bluuebunny/crossref_metadata_2025 huggingface dataset:
The ‘big spenders’ of the steppe: sex-specific maternal allocation and twinning in the saiga antelope
Authors: Kühl Aline , Mysterud Atle , Erdnenov Gennadiy I , Lushchekina Anna A , Grachev Iuri A , Bekenov Amankul B , Milner-Gulland E.J
Published: March 2007

In polygynous mammals, males generally benefit more from extra allocation of maternal resources than females. However, limitations to sex-specific allocation are usually ignored. We propose the ‘allocation constraint’ hypothesis, whereby maternal resource allocation is more likely to follow life-history predictions in single sex litters than in mixed sex litters, due to limitations in prenatal resource targeting. Consequently, for polygynous species, males in mixed litters are likely to receive suboptimal maternal investment, which may have a negative effect on lifetime reproductive success. We test this hypothesis for the saiga antelope (
Saiga tatarica
), a highly polygynous species with the highest level of maternal allocation reported among ungulates. At such high reproductive output levels, the limitations on additional investment in males are likely to be particularly acute. However, we demonstrate high levels of sexual dimorphism in both late-stage foetuses and newborn calves, including within the same litter. Male twins with a brother tended to be heavier than those with a sister. This may be due to allocation constraints or differences in maternal quality. We conclude that an explicit focus on potential constraints can enhance the progress in the field of sex-specific maternal allocation in polytocous species.
Stem cell research in China
Authors: Liao Lianming , Li Lingsong , Zhao Robert Chunhua
Published: March 2007

In the past 5 years, China has increased its efforts in the field of stem cell research and practice. Basic research mainly focuses on bone marrow and embryonic stem cells. Clinical applications of stem cells in the treatment of acute heart failure, acute liver failure and lower limb ischaemia have been reported by many hospitals. China enacted its ‘Ethical Guidelines for Human Embryonic Stem Cell Research’ in 2003. At present, China has the most liberal and favourable environments for human embryonic stem cell research.
Coupling Diurnal Cytosolic Ca
2+
Oscillations to the CAS-IP
3
Pathway in
Arabidopsis
Authors: Tang Ru-Hang , Han Shengcheng , Zheng Hailei , Cook Charles W. , Choi Christopher S. , Woerner Todd E. , Jackson Robert B. , Pei Zhen-Ming
Published: March 2007

Various signaling pathways rely on changes in cytosolic calcium ion concentration ([Ca
2+
]
i
). In plants, resting [Ca
2+
]
i
oscillates diurnally. We show that in
Arabidopsis thaliana
, [Ca
2+
]
i
oscillations are synchronized to extracellular Ca
2+
concentration ([Ca
2+
]
o
) oscillations largely through the Ca
2+
-sensing receptor CAS. CAS regulates concentrations of inositol 1,4,5-trisphosphate (IP
3
), whichinturndirects release of Ca
2+
from internal stores. The oscillating amplitudes of [Ca
2+
]
o
and [Ca
2+
]
i
are controlled by soil Ca
2+
concentrations and transpiration rates. The phase and period of oscillations are likely determined by stomatal conductance. Thus, the internal concentration of Ca
2+
in plant cells is constantly being actively revised.
From Swimming to Walking with a Salamander Robot Driven by a Spinal Cord Model
Authors: Ijspeert Auke Jan , Crespi Alessandro , Ryczko Dimitri , Cabelguen Jean-Marie
Published: March 2007

The transition from aquatic to terrestrial locomotion was a key development in vertebrate evolution. We present a spinal cord model and its implementation in an amphibious salamander robot that demonstrates how a primitive neural circuit for swimming can be extended by phylogenetically more recent limb oscillatory centers to explain the ability of salamanders to switch between swimming and walking. The model suggests neural mechanisms for modulation of velocity, direction, and type of gait that are relevant for all tetrapods. It predicts that limb oscillatory centers have lower intrinsic frequencies than body oscillatory centers, and we present biological data supporting this.
Ecological Speciation in South Atlantic Island Finches
Authors: Ryan Peter G. , Bloomer Paulette , Moloney Coleen L. , Grant Tyron J. , Delport Wayne
Published: March 2007

Examples of sympatric speciation in nature are rare and hotly debated. We describe the parallel speciation of finches on two small islands in the Tristan da Cunha archipelago in the South Atlantic Ocean.
Nesospiza
buntings are a classic example of a simple adaptive radiation, with two species on each island: an abundant small-billed dietary generalist and a scarce large-billed specialist. Their morphological diversity closely matches the available spectrum of seed sizes, and genetic evidence suggests that they evolved independently on each island. Speciation is complete on the smaller island, where there is a single habitat with strongly bimodal seed size abundance, but is incomplete on the larger island, where a greater diversity of habitats has resulted in three lineages. Our study suggests that the buntings have undergone parallel ecological speciation.
Many Players in the Concerto of Sex
Authors: Eder Sandra
Published: March 2007

The Most Secret Quintessence of Life
. Sex, Glands, and Hormones, 1850-1950.
By Chandak Sengoopta
. University of Chicago Press, Chicago, 2006. 366 pp. $45, £28.50. ISBN 9780226748634.

