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Biology, Volume 2, Issue 3 (September 2013), Pages 841-1188

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Research

Jump to: Review

Open AccessArticle A Versatile Tool for Stable Inhibition of microRNA Activity
Biology 2013, 2(3), 861-871; doi:10.3390/biology2030861
Received: 11 April 2013 / Revised: 13 May 2013 / Accepted: 15 May 2013 / Published: 28 June 2013
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Abstract
MicroRNAs (miRNAs) are a class of small RNAs (18–22 nt) that post transcriptionally regulate gene expression by binding to complementary sequences on target mRNAs, resulting in translational repression or target degradation and gene silencing. As aberrant expression of miRNAs is implicated in [...] Read more.
MicroRNAs (miRNAs) are a class of small RNAs (18–22 nt) that post transcriptionally regulate gene expression by binding to complementary sequences on target mRNAs, resulting in translational repression or target degradation and gene silencing. As aberrant expression of miRNAs is implicated in important diseases including cancer miRNA-based therapies are under intensive investigation. We optimized strategies to stably or conditionally generate miRNA inhibitors for a continuous block of miRNA activity that allows for probing miRNA function in long-term cell culture experiments, cancer xenografts, 3D tissue models and for in vivo studies with transgenic organisms. Full article
(This article belongs to the Special Issue Gene Expression and Regulation)
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Open AccessArticle The Vulnerability of Threatened Species: Adaptive Capability and Adaptation Opportunity
Biology 2013, 2(3), 872-893; doi:10.3390/biology2030872
Received: 2 May 2013 / Revised: 30 May 2013 / Accepted: 31 May 2013 / Published: 1 July 2013
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Abstract
Global targets to halt the loss of biodiversity have not been met, and there is now an additional Aichi target for preventing the extinction of known threatened species and improving their conservation status. Climate change increasingly needs to be factored in to [...] Read more.
Global targets to halt the loss of biodiversity have not been met, and there is now an additional Aichi target for preventing the extinction of known threatened species and improving their conservation status. Climate change increasingly needs to be factored in to these, and thus there is a need to identify the extent to which it could increase species vulnerability. This paper uses the exposure, sensitivity, and adaptive capacity framework to assess the vulnerability of a selection of WWF global priority large mammals and marine species to climate change. However, it divides adaptive capacity into adaptive capability and adaptation opportunity, in order to identify whether adaptation is more constrained by the biology of the species or by its environmental setting. Lack of evidence makes it difficult to apply the framework consistently across the species, but it was found that, particularly for the terrestrial mammals, adaptation opportunities seems to be the greater constraint. This framework and analysis could be used by conservationists and those wishing to enhance the resilience of species to climate change. Full article
(This article belongs to the Special Issue Biological Implications of Climate Change)
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Open AccessArticle Structural Sampling of Glycan Interaction Profiles Reveals Mucosal Receptors for Fimbrial Adhesins of Enterotoxigenic Escherichia coli
Biology 2013, 2(3), 894-917; doi:10.3390/biology2030894
Received: 1 April 2013 / Revised: 15 May 2013 / Accepted: 17 May 2013 / Published: 1 July 2013
Cited by 7 | PDF Full-text (1464 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fimbriae are long, proteinaceous adhesion organelles expressed on the bacterial envelope, evolutionarily adapted by Escherichia coli strains for the colonization of epithelial linings. Using glycan arrays of the Consortium for Functional Glycomics (CFG), the lectin domains were screened of the fimbrial adhesins [...] Read more.
