bluuebunny/crossref_metadata_2025 huggingface dataset:
The day/night switch in KaiC, a central oscillator component of the circadian clock of cyanobacteria
Authors: Kim Yong-Ick , Dong Guogang , Carruthers Carl W. , Golden Susan S. , LiWang Andy
Published: August 2008

The circadian oscillator of the cyanobacterium
Synechococcus elongatus
is composed of only three proteins, KaiA, KaiB, and KaiC, which, together with ATP, can generate a self-sustained ≈24 h oscillation of KaiC phosphorylation for several days. KaiA induces KaiC to autophosphorylate, whereas KaiB blocks the stimulation of KaiC by KaiA, which allows KaiC to autodephosphorylate. We propose and support a model in which the C-terminal loops of KaiC, the “A-loops”, are the master switch that determines overall KaiC activity. When the A-loops are in their buried state, KaiC is an autophosphatase. When the A-loops are exposed, however, KaiC is an autokinase. A dynamic equilibrium likely exists between the buried and exposed states, which determines the steady-state level of phosphorylation of KaiC. The data suggest that KaiA stabilizes the exposed state of the A-loops through direct binding. We also show evidence that if KaiA cannot stabilize the exposed state, KaiC remains hypophosphorylated. We propose that KaiB inactivates KaiA by preventing it from stabilizing the exposed state of the A-loops. Thus, KaiA and KaiB likely act by shifting the dynamic equilibrium of the A-loops between exposed and buried states, which shifts the balance of autokinase and autophosphatase activities of KaiC. A-loop exposure likely moves the ATP closer to the sites of phosphorylation, and we show evidence in support of how this movement may be accomplished.
Regulation of the SigH stress response regulon by an essential protein kinase in
Mycobacterium tuberculosis
Authors: Park Sang Tae , Kang Choong-Min , Husson Robert N.
Published: August 2008

SigH is a key regulator of an extensive transcriptional network that responds to oxidative, nitrosative, and heat stresses in
Mycobacterium tuberculosis
, and this sigma factor is required for virulence in animal models of infection. SigH is negatively regulated by RshA, its cognate anti-sigma factor, which functions as a stress sensor and redox switch. While RshA provides a direct mechanism for sensing stress and activating transcription, bacteria use several types of signal transduction systems to sense the external environment.
M. tuberculosis
encodes several serine-threonine protein kinase signaling molecules, 2 of which, PknA and PknB, are essential and have been shown to regulate cell morphology and cell wall synthesis. In this work, we demonstrate that SigH and RshA are phosphorylated
in vitro
and
in vivo
by PknB. We show that phosphorylation of RshA, but not SigH, interferes with the interaction of these 2 proteins
in vitro
. Consistent with this finding, negative regulation of SigH activity by RshA
in vivo
is partially relieved in strains in which
pknB
is over-expressed, resulting in increased resistance to oxidative stress. These findings demonstrate an interaction between the signaling pathways mediated by PknB and the stress response regulon controlled by SigH. The intersection of these apparently discrete regulatory systems provides a mechanism by which limited activation of the SigH-dependent stress response in
M. tuberculosis
can be achieved. Coordination of the PknB and SigH regulatory pathways through phosphorylation of RshA may lead to adaptive responses that are important in the pathogenesis of
M. tuberculosis
infection.
Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids
Authors: Agbaga Martin-Paul , Brush Richard S. , Mandal Md Nawajes A. , Henry Kimberly , Elliott Michael H. , Anderson Robert E.
Published: August 2008

Stargardt-like macular dystrophy (STGD3) is a dominantly inherited juvenile macular degeneration that eventually leads to loss of vision. Three independent mutations causing STGD3 have been identified in exon six of a gene named
Elongation of very long chain fatty acids 4
(
ELOVL4
). The ELOVL4 protein was predicted to be involved in fatty acid elongation, although evidence for this and the specific step(s) it may catalyze have remained elusive. Here, using a gain-of-function approach, we provide direct and compelling evidence that ELOVL4 is required for the synthesis of C28 and C30 saturated fatty acids (VLC-FA) and of C28-C38 very long chain polyunsaturated fatty acids (VLC-PUFA), the latter being uniquely expressed in retina, sperm, and brain. Rat neonatal cardiomyocytes and a human retinal epithelium cell line (ARPE-19) were transduced with recombinant adenovirus type 5 carrying mouse
Elovl4
and supplemented with 24:0, 20:5n3, or 22:5n3. The 24:0 was elongated to 28:0 and 30:0; 20:5n3 and 22:5n3 were elongated to a series of C28-C38 PUFA. Because retinal degeneration is the only known phenotype in STGD3 disease, we propose that reduced VLC-PUFA in the retinas of these patients may be the cause of photoreceptor cell death.
EPAC and PKA allow cAMP dual control over DNA-PK nuclear translocation
Authors: Huston Elaine , Lynch Martin J. , Mohamed Ahmed , Collins Daniel M. , Hill Elaine V. , MacLeod Ruth , Krause Eberhard , Baillie George S. , Houslay Miles D.
Published: August 2008

