bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of Separase induces aneuploidy and mammary tumorigenesis
Authors: Zhang Nenggang , Ge Gouquing , Meyer Rene , Sethi Sumita , Basu Dipanjan , Pradhan Subhashree , Zhao Yi-Jue , Li Xiao-Nan , Cai Wei-Wen , El-Naggar Adel K. , Baladandayuthapani Veerabhadran , Kittrell Frances S. , Rao Pulivarthi H. , Medina Daniel , Pati Debananda
Published: August 2008

Separase is an endopeptidase that separates sister chromatids by cleaving cohesin Rad21 during the metaphase-to-anaphase transition. Conditional expression of Separase in tetracycline-inducible diploid FSK3 mouse mammary epithelial cells with both p53 WT and mutant (Ser-233-234) alleles of unknown physiological significance develops aneuploidy within 5 days of Separase induction
in vitro
. Overexpression of Separase induces premature separation of chromatids, lagging chromosomes, and anaphase bridges. In an
in vivo
mouse mammary transplant model, induction of Separase expression in the transplanted FSK3 cells for 3–4 weeks results in the formation of aneuploid tumors in the mammary gland. Xenograft studies combined with histological and cytogenetic analysis reveal that Separase-induced tumors are clonal in their genomic complements and have a mesenchymal phenotype suggestive of an epithelial–mesenchymal transition. Induction of Separase resulted in trisomies for chromosomes 8, 15, and 17; monosomy for chromosome 10; and amplification of the distal region of chromosomes 8 and 11. Separase protein is found to be significantly overexpressed in human breast tumors compared with matched normal tissue. These results collectively suggest that Separase is an oncogene, whose overexpression alone in mammary epithelial cells is sufficient to induce aneuploidy and tumorigenesis in a p53 mutant background.
Replica exchange simulations of transient encounter complexes in protein–protein association
Authors: Kim Young C. , Tang Chun , Clore G. Marius , Hummer Gerhard
Published: August 2008

Recent paramagnetic relaxation enhancement (PRE) studies on several weakly interacting protein complexes have unequivocally demonstrated the existence of transient encounter complexes. Here, we present a computational method to study protein–protein binding by creating equilibrium ensembles that include both specific and nonspecific protein complexes. In a joint analysis of simulation and experiment we explore the physical nature and underlying physicochemical characteristics of encounter complexes involving three protein–protein interactions of the bacterial phosphotransferase system. Replica exchange Monte Carlo simulations using a coarse-grained energy function recover the structures of the specific complexes and produce binding affinities in good agreement with experiment. Together with the specific complex, a relatively small number of distinct nonspecific complexes largely accounts for the measured PRE data. The combined relative population of the latter is less than ∼10%. The binding interfaces of the specific and nonspecific complexes differ primarily in size but exhibit similar amino acid compositions. We find that the overall funnel-shaped energy landscape of complex formation is dominated by the specific complex, a small number of structured nonspecific complexes, and a diffuse cloud of loosely bound complexes connecting the specific and nonspecific binding sites with each other and the unbound state. Nonspecific complexes may not only accelerate the binding kinetics by enhancing the rate of success of random diffusional encounters but also play a role in protein function as alternative binding modes.
Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling
Authors: Breunig Joshua J. , Sarkisian Matthew R. , Arellano Jon I. , Morozov Yury M. , Ayoub Albert E. , Sojitra Sonal , Wang Baolin , Flavell Richard A. , Rakic Pasko , Town Terrence
Published: August 2008

Primary cilia are present on mammalian neurons and glia, but their function is largely unknown. We generated conditional homozygous mutant mice for a gene we termed
Stumpy
. Mutants lack cilia and have conspicuous abnormalities in postnatally developing brain regions, including a hypoplasic hippocampus characterized by a primary deficiency in neural stem cells known as astrocyte-like neural precursors (ALNPs). Previous studies suggested that primary cilia mediate sonic hedgehog (Shh) signaling. Here, we find that loss of ALNP cilia leads to abrogated Shh activity, increased cell cycle exit, and morphological abnormalities in ALNPs. Processing of Gli3, a mediator of Shh signaling, is also altered in the absence of cilia. Further, key mediators of the Shh pathway localize to ALNP cilia. Thus, selective targeting of Shh machinery to primary cilia confers to ALNPs the ability to differentially respond to Shh mitogenic signals compared to neighboring cells. Our data suggest these organelles are cellular “antennae” critically required to modulate ALNP behavior.
Short Article: Single-probe serial position recall: Evidence of modularity for olfactory, visual, and auditory short-term memory
Authors: Johnson Andrew J. , Miles Christopher
Published: August 2008

The present study examined and compared order memory for a list of sequentially presented odours, unfamiliar faces, and pure tones. Employing single-probe serial position recall and following a correction for a response bias, qualitatively different serial position functions were observed across stimuli. Participants demonstrated an ability to perform absolute order memory judgments for odours. Furthermore, odours produced an absence of serial position effects, unfamiliar faces produced both primacy and recency, and pure tones produced recency but not primacy. Such a finding is contrary to the proposal by Ward, Avons, and Melling (2005) that the serial position function is task, rather than modality, dependent. In contrast, the observed functions support a modular conceptualization of short-term memory (e.g., Andrade & Donaldson, 2007; Baddeley & Hitch, 1974), whereby separate modality-specific memorial systems operate. An alternative amodal interpretation is also discussed wherein serial position function disparities are accommodated via differences in the psychological distinctiveness of stimuli (Hay, Smyth, Hitch, & Horton, 2007).
Area, capacity and diameter versions of Schwarz’s Lemma
Authors: Burckel Robert , Marshall Donald , Minda David , Poggi-Corradini Pietro , Ransford Thomas
Published: August 2008

