bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Skin Test for Bovine Tuberculosis for Differentiating Infected from Vaccinated Animals
Authors: Whelan Adam O. , Clifford Derek , Upadhyay Bhagwati , Breadon Eleanor L. , McNair James , Hewinson Glyn R. , Vordermeier Martin H.
Published: July 2010

The tuberculin skin test has been used for the diagnosis of bovine and human tuberculosis (TB) for over a hundred years. However, the specificity of the test is compromised by vaccination with theMycobacterium bovis-derived vaccine strain bacille Calmette-Guérin (BCG). Since current promising vaccines against bovine TB are based on heterologous prime-boost combinations that include BCG, there is a need for diagnostic tests for differentiating infected from vaccinated animals (DIVA). The application of antigens such as ESAT-6 and CFP-10 for DIVA has so far been realized largely through their application in the blood-based gamma interferon release assay. In the current study, we have reassessed the potential of such antigens as skin test reagents for DIVA in cattle. A cocktail of theMycobacterium tuberculosiscomplex recombinant protein antigens ESAT-6, CFP-10, MPB70, and MPB83 elicited delayed-type hypersensitivity (DTH) skin test responses in 78% of naturally infected tuberculin-positive cattle. Importantly, this cocktail induced no skin responses in BCG-vaccinated cattle despite them being sensitized for strong tuberculin responses. Further optimization of skin test antigen combinations identified that the inclusion of Rv3615c (Mb3645c) enhanced skin test sensitivity in naturally infected cattle without compromising specificity. In addition, we demonstrate for the first time the utility of synthetic peptides as promising skin test antigens for bovine TB for DIVA. Our data provide a promising basis for the future development of skin tests for DIVA with practical relevance for TB diagnosis in both veterinary and clinical settings.
Wild-Type MIC Distributions and Epidemiological Cutoff Values for the Triazoles and Six
Aspergillus
spp. for the CLSI Broth Microdilution Method (M38-A2 Document)
Authors: Espinel-Ingroff A. , Diekema D. J. , Fothergill A. , Johnson E. , Pelaez T. , Pfaller M. A. , Rinaldi M. G. , Canton E. , Turnidge J.
Published: July 2010

Clinical breakpoints have not been established for mold testing. Wild-type (WT) MIC distributions (organisms in a species/drug combination with no detectable acquired resistance mechanisms) were defined in order to establish epidemiologic cutoff values (ECVs) for five
Aspergillus
spp. and itraconazole, posaconazole, and voriconazole. Also, we have expanded prior ECV data for
Aspergillus fumigatus.
The number of available isolates varied according to the species/triazole combination as follows: 1,684 to 2,815 for
A. fumigatus
, 323 to 592 for
A. flavus
, 131 to 143 for
A. nidulans
, 366 to 520 for
A. niger
, 330 to 462 for
A. terreus
, and 45 to 84 for
A. versicolor
. CLSI broth microdilution MIC data gathered in five independent laboratories in Europe and the United States were aggregated for the analyses. ECVs expressed in μg/ml were as follows (percentages of isolates for which MICs were equal to or less than the ECV are in parentheses):
A. fumigatus
, itraconazole, 1 (98.8%); posaconazole, 0.5 (99.2%); voriconazole, 1 (97.7%);
A. flavus
, itraconazole, 1 (99.6%); posaconazole, 0.25 (95%); voriconazole, 1 (98.1%);
A. nidulans
, itraconazole, 1 (95%); posaconazole, 1 (97.7%); voriconazole, 2 (99.3%);
A. niger
, itraconazole, 2 (100%); posaconazole, 0.5 (96.9%); voriconazole, 2 (99.4%);
A. terreus
, itraconazole, 1 (100%); posaconazole, 0.5 (99.7%); voriconazole, 1 (99.1%);
A. versicolor
, itraconazole, 2 (100%); posaconazole, 1 (not applicable); voriconazole, 2 (97.5%). Although ECVs do not predict therapy outcome as clinical breakpoints do, they may aid in detection of azole resistance (non-WT MIC) due to
cyp51A
mutations, a resistance mechanism in some
Aspergillus
spp. These ECVs should be considered for inclusion in the future CLSI M38-A2 document revision.
Incidence, Characteristics, and Outcomes of
Staphylococcus lugdunensis
Bacteremia
Authors: Choi Seong-Ho , Chung Jin-Won , Lee Eun Jung , Kim Tae Hyong , Lee Mi Suk , Kang Jae Myung , Song Eun Hee , Jun Jae-Bum , Kim Mi-Na , Kim Yang Soo , Woo Jun Hee , Choi Sang-Ho
Published: July 2010

Of 63 patients with
Staphylococcus lugdunensis
bacteremia, 15 (23.8%) had clinically significant bacteremia, with an incidence of 1.3 cases per 100,000 admissions. Of the five patients with community-acquired
S. lugdunensis
bacteremia, three had endocarditis. Catheters were the most common portal of entry for health-care-associated or hospital-acquired bacteremia. Only one patient died of bacteremia-related causes.
Epidemiology and Genetic Characterization of Hepatitis A Virus Genotype IIA
Authors: Desbois Delphine , Couturier Elisabeth , Mackiewicz Vincent , Graube Arielle , Letort Marie-José , Dussaix Elisabeth , Roque-Afonso Anne-Marie
Published: July 2010

