bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroid peroxidase antibodies in pregnant women with type 1 diabetes: Impact on thyroid function, metabolic control and pregnancy outcome
Authors: VESTGAARD MARIANNE , NIELSEN LENE RINGHOLM , RASMUSSEN ÅSE KROGH , DAMM PETER , MATHIESEN ELISABETH R. 
Published: October 2008

AbstractObjective. In pregnant women with type 1 diabetes, we evaluated whether the presence of thyroid peroxidase autoantibodies (anti‐TPO) was associated with changes in thyroid function, metabolic control and pregnancy outcome. Design/setting. Prospective study, Denmark. Population. Ninety‐six consecutive pregnant women with type 1 diabetes. Twenty‐five healthy pregnant controls. Methods. At 8, 14, 21, 27 and 33 weeks, the diabetic women self‐monitored plasma glucose (SMPG) (8/day) for 3 days and had blood samplings obtained. Main outcome measures. Thyroid‐stimulating hormone (TSH), free thyroxin (T4), hemoglobin A1C (HbA1C), anti‐TPO, pregnancy outcome. Results. Anti‐TPO was detected in 31 (32%) of the pregnant diabetic women compared with two women (8%) in the healthy controls (p = 0.015). The presence of anti‐TPO was associated with higher TSH at 8 (p <0.0001) and 14 weeks (p <0.05) and lower free T4 at 8 weeks (p <0.05) compared with anti‐TPO negative women. Twenty untreated anti‐TPO positive women had higher TSH compared with untreated, anti‐TPO negative women (p <0.05), but comparable free T4. At inclusion, 25% had TSH above the recommended treatment goal for levothyroxine (TSH>2.5 mIU/l), most prevalently among anti‐TPO positive women. Sixteen women (17%) were treated for thyroid disorder during pregnancy. No differences were detected between the diabetic women with and without anti‐TPO regarding HbA1C, insulin dose, median SMPG or pregnancy outcome. Conclusions. Anti‐TPO was present in one‐third of pregnant women with type 1 diabetes and associated with slightly higher TSH, but not poorer glycemic control or adverse birth outcome. A total of 17% of women with type 1 diabetes were treated for thyroid disorder during pregnancy.
Protease substrate site predictors derived from machine learning on multilevel substrate phage display data
Authors: Chen Ching-Tai , Yang Ei-Wen , Hsu Hung-Ju , Sun Yi-Kun , Hsu Wen-Lian , Yang An-Suei 
Published: October 2008

Abstract
Motivation: Regulatory proteases modulate proteomic dynamics with a spectrum of specificities against substrate proteins. Predictions of the substrate sites in a proteome for the proteases would facilitate understanding the biological functions of the proteases. High-throughput experiments could generate suitable datasets for machine learning to grasp complex relationships between the substrate sequences and the enzymatic specificities. But the capability in predicting protease substrate sites by integrating the machine learning algorithms with the experimental methodology has yet to be demonstrated.
Results: Factor Xa, a key regulatory protease in the blood coagulation system, was used as model system, for which effective substrate site predictors were developed and benchmarked. The predictors were derived from bootstrap aggregation (machine learning) algorithms trained with data obtained from multilevel substrate phage display experiments. The experimental sampling and computational learning on substrate specificities can be generalized to proteases for which the active forms are available for the in vitro experiments.
Availability: http://asqa.iis.sinica.edu.tw/fXaWeb/
Contact: hsu@iis.sinica.edu.tw; yangas@gate.sinica.edu.tw
Supplementary information: Supplementary data are available at Bioinformatics online.
Bundle Sheath Leakiness and Light Limitation during C4 Leaf and Canopy CO2 Uptake
Authors: Kromdijk Johannes , Schepers Hans E. , Albanito Fabrizio , Fitton Nuala , Carroll Faye , Jones Michael B. , Finnan John , Lanigan Gary J. , Griffiths Howard 
Published: October 2008