The now canonical proof of Schwarz’s Lemma appeared in a 1907 paper of Carathéodory, who attributed it to Erhard Schmidt. Since then, Schwarz’s Lemma has acquired considerable fame, with multiple extensions and generalizations. Much less known is that, in the same year 1907, Landau and Toeplitz obtained a similar result where the diameter of the image set takes over the role of the maximum modulus of the function. We give a new proof of this result and extend it to include bounds on the growth of the maximum modulus. We also develop a more general approach in which the size of the image is estimated in several geometric ways via notions of radius, diameter, perimeter, area, capacity, etc.
PathCase: pathways database system
Authors: Elliott Brendan , Kirac Mustafa , Cakmak Ali , Yavas Gokhan , Mayes Stephen , Cheng En , Wang Yuan , Gupta Chirag , Ozsoyoglu Gultekin , Meral Ozsoyoglu Zehra
Published: August 2008

Motivation: As the blueprints of cellular actions, biological pathways characterize the roles of genomic entities in various cellular mechanisms, and as such, their availability, manipulation and queriability over the web is important to facilitate ongoing biological research.

Results: In this article, we present the new features of PathCase, a system to store, query, visualize and analyze metabolic pathways at different levels of genetic, molecular, biochemical and organismal detail. The new features include: (i) a web-based system with a new architecture, containing a server-side and a client-side, and promoting scalability, and flexible and easy adaptation of different pathway databases, (ii) an interactive client-side visualization tool for metabolic pathways, with powerful visualization capabilities, and with integrated gene and organism viewers, (iii) two distinct querying capabilities: an advanced querying interface for computer savvy users, and built-in queries for ease of use, that can be issued directly from pathway visualizations and (iv) a pathway functionality analysis tool. PathCase is now available for three different datasets, namely, KEGG pathways data, sample pathways from the literature and BioCyc pathways for humans.

Availability: Available online at http://nashua.case.edu/pathways

Contact:  pathcase@case.edu
The Intensity–Pitch Relation Revisited: Monopolar Versus Bipolar Cochlear Stimulation
Authors: Arnoldner Christoph , Riss Dominik , Kaider Alexandra , Mair Alois , Wagenblast Jens , Baumgartner Wolf‐Dieter , Gstöttner Wolfgang , Hamzavi Jafar‐Sasan
Published: August 2008

Objective/Hypothesis: The very high speech perception scores now being achieved with cochlear implants have led to demands for similar levels of achievement in music perception and perception in noisy environments. One of the crucial factors in these fields is pitch perception. The aim of the present study was to investigate the extent to which pitch perception is influenced by the intensity of the stimulus, through the use of different stimulation modes (monopolar, bipolar) and different electrodes (lateral and perimodiolar).

Study Design: Sixteen postlingually deafened patients with an average implant use of 3.1 years were included in this study. All patients were using a Cochlear (CI24M, CI24R, CI24RE) cochlear implant.

Methods: Subjects were asked to compare the pitch of an intensity‐constant reference tone with the pitch of a test tone of varying intensity. The test was repeated for apical, mediocochlear, and basal channel locations, and also for monopolar and bipolar stimulation.

Results: It was found that in monopolar stimulation 87.5% and in bipolar stimulation 85.7% of the patients perceived a clear pitch change with changing intensity of the stimulus (Spearman correlation coefficients r < −0.3 or r > 0.3, respectively). A total of 73.1% of these patients perceived lower pitches with increasing intensity, 26.9% reported the opposite effect. No statistically significant difference in the intensity–pitch correlation could be found between mono‐ and bipolar stimulation. Neither the mean dynamic range nor the type of electrode used was found to be related to the correlation coefficient.

Conclusion: Although the majority of today's cochlear implant recipients perform well and the intensity–pitch relation in cochlear implant recipients is still poorly understood, rising demands on speech‐coding strategies may soon make a compensation of the pitch shifts desirable. Although the results of our study tend to argue against a peripheral mechanism, the exact origin of this phenomenon remains unclear.
Nasal Lavage With Mupirocin for the Treatment of Surgically Recalcitrant Chronic Rhinosinusitis
Authors: Uren Brent , Psaltis Alkis , Wormald Peter‐John
Published: August 2008

Objectives/Hypothesis: To examine the efficacy and tolerability of topical mupirocin for the management of surgically recalcitrant chronic rhinosinusitis (CRS) associated with Staphylococcus aureus infection.

Study Design: Prospective open‐label pilot study.

Methods: Patients with surgically recalcitrant CRS who had positive nasendoscopically guided cultures for Staphylococcus aureus were treated with twice daily nasal lavages containing 0.05% Mupirocin and lactated ringers salts. The duration of treatment was 3 weeks. Patients were assessed before and after treatment in terms of nasendoscopic findings, microbiology results, and Sinonasal Outcome Test (SNOT‐20) and visual analogue scale questionnaires.