Three hepatitis A virus (HAV) genotypes, I, II, and III, divided into subtypes A and B, infect humans. Genotype I is the most frequently reported, while genotype II is hardly ever isolated, and its genetic diversity is unknown. From 2002 to 2007, a French epidemiological survey of HAV identified 6 IIA isolates, mostly from patients who did not travel abroad. The possible African origin of IIA strains was investigated by screening the 2008 mandatory notification records of HAV infection: 171 HAV strains from travelers to West Africa and Morocco were identified. Genotyping was performed by sequencing of the VP1/2A junction in 68 available sera. Entire P1 and 5′ untranslated regions of IIA strains were compared to reference sequences of other genotypes. The screening retrieved 5 imported IIA isolates. An additional autochthonous case and 2 more African cases were identified in 2008 and 2009, respectively. A total of 14 IIA isolates (8 African and 6 autochthonous) were analyzed. IIA sequences presented lower nucleotide and amino acid variability than other genotypes. The highest variability was observed in the N-terminal region of VP1, while for other genotypes the highest variability was observed at the VP1/2A junction. Phylogenetic analysis identified 2 clusters, one gathering all African and two autochthonous cases and a second including only autochthonous isolates. In conclusion, most IIA strains isolated in France are imported by travelers returning from West Africa. However, the unexplained contamination mode of autochthonous cases suggests another, still to be discovered geographical origin or a French reservoir to be explored.
Leukoencephalopathy Associated with Parvovirus Infection in Cretan Hound Puppies
Authors: Schaudien D. , Polizopoulou Z. , Koutinas A. , Schwab S. , Porombka D. , Baumgärtner W. , Herden C.
Published: July 2010

Leukoencephalopathies in dogs encompass presumably inherited conditions such as leukodystrophies, hypomyelination or spongiform degeneration, but other causes, such as virus infections and toxic or nutritional factors, might also play a contributory role. In this report, we provide evidence of parvovirus infection and replication in the brains of five 6-week-old Cretan hound puppies suffering from a puppy shaker syndrome and leukoencephalopathy. Although these puppies belonged to two different litters, they were closely related, tracing back two generations to the same sire. Histologically, a mild to moderate lymphohistiocytic meningitis, with focal lymphohistiocytic leukoencephalitis in two animals, and a mild to moderate vacuolation with myelin loss, mainly in the white matter of the cerebellum was detected. Vacuolation was also found in the corpus callosum, fimbria hippocampi, mesencephalon, capsula interna, basal ganglia, and hypothalamus. By immunohistology andin situhybridization, either parvoviral antigen, DNA, mRNA, or replicative intermediate DNA were detected in the cerebellum, hippocampus, periventricular areas, corpus callosum, cerebral cortex, medulla oblongata, and spinal cord. Parvovirus antigen, DNA, and mRNA were present in cells of the outer granular layer of the cerebellum and in periventricular cells, most likely representing spongioblasts, glial cells, neurons, endothelial cells, occasional macrophages, and ependymal cells. Sequencing revealed canine parvovirus type 2 stretches. Thus, an association of parvovirus infection with the leukoencephalopathy seems likely, possibly facilitated by a genetic predisposition due to the mode of inbreeding in this particular dog breed.
Induction and Inhibition of Type I Interferon Responses by Distinct Components of Lymphocytic Choriomeningitis Virus
Authors: Zhou Shenghua , Cerny Anna M. , Zacharia An , Fitzgerald Katherine A. , Kurt-Jones Evelyn A. , Finberg Robert W.
Published: July 2010

Type I interferons (IFNs) play a critical role in the host defense against viruses. Lymphocytic choriomeningitis virus (LCMV) infection induces robust type I IFN production in its natural host, the mouse. However, the mechanisms underlying the induction of type I IFNs in response to LCMV infection have not yet been clearly defined. In the present study, we demonstrate that IRF7 is required for both the early phase (day 1 postinfection) and the late phase (day 2 postinfection) of the type I IFN response to LCMV, and melanoma differentiation-associated gene 5 (MDA5)/mitochondrial antiviral signaling protein (MAVS) signaling is crucial for the late phase of the type I IFN response to LCMV. We further demonstrate that LCMV genomic RNA itself (without other LCMV components) is able to induce type I IFN responses in various cell types by activation of the RNA helicases retinoic acid-inducible gene I (RIG-I) and MDA5. We also show that expression of the LCMV nucleoprotein (NP) inhibits the type I IFN response induced by LCMV RNA and other RIG-I/MDA5 ligands. These virus-host interactions may play important roles in the pathogeneses of LCMV and other human arenavirus diseases.
Prophylactic Treatment with a G Glycoprotein Monoclonal Antibody Reduces Pulmonary Inflammation in Respiratory Syncytial Virus (RSV)-Challenged Naïve and Formalin-Inactivated RSV-Immunized BALB/c Mice
Authors: Radu Gertrud U. , Caidi Hayat , Miao Congrong , Tripp Ralph A. , Anderson Larry J. , Haynes Lia M.
Published: July 2010

We examined whether prophylactically administered anti-respiratory syncytial virus (anti-RSV) G monoclonal antibody (MAb) would decrease the pulmonary inflammation associated with primary RSV infection and formalin-inactivated RSV (FI-RSV)-enhanced disease in mice. MAb 131-2G administration 1 day prior to primary infection reduced the pulmonary inflammatory response and the level of RSV replication. Further, intact or F(ab′)
2
forms of MAb 131-2G administered 1 day prior to infection in FI-RSV-vaccinated mice reduced enhanced inflammation and disease. This study shows that an anti-RSV G protein MAb might provide prophylaxis against both primary infection and FI-RSV-associated enhanced disease. It is possible that antibodies with similar reactivities might prevent enhanced disease and improve the safety of nonlive virus vaccines.
RNA 5′-Triphosphatase Activity of the Hepatitis E Virus Helicase Domain
Authors: Karpe Yogesh A. , Lole Kavita S.
Published: July 2010