Fimbriae are long, proteinaceous adhesion organelles expressed on the bacterial envelope, evolutionarily adapted by Escherichia coli strains for the colonization of epithelial linings. Using glycan arrays of the Consortium for Functional Glycomics (CFG), the lectin domains were screened of the fimbrial adhesins F17G and FedF from enterotoxigenic E. coli (ETEC) and of the FimH adhesin from uropathogenic E. coli. This has led to the discovery of a more specific receptor for F17G, GlcNAcb1,3Gal. No significant differences emerged from the glycan binding profiles of the F17G lectin domains from five different E. coli strains. However, strain-dependent amino acid variations, predominantly towards the positively charged arginine, were indicated by sulfate binding in FedF and F17G crystal structures. For FedF, no significant binders could be observed on the CFG glycan array. Hence, a shotgun array was generated from microvilli scrapings of the distal jejunum of a 3-week old piglet about to be weaned. On this array, the blood group A type 1 hexasaccharide emerged as a receptor for the FedF lectin domain and remarkably also for F18-fimbriated E. coli. F17G was found to selectively recognize glycan species with a terminal GlcNAc, typifying intestinal mucins. In conclusion, F17G and FedF recognize long glycan sequences that could only be identified using the shotgun approach. Interestingly, ETEC strains display a large capacity to adapt their fimbrial adhesins to ecological niches via charge-driven interactions, congruent with binding to thick mucosal surfaces displaying an acidic gradient along the intestinal tract. Full article
(This article belongs to the Special Issue Bacterial Adhesion)
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Open AccessArticle Characterizing Microbial Diversity and the Potential for Metabolic Function at −15 °C in the Basal Ice of Taylor Glacier, Antarctica
Biology 2013, 2(3), 1034-1053; doi:10.3390/biology2031034
Received: 18 June 2013 / Revised: 12 July 2013 / Accepted: 16 July 2013 / Published: 26 July 2013
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Abstract
Measurement of gases entrapped in clean ice from basal portions of the Taylor Glacier, Antarctica, revealed that CO2 ranged from 229 to 328 ppmv and O2 was near 20% of the gas volume. In contrast, vertically adjacent sections of the [...] Read more.
Measurement of gases entrapped in clean ice from basal portions of the Taylor Glacier, Antarctica, revealed that CO2 ranged from 229 to 328 ppmv and O2 was near 20% of the gas volume. In contrast, vertically adjacent sections of the sediment laden basal ice contained much higher concentrations of CO2 (60,000 to 325,000 ppmv), whereas O2 represented 4 to 18% of the total gas volume. The deviation in gas composition from atmospheric values occurred concurrently with increased microbial cell concentrations in the basal ice profile, suggesting that in situ microbial processes (i.e., aerobic respiration) may have altered the entrapped gas composition. Molecular characterization of 16S rRNA genes amplified from samples of the basal ice indicated a low diversity of bacteria, and most of the sequences characterized (87%) were affiliated with the phylum, Firmicutes. The most abundant phylotypes in libraries from ice horizons with elevated CO2 and depleted O2 concentrations were related to the genus Paenisporosarcina, and 28 isolates from this genus were obtained by enrichment culturing. Metabolic experiments with Paenisporosarcina sp. TG14 revealed its capacity to conduct macromolecular synthesis when frozen in water derived from melted basal ice samples and incubated at −15 °C. The results support the hypothesis that the basal ice of glaciers and ice sheets are cryospheric habitats harboring bacteria with the physiological capacity to remain metabolically active and biogeochemically cycle elements within the subglacial environment. Full article
Open AccessArticle Effect of Aminophenyl and Aminothiahexyl α-D-Glycosides of the Manno-, Gluco-, and Galacto-Series on Type 1 Fimbriae-Mediated Adhesion of Escherichia coli
Biology 2013, 2(3), 1135-1149; doi:10.3390/biology2031135
Received: 15 July 2013 / Revised: 17 August 2013 / Accepted: 28 August 2013 / Published: 3 September 2013
Cited by 4 | PDF Full-text (630 KB) | HTML Full-text | XML Full-text
Abstract
Adhesion of bacteria to the glycosylated surface of their target cells is typically mediated by fimbrial lectins, exposed on the bacterial surface. Among the best-investigated and most important fimbriae are type 1 fimbriae, for which α-d-mannopyranoside-specificity has been described. This carbohydrate specificity [...] Read more.