We identify a compartmentalized signaling system that identifies a functional role for the GTP exchange factor, exchange protein activated by cAMP (EPAC) coupled to Rap2 in the nucleus. In this system, cAMP regulates the nuclear/cytoplasmic trafficking of DNA-dependent protein kinase (DNA-PK), a critical kinase that acts to repair double-stranded breaks (DSBs) in damaged DNA and to phosphorylate the cell survival kinase, PKB/Akt. Intersecting regulatory inputs for cAMP employ EPAC to transduce positive effects, namely the Rap2-dependent nuclear exit and activation of DNA-PK, whereas protein kinase A (PKA) provides the negative input by antagonizing these actions. We identify this as a compartmentalized regulatory system where modulation of cAMP input into the stimulatory, EPAC and inhibitory, PKA intersecting arms is provided by spatially discrete, cAMP degradation systems. The distribution of DNA-PK between nuclear and cytoplasmic compartments can thus potentially be influenced by relative inputs of cAMP signaling through the EPAC and PKA pathways. Through this signaling system EPAC activation can thereby impact on the Ser-473 phosphorylation status of PKB/Akt and the repair of etoposide-induced DSBs.
Identification of two major types of age-associated CD8 clonal expansions with highly divergent properties
Authors: Clambey Eric T. , White Janice , Kappler John W. , Marrack Philippa
Published: August 2008

CD8 memory T cells are tightly regulated in young, healthy individuals but are often perturbed in aged animals by the appearance of large CD8 T cell clones. These clones are associated with impaired immunity in the aged. The molecular basis of this phenomenon remains unclear. Here, it is shown that the issue is confused by the fact that the clones are heterogeneous. Some clones bear high, and others, low levels of integrin α4(itgα4). These subtypes differ by multiple criteria. They appear in mice of different ages, concentrate in different tissues, and have different stabilitiesin vivoand responses to stimulationin vitro. itgα4high, but not itgα4low, CD8 clonal expansions have several characteristics consistent with a chronically stimulated phenotype. These properties include lowered levels of CD8, decreased expression of some cytokine receptors, and elevated expression of various inhibitory receptors, including the programmed death-1 (PD1) receptor and the killer cell lectin-like receptor G1 (KLRG1). The characteristics of itgα4highclonal expansions suggest that they may arise from age-dependent alterations in antigen expression and tolerance. These data redefine CD8 clonal expansions into at least two distinct entities and indicate that there are multiple mechanisms that drive age-related alterations of CD8 T cell homeostasis.
Functional disturbances in the striatum by region-specific ablation of NMDA receptors
Authors: Ohtsuka Nobuhisa , Tansky Morris F. , Kuang Hui , Kourrich Saïd , Thomas Mark J. , Rubenstein John L. R. , Ekker Marc , Leeman Susan E. , Tsien Joe Z.
Published: August 2008

To study the role of NMDA receptors in dopamine signaling of the striatum, the brain area that receives glutamatergic inputs from various cortical areas and most dopaminergic inputs, we generated striatum-specific NMDA receptor-deficient mice. The mutant pups showed reduced food intake and retarded growth starting at the second postnatal week and died on approximately postnatal day 20 (P20). The time course of postnatal lethality is similar to that of compound mutant, double knockout of dopamine D1/D2 receptors, or genetically engineered dopamine-deficient mouse.
In vivo
electrophysiological recordings in the mutant pups showed that frequencies in the range of gamma oscillation were reduced in the striatal circuits. Moreover, the number of functional dopamine receptors in the striatum as measured by D1- and D2-binding experiments was greatly diminished in the mutants as compared with control animals. A consequence of diminished dopamine binding in the striatum manifested in an increase of locomotor activity. The administration of D1/D2 agonists paradoxically reduced the hyperactivity of the mutant mice as compared with an increase in locomotor activity in control mice. These results demonstrate that the NMDA receptor plays an essential role in the integration of dopamine signaling in the striatum and that is required in behavioral function.
Nasofacial Reconstruction with Calvarial Bone Grafts in Compromised Defects
Authors: Emerick Kevin S. , Hadlock Tessa A. , Cheney Mack L.
Published: August 2008

Objectives/Hypothesis: To determine the utility of calvarial bone grafting in multiple reconstructive settings. In particular to examine the success of calvarial bone grafting of the nasofacial skeleton in a compromised wound bed.

Study Design: Case series.

Methods: A retrospective review was performed to identify patients undergoing calvarial bone graft reconstruction of the nasofacial skeleton. Patients were identified from operative records and the medical record was reviewed to identify age, gender, site of defect, indication for the operation, size of bone graft harvested, postoperative and delayed complications, radiation exposure, need for additional soft tissue, and graft loss.

Results: Eighty‐seven patients who underwent split calvarial bone grafts were identified and had a complete medical record available for review. Ninety grafts were harvested. Five subsites in the nasofacial skeleton were identified as sites for reconstruction. Forty cases were performed for revision of a previous complication, including 13 who had a previous alloplastic implant. Twenty‐four additional cases were performed in a compromised wound bed and 64% of all cases were performed in either a revision or compromised setting. There was an 11% incidence of early postoperative complications, but there were no major complications at the donor site and only two major complications at the recipient site.

Conclusion: Calvarial bone is a very useful material in the primary, revision, and compromised settings. This series suggests that split calvarial bone grafts is an adaptable, durable, and reliable material. It can be reliably used in the setting of radiation, infection, and inflammation.
Perilymph Osmolality Modulates Cochlear Function
Authors: Choi Chul‐Hee , Oghalai John S.
Published: August 2008

Objectives/Hypothesis: The cochlear amplifier is required for the exquisite sensitivity of mammalian hearing. Outer hair cells underlie the cochlear amplifier and they are unique in that they maintain an intracellular turgor pressure. Changing the turgor pressure of an isolated outer hair cells through osmotic challenge modulates its ability to produce electromotile force. We sought to determine the effect of osmotic challenge on cochlear function.