Hepatitis E virus (HEV) has a positive-sense RNA genome with a 5′-m7G cap. HEV open reading frame 1 (ORF1) encodes a polyprotein with multiple enzyme domains required for replication. HEV helicase is a nucleoside triphosphatase (NTPase) with the ability to unwind RNA duplexes in the 5′-to-3′ direction. When incubated with 5′-[γ-
32
P]RNA and 5′-[α-
32
P]RNA, HEV helicase released
32
P only from 5′-[γ-
32
P]RNA, showing specificity for the γ-β-triphosphate bond. Removal of γ-phosphate from the 5′ end of the primary transcripts (pppRNA to ppRNA) by RNA triphosphatase is an essential step during cap formation. It is suggested that HEV employs the helicase to mediate the first step of 5′ cap synthesis.
Dendritic Cells Loaded with Tumor B Cells Elicit Broad Immunity against Murine Gammaherpesvirus 68 but Fail To Prevent Long-Term Latency
Authors: Weslow-Schmidt Janet , Ye Fang , Cush Stephanie S. , Stuller Kathleen A. , Blackman Marcia A. , Flaño Emilio
Published: July 2010

It is still unknown whether a noninfectious gammaherpesvirus vaccine is able to prevent or reduce virus persistence. This led us to use dendritic cells loaded with tumor B cells as a vaccine approach for the murine gammaherpesvirus 68 (γHV68) model of infection. Dendritic cells loaded with UV-irradiated latently infected tumor B cells induce broad, strong, and long-lasting immunity against γHV68. Dendritic cell vaccination prevents the enlargement of lymph nodes and severely limits acute infection and early latency but does not prevent γHV68 from establishing long-term latency. Our findings support the concept that attenuated viruses may be the best vaccine option for preventing gammaherpesvirus persistence.
Mutational Mapping of UL130 of Human Cytomegalovirus Defines Peptide Motifs within the C-Terminal Third as Essential for Endothelial Cell Infection
Authors: Schuessler Andrea , Sampaio Kerstin Laib , Scrivano Laura , Sinzger Christian
Published: July 2010

The UL130 gene is one of the major determinants of endothelial cell (EC) tropism of human cytomegalovirus (HCMV). In order to define functionally important peptides within this protein, we have performed a charge-cluster-to-alanine (CCTA) mutational scanning of UL130 in the genetic background of a bacterial artificial chromosome-cloned endotheliotropic HCMV strain. A total of 10 charge clusters were defined, and in each of them two or three charged amino acids were replaced with alanines. While the six N-terminal clusters were phenotypically irrelevant, mutation of the four C-terminal clusters each caused a reduction of EC tropism. The importance of this protein domain was further emphasized by the fact that the C-terminal pentapeptide PNLIV was essential for infection of ECs, and the cell tropism could not be rescued by a scrambled version of this sequence. We conclude that the C terminus of the UL130 protein serves an important function for infection of ECs by HCMV. This makes UL130 a promising molecular target for antiviral strategies, e.g., the development of antiviral peptides.
Inhibition of Cellular Proteasome Activities Mediates HBX-Independent Hepatitis B Virus ReplicationIn Vivo
Authors: Zhang Zhensheng , Sun Eun , Ou Jing-hsiung James , Liang T. Jake
Published: July 2010

The X protein (HBX) of the hepatitis B virus (HBV) is essential for HBV productive infectionin vivo. Our previous study (Z. Hu, Z. Zhang, E. Doo, O. Coux, A. L. Goldberg, and T. J. Liang, J. Virol. 73:7231-7240, 1999) shows that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. Previously, we demonstrated that HBX affects hepadnaviral replication through a proteasome-dependent pathway in cell culture models. In the present study, we studied the effect of the proteasome inhibitor MLN-273 in two HBV mouse models. We demonstrated that administration of MLN-273 to transgenic mice containing the replication-competent HBV genome with the defective HBX gene substantially enhanced HBV replication, while the compound had a minor effect on wild-type HBV transgenic mice. Similar results were obtained by using C57BL/6 mice infected with recombinant adenoviruses expressing the replicating HBV genome. Our data suggest that HBV replication is subjected to regulation by cellular proteasome and HBX functions through the inhibition of proteasome activities to enhance HBV replicationin vivo.
Foot-and-Mouth Disease Virus Replicates Only Transiently in Well-Differentiated Porcine Nasal Epithelial Cells
Authors: Dash Pradyot , Barnett Paul V. , Denyer Michael S. , Jackson Terry , Stirling Catrina M. A. , Hawes Philippa C. , Simpson Jennifer L. , Monaghan Paul , Takamatsu Haru-H.
Published: July 2010

Three-dimensional (3D) porcine nasal mucosal and tracheal mucosal epithelial cell cultures were developed to analyze foot-and-mouth disease virus (FMDV) interactions with mucosal epithelial cells. The cells in these cultures differentiated and polarized until they closely resemble the epithelial layers seenin vivo. FMDV infected these cultures predominantly from the apical side, primarily by binding to integrin αvβ6, in an Arg-Gly-Asp (RGD)-dependent manner. However, FMDV replicated only transiently without any visible cytopathic effect (CPE), and infectious progeny virus could be recovered only from the apical side. The infection induced the production of beta interferon (IFN-β) and the IFN-inducible gene Mx1 mRNA, which coincided with the disappearance of viral RNA and progeny virus. The induction of IFN-β mRNA correlated with the antiviral activity of the supernatants from both the apical and basolateral compartments. IFN-α mRNA was constitutively expressed in nasal mucosal epithelial cellsin vitroandin vivo. In addition, FMDV infection induced interleukin 8 (IL-8) protein, granulocyte-macrophage colony-stimulating factor (GM-CSF), and RANTES mRNA in the infected epithelial cells, suggesting that it plays an important role in modulating the immune response.
The Architecture and Chemical Stability of the Archaeal
Sulfolobus
Turreted Icosahedral Virus
Authors: Khayat Reza , Fu Chi-yu , Ortmann Alice C. , Young Mark J. , Johnson John E.
Published: July 2010