Results: Fifteen of 16 patients had improved nasendoscopic findings after treatment. Twelve of 16 patients noted overall symptom improvement. Fifteen of 16 patients had negative swab results for Staphylococcus aureus after treatment. Only minimal adverse effects were experienced.

Conclusions: Nasal Lavage with 0.05% Mupirocin may represent an effective and well tolerated alternative treatment for postsurgical recalcitrant CRS.
Characteristics of Age‐Related Changes in Cultured Human Vocal Fold Fibroblasts
Authors: Chen Xia , Thibeault Susan L.
Published: August 2008

Objectives/Hypothesis: Normal human vocal fold fibroblast (hVFF) primary cell lines are unavailable commercially and are very difficult to acquire, subsequently little is known about their characteristics. The purpose of this study was to compare the morphological and proliferation characteristics and gene expression of hVFFs from different aged donors.

Study Design: In vitro.

Methods: We developed three normal hVFF primary cell lines from donors aged 21 (21T), 59 (59T) and 79 (79T) years. We characterized their morphological features, proliferative abilities, telomere lengths, and their functional gene expression by quantitative real‐time PCR.

Results: The 21T line maintained a typical spindle shape until passage 14 whereas 59T and 79T changed morphology to wider, shorter cells at passage 7. Proliferation rates were constant for the 21T through passage 14; 59T's proliferative half‐life was passage 9, whereas 79T maintained lower proliferation rates from passage 4. Gene expression levels for fibronectin, collagen I, collagen VI, procollagen I and elastin demonstrated similar patterns for all lines, however, relative amounts decreased with the age of donor. Telomere lengths did not show differences related with donor age.

Conclusions: hVFF primary cultures have limited proliferative capacity. The morphology, proliferation, differentiation, and gene expression levels of VFF can be affected by age, but senescence patterns were similar across the ages.
Is there a Relationship Between Eagle Syndrome and Cervicofacial Painful Soft Tissue Rheumatisms?
Authors: Zinnuroglu Murat , Ural Ahmet , Günendi Zafer , Meray Jale , Köybaşoğlu Ahmet
Published: August 2008

Objectives/Hypothesis: To investigate the incidence of locomotor system pathologies such as myofacial pain syndrome (MPS), fibromyalgia syndrome (FMS), and temporomandibular dysfunction in patients with Eagle Syndrome.

Study Design: Prospective study.

Patients and Methods: Fourteen patients with Eagle Syndrome, who were treated surgically, were enrolled in the study. Etiologic factors for cervicofacial pain were assessed, pain status was compared preoperatively and postoperatively using visual analogue scale. Palpation of tonsillar fossa, neck and shoulder examination, neurologic examination, evaluation of occlusion status, trigger points, and painful zones were done. Plain anteroposterior and lateral radiographs of the cervical spine were obtained and the lengths of the transverse processes of the seventh cervical vertebrae were measured bilaterally.

Results: MPS, FMS, and temporomandibular dysfunction were diagnosed in 9 (64.3%), 3 (21.4%), and 2 (14.3%) patients, respectively. Visual analogue scale scores decreased significantly after the surgical excision of elongated styloid processes (from 6.7 ± 2.3 to 2.1 ± 1.8), and all the complaints except for headache had diminished (P < .05). Lengths of transverse processes of seventh cervical vertebra were found to be correlated with the length of styloid process (right; r = 0.644, P = .024, left; r = 0.616, P = .033).

Conclusions: Cervicofacial pain is a common complaint in patients with Eagle Syndrome. It frequently coexists with rheumatic disorders resulting in chronic pain such as MPS and FMS. Even though Eagle Syndrome is a rare condition, it should be kept in mind in patients suffering from chronic cervicofacial pain that is refractory to treatment. Clinicians should be alert to diagnose and treat coexisting locomotor system disorders.
Titanium versus Nontitanium Prostheses in Ossiculoplasty
Authors: Coffey Charles S. , Lee Fu‐Shing , Lambert Paul R.
Published: August 2008

Objectives/Hypothesis: To compare the hearing outcomes and complications observed using either titanium or nontitanium prostheses in a 7‐year consecutive series of ossiculoplasties performed by a single surgeon.

Study Design: Retrospective.

Methods: A database of ossicular reconstruction surgeries was reviewed for preoperative and postoperative audiometric data including air and bone conduction thresholds at four frequencies and speech reception thresholds. Outcomes were evaluated at time points less than and greater than 6 months postoperatively. Baseline demographic and surgical characteristics and postoperative complications were also noted.

Results: A total of 105 cases had sufficient audiometric data available for analysis, including 80 performed with titanium and 25 with nontitanium implants. Follow‐up ranged from 1.2 to 74.2 months, with a mean of 14.9 months. Mean air‐bone gap at initial follow‐up was 21.7 dB in the nontitanium group and 15.4 dB in the titanium group; this difference was significant (P = .01). Postoperative air‐bone gap of less than 20 dB at initial follow‐up was achieved in 50.0% of nontitanium cases and 77.1% of titanium cases (P = .012). This difference in “success” rates persisted at longer follow‐up but did not achieve statistical significance. Mean speech reception thresholds at <6 months was 29.7 dB in the nontitanium group and 22.6 dB in the titanium group (P = .049). Extrusion was observed with two nontitanium prostheses (8.0%) and three titanium prostheses (3.8%) (P > .05).