Abstract
Perennial species with the C4 pathway hold promise for biomass-based energy sources. We have explored the extent that CO2 uptake of such species may be limited by light in a temperate climate. One energetic cost of the C4 pathway is the leakiness (ϕ) of bundle sheath tissues, whereby a variable proportion of the CO2, concentrated in bundle sheath cells, retrodiffuses back to the mesophyll. In this study, we scale ϕ from leaf to canopy level of a Miscanthus crop (Miscanthus × giganteus hybrid) under field conditions and model the likely limitations to CO2 fixation. At the leaf level, measurements of photosynthesis coupled to online carbon isotope discrimination showed that leaves within a 3.3-m canopy (leaf area index = 8.3) show a progressive increase in both carbon isotope discrimination and ϕ as light decreases. A similar increase was observed at the ecosystem scale when we used eddy covariance net ecosystem CO2 fluxes, together with isotopic profiles, to partition photosynthetic and respiratory isotopic flux densities (isofluxes) and derive canopy carbon isotope discrimination as an integrated proxy for ϕ at the canopy level. Modeled values of canopy CO2 fixation using leaf-level measurements of ϕ suggest that around 32% of potential photosynthetic carbon gain is lost due to light limitation, whereas using ϕ determined independently from isofluxes at the canopy level the reduction in canopy CO2 uptake is estimated at 14%. Based on these results, we identify ϕ as an important limitation to CO2 uptake of crops with the C4 pathway.
Varicella-Zoster Virus Immediate-Early 63 Protein Interacts with Human Antisilencing Function 1 Protein and Alters Its Ability To Bind Histones H3.1 and H3.3
Authors: Ambagala Aruna P. , Bosma Trent , Ali Mir A. , Poustovoitov Maxim , Chen Jason J. , Gershon Michael D. , Adams Peter D. , Cohen Jeffrey I. 
Published: October 2008

ABSTRACT
Varicella-zoster virus (VZV) immediate-early 63 protein (IE63) is abundantly expressed during both acute infection in vitro and latent infection in human ganglia. Using the yeast two-hybrid system, we found that VZV IE63 interacts with human antisilencing function 1 protein (ASF1). ASF1 is a nucleosome assembly factor which is a member of the H3/H4 family of histone chaperones. IE63 coimmunoprecipitated and colocalized with ASF1 in transfected cells expressing IE63 and in VZV-infected cells. IE63 also colocalized with ASF1 in both lytic and latently VZV-infected enteric neurons. ASF1 exists in two isoforms, ASF1a and ASF1b, in mammalian cells. IE63 preferentially bound to ASF1a, and the amino-terminal 30 amino acids of ASF1a were critical for its interaction with IE63. VZV IE63 amino acids 171 to 208 and putative phosphorylation sites of IE63, both of which are critical for virus replication and latency in rodents, were important for the interaction of IE63 with ASF1. Finally, we found that IE63 increased the binding of ASF1 to histone H3.1 and H3.3, which suggests that IE63 may help to regulate levels of histones in virus-infected cells. Since ASF1 mediates eviction and deposition of histones during transcription, the interaction of VZV IE63 with ASF1 may help to regulate transcription of viral or cellular genes during lytic and/or latent infection.
The M Type K15 Protein of Kaposi's Sarcoma-Associated Herpesvirus Regulates MicroRNA Expression via Its SH2-Binding Motif To Induce Cell Migration and Invasion
Authors: Tsai Yuan-Hau , Wu Min-Fen , Wu Yu-Hsuan , Chang Shing-Jyh , Lin Su-Fang , Sharp Tyson V. , Wang Hsei-Wei 
Published: October 2008

ABSTRACT
Kaposi's sarcoma (KS) associated herpesvirus (KSHV) is the etiological agent of KS. In vivo, KS is a tumor capable of spreading throughout the body, and pulmonary metastasis is observed clinically. In vitro, KSHV induces the invasiveness of endothelial cells. The KSHV open reading frame K15 is a KSHV-specific gene encoding a transmembrane protein. Two highly divergent forms of K15, the predominant (P) and minor (M) forms (K15P and K15M, respectively), have been identified in different KSHV strains. The two K15 alleles resemble the latent membrane protein 2A (LMP2A) gene of Epstein-Barr virus (EBV) in their genomic locations and protein topology. Also, both K15 proteins have motifs similar to those found in the EBV LMP1 protein. K15 therefore appears to be a hybrid of a distant evolutionary relative of EBV LMP1 and LMP2A. Since both LMP1 and LMP2A proteins are capable of inducing cell motility, we sought to determine whether K15 has similar abilities. In this study, we show that K15M is latently expressed in KSHV-positive PEL cells and knockdown of K15M in PEL cells reduces cell motility. K15M localizes to lysosomal membranes and induces cell migration, invasion, and NF-κB (but not AP-1) activity via its conserved SH2-binding motif. K15M also induces the expression of microRNAs miR-21 and miR-31 via this conserved motif, and knocking down both these microRNAs eliminates K15M-induced cell motility. Therefore, K15M may contribute to KSHV-mediated tumor metastasis and angiogenesis via regulation of miR-21 and miR-31, which we show here for the first time to be a specific regulator of cell migration. In light of these findings, the targeting of K15 or the downstream microRNAs regulated by it may represent novel therapies for treatment of KSHV-associated neoplasia.
Mechanism of NS2B-Mediated Activation of NS3pro in Dengue Virus: Molecular Dynamics Simulations and Bioassays
Authors: Zuo Zhili , Liew Oi Wah , Chen Gang , Chong Pek Ching Jenny , Lee Siew Hui , Chen Kaixian , Jiang Hualiang , Puah Chum Mok , Zhu Weiliang 
Published: October 2008