Viruses utilize a diverse array of mechanisms to deliver their genomes into hosts. While great strides have been made in understanding the genome delivery of eukaryotic and prokaryotic viruses, little is known about archaeal virus genome delivery and the associated particle changes. The
Sulfolobus
turreted icosahedral virus (STIV) is a double-stranded DNA (dsDNA) archaeal virus that contains a host-derived membrane sandwiched between the genome and the proteinaceous capsid shell. Using cryo-electron microscopy (cryo-EM) and different biochemical treatments, we identified three viral morphologies that may correspond to biochemical disassembly states of STIV. One of these morphologies was subtly different from the previously published 27-Å-resolution electron density that was interpreted with the crystal structure of the major capsid protein (MCP). However, these particles could be analyzed at 12.5-Å resolution by cryo-EM. Comparing these two structures, we identified the location of multiple proteins forming the large turret-like appendages at the icosahedral vertices, observed heterogeneous glycosylation of the capsid shell, and identified mobile MCP C-terminal arms responsible for tethering and releasing the underlying viral membrane to and from the capsid shell. Collectively, our studies allow us to propose a fusogenic mechanism of genome delivery by STIV, in which the dismantled capsid shell allows for the fusion of the viral and host membranes and the internalization of the viral genome.
Structure and Function Analysis of Therapeutic Monoclonal Antibodies against Dengue Virus Type 2
Authors: Sukupolvi-Petty Soila , Austin S. Kyle , Engle Michael , Brien James D. , Dowd Kimberly A. , Williams Katherine L. , Johnson Syd , Rico-Hesse Rebeca , Harris Eva , Pierson Theodore C. , Fremont Daved H. , Diamond Michael S.
Published: July 2010

Dengue virus (DENV) is the most prevalent insect-transmitted viral disease in humans globally, and currently no specific therapy or vaccine is available. Protection against DENV and other related flaviviruses is associated with the development of antibodies against the viral envelope (E) protein. Although prior studies have characterized the neutralizing activity of monoclonal antibodies (MAbs) against DENV type 2 (DENV-2), none have compared simultaneously the inhibitory activity against a genetically diverse range of strains
in vitro
, the protective capacity in animals, and the localization of epitopes. Here, with the goal of identifying MAbs that can serve as postexposure therapy, we investigated in detail the functional activity of a large panel of new anti-DENV-2 mouse MAbs. Binding sites were mapped by yeast surface display and neutralization escape, cell culture inhibition assays were performed with homologous and heterologous strains, and prophylactic and therapeutic activity was evaluated with two mouse models. Protective MAbs localized to epitopes on the lateral ridge of domain I (DI), the dimer interface, lateral ridge, and fusion loop of DII, and the lateral ridge, C-C′ loop, and A strand of DIII. Several MAbs inefficiently inhibited at least one DENV-2 strain of a distinct genotype, suggesting that recognition of neutralizing epitopes varies with strain diversity. Moreover, antibody potency generally correlated with a narrowed genotype and serotype specificity. Five MAbs functioned efficiently as postexposure therapy when administered as a single dose, even 3 days after intracranial infection of BALB/c mice. Overall, these studies define the structural and functional complexity of antibodies against DENV-2 with protective potential.
Mycobacterium tuberculosisPromotes HIVtrans-Infection and Suppresses Major Histocompatibility Complex Class II Antigen Processing by Dendritic Cells
Authors: Reuter Morgan A. , Pecora Nicole D. , Harding Clifford V. , Canaday David H. , McDonald David
Published: July 2010

Mycobacteriumtuberculosisis a leading killer of HIV-infected individuals worldwide, particularly in sub-Saharan Africa, where it is responsible for up to 50% of HIV-related deaths. Infection by HIV predisposes individuals toM. tuberculosisinfection, and coinfection accelerates the progression of both diseases. In contrast to most other opportunistic infections associated with HIV, an increased risk ofM. tuberculosisinfection occurs during early-stage HIV disease, long before CD4 T cell counts fall below critical levels. We hypothesized thatM. tuberculosisinfection contributes to HIV pathogenesis by interfering with dendritic cell (DC)-mediated immune control. DCs carry pathogens likeM. tuberculosisand HIV from sites of infection into lymphoid tissues, where they process and present antigenic peptides to CD4 T cells. Paradoxically, DCs can also deliver infectious HIV to T cells without first becoming infected, a process known astrans-infection. Lipopolysaccharide (LPS)-activated DCs sequester HIV in pocketlike membrane invaginations that remain open to the cell surface, and individual virions are delivered from the pocket into T cells at the site of contact duringtrans-infection. Here we report thatM. tuberculosisexposure increases HIVtrans-infection and induces viral sequestration within surface-accessible compartments identical to those seen in LPS-stimulated DCs. At the same time,M. tuberculosisdramatically decreases the degradative processing and major histocompatibility complex class II (MHC-II) presentation of HIV antigens to CD4 T cells. Our data suggest thatM. tuberculosisinfection promotes a shift in the dynamic balance between antigen processing and intact virion presentation, favoring DC-mediated amplification of HIV infections.
Population density and mortality among individuals in motor vehicle crashes
Authors: Gedeborg Rolf , Thiblin Ingemar , Byberg Liisa , Melhus Håkan , Lindbäck Johan , Michaelsson Karl
Published: July 2010

Objective

To assess whether higher mortality rates among individuals in motor vehicle crashes in areas with low population density depend on injury type and severity or are related to the performance of emergency medical services (EMS).

Methods

Prehospital and hospital deaths were studied in a population-based cohort of 41 243 motor vehicle crashes that occurred in Sweden between 1998 and 2004. The final multivariable analysis was restricted to 6884 individuals in motor vehicle crashes, to minimise the effects of confounding factors.