Conclusions: Titanium ossicular prostheses provide hearing outcomes superior to those of nontitanium prostheses when evaluated within 6 months after ossiculoplasty.
Paradigms and Progress in Vocal Fold Restoration
Authors: Ford Charles N. , Baker Daniel C.
Published: August 2008

Science advances occur through orderly steps, puzzle‐solving leaps, or divergences from the accepted disciplinary matrix that occasionally result in a revolutionary paradigm shift. Key advances must overcome bias, criticism, and rejection. Examples in biological science include use of embryonic stem cells, recognition of Helicobacter pylori in the etiology of ulcer disease, and the evolution of species. Our work in vocal fold restoration reflects these patterns. We progressed through phases of tissue replacement with fillers and biological implants, to current efforts at vocal fold regeneration through tissue engineering, and face challenges of a new “systems biology” paradigm embracing genomics and proteomics.
Secondary Apoptosis of Spiral Ganglion Cells Induced by Aminoglycoside: Fas–Fas Ligand Signaling Pathway
Authors: Bae Woo Yong , Kim Lee Suk , Hur Dae Young , Jeong Sung Wook , Kim Jae Ryong
Published: August 2008

Objectives/Hypothesis: Hair cell loss results in the secondary loss of spiral ganglion neurons (SGNs), over a period of several weeks. The death of the SGNs themselves results from apoptosis. Previous studies have shown that several molecules are involved in the apoptosis of SGNs that occurred secondary to hair cell loss. However, the precise mechanism of apoptosis of the SGNs remains unclear. The aim of this study was to ascertain the secondary apoptosis of spiral ganglion cells induced by aminoglycoside and to investigate the role of the Fas–FasL signaling pathway using guinea pigs as an experimental animal model.

Study Design: Laboratory study using experimental animals.

Methods: Guinea pigs weighing 250 to 300 g (n = 21) from 3 to 4 weeks of age were used. Gentamicin (60 μL) was injected through a cochleostomy site on their left side. At 1 (n = 7), 2 (n = 7), and 3 (n = 7) weeks after gentamicin treatment, their cochleas were obtained from their temporal bone. Hematoxylin and eosin and terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labeling staining were performed to observe apoptosis. To investigate the involvement of the Fas–FasL signaling pathway in the secondary apoptosis of SGNs, we performed reverse transcription‐polymerase chain reaction (RT‐PCR), western blotting, and immunohistochemistry.

Results: A progressive loss of spiral ganglion cells with increasing time after gentamicin treatment was observed on light microscopic examination. Terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labeling staining demonstrated induction of apoptotic cell death in SGNs after gentamicin treatment. Expression of FasL increased over time after gentamicin treatment as determined by RT‐PCR and western blotting. On immunohistochemical staining, we observed the localization of FasL in the SGNs. The proapoptotic molecules Bax and Bad were increased, but levels of the antiapoptotic molecule Bcl‐2 were decreased at increasing survival times after gentamicin treatment on RT‐PCR. The gentamicin‐treated group displayed initial activation of caspase‐8 and increased the cleavage of caspase‐3, caspase‐8, and PARP protein in a time‐dependent manner.

Conclusions: The secondary apoptosis of SGNs could be a result of the apoptotic Fas–FasL signaling pathway. Blocking the Fas–FasL signaling pathway could be considered as a method for preventing secondary degeneration of SGNs, and further studies are needed to confirm this.
Identification of HLA-A*01- and HLA-A*02-restricted CD8+ T-cell epitopes shared among group B enteroviruses
Authors: Weinzierl Andreas O. , Rudolf Despina , Maurer Dominik , Wernet Dorothee , Rammensee Hans-Georg , Stevanović Stefan , Klingel Karin
Published: August 2008

Acute enteroviral infections ranging from meningitis, pancreatitis to myocarditis are common and normally well controlled by the host immune system comprising virus-specific CD8+ cytotoxic T lymphocytes (CTL). However, in some patients enteroviruses and especially coxsackieviruses of group B are capable of inducing severe chronic forms of diseases such as chronic myocarditis. Currently, it is not known whether divergences in the CTL-related immune response may contribute to the different outcome and course of enterovirus myocarditis. A pre-requisite for the study of CTL reactions in patients with acute and chronic myocarditis is the identification of CTL epitopes. In order to define dominant enterovirus CTL epitopes, we have screened, by using gamma interferon (IFN-γ) ELISPOT, 62 HLA-A*01- and 59 HLA-A*02-positive healthy blood donors for pre-existing CTL reactions against 12 HLA-A*01 and 20 HLA-A*02 predicted CTL epitopes derived from coxsackieviruses of group B. Positive CTL reactions were verified by FACS analysis in a combined major histocompatibility complex-tetramer IFN-γ staining. A total of 14.8 % of all donors reacted against one of the three identified epitopes MLDGHLIAFDY, YGDDVIASY or GIIYIIYKL. The HLA-A*02-restricted epitope ILMNDQEVGV was recognized by 25 % of all tested blood donors. For this peptide, we could demonstrate specific granzyme B secretion, a strong cytolytic potential and endogenous processing. All four epitopes were homologous in 36–92 % of group B enteroviruses, providing a strong basis for monitoring the divergence of T-cell-based immune responses in enterovirus-induced acute and chronic diseases.
A third genotype of the human parvovirus PARV4 in sub-Saharan Africa
Authors: Simmonds Peter , Douglas Jill , Bestetti Giovanna , Longhi Erika , Antinori Spinello , Parravicini Carlo , Corbellino Mario
Published: August 2008

