bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic analysis of Indian subjects with clinical features of possible type IIa hypercholesterolemia
Authors: Kondkar Altaf A. , Nair Kappiareth G. , Ashavaid Tester F.
Published: November 2007

We performed genetic analysis in 55 patients with clinical features of possible type IIa hypercholesterolemia and 76 normolipemic healthy subjects for mutations and polymorphisms in the low‐density lipoprotein (LDL) receptor (LDLR), apolipoprotein B‐100 (APOB), apolipoprotein E (APOE), and hepatic lipase (LIPC) genes to elucidate the important genetic factors that can influence cholesterol levels in our population. None of the subjects showed mutations in part of exon 26 of the APOB gene, whereas two class 5 mutations were identified in exon 9 of the LDLR gene. First, an E387K mutation was observed in a Gujarati family in which both the parents were heterozygous for the mutation. Second, a L393R mutation was observed in a 38‐year‐old female. We found no correlation between LIPC −514C/T genotypes and cholesterol levels whereas the apoε4 allele frequency was significantly higher in cases and the apoE4 genotype was found to influence total cholesterol levels. J. Clin. Lab. Anal. 21:375–381, 2007. © 2007 Wiley‐Liss, Inc.
Diagnostic utility of pleural fluid carcinoembryonic antigen and CYFRA 21‐1 in patients with pleural effusion: a systematic review and meta‐analysis
Authors: Gu Ping , Huang Gang , Chen Yumei , Zhu Cuiying , Yuan Jimin , Sheng Shile
Published: November 2007

Pleural effusions (PE) are the most common complications that may be produced by a wide variety of diseases. A large number of studies exploring the role of carcinoembryonic antigen (CEA) and cytokeratin fragment 19 (CYFRA 21‐1) marker in differential diagnosis of PE have been published, employing differing methodologies with sometimes conflicting results. A comprehensive systematic review would be useful to synthesize the currently available bulk of information. The objective of this work was to assess and compare the overall value of pleural fluid CEA and CYFRA 21‐1 in differential diagnosis of PEs with a meta‐analysis. All the English and Chinese published studies for differential diagnosis of PEs by pleural fluid CEA and CYFRA 21‐1 were collected. Methodological quality of the included studies was evaluated. Pooled sensitivity and specificity were calculated, the threshold effect and the possible sources of heterogeneity were also analyzed. Summary receiver operating characteristic (SROC) curve analysis was used to compare the differential diagnostic ability of pleural fluid CEA and CYFRA 21‐1. A total of 19 studies were included in the meta‐analysis, with a total of 3,228 subjects. Pooled sensitivity and specificity of CEA and CYFRA 21‐1 were 45.9% (43.2–48.5%) and 97.0% (96.0–97.8%), and 47.3% (44.0–50.6%) and 91.8% (89.5–93.7%), respectively. Both CEA and CYFRA 21‐1 have a threshold effect, the main source of heterogeneity was from variable assay methods. The areas under the SROC curve (AUCs) of CEA and CYFRA 21‐1 were 0.7691 and 0.8213, respectively. There was no statistical significance between the AUC of CEA and CYFRA 21‐1 (P>0.05). Both CEA and CYFRA 21‐1 have good performance in the differential diagnosis of PE, when compared with CEA, CYFRA 21‐1 has no advantage. J. Clin. Lab. Anal. 21:398–405, 2007. © 2007 Wiley‐Liss, Inc.
Determination of urinary enzymes as a marker of early renal damage in diabetic patients
Authors: Mohammadi‐Karakani Ali , Asgharzadeh‐Haghighi Solmaz , Ghazi‐Khansari Mahmoud , Hosseini Rohollah
Published: November 2007

Diagnosis of diabetic nephropathy in the early stages is very important since there are no clinical signs or symptoms. Urinary N‐acetyl‐β‐D‐glucosaminidase (NAG) excretion has been recommended as a tubular dysfunction marker that elevates before other markers, such as microalbuminuria and a decrease in creatinine clearance. In this study, we compared excretion of urinary enzymes with other markers that are used routinely in diabetic nephropathy assessment. Urinary NAG, lactate dehydrogenase (LDH), alkaline phosphatase (AP) activities, urea, creatinine, and albumin, with levels of serum glucose and creatinine and whole blood glycosylated hemoglobin (HbA1c) were measured in 32 diabetes mellitus patients and 25 healthy subjects (controls). Notably, urinary NAG, AP, LDH excretion, and microalbuminuria in the diabetic patients group were significantly increased compared to those in the control groups (P<0.001, P<0.05, P<0.01, and P<0.01, respectively). Meanwhile, our results showed that the urinary NAG excretion had the highest sensitivity and specificity (100% and 87.5%, respectively) compared to other markers. We showed that measuring urinary NAG excretion could be useful for the assessment of renal failure in diabetes mellitus patients and confirmed the use of NAG as a routine screening test. J. Clin. Lab. Anal. 21:413–417, 2007. © 2007 Wiley‐Liss, Inc.
Catheter-induced urethral trauma in cats with urethral obstruction
Authors: Corgozinho Katia B. , de Souza Heloisa J.M. , Pereira Adriana N. , Belchior Cristiane , da Silva Michel A. , Martins Marina C.L. , Damico Cristiane B.
Published: November 2007