Exploring the development of endocrine research and therapeutics, Sengoopta highlights the cultural framing of the studies of hormonal influence on aging, youthfulness, creativity, sexuality, and gender.
Social Mixing with Other Children during Infancy Enhances Antibody Response to a Pneumococcal Conjugate Vaccine in Early Childhood
Authors: Salt Penny , Banner Carly , Oh Sarah , Yu Ly-mee , Lewis Susan , Pan Dingxin , Griffiths David , Ferry Berne , Pollard Andrew
Published: March 2007

Children who have siblings and/or who attend day care have higher rates of nasopharyngeal colonization with pneumococci than lone children do. Pneumococcal colonization is usually asymptomatic but is a prerequisite for invasive disease. We studied the effect of social mixing with other children on immunity to a pneumococcal vaccine. One hundred sixty children aged 1 year were immunized with a 7-valent conjugate pneumococcal vaccine. A blood sample was obtained before and 9 to 11 days after the vaccine. The concentration and avidity of antibody against vaccine pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) were studied in relation to pneumococcal carriage rate and measures of social mixing. Children with increased social mixing had higher antibody concentrations against serotypes 4, 9V, 14, and 23F than lone children did. The least-carried serotype, serotype 4, was the one of the most immunogenic. This contrasts with serotype 6B, the most common nasopharyngeal isolate but the least immunogenic. Social mixing in infancy enhances the immune response to aStreptococcus pneumoniaepolysaccharide-protein conjugate vaccine at 1 year of age. Exposure to pneumococci in the first year of life may induce immunological priming. An alternative explanation is that differences in immunological experience, such as increased exposure to respiratory viral infections in early childhood, alters the response to vaccines perhaps by affecting the balance between Th1 and Th2 cytokines. The low immunogenicity of serotype 6B polysaccharide might make conditions more favorable for carriage of the 6B organism and explain why 6B pneumococci were more frequently isolated than other serotypes.
Borreliacidal OspC Antibody Response of Canines with Lyme Disease Differs Significantly from That of Humans with Lyme Disease
Authors: Lovrich Steven D. , La Fleur Rhonda L. , Jobe Dean A. , Johnson Jennifer C. , Asp Krista E. , Schell Ronald F. , Callister Steven M.
Published: March 2007

Humans reliably produce high concentrations of borreliacidal OspC antibodies specific for the seven C-terminal amino acids shortly after infection with
Borrelia burgdorferi
. We show that dogs also produce OspC borreliacidal antibodies but that their frequencies, intensities, and antigenicities differ significantly. The findings therefore confirm a major difference between the borreliacidal antibody responses of humans and canines with Lyme disease.
Inadequacy of Colominic Acid as an Absorbent Intended To Facilitate Use of Complement-Preserved Baby Rabbit Serum in theNeisseria meningitidisSerogroup B Serum Bactericidal Antibody Assay
Authors: Findlow Jamie , Holland Ann , Martin Diana , Oster Philipp , Balmer Paul , Borrow Ray
Published: March 2007

The surrogate of protection againstNeisseria meningitidisserogroup B (MenB) is the serum bactericidal antibody (SBA) assay, which measures the functional activity of antibody by using an exogenous complement source. Despite baby rabbit complement having been used in meningococcal serogroup A, C, Y, and W135 SBA assays, it is not recommended for use in the MenB SBA assay due to elevated SBA titers caused by low-avidity anti-MenB capsular antibody in test sera. Therefore, the possibility of absorbing anti-MenB capsular antibody from test sera to enable the use of baby rabbit complement in the MenB SBA assay was investigated by comparing the results with those gained using human complement. Colominic acid fromEscherichia coliK1, which shares the same linkage residue as MenB polysaccharide, was used as an absorbent due to the commercial unavailability of purified MenB polysaccharide. Inclusion of soluble colominic acid as an absorbent with baby rabbit complement resulted in a general reduction in SBA titers compared with those obtained using baby rabbit complement alone. However, these were not comparable to human SBA titers for all samples. Further optimization and investigations demonstrated that for some samples, colominic acid reduced titers to less than those achieved with human complement, and for others, it was not possible to inhibit titers by using colominic acid. The results suggested that the use of colominic acid will not result in the ability to use baby rabbit complement in the MenB SBA assay, thus not alleviating the difficulties in procuring human complement. However, alternative absorbents, such as purified MenB polysaccharide, may warrant further evaluation.
Carotenoid Biosynthesis in the Primitive Red Alga
Cyanidioschyzon merolae
Authors: Cunningham Francis X. , Lee Hansel , Gantt Elisabeth
Published: March 2007

Cyanidioschyzon merolae
is considered to be one of the most primitive of eukaryotic photosynthetic organisms. To obtain insights into the origin and evolution of the pathway of carotenoid biosynthesis in eukaryotic plants, the carotenoid content of
C. merolae
was ascertained, genes encoding enzymes of carotenoid biosynthesis in this unicellular red alga were identified, and the activities of two candidate pathway enzymes of particular interest, lycopene cyclase and β-carotene hydroxylase, were examined.
C. merolae
contains perhaps the simplest assortment of chlorophylls and carotenoids found in any eukaryotic photosynthetic organism: chlorophyll
a
, β-carotene, and zeaxanthin. Carotenoids with ε-rings (e.g., lutein), found in many other red algae and in green algae and land plants, were not detected, and the lycopene cyclase of
C. merolae
quite specifically produced only β-ringed carotenoids when provided with lycopene as the substrate in
Escherichia coli
. Lycopene β-ring cyclases from several bacteria, cyanobacteria, and land plants also proved to be high-fidelity enzymes, whereas the structurally related ε-ring cyclases from several plant species were found to be less specific, yielding products with β-rings as well as ε-rings.
C. merolae
lacks orthologs of genes that encode the two types of β-carotene hydroxylase found in land plants, one a nonheme diiron oxygenase and the other a cytochrome P450. A
C. merolae
chloroplast gene specifies a polypeptide similar to members of a third class of β-carotene hydroxylases, common in cyanobacteria, but this gene did not produce an active enzyme when expressed in
E. coli
. The identity of the
C. merolae
β-carotene hydroxylase therefore remains uncertain.
Posaconazole Treatment for
Apophysomyces elegans
Rhino-Orbital Zygomycosis following Trauma for a Male with Well-Controlled Diabetes
Authors: Ferguson T. D. , Schniederjan S. D. , Dionne-Odom J. , Brandt M. E. , Rinaldi M. G. , Nolte F. S. , Langston A. , Zimmer S. M.
Published: March 2007