ABSTRACT
The NS2B cofactor is critical for proteolytic activation of the flavivirus NS3 protease. To elucidate the mechanism involved in NS2B-mediated activation of NS3 protease, molecular dynamic simulation, principal component analysis, molecular docking, mutagenesis, and bioassay studies were carried out on both the dengue virus NS3pro and NS2B-NS3pro systems. The results revealed that the NS2B-NS3pro complex is more rigid than NS3pro alone due to its robust hydrogen bond and hydrophobic interaction networks within the complex. These potent networks lead to remodeling of the secondary and tertiary structures of the protease that facilitates cleavage sequence recognition and binding of substrates. The cofactor is also essential for proper domain motion that contributes to substrate binding. Hence, the NS2B cofactor plays a dual role in enzyme activation by facilitating the refolding of the NS3pro domain as well as being directly involved in substrate binding/interactions. Kinetic analyses indicated for the first time that Glu92 and Asp50 in NS2B and Gln27, Gln35, and Arg54 in NS3pro may provide secondary interaction points for substrate binding. These new insights on the mechanistic contributions of the NS2B cofactor to NS3 activation may be utilized to refine current computer-based search strategies to raise the quality of candidate molecules identified as potent inhibitors against flaviviruses.
Temporal Control of Message Stability in the Life Cycle of Double-Stranded RNA Bacteriophage Φ8
Authors: Qiao Xueying , Sun Yang , Qiao Jian , Mindich Leonard 
Published: October 2008

ABSTRACT

The cystoviruses have genomes of three double-stranded RNA segments. The genes of the L transcript are expressed early in infection, while those of M and S are expressed late. In all cystovirus groups but one, the quantity of the L transcript late in infection is lower than those of the other two because of transcriptional control. In bacteriophage Φ8 and its close relatives, transcription of L is not controlled; instead, the L transcript is turned over rapidly late in infection. The three messages are produced in approximately equal amounts early in infection, but the amount of L is less than 10% of the amounts of the others late in infection. The decay of the Φ8 L message depends upon the production of protein Hb, which is encoded in segment L. It also depends upon a target site within the
H
gene region. Phage mutants lacking either the
Hb
gene or the target region do not show the late control of L message quantity. In addition to having a role as a negative regulator, Hb functions to neutralize the activity of protein J, encoded by segment S, which causes the degradation of all viral transcripts.
The p14 FAST Protein of Reptilian Reovirus Increases Vesicular Stomatitis Virus Neuropathogenesis
Authors: Brown Christopher W. , Stephenson Kyle B. , Hanson Stephen , Kucharczyk Michael , Duncan Roy , Bell John C. , Lichty Brian D. 
Published: October 2008

ABSTRACT
The fusogenic orthoreoviruses express nonstructural fusion-associated small transmembrane (FAST) proteins that induce cell-cell fusion and syncytium formation. It has been speculated that the FAST proteins may serve as virulence factors by promoting virus dissemination and increased or altered cytopathology. To directly test this hypothesis, the gene encoding the p14 FAST protein of reptilian reovirus was inserted into the genome of a heterologous virus that does not naturally form syncytia, vesicular stomatitis virus (VSV). Expression of the p14 FAST protein by the VSV/FAST recombinant gave the virus a highly fusogenic phenotype in cell culture. The growth of this recombinant fusogenic VSV strain was unaltered in vitro but was significantly enhanced in vivo. The VSV/FAST recombinant consistently generated higher titers of virus in the brains of BALB/c mice after intranasal or intravenous infection compared to the parental VSV/green fluorescent protein (GFP) strain that expresses GFP in place of p14. The VSV/FAST recombinant also resulted in an increased incidence of hind-limb paralysis, it infected a larger volume of brain tissue, and it induced more extensive neuropathology, thus leading to a lower maximum tolerable dose than that for the VSV/GFP parental virus. In contrast, an interferon-inducing mutant of VSV expressing p14 was still attenuated, indicating that this interferon-inducing phenotype is dominant to the fusogenic properties conveyed by the FAST protein. Based on this evidence, we conclude that the reovirus p14 FAST protein can function as a bona fide virulence factor.
Activation of Pattern Recognition Receptor-Mediated Innate Immunity Inhibits the Replication of Hepatitis B Virus in Human Hepatocyte-Derived Cells
Authors: Guo Haitao , Jiang Dong , Ma Dongling , Chang Jinhong , Dougherty Anne Marie , Cuconati Andrea , Block Timothy M. , Guo Ju-Tao 
Published: October 2008