PARV4 is a recently discovered human parvovirus widely distributed in injecting drug users in the USA and Europe, particularly in those co-infected with human immunodeficiency virus (HIV). Like parvovirus B19, PARV4 persists in previously exposed individuals. In bone marrow and lymphoid tissue, PARV4 sequences were detected in two sub-Saharan African study subjects with AIDS but without a reported history of parenteral exposure and who were uninfected with hepatitis C virus. PARV4 variants infecting these subjects were phylogenetically distinct from genotypes 1 and 2 (formerly PARV5) that were reported previously. Analysis of near-complete genome sequences demonstrated that they should be classified as a third (equidistant) PARV4 genotype. The availability of a further near-complete genome sequence of this novel genotype facilitated identification of conserved novel open reading frames embedded in the ORF2 coding sequence; one encoded a putative protein with identifiable homology to SAT proteins of members of the genusParvovirus.
A 3′-untranslated region polymorphism in the TBX21 gene encoding T-bet is a risk factor for genital herpes simplex virus type 2 infection in humans
Authors: Svensson Alexandra , Bergin Ann-Marie H. , Löwhagen Gun-Britt , Tunbäck Petra , Bellner Lars , Padyukov Leonid , Eriksson Kristina
Published: August 2008

It was recently shown that the transcription factor T-bet is crucial for adequate innate and acquired immune responses to genital herpes simplex virus type 2 (HSV-2) infection in mice. To test the possible genetic influence of variations in the TBX21 gene encoding T-bet on susceptibility to infection, this study evaluated the frequencies of five different single-nucleotide polymorphisms (SNPs) in the human TBX21 gene in 159 HSV-2-infected individuals and compared them with those in 186 healthy HSV-2-seronegative controls. The data showed that one variation (rs17244587) in the 3′-untranslated region of TBX21 was strongly associated with the incidence of genital HSV-2 infection. The frequency of the A allele at this position was 0.19 in the group of HSV-2-infected individuals compared with 0.05 in the group of uninfected controls (P=9.3×10−8). Furthermore, a homozygous AA genotype was found only among HSV-2-infected individuals and not in seronegative controls. These results indicate that the host genetic background may affect susceptibility to HSV-2 infection in humans, with TBX21 as a strong candidate gene.
Genomic and host range studies of Maruca vitrata nucleopolyhedrovirus
Authors: Chen Yun-Ru , Wu Chih-Yu , Lee Song-Tay , Wu Yan-Jheng , Lo Chu-Fang , Tsai Meng-Feng , Wang Chung-Hsiung
Published: August 2008

The complete genome of the Maruca vitrata nucleopolyhedrovirus (MaviNPV) isolated from the legume pod borer, Maruca vitrata (Lepidoptera: Pyralidae), was sequenced. It was found to be 111 953 bp in length, with an overall 39 % G+C content, and contained 126 open reading frames (ORFs) encoding predicted proteins of over 50 aa. The gene content and gene order of MaviNPV have the highest similarity to those of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and their shared homologous genes are 100 % collinear. In fact, MaviNPV seems to be a mini-AcMNPV that is native to Taiwan and possesses a smaller genome with fewer auxiliary genes than the AcMNPV type species. Except for one ORF (Mv74), all of the MaviNPV ORFs have homologues in the AcMNPV genome. MaviNPV is the first lepidopteran-specific baculovirus to lack homologues of vfgf and odv-e66. In addition, MaviNPV lacks the baculovirus repeat ORF (bro) gene that corresponds to AcMNPV ORF2. Five homologous regions (hrs) were located within the MaviNPV genome, and these contained a total of 44 imperfect palindromes. Phylogenetic analysis of the whole genome revealed that MaviNPV was separated from the common ancestor of AcMNPV and Bombyx mori nucleopolyhedrovirus before these two viral species diverged from each other. Moreover, replication of MaviNPV in several cell lines and an egfp–MaviNPV infection assay revealed that IPLB-LD-652Y cells are only partially permissive to MaviNPV, which supports our conclusion that MaviNPV is a distinct species of the group I lepidopteran NPVs.
Resistance to superinfection by a vigorously replicating, uncloned stock of simian immunodeficiency virus (SIVmac251) stimulates replication of a live attenuated virus vaccine (SIVmacC8)
Authors: Berry Neil , Stebbings Richard , Ferguson Debbie , Ham Claire , Alden Jack , Brown Stuart , Jenkins Adrian , Lines Jenny , Duffy Laura , Davis Leanne , Elsley William , Page Mark , Hull Robin , Stott Jim , Almond Neil
Published: August 2008