Fifteen cats were evaluated with urethral obstruction. Penile trauma by catheterization was the major indication for perineal urethrostomy. Ten cats had developed a urethral stricture and five had rupture of the urethra following medical management. All cats had abnormalities in penis and/or prepuce and/or scrotal sacs including hyperemia or swelling. Perineal urethrostomy was performed in all cases and they were evaluated for 6 months after surgery. Few complications were noted. Urinary tract infection was the most frequent complication observed. The clients considered their cats to have a good quality of life following surgery.
Inhibition of HeLa Cell Apoptosis by Storage‐Protein 2
Authors: Rhee Won Jong , Lee Eun Hee , Park Ju Hyun , Lee Ji Eun , Park Tai Hyun
Published: November 2007

Apoptosis is a barrier to maintaining high viable cell densities in animal cell culture. Silkworm hemolymph and its 30K protein have been reported to exhibit anti‐apoptotic activity in various mammalian and insect cell systems. The 30K protein is thermally unstable at temperatures higher than 60 °C; however, the silkworm hemolymph heat‐treated at 70–80 °C still exhibited anti‐apoptotic activity. This indicates that silkworm hemolymph contains another anti‐apoptotic compound other than 30K protein. In this article, the anti‐apoptotic molecule other than 30K protein was found from the silkworm hemolymph and identified. This molecule was storage‐protein 2 (SP2), which has no homology with any known anti‐apoptotic protein. This molecule was heat‐stable up to 80 °C, while 30K protein lost its activity at temperatures higher than 60 °C. When apoptosis was induced by staurosporine in HeLa cells, SP2 protein suppressed nuclear fragmentation and apoptotic body formation. Moreover, the generation of reactive oxygen species after apoptosis induction was inhibited, which means the inhibition occurred in an early step of the apoptotic process. Inhibition of apoptosis by the SP2 protein would lead to the minimization of cell death during commercial mammalian cell culture.
Plexin-B1 mutations in prostate cancer
Authors: Wong Oscar Gee-Wan , Nitkunan Tharani , Oinuma Izumi , Zhou Chun , Blanc Veronique , Brown Richard S. D. , Bott Simon R. J. , Nariculam Joseph , Box Gary , Munson Phillipa , Constantinou Jason , Feneley Mark R. , Klocker Helmut , Eccles Suzanne A. , Negishi Manabu , Freeman Alex , Masters John R. , Williamson Magali
Published: November 2007

Semaphorins are a large class of secreted or membrane-associated proteins that act as chemotactic cues for cell movement via their transmembrane receptors, plexins. We hypothesized that the function of the semaphorin signaling pathway in the control of cell migration could be harnessed by cancer cells during invasion and metastasis. We now report 13 somatic missense mutations in the cytoplasmic domain of the Plexin-B1 gene. Mutations were found in 89% (8 of 9) of prostate cancer bone metastases, in 41% (7 of 17) of lymph node metastases, and in 46% (41 of 89) of primary cancers. Forty percent of prostate cancers contained the same mutation. Overexpression of the Plexin-B1 protein was found in the majority of primary tumors. The mutations hinder Rac and R-Ras binding and R-RasGAP activity, resulting in an increase in cell motility, invasion, adhesion, and lamellipodia extension. These results identify a key role for Plexin-B1 and the semaphorin signaling pathway it mediates in prostate cancer.
Molecular crowding enhances native structure and stability of α/β protein flavodoxin
Authors: Stagg Loren , Zhang Shao-Qing , Cheung Margaret S. , Wittung-Stafshede Pernilla
Published: November 2007

To investigate the consequences of macromolecular crowding on the behavior of a globular protein, we performed a combined experimental and computational study on the 148-residue single-domain α/β protein,Desulfovibrio desulfuricansapoflavodoxin.In vitrothermal unfolding experiments, as well as assessment of native and denatured structures, were probed by using far-UV CD in the presence of various amounts of Ficoll 70, an inert spherical crowding agent. Ficoll 70 has a concentration-dependent effect on the thermal stability of apoflavodoxin (ΔTmof 20°C at 400 mg/ml; pH 7). As judged by CD, addition of Ficoll 70 causes an increase in the amount of secondary structure in the native-state ensemble (pH 7, 20°C) but only minor effects on the denatured state. Theoretical calculations, based on an off-lattice model and hard-sphere particles, are in good agreement with thein vitrodata. The simulations demonstrate that, in the presence of 25% volume occupancy of spheres, native flavodoxin is thermally stabilized, and the free energy landscape shifts to favor more compact structures in both native and denatured states. The difference contact map reveals that the native-state compaction originates in stronger interactions between the helices and the central β-sheet, as well as by less fraying in the terminal helices. This study demonstrates that macromolecular crowding has structural effects on the folded ensemble of polypeptides.
Telomerase reverse transcriptase expression elevated by avian leukosis virus integration in B cell lymphomas
Authors: Yang Feng , Xian Rena R. , Li Yingying , Polony Tatjana S. , Beemon Karen L.
Published: November 2007