Results

Crude mortality rates following motor vehicle crashes were inversely related to regional population density. In regions with low population density, the unadjusted rate ratio for prehospital death was 2.2 (95% CI 1.9 to 2.5) and for hospital death 1.5 (95% CI 1.1 to 1.9), compared with a high-density population. However, after controlling for regional differences in age, gender and the type/severity of injuries among 6884 individuals in motor vehicle crashes, low population density was no longer associated with increased mortality. At 25 years of age, predicted prehospital mortality was 9% lower (95% CI 5% to 12%) in regions with low population density compared with high population density. This difference decreased with increasing age, but was still 3% lower (95% CI 0.5% to 5%) at 65 years of age.

Conclusions

The inverse relationship between population density and mortality among individuals in motor vehicle crashes is related to pre-crash factors that influence the type and severity of injuries and not to differences in EMS.
Evaluation of touch preparation cytology during frozen-section diagnoses of pulmonary lesions
Authors: Rakha E A , Haider A , Patil S , Fourtan H , Chaudry Z , Soomro I N
Published: July 2010

Background

Intraoperative frozen section (FS) examination in thoracic surgery is a reliable method for diagnosis and staging of pulmonary lesions and provides a valuable guide in directing the extent of the ongoing surgical procedure. However, the contribution of touch preparation cytology (TPC) to FS diagnosis remains unclear.

Aim

To assess the utility of routinely performed TPC during FS diagnoses of pulmonary lesions.

Methods

In this study FS and TPC for all patients who had undergone FS diagnoses of pulmonary lesions in a 6-year period were reviewed by two pathologists.

Results

A total of 155 consecutive patients underwent intraoperative FS procedure, and 110 of those cases had TPC available for review. TPC was diagnostic or contributory to FS diagnosis in 97 (88%) cases, and non-contributory in 13 cases, mainly due to low or inadequate cellularity. TPC provided useful information regarding tumour subtyping, but it was less sensitive in the diagnosis of mucinous neoplasms and was less specific in the assessment of bronchial resection margins. In granulomatous lesions with or without necrosis, TPC was diagnostic in 10 (91%) cases. In five cases (including four cases of tuberculosis), TPC was the only diagnostic tool since FS was not completed. In conclusion, TPC showed high sensitivity and specificity rates and was contributory to FS diagnosis of pulmonary lesions. TPC provides a fast, less-expensive method of diagnosis, utilises a minimal amount of tissue, and can save processing of fresh frozen tissues in certain situations such as tuberculous lesions.
More specific bands in the IgG western blot in sera from Scottish patients with suspected Lyme borreliosis
Authors: Evans Roger , Mavin Sally , McDonagh Susan , Chatterton Jean M W , Milner Rachel , Ho-Yen Darrel O
Published: July 2010

Aims

To identify further Western blot bands that may be specific in the diagnosis of Lyme borreliosis.

Methods

TheBorrelia burgdorferiantibody profiles of 270 western blot positive patients and 241 western blot negative patients from 2008 were examined.

Results

27 different non-specific bands were detected in both groups. Six of 27 (22%) of the non-specific bands were detected significantly more in the western blot positive patients compared to the western blot negative patients (20 kDa, p<0.0001; 28 kDa, p<0.002; 36 kDa, p<0.002; 37 kDa, p<0.007; 48 kDa, p<0.023; 56 kDa, p<0.028; two-tailed F test).

Conclusion

Results suggest that the 20, 28 and 48 kDa bands should be regarded as specific.
Quantitative detection of the new polyomaviruses KI, WU and Merkel cell virus in transbronchial biopsies from lung transplant recipients: Table 1
Authors: Bergallo Massimiliano , Costa Cristina , Terlizzi Maria Elena , Astegiano Sara , Curtoni Antonio , Solidoro Paolo , Delsedime Luisa , Cavallo Rossana
Published: July 2010

Background

Recently, three new polyomaviruses—KI, WU and Merkel cell (MCV)—have been discovered and their detection has been reported in different types of specimens, including respiratory samples, suggesting their shedding in the airways. In lung graft recipients, viral agents are associated with events that may limit the success of transplantation, including organ infection/disease and allograft rejection.

Aims

To evaluate the prevalence of KI, WU and MCV in transbronchial biopsies from lung transplant recipients and investigate the association with clinical and histopathological features.

Methods

The quantitation of new polyomaviruses DNA by real-time PCR and association with clinical and histopathological findings were evaluated in 66 transbronchial biopsies from lung transplant recipients.

Results

KI, WU and MCV were detected in 9.2%, 12.3% and 33.8% of specimens, respectively; with mean viral load ranging from 81 copies/104cells for WU to 258 for MCV, thus not differing from that previously reported in native lungs. No significant association with clinical and histopathological findings (including acute respiratory insufficiency, interstitial and organising pneumonia, acute and chronic rejection) was found.