Vaccination with live attenuated simian immunodeficiency virus (SIVmacC8) confers potent, reproducible protection against homologous wild-type virus challenge (SIVmacJ5). The ability of SIVmacC8 to confer resistance to superinfection with an uncloned ex vivo derivative of SIVmac251 (SIVmac32H/L28) was investigated. In naïve, Mauritian-derived cynomolgus macaques (Macaca fascicularis), SIVmac32H/L28 replicated to high peak titres (>108 SIV RNA copies ml−1), persisted at high levels and induced distinctive pathology in lymphoid tissues. In cynomolgus macaques vaccinated with SIVmacC8, no evidence of detectable superinfection was observed in 3/8 vaccinates following challenge 3 or 20 weeks later with SIVmac32H/L28. Analyses after SIVmac32H/L28 challenge revealed a significant reduction in viral RNA (P<0.001) and DNA levels between 20 week vaccinates and challenge controls. Amongst 3 week vaccinates, less potent protection was observed. However, analysis of env from breakthrough virus indicated >99 % sequence similarity with the vaccine virus. Highly sensitive PCR assays that distinguish vaccine and challenge virus stocks demonstrated restimulation of replication of the vaccine virus SIVmacC8 in the face of potent protection against a vigorous, homologous challenge virus. Vaccine-induced antiviral neutralizing antibodies and anti-Nef CD8+ cytotoxic T cell responses did not correlate with the outcome of the challenge. Defining the mechanism of vaccine protection will need to account for the effective control of a genetically closely related challenge virus whilst remaining unable to suppress replication of the pre-existing vaccine virus. The role of innate and intrinsic anti-retroviral immunity in the protection conferred by live attenuated SIV vaccines warrants careful study.
Phylogeographical structure and evolutionary history of two Buggy Creek virus lineages in the western Great Plains of North America
Authors: Padhi Abinash , Moore Amy T. , Brown Mary Bomberger , Foster Jerome E. , Pfeffer Martin , Gaines Kathryn P. , O'Brien Valerie A. , Strickler Stephanie A. , Johnson Allison E. , Brown Charles R.
Published: August 2008

Buggy Creek virus (BCRV) is an unusual arbovirus within the western equine encephalitis complex of alphaviruses. Associated with cimicid swallow bugs (Oeciacus vicarius) as its vector and the cliff swallow (Petrochelidon pyrrhonota) and house sparrow (Passer domesticus) as its amplifying hosts, this virus is found primarily in the western Great Plains of North America at spatially discrete swallow nesting colonies. For 342 isolates collected in Oklahoma, Nebraska, Colorado and North Dakota, from 1974 to 2007, we sequenced a 2076 bp region of the 26S subgenomic RNA structural glycoprotein coding region, and analysed phylogenetic relationships, rates of evolution, demographical histories and temporal genetic structure of the two BCRV lineages found in the Great Plains. The two lineages showed distinct phylogeographical structure: one lineage was found in the southern Great Plains and the other in the northern Great Plains, and both occurred in Nebraska and Colorado. Within each lineage, there was additional latitudinal division into three distinct sublineages. One lineage is showing a long-term population decline. In comparing sequences taken from the same sites 8–30 years apart, in one case one lineage had been replaced by the other, and in the other cases there was little evidence of the same haplotypes persisting over time. The evolutionary rate of BCRV is in the order of 1.6–3.6×10−4substitutions per site per year, similar to that estimated for other temperate-latitude alphaviruses. The phylogeography and evolution of BCRV could be better understood once we determine the nature of the ecological differences between the lineages.
Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines
Authors: See Raymond H. , Petric Martin , Lawrence David J. , Mok Catherine P. Y. , Rowe Thomas , Zitzow Lois A. , Karunakaran Karuna P. , Voss Thomas G. , Brunham Robert C. , Gauldie Jack , Finlay B. Brett , Roper Rachel L.
Published: August 2008

Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.
Me Tri virus: a Semliki Forest virus strain from Vietnam?
Authors: Tan Le Van , Ha Do Quang , Hien Vo Minh , van der Hoek Lia , Farrar Jeremy , de Jong Menno D.
Published: August 2008

Me Tri virus (MTV) is a member of the Semliki Forest virus (SFV) complex in the genus Alphavirus, first isolated from Culex tritaeniorhynchus mosquitoes in Vietnam in 1971 and described as a newly recognized alphavirus, based on antigenic characterization. However, based on a partial nucleotide sequence of the E1 envelope glycoprotein gene, it has recently been argued that MTV may represent a variant of SFV rather than a separate species. To enable definitive classification, we determined the complete genome sequence of MTV from original virus stock. Nucleotide homology, as well as phylogenetic analyses based on whole and partial genome sequences confirmed that MTV is an isolate of SFV. Notable differences to other reported SFV sequences included a 122 nt insertion at the 5′ non-translated region (NTR), likely resulting from homologous recombination of part of the nsP2 gene, and differences in the sequence length of the 3′ NTR. To our knowledge, this is the first and only documentation of SFV isolation outside Africa. Further research is needed to clarify whether SFV continues to circulate in Vietnam.
Recombination, decreased host specificity and increased mobility may have driven the emergence of maize streak virus as an agricultural pathogen
Authors: Varsani Arvind , Shepherd Dionne N. , Monjane Adérito L. , Owor Betty E. , Erdmann Julia B. , Rybicki Edward P. , Peterschmitt Michel , Briddon Rob W. , Markham Peter G. , Oluwafemi Sunday , Windram Oliver P. , Lefeuvre Pierre , Lett Jean-Michel , Martin Darren P.
Published: August 2008