Study Design: In vivo animal study.

Methods: Hypotonic and hypertonic artificial perilymph was perfused through the scala tympani of anesthetized guinea pigs. Cochlear function was assessed by measuring the compound action potential, distortion product otoacoustic emissions, the cochlear microphonic, and the endocochlear potential.

Results: Hypotonic perilymph decreased and hypertonic perilymph increased compound action potential and distortion product otoacoustic emission thresholds in a dose‐dependent and reversible manner. The cochlear microphonic quadratic distortion product magnitude increased after hypotonic perfusion and decreased with hypertonic perfusion. There were no changes in the stimulus intensity growth curve of the low‐frequency cochlear microphonic. The endocochlear potential was not affected by perilymph osmolality.

Conclusions: These data demonstrate that perilymph osmolality can modulate cochlear function and are consistent with what would be expected if outer hair cells turgor pressure changes the gain of the cochlear amplifier in vivo.
Adult Subglottic Stenosis: Management With Laser Incisions and Mitomycin‐C
Authors: Roediger Frederick C. , Orloff Lisa A. , Courey Mark S.
Published: August 2008

Objectives/Hypothesis: To assess the efficacy of endoscopic laser radial incisions with mitomycin‐C application (ELRM) in managing adult subglottic stenosis (SGS).

Study Design: Retrospective case series review.

Methods: Fifteen consecutive cases of adult SGS treated with ELRM at a single tertiary referral center over three years were reviewed. Subjects with SGS secondary to Wegener's granulomatosis (WG) and idiopathic SGS were included. Patients with cartilaginous SGS were excluded. The primary outcome measure was postoperative reduction in symptoms. Secondary outcome measures included total number of procedures required to relieve symptoms, interval between procedures, and improvement in pulmonary function tests when available. In addition to surgery, 14 of 15 patients were treated medically for reflux.

Results: Ten women and five men with average age 48 years were identified. Ten patients had idiopathic SGS and five had WG. The predominant presenting symptom was dyspnea on exertion in all patients. All subjects reported at least a temporary postoperative reduction in symptoms. Six patients (40%) required only one ELRM and nine patients (60%) required repeat ELRM at an average interval of 9 months. The average interval for the six patients with idiopathic etiology requiring a second procedure was 9 months. One subject with WG required four procedures. His interval improved from 2.5 to 7 months between procedures. Evidence of extrathoracic airway obstruction resolved in three of four patients with pre and postoperative pulmonary function tests.

Conclusions: ELRM is an effective method of managing SGS associated with idiopathic causes. In patients with WG, ELRM reduced airway associated symptoms and avoided need for tracheotomy.
Multiple Analyses of Factors Related to Intraoperative Blood Loss and the Role of Reverse Trendelenburg Position in Endoscopic Sinus Surgery
Authors: Ko Ming‐Tse , Chuang Kuan‐Chih , Su Chih‐Ying
Published: August 2008

Objective/Hypothesis: To find out the factors related to the volume of intraoperative blood loss during endoscopic sinus surgery and to validate the role of reverse Trendelenburg position (RTP) in controlling blood loss.

Study Design: Prospective, controlled, single‐blind study.

Methods: Endoscopic sinus surgeries for chronic rhinosinusitis with or without polyposis were performed in 60 patients, which were randomly categorized into two groups. The study group (RTP group) consisted of 30 patients laid on operation table with the RTP of 10° during the whole surgery, and the control group with 30 patients completely laid supine. All operations were performed by the same operator (the first author) without using hemostatic agents during the operation. Intraoperative blood loss was estimated by total volume of blood loss, blood loss per minute, and surgical field scale. Multiple factors related to blood loss, such as computed tomography scores, operation time, mean arterial pressure, polyposis, fungal sinusitis, and anesthetic agents were compared.

Results: There existed significant differences in total blood loss, blood loss per minute, and surgical field between the RTP group and supine group. In multiple analyses within the two groups, presence of polyp, non‐fungal sinusitis and use of microdebrider exhibited a significant higher blood loss rate in the RTP group.

Conclusion: RTP may reduce intraoperative blood loss. Besides, fungal sinusitis and rhinosinusitis without polyposis may contribute to a lesser intraoperative blood loss.
The Role of Allergy and Smoking in Chronic Rhinosinusitis and Polyposis
Authors: Houser Steven M. , Keen Kevin J.
Published: August 2008

Objectives/Hypothesis: The article considers the interrelatedness of allergic rhinitis and chronic rhinosinusitis (CRS). The negative impact of perennial allergy and tobacco use on polyposis in sinus surgery patients is explored.

Study Design: A retrospective chart review, performed by the first author over a 6‐year period, of patients who underwent functional endoscopic sinus surgery for CRS.

Methods: The subjects' allergy status and smoking history are scrutinized by summary statistics and a multiple linear logistic model for predicting the presence of polyps.

Results: High prevalence of perennial allergic rhinitis (PAR) is seen in the subject population (56.4%). Both PAR and tobacco use are associated with nasal polyposis (P = .0073 and P = .0114, respectively).