Simple retroviruses induce tumors by integrating into the host genome, activating cellular oncogenes and microRNAs, or inactivating tumor suppressor genes. The identification of these genes elucidates molecular mechanisms of tumorigenesis. In this study, we identified avian leukosis virus (ALV) proviral integration sites in rapid-onset B cell lymphomas arising <12 weeks after infection of chicken embryos. By using inverse PCR, 28 unique viral integration sites were identified in rapid-onset tumors. Integrations in the telomerase reverse transcriptase (TERT) promoter/enhancer region were observed in four different tumors, suggesting that this is a common integration site. These provirus integrations ranged from 217 to 2,584 bp upstream of the TERT transcription initiation site and were all in the opposite transcriptional orientation to TERT. Southern blots of tumor samples demonstrated that these integrations are clonal and therefore occurred early in the process of tumorigenesis. Real-time RT-PCR showed overexpression of TERT mRNA in tumors harboring viral integrations in the TERT promoter. Telomerase activity was also up-regulated in these tumors; however, telomere-length alterations were not detected. Furthermore, viral LTR sequences directly enhanced the expression of luciferase reporters containing the TERT promoter sequences. This study documents retroviral up-regulation of cellular TERT by insertional activation to initiate or enhance tumor progression.
X-ray structure of EmrE supports dual topology model
Authors: Chen Yen-Ju , Pornillos Owen , Lieu Samantha , Ma Che , Chen Andy P. , Chang Geoffrey
Published: November 2007

EmrE, a multidrug transporter from
Escherichia coli
, functions as a homodimer of a small four-transmembrane protein. The membrane insertion topology of the two monomers is controversial. Although the EmrE protein was reported to have a unique orientation in the membrane, models based on electron microscopy and now defunct x-ray structures, as well as recent biochemical studies, posit an antiparallel dimer. We have now reanalyzed our x-ray data on EmrE. The corrected structures in complex with a transport substrate are highly similar to the electron microscopy structure. The first three transmembrane helices from each monomer surround the substrate binding chamber, whereas the fourth helices participate only in dimer formation. Selenomethionine markers clearly indicate an antiparallel orientation for the monomers, supporting a “dual topology” model.
A simplified oral glucose tolerance test in pregnancy: compliance and results
Authors: ANDERBERG EVA , Källén Karin , BERNTORP KERSTIN , FRID ANDERS , ÅBERG ANDERS
Published: November 2007

Background. To describe a reliable method for a general oral glucose tolerance test (OGTT) during pregnancy, to evaluate adherence to the method, and to compare the frequency of reported gestational diabetes mellitus (GDM) and perinatal outcome in affected pregnancies in Skåne, using direct diagnostic OGTT, with those from a comparable area, Halmstad‐Ljungby‐Växjö (HLV), using random glucose measurements (RGM) to identify women for the OGTT. Methods. The OGTT program and quality assurance in Skåne is described. Antenatal records on deliveries in May 2003 were scrutinised to ascertain if OGTT had been performed. Frequencies of GDM, prematurity and large for gestational age (LGA) infants were estimated using a population‐based perinatal database (PRS). Results. OGTT was performed in 93% of pregnant women in Skåne. In 2000–2003 GDM frequency in Skåne was twice as high as in HLV (1.9 versus 1%), while the frequency of LGA and prematurity among infants of mothers who were diagnosed with GDM were similar. Conclusions. Decentralised general OGTT is a reliable and effective method to diagnose GDM. OGTT is twice as sensitive as RGM, and the severity of GDM in the cases identified with OGTT did not differ from the severity of those identified with RGM.
Laparoscopic laser resection of rectovaginal pouch and rectovaginal septum endometriosis: the impact on pelvic pain and quality of life
Authors: KRISTENSEN JENS , Jørgen Kjer Jens
Published: November 2007

Background. The aim of this study was to assess the impact on pelvic pain and quality of life of laparoscopic resection of the rectovaginal pouch (RV) and RV septum in patients with endometriosis. Methods. The design was a descriptive retrospective study. The study included 48 women presenting to the Department of Obstetrics and Gynaecology with RV pouch and RV septum endometriosis, between 1 January 2003 and 1 January 2006. The setting was a university teaching hospital, one of two referral centres in Denmark for the surgical treatment of stage III and IV endometriosis. Questionnaires and Visual Analogue Scale (VAS) scores for a number of different symptoms associated with endometriosis were used. The main outcome measures were: effect of laparoscopic excision on pain scores and quality of life, operative findings, type of surgery, duration of surgery, and incidence of intra‐ and postoperative complications. Results. Significant statistical differences were found between preoperative and postoperative pain scores, quality of life, frequency of sexual activity, percentage taking analgesics or non‐steroidal anti‐inflammatory drugs, percentage having work difficulties due to pain, and percentage of women having sick‐leave. Conclusion. Endometriosis in the RV pouch and RV septum can be effectively treated with laser laparoscopy performed by experienced endoscopic gynaecologists.
Does acupuncture used in nulliparous women reduce time from prelabour rupture of membranes at term to active phase of labour? A randomised controlled trial
Authors: SELMER‐OLSEN TONE , LYDERSEN STIAN , MØRKVED SIV
Published: November 2007