Conclusions

Results showed a relatively high frequency of detection of the novel polyomaviruses in transbronchial biopsies from lung transplant recipients. It is likely that this accounted for the positive results found in some cases with different pathological background, although no significant association with a specific clinical and/or histopathological pattern was found.
COMPETITIVE COMPLEXITY OF MOBILE ROBOT ON-LINE MOTION PLANNING PROBLEMS
Authors: GABRIELY YOAV , RIMON ELON
Published: July 2010

This paper classifies common mobile robot on-line motion planning problems according to their competitive complexity. The competitiveness of an on-line algorithm measures its worst case performance relative to the optimal off-line solution to the problem. Competitiveness usually means constant relative performance. This paper generalizes competitiveness to any functional relationship between on-line performance and optimal off-line solution. The constants in the functional relationship must be scalable and may depend only upon on-line information. Given an on-line task, its competitive complexity class is a pair of lower and upper bounds on the competitive performance of all on-line algorithms for the task, such that the two bounds satisfy the same functional relationship. The paper classifies the following on-line motion planning problems into competitive classes: area coverage, navigation to a target, and on-line search for an optimal path. In particular, it is shown that navigation to a target whose position is either apriori known or recognized upon arrival belongs to a quadratic competitive complexity class. The hardest on-line problem involves navigation in unknown variable traversibility environments. Under certain restriction on traversibility, this last problem belongs to an exponential competitive complexity class.
A LOWER BOUND ON THE AREA OF A 3-COLOURED DISK PACKING
Authors: BRASS PETER , HURTADO FERRAN , LAFRENIERE BENJAMIN , LUBIW ANNA
Published: July 2010

Given a set of unit disks in the plane with union area A, what fraction of A can be covered by selecting a pairwise disjoint subset of the disks? Rado conjectured 1/4 and proved 1/4.41. Motivated by the problem of channel assignment for wireless access points, in which use of 3 channels is a standard practice, we consider a variant where the selected subset of disks must be 3-colourable with disks of the same colour pairwise-disjoint. For this variant of the problem, we conjecture that it is always possible to cover at least 1/1.41 of the union area and prove 1/2.09. We also provide an O(n2) algorithm to select a subset achieving a 1/2.77 bound. Finally, we discuss some results for other numbers of colours.
FLOODING COUNTRIES AND DESTROYING DAMS
Authors: SILVEIRA RODRIGO I. , VAN OOSTRUM RENÉ
Published: July 2010

In many applications of terrain analysis, pits or local minima are considered artifacts that must be removed before the terrain can be used. Most of the existing methods for local minima removal work only for raster terrains. In this paper we consider algorithms to remove local minima from polyhedral terrains, by modifying the heights of the vertices. To limit the changes introduced to the terrain, we also try to minimize the total displacement of the vertices. Two approaches to remove local minima are analyzed: lifting vertices and lowering vertices. For the former we show that all local minima in a terrain with n vertices can be removed in the optimal way in [Formula: see text] time. For the latter we prove that the problem is NP-hard, and present an approximation algorithm with factor 2 ln k, where k is the number of local minima in the terrain.
ON THE DESIGN OF OPTIMIZATION ALGORITHMS FOR PREDICTION OF MOLECULAR INTERACTIONS
Authors: CHANG DARBY TIEN-HAO , LIN JUNG-HSIN , HSIEH CHIH-HUNG , OYANG YEN-JENG
Published: July 2010

This article presents a comprehensive study on the main characteristics of a novel optimization algorithm specifically designed for simulation of protein-ligand interactions. Though design of optimization algorithms has been a research issue extensively studied by computer scientists for decades, the emerging applications in bioinformatics such as simulation of protein-ligand interactions and protein folding introduce additional challenges due to (1) the high dimensionality nature of the problem and (2) the highly rugged landscape of the energy function. As a result, optimization algorithms that are not carefully designed to tackle these two challenges may fail to deliver satisfactory performance. This study has been motivated by the observation that the RAME (Rank-based Adaptive Mutation Evolutionary) optimization algorithm specifically designed for simulation of protein-ligand docking has consistently outperformed the conventional optimization algorithms by a significant degree. The experimental results reveal that the RAME algorithm is capable of delivering superior performance to several alternative versions of the genetic algorithm in handling highly-rugged functions in the high-dimensional vector space. This article also reports experiments conducted to analyze the causes of the observed performance difference. The experiences learned provide valuable clues for how the proposed algorithm can be effectively exploited to tackle other computational biology problems.
A Seven-Gene Set Associated with Chronic Hypoxia of Prognostic Importance in Hepatocellular Carcinoma
Authors: van Malenstein Hannah , Gevaert Olivier , Libbrecht Louis , Daemen Anneleen , Allemeersch Joke , Nevens Frederik , Van Cutsem Eric , Cassiman David , De Moor Bart , Verslype Chris , van Pelt Jos
Published: July 2010

Purpose: Hepatocellular carcinomas (HCC) have an unpredictable clinical course, and molecular classification could provide better insights into prognosis and patient-directed therapy. We hypothesized that in HCC, certain microenvironmental regions exist with a characteristic gene expression related to chronic hypoxia which would induce aggressive behavior.

Experimental Design: We determined the gene expression pattern for human HepG2 liver cells under chronic hypoxia by microarray analysis. Differentially expressed genes were selected and their clinical values were assessed. In our hypothesis-driven analysis, we included available independent microarray studies of patients with HCC in one single analysis. Three microarray studies encompassing 272 patients were used as training sets to determine a minimal prognostic gene set, and one recent study of 91 patients was used for validation.

Results: Using computational methods, we identified seven genes (out of 3,592 differentially expressed under chronic hypoxia) that showed correlation with poor prognostic indicators in all three training sets (65/139/73 patients) and this was validated in a fourth data set (91 patients). Retrospectively, the seven-gene set was associated with poor survival (hazard ratio, 1.39; P = 0.007) and early recurrence (hazard ratio, 2.92; P = 0.007) in 135 patients. Moreover, using a hypoxia score based on this seven-gene set, we found that patients with a score of >0.35 (n = 42) had a median survival of 307 days, whereas patients with a score of ≤0.35 (n = 93) had a median survival of 1,602 days (P = 0.005).