Conclusions: The close association of PAR and CRS suggests a possible causal link. Management of allergic rhinitis and tobacco cessation may provide greater control of chronic hyperplastic rhinosinusitis.
Investigating antibody neutralization of lyssaviruses using lentiviral pseudotypes: a cross-species comparison
Authors: Wright Edward , Temperton Nigel J. , Marston Denise A. , McElhinney Lorraine M. , Fooks Anthony R. , Weiss Robin A.
Published: August 2008

Cross-neutralization between rabies virus (RABV) and two European bat lyssaviruses (EBLV-1 and -2) was analysed using lentiviral pseudotypes as antigen vectors. Glycoprotein (G-protein) cDNA from RABV challenge virus standard-11 (CVS-11) and EBLV-1 and -2 were cloned and co-expressed with human immunodeficiency virus (HIV) or murine leukemia virus (MLV) gag–pol and packageable green fluorescent protein (GFP) or luciferase reporter genes in human cells. The harvested lentiviral (HIV) vector infected over 40 % of baby hamster kidney (BHK) target cells, providing high-titre pseudotype stocks. Tests on blinded antibody-positive (n=15) and -negative (n=45) sera, predetermined by the fluorescent antibody virus neutralization (FAVN) test approved by the World Health Organization (WHO) and Office International des Epizooties (OIE), revealed that the CVS-11 pseudotype assay had 100 % concordance with FAVN and strongly correlated with neutralization titres (r
2=0.89). Cross-neutralization tests using sera from RABV-vaccinated humans and animals on pseudotypes with CVS-11, EBLV-1 and EBLV-2 envelopes showed that the relative neutralization titres correlated broadly with the degree of G-protein diversity. Pseudotypes have three major advantages over live-virus neutralization tests: (i) they can be handled in low-biohazard-level laboratories; (ii) the use of reporter genes such as GFP or β-galactosidase will allow the assay to be undertaken at low cost in laboratories worldwide; (iii) each assay requires <10 μl serum. This robust microassay will improve our understanding of the protective humoral immunity that current rabies vaccines confer against emerging lyssaviruses, and will be applicable to surveillance studies, thus helping to control the spread of rabies.
Glucose-6-phosphate dehydrogenase deficiency enhances enterovirus 71 infection
Authors: Ho Hung-Yao , Cheng Mei-Ling , Weng Shiue-Fen , Chang Lo , Yeh Tsun-Tsun , Shih Shin-Ru , Chiu Daniel Tsun-Yee
Published: August 2008

Variations in the cellular microenvironment affect the host's susceptibility to pathogens. Using glucose-6-phosphate dehydrogenase (G6PD)-deficient fibroblasts as a model, this study demonstrated that the cellular redox status affects infectivity as well as the outcome of enterovirus 71 (EV71) infection. Compared with their normal counterparts, G6PD-deficient cells supported EV71 replication more efficiently and showed greater cytopathic effect and loss of viability. Mechanistically, viral infection led to increased oxidative stress, as indicated by increased dichlorofluorescein fluorescence and a diminished ratio of glutathione (GSH) to its disulfide form (GSSG), with the effect being greater in G6PD-deficient cells. Exogenous expression of active G6PD in the deficient cells, which increased the intracellular GSH : GSSG ratio, suppressed the generation of viral progeny. Consistent with this, treatment with N-acetylcysteine offered resistance to EV71 propagation and a cytoprotective effect on the infected cells. These findings support the notion that G6PD status, and thus redox balance, is an important determinant of enteroviral infection.
Characterization of cell-death pathways in Punta Toro virus-induced hepatocyte injury
Authors: Xu Fangling , Liang Xiaodong , Tesh Robert B. , Xiao Shu-Yuan
Published: August 2008

Punta Toro virus (PTV; genus Phlebovirus, family Bunyaviridae) causes apoptosis of hepatocytes in vivo in experimentally infected hamsters and in vitro in cultured HepG2 cells. Screening for expression of apoptosis-related genes has shown alterations in the genes for tumour necrosis factor-α (TNF-α) and the TNF receptor family. This study examined the roles of the TNF receptor-related extrinsic pathway and the Bcl-2 family-associated mitochondrial pathway in PTV-induced cell death. The effects of caspase inhibitors (caspIs) and TNF on cellular viability, virus replication, and morphological and biochemical changes in apoptosis were examined in HepG2 cells at different time points after infection with PTV (Adames strain). The results showed that caspIs dampened the virus-induced reduction in cellular viability, partially suppressed and delayed viral titres and antigen expression, and partially decreased the expression of apoptotic genes, caspase activities and DNA fragmentation. TNF treatment further decreased cellular viability after PTV infection and increased the level of apoptosis, whilst caspIs partially inhibited these effects. These findings indicate that TNF, caspase-8 and caspase-9 contribute to PTV-induced hepatocytic apoptosis and that additional mediators are probably also involved in this process. These mediators from different pathways correlated with one another and may be interlinked.
Genotypic diversity of H5N1 highly pathogenic avian influenza viruses
Authors: Zhao Zi-Ming , Shortridge Kennedy F. , Garcia Maricarmen , Guan Yi , Wan Xiu-Feng
Published: August 2008