Background. To assess if acupuncture influences the onset of labour and the need for induction after prelabour rupture of membranes (PROM) in nulliparous women. Further, to investigate a possible effect of acupuncture on the woman's wellbeing. Methods. In a randomised controlled trial (RCT), 106 nulliparous women with PROM were allocated to an acupuncture group (AG) or a control group (CG). The outcome measures were time from PROM to onset of active phase of labour, and rate of inductions if labour was absent after 2 days. The women's self‐reported wellbeing was registered on a Visual Analogue Scale (VAS). Results. There was no statistically significant difference between the 2 groups regarding time from PROM to active phase (median times in AG versus CG: 15 versus 20.5 h, p = 0.34). Additionally, there was no difference between the 2 groups in the need for induction. We found no significant differences in self‐reported wellbeing, but the women receiving acupuncture considered their treatment to be more positive than the controls (p = 0.003). No adverse effects were reported. Conclusions. Acupuncture treatment used in nulliparas after PROM showed no significant effect in reducing time to active labour or in reducing rate of inductions. There was no change in wellbeing as a result of acupuncture, but it was considered positive to receive this kind of treatment while waiting for labour to begin.
Utero‐vaginal anastomosis in the treatment of cervical atresia
Authors: JASONNI VALERIO M. , LA MARCA ANTONIO , MATONTI GIUSEPPE
Published: November 2007

Cervical atresia is an extremely rare malformation. Its incidence is not well known and management is controversial. The surgical technique and results of utero‐vaginal anastomosis in 3 women affected by cervical atresia are described.
Expression of human Biot2 and its potential function on carcinogenesis in endometrial cancer
Authors: YANGMEI SHEN , YANGMEI SHEN , XIANG HE , HONGXIN DENG , HANSHUO YANG , FENG PENG , YUPING XIE , YUQUAN WEI , XIA ZHAO
Published: November 2007

Background. Rat Biot2 is a novel gene first reported and named by our laboratory. We wanted to study the expression profile and reveal the function of its human homologous gene (human Biot2, hBiot2) on carcinogenesis in endometrial cancer. Methods. Using RT‐PCR, we tested hBiot2 expression profile in normal human tissues from infants and adults. Using real‐time RT‐PCR, we tested different expression quantities of hBiot2 between an endometrial cancer group and a normal endometrium group, between different histological grading groups in endometrial cancer, and between different stage groups during the menstrual cycle. RNA‐RNA ISH tested the expression location of hBiot2 in normal and cancer tissues. Results. Three kinds of novel shearings of hBiot2 in different normal tissues were obtained. Normal organs expressing hBiot2 in infants, did not express hBiot2 in adults. hBiot2 expression was higher in endometrial cancer tissue compared to normal endometrium tissue. hBiot2 expression was higher in the Grade 2–3 group with endometrial cancer compared to the Grade 1 group, and it was higher in the proliferative phase than in the secretory phase of a normal endometrium. hBiot2 was expressed mainly in the parenchymal cells. Conclusions. Three shearings of hBiot2 may suggest that it has different functions in different organs. The expression difference of hBiot2 between infants and adults, cancerous and normal tissues, different histological gradings in endometrial cancer, different stages during the menstrual cycle in the normal endometrium suggests that hBiot2 may have the potential to induce carcinogenesis in endometrial cancer.
Impact of recent studies on attitudes and use of hormone therapy among Scandinavian gynaecologists
Authors: TØNNES PEDERSEN ANETTE , IVERSEN OLE‐ERIK , LØKKEGAARD ELLEN , MATTSSON LARS‐ÅKE , MILSOM IAN , TORE NILSEN STEIN , OTTESEN BENT , HAASE MOEN METTE
Published: November 2007

Background. Climacteric medicine has been in focus during the last 2 decades, and an intensive debate has been ongoing regarding the positive and negative aspects of postmenopausal hormone therapy (HT). Recent randomised controlled studies have been unable to confirm data from observational studies of primary or secondary preventive effects of HT on coronary heart disease, and other studies have indicated an increased risk of breast cancer, stroke and venous thromboembolism among HT users. In 2001, we reported on knowledge, attitudes, management strategies and use of HT among Scandinavian gynaecologists. The aim of the present study was to re‐assess the same parameters concerning HT among Scandinavian gynaecologists in 2002–2003, and compare the results with the data collected in 1995–1997. Methods. All practicing gynaecologists in Denmark, Sweden and Norway were invited by letter to complete and return a questionnaire regarding their knowledge, attitudes and management strategies concerning HT. Female gynaecologists were questioned if they were currently using HT, and the same question was posed concerning spouses of male gynaecologists. Results. The questionnaire was completed and returned by 60, 76 and 72%, respectively of gynaecologists in Denmark, Sweden and Norway. Of the 1,591 physicians who responded, 13% thought that all women should be offered HT provided there were no contraindications, while 86% recommended HT only to selected women after considering the individual advantages and disadvantages of the treatment. Of the gynaecologists, 37% considered HT to be without relevance in the primary prevention of osteoporosis in healthy women. As for duration of the treatment, 40% of the gynaecologists would recommend HT for <5 years for the treatment of climacteric complaints, and only 8% would recommend HT for >10 years. The prevalence of HT use among the menopausal female gynaecologists varied between 71 and 74%. Among the menopausal spouses of male gynaecologists, 68–72% were current users of HT. Conclusion. During the last years of ongoing debate, gynaecologists from Denmark, Sweden and Norway have become more modest in their recommendations of postmenopausal HT. Scandinavian specialists are more cautious in prescribing hormones for women with symptomatic CVD or previously treated for breast cancer, however, their personal use of HT has not changed dramatically and still reflects a positive attitude.
Updating on primary fallopian tube carcinoma
Authors: RISKA ANNIKA , LEMINEN ARTO
Published: November 2007