ABSTRACT
Recognition of virus infections by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I), and melanoma differentiation associated gene 5 (MDA5), activates signaling pathways, leading to the induction of inflammatory cytokines that limit viral replication. To determine the effects of PRR-mediated innate immune response on hepatitis B virus (HBV) replication, a 1.3mer HBV genome was cotransfected into HepG2 or Huh7 cells with plasmid expressing TLR adaptors, myeloid differentiation primary response gene 88 (MyD88), and TIR-domain-containing adaptor-inducing beta interferon (TRIF), or RIG-I/MDA5 adaptor, interferon promoter stimulator 1 (IPS-1). The results showed that expressing each of the three adaptors dramatically reduced the levels of HBV mRNA and DNA in both HepG2 and Huh7 cells. However, HBV replication was not significantly affected by treatment of HBV genome-transfected cells with culture media harvested from cells transfected with each of the three adaptors, indicating that the adaptor-induced antiviral response was predominantly mediated by intracellular factors rather than by secreted cytokines. Analyses of involved signaling pathways revealed that activation of NF-κB is required for all three adaptors to elicit antiviral response in both HepG2 and Huh7 cells. However, activation of interferon regulatory factor 3 is only essential for induction of antiviral response by IPS-1 in Huh7 cells, but not in HepG2 cells. Furthermore, our results suggest that besides NF-κB, additional signaling pathway(s) are required for TRIF to induce a maximum antiviral response against HBV. Knowing the molecular mechanisms by which PRR-mediated innate defense responses control HBV infections could potentially lead to the development of novel therapeutics that evoke the host cellular innate antiviral response to control HBV infections.
Efficacy of intravitreal and periocular triamcinolone associated with photodynamic therapy for treatment of retinal angiomatous proliferation
Authors: Montero J A , Ruiz-Moreno J M , Sanabria M R , Fernandez-Munoz M 
Published: October 2008

Aims:To compare the relative efficacy of photodynamic therapy (PDT), PDT associated with intravitreal triamcinolone (PDT–IT) and PDT associated with periocular triamcinolone (PDT–PT) for treatment of retinal angiomatous proliferation (RAP) stage III.Methods:Retrospective, interventional, non-randomised multicentric study. The files, optical coherence tomography scans, indocyanine green and fluorescein angiograms of patients with RAP stage III who had been referred to a regional centre for PDT were retrospectively examined. Final visual acuity and chorioretinal atrophy were considered to be the main outcome indicators. The need to re-treat and recurrences were also considered.Results:Forty-two eyes were treated by PDT as monotherapy, 18 eyes by PDT–PT, and 19 eyes by PDT–IT. The mean (SD) age in each group was 79.1 (5.2), 77.0 (5.9) and 80.2 (5.1) years, respectively. The mean (SD) initial best corrected visual acuity (BCVA) was 0.17 (0.19), 0.21 (0.20) and 0.20 (0.18), respectively. Mean BCVA was 0.14 (0.19), 0.17 (0.15) and 0.17 (0.23), respectively, at 6 months (p = 0.27, 0.33 and 0.21, respectively) and 0.12 (0.18), 0.10 (0.10) and 0.17 (0.26), respectively, at 12 months (p = 0.12, 0.05 and 0.60, respectively, comparing vision at 6 months and 12 months with baseline; Student t test for paired data). Retinal pigment epithelium rips appeared in three eyes in group 1, in one eye in group 2, and in two eyes in group 3.Conclusion:Combined PDT–IT may offer better results than PDT monotherapy or PDT–PT in patients with RAP stage III.
Long-term control of choroidal neovascularisation secondary to angioid streaks treated with intravitreal bevacizumab (Avastin)
Authors: Neri P , Salvolini S , Mariotti C , Mercanti L , Celani S , Giovannini A 
Published: October 2008

