bluuebunny/crossref_metadata_2025 huggingface dataset:
The Institutionalization of Just Decision Making: Analyzing Planning Practice in Portugal
Authors: Cardoso Ricardo , Breda-Vázquez Isabel
Published: February 2009

The institutionalization of just decision making in urban policy and planning is fundamental for the achievement of social justice in the city. In this paper we highlight the importance of generating adequate institutional conditions for the constitution of cosmopolis, Sandercock's postmodern utopia of justice. In doing that we resort to sociological institutionalist approaches to planning and policy analysis to evaluate a specific planning practice in the Portuguese planning system. Hence, after putting forward an appropriate analytical framework we tell the story of the decision-making process in the revision of Porto's Municipal Director Plan by delving through its intertwined history and evaluating it against the chosen criteria of social justice. The transcendent aim of this paper is to help to find opportunities for institutional improvements which can open the way for nonoppressive decision making and a more socially just urban future in Portugal and elsewhere.
A nonperturbative approximation for the moderate Reynolds number Navier–Stokes equations
Authors: Roper Marcus , Brenner Michael P.
Published: February 2009

The nonlinearity of the Navier–Stokes equations makes predicting the flow of fluid around rapidly moving small bodies highly resistant to all approaches save careful experiments or brute force computation. Here, we show how a linearization of the Navier–Stokes equations captures the drag-determining features of the flow and allows simplified or analytical computation of the drag on bodies up to Reynolds number of order 100. We illustrate the utility of this linearization in 2 practical problems that normally can only be tackled with sophisticated numerical methods: understanding flow separation in the flow around a bluff body and finding drag-minimizing shapes.
Cytokinins modulate auxin-induced organogenesis in plants via regulation of the auxin efflux
Authors: Pernisová Markéta , Klíma Petr , Horák Jakub , Válková Martina , Malbeck Jiří , Souček Přemysl , Reichman Pavel , Hoyerová Klára , Dubová Jaroslava , Friml Jiří , Za;žímalová Eva , Hejátko Jan
Published: February 2009

Postembryonic de novo organogenesis represents an important competence evolved in plants that allows their physiological and developmental adaptation to changing environmental conditions. The phytohormones auxin and cytokinin (CK) are important regulators of the developmental fate of pluripotent plant cells. However, the molecular nature of their interaction(s) in control of plant organogenesis is largely unknown. Here, we show that CK modulates auxin-induced organogenesis (AIO) via regulation of the efflux-dependent intercellular auxin distribution. We used the hypocotyl explants-based in vitro system to study the mechanism underlying de novo organogenesis. We show that auxin, but not CK, is capable of triggering organogenesis in hypocotyl explants. The AIO is accompanied by endogenous CK production and tissue-specific activation of CK signaling. CK affects differential auxin distribution, and the CK-mediated modulation of organogenesis is simulated by inhibition of polar auxin transport. CK reduces auxin efflux from cultured tobacco cells and regulates expression of auxin efflux carriers from the PIN family in hypocotyl explants. Moreover, endogenous CK levels influence
PIN
transcription and are necessary to maintain intercellular auxin distribution
in planta
. Based on these findings, we propose a model in which auxin acts as a trigger of the organogenic processes, whose output is modulated by the endogenously produced CKs. We propose that an important mechanism of this CK action is its effect on auxin distribution via regulation of expression of auxin efflux carriers.
Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air
Authors: Van Hoeven Neal , Pappas Claudia , Belser Jessica A. , Maines Taronna R. , Zeng Hui , García-Sastre Adolfo , Sasisekharan Ram , Katz Jacqueline M. , Tumpey Terrence M.
Published: February 2009

The influenza virus genes that confer efficient transmission of epidemic and pandemic strains in humans have not been identified. The rapid spread and severe disease caused by the 1918 influenza pandemic virus makes it an ideal virus to study the transmissibility of potentially pandemic influenza strains. Here, we used a series of human 1918-avian H1N1 influenza reassortant viruses to identify the genetic determinants that govern airborne transmission of avian influenza viruses. We have demonstrated that the 1918 HA gene was necessary for efficient direct contact transmission, but did not allow respiratory droplet transmission between ferrets of an avian influenza virus possessing an avian polymerase subunit PB2. The 1918 PB2 protein was found to be both necessary and sufficient for airborne transmission of a virus expressing the 1918 HA and neuraminidase. Also, it was found that influenza viruses that were able to transmit efficiently in ferrets were able to replicate efficiently at the lower temperature (33 °C) found in the environment of mammalian airway. These findings demonstrate that the adaptation of the HA and PB2 proteins are critical for the development of pandemic influenza strains from avian influenza viruses.
Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity
Authors: Guillonneau Carole , Mintern Justine D. , Hubert François-Xavier , Hurt Aeron C. , Besra Gurdyal S. , Porcelli Steven , Barr Ian G. , Doherty Peter C. , Godfrey Dale I. , Turner Stephen J.
Published: February 2009