Primary fallopian tube carcinoma (PFTC) is rare, constituting about 1% of female genital tract malignancies, and little is known about its etiological, protective, risk or prognostic factors. Earlier, such factors were thought to be similar to those seen in ovarian cancer. The incidence of PFTC has been rising during the last decades, especially in higher social classes and among women in certain occupations. Parity is a strong protective factor for PFTC, with a lower incidence associated with an increasing number of deliveries. Previous sterilisation seems to offer some protection. Earlier suggestions of previous genital infections as risk factors appear not to hold. Previous cancers are frequent among PFTC patients, especially breast cancer. Second primary cancers after PFTC are also frequent, especially non‐lymphoid leukemia, colorectal, breast, bladder and lung cancer. Only 4% of primary fallopian carcinomas are correctly diagnosed before operation. Treatment consists of aggressive cytoreductive surgery and adjuvant chemotherapy with a platinum‐taxane combination. A high preoperative serum hCGß is a strong prognostic factor for worse prognosis. The 5‐year survival rates vary between 22 and 57%.
Completeness of registration of oral clefts in a medical birth registry: a population‐based study
Authors: KUBON CHRISTER , SIVERTSEN ÅSE , ANDREAS VINDENES HALLVARD , Åbyholm Frank , WILCOX ALLEN , TERJE LIE ROLV
Published: November 2007

Background. Epidemiological surveillance and research on birth defects require accurate diagnosis and adequate registration. In this regard, the performance of national birth registries is not well described. Methods. We linked clinical data from all 3,616 cleft cases treated in Norway between 1967 and 1998 with data from the Medical Birth Registry of Norway, and calculated the proportion of clinically verified cases reported to the Registry, stratified by severity. Results. The cleft type most completely ascertained was cleft lip and palate (CLP), of which 94% were reported. Ascertainment was less complete for cleft lip alone (83% recorded), and cleft palate only (CPO) (57% recorded). For each of the three types of clefts, completeness of reporting depended on severity of the cleft. For example, 71% of cases with severe CPO were reported, while only 11% of cases with mild CPO were reported. Conclusions. Ascertainment was strongly related to cleft type and severity. To the degree that severity of birth defects may be related to their cause, these patterns of registration have implications for surveillance of birth defects as well as the conduct of etiologic studies. The large proportion of cleft palate cases unrecorded at birth suggests that clinical examination of the newborn palate is often inadequate.
Nonlinear visuomotor transformations: Locus and modularity
Authors: Verwey Willem B. , Heuer Herbert
Published: November 2007

Participants in two experiments moved a mouse-like device to the right to move a cursor on a computer screen to a target position. The cursor was invisible during motion but reappeared at the end of each movement. The relationship between the amplitudes of the cursor movement and the mouse movement was exponential in Experiment 1 and logarithmic in Experiment 2 for two groups of participants, while it was linear for the control groups in both experiments. The results of both experiments indicate that participants adjusted well to the external transformation by developing an internal model that approximated the inverse of the external transformation. We introduce a method to determine the locus of the internal model. It indicates that the internal model works at a processing level that either preceded specification of movement amplitude, or had become part of movement amplitude specification. Limited awareness of the nonlinear mouse–cursor relationship and the fact that a working-memory task had little effect on performance suggest that the internal model is modular and not dependent on high-level cognitive processes.
Locating targets from imagined perspectives: Comparing labelling with pointing responses
Authors: Avraamides Marios N. , Ioannidou Louiza M. , Kyranidou Melina N.
Published: November 2007

Participants in two experiments adopted imagined perspectives in a perceptually available spatial scene and located targets by using either verbal terms (labelling) or arrows (pointing). Results revealed that performance was faster and more accurate for labelling than for pointing and more so when the adopted perspectives were misaligned with the physical orientation of the participant. This finding was obtained even when an orientation cue allowed participants to adopt the imagined perspective in advance of target presentation. A third experiment replicated these findings using traditional pointing and verbal responding. We argue that performance from misaligned perspectives in perspective-taking tasks suffers due to reference frame conflicts and that these conflicts are more pronounced with pointing and other manual responses that rely more on the reference frame of the physical body.
Subjective shortening with filled and unfilled auditory and visual intervals in humans?
Authors: Wearden J. H. , Goodson Greg , Foran Karin
Published: November 2007

Two experiments tested humans on a memory for duration task based on the method of Wearden and Ferrara (1993), which had previously provided evidence for subjective shortening in memory for stimulus duration. Auditory stimuli were tones (filled) or click-defined intervals (unfilled). Filled visual stimuli were either squares or lines, with the unfilled interval being the time between two line presentations. In Experiment 1, good evidence for subjective shortening was found when filled and unfilled visual stimuli, or filled auditory stimuli, were used, but evidence for subjective shortening with unfilled auditory stimuli was more ambiguous. Experiment 2 used a simplified variant of the Wearden and Ferrara task, and evidence for subjective shortening was obtained from all four stimulus types.
Shallow processing of ambiguous pronouns: Evidence for delay
Authors: Stewart Andrew J. , Holler Judith , Kidd Evan
Published: November 2007

