bluuebunny/crossref_metadata_2025_split huggingface dataset:
Base of skull recurrences after treatment of salivary gland cancer with perineural invasion reduced by postoperative radiotherapy
Authors: Chen A.M. , Garcia J. , Granchi P. , Bucci M.K. , Lee N.Y. 
Published: December 2009

Objectives:  To determine the effect of postoperative radiation therapy for salivary gland carcinomas in the presence of microscopic perineural invasion.Design and setting:  Retrospective review at an academic tertiary center.Participants:  One hundred and forty patients with pathological evidence of perineural invasion at the time of initial surgery for salivary gland carcinomas were analysed. Sixteen patients (11%) had major (named) nerve involvement. Ninety‐four patients (67%) received postoperative radiation therapy to the primary site, and the portal films of 65 of these patients were available for review.Main outcome measures:  The incidence of skull base recurrences among patients treated by surgery with or without postoperative radiation therapy.Results:  Ten patients experienced skull base recurrences. T4 disease and the omission of postoperative radiation therapy were identified as significant predictors of skull base recurrence. Postoperative radiation therapy reduced the actuarial probability of skull base recurrence from 15% to 5% (P = 0.03). The crude rates of skull base recurrence were 6% (2/35) and 10% (3/30), respectively, for patients whose skull base were and were not confirmed to be encompassed in the irradiation field. The 5‐year overall survival for patients who experienced a skull base recurrence was 19% compared to 91% for those who did not (P < 0.001).Conclusion:  The use of postoperative radiation therapy significantly reduced the incidence of skull base recurrence among salivary gland carcinoma patients with perineural invasion. Clin. Otolaryngol. 2009, 34, 539–545.
Correlation between subjective and objective evaluation of the nasal airway. A systematic review of the highest level of evidence
Authors: André R.F. , Vuyk H.D. , Ahmed A. , Graamans K. , Nolst Trenité G.J. 
Published: December 2009

Background:  There is no consensus about the value of objective measurements of nasal patency.Objective:  To assess the correlation between the subjective sense of nasal patency and the outcomes found with rhinomanometry and acoustic rhinometry.Type of review:  Structured literature search.Search strategy and evaluation method:  Review of English‐language articles in which correlations were sought between subjective nasal patency symptoms and objective scores as found with rhinomanometry [nasal airway resistance (NAR)] and acoustic rhinometry [minimal cross‐sectional area (MCA)]. Correlations were related to unilateral or combined assessment of nasal passages and to symptomatic nasal obstruction or unobstructed nasal breathing.Results:  Sixteen studies with a level of evidence II‐a or II‐b fit the inclusion criteria and were further analysed. Almost every possible combination of correlations or lack thereof in relation to the variables included was found. However, when obstructive symptoms were present, a correlation between the patency symptoms with nasal airway resistance and minimal crosssectional area was found more often than in the absence of symptoms. In cases of bilateral assessment a correlation was found almost as often as it was not between patency symptoms and total nasal airway resistance or combined minimal crosssectional areas, while in the limited amount of studies in which unilateral assessment was done a correlation was found each time between patency symptoms and nasal airway resistance.Conclusions:  The correlation between the outcomes found with rhinomanometry and acoustic rhinometry and an individual’s subjective sensation of nasal patency remains uncertain. Based on this review, it seems that the chance of a correlation is greater when each nasal passage is assessed individually and when obstructive symptoms are present. There still seems to be only a limited argument for the use of rhinomanometry or acoustic rhinometry in routine rhinologic practice or for quantifying surgical results. Clin. Otolaryngol. 2009, 34, 518–525.
Temporal patterns in the size of conservation land transactions
Authors: Davies Zoe G. , Kareiva Peter , Armsworth Paul R. 
Published: December 2009