Current influenza A virus vaccines do not generate significant immunity against serologically distinct influenza A virus subtypes and would thus be ineffective in the face of a pandemic caused by a novel variant emerging from, say, a wildlife reservoir. One possible solution would be to modify these vaccines so that they prime cross-reactive CD8
+
cytotoxic T lymphocytes (CTL) cell-mediated immunity directed at conserved viral epitopes. A further strategy is to use novel adjuvants, such as the immunomodulatory glycolipid α-galactosylceramide (α-GalCer). We show here that giving α-GalCer with an inactivated influenza A virus has the paradoxical effect of diminishing acute CTL immunity via natural killer T (NKT) cell-dependent expression of indoleamine 2,3-dioxygenase (IDO), an important mediator of immune suppression, while at the same time promoting the survival of long-lived memory CTL populations capable of boosting protection against heterologous influenza A virus challenge. This enhancement of memory was likely due to the α-GalCer-induced upregulation of prosurvival genes, such as bcl-2, and points to the potential of α-GalCer as an adjuvant for promoting optimal, vaccine-induced CD8
+
T cell memory.
Decreased EBNA-1-specific CD8+ T cells in patients with Epstein–Barr virus-associated nasopharyngeal carcinoma
Authors: Fogg Mark H. , Wirth Lori J. , Posner Marshall , Wang Fred
Published: February 2009

The Epstein–Barr virus (EBV) nuclear antigen-1 (EBNA-1) is potentially a universal target for immune recognition of EBV-infected normal or malignant cells. EBNA-1-specific CD8+ T-cell responses have been assessed against a few epitopes presented on a limited number of HLA class I alleles. We now assess CD8+ T-cell responses to a complete panel of EBNA-1 peptides in an HLA-characterized population. We detected EBNA-1-specific CD8+ T cells in 10 of 14 healthy donors by analysis of peripheral blood mononuclear cells and EBV-specific T-cell lines. The frequent detection of CD8+ T-cell responses was confirmed by mapping EBNA-1 epitopes and demonstrating HLA class I presentation to CD8+ T cells in 6 of 6 donors, including 2 new EBNA-1 epitopes presented by HLA A0206 and A6802. Importantly, EBNA-1-specific CD8+ T cells were significantly less frequent in EBV-specific T-cell lines from patients with EBV-associated nasopharyngeal carcinoma (3 out of 22,
P
= 0.0003), whereas the frequency of LMP2-specific responses (14 out of 22) was not significantly different from healthy donors (11 out of 14). EBNA-1-specific CD8+ T-cell responses were rescued in approximately half of nasopharyngeal carcinoma patients by peptide and cytokine stimulation of peripheral blood mononuclear cells, suggesting these EBNA-1-specific CD8+ T cells were functionally defective in their response to EBV-infected cells. These results indicate that humans normally mount a significant EBNA-1-specific CD8+ T-cell response to EBV infection, but the immune response to this tumor antigen has been significantly altered in nasopharyngeal carcinoma patients. Overcoming this defect in EBV-specific immunity may prevent or enhance treatment of EBV-associated nasopharyngeal carcinoma.
GIV is a nonreceptor GEF for Gαi with a unique motif that regulates Akt signaling
Authors: Garcia-Marcos Mikel , Ghosh Pradipta , Farquhar Marilyn G.
Published: February 2009

Heterotrimeric G proteins are molecular switches that control signal transduction. Ligand-occupied, G protein-coupled receptors serve as the canonical guanine nucleotide exchange factors (GEFs) that activate heterotrimeric G proteins. A few unrelated nonreceptor GEFs have also been described, but little or nothing is known about their structure, mechanism of action, or cellular functions in mammals. We have discovered that GIV/Girdin serves as a nonreceptor GEF for Gαi through an evolutionarily conserved motif that shares sequence homology with the synthetic GEF peptide KB-752. Using the available structure of the KB-752·Gαi1 complex as a template, we modeled the Gαi-GIV interface and identified the key residues that are required to form it. Mutation of these key residues disrupts the interaction and impairs Akt enhancement, actin remodeling, and cell migration in cancer cells. Mechanistically, we demonstrate that the GEF motif is capable of activating as well as sequestering the Gα-subunit, thereby enhancing Akt signaling via the Gβγ-PI3K pathway. Recently, GIV has been implicated in cancer metastasis by virtue of its ability to enhance Akt activity and remodel the actin cytoskeleton during cancer invasion. Thus, the novel regulatory motif described here provides the structural and biochemical basis for the prometastatic features of GIV, making the functional disruption of this unique Gαi-GIV interface a promising target for therapy against cancer metastasis.
Blocking of conditioning of tentacle lowering in the snail (Helix aspersa)
Authors: Acebes Félix , Solar Patricia , Carnero Susana , Loy Ignacio
Published: February 2009

Experiment 1 established the effectiveness of an appetitive conditioning of odours procedure with snails ( Helix aspersa) that was subsequently used for the study of blocking. In this important phenomenon, the conditioning of a CS1 (where CS is the conditioned stimulus) prior to conditioning of a compound, CS1CS2, blocked the conditioning to the CS2. Experiments 2a, 2b, and 2c demonstrated this associative effect using three different experimental controls. Experiments 3a and 3b replicated the blocking effect and allowed us to reject an explanation of blocking based on generalized effects of several treatments of diverse stimuli in blocking and control groups (the pseudoblocking effect). The implications of these results for the study of invertebrate cognition by means of conditioning techniques are discussed.
Is there room for the BBC in the mental lexicon? On the recognition of acronyms
Authors: Brysbaert Marc , Speybroeck Sara , Vanderelst Dieter
Published: February 2009