Two self-paced reading-time experiments examined how ambiguous pronouns are interpreted under conditions that encourage shallow processing. In Experiment 1 we show that sentences containing ambiguous pronouns are processed at the same speed as those containing unambiguous pronouns under shallow processing, but more slowly under deep processing. We outline three possible models to account for the shallow processing of ambiguous pronouns. Two involve an initial commitment followed by possible revision, and the other involves a delay in interpretation. In Experiment 2 we provide evidence that supports the delayed model of ambiguous pronoun resolution under shallow processing. We found no evidence to support a processing system that makes an initial commitment to an interpretation of the pronoun when it is encountered. We extend the account of pronoun resolution proposed by Rigalleau, Caplan, and Baudiffier (2004) to include the treatment of ambiguous pronouns under shallow processing.
Short Article: Knowing When to Hear Aids What to Hear
Authors: Bausenhart Karin M. , Rolke Bettina , Ulrich Rolf
Published: November 2007

Temporal preparation often has been assumed to influence motor stages of information processing. Recent studies, however, challenge this notion and provide evidence for a facilitation of visual processing. The present study was designed to investigate whether perceptual processing in the auditory domain also benefits from temporal preparation. To this end, we employed a pitch discrimination task. In Experiment 1, discrimination performance was clearly improved when participants were temporally prepared. This finding was confirmed in Experiment 2, which ruled out possible influences of short-term memory. The results support the notion that temporal preparation enhances perceptual processing not only in the visual, but also in the auditory, modality.
Previous attentional set can induce an attentional blink with task-irrelevant initial targets
Authors: Thompson Catherine , Underwood Geoffrey , Crundall David
Published: November 2007

Identification of a second target is often impaired by the requirement to process a prior target in a rapid serial visual presentation (RSVP). This is termed the attentional blink. Even when the first target is task irrelevant an attentional blink may occur providing this first target shares similar features with the second target ( contingent capture). An RSVP experiment was undertaken to assess whether this first target can still cause an attentional blink when it did not require a response and did not share any features with the following target. The results revealed that such task-irrelevant targets can induce an attentional blink providing that they were task relevant on a previous block of trials. This suggests that irrelevant focal stimuli can distract attention on the basis of a previous attentional set.
Hepatitis B virus polymerase inhibits the interferon-inducible MyD88 promoter by blocking nuclear translocation of Stat1
Authors: Wu Min , Xu Yang , Lin Shanshan , Zhang Xiaonan , Xiang Li , Yuan Zhenghong
Published: November 2007

Previous studies have suggested that hepatitis B virus (HBV) blocks expression of the alpha interferon (IFN-α)-inducible myeloid differential primary response protein (MyD88) gene. To study the molecular mechanism(s) of the inhibition of MyD88 expression by HBV, MyD88 promoter reporter plasmids and vectors expressing different HBV viral proteins were constructed. Co-transfection experiments showed that IFN-induced MyD88 promoter activity was inhibited by HBV polymerase expression in a dose-dependent manner and that the terminal protein (TP) domain of HBV polymerase was responsible for this antagonistic activity. Analysis of site mutants showed that the region targeted by the polymerase protein contained the signal transducer and activator of transcription (Stat) binding site. Chromatin immunoprecipitation analysis showed that the IFN-induced DNA-binding activity of Stat1 was affected. Further study demonstrated that the HBV polymerase protein inhibited the Stat1 nuclear translocation induced by IFN-α, but did not induce Stat1 degradation nor interfere with its phosphorylation. In addition, HBV polymerase could inhibit the transcriptional activity of other IFN-stimulated response element-driven promoters and the expression of interferon-stimulated genes (ISGs), such as Stat1 and ISG15. In summary, these results indicate that HBV polymerase is a general inhibitor of IFN signalling and can inhibit IFN-inducible MyD88 expression by inhibiting the activity of the MyD88 promoter through blocking the nuclear translocation of Stat1.
Cauliflower mosaic virus protein P6 is a suppressor of RNA silencing
Authors: Love Andrew J. , Laird Janet , Holt Justin , Hamilton Andrew J. , Sadanandom Ari , Milner Joel J.
Published: November 2007

We infected a transgenic Arabidopsis line (GxA), containing an amplicon-silenced 35S : : GFP transgene, with cauliflower mosaic virus (CaMV), a plant pararetrovirus with a DNA genome. Systemically infected leaves showed strong GFP fluorescence and amplicon transcripts were detectable in Northern blots, indicating that silencing of GFP had been suppressed during CaMV-infection. Transgenic Arabidopsis lines expressing CaMV protein P6, the major genetic determinant of symptom severity, were crossed with GxA. Progeny showed strong GFP fluorescence throughout and amplicon transcripts were detectable in Northern blots, indicating that P6 was suppressing local and systemic silencing. However, levels of 21 nt siRNAs derived from the GFP transgene were not reduced. In CaMV-infected plants, the P6 transgene did not reduce levels of CaMV leader-derived 21 and 24 nt siRNAs relative to levels of CaMV 35S RNA. These results demonstrate that CaMV can efficiently suppress silencing of a GFP transgene, and that P6 acts as a silencing suppressor.
Multiple recombinant dengue type 1 viruses in an isolate from a dengue patient
Authors: Aaskov John , Buzacott Katie , Field Emma , Lowry Kym , Berlioz-Arthaud Alain , Holmes Edward C.
Published: November 2007