Adhesion of bacteria to the glycosylated surface of their target cells is typically mediated by fimbrial lectins, exposed on the bacterial surface. Among the best-investigated and most important fimbriae are type 1 fimbriae, for which α-d-mannopyranoside-specificity has been described. This carbohydrate specificity is mediated by the type 1 fimbrial lectin FimH. In this account, we have employed four different set-ups to assay type 1 fimbriae-mediated bacterial adhesion, including tailor-made glycoarrays. The focus of our study was on testing FimH specificity with regard to the glycone part of a glycosidic ligand by testing a series of synthetic α-mannosides, as well as α-glucosides and α-galactosides. Unexpectedly, it was found that in solution all tested aminothiahexyl glycosides inhibit bacterial adhesion but that this effect is unspecific. Instead it is due to cytotoxicity of the respective glycosides at high mm concentrations. Full article
(This article belongs to the Special Issue Bacterial Adhesion)
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Open AccessArticle Phylogenomics of MADS-Box Genes in Plants — Two Opposing Life Styles in One Gene Family
Biology 2013, 2(3), 1150-1164; doi:10.3390/biology2031150
Received: 6 August 2013 / Revised: 2 September 2013 / Accepted: 5 September 2013 / Published: 12 September 2013
Cited by 7 | PDF Full-text (1856 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The development of multicellular eukaryotes, according to their body plan, is often directed by members of multigene families that encode transcription factors. MADS (for MINICHROMOSOME MAINTENANCE1, AGAMOUS, DEFICIENS and SERUM RESPONSE FACTOR)-box genes form one of those families controlling nearly all major [...] Read more.
The development of multicellular eukaryotes, according to their body plan, is often directed by members of multigene families that encode transcription factors. MADS (for MINICHROMOSOME MAINTENANCE1, AGAMOUS, DEFICIENS and SERUM RESPONSE FACTOR)-box genes form one of those families controlling nearly all major aspects of plant development. Knowing the complete complement of MADS-box genes in sequenced plant genomes will allow a better understanding of the evolutionary patterns of these genes and the association of their evolution with the evolution of plant morphologies. Here, we have applied a combination of automatic and manual annotations to identify the complete set of MADS-box genes in 17 plant genomes. Furthermore, three plant genomes were reanalyzed and published datasets were used for four genomes such that more than 2,600 genes from 24 species were classified into the two types of MADS-box genes, Type I and Type II. Our results extend previous studies, highlighting the remarkably different evolutionary patterns of Type I and Type II genes and provide a basis for further studies on the evolution and function of MADS-box genes. Full article
(This article belongs to the Special Issue Insights from Plant Genomes)
Open AccessArticle Contrasting Responses to Nutrient Enrichment of Prokaryotic Communities Collected from Deep Sea Sites in the Southern Ocean
Biology 2013, 2(3), 1165-1188; doi:10.3390/biology2031165
Received: 2 May 2013 / Revised: 2 August 2013 / Accepted: 4 September 2013 / Published: 13 September 2013
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Abstract
Deep water samples (ca. 4,200 m) were taken from two hydrologically-similar sites around the Crozet islands with highly contrasting surface water productivities. Site M5 was characteristic of high productivity waters (high chlorophyll) whilst site M6 was subject to a low [...] Read more.