We report a case of rhino-orbital zygomycosis in a 43-year-old male with well-controlled diabetes mellitus. The patient initially received liposomal amphotericin B, but the infection continued to progress, so posaconazole treatment was begun and eventually led to the cure of his infection. The causative agent was identified as
Apophysomyces elegans
, an emerging cause of zygomycosis in immunocompetent hosts.
Variation in the Number of Tandem Repeats and Profile of Surface Protein Genes among Invasive Group B Streptococci Correlates with Patient Age
Authors: Ho Yueh-Ren , Li Chien-Ming , Su Hsin-Pi , Wu Jane-Hong , Tseng Yu-Ching , Lin Yuh-Jyh , Wu Jiunn-Jong
Published: March 2007

The average number of tandem repeats of the
rib
gene (which encodes the Rib surface protein) in invasive group B streptococci from 29 neonates was smaller than that from 20 adults (6.8 and 8.6, respectively;
P
< 0.05), implying a distinct contribution of immunity toward this age-related variation.
Prevalence and Characteristics of Heteroresistant Vancomycin-Intermediate
Staphylococcus aureus
Bacteremia in a Tertiary Care Center
Authors: Maor Yasmin , Rahav Galia , Belausov Natasha , Ben-David Debby , Smollan Gill , Keller Nathan
Published: March 2007

Infections with
S. aureus
with heterogeneous intermediate resistance to vancomycin (hVISA) are occurring more frequently. The detection of these infections, their prevalence, clinical characteristics, and significance are controversial. During 2003 and 2004, all blood culture isolates of methicillin-resistant
Staphylococcus aureus
(264 patients) at the Sheba Medical Center, Tel Hashomer, Israel, were assessed for hVISA by using the Etest macromethod. A total of 16 patients (6%) were positive for hVISA. Resistance to teicoplanin alone and to vancomycin alone using the Etest macromethod was found in 14 and 10 patients, respectively. Standard MICs to vancomycin were between 1 to 4 mg/ml. Most of these isolates (12 of 16 [75%]) would have been missed without specific testing. The median number of bacteremic days was 4. Seven patients had positive blood cultures for more than 5 days. Twelve patients died, and for eight of these the deaths were directly related to hVISA sepsis. We found that hVISA bacteremia was prevalent in our institution, and we suggest seeking hVISA in patients with persistent
S. aureus
bacteremia.
Characterization of the Epidemic European Fusidic Acid-Resistant Impetigo Clone of
Staphylococcus aureus
Authors: O'Neill A. J. , Larsen A. R. , Skov R. , Henriksen A. S. , Chopra I.
Published: March 2007

Resistance to the antibiotic fusidic acid in European strains of
Staphylococcus aureus
causing impetigo has increased in recent years. This increase appears to have resulted from clonal expansion of a strain we have designated the epidemic European fusidic acid-resistant impetigo clone (EEFIC), which carries the fusidic acid resistance determinant
fusB
on its chromosome. To understand better the properties of the EEFIC responsible for its success, we have performed detailed phenotypic and genotypic characterization of this clone. Molecular typing revealed the EEFIC to be ST123,
spa
type t171, and
agr
type IV and therefore unrelated to earlier prevalent
fusB
+
strains found in the United Kingdom. EEFIC strains exhibited resistance to fusidic acid, penicillin, and, in some cases, erythromycin, which are all used in the treatment of impetigo. PCR analysis of the EEFIC and complete DNA sequencing of the 39.3 Kb plasmid it harbors identified genes encoding several toxins previously implicated in impetigo (exfoliative toxins A and B and EDIN-C). The location of
fusB
was mapped on the chromosome and found to be associated with a novel 16.6-kb genomic island integrated downstream of
groEL
. Although this element is related to classical staphylococcal pathogenicity islands, it does not encode any known virulence factors and consequently has been designated SaRI

fusB

(for “
S. aureus
resistance island carrying
fusB
”).
Molecular Epidemiology of
Staphylococcus saprophyticus
Isolated from Women with Uncomplicated Community-Acquired Urinary Tract Infection
Authors: Widerström Micael , Wiström Johan , Ferry Sven , Karlsson Carina , Monsen Tor
Published: March 2007

Staphylococcus saprophyticus
is a common cause of urinary tract infections (UTIs) in women. Little is known about the molecular epidemiology of
S. saprophyticus
UTIs. In the current study, we compared 76 isolates of
S. saprophyticus
prospectively isolated from women with uncomplicated UTI participating in a randomized placebo-controlled treatment trial performed in northern Sweden from 1995 to 1997 with 50 strains obtained in 2006 from five different locations in northern Europe with pulsed-field gel electrophoresis (PFGE). The aim was to elucidate the molecular epidemiology of this uropathogenic species and to investigate whether specific clones are associated with UTI in women. A total of 47 different PFGE profiles were detected among the 126 analyzed isolates. Ten clusters consisting of 5 to 12 isolates each showing PFGE DNA similarity of >85% were identified. Several clusters of genetically highly related isolates were detected in the original trial as well as among isolates obtained during 2006 from different locations. In the original trial, clonal persistence was found among 16 of 21 (76%) patients examined in the placebo group at follow-up 8 to 10 days after inclusion, indicating a low spontaneous short-time bacteriological cure rate. We conclude that multiple clones of
S. saprophyticus
were causing lower UTIs in women. The result suggests that some human-pathogenic clones of
S. saprophyticus
are spread over large geographical distances and that such clones may persist over long periods of time.
Corynebacterium accolens
Isolated from Breast Abscess: Possible Association with Granulomatous Mastitis
Authors: Ang Lei M. N. , Brown Hamish
Published: March 2007