Maize streak virus (MSV; family Geminiviridae, genus Mastrevirus), the causal agent of maize streak disease, ranks amongst the most serious biological threats to food security in subSaharan Africa. Although five distinct MSV strains have been currently described, only one of these – MSV-A – causes severe disease in maize. Due primarily to their not being an obvious threat to agriculture, very little is known about the ‘grass-adapted’ MSV strains, MSV-B, -C, -D and -E. Since comparing the genetic diversities, geographical distributions and natural host ranges of MSV-A with the other MSV strains could provide valuable information on the epidemiology, evolution and emergence of MSV-A, we carried out a phylogeographical analysis of MSVs found in uncultivated indigenous African grasses. Amongst the 83 new MSV genomes presented here, we report the discovery of six new MSV strains (MSV-F to -K). The non-random recombination breakpoint distributions detectable with these and other available mastrevirus sequences partially mirror those seen in begomoviruses, implying that the forces shaping these breakpoint patterns have been largely conserved since the earliest geminivirus ancestors. We present evidence that the ancestor of all MSV-A variants was the recombinant progeny of ancestral MSV-B and MSV-G/-F variants. While it remains unknown whether recombination influenced the emergence of MSV-A in maize, our discovery that MSV-A variants may both move between and become established in different regions of Africa with greater ease, and infect more grass species than other MSV strains, goes some way towards explaining why MSV-A is such a successful maize pathogen.
Specific betapapillomaviruses associated with squamous cell carcinoma of the skin inhibit UVB-induced apoptosis of primary human keratinocytes
Authors: Struijk Linda , van der Meijden Els , Kazem Siamaque , ter Schegget Jan , de Gruijl Frank R. , Steenbergen Renske D. M. , Feltkamp Mariet C. W.
Published: August 2008

Epidemiological studies have shown an association between infections by specific betapapillomaviruses, such as human papillomavirus (HPV) types 5 and 8, and cutaneous squamous cell carcinoma (SCC). The role of betapapillomaviruses in the development of cutaneous SCC is, however, still enigmatic. The ability to inhibit UVB-induced apoptosis, as demonstrated for HPV5 in vitro, may be important in this respect, as survival of DNA-damaged and mutated cells increases the risk of transformation. The aim of this study was to assess whether inhibition of UVB-induced apoptosis is a general property of betapapillomaviruses and to identify apoptotic factors that are potentially involved in this process. Primary human keratinocytes transduced with E6 and E7 of selected betapapillomaviruses (HPV5, HPV8, HPV15, HPV20, HPV24 and HPV38) were characterized and subjected to UVB irradiation. HPV8- and HPV20-expressing keratinocytes in particular showed fewer signs of apoptosis, as demonstrated by lower levels of active caspase 3, less enzymic caspase activity and less DNA fragmentation. The observed inhibition of UVB-induced apoptosis was mediated by E6 and coincided with reduced steady-state expression of the pro-apoptotic protein Bax. In conclusion, E6 of HPV8 and HPV20 reduces the apoptotic responses upon UVB irradiation when expressed in primary human keratinocytes. Infections with HPV8 and HPV20 may therefore augment the carcinogenic effect of UV radiation and potentially contribute to oncogenic transformation of the skin.
Wages and Wage Determination in 2003
Authors: Watts Martin J. , Mitchell William
Published: August 2008

There was evidence of a very modest acceleration of wage growth in late 2003. The workplace reform agenda slowed in 2003, with the federal government attempting to outlaw any apparent manifestations of union power, such as pattern bargaining and bargaining fees, through legislative reform. No real progress was made with respect to family friendly initiatives, which might challenge the managerial prerogative for determining hours and other conditions of employment.
Industrial Legislation in 2003
Authors: Riley Joellen
Published: August 2008

Despite the promise of cataclysmic change, 2003 saw very few, and very moderate reforms to industrial laws. The great debates—about a unitary industrial relations system, greater legal discipline for the building and construction industry, paid maternity leave, compulsory individual contracts in the higher education sector—left no lasting footprints in 2003. The most significant reform, achieved at the very end of the year, was the enactment of more safety net protection for Victorian workers. Otherwise, legislative change represented small incremental steps. This review notes the highlights from the year’s debates, and explains the changes that were actually introduced.
Major Tribunal Decisions in 2003
Authors: Catanzariti Joseph , Shariff Yaseen
Published: August 2008

The authors review the major decisions of the previous year. The review is focussed upon decisions that in some way affected or are likely to affect individual rights and obligations more so than collective ones. First, the article offers an analysis of the concept of joint employment and its potential application in Australian courts and tribunals. Second, the High Court’s ruling in respect of the duty owed by employers to their employees’ children is considered. The authors comment that the decision is indicative of the ever expanding duty of care owed by employers. Third, the authors analyse a decision that considers the application of the Trade Practices Act 1974 to employment matters. Fourth, a decision of the Queensland District Court is reviewed because it is the first decision of an Australian court recognising an actionable right to privacy. The authors note that this decision is subject to appeal and therefore is likely to be scrutinised by superior courts. Finally, the authors comment that the growth in the assertion of individual rights raises important cultural challenges for collective organisations, which are likely to be ventilated in the next 12 months through some important test cases.
Phylogeny of the great cats (Felidae: Pantherinae), and the influence of fossil taxa and missing characters
Authors: Christiansen Per
Published: August 2008