Deep water samples (ca. 4,200 m) were taken from two hydrologically-similar sites around the Crozet islands with highly contrasting surface water productivities. Site M5 was characteristic of high productivity waters (high chlorophyll) whilst site M6 was subject to a low productivity regime (low chlorophyll) in the overlying waters. Samples were incubated for three weeks at 4 °C at in-situ and surface pressures, with and without added nutrients. Prokaryotic abundance increased by at least two-fold for all nutrient-supplemented incubations of water from M5 with little difference in abundance between incubations carried out at atmospheric and in-situ pressures. Abundance only increased for incubations of M6 waters (1.6-fold) when they were carried out at in-situ pressures and with added nutrients. Changes in community structure as a result of incubation and enrichment (as measured by DGGE banding profiles and phylogenetic analysis) showed that diversity increased for incubations of M5 waters but decreased for those with M6 waters. Moritella spp. came to dominate incubations carried out under in-situ pressure whilst the Archaeal community was dominated by Crenarchaea in all incubations. Comparisons between atmospheric and in situ pressure incubations demonstrated that community composition was significantly altered and community structure changes in unsuspplemented incubations at in situ pressure was indicative of the loss of functional taxa as a result of depressurisation during sampling. The use of enrichment incubations under in-situ conditions has contributed to understanding the different roles played by microorganisms in deep sea ecosystems in regions of low and high productivity. Full article

Review

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Open AccessReview Ordered and Ushered; the Assembly and Translocation of the Adhesive Type I and P Pili
Biology 2013, 2(3), 841-860; doi:10.3390/biology2030841
Received: 12 April 2013 / Revised: 21 May 2013 / Accepted: 24 May 2013 / Published: 26 June 2013
Cited by 5 | PDF Full-text (712 KB) | HTML Full-text | XML Full-text
Abstract
Type I and P pili are chaperone-usher pili of uropathogenic Escherichia coli, which allow bacteria to adhere to host cell receptors. Pilus formation and secretion are orchestrated by two accessory proteins, a chaperone, which catalyses pilus subunit folding and maintains them [...] Read more.
Type I and P pili are chaperone-usher pili of uropathogenic Escherichia coli, which allow bacteria to adhere to host cell receptors. Pilus formation and secretion are orchestrated by two accessory proteins, a chaperone, which catalyses pilus subunit folding and maintains them in a polymerization-competent state, and an outer membrane-spanning nanomachine, the usher, which choreographs their assembly into a pilus and drives their secretion through the membrane. In this review, recent structures and kinetic studies are combined to examine the mechanism of type I and P pili assembly, as it is currently known. We also investigate how the knowledge of pilus biogenesis mechanisms has been exploited to design selective inhibitors of the process. Full article
(This article belongs to the Special Issue Bacterial Adhesion)
Open AccessReview Bacterial Adhesion of Streptococcus suis to Host Cells and Its Inhibition by Carbohydrate Ligands
Biology 2013, 2(3), 918-935; doi:10.3390/biology2030918
Received: 2 May 2013 / Revised: 22 May 2013 / Accepted: 22 May 2013 / Published: 1 July 2013
Cited by 5 | PDF Full-text (259 KB) | HTML Full-text | XML Full-text
Abstract
Streptococcus suis is a Gram-positive bacterium, which causes sepsis and meningitis in pigs and humans. This review examines the role of known S. suis virulence factors in adhesion and S. suis carbohydrate-based adhesion mechanisms, as well as the inhibition of S. suis [...] Read more.