Corynebacterium accolens
is rarely isolated as a human pathogen. We describe here a case of
C. accolens
isolated from a breast abscess in a patient previously diagnosed with granulomatous mastitis. The possible association of
Corynebacterium accolens
and granulomatous mastitis in this patient is discussed.
Evaluation of the AdvanDx VRE EVIGENE Assay for Detection of
vanA
in Vancomycin-Resistant
Staphylococcus aureus
Authors: Fosheim G. E. , Carey R. B. , Limbago B. M.
Published: March 2007

AdvanDx VRE EVIGENE, a commercial
vanA
/
vanB
DNA hybridization assay to identify vancomycin-resistant enterococci (VRE), was evaluated for the detection of
vanA
in
Staphylococcus aureus
. Performance was assessed using
S. aureus
, VRE, and vancomycin-intermediate and -susceptible isolates. The assay demonstrated 100% sensitivity and specificity when analyzed visually and by optical density.
Identification of Determinants Involved in Initiation of Hepatitis C Virus RNA Synthesis by Using Intergenotypic Replicase Chimeras
Authors: Binder Marco , Quinkert Doris , Bochkarova Olga , Klein Rahel , Kezmic Nikolina , Bartenschlager Ralf , Lohmann Volker
Published: March 2007

The 5′ nontranslated region (NTR) and the X tail in the 3′ NTR are the least variable parts of the hepatitis C virus (HCV) genome and play an important role in the initiation of RNA synthesis. By using subgenomic replicons of the HCV isolates Con1 (genotype 1) and JFH1 (genotype 2), we characterized the genotype specificities of the replication signals contained in the NTRs. The replacement of the JFH1 5′ NTR and X tail with the corresponding Con1 sequence resulted in a significant decrease in replication efficiency. Exchange of the X tail specifically reduced negative-strand synthesis, whereas substitution of the 5′ NTR impaired the generation of progeny positive strands. In search for the proteins involved in the recognition of genotype-specific initiation signals, we analyzed recombinant nonstructural protein 5B (NS5B) RNA polymerases of both isolates and found some genotype-specific template preference for the 3′ end of positive-strand RNA in vitro. To further address genotype specificity, we constructed a series of intergenotypic replicon chimeras. When combining NS3 to NS5A of Con1 with NS5B of JFH1, we observed more-efficient replication with the genotype 2a X tail, indicating that NS5B recognizes genotype-specific signals in this region. In contrast, a combination of the NS3 helicase with NS5A and NS5B was required to confer genotype specificity to the 5′ NTR. These results present the first genetic evidence for an interaction between helicase, NS5A, and NS5B required for the initiation of RNA synthesis and provide a system for the specific analysis of HCV positive- and negative-strand syntheses.
Herpes Simplex Virus Immediate-Early Protein ICP22 Triggers Loss of Serine 2-Phosphorylated RNA Polymerase II
Authors: Fraser Kathryn A. , Rice Stephen A.
Published: March 2007

During eukaryotic mRNA transcription, the synthetic activity and mRNA processing factor interactions of RNA polymerase II (RNAP II) are regulated by phosphorylation of its carboxyl-terminal domain (CTD), with modification occurring primarily on serines 2 and 5 of the CTD. We previously showed that herpes simplex virus type 1 (HSV-1) infection rapidly triggers the loss of RNAP II forms bearing serine 2 phosphorylation (Ser-2P RNAP II). Here we show that the HSV-1 immediate-early (IE) protein ICP22 is responsible for this effect during the IE phase of infection. This activity does not require the viral UL13 protein kinase, which is required for several other regulatory functions of ICP22. Additionally, we show that transient expression of ICP22 can trigger the loss of Ser-2P RNAP II in transfected cells. Thus, the ability of ICP22 to cause the loss of Ser-2 RNAP II does not require other viral factors or the context of the infected cell. Expression of the HSV-1 ICP22-related protein US1.5, which corresponds to residues 147 to 420 of ICP22, also triggers a loss of Ser-2P RNAP II in transfected cells, whereas expression of the varicella-zoster virus ICP22 homolog, ORF63, does not. Our study also provides evidence for a second, viral late gene-dependent pathway that triggers loss of Ser-2P RNAP II in infected cells, consistent with the recent work of Dai-Ju et al. (J. Q. Dai-Ju, L. Li, L. A. Johnson, and R. M. Sandri-Goldin, J. Virol. 80:3567-3581, 2006). Therefore, it appears that HSV-1 has evolved redundant mechanisms for triggering the loss of a specific phosphorylated form of RNAP II.
A Phylogenetically Conserved RNA Structure in the Poliovirus Open Reading Frame Inhibits the Antiviral Endoribonuclease RNase L
Authors: Han Jian-Qiu , Townsend Hannah L. , Jha Babal Kant , Paranjape Jayashree M. , Silverman Robert H. , Barton David J.
Published: March 2007