Besides enormous economic losses to the poultry industry, recent H5N1 highly pathogenic avian influenza viruses (HPAIVs) originating in eastern Asia have posed serious threats to public health. Up to April 17, 2008, 381 human cases had been confirmed with a mortality of more than 60 %. Here, we attempt to identify potential progenitor genes for H5N1 HPAIVs since their first recognition in 1996; most were detected in the Eurasian landmass before 1996. Combinations among these progenitor genes generated at least 21 reassortants (named H5N1 progenitor reassortant, H5N1-PR1–21). H5N1-PR1 includes A/Goose/Guangdong/1/1996(H5N1). Only reassortants H5N1-PR2 and H5N1-PR7 were associated with confirmed human cases: H5N1-PR2 in the Hong Kong H5N1 outbreak in 1997 and H5N1-PR7 in laboratory confirmed human cases since 2003. H5N1-PR7 also contains a majority of the H5N1 viruses causing avian influenza outbreaks in birds, including the first wave of genotype Z, Qinghai-like and Fujian-like virus lineages. Among the 21 reassortants identified, 13 are first reported here. This study illustrates evolutionary patterns of H5N1 HPAIVs, which may be useful toward pandemic preparedness as well as avian influenza prevention and control.
Phylogenetic analysis reveals the emergence, evolution and dispersal of carnivore parvoviruses
Authors: Hoelzer Karin , Shackelton Laura A. , Parrish Colin R. , Holmes Edward C.
Published: August 2008

Canine parvovirus (CPV), first recognized as an emerging virus of dogs in 1978, resulted from a successful cross-species transmission. CPV emerged from the endemic feline panleukopenia virus (FPV), or from a closely related parvovirus of another host. Here we refine our current understanding of the evolution and population dynamics of FPV and CPV. By analysing nearly full-length viral sequences we show that the majority of substitutions distinguishing CPV from FPV are located in the capsid protein gene, and that this gene is under positive selection in CPV, resulting in a significantly elevated rate of molecular evolution. This provides strong phylogenetic evidence for a prominent role of the viral capsid in host adaptation. In addition, an analysis of the population dynamics of more recent CPV reveals, on a global scale, a strongly spatially subdivided CPV population with little viral movement among countries and a relatively constant population size. Such limited viral migration contrasts with the global spread of the virus observed during the early phase of the CPV pandemic, but corresponds to the more endemic nature of current CPV infections.
Oligomerization of hantaviral nucleocapsid protein: charged residues in the N-terminal coiled-coil domain contribute to intermolecular interactions
Authors: Alminaite Agne , Backström Vera , Vaheri Antti , Plyusnin Alexander
Published: August 2008

The nucleocapsid (N) protein of hantaviruses (family Bunyaviridae) is the most abundant component of the virion; it encapsidates genomic RNA segments and participates in viral genome transcription and replication, as well as in virus assembly. During RNA encapsidation, the N protein forms intermediate trimers and then oligomers via ‘head-to-head, tail-to-tail’ interactions. In previous work, using Tula hantavirus (TULV) N protein as a model, it was demonstrated that an intact coiled-coil structure of the N terminus is crucial for the oligomerization capacity of the N protein and that the hydrophobic ‘a’ residues from the second α-helix are especially important. Here, the importance of charged amino acid residues located within the coiled-coil for trimer formation and oligomerization was analysed. To predict the interacting surfaces of the monomers, the previous in silico model of TULV coiled-coils was first upgraded, taking advantage of the recently published crystal structure of the N-terminal coiled-coil of the Sin Nombre virus N protein. The results obtained using a mammalian two-hybrid assay suggested that conserved, charged amino acid residues within the coiled-coil make a substantial contribution to N protein oligomerization. This contribution probably involves (i) the formation of interacting surfaces of the N monomers (residues D35 and D38, located at the tip of the coiled-coil loop, and R63 appear particularly important) and (ii) stabilization of the coiled-coil via intramolecular ionic bridging (with E55 as a key player). It is hypothesized that the tips of the coiled-coils are the first to come into direct contact and thus to initiate tight packing of the three structures.
The dual role of dendritic cells in the immune response to human immunodeficiency virus type 1 infection
Authors: Hogue Ian B. , Bajaria Seema H. , Fallert Beth A. , Qin Shulin , Reinhart Todd A. , Kirschner Denise E.
Published: August 2008

Many aspects of the complex interaction between human immunodeficiency virus type 1 (HIV-1) and the human immune system remain elusive. Our objective was to study these interactions, focusing on the specific roles of dendritic cells (DCs). DCs enhance HIV-1 infection processes as well as promote an antiviral immune response. We explored the implications of these dual roles. A mathematical model describing the dynamics of HIV-1, CD4+ and CD8+ T-cells, and DCs interacting in a human lymph node was analysed and is presented here. We have validated the behaviour of our model against non-human primate simian immunodeficiency virus experimental data and published human HIV-1 data. Our model qualitatively and quantitatively recapitulates clinical HIV-1 infection dynamics. We have performed sensitivity analyses on the model to determine which mechanisms strongly affect infection dynamics. Sensitivity analysis identifies system interactions that contribute to infection progression, including DC-related mechanisms. We have compared DC-dependent and -independent routes of CD4+ T-cell infection. The model predicted that simultaneous priming and infection of T cells by DCs drives early infection dynamics when activated T-helper cell numbers are low. Further, our model predicted that, while direct failure of DC function and an indirect failure due to loss of CD4+ T-helper cells are both significant contributors to infection dynamics, the former has a more significant impact on HIV-1 immunopathogenesis.
Classification of hepatitis C virus and human immunodeficiency virus-1 sequences with the branching index
Authors: Hraber Peter , Kuiken Carla , Waugh Mark , Geer Shaun , Bruno William J. , Leitner Thomas
Published: August 2008