Aim:To evaluate the efficacy of intravitreal bevacizumab (IB) in the long-term control of subfoveal choroidal neovascularisation (CNV) associated with angioid streaks (AS).Methods:Patients with unilateral active CNV associated with AS were enrolled. Exclusion criteria were previous treatment for CNV and comorbidity. Postoperative visual acuity was defined as a gain or loss of two or more lines of best-corrected visual acuity (BCVA). Post-treatment CNV size was dichotomised into “increased,” if the CNV area had grown by ⩾200 μm2, and “stable/reduced” if it had decreased by ⩾200 μm2 or had not changed by more than 200 μm2. Patients were retreated if no further improvement or worsening was noted.Results:Patients were five males and six females aged 33 to 58 years (mean 46.8 (SD 9.2)), who received a mean number of 3.5 (1.3) IB treatments (min: 2; max: 6). The mean retreatment interval was 3 (1.5) months (min: 1; max: 6). The mean follow-up duration was 23.8 (2.9) months. At 20 months all patients had stable/reduced CNV size and stable/improved BCVA. The mean BCVA rose significantly from 0.28 (0.2) at baseline to 0.56 (0.29) at 20 months (p<0.0001).Conclusion:IB is a promising tool for the long-term control of CNV in AS. Further studies are required to validate these findings.
Is informed consent effective in trauma patients?
Authors: Bhangu A , Hood E , Datta A , Mangaleshkar S 
Published: October 2008

Background:Informed consent in the modern era is a common and important topic both for the well-informed patient and to prevent unnecessary litigation. However, the effectiveness of informed consent in trauma patients is an under-researched area. This paper aims to assess the differences in patient recall of the consent process and desire for information by performing a comparative analysis between orthopaedic trauma and elective patients.Methods:Information from 41 consecutive elective operations and 40 consecutive trauma operations was collected on the first post-operative day.Results:100% of elective patients and 90% of trauma patients knew what operation they had received (p = 0.06). Overall recall of complications was poor, but was significantly lower in trauma patients compared with elective patients (62% vs 22%, p<0.001). 30% of trauma patients desired more information about their operation compared to 12% of elective patients (p = 0.049), although only 35% of trauma patients wanted written as well as verbal explanations, compared to 85% of elective patients p<0.001). Overall 100% of elective and 90% of trauma patients were happy with the consent process (p = 0.06). Subset analysis of neck of femur compared to other trauma patients showed that the above factors were not significantly different between the two groups.Conclusions:Recall of complications in the trauma patients is significantly lower than in elective patients, although both groups scored poorly overall. Repeated verbal explanations should be reinforced with the option of additional information leaflets for trauma operations. Further research into the usefulness of DVDs for commonly performed operations is warranted, although official internet resources may be more cost-effective.
Communication in geology: a personal perspective and lessons from volcanic, mining, exploration, geotechnical, police and geoforensic investigations
Authors: Donnelly Laurance J. 
Published: October 2008

Abstract
Geologists are frequently required to convey the results, advice and recommendations from geological investigations to a variety of end users. Often, it is the communication of the information that is the most challenging and can be more difficult than the investigation itself. Most of these investigations use highly sophisticated scientific techniques and geological terminology. When combined with cultural and language barriers, and social, political, religious or economic constraints, this makes it difficult to convey the correct message, and for the recipient to understand the implications of the geological information. The failure to effectively and accurately communicate this message may reduce the usefulness of the information being provided. Communication must be considered part of a geological investigation because if the correct message is not conveyed properly, or is misunderstood, the consequences can be catastrophic. Communication is an ability that professional geologists must have to interact successfully with colleagues, other professionals and the public. It is a skill learnt by training and experience. Spoken communication relies on interpersonal skills and the ability to convey information effectively, confidently and consistently. This paper provides case studies and draws upon the experiences of the author.
Communicating uncertainty in climate-change adaptation and decision support; further development of the Gdańsk case study
Authors: Schmidt-Thomé Philipp , Kaulbarsz Dorota 
Published: October 2008

Abstract
The impact of climate change on European society is an issue of increasing concern on the agenda of European regional development policy. Using sea-level rise and changing flood-prone areas as an example of climate-change impact, this paper reviews an approach to stakeholder communication developed in the Baltic Sea Region. The application of climate- and sea-level change scenarios in spatial planning, as well as the communication between scientists and stakeholders, was integrated into a set of tools called the ‘decision support frame’ (DSF), which focuses especially on uncertainty aspects. By specifically addressing the communication process the DSF distances itself from pure computer-based decision-making. The city of Gdańsk is a good example where a combination of climate-change models, maps and various discussion rounds led to a communication process that has integrated several planning authorities and decision-makers.