RNase L is an antiviral endoribonuclease that cleaves viral mRNAs after single-stranded UA and UU dinucleotides. Poliovirus (PV) mRNA is surprisingly resistant to cleavage by RNase L due to an RNA structure in the 3C
Pro
open reading frame (ORF). The RNA structure associated with the inhibition of RNase L is phylogenetically conserved in group C enteroviruses, including PV type 1 (PV1), PV2, PV3, coxsackie A virus 11 (CAV11), CAV13, CAV17, CAV20, CAV21, and CAV24. The RNA structure is not present in other human enteroviruses (group A, B, or D enteroviruses). Coxsackievirus B3 mRNA and hepatitis C virus mRNA were fully sensitive to cleavage by RNase L. HeLa cells expressing either wild-type RNase L or a dominant-negative mutant RNase L were used to examine the effects of RNase L on PV replication. PV replication was not inhibited by RNase L activity, but rRNA cleavage characteristic of RNase L activity was detected late during the course of PV infection, after assembly of intracellular virus. Rather than inhibiting PV replication, RNase L activity was associated with larger plaques and better cell-to-cell spread. Mutations in the RNA structure associated with the inhibition of RNase L did not affect the magnitude of PV replication in HeLa cells expressing RNase L, consistent with the absence of observed RNase L activity until after virus assembly. Thus, PV carries an RNA structure in the 3C protease ORF that potently inhibits the endonuclease activity of RNase L, but this RNA structure does not prevent RNase L activity late during the course of infection, as virus assembly nears completion.
Novel Nuclear Import of Vpr Promoted by Importin α Is Crucial for Human Immunodeficiency Virus Type 1 Replication in Macrophages
Authors: Nitahara-Kasahara Yuko , Kamata Masakazu , Yamamoto Takuya , Zhang Xianfeng , Miyamoto Yoichi , Muneta Koho , Iijima Sayuki , Yoneda Yoshihiro , Tsunetsugu-Yokota Yasuko , Aida Yoko
Published: March 2007

Monocytes/macrophages are major targets of human immunodeficiency virus type 1 (HIV-1) infection. The viral preintegration complex (PIC) of HIV-1 enters the nuclei of monocyte-derived macrophages, but very little PIC migrates into the nuclei of immature monocytes. Vpr, one of the accessory gene products of HIV-1, is essential for the nuclear import of PIC in these cells, although the role of Vpr in the entry mechanism of PIC remains to be clarified. We have shown previously that Vpr is targeted to the nuclear envelope and then transported into the nucleus by importin α alone, in an importin β-independent manner. Here we demonstrate that the nuclear import of Vpr is strongly promoted by the addition of cytoplasmic extract from macrophages but not of that from monocytes and that the nuclear import activity is lost with immunodepletion of importin α from the cytoplasmic extract. Immunoblot analysis and real-time PCR demonstrate that immature monocytes express importin α at low levels, whereas the expression of three major importin α isoforms markedly increases upon their differentiation into macrophages, indicating that the expression of importin α is required for nuclear import of Vpr. Furthermore, interaction between importin α and the N-terminal α-helical domain of Vpr is indispensable, not only for the nuclear import of Vpr but also for HIV-1 replication in macrophages. This study suggests the possibility that the binding of Vpr to importin α, preceding a novel nuclear import process, is a potential target for therapeutic intervention.
La Crosse Bunyavirus Nonstructural Protein NSs Serves To Suppress the Type I Interferon System of Mammalian Hosts
Authors: Blakqori Gjon , Delhaye Sophie , Habjan Matthias , Blair Carol D. , Sánchez-Vargas Irma , Olson Ken E. , Attarzadeh-Yazdi Ghassem , Fragkoudis Rennos , Kohl Alain , Kalinke Ulrich , Weiss Siegfried , Michiels Thomas , Staeheli Peter , Weber Friedemann
Published: March 2007

La Crosse virus (LACV) is a mosquito-transmitted member of the
Bunyaviridae
family that causes severe encephalitis in children. For the LACV nonstructural protein NSs, previous overexpression studies with mammalian cells had suggested two different functions, namely induction of apoptosis and inhibition of RNA interference (RNAi). Here, we demonstrate that mosquito cells persistently infected with LACV do not undergo apoptosis and mount a specific RNAi response. Recombinant viruses that either express (rLACV) or lack (rLACVdelNSs) the NSs gene similarly persisted and were prone to the RNAi-mediated resistance to superinfection. Furthermore, in mosquito cells overexpressed LACV NSs was unable to inhibit RNAi against Semliki Forest virus. In mammalian cells, however, the rLACVdelNSs mutant virus strongly activated the antiviral type I interferon (IFN) system, whereas rLACV as well as overexpressed NSs suppressed IFN induction. Consequently, rLACVdelNSs was attenuated in IFN-competent mouse embryo fibroblasts and animals but not in systems lacking the type I IFN receptor. In situ analyses of mouse brains demonstrated that wild-type and mutant LACV mainly infect neuronal cells and that NSs is able to suppress IFN induction in the central nervous system. Thus, our data suggest little relevance of the NSs-induced apoptosis or RNAi inhibition for growth or pathogenesis of LACV in the mammalian host and indicate that NSs has no function in the insect vector. Since deletion of the viral NSs gene can be fully complemented by inactivation of the host's IFN system, we propose that the major biological function of NSs is suppression of the mammalian innate immune response.
Influenza Virus Infection Causes Specific Degradation of the Largest Subunit of Cellular RNA Polymerase II
Authors: Rodriguez A. , Pérez-González A. , Nieto A.
Published: March 2007