Classification of viral sequences should be fast, objective, accurate and reproducible. Most methods that classify sequences use either pair-wise distances or phylogenetic relations, but cannot discern when a sequence is unclassifiable. The branching index (BI) combines distance and phylogeny methods to compute a ratio that quantifies how closely a query sequence clusters with a subtype clade. In the hypothesis-testing framework of statistical inference, the BI is compared with a threshold to test whether sufficient evidence exists for the query sequence to be classified among known sequences. If above the threshold, the null hypothesis of no support for the subtype relation is rejected and the sequence is taken as belonging to the subtype clade with which it clusters on the tree. This study evaluates statistical properties of the BI for subtype classification in hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1). Pairs of BI values with known positive- and negative-test results were computed from 10  000 random fragments of reference alignments. Sampled fragments were of sufficient length to contain phylogenetic signals that grouped reference sequences together properly into subtype clades. For HCV, a threshold BI of 0.71 yields 95.1 % agreement with reference subtypes, with equal false-positive and false-negative rates. For HIV-1, a threshold of 0.66 yields 93.5 % agreement. Higher thresholds can be used where lower false-positive rates are required. In synthetic recombinants, regions without breakpoints are recognized accurately; regions with breakpoints do not represent any known subtype uniquely. Web-based services for viral subtype classification with the BI are available online.
The Australian Labour Market in 2003
Authors: Burgess John , Lee Julie , O’Brien Martin
Published: August 2008

The labour market remained strong throughout 2003 with ongoing jobs growth and a continuation of the trend towards a lower unemployment rate. Unlike previous years, in 2003, additional jobs were mainly full-time jobs and the female labour force participation rate declined. After 11 years of ongoing improvement in the condition of the labour market, this boom is lacking the three developments associated with past improvement in the labour market: strong wages growth, strong growth in labour force participation rates, and increased industrial disputation. The review also considers the ongoing growth in the employment services sector associated with the spread of temporary agency employment. The topical issue of the ageing of the population is then considered with a critical examination of the current policy direction of extending the working life of Australian workers. Finally, a related issue is reviewed: the provision of child care services in Australia.
Trade Unionism in 2003
Authors: Cooper Rae
Published: August 2008

In 2003 Australian trade unions continued the campaign to improve employees’ ability to balance work and family responsibilities. This, along with push for the introduction of ‘industrial manslaughter’ legislation, was the key industrial priority of the year. During the year, unions witnessed a political changing of the guard. There were no union tears when Workplace Relations Minister, Tony Abbott, departed the industrial relations scene. On the other side of politics, Mark Latham was elevated to the leadership of the Federal Parliamentary Labor Party. While his candidature was not strongly supported by union leaders, Latham has won himself a number of union admirers since his election. Despite the enthusiasm for revitalising the union movement exhibited at the Australian Council of Trade Unions’ Organising Conference, statistics from the Australian Bureau of Statistics released in 2003 showed that both union density and aggregate membership had slipped. The biggest ‘organising story’ of the year was the disintegration of the joint union campaign to reorganise the Pilbara, which in 2003 fell victim to competitive union pressure.
Employer Matters in 2003
Authors: Mackinnon Bruce Hearn
Published: August 2008

The year 2003 was characterised by employer proactivism, and a preparedness to pursue new legal manoeuvres to prevent or terminate protected industrial action. A number of employers also resorted to lengthy lockouts (with few positive results) as bargaining tactics in enterprise negotiations. It was the year employers in the manufacturing and metals sector saw off the unions’ ‘Campaign 2003’, giving little ground on the key issues of reduced hours and contributions to trust funds for worker entitlements. The year was a joyous one for employers in the building and construction industry, as their dreams of a shackled and weakened union movement came a step closer to being realised, with the introduction of draconian industry-specific legislation by the Howard Government, arising from the recommendations of the Cole Royal Commission. On a positive note, the year also witnessed all the members of the ‘industrial relations club’ embrace and declare a common concern for work and family balance issues.
A key to the genus Chelonopsis (Lamiaceae) and two new combinations: C. rosea var. siccanea and C. souliei var. cashmerica comb. nov
Authors: Xiang Chun‐Lei , Liu En‐De , Peng Hua
Published: August 2008

Two new combinations in the genus Chelonopsis (Lamiaceae) are proposed based on a wide range of herbarium and field investigations. Chelonopsis rosea W. W. Smith and Chelonopsis siccanea W. W. Smith are treated as conspecific and the latter taxon, is here recombined as C. rosea var. siccanea (W. W. Smith) C. L. Xiang & H. Peng, comb. et stat. nov. Another species, C. albiflora Pax & K. Hoffmann ex Limpricht var. cashmerica Mukerjee is recombined as C. souliei (Bonati) Merr. var. cashmerica (Mukerjee) C. L. Xiang & H. Peng. In addition, C. pseudobracteata C. Y. Wu et H. W. Li is newly synonymized with C. lichiangensis W. W. Smith and C. odontochila Diels var. smithii (Kudo) C. Y. Wu with C. odontochila Diels var. odontochila. An updated key to the genus is also provided.
A Broader View of Language in School: Research from Linguistic Ethnography
Authors: Maybin Janet
Published: August 2008

Arguing that educational research into language and literacy has neglected the social and cultural dimensions of children’s language use, this article presents a review of recent research from linguistic ethnography which combines close attention to children and teachers’ language use with an analysis of context and social practice. This research reemphasises the complex role of language in children’s socialisation and learning and the importance of recognising connections and disjunctions between children’s language and literacy practices in and outside school, the influence of societal patterns of linguistic inequality and children and young people’s uses of language among themselves.
Short‐term larval food stress and associated compensatory growth reduce adult immune function in a damselfly
Authors: DeBLOCK MARJAN , STOKS ROBBY
Published: August 2008

Abstract 1. In animals with a complex life cycle, larval stressors may carry over to the adult stage. Carry‐over effects not mediated through age and size at metamorphosis have rarely been studied. The present study focuses on the poorly documented immune costs of short‐term food stress both in the larval stage and after metamorphosis in the adult stage.