It has been suggested that acronyms like BBC are processed like real words. This claim has been based on improved performance with acronyms in the Reicher–Wheeler task, the letter string matching task, the visual feature integration task, and the N400 component in event-related potential (ERP) studies. Unfortunately, in all these tasks performance on acronyms resembled performance on pseudowords more than performance on words. To further assess the similarity of acronyms and words, we focused on the meaning of the acronyms and used masked priming to examine whether target words can be primed to the same extent with associatively related acronyms as with associatively related words. Such priming was possible at a stimulus onset asynchrony (SOA) of 84 ms. In addition, the priming of the acronyms did not depend on the letter case in which they were presented: The target word “books” was primed as much by isbn and iSbN as by ISBN.
Further analyses of the effects of practice, dropout, sex, socio-economic advantage, and recruitment cohort differences during the University of Manchester longitudinal study of cognitive change in old age
Authors: Rabbitt Patrick , Lunn Mary , Ibrahim Said , McInnes Lynn
Published: February 2009

A sample of 4,314 volunteers who, when first recruited, were aged from 41 to 93 years were quadrennially tested from 2 to 4 occasions during the next 4 to 20 years on the Cattell Culture Fair intelligence test, 2 tests of information-processing speed, the Wechsler Adult Intelligence Scale (WAIS) vocabulary test, and 3 memory tests. After significant effects of practice, sex, demographics, socio-economic advantage, and recruitment cohort had been identified and considered, performance on all tests declined with age. These age-related declines accelerated for the Cattell and WAIS, 2 tests of information speed, and 2 of the memory tests. For all tests individuals’ trajectories of age-related change diverged with increasing age but, unexpectedly, were not affected by demographic factors. Practice gains from an initial experience of the cognitive tests remained undiminished as the interval before the second experience increased from 4 to 8 + years.
DNA Damage Triggers p21WAF1-dependent Emi1 Down-Regulation That Maintains G2 Arrest
Authors: Lee Jinho , Kim Jin Ah , Barbier Valerie , Fotedar Arun , Fotedar Rati
Published: February 2009

Several regulatory proteins control cell cycle progression. These include Emi1, an anaphase-promoting complex (APC) inhibitor whose destruction controls progression through mitosis to G1, and p21WAF1, a cyclin-dependent kinase (CDK) inhibitor activated by DNA damage. We have analyzed the role of p21WAF1in G2-M phase checkpoint control and in prevention of polyploidy after DNA damage. After DNA damage, p21+/+cells stably arrest in G2, whereas p21−/−cells ultimately progress into mitosis. We report that p21 down-regulates Emi1 in cells arrested in G2 by DNA damage. This down-regulation contributes to APC activation and results in the degradation of key mitotic proteins including cyclins A2 and B1 in p21+/+cells. Inactivation of APC in irradiated p21+/+cells can overcome the G2 arrest. siRNA-mediated Emi1 down-regulation prevents irradiated p21−/−cells from entering mitosis, whereas concomitant down-regulation of APC activity counteracts this effect. Our results demonstrate that Emi1 down-regulation and APC activation leads to stable p21-dependent G2 arrest after DNA damage. This is the first demonstration that Emi1 regulation plays a role in the G2 DNA damage checkpoint. Further, our work identifies a new p21-dependent mechanism to maintain G2 arrest after DNA damage.
The Role of MRN in the S-Phase DNA Damage Checkpoint Is Independent of Its Ctp1-dependent Roles in Double-Strand Break Repair and Checkpoint Signaling
Authors: Porter-Goff Mary E. , Rhind Nicholas
Published: February 2009

The Mre11-Rad50-Nbs1 (MRN) complex has many biological functions: processing of double-strand breaks in meiosis, homologous recombination, telomere maintenance, S-phase checkpoint, and genome stability during replication. In the S-phase DNA damage checkpoint, MRN acts both in activation of checkpoint signaling and downstream of the checkpoint kinases to slow DNA replication. Mechanistically, MRN, along with its cofactor Ctp1, is involved in 5′ resection to create single-stranded DNA that is required for both signaling and homologous recombination. However, it is unclear whether resection is essential for all of the cellular functions of MRN. To dissect the various roles of MRN, we performed a structure–function analysis of nuclease dead alleles and potential separation-of-function alleles analogous to those found in the human disease ataxia telangiectasia-like disorder, which is caused by mutations in Mre11. We find that several alleles of rad32 (the fission yeast homologue of mre11), along with ctp1Δ, are defective in double-strand break repair and most other functions of the complex, but they maintain an intact S phase DNA damage checkpoint. Thus, the MRN S-phase checkpoint role is separate from its Ctp1- and resection-dependent role in double-strand break repair. This observation leads us to conclude that other functions of MRN, possibly its role in replication fork metabolism, are required for S-phase DNA damage checkpoint function.
Nucleolar Separation from Chromosomes duringAspergillus nidulansMitosis Can Occur Without Spindle Forces
Authors: Ukil Leena , De Souza Colin P. , Liu Hui-Lin , Osmani Stephen A.
Published: February 2009