It has been described that influenza virus polymerase associates with RNA polymerase II (RNAP II). To gain information about the role of this interaction, we explored if changes in RNAP II occur during infection. Here we show that influenza virus causes the specific degradation of the hypophosphorylated form of the largest subunit of RNAP II without affecting the accumulation of its hyperphosphorylated forms. This effect is independent of the viral strain and the origin of the cells used. Analysis of synthesized mRNAs in isolated nuclei of infected cells indicated that transcription decreases concomitantly with RNAP II degradation. Moreover, this degradation correlated with the onset of viral transcription and replication. The ubiquitin-mediated proteasome pathway is not involved in virally induced RNAP II proteolysis. The expression of viral polymerase from its cloned cDNAs was sufficient to cause the degradation. Since the PA polymerase subunit has proteolytic activity, we tested its participation in the process. A recombinant virus that encodes a PA point mutant with decreased proteolytic activity and that has defects in replication delayed the effect, suggesting that PA's contribution to RNAP II degradation occurs during infection.
APOBEC3G Multimers Are Recruited to the Plasma Membrane for Packaging into Human Immunodeficiency Virus Type 1 Virus-Like Particles in an RNA-Dependent Process Requiring the NC Basic Linker
Authors: Burnett Atuhani , Spearman Paul
Published: March 2007

APOBEC3G is an endogenous host restriction factor that inhibits human immunodeficiency virus (HIV) replication. The antiviral activity of APOBEC3G is dependent upon its incorporation into the virus particle. The mechanisms governing incorporation of APOBEC3G into virus particles are not completely understood. In particular, some investigators have reported that APOBEC3G interacts directly with the nucleocapsid (NC) subunit of Gag, while others have found that an RNA intermediate is required for Gag-APOBEC3G interactions. In this study, we confirmed the RNA dependence of APOBEC3G packaging and performed detailed mapping of the determinants within NC that are required for virion incorporation. Surprisingly, APOBEC3G packaging did not correlate well with the presence of the N-terminal “I,” or interaction, domain within NC. Specifically, Gag constructs containing only the N-terminal region of NC packaged minimal amounts of APOBEC3G, while significant levels of APOBEC3G packaging were achieved with Gag constructs containing the basic linker region of NC. Furthermore, membrane-binding experiments revealed that the basic linker region was essential for the membrane association of APOBEC3G in a Gag-APOBEC3G complex. Fluorescence resonance energy transfer was detected between labeled APOBEC3G in cells and in particles, indicating that APOBEC3G is packaged as a multimer that is bound to packaged RNA. Regions of APOBEC3G-Gag colocalization at the plasma membrane were detected that were distinct from the punctate cytoplasmic bodies where APOBEC3G accumulates within the cell. Together, our results indicate that APOBEC3G multimerizes in an RNA-dependent fashion and that RNA-APOBEC3G multimers are recruited to the plasma membrane and subsequently into virion particles by Gag.
Role of the Sonchus Yellow Net Virus N Protein in Formation of Nuclear Viroplasms
Authors: Deng Min , Bragg Jennifer N. , Ruzin Steven , Schichnes Denise , King David , Goodin Michael M. , Jackson Andrew O.
Published: March 2007

Sonchus yellow net virus
is a plant nucleorhabdovirus whose nucleocapsid (N), phosphoprotein (P), and polymerase (L) proteins form large viroplasms in the nuclei of infected plants (C. R. F. Martins, J. A. Johnson, D. M. Lawrence, T. J. Choi, A. Pisi, S. L. Tobin, D. Lapidus, J. D. O. Wagner, S. Ruzin, K. McDonald, and A. O. Jackson, J. Virol. 72:5669-5679, 1998). When expressed alone, the N protein localizes to the nuclei of plant and yeast (
Saccharomyces cerevisiae
) cells and the P protein is distributed throughout the cells, but coexpression of N and P results in formation of subnuclear viroplasm-like foci (M. M. Goodin, J. Austin, R. Tobias, M. Fujita, C. Morales, and A. O. Jackson, J. Virol. 75:9393-9406, 2001; M. M. Goodin, R. G. Dietzgen, D. Schichnes, S. Ruzin, and A. O. Jackson, Plant J. 31:375-383, 2002). We now show that the N protein and various fluorescent derivatives form similar subnuclear foci in plant cells and that homologous interactions mediated by a helix-loop-helix region near the amino terminus are required for formation of the foci. Mutations within the helix-loop-helix region also interfere with N- and P-protein interactions that are required for N and P colocalization in the subnuclear foci. Affinity purification of N proteins harboring single mutations within the motif revealed that Tyr40 is critical for N-N and N-P interactions. Additional in vitro binding assays also indicated that the N protein binds to yeast and plant importin α homologues, whereas mutations in the carboxy-terminal nuclear localization signal abrogate importin α binding. The P protein did not bind to the importin α homologues, suggesting that the N and P proteins use different pathways for nuclear entry. Our results in toto support a model suggesting that during infection, the N and P proteins enter the nucleus independently, that viroplasm formation requires homologous N-protein interactions, and that P protein targeting to the viroplasm requires N-P protein interactions that occur after N and P protein import into the nucleus.
In Vivo Fitness Costs of Different Gag CD8 T-Cell Escape Mutant Simian-Human Immunodeficiency Viruses for Macaques
Authors: Loh Liyen , Batten C. Jane , Petravic Janka , Davenport Miles P. , Kent Stephen J.
Published: March 2007

The kinetics of immune escape and reversion depend upon the efficiency of CD8 cytotoxic T lymphocytes (CTL) and the fitness cost of escape mutations. Escape kinetics of three simian immunodeficiency virus Gag CTL epitopes in pigtail macaques were variable; those of KP9 and AF9 were faster than those of KW9. Kinetics of reversion of escape mutant virus to wild type upon passage to naïve major histocompatibility complex-mismatched macaques also varied. Rapid reversion occurred at KP9, gradual biphasic reversion occurred at AF9, and escape mutant KW9 virus failed to revert. The fitness impact of these mutations is KP9 > AF9 > KW9. These data provide insights into the differential utility of CTL in controlling viremia.
Quantum Effects on the Caloric Curves of Lithium Clusters
Authors: Spiegelman Fernand , Calvo Florent
Published: March 2007