AbstractThe full or partial acquisition of land remains a predominant focus of terrestrial conservation strategies. Non‐governmental organizations play an important role in habitat protection, yet few studies investigate their contribution to conservation investment. Here we examine temporal trends in the size of land transactions made by the world's largest land trust, The Nature Conservancy (TNC). We consider three dimensions of deal size (area, upfront cost, and relative cost per hectare) for two commonly used conservation approaches (fee simple acquisitions and conservation easements). Mean area of protected land parcels has been robust to the growing subdivision of properties for sale. Variation in the area and cost of transactions ranged between six and eight orders of magnitude, and increased through time as TNC undertook occasional large deals once established. Conservation planning approaches need to better account for the variation in deal sizes, and how this may change in response to dynamic budgets and priorities.
The relative contributions of changes in yield and land area to increasing crop output
Authors: LYWOOD WARWICK , PINKNEY JOHN , COCKERILL SAM 
Published: December 2009

AbstractGlobal average yields of the world's main food crops have increased over the past 50 years, and these yield increases have varied over time. For most crops, yields have grown significantly faster during periods of higher demand growth, and the contribution of yield growth to output growth has varied between crops. These variations reflect the range of measures available to growers to enhance yields of each crop, which are typically not fully deployed during periods of low demand growth and low relative price. This paper applies two methods using consistent, long‐term historic relationships to demonstrate that crop yield, area and price changes are not independent, and that area changes and yield changes in response to market signals are different for different crops and regions. One of these methods is used to show the expected percentages of exogenous estimates of overall demand growth that will be met by yield growth and by land use change for a range of biofuel crops. The estimated percentage of incremental output growth delivered by yield growth is 78% for EU cereals, with the remainder being met by area growth.
Cellular Immune Responses of Preterm Infants after Vaccination with Whole-Cell or Acellular Pertussis Vaccines
Authors: Vermeulen Françoise , Verscheure Virginie , Damis Eliane , Vermeylen Danièle , Leloux Gaëlle , Dirix Violette , Locht Camille , Mascart Françoise 
Published: December 2009

ABSTRACTBased on studies reporting specific antibody titers, it is recommended to vaccinate preterm infants againstBordetella pertussisaccording to their chronological age. However, as specific T-cell responses also are involved in the protection againstB. pertussis, we have determined whether highly preterm infants (<31 weeks) are able to mount these immune responses during vaccination. Forty-eight premature infants were vaccinated at 2, 3, and 4 months of their chronological age with an acellular (Pa;n= 24) or a whole-cell (Pw;n= 24) tetravalent diphtheria-tetanus-pertussis-polio vaccine, and blood samples were collected at 2, 3, and 6 months of age. Most of the Pa- and Pw-vaccinated infants developed at 3 or 6 months of age a gamma interferon (IFN-γ) response to theB. pertussisantigens, accompanied by an interleukin-5 (IL-5) and IL-13 secretion for the Pa-vaccinated infants. No association was found between a very low infant birth weight, the occurrence of severe infections, and corticosteroid treatment or the administration of gammaglobulins with a low level of antigen-induced IFN-γ secretion. We conclude that like full-term infants, most preterm infants are able to mount a specific cellular immune response to the administration of the first doses of an acellular or a whole-cell pertussis vaccine.
Rational Design and Evaluation of a Multiepitope Chimeric Fusion Protein with the Potential for Leprosy Diagnosis
Authors: Duthie Malcolm S. , Hay Marah N. , Morales Cecile Z. , Carter Lauren , Mohamath Raodoh , Ito Lucia , Oyafuso Luiza K. M. , Manini Marli I. P. , Balagon Marivic V. , Tan Esterlina V. , Saunderson Paul R. , Reed Steven G. , Carter Darrick 
Published: December 2009

