidelines. Taken in totality the checklist can provide a framework for the validation study; an internal quality assurance check on the validation and the controls of the chromatographic system; and the FDA‐required documentary evidence of managerial oversight.