Molecular phylogenetic studies of the extant Pantherinae have resulted in a variety of different hypotheses of relationships. This study presents the results of a cladistic study encompassing 45 osteological and dental characters in the skull and mandible, as well as 13 soft‐tissue and behavioural characters. Analyzing extant pantherines with osteological data only resulted in two equally parsimonious trees, which differed only with respects to the jaguar, a taxon which shows morphological affinity to the tiger as well as the lion + leopard. Addition of soft‐tissue characters resolved this ambiguity, and led to markedly improved bootstrap values. The inclusion of fossil taxa did not have an impact on topology, but was important for a correct understanding of character evolution, due to the fossils having a combination of characters unlike those of any extant taxon. The clouded leopard is the most basal pantherine, followed by the snow leopard. The large pantherines are a well supported group, to which the snow leopard does not belong, contrary to some molecular studies. Panthera palaeosinensis is no tiger, but may be close to the stem group from which the tiger evolved. P. atrox and P. spelaea are not on the lion lineage, as traditionally assumed, but are successive outgroups to the lion + leopard, although the position of P. spelaea is tentative, but is supported by other lines of evidence such as brain anatomy.

© The Willi Hennig Society 2008.
The relative sensitivity of different alignment methods and character codings in sensitivity analysis
Authors: Simmons Mark P. , Müller Kai F. , Webb Colleen T.
Published: August 2008

Sensitivity analysis provides a way to measure robustness of clades in sequence‐based phylogenetic analyses to variation in alignment parameters rather than measuring their branch support. We compared three different approaches to multiple sequence alignment in the context of sensitivity analysis: progressive pairwise alignment, as implemented in MUSCLE; simultaneous multiple alignment of sequence fragments, as implemented in DCA; and direct optimization followed by generation of the implied alignment(s), as implemented in POY. We set out to determine the relative sensitivity of these three alignment methods using rDNA sequences and randomly generated sequences. A total of 36 parameter sets were used to create the alignments, varying the transition, transversion, and gap costs. Tree searches were performed using four different character‐coding and weighting approaches: the cost function used for alignment or equally weighted parsimony with gap positions treated as missing data, separate characters, or as fifth states. POY was found to be as sensitive, or more sensitive, to variation in alignment parameters than DCA and MUSCLE for the three empirical datasets, and POY was found to be more sensitive than MUSCLE, which in turn was found to be as sensitive, or more sensitive, than DCA when applied to the randomly generated sequences when sensitivity was measured using the averaged jackknife values. When significant differences in relative sensitivity were found between the different ways of weighting character‐state changes, equally weighted parsimony, for all three ways of treating gapped positions, was less sensitive than applying the same cost function used in alignment for phylogenetic analysis. When branch support is incorporated into the sensitivity criterion, our results favour the use of simultaneous alignment and progressive pairwise alignment using the similarity criterion over direct optimization followed by using the implied alignment(s) to calculate branch support.
Clade support measures and their adequacy
Authors: Grant Taran , Kluge Arnold G.
Published: August 2008

In addition to hypothesis optimality, the evaluation of clade (group, edge, split, node) support is an important aspect of phylogenetic analysis. Here we clarify the logical relationship between support and optimality and formulate adequacy conditions for support measures. Support, S, and optimality, O, are both empirical knowledge claims about the strength of hypotheses, h1, h2, …hn, in relation to evidence, e, given background knowledge, b. Whereas optimality refers to the absolute strength of hypotheses, support refers to the relative strength of hypotheses. Consequently, support and optimality are logically related such that they vary in direct proportion to each other, S(h | e,b) ∝ O(h | e,b). Furthermore, in order for a support measure to be objective it must quantify support as a function of explanatory power. For example, Goodman–Bremer support and ratio of explanatory power (REP) support satisfy the adequacy requirement S(h | e,b) ∝ O(h | e,b) and calculate support as a function of explanatory power. As such, these are adequate measures of objective support. The equivalent measures for statistical optimality criteria are the likelihood ratio (or log‐likelihood difference) and likelihood difference support measures for maximum likelihood and the posterior probability ratio and posterior probability difference support measures for Bayesian inference. These statistical support measures satisfy the adequacy requirement S(h | e,b) ∝ O(h | e,b) and to that extent are internally consistent; however, they do not quantify support as a function of explanatory power and therefore are not measures of objective support. Neither the relative fit difference (RFD; relative GB support) nor any of the parsimony (bootstrap and jackknife character resampling) or statistical [bootstrap character resampling, Markov chain Monte Carlo (MCMC) clade frequencies] support measures based on clade frequencies satisfy the adequacy condition S(h | e,b) ∝ O(h | e,b) or calculate support as a function of explanatory power. As such, they are not adequate support measures.

© The Willi Hennig Society 2008.