How the nucleolus is segregated during mitosis is poorly understood and occurs by very different mechanisms during closed and open mitosis. Here we report a new mechanism of nucleolar segregation involving removal of the nucleolar-organizing regions (NORs) from nucleoli during Aspergillus nidulans mitosis. This involves a double nuclear envelope (NE) restriction which generates three NE-associated structures, two daughter nuclei (containing the NORs), and the nucleolus. Therefore, a remnant nucleolar structure can exist in the cytoplasm without NORs. In G1, this parental cytoplasmic nucleolus undergoes sequential disassembly releasing nucleolar proteins to the cytoplasm as nucleoli concomitantly reform in daughter nuclei. By depolymerizing microtubules and mutating spindle assembly checkpoint function, we demonstrate that a cycle of nucleolar “segregation” can occur without a spindle in a process termed spindle-independent mitosis (SIM). During SIM physical separation of the NOR from the nucleolus occurs, and NE modifications promote expulsion of the nucleolus to the cytoplasm. Subsequently, the cytoplasmic nucleolus is disassembled and rebuilt at a new site around the nuclear NOR. The data demonstrate the existence of a mitotic machinery for nucleolar segregation that is normally integrated with mitotic spindle formation but that can function without it.
Tetraspanin Proteins Regulate Membrane Type-1 Matrix Metalloproteinase-dependent Pericellular Proteolysis
Authors: Lafleur Marc A. , Xu Daosong , Hemler Martin E.
Published: February 2009

Membrane type-1 matrix metalloproteinase (MT1-MMP) supports tumor cell invasion through extracellular matrix barriers containing fibrin, collagen, fibronectin, and other proteins. Here, we show that simultaneous knockdown of two or three members of the tetraspanin family (CD9, CD81, and TSPAN12) markedly decreases MT1-MMP proteolytic functions in cancer cells. Affected functions include fibronectin proteolysis, invasion and growth in three-dimensional fibrin and collagen gels, and MMP-2 activation. Tetraspanin proteins (CD9, CD81, and TSPAN2) selectively coimmunoprecipitate and colocalize with MT1-MMP. Although tetraspanins do not affect the initial biosynthesis of MT1-MMP, they do protect the newly synthesized protein from lysosomal degradation and support its delivery to the cell surface. Interfering with MT1-MMP-tetraspanin collaboration may be a useful therapeutic approach to limit cancer cell invasion and metastasis.
Low‐dose nitroglycerin improves microcirculation in hospitalized patients with acute heart failure
Authors: den Uil Corstiaan A. , Lagrand Wim K. , Spronk Peter E. , van der Ent Martin , Jewbali Lucia S.D. , Brugts Jasper J. , Ince Can , Simoons Maarten L.
Published: February 2009

Aims

Impaired tissue perfusion is often observed in patients with acute heart failure. We tested whether low‐dose nitroglycerin (NTG) improves microcirculatory perfusion in patients admitted for acute heart failure.

Methods and results

In 20 acute heart failure patients, NTG was given as intravenous infusion at a fixed dose of 33 µg/min. Using Sidestream Dark Field (SDF) imaging, sublingual microvascular perfusion was evaluated before (T0, average of two baseline measurements) and 15 min after initiation of NTG (T1). In a subgroup of seven patients, SDF measurements were repeated after NTG had been stopped for 20 min. Capillaries were defined as microvessels with a diameter of <20 µm. Perfused capillary density (PCD) was determined as the parameter of tissue perfusion. Values are expressed as median and interquartile range (P25; P75). The median age of the subjects was 60 (52; 73) years, and 65% were male. Patients were stable before starting NTG. Nitroglycerin decreased central venous pressure [17 (13; 19) mmHg at T0 vs. 16 (13; 17) mmHg at T1, P = 0.03] and pulmonary capillary wedge pressure [23 (18; 31) mmHg at T0 vs. 19 (16; 25) mmHg at T1, P = 0.03]. It increased PCD [10.7 (9.9; 12.5) mm mm−2 at T0 vs. 12.4 (11.4; 13.6) mm mm−2 at T1, P = 0.01]. After cessation of NTG, PCD returned to baseline values (P = 0.04).

Conclusion

Low‐dose NTG significantly reduces cardiac filling pressures and improves microvascular perfusion in patients admitted for acute heart failure.
The influence of midwater hypoxia on nekton vertical migration
Authors: Parker-Stetter Sandra L. , Horne John K. , Langness Mariko M.
Published: February 2009

Parker-Stetter, S. L., Horne, J. K., and Langness, M. M. 2009. The influence of midwater hypoxia on nekton vertical migration. – ICES Journal of Marine Science, 66: 1296–1302. Hypoxia affects pelagic nekton, fish and large zooplankton, distributions in marine and fresh-water ecosystems. Bottom hypoxia is common, but midwater oxygen minimum layers (OMLs) may also affect nekton that undergo diel vertical migration (DVM). This study examined the response of pelagic nekton to an OML in a temperate fjord (Hood Canal, WA, USA). A 2006 study suggested that the OML created a prey refuge for zooplankton. Using acoustics (38 and 120 kHz), the 2007 night DVM patterns of nekton were quantified before (June, August) and during (September) an OML. All months had similar precrepuscular distributions (>50-m depth) of fish and invertebrates. During the September evening crepuscular period, a zooplankton layer migrated upwards (>1.5 m min−1), but the layer's rate of ascent slowed to <0.5 m min−1 when it reached the lower edge of the OML. The bottom edge of the layer then moved below the OML and remained there for 13 minutes before moving through the OML at >1.0 m min−1. As in June and August, fish in September followed the upward migration of the zooplankton layer to the surface, crossing through the OML. Our results suggest that the 2007 OML did not affect zooplankton or fish vertical distributions.
Combining acoustic and CUFES data for the quality control of fish-stock survey estimates
Authors: Petitgas Pierre , Goarant Anne , Massé Jacques , Bourriau Paul
Published: February 2009