2. The present study quantified immune function [number of haemocytes, activity of prophenoloxidase (proPO) and phenoloxidase (PO)] in an experiment where larvae of the damselfly Lestes viridis were exposed to a transient starvation period.

3. Directly after starvation, immune variables were reduced in starved larvae. Levels of proPO and PO remained low after starvation, even after metamorphosis. In contrast, haemocyte numbers were fully compensated by the end of the larval stage, yet were lower in previously starved animals after metamorphosis. This can be explained as a cost of the observed compensatory growth after starvation. Focusing only on potential costs of larval stressors within the larval stage may therefore be misleading.

4. The here‐identified immunological cost in the adult stage of larval short‐term food stress and associated compensatory growth strongly indicates that physiological costs may explain hidden carry‐over effects bridging metamorphosis. This adds to the increasing awareness that the larval and adult stages in animals with a complex life cycle should be jointly studied, as trade‐offs may span metamorphosis.
Climate change, diapause termination and zooplankton population dynamics: an experimental and modelling approach
Authors: DUPUIS ALAIN P. , HANN BRENDA J.
Published: August 2008

1. Earlier spring warming as predicted for climate change will alter combinations of water temperature and photoperiod that act as emergence cues for zooplankton resting stages. As a result, water temperature cue thresholds will be experienced at shorter photoperiods, a variable independent of weather variations. Also, light intensity, another potentially important cue for zooplankton emergence, could decrease in many lakes if symptoms of climate change resemble those of eutrophication.

2. We designed a laboratory experiment to test the effects of three factors, temperature (6, 9 and 12 °C), photoperiod (13L : 11D and 16L : 8D) and light intensity (20 and 35 μE m−2 s−1) on hatchling abundance and timing of hatching of daphniids (Daphnia ambigua) and rotifers (Keratella spp. and Synchaeta pectinata) from resting eggs. Further, we investigated the implications of potential changes in hatching dynamics, following variations in hatching cues, on zooplankton spring population development using predator–prey simulation models.

3. For hatchling abundance and timing of hatching, photoperiod had a significant effect for D. ambigua but not rotifers. Daphnia ambigua hatchling abundance decreased by 50% when incubated at conditions mimicking early spring (12 °C + 13‐h photoperiod) compared to a later spring (12 °C + 16‐h photoperiod). Light intensity has a significant effect only for S. pectinata, producing greater hatchling abundance at lower light intensity.

4. Simulation models suggest that in contrast to a later spring, an early warming produces a shift in spring zooplankton community composition, from daphniid to rotifer dominance. These patterns are primarily driven by differential zooplankton emergence response with variations in temperature–photoperiod cues.

5. Overall, our laboratory experiments and simulation models suggest that lakes with strong dependence on the ‘resting egg‐bank’, characteristic of many shallow north‐temperate lakes or in years with low winter survivorship of adult zooplankton, may be most susceptible to climate change. Further, fewer large grazers such as daphniids with an earlier spring may result in less control of cyanobacterial blooms in eutrophic lakes.
Identification and characterization of a Jem1p ortholog of Candida albicans: dissection of Jem1p functions in karyogamy and protein quality control in Saccharomyces cerevisiae
Authors: Makio Tadashi , Nishikawa Shuh‐ichi , Nakayama Takeshi , Nagai Hiroyuki , Endo Toshiya
Published: August 2008

Jem1p of yeast Saccharomyces cerevisiae is a J‐domain containing co‐chaperone (J protein) in the endoplasmic reticulum (ER) lumen. Jem1p is required for nuclear fusion during mating (karyogamy) and functions together with another J protein, Scj1p, in protein folding and quality control in the ER as a partner for the ER Hsp70 (BiP/Kar2p). Candida albicans has a gene encoding a homolog of S. cerevisiae Jem1p, CaJem1p. CaJem1p localized in the ER when expressed in S. cerevisiae, and expression of CaJem1p from a single‐copy plasmid suppressed the temperature sensitive growth and the ER quality control defect of the jem1Δscj1Δ mutant, indicating that CaJem1p is functional in S. cerevisiae. However, CaJem1p suppressed the karyogamy defect of the jem1Δmutant only when it was over‐expressed from a multicopy plasmid. Domain‐swapping experiments showed that this was due to the difference between the N‐terminal domains of ScJem1p and CaJem1p. The N‐terminal domain of ScJem1p is essential for its function and interacts with Nep98p, a component of the spindle pole body involved in karyogamy. Since the interaction of CaJem1p with Nep98p is weaker than that of ScJem1p, the Nep98p‐ScJem1p interaction is likely important for promoting karyogamy in S. cerevisiae.
Cost and effectiveness of treatments for mild‐to‐moderate bleeding episodes in haemophilia patients with inhibitors in Korea
Authors: YOU C. W. , LEE S. Y. , PARK S. K.
Published: August 2008