Between 2000 and 2004, dengue virus type 1 (DENV-1) genotypes I and II from Asia were introduced into the Pacific region and co-circulated in some localities. Envelope protein gene sequences of DENV-1 from 12 patients infected on the island of New Caledonia were obtained, five of which carried genotype I viruses and six, genotype II viruses. One patient harboured a mixed infection, containing viruses assigned to both genotypes I and II, as well as a number of inter-genotypic recombinants. This is the first report of a population of dengue viruses isolated from a patient containing both parental and recombinant viruses.
Effects of point mutations in the cytidine deaminase domains of APOBEC3B on replication and hypermutation of hepatitis B virus in vitro
Authors: Bonvin Marianne , Greeve Jobst
Published: November 2007

APOBEC3 cytidine deaminases hypermutate hepatitis B virus (HBV) and inhibit its replication in vitro. Whether this inhibition is due to the generation of hypermutations or to an alternative mechanism is controversial. A series of APOBEC3B (A3B) point mutants was analysed in vitro for hypermutational activity on HBV DNA and for inhibitory effects on HBV replication. Point mutations inactivating the carboxy-terminal deaminase domain abolished the hypermutational activity and reduced the inhibitory activity on HBV replication to approximately 40 %. In contrast, the point mutation H66R, inactivating the amino-terminal deaminase domain, did not affect hypermutations, but reduced the inhibition activity to 63 %, whilst the mutant C97S had no effect in either assay. Thus, only the carboxy-terminal deaminase domain of A3B catalyses cytidine deaminations leading to HBV hypermutations, but induction of hypermutations is not sufficient for full inhibition of HBV replication, for which both domains of A3B must be intact.
The A5 gene of alcelaphine herpesvirus 1 encodes a constitutively active G-protein-coupled receptor that is non-essential for the induction of malignant catarrhal fever in rabbits
Authors: Boudry C. , Markine-Goriaynoff N. , Delforge C. , Springael J.-Y. , de Leval L. , Drion P. , Russell G. , Haig D. M. , Vanderplasschen A. F. , Dewals B.
Published: November 2007

Many gammaherpesviruses encode G-protein-coupled receptors (GPCRs). Several in vivo studies have revealed that gammaherpesvirus GPCRs are important for viral replication and for virus-induced pathogenesis. The gammaherpesvirus alcelaphine herpesvirus 1 (AlHV-1) is carried asymptomatically by wildebeest, but causes malignant catarrhal fever (MCF) following cross-species transmission to a variety of susceptible species. The A5 ORF of the AlHV-1 genome encodes a putative GPCR. In the present study, we investigated whether A5 encodes a functional GPCR and addressed its role in viral replication and in the pathogenesis of MCF. In silico analysis supported the hypothesis that A5 could encode a functional GPCR as its expression product contained several hallmark features of GPCRs. Expression of A5 as tagged proteins in various cell lines revealed that A5 localizes in cell membranes, including the plasma membrane. Using [35S]GTPγS and reporter gene assays, we found that A5 is able to constitutively couple to α
i-type G-proteins in transfected cells, and that this interaction is able to inhibit forskolin-triggered cAMP response element-binding protein (CREB) activation. Finally, using an AlHV-1 BAC clone, we produced a strain deleted for A5 and a revertant strain. Interestingly, the strain deleted for A5 replicated comparably to the wild-type parental strain and induced MCF in rabbits that was indistinguishable from that of the parental strain. The present study is the first to investigate the role of an individual gene of AlHV-1 in MCF pathogenesis.
Genomic sequence of chorioallantois vaccinia virus Ankara, the ancestor of modified vaccinia virus Ankara
Authors: Meisinger-Henschel Christine , Schmidt Michaela , Lukassen Susanne , Linke Burkhard , Krause Lutz , Konietzny Sebastian , Goesmann Alexander , Howley Paul , Chaplin Paul , Suter Mark , Hausmann Jürgen
Published: November 2007

Chorioallantois vaccinia virus Ankara (CVA) is the parental virus of modified vaccinia virus Ankara (MVA), which was derived from CVA by more than 570 passages in chicken embryo fibroblasts (CEF). MVA became severely host-cell-restricted to avian cells and has strongly diminished virulence in mammalian hosts, while maintaining good immunogenicity. We determined the complete coding sequence of the parental CVA and mapped the exact positions of the six major deletions that emerged in the MVA genome. All six major deletions occurred in regions of the CVA genome where one or more truncated or fragmented open reading frames (ORFs) pre-existed. The CVA genome contains 229 ORFs of which 51 are fragments of full-length orthopoxvirus (OPV) genes, including fragmented orthologues of C9L and M1L (encoding two well-conserved ankyrin-like proteins), A39R (encoding a semaphorin-like protein) and A55R (encoding a kelch-like protein). Phylogenetic analysis demonstrated that MVA was most closely related to CVA, followed by the vaccinia virus (VACV) strain DUKE, a patient-derived isolate of the Dryvax vaccine virus. Loss or mutation of genes outside the six major deletions are assumed to contribute to the restricted host range phenotype of MVA. In support of this notion, deletions, insertions and non-synonymous mutations were found in 122 of the 195 ORFs remaining in MVA when compared with their CVA counterparts. Thus, detailed knowledge of the CVA genomic sequence is a prerequisite to further dissect the genetic basis of the MVA host range phenotype as well as the particular immunological properties of MVA.
Rescue of Akabane virus (family Bunyaviridae) entirely from cloned cDNAs by using RNA polymerase I
Authors: Ogawa Yohsuke , Sugiura Keita , Kato Kentaro , Tohya Yukinobu , Akashi Hiroomi
Published: November 2007