Petitgas, P., Goarant, A., Massé, J., and Bourriau, P. 2009. Combining acoustic and CUFES data for the quality control of fish-stock survey estimates. – ICES Journal of Marine Science, 66: 1384–1390. Fish behaviour may cause bias in the acoustic estimates of fish stocks, which are difficult to assess using acoustic data alone. In contrast, fish eggs are passive particles that can be sampled with little avoidance. The combination of CUFES (continuous, underway, fish-egg sampler) data with acoustic sampling has the potential to cross-validate methods and address the question of relative bias. For anchovy in the Bay of Biscay, a CUFES has been used in conjunction with acoustics along the transect lines of IFREMER’s spring acoustic survey since 2001. Subsurface CUFES egg concentrations were converted to vertically integrated egg abundances using a biophysical model of egg vertical distribution. Then, a procedure similar to the daily egg production method (DEPM) was applied to map an index of daily egg production. Maps of fish abundance and egg production were combined to derive a second index of daily specific fecundity over the survey area, which served as a quality-control indicator of the survey estimate. Over the series of surveys analysed, the quality-control indicator provided two warnings and in both cases the reasons for these were identified.
Porcine endogenous retroviruses PERV A and A/C recombinant are insensitive to a range of divergent mammalian TRIM5α proteins including human TRIM5α
Authors: Wood Andrew , Webb Benjamin L. J. , Bartosch Birke , Schaller Torsten , Takeuchi Yasuhiro , Towers Greg J.
Published: February 2009

The potential risk of cross-species transmission of porcine endogenous retroviruses (PERV) to humans has slowed the development of xenotransplantation, using pigs as organ donors. Here, we show that PERVs are insensitive to restriction by divergent TRIM5α molecules despite the fact that they strongly restrict a variety of divergent lentiviruses. We also show that the human PERV A/C recombinant clone 14/220 reverse transcribes with increased efficiency in human cells, leading to significantly higher infectivity. We conclude that xenotransplantation studies should consider the danger of highly infectious TRIM5α-insensitive human-tropic PERV recombinants.
Identification of a response element in a herpesvirus saimiri mRNA recognized by the ORF57 protein
Authors: Colgan Kevin J. , Boyne James R. , Whitehouse Adrian
Published: February 2009

The herpesvirus saimiri (HVS) ORF57 protein binds viral RNA, enabling the efficient nuclear export of intronless viral mRNAs. However, it is not known how ORF57 recognizes these viral mRNAs. In this study, a systematic evolution of ligands by exponential enrichment (SELEX) approach was used to select RNA sequences that are preferentially bound by the ORF57 protein. Results identified a recurring motif, GAAGRG, within the majority of selected RNAs, which is also present in many late HVS mRNAs. RNA immunopreciptations demonstrated that disruption of this motif within a viral intronless RNA ablates ORF57 binding. These data suggest that the GAAGRG motif may be required within a HVS intronless mRNA for recognition by the ORF57 protein.
mtDNA mutation pattern in tumors and human evolution are shaped by similar selective constraints
Authors: Zhidkov Ilia , Livneh Erez A. , Rubin Eitan , Mishmar Dan
Published: February 2009

Multiple human mutational landscapes of normal and cancer conditions are currently available. However, while the unique mutational patterns of tumors have been extensively studied, little attention has been paid to similarities between malignant and normal conditions. Here we compared the pattern of mutations in the mitochondrial genomes (mtDNAs) of cancer (98 sequences) and natural populations (2400 sequences). De novo mtDNA mutations in cancer preferentially colocalized with ancient variants in human phylogeny. A significant portion of the cancer mutations was organized in recurrent combinations (COMs), reaching a length of seven mutations, which also colocalized with ancient variants. Thus, by analyzing similarities rather than differences in patterns of mtDNA mutations in tumor and human evolution, we discovered evidence for similar selective constraints, suggesting a functional potential for these mutations.
Alternative splicing of anciently exonized 5S rRNA regulates plant transcription factor TFIIIA
Authors: Fu Yan , Bannach Oliver , Chen Hao , Teune Jan-Hendrik , Schmitz Axel , Steger Gerhard , Xiong Liming , Barbazuk W. Brad
Published: February 2009

Identifying conserved alternative splicing (AS) events among evolutionarily distant species can prioritize AS events for functional characterization and help uncover relevant cis- and trans-regulatory factors. A genome-wide search for conserved cassette exon AS events in higher plants revealed the exonization of 5S ribosomal RNA (5S rRNA) within the gene of its own transcription regulator, TFIIIA (transcription factor for polymerase III A). The 5S rRNA-derived exon in TFIIIA gene exists in all representative land plant species but not in green algae and nonplant species, suggesting it is specific to land plants. TFIIIA is essential for RNA polymerase III-based transcription of 5S rRNA in eukaryotes. Integrating comparative genomics and molecular biology revealed that the conserved cassette exon derived from 5S rRNA is coupled with nonsense-mediated mRNA decay. Utilizing multiple independent Arabidopsis overexpressing TFIIIA transgenic lines under osmotic and salt stress, strong accordance between phenotypic and molecular evidence reveals the biological relevance of AS of the exonized 5S rRNA in quantitative autoregulation of TFIIIA homeostasis. Most significantly, this study provides the first evidence of ancient exaptation of 5S rRNA in plants, suggesting a novel gene regulation model mediated by the AS of an anciently exonized noncoding element.
Auxin and Ethylene Regulate Elongation Responses to Neighbor Proximity Signals Independent of Gibberellin and DELLA Proteins in Arabidopsis
Authors: Pierik Ronald , Djakovic-Petrovic Tanja , Keuskamp Diederik H. , de Wit Mieke , Voesenek Laurentius A.C.J.
Published: February 2009