A tight-binding quantum Hamiltonian and an empirical embedded-atom model (EAM) potential are used to get insight into the finite-temperature behavior of small Lin clusters, n = 8, 20, and 55. Exchange Monte Carlo simulations provide an extensive sampling of configuration space, including the putative global minimum and many relevant isomers. The heat capacities obtained from the classical simulations are corrected for low-temperature quantum delocalization using the Pitzer-Gwinn approximation. Alternatively, the caloric curves are estimated from the database of local minima using the quantum harmonic superposition approximation. While the two atomistic models predict qualitatively similar features, including some premelting effects in Li20 but none in Li55, strong variations are observed in the melting temperatures, the EAM potential giving unexpectedly low values.
Recurrent prostatic stromal sarcoma with massive high-grade prostatic intraepithelial neoplasia
Authors: Morikawa Teppei , Goto Akiteru , Tomita Kyoichi , Tsurumaki Yuzuri , Ota Satoshi , Kitamura Tadaichi , Fukayama Masashi
Published: March 2007

A unique case of prostatic stromal sarcoma (PSS) that recurred in the pelvic cavity with massive high-grade prostatic intraepithelial neoplasia is described. A 52-year-old man who presented with urinary retention underwent a radical cystoprostatectomy. Tumour tissues of the prostate showed an admixture of hyperplastic glands and markedly cellular stroma of spindle cells arranged in a fascicular pattern, and the tumour was diagnosed as PSS. 66 months after the operation, CT scans revealed three recurrent tumours around the bilateral obturator and left fore iliopsoas. The recurrent tumours were biphasic neoplasms, as before, but the epithelial component had grown prominent and manifested overt atypia in a manner resembling high-grade prostatic intraepithelial neoplasia. Our findings suggest that not only the stromal component but also and the epithelial components of PSS may have malignant potential.
Cervical embryonal rhabdomyosarcoma and ovarian Sertoli–Leydig cell tumour: a more than coincidental association of two rare neoplasms?
Authors: McClean Gareth E , Kurian Susy , Walter Noel , Kekre A , Glenn McCluggage W
Published: March 2007

A case in which an embryonal rhabdomyosarcoma of the cervix and an ovarian Sertoli–Leydig cell tumour of intermediate differentiation occurred in a 13-year-old girl is described. Although initially considered as a chance association, a review of the literature showed the co-occurrence of these two uncommon neoplasms in three previous cases. The reason for this association, which is thought to be more than coincidental, is not known, although an underlying genetic abnormality is a possibility. The ovarian tumour in this case was characterised by the presence of foci of cells with extremely pleomorphic nuclei, which initially raised the possibility of metastatic rhabdomyosarcoma. These were interpreted as foci of bizarre nuclei within the Sertoli–Leydig cell tumour.
Sarcoidosis of the prostate
Authors: Furusato Bungo , Koff Stacey , McLeod David G , Sesterhenn Isabell A
Published: March 2007

A 55-year-old African-American man with clinical stage T1c prostate cancer underwent prostatectomy. Non-caseating, epithelioid granulomata adjacent to the anterior fibromuscular stroma were found incidentally. The granulomata included Langhans giant cells with rare conchoidal bodies. The distribution of the granulomata was not that of non-specific granulomatous prostatitis centred around ducts and glands. By immunohistochemistry, the epithelioid cells were positive for angiotensin-converting enzyme. The histological appearance suggested sarcoidosis, which was confirmed by the clinical history. Four years earlier, the patient had been treated for sarcoidosis.
Coronary artery bypass surgery in elderly people
Authors: Natarajan Arun , Samadian Samad , Clark Stephen
Published: March 2007

An increasing number of elderly individuals are now undergoing coronary artery bypass surgery. Elderly patients, compared with patients of a younger age group, present for surgery with a greater burden of risk factors and reduced functional levels. Short-term outcomes are hence poorer in them. But symptom relief occurs in most survivors and is accompanied by excellent rates of long-term survival and a good quality of life. Therefore, an individualised risk–benefit profile must be carefully constructed by clinicians, taking into account several different factors and not just age alone. This review summarises the current concepts of coronary artery bypass surgery from the perspective of the very old.
Clinical attachments: fond farewell or new beginning? A survey of the attitudes and practice of medical consultants and international medical graduates
Authors: Wawdhane Sudhir , Saraf Vivek , Davidson Sharon , Trewby Peter
Published: March 2007

Objectives

To analyse the experience of clinical attachment (CA) of international medical graduates (IMGs) and consultants.

Design

Analysis of questionnaires and CVs.

Setting and participants

573 IMGs applying for a house officer post and 102 consultant physicians working in North East England.

Results

IMGs had spent a mean of 16 months unemployed, of which 3.8 months was spent on CAs. The median number of CAs was two and the average number of applications sent before obtaining a CA was 73. 90% of IMGs found their CA helpful and 57% would not take up a post without a CA first. Criticisms related to lack of responsibility, isolation and poor job prospects. 90% would apply for honorary posts if advertised. 73% had received induction at the onset of placement, but only 32% had been assessed at the end. 50% of consultants took CAs and only 4% were thinking of stopping doing so. Those without CAs blamed work pressure (43%) and pressure from their employer (23%).