Conclusions: We identified a unique, liver-specific, seven-gene signature associated with chronic hypoxia that correlates with poor prognosis in HCCs. Clin Cancer Res; 16(16); 4278–88. ©2010 AACR.
CSF-Tau and CSF-Aβ1–42 in Posterior Cortical Atrophy
Authors: Baumann Thomas P. , Duyar Hüseyin , Sollberger Marc , Kuhle Jens , Regeniter Axel , Gomez-Mancilla Baltazar , Schmidtke Klaus , Monsch Andreas U.
Published: July 2010

Objective: Our purpose was to measure Aβ1–42, T-tau and P-tau181 in the cerebrospinal fluid (CSF) of patients with posterior cortical atrophy (PCA), a presenile dementia likely to represent a variant of Alzheimer’s disease (AD). Methods: CSF samples from 34 subjects including 9 patients with PCA, 11 age-matched patients with AD and 14 age-matched cognitively healthy controls were analyzed using commercially available ELISA kits. Results: The Aβ1–42, T-tau and P-tau181 levels in PCA patients differed significantly (p < 0.02) from those in healthy controls but were indistinguishable from subjects with a clinical diagnosis of AD. Conclusion: High T-tau and P-tau181 and low Aβ1–42 levels in PCA – typically observed in AD – indicate that the underlying pathology of PCA is usually AD. If these findings are replicated in PCA patients with autopsy-confirmed AD neuropathology, PCA patients may be eligible for disease-modifying AD treatments.
Cerebral Glucose Metabolism of Parkinson’s Disease Patients with Mild Cognitive Impairment
Authors: Lyoo Chul Hyoung , Jeong Yong , Ryu Young Hoon , Rinne Juha O. , Lee Myung Sik
Published: July 2010

Background: Half of Parkinson’s disease (PD) patients with mild cognitive impairment (MCI) develop dementia. We studied topographic distribution of cerebral hypometabolism in PD with different types of MCI. Methods: This study included 61 nondemented PD patients and 14 age-matched controls. PD patients were grouped into normal cognition (PD-NC, n = 20), single amnestic (PD-SA, n = 12), single nonamnestic (PD-SN, n = 11), and multidomain MCI (PD-MD, n = 18). Using [18F]-fluorodeoxy-glucose PET, cerebral glucose metabolism of MCI groups was compared with that of controls and the PD-NC group. Results: In comparison with controls, PD-NC and PD-SA groups showed no hypometabolic brain areas. However, the PD-SN group showed hypometabolism in parieto-temporo-occipital cortices. The PD-MD group showed widespread hypometabolism that predominantly involved parieto-occipital cortices. In comparison with the PD-NC group, only the PD-MD group showed hypometabolism in lateral frontal, cingulate, and parieto-temporo-occipital cortices. Conclusions: The distribution of hypometabolic brain areas of the PD-MD group suggests that PD-MD seems to be caused by a common pathology with PD dementia. PD-SA and PD-SN seem to be caused by very mild or topographically heterogeneous cerebral dysfunction. Longitudinal clinical and neuroimaging studies are needed to define whether PD patients with single domain MCI progress to PD-MD and finally to dementia.
Multiple Socioeconomic Risks and Cognitive Impairment in Older Adults
Authors: Lee Yunhwan , Back Joung Hwan , Kim Jinhee , Byeon Haewon
Published: July 2010

Background/Aim: To investigate the multiple effects of socioeconomic factors on cognitive impairment in older persons. Methods: Subjects were a nationally representative sample (n = 4,155) aged ≧65 years of the Korean Longitudinal Study of Aging. Cognitive status was assessed by the Mini-Mental State Examination. Education, income, wealth and occupation were measured, with low levels on each factor combined to produce an aggregate risk score. Multiple logistic regression was used to analyze the combined effects of socioeconomic risks on cognitive impairment. Results: A socioeconomic risk gradient was evident, with the combined effect being stronger than any one of the risk factors acting alone. Compared with those with no risks, the odds ratios were 2.4 (for 2 socioeconomic risks), 3.4 (3 risks) and 7.7 (4 risks) for men, and 2.8 (2 risks), 3.5 (3 risks) and 5.4 (4 risks) for women. For individual socioeconomic risks, income and occupation were significant predictors of cognitive impairment in men, whereas in women, all 4 factors were independently associated. Conclusion: Multiple socioeconomic risks have a combined effect on cognitive impairment in older adults.
Elevated Preoperative Phosphorus Levels Are an Independent Risk Factor for Cardiovascular Mortality
Authors: van Kuijk Jan-Peter , Flu Willem-Jan , Chonchol Michel , Valentijn Tabita M. , Verhagen Hence J.M. , Bax Jeroen J. , Poldermans Don
Published: July 2010

Background/Aims: Serum phosphorus levels have been associated with adverse long-term outcome in several populations, however, no prior studies evaluated short-term postoperative outcome. The present study evaluated the predictive value of phosphorus levels on 30-day outcome after vascular surgery. Methods: The study included patients scheduled for major vascular surgery (aortic aneurysm repair, lower extremity revascularization or carotid surgery), divided into four quartiles based on the preoperative fasting phosphorus level. The endpoints of the analyses were all-cause and cardiovascular mortality during the first 30 postoperative days and during long-term follow-up (median 3.6 years, interquartile range 1.8–8.0). Results: Prior to surgery, 1,798 patients were categorized into the following quartiles: <2.9 mg/dl (n = 459), 2.9–3.4 mg/dl (n = 456), 3.4–3.8 mg/dl (n = 444) and >3.8 mg/dl (n = 439), respectively. During the first 30 postoperative days, 81 (4.5%) patients died of which 66 (81%) secondary to a cardiovascular cause. In multivariate analyses, an independent association was observed between phosphorus level >3.8 mg/dl and all-cause (OR 2.53, 95% CI 1.2–5.4) or cardiovascular mortality (OR 2.37, 95% CI 1.1–5.7). Baseline serum phosphorus >3.8 mg/dl was also significantly associated with long-term all-cause mortality (HR 1.38, 95% CI 1.1–1.7). Conclusions: Preoperative elevated serum phosphorus demonstrated an independent relationship with the occurrence of all-cause and cardiovascular mortality during the first 30 days after major vascular surgery. In addition, an elevated serum phosphorus was independently associated with long-term mortality.
Renoprotection by Rosiglitazone in Accelerated Type 2 Diabetic Nephropathy: Role of STAT1 Inhibition and Nephrin Restoration
Authors: Tang Sydney C.W. , Leung Joseph C.K. , Chan Loretta Y.Y. , Cheng Amy Shan , Lan Hui Yao , Lai Kar Neng
Published: July 2010