Plants modify growth in response to the proximity of neighbors. Among these growth adjustments are shade avoidance responses, such as enhanced elongation of stems and petioles, that help plants to reach the light and outgrow their competitors. Neighbor detection occurs through photoreceptor-mediated detection of light spectral changes (i.e. reduced red:far-red ratio [R:FR] and reduced blue light intensity). We recently showed that physiological regulation of these responses occurs through light-mediated degradation of nuclear, growth-inhibiting DELLA proteins, but this appeared to be only part of the full mechanism. Here, we present how two hormones, auxin and ethylene, coregulate DELLAs but regulate shade avoidance responses through DELLA-independent mechanisms in Arabidopsis (Arabidopsis thaliana). Auxin appears to be required for both seedling and mature plant shoot elongation responses to low blue light and low R:FR, respectively. Auxin action is increased upon exposure to low R:FR and low blue light, and auxin inhibition abolishes the elongation responses to these light cues. Ethylene action is increased during the mature plant response to low R:FR, and this growth response is abolished by ethylene insensitivity. However, ethylene is also a direct volatile neighbor detection signal that induces strong elongation in seedlings, possibly in an auxin-dependent manner. We propose that this novel ethylene and auxin control of shade avoidance interacts with DELLA abundance but also controls independent targets to regulate adaptive growth responses to surrounding vegetation.
Leaf species identity and combination affect performance and oviposition choice of two container mosquito species
Authors: REISKIND MICHAEL H. , GREENE KRYSTLE L. , LOUNIBOS L. PHILIP
Published: February 2009

Abstract1. Resource diversity can be an important determinant of individual and population performance in insects. Fallen parts of plants form the nutritive base for many aquatic systems, including mosquito habitats, but the effect of plant diversity on mosquito production is poorly understood.

2. To determine the effects of diverse plant inputs on larval mosquitoes, experiments were conducted that examined how leaves ofVitis aestivalis,Quercus virginiana,Psychotria nervosa, andNephrolepis exaltataaffected the container speciesAedes triseriatusandAedes albopictus.

3. The hypothesis that leaf species have different effects on larval survival, growth, population performance, and oviposition choice of the two mosquito species was tested. The hypothesis that larval performance ofA. albopictusresponds additively to combinations of the four plant species was also tested.

4. Larval survival and growth differed among the four leaf species, and oviposition preference differed among the two leaf species examined. Measurements of population performance demonstrated significant variation between leaf treatments. Larval outcomes forA. albopictuswere significantly affected by leaf combination, and the hypothesis of additivity could be rejected.

5. These results indicate that individual leaf species are important in determining the performance of container dwelling mosquitoes, which grow larger and survive better on mixed‐species resource than expected, based on an additive model of resource utilisation.
Effect of spring defoliation pattern on the mid‐season production and morphology of swards of perennial ryegrass cultivars of different maturity
Authors: Hurley G. , O’Donovan M. , Gilliland T. J.
Published: February 2009

The effect of three spring management treatments on the vertical distribution of dry‐matter (DM) yield and morphology of four cultivars of perennial ryegrass (Fennema, Corbet, Foxtrot, Melle) in mid‐season was investigated. The management treatments commenced with cuts on 15 February (Early), 1 March (Medium) and 29 March (Late), each followed by a 28‐day re‐growth period until the next cut and then further 21‐day re‐growth periods after each subsequent cut. This created four mid‐season measurement periods across the management treatments at cut 3 (5 April–17 May), cut 5 (17 May–28 June), cut 6 (7 June–19 July) and cut 7 (28 June–9 August). Tiller and sheath height and their ratio, and leaf lamina length, were measured prior to the four mid‐season cuts (cuts 3, 5, 6 and 7) when measurements of DM yield and proportions of leaf, stem and dead material in three herbage horizons (Lower, 0–8 cm; Middle, 8–15 cm; Upper, >15 cm) were made. There were significant responses in mid‐season to the management treatments involved complex interactions between management treatment and cutting date, which modified seasonal patterns in DM yield and leaf:stem ratio. There were significantly greater tiller heights, tiller:sheath ratios and leaf lamina lengths but lower sheath heights from the Early to Late management treatments. The greatest responses in morphological characteristics occurred in the Middle horizon compared with either the Lower (predominately stem and pseudo‐stem), or the Upper (predominately leafy) horizons. Distribution of DM yield between Middle and Lower horizons but not overall DM yields was significantly affected by management treatment. Morphological differences between cultivars were mostly in the Middle horizon and ranking of the cultivars was similar across the management treatments. The different responses of cultivars Fennema and Melle showed that genotype had a significant effect regardless of management. The leafiest mid‐season swards were achieved by delaying initial spring defoliation in the cultivar which had the lowest stem production.
What explains property‐level variation in avian diversity? An inter‐disciplinary approach
Authors: Dallimer Martin , Acs Szvetlana , Hanley Nick , Wilson Paul , Gaston Kevin J. , Armsworth Paul R.
Published: February 2009

Modern farmed landscapes have witnessed substantial losses in biodiversity principally driven by the ecological changes associated with agricultural intensification. The causes of declines are often well described, but current management practices seem unlikely to deliver the EU‐wide policy objective of halting biodiversity losses.