Conclusions

There are deficiencies in pastoral care, the application process and assessment, but CAs are valued by IMGs and offered by half the consultants surveyed. New immigration rules will mean fewer IMGs will come to the UK, but CAs will be needed by those that do, as well by refugees and European Economic Area (EEA) graduates. The tradition of CAs for international graduates could be used to accommodate those coming to the UK on exchanges and scholarships and form part of the recently announced Medical Training Initiative for IMGs.
Paradoxical vocal cord motion disorder: past, present and future
Authors: Ibrahim Wanis H , Gheriani Heitham A , Almohamed Ahmed A , Raza Tasleem
Published: March 2007

Paradoxical vocal cord motion disorder (PVCM), also called vocal cord dysfunction, is an important differential diagnosis for asthma. The disorder is often misdiagnosed as asthma leading to unnecessary drug use, very high medical utilisation and occasionally tracheal intubation or tracheostomy. Laryngoscopy is the gold standard for diagnosis of PVCM. Speech therapy and psychotherapy are considered the cornerstone of management of this disorder. The aim of this article is to increase the awareness of PVCM among doctors, highlighting the main characteristics that distinguish it from asthma and discuss the recent medical achievements and the possible future perspectives related to this disorder.
Performance of clay samples reinforced with vertical granular columns
Authors: Black J , Sivakumar V , McKinley J D
Published: March 2007

This paper reports an experimental study in which samples of soft kaolin clay (100 mm in diameter and 200 mm in height) were reinforced with vertical columns of sand and tested under triaxial conditions. Samples were reinforced with either a single column of sand of 32 mm diameter or three columns of sand, each of 20 mm diameter. The replacement method was used to form the columns. The columns were installed in the clay to depths of 120 and 200 mm. Tests were also carried out on samples that were not reinforced with sand columns. The samples were compressed under both drained and undrained conditions. It was found that the undrained shear strength of samples containing full-depth columns was greatly improved compared with that of the unreinforced samples. In the fully drained tests, the sample installed with a single column of 32 mm diameter exhibited better performance than the sample with three columns of 20 mm diameter, although the area replacement ratio in the case of the three 20 mm diameter columns was higher than that of the single 32 mm diameter column. However, the undrained strength of the composite material was not particularly affected by the number of columns.Key words: Ground improvement, undrained shear strength, consolidation, stress path, settlement.
Reanalysis of a municipal landfill slope failure near Cincinnati, Ohio, USA
Authors: Chugh Ashok K , Stark Timothy D , DeJong Kees A
Published: March 2007

The March 1996 slope failure in a municipal solid waste landfill near Cincinnati, Ohio, USA, is reanalyzed using continuum-mechanics-based procedures implemented in the computer programs FLAC and FLAC3D. A failure mechanism, based on the field observations of the failure, is used for the analyses. The failure mechanism is also implemented in a limit-equilibrium-based slope stability analysis computer program, SSTAB2, to simulate the observed translational character of the failure. The reanalysis results (failure surface, factor-of-safety (FoS), and displacement) from the continuum models are in general agreement with the field data. The FoS values from SSTAB2, FLAC, and FLAC3D range in the expected order. Overall, the reanalysis results supplement previously reported failure analyses. This paper serves two functions: (1) it documents the results of reanalysis using a different (from the previously published) failure mechanism hypothesis for the 1996 landfill slope failure near Cincinnati, Ohio; and (2) it demonstrates the use of 2-D and 3-D continuum models to study: (i) onset of instability; (ii) failure surface geometry and location; and (iii) displacements associated with slope failures.Key words: municipal landfill, slope failure, numerical analysis, limit equilibrium, continuum mechanics, displacement.
Effect of centrifuge radius on hydraulic conductivity measured in a falling-head test
Authors: Sharma Jitendra S , Samarasekera Lal
Published: March 2007

An equation for the estimation of hydraulic conductivity from a falling-head test conducted in a centrifuge is derived that takes into account linearly increasing centrifugal acceleration across the soil sample. This equation indicates that, in the case of a falling-head test conducted using a small radius centrifuge, the assumption of constant centrifugal acceleration could result in significant underestimation of hydraulic conductivity. It is also shown that ignoring the curvature of the water table in a centrifuge model could also result in slight overestimation of hydraulic conductivity. The importance of setting the centrifuge acceleration level at an appropriate radial distance to achieve correct modelling of the prototype is also emphasized.Key words: hydraulic conductivity, centrifuge modelling, falling-head test.
On yield stresses and the influence of curing stresses on stress paths and strength measured in triaxial testing of stabilized soils
Authors: Åhnberg Helen
Published: March 2007

Studies on the behaviour of stabilized soils under different loading conditions are essential to identify which parameters are relevant in the design of deep mixing. An investigation has been performed on soils stabilized with different types of binders with the purpose of demonstrating the effects of quasi-preconsolidation pressures, i.e., yield stresses that are not primarily linked to previous consolidation pressures but to the cementation taking place, on the strength behaviour of stabilized soil. The effect of stresses applied during curing has also been studied. Drained triaxial compression tests and undrained triaxial compression and extension tests were performed on two stabilized clays. The binders used were cement, lime, slag, and fly ash in different combinations. Comparisons have also been made with results from previous tests on two organic soils stabilized with much the same types of binder. The results show that both the cementation processes involved and the stresses applied during curing affect the quasi-preconsolidation pressure. This pressure is strongly linked to the strength of the stabilized soil and has a considerable influence on its deformation behaviour. A model is proposed which describes the strength behaviour in the same effective stress plane that is commonly used for natural clays.Key words: stabilization, triaxial tests, strength, quasi-preconsolidation pressure, strain, binders.