Streptococcus suis is a Gram-positive bacterium, which causes sepsis and meningitis in pigs and humans. This review examines the role of known S. suis virulence factors in adhesion and S. suis carbohydrate-based adhesion mechanisms, as well as the inhibition of S. suis adhesion by anti-adhesion compounds in in vitro assays. Carbohydrate-binding specificities of S. suis have been identified, and these studies have shown that many strains recognize Galα1-4Gal-containing oligosaccharides present in host glycolipids. In the era of increasing antibiotic resistance, new means to treat infections are needed. Since microbial adhesion to carbohydrates is important to establish disease, compounds blocking adhesion could be an alternative to antibiotics. The use of oligosaccharides as drugs is generally hampered by their relatively low affinity (micromolar) to compete with multivalent binding to host receptors. However, screening of a library of chemically modified Galα1-4Gal derivatives has identified compounds that inhibit S. suis adhesion in nanomolar range. Also, design of multivalent Galα1-4Gal-containing dendrimers has resulted in a significant increase of the inhibitory potency of the disaccharide. The S. suis adhesin binding to Galα1-4Gal-oligosaccharides, Streptococcal adhesin P (SadP), was recently identified. It has a Galα1-4Gal-binding N-terminal domain and a C-terminal LPNTG-motif for cell wall anchoring. The carbohydrate-binding domain has no homology to E. coli P fimbrial adhesin, which suggests that these Gram-positive and Gram-negative bacterial adhesins recognizing the same receptor have evolved by convergent evolution. SadP adhesin may represent a promising target for the design of anti-adhesion ligands for the prevention and treatment of S. suis infections. Full article
(This article belongs to the Special Issue Bacterial Adhesion)
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Open AccessReview Oncolytic Newcastle Disease Virus as Cutting Edge between Tumor and Host
Biology 2013, 2(3), 936-975; doi:10.3390/biology2030936
Received: 6 May 2013 / Revised: 11 June 2013 / Accepted: 18 June 2013 / Published: 2 July 2013
Cited by 9 | PDF Full-text (1011 KB) | HTML Full-text | XML Full-text
Abstract
Oncolytic viruses (OVs) replicate selectively in tumor cells and exert anti-tumor cytotoxic activity. Among them, Newcastle Disease Virus (NDV), a bird RNA virus of the paramyxovirus family, appears outstanding. Its anti-tumor effect is based on: (i) oncolytic activity and (ii) immunostimulation. Together [...] Read more.
Oncolytic viruses (OVs) replicate selectively in tumor cells and exert anti-tumor cytotoxic activity. Among them, Newcastle Disease Virus (NDV), a bird RNA virus of the paramyxovirus family, appears outstanding. Its anti-tumor effect is based on: (i) oncolytic activity and (ii) immunostimulation. Together these activities facilitate the induction of post-oncolytic adaptive immunity. We will present milestones during the last 60 years of clinical evaluation of this virus. Two main strategies of clinical application were followed using the virus (i) as a virotherapeutic agent, which is applied systemically or (ii) as an immunostimulatory agent combined with tumor cells for vaccination of cancer patients. More recently, a third strategy evolved. It combines the strategies (i) and (ii) and includes also dendritic cells (DCs). The first step involves systemic application of NDV to condition the patient. The second step involves intradermal application of a special DC vaccine pulsed with viral oncolysate. This strategy, called NDV/DC, combines anti-cancer activity (oncolytic virotherapy) and immune-stimulatory properties (oncolytic immunotherapy) with the high potential of DCs (DC therapy) to prime naive T cells. The aim of such treatment is to first prepare the cancer-bearing host for immunocompetence and then to instruct the patient’s immune system with information about tumor-associated antigens (TAAs) of its own tumor together with danger signals derived from virus infection. This multimodal concept should optimize the generation of strong polyclonal T cell reactivity targeted against the patient’s TAAs and lead to the establishment of a long-lasting memory T cell repertoire. Full article
(This article belongs to the Special Issue RNA Viruses and Cancer)
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Open AccessReview The Role of Nuclear Bodies in Gene Expression and Disease
Biology 2013, 2(3), 976-1033; doi:10.3390/biology2030976
Received: 15 May 2013 / Revised: 13 June 2013 / Accepted: 20 June 2013 / Published: 9 July 2013
Cited by 8 | PDF Full-text (574 KB) | HTML Full-text | XML Full-text
Abstract
This review summarizes the current understanding of the role of nuclear bodies in regulating gene expression. The compartmentalization of cellular processes, such as ribosome biogenesis, RNA processing, cellular response to stress, transcription, modification and assembly of spliceosomal snRNPs, histone gene synthesis and [...] Read more.