Available evidence suggests that property‐scale factors can be influential in shaping patterns of biodiversity; however, they are rarely included in studies. Using 44 upland farms in the Peak District, northern England, we investigate the roles of ecological, agricultural and socio‐economic factors in determining avian species richness, for the first time incorporating information from all three influences.

Although we might expect that habitat quality would be the main factor affecting species richness, these variables had little influence. The landscape context of each property was unimportant in explaining any of the three measures of species richness (Total, Upland and Conservation Concern) used here. Within‐property habitat quality did explain 42% of the variation in richness of upland specialist species, but had no influence on Total or Conservation Concern Richness.

Socio‐economic circumstances of farms alone accounted for 24% of the variation in Total Richness, with land tenure and labour inputs important predictors of avian diversity. However, net income, rental value and the level of Agri‐Environment Scheme (AES) payments did not play a role in predicting species richness.

Farm management variables, including many of the main prescriptions outlined in AES, accounted for 23% of the variation in the richness of species of Conservation Concern, but less than 10% for Total Richness. However, no farm management variable alone was shown to offer better predictive power of avian species richness than random.

Synthesis and applications. The agricultural landscape is managed by a mosaic of landowners, all of whom can influence biodiversity conservation. We demonstrate that variation at the property‐scale in habitat, management and socio‐economics can feed into determining patterns of biodiversity. Currently, farmland conservation policy largely assumes that socio‐economic barriers and financial costs of implementing conservation measures are constant. Incorporating a consideration of the varying circumstances of individual properties into policy design is likely to result in substantial biodiversity gains.
Enhancement of transdermal delivery of phenylbutazone from liposomal gel formulations through deer skin
Authors: JAYACHANDRA BABU R. , RAVIS W. R. , DURAN S. H. , SCHUMACHER J. , COX E. , STAHL R. , JONES K. , JEAN LIN Y.‐J. , PHILLIP LEE Y.‐H. , PARSONS D. L. , PORTMAN E. M. , BROWN S. C. R.
Published: February 2009

Phenylbutazone (PBZ) is a nonsteroidal anti‐inflammatory drug used in the treatment of chronic pain and arthritis. Topical and transdermal administration of PBZ would be beneficial in large animals in terms of minimizing gastro‐intestinal ulcerations and other side effects, easy administration to legs and joints and minimizing the dose to reduce systemic toxicity of the drug. A topical liposomal preparation with different concentrations of a mono‐substituted alkyl amide (MSA) and PBZ was formulated. The formulations were evaluated by in vitro skin‐permeation kinetics through deer skin using Franz diffusion cells. By increasing drug loading from 1% to 5% w/w, the steady‐state flux (μg/cm2/h) of PBZ was increased twofold (P < 0.001). Similarly, by increasing the MSA concentration from 0% to 4%, the steady‐state flux (μg/cm2/h) of PBZ was increased twofold (P < 0.001). Overall, by increasing the drug load and the use of an appropriate amount of the penetration enhancer, the steady‐state flux of PBZ through skin was increased fourfold (P < 0.001). MSA at both 2% and 4% w/w concentrations significantly increased the skin levels of PBZ as compared with control (P < 0.05). In conclusion, MSA served as an effective skin‐penetration enhancer in the liposomal gel of PBZ for deer.
Thyroid function and changes in ultrasound morphology during antiviral therapy with pegylated interferon and ribavirin in patients with chronic hepatitis C
Authors: Friedrich‐Rust M. , Theobald J. , Zeuzem S. , Bojunga J.
Published: February 2009

Summary.  Thyroid disease is a common side‐effect of interferon‐based antiviral therapy for chronic hepatitis C, which may lead to dose reduction or discontinuation of therapy. The aim of this study was to investigate changes in ultrasound morphology, thyroid function, autoimmunity as well as predictive factors for the development of thyroid dysfunction in patients with hepatitis C virus infection treated with pegylated interferon‐α (PEG‐IFN‐α) and ribavirin. A total of 59 patients with chronic hepatitis C assigned for antiviral treatment with PEG‐IFN‐α and ribavirin were enrolled into the study. All patients were subjected to an ultrasound examination of the thyroid gland before treatment, and after 1, 3 and 6 months of antiviral therapy. In addition, thyroid function and autoimmune status were determined at fixed time‐points. Prior and during the course of therapy, 11 patients (19%) developed thyroid dysfunction (one hypothyroidism, nine hyperthyroidism, one hyperthyroidism followed by hypothyroidism). Hyperthyroidism was shown to be Graves’ disease in one patient and destructive thyroiditis in nine patients. Power‐Doppler ultrasound could differentiate between destructive thyroiditis and Graves’ disease. A reduction in echogenicity suggestive for a destructive process of the thyroid gland was observed even before changes in thyroid function of antibody status could be measured. Risk factors for the development of thyroid dysfunction were age, female gender, pre‐treatment thyroid volume, pre‐existing thyroglobulin/thyroid peroxidase antibodies and viral load. Changes in thyroid function are a common side‐effect occurring during antiviral therapy with PEG‐IFN‐α and ribavirin. Ultrasound presents a simple complementary tool for screening and follow‐up during antiviral therapy, which helps to differentiate between the common types of hyperthyroidism and gives insight into morphological changes of the thyroid gland during antiviral therapy.
An independent and prospective comparison of two commercial fibrosis marker panels (HCV FibroSURE and FIBROSpect II) during albinterferon alfa‐2b combination therapy for chronic hepatitis C
Authors: Patel K. , Benhamou Y. , Yoshida E. M. , Kaita K. D. , Zeuzem S. , Torbenson M. , Pulkstenis E. , Subramanian G. M. , McHutchison J. G.
Published: February 2009