Summary. First‐line treatment for mild‐to‐moderate bleeding episodes in patients with haemophilia and inhibitors in Korea is currently activated prothrombin complex concentrate (aPCC) with recombinant activated factor VII (rFVIIa) as second‐line therapy or as a last resort. The aim of this study was to estimate the cost and effectiveness of aPCC vs. rFVIIa for treating mild‐to‐moderate bleeds in inhibitor patients from the Korean reimbursement authorities’ perspective. Clinical outcomes and resource utilization data (number of doses, average dose, number of outpatient visits, inpatient stays, ambulance transport and concomitant medications) were collected from an observational study involving four Korean paediatric haemophilia centres. Cost‐effectiveness was modelled using a decision analysis approach and sensitivity analyses undertaken. rFVIIa was a more effective haemostatic therapy (87.1% efficacy in bleed resolution) than aPCC (64.0%). rFVIIa effected more rapid haemostasis, resolving bleeding in a mean of 6.6 h vs. 25.2 h for aPCC. Fewer rFVIIa doses were required per bleed vs. aPCC (means 1.7 and 2.3). Mean total direct medical costs from bleed initiation to cessation were estimated at Korean Won (KRW)12 460 thousand (US$12 311) for rFVIIa given as first‐line therapy and KRW18 304 thousand (US$18 085) for aPCC given as first‐line therapy. Sensitivity analyses confirmed the cost‐effectiveness of rFVIIa vs. aPCC given as first‐line therapy. In Korea, use of rFVIIa as first‐line therapy for treatment of mild‐to‐moderate bleeding episodes in inhibitor patients is both clinically effective and cost‐effective compared with initial aPCC treatment. rFVIIa should be considered as the first‐line treatment for mild‐to‐moderate bleeding episodes in patients with haemophilia and inhibitors in Korea.
The cloning and expression of α‐tubulin in Monochamus alternatus
Authors: Song L. , Liu X.‐X. , Zhang Y.‐A. , Zhang Q.‐W. , Zhao Z.‐W.
Published: August 2008

The Japanese pine sawyer Monochamus alternatus is one of the major forest pests. It damages pine directly and transfers the nematode Bursaphelenchus xylophilus to pine wood; resulting in serious economic losses around the world every year. α‐tubulin is one of most important proteins in most species. We cloned a ubiquitously expressed M. alternatusα‐tubulin gene and analysed its nucleotides and protein structure; its sequence characters are consistent with what have been reported in other insects. The alignment of proteins showed that there is high homology of α‐tubulin between M. alternatus and other species. Western blot and immunocytochemistry analyses suggested a common epitope of α‐tubulin between M. alternatus and Strongylcentrotus purpuratus. We also expressed the protein in Escherichia coli for further functional studies.
Specific insulin sensitivity and leptin responses to a nutritional treatment of obesity via a combination of energy restriction and fatty fish intake
Authors: Abete I. , Parra D. , Crujeiras A. B. , Goyenechea E. , Martinez J. A.
Published: August 2008

Background Nutritional strategies to treat obesity often influence neuroendocrine factors related to body weight control. The present study aimed to investigate whether the inclusion of three fatty fish servings per week within a hypocaloric diet may have specific healthy effects on insulin and leptin functions.

Methods Thirty‐two subjects (body mass index = 31.6 ± 3.5 kg m−2) aged 36 ± 7 years, were assigned to a control or fish‐based energy‐restricted diet over an 8‐week period. Anthropometry, body composition, lipid profile, leptin and insulin values were measured at the start and at the end of the dietary intervention.

Results Both experimental diets resulted in a similar mean weight loss (control = 5.3 ± 2.6% versus fish‐based = 5.5 ± 2.5%;P = 0.783). A significant reduction in insulin resistance, as determined by the homeostatic model assessment index (HOMA‐IR = insulin × glucose/22.5), was observed after the fish‐based intervention. The change in circulating leptin was higher in the fish‐based diet compared to the control group. Sixteen percent of the variability in the change of adjusted‐leptin could be explained (P = 0.034) by the HOMA index change and the type of diet.

Conclusions Three servings a week of fatty fish included in an energy‐restricted diet appears to be a valid strategy for specifically improving insulin sensitivity and leptin levels in obese subjects, which could involve a better body weight regulation after a nutritional intervention period.
Pharmacokinetics of ketamine and its metabolite norketamine administered at a sub‐anesthetic dose together with xylazine to calves prior to castration
Authors: GEHRING R. , COETZEE J. F. , TARUS‐SANG J. , APLEY M. D.
Published: August 2008

The objective of this study was to evaluate the plasma pharmacokinetics of ketamine and its active metabolite norketamine administered intravenously at a dose of 0.1 mg/kg together with xylazine (0.05 mg/kg) to control the pain associated with castration in calves. A two‐compartment model with an additional metabolite compartment linked to the central compartment was used to simultaneously describe the time‐concentration profiles of both ketamine and its major metabolite norketamine. Parameter values estimated from the time‐concentration profiles observed in this study were volume of the central compartment (Vc = 132.82 ± 68.23 mL/kg), distribution clearance (CLD = 15.49 ± 2.56 mL/min/kg), volume of the peripheral compartment (VT = 257.05 ± 41.65 mL/kg), ketamine clearance by the formation of the norketamine metabolite (CL2M = 8.56 ± 7.37 mL/kg/min) and ketamine clearance by other routes (CLo = 16.41 ± 3.42 mL/kg/min). Previously published data from rats suggest that the metabolite norketamine contributes to the analgesic effect of ketamine, with a potency that is one‐third of the parent drug. An understanding of the time‐concentration relationships and the disposition of the parent drug and its metabolite is therefore important for a better understanding of the analgesic potential of ketamine in cattle.