ABSTRACT

Despite the reduction in the number of leprosy cases registered worldwide as a result of the widespread use of multidrug therapy, the number of new cases detected each year remains stable in many countries. This indicates that
Mycobacterium leprae
, the causative agent of leprosy, is still being transmitted and that, without an earlier diagnosis, transmission will continue and infection will remain a health problem. The current means of diagnosis of leprosy is based on the appearance of clinical symptoms, which in many cases occur after significant and irreversible nerve damage has occurred. Our recent work identified several recombinant antigens that are specifically recognized by leprosy patients. The goal of the present study was to produce and validate the reactivity of a chimeric fusion protein that possesses the antibody binding properties of several of these proteins. The availability of such a chimeric fusion protein will simplify future test development and reduce production costs. We first identified the antibody binding regions within our top five antigen candidates by performing enzyme-linked immunosorbent assays with overlapping peptides representing the amino acid sequences of each protein. Having identified these regions, we generated a fusion construct of these components (protein advances diagnostic of leprosy [PADL]) and demonstrated that the PADL protein retains the antibody reactivity of the component antigens. PADL was able to complement a protein that we previously produced (the leprosy IDRI [Infectious Disease Research Institute] diagnostic 1 [LID-1] protein) to permit the improved diagnosis of multibacillary leprosy and that had a good ability to discriminate patients with multibacillary leprosy from control individuals. A serological diagnostic test consisting of these antigens could be applied within leprosy control programs to reduce transmission and to limit the appearance of leprosy-associated disabilities and stigmatizing deformities by directing treatment.
Molecular Evidence of Persistent Epidemic and Evolution of Subgenotype B1 Coxsackievirus A16-Associated Hand, Foot, and Mouth Disease in China
Authors: Zhang Yong , Wang Dongyan , Yan Dongmei , Zhu Shuangli , Liu Jianfeng , Wang Haiyan , Zhao Shengcang , Yu Deshan , Nan Lijuan , An Junjing , Chen Li , An Hongqiu , Xu Aiqiang , Xu Wenbo 
Published: December 2009

ABSTRACTThe molecular epidemiology of CVA16 in China between 1999 and 2008 reflects a pattern of endemic cocirculation of clusters B1a and B1b within subgenotype B1 viruses. The annual evolution rate of CVA16 was estimated as approximately 0.91 × 10−2substitutions per synonymous nucleotide/year and is slightly lower than that of HEV71.
ICP27 Phosphorylation Site Mutants Display Altered Functional Interactions with Cellular Export Factors Aly/REF and TAP/NXF1 but Are Able To Bind Herpes Simplex Virus 1 RNA
Authors: Corbin-Lickfett Kara A. , Rojas Santos , Li Ling , Cocco Melanie J. , Sandri-Goldin Rozanne M. 
Published: December 2009

ABSTRACT

Herpes simplex virus 1 (HSV-1) protein ICP27 is a multifunctional regulatory protein that is phosphorylated. Phosphorylation can affect protein localization, protein interactions, and protein function. The major sites of ICP27 that are phosphorylated are serine residues 16 and 18, within a CK2 site adjacent to a leucine-rich region required for ICP27 export, and serine 114, within a PKA site in the nuclear localization signal. Viral mutants bearing serine-to-alanine or glutamic acid substitutions at these sites are defective in viral replication and gene expression. To determine which interactions of ICP27 are impaired, we analyzed the subcellular localization of ICP27 and its colocalization with cellular RNA export factors Aly/REF and TAP/NXF1. In cells infected with phosphorylation site mutants, ICP27 was confined to the nucleus even at very late times after infection. ICP27 did not colocalize with Aly/REF or TAP/NXF1, and overexpression of TAP/NXF1 did not promote the export of ICP27 to the cytoplasm. However,
in vitro
binding experiments showed that mutant ICP27 was able to bind to the same RNA substrates as the wild type. Nuclear magnetic resonance (NMR) analysis of the N terminus of ICP27 from amino acids 1 to 160, compared to mutants with triple substitutions to alanine or glutamic acid, showed that the mutations affected the overall conformation of the N terminus, such that mutant ICP27 was more flexible and unfolded. These results indicate that these changes in the structure of ICP27 altered
in vivo
protein interactions that occur in the N terminus but did not prevent RNA binding.
Novel Functions of the Alphavirus Nonstructural Protein nsP3 C-Terminal Region
Authors: Varjak Margus , Žusinaite Eva , Merits Andres 
Published: December 2009