This review summarizes the current understanding of the role of nuclear bodies in regulating gene expression. The compartmentalization of cellular processes, such as ribosome biogenesis, RNA processing, cellular response to stress, transcription, modification and assembly of spliceosomal snRNPs, histone gene synthesis and nuclear RNA retention, has significant implications for gene regulation. These functional nuclear domains include the nucleolus, nuclear speckle, nuclear stress body, transcription factory, Cajal body, Gemini of Cajal body, histone locus body and paraspeckle. We herein review the roles of nuclear bodies in regulating gene expression and their relation to human health and disease. Full article
(This article belongs to the Special Issue Gene Expression and Regulation)
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Open AccessReview The Biology of Neisseria Adhesins
Biology 2013, 2(3), 1054-1109; doi:10.3390/biology2031054
Received: 2 May 2013 / Revised: 1 July 2013 / Accepted: 3 July 2013 / Published: 29 July 2013
Cited by 3 | PDF Full-text (1122 KB) | HTML Full-text | XML Full-text
Abstract
Members of the genus Neisseria include pathogens causing important human diseases such as meningitis, septicaemia, gonorrhoea and pelvic inflammatory disease syndrome. Neisseriae are found on the exposed epithelia of the upper respiratory tract and the urogenital tract. Colonisation of these exposed epithelia [...] Read more.
Members of the genus Neisseria include pathogens causing important human diseases such as meningitis, septicaemia, gonorrhoea and pelvic inflammatory disease syndrome. Neisseriae are found on the exposed epithelia of the upper respiratory tract and the urogenital tract. Colonisation of these exposed epithelia is dependent on a repertoire of diverse bacterial molecules, extending not only from the surface of the bacteria but also found within the outer membrane. During invasive disease, pathogenic Neisseriae also interact with immune effector cells, vascular endothelia and the meninges. Neisseria adhesion involves the interplay of these multiple surface factors and in this review we discuss the structure and function of these important molecules and the nature of the host cell receptors and mechanisms involved in their recognition. We also describe the current status for recently identified Neisseria adhesins. Understanding the biology of Neisseria adhesins has an impact not only on the development of new vaccines but also in revealing fundamental knowledge about human biology. Full article
(This article belongs to the Special Issue Bacterial Adhesion)
Open AccessReview The Role of Helicobacter pylori Outer Membrane Proteins in Adherence and Pathogenesis
Biology 2013, 2(3), 1110-1134; doi:10.3390/biology2031110
Received: 4 June 2013 / Revised: 26 July 2013 / Accepted: 13 August 2013 / Published: 27 August 2013
Cited by 10 | PDF Full-text (787 KB) | HTML Full-text | XML Full-text
Abstract
Helicobacter pylori is one of the most successful human pathogens, which colonizes the mucus layer of the gastric epithelium of more than 50% of the world’s population. This curved, microaerophilic, Gram-negative bacterium induces a chronic active gastritis, often asymptomatic, in all infected [...] Read more.
Helicobacter pylori is one of the most successful human pathogens, which colonizes the mucus layer of the gastric epithelium of more than 50% of the world’s population. This curved, microaerophilic, Gram-negative bacterium induces a chronic active gastritis, often asymptomatic, in all infected individuals. In some cases, this gastritis evolves to more severe diseases such as peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. H. pylori has developed a unique set of factors, actively supporting its successful survival and persistence in its natural hostile ecological niche, the human stomach, throughout the individual’s life, unless treated. In the human stomach, the vast majority of H. pylori cells are motile in the mucus layer lining, but a small percentage adheres to the epithelial cell surfaces. Adherence to the gastric epithelium is important for the ability of H. pylori to cause disease because this intimate attachment facilitates: (1) colonization and persistence, by preventing the bacteria from being eliminated from the stomach, by mucus turnover and gastric peristalsis; (2) evasion from the human immune system and (3) efficient delivery of proteins into the gastric cell, such as the CagA oncoprotein. Therefore, bacteria with better adherence properties colonize the host at higher densities. H. pylori is one of the most genetically diverse bacterial species known and is equipped with an extraordinarily large set of outer membrane proteins, whose role in the infection and persistence process will be discussed in this review, as well as the different receptor structures that have been so far described for mucosal adherence. Full article
(This article belongs to the Special Issue Bacterial Adhesion)

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