Summary.  Noninvasive markers that accurately follow changes in fibrosis may provide alternatives to liver biopsy for assessment of histological endpoints of antiviral therapy in chronic hepatitis C (CHC). This study compared two commercially available serum marker panels (HCV FibroSURE™ and FIBROSpect II®) during interferon‐based therapy. Ninety‐five interferon‐naïve patients with genotype 1 CHC were enrolled in a phase 2b, active‐controlled study of albinterferon alfa‐2b/ribavirin for 48 weeks. Proprietary and simple biochemical marker panels were independently evaluated in serum before and during the study. Baseline liver biopsies were evaluated for METAVIR fibrosis by a single pathologist. Index scores were obtained for HCV FibroSURE (n = 84) and FIBROSpect II (n = 95); mean biopsy length: 17.8 ± 8.0 mm. For detecting fibrosis stages 2–4 (prevalence 23% [22/95] and 21% [18/84]), HCV FibroSURE and FIBROSpect II indicated high sensitivity (1.00 and 0.95, respectively), lower but comparable specificity (0.61 and 0.66, respectively), and a good area under the receiver operating characteristic curve (0.89 and 0.90, respectively). Simple indices had high indeterminate rates (31–40%) at baseline. Patients with a sustained virological response had lower baseline scores than nonresponders, and reduced median percent changes in index scores for HCV FibroSURE (−20.0%vs 2.9%; P = 0.14) and FIBROS Spect II (−6.8%vs 18.4%; P = 0.05). The panels demonstrated comparable performance characteristics for differentiating mild from moderate–severe stage disease in CHC. Lower index scores at baseline that continue to decline likely reflect reduced fibrogenesis activity in patients with successful antiviral responses to therapy.
Reverse genetic analysis of a putative, influenza virus M2 HXXXW‐like motif in the p7 protein of hepatitis C virus
Authors: Meshkat Z. , Audsley M. , Beyer C. , Gowans E. J. , Haqshenas G.
Published: February 2009

Summary.  The p7 protein of hepatitis C virus (HCV) has been classified into a family of viral proteins, designated viroporins that form ion channels. The M2 protein of influenza virus is the prototype viroporin and encodes a HXXXW motif that constitutes the main functional element of the M2 channels. Alignment of different p7 proteins revealed that a HXXXW sequence (positions 17–21) is also highly conserved among some HCV genotypes. To study the putative HXXXW motif in p7, five mutants of the Japanese fulminant hepatitis 1 strain of HCV that encoded H17A, H17G, H17E, Y21A and Y21W were generated. After transfection of human hepatoma cells with the mutant transcripts, unlike H17A and H17G that produced up to 1 log lower viral titres than wild type, H17E and Y21W showed slightly higher infectivity. In conclusion, this study demonstrated that the HXXXW sequence exists in the p7 proteins of some HCV genotypes and that H17 plays an important role in virus replication.
Interferon therapy in chronic hepatitis B reduces progression to cirrhosis and hepatocellular carcinoma: a meta‐analysis
Authors: Yang Y.‐F. , Zhao W. , Zhong Y.‐D. , Xia H.‐M. , Shen L. , Zhang N.
Published: February 2009

Summary.  Interferon (IFN) has been used in the treatment of chronic hepatitis B for decades. Beneficial effects including hepatitis B e antigen/HBV DNA seroclearance have been documented. However, the effect of treatment on the prevention of cirrhosis and hepatocellular carcinoma (HCC) development remains controversial. We conducted a meta‐analysis of available literature to evaluate whether IFN reduces the incidence of liver cirrhosis and HCC in patients with chronic hepatitis B. Twelve clinical controlled trials, including 2082 patients and comparing IFN with no treatment, were selected. Data on the incidence of liver cirrhosis and HCC in IFN treated and untreated patients were extracted from each study. The evaluation of preventive effectiveness was performed with an intention‐to‐treat method. The relative risk (RR) and 95% confidence interval (CI) of the main outcomes as a measure of efficacy were used. Meta‐analysis was performed using fixed‐effect or random‐effect methods, depending on absence or presence of significant heterogeneity. Analyses were performed with stata version 9.0 and Review Manager Version 4.2. Five studies including the data on development of liver cirrhosis, and eleven studies including the data on development of HCC were analyzed. There was no evidence for publication bias on the funnel plot or by Egger’s test, and the heterogeneity test indicated that the variation of trial‐specific RR was not statistically significant. A different incidence of liver cirrhosis and HCC was observed between treated and untreated patients. The RR of liver cirrhosis and HCC was 0.65 (95% CI: 0.47, 0.91) and 0.59 (95% CI: 0.43, 0.81), respectively. In conclusion, the results of this meta‐analysis indicate that IFN prevents or delays the development of liver cirrhosis and HCC in patients with chronic hepatitis B.