ABSTRACT

The functions of the alphavirus-encoded nonstructural protein nsP3 during infection are poorly understood. In contrast, nsP1, nsP2, and nsP4 have known enzymatic activities and functions. A functional analysis of the C-terminal region of nsP3 of Semliki Forest virus revealed the presence of a degradation signal that overlaps with a sequence element located between nsP3 and nsP4 that is required for proteolytic processing. This element was responsible for the short half-life (1 h) of individually expressed nsP3, and it also was functionally transferable to other proteins. Inducible cell lines were used to express native nsP3 or truncated mutants. The removal of 10 C-terminal amino acid (aa) residues from nsP3 increased the half-life of the protein approximately 8-fold. While the deletion of 30 C-terminal aa residues resulted in a similar stabilization, this deletion also changed the cellular localization of nsP3. This truncated mutant no longer exhibited a punctate localization in the cytoplasm, but instead filamentous stretches could be formed around the nuclei of induced cells, suggesting the existence of an additional functional element upstream of the degradation signal. C-terminally truncated uncleavable polyprotein P12
CA
3del30 was localized diffusely, which is in contrast to P12
CA
3, which is known to be associated with vesicle membranes. The induction of nsP3 or its truncated forms reduced the efficiency of virus multiplication in corresponding cells by affecting different steps of the infection cycle. The expression of nsP3 or a mutant lacking the 10 C-terminal aa residues repressed the establishment of infection, while the expression of nsP3 lacking 30 C-terminal aa residues led to the reduced synthesis of subgenomic RNA.
Testing the Balanced Electrostatic Interaction Hypothesis of Hepatitis B Virus DNA Synthesis by Using an
In Vivo
Charge Rebalance Approach
Authors: Chua Pong Kian , Tang Fan-Mei , Huang Jyuan-Yuan , Suen Ching-Shu , Shih Chiaho 
Published: December 2009

ABSTRACT

Previously, a charge balance hypothesis was proposed to explain hepatitis B virus (HBV) capsid stability, assembly, RNA encapsidation, and DNA replication. This hypothesis emphasized the importance of a balanced electrostatic interaction between the positive charge from the arginine-rich domain (ARD) of the core protein (HBc) and the negative charge from the encapsidated nucleic acid. It remains unclear if any of the negative charge involved in this electrostatic interaction could come from the HBc protein
per se
, in addition to the encapsidated nucleic acid. HBc ARD IV mutant 173GG and ARD II mutant 173RR/R157A/R158A are arginine deficient and replication defective. Not surprisingly, the replication defect of ARD IV mutant 173GG can be rescued by restoring positively charged amino acids at the adjacent positions 174 and 175. However, most interestingly, it can be at least partially rescued by reducing negatively charged residues in the assembly domain, such as by glutamic acid-to-alanine (E-to-A) substitutions at position 46 or 117 and to a much lesser extent at position 113. Similar results were obtained for ARD II mutant 173RR/R157A/R158A. These amino acids are located on the inner surfaces of HBc icosahedral particles, and their acidic side chains point toward the capsid interior. For HBV DNA synthesis, the relative amount of positive versus negative charge in the electrostatic interactions is more important than the absolute amount of positive or negative charge. These results support the concept that balanced electrostatic interaction is important during the viral life cycle.
Inhibition of Sterol Biosynthesis Reduces Tombusvirus Replication in Yeast and Plants
Authors: Sharma Monika , Sasvari Zsuzsanna , Nagy Peter D. 
Published: December 2009

ABSTRACT

The replication of plus-strand RNA viruses depends on subcellular membranes. Recent genome-wide screens have revealed that the sterol biosynthesis genes
ERG25
and
ERG4
affected the replication of
Tomato bushy stunt virus
(TBSV) in a yeast model host. To further our understanding of the role of sterols in TBSV replication, we demonstrate that the downregulation of
ERG25
or the inhibition of the activity of
Erg25p
with an inhibitor (6-amino-2-
n
-pentylthiobenzothiazole; APB) leads to a 3- to 5-fold reduction in TBSV replication in yeast. In addition, the sterol biosynthesis inhibitor lovastatin reduced TBSV replication by 4-fold, confirming the importance of sterols in viral replication. We also show reduced stability for the p92
pol
viral replication protein as well as a decrease in the
in vitro
activity of the tombusvirus replicase when isolated from APB-treated yeast. Moreover, APB treatment inhibits TBSV RNA accumulation in plant protoplasts and in
Nicotiana benthamiana
leaves. The inhibitory effect of APB on TBSV replication can be complemented by exogenous stigmasterol, the main plant sterol, suggesting that sterols are required for TBSV replication. The silencing of
SMO1
and
SMO2
genes, which are orthologs of
ERG25
, in
N. benthamiana
reduced TBSV RNA accumulation but had a lesser inhibitory effect on the unrelated
Tobacco mosaic virus
, suggesting that various viruses show different levels of dependence on sterol biosynthesis for their replication.
Role of Untranslated Regions in Regulation of Gene Expression, Replication, and Pathogenicity of Newcastle Disease Virus Expressing Green Fluorescent Protein
Authors: Kim Shin-Hee , Samal Siba K. 
Published: December 2009