Background: Rosiglitazone (Ros) has been shown to attenuate CXCL8 and ICAM-1 overexpression in renal tubular cells exposed to glycated albumin. The present study explores whether this can be translated into renoprotection in vivo. Uninephrectomized (Unx) type 2 diabetic db/db mice were chosen as a model of accelerated diabetic nephropathy. Methods: Uninephrectomy was performed in 10-week-old db/db mice. They were then treated with vehicle, metformin or Ros for 8 weeks. Results: Unx-db/db mice treated with Ros had lower serum creatinine and albuminuria, less severe glomerulosclerosis, tubulointerstitial injury, fewer infiltrating macrophages, and less proliferating nuclear antigen-positive tubular cells compared with mice treated with metformin that had a similar level of glycemic control and insulin resistance. In addition, Ros but not metformin attenuated renal cortical expression of CCL2, MIP-2, and ICAM-1 and inhibited p-STAT1 signal activation. Ros also increased glomerular nephrin expression. Conclusions: Our results delineated the biochemical and histologic characteristics of Unx-db/db mice and demonstrated the in vivo glucose-independent anti-inflammatory mechanisms of Ros in nephropathy of accelerated murine type 2 diabetes.
Ecological Studies On Carabid Beetles
Authors: Richter C.J.J. , Hartsuijker L. , Vlijm L.
Published: July 2010

With the aid of a trapping techniques with tins (one tin to the square meter) carabid beetles were collected at Schiermonnikoog, one of the Wadden-islands, in 1958, 1959 and 1960. Calathus melanocephalus was most active at the beginning of the nocturnal period. The number of animals which were caught in different nights is related to the temperature. The higher temperature in the nocturnal period, the more animals are trapped. The animals in some periods prefer a very dense vegetation as LINDROTH (1945) has remarked; at other times (as LARSSON, 1939, noted), a scarce vegetation. This is most probably related to the amount of rainfall. In dryer periods Calathus melanocephalus prefers dense vegetation, whereas in periods with a good amount of rainfall areas with scarce vegetation are preferred.
Drosophila Andalusiaca, a Polymorphic Species New To Holland
Authors: Beardmore J.A.
Published: July 2010

Drosophila andalusiaca, with one qualified exception hitherto unreported from Holland, has been found in various localities including some of the coastal islands. The sex-limited polymorphism for abdomen colour is also found to occur in some populations, the gene frequencies for the two alleles in one population being roughly equal.
De schiet- en loterijprijzen van de Delftse schutters uit 1621 en 1631
Authors: Huys Janssen Paul
Published: July 2010

In the municipal archives in Delft are two unique printed lists that inform us about events organised by the Delft civic guard in 1621 and 1631. In 1621 a shooting contest was being held and the prices were several pieces of silver and a number of paintings. These were mainly by Esaias van de Velde, but there were also works by Bartholomeus van Bassen, Cornelis Jacobsz Delff, Joos de Momper together with Jan Brueghel the Elder, Pieter van Bronckhorst, the unknown Pieter Jacobsz Lupert and two works by Hendrick Gerritsz Pot. In the document he titles of the paintings are given, but it is not possible to trace any of these works. In 1631 the civic guard organised a lottery. A large number of paintings were to be won, mainly by painters from Utrecht. The first prize was a series of the five senses by Gerard van Honthorst, Abraham (or maybe Hendrick ?) Bloemaert, Paulus Moreelse, Jan van Bijlert and Hendrick ter Brugghen. There were also paintings by Roelandt Saverij, Adam Willaerts, Joost Cornelisz Droochsloot and Gijsbert and Gillis Hondecoeter. Prom Delft Leonaert Bramer, Cornelis Jacobsz Delff, Anthonie Palamedesz together with Barthomeus van Bassen, Palamedes Palamedesz and Jacob Vosmaer are represented. Also two paintings by Esaias van de Velde are mentioned. Again the titles are given, but they offer no clues to any present whereabouts. From a notarial act it appears that in 1644 again a shooting contest was being held. Now there were only seven paintings to be won. They were supplied by the still life painter Evert van Aelst, and he undoubtedly painted them. No titles are given. Again in 1647 and 1661 shooting contests were being held. Now the prices were simple pieces of silver. According to this pattern, over the decades the populariry of paintings in Delft was diminishing.
Twee onbekende luiken met stichtersportretten door Aertgen van Leyden
Authors: Ekkart Rudolf E.O.
Published: July 2010

In the Musée des Beaux-Arts at Lille there are two shutters from a North-Netherlandish commemorative painting (fig. 2/3) which on comparison with two others in the museums at Valenciennes (fig. i) and La Fère may be attributed to the painter Aertgen van Leyden. The coats of arms painted on the outsides of the shutters (fig-4/5) identify the sitters as Claes Alewijn Claeszz., burgomaster of Leiden (d. 1561), and his wife Anna Cornelisdr. van der Hooch (d.1558) with their children. The whereabouts of the central panel are unknown, but the work must have been painted for the Pieterskerk in Leiden, where the same couple's tombstone, made by the Frisian carver Pieter Dircksz., still is (fig. 6).