ABSTRACT
To gain insight into the role of untranslated regions (UTRs) in regulation of foreign gene expression, replication, and pathogenicity of Newcastle disease virus (NDV), a green fluorescent protein (GFP) gene flanked by 5′ and 3′ UTRs of each NDV gene was individually expressed by recombinant NDVs. UTRs of each gene modulated GFP expression positively or negatively. In particular, UTRs of the M and F genes enhanced levels of GFP expression at the junction of the P and M genes without altering replication of NDV, suggesting that UTRs could be used for enhanced expression of a foreign gene by NDV.
Stability of Murine Cytomegalovirus Genome after
In Vitro
and
In Vivo
Passage
Authors: Cheng Tammy P. , Valentine Mark C. , Gao Jian , Pingel Jeanette T. , Yokoyama Wayne M. 
Published: December 2009

ABSTRACT

While large DNA viruses are thought to have low mutation rates, only a small fraction of their genomes have been analyzed at the single-nucleotide level. Here, we defined the genetic stability of murine cytomegalovirus (MCMV) by whole-genome sequencing. Independently assembled sequences of three sister plaques showed only two single-base-pair substitutions after
in vitro
passage.
In vivo
-passaged MCMV likewise demonstrated low mutation rates, comparable to those after
in vitro
passage, indicating high genome stability of MCMV at the single-nucleotide level in the absence of obvious selection pressure.
HIV-1 Nef Inhibits Ruffles, Induces Filopodia, and Modulates Migration of Infected Lymphocytes
Authors: Nobile Cinzia , Rudnicka Dominika , Hasan Milena , Aulner Nathalie , Porrot Françoise , Machu Christophe , Renaud Olivier , Prévost Marie-Christine , Hivroz Claire , Schwartz Olivier , Sol-Foulon Nathalie 
Published: December 2009

ABSTRACTThe HIV-1 Nef protein is a pathogenic factor modulating the behavior of infected cells. Nef induces actin cytoskeleton changes and impairs cell migration toward chemokines. We further characterized the morphology, cytoskeleton dynamics, and motility of HIV-1-infected lymphocytes. By using scanning electron microscopy, confocal immunofluorescence microscopy, and ImageStream technology, which combines flow cytometry and automated imaging, we report that HIV-1 induces a characteristic remodeling of the actin cytoskeleton. In infected lymphocytes, ruffle formation is inhibited, whereas long, thin filopodium-like protrusions are induced. Cells infected with HIV withnefdeleted display a normal phenotype, and Nef expression alone, in the absence of other viral proteins, induces morphological changes. We also used an innovative imaging system to immobilize and visualize living individual cells in suspension. When combined with confocal “axial tomography,” this technique greatly enhances three-dimensional optical resolution. With this technique, we confirmed the induction of long filopodium-like structures in unfixed Nef-expressing lymphocytes. The cytoskeleton reorganization induced by Nef is associated with an important impairment of cell movements. The adhesion and spreading of infected cells to fibronectin, their spontaneous motility, and their migration toward chemokines (CXCL12, CCL3, and CCL19) were all significantly decreased. Therefore, Nef induces complex effects on the lymphocyte actin cytoskeleton and cellular morphology, which likely impacts the capacity of infected cells to circulate and to encounter and communicate with bystander cells.