Reverse-genetic systems are often used to study different aspects of the viral life cycle. To date, three rescue systems have been developed for the family Bunyaviridae. These systems use T7 RNA polymerase, which is generally used in rescue systems for Mononegavirales. In the present study, we describe a rescue system for Akabane virus (family Bunyaviridae) that uses cDNAs and RNA polymerase I instead of T7 RNA polymerase. The utility of this system was demonstrated by the generation of a mutant with a deletion of the non-structural protein (NSs) on the S RNA segment. These results offer a new option for bunyavirus rescue.
Prion propagation in a nerve conduit model containing segments devoid of axons
Authors: Kratzel Christine , Krüger Dominique , Beekes Michael
Published: November 2007

Prions, the putative causative agents of transmissible spongiform encephalopathies, are neurotropic pathogens that spread to the central nervous system via synaptically linked neural conduits upon peripheral infection. Axons and their transport processes have been suggested as mediators of nerve-associated prion dissemination. However, the exact cellular components and molecular mechanisms underlying neural spread are unknown. This study used an established hamster scrapie model to pursue a novel experimental approach using nerve conduits containing segments devoid of neurites generated by incomplete nerve regeneration following Wallerian degeneration to probe the necessity of axons for the neural propagation of prions. For this purpose, animals were subjected to unilateral sciatic neurectomy 4 weeks before footpad inoculation with scrapie agent. The results showed that the regional nerve is the prime conduit for cerebral neuroinvasion and revealed, as evidenced by the accumulation of pathological prion protein PrPTSE, that prions can proceed along segments of peripheral neural projections without detectable axonal structures.
Relationship between adenovirus DNA replication proteins and nucleolar proteins B23.1 and B23.2
Authors: Hindley Clemence E. , Davidson Andrew D. , Matthews David A.
Published: November 2007

Adenovirus infection subverts nucleolar structure and function. B23 is a nucleolar protein present in two isoforms (B23.1 and B23.2) and both isoforms have been identified as stimulatory factors for adenovirus DNA replication. Here, it is demonstrated that the two isoforms of B23, B23.1 and B23.2, interact and co-localize differently with viral DNA replication proteins pTP and DBP in adenovirus-infected cells. Thus, the mechanism by which the two proteins stimulate viral DNA replication is likely to differ. These data also demonstrate the importance of testing both isoforms of B23 for interactions with viral proteins and nucleic acids.
Identification of amino acid sequences determining interaction between the cucumber mosaic virus-encoded 2a polymerase and 3a movement proteins
Authors: Hwang Min Sook , Kim Kyung Nam , Lee Jeong Hyun , Park Young In
Published: November 2007

The cucumber mosaic virus (CMV)-encoded 3a movement protein (MP) is indispensable for CMV movement in plants. We have previously shown that MP interacts directly with the CMV-encoded 2a polymerase protein in vitro. Here, we further dissected this interaction and determined the amino acid sequences that are responsible for the MP and 2a polymerase protein interaction. Both the N-terminal 21 amino acids and the central GDD motif of the 2a polymerase protein were important for interacting with the MP. Although each of the regions alone was sufficient for the interaction with MP, quantitative yeast two-hybrid analyses showed that they acted synergistically to enhance the binding affinity. The MP N-terminal 20 amino acids were sufficient for interacting with the 2a polymerase protein, and the serine residue at position 14 played a critical role in the interaction. Multiple sequence alignment showed that the 2a protein interacting regions and the serine at position 14 in the MP are highly conserved among subgroup I and II CMV isolates.
The hepatitis B x antigen effector, URG7, blocks tumour necrosis factor α-mediated apoptosis by activation of phosphoinositol 3-kinase and β-catenin
Authors: Pan Jingbo , Lian Zhaorui , Wallet Sarah , Feitelson Mark A.
Published: November 2007

Hepatitis B x antigen (HBxAg) contributes significantly to the pathogenesis of chronic infection and development of hepatocellular carcinoma. To discern some of its operative pathways, HepG2 cells were stably transduced with HBx or the bacterial chloramphenicol acetyltransferase (CAT) gene. Differential gene expression has previously revealed an upregulated gene, clone 7 (URG7), that conferred resistance to anti-Fas killing on HepG2X cells. Given that tumour necrosis factor alpha (TNFα) is also an important mediator of chronic hepatitis, and partially shares signalling with Fas, experiments were designed to test whether URG7 blocks TNFα killing of HepG2X cells. HepG2X cells expressing URG7 and HepG2 cells overexpressing URG7 in the absence of HBxAg were resistant to TNFα killing compared with HepG2CAT cells. URG7 small interfering RNA restored the sensitivity of HepG2X cells to TNFα killing. Killing was associated with the activation of caspases 3 and 8, suggesting that URG7 blocked these caspases. This resistance was also associated with activation of phosphoinositol 3-kinase/Akt. Given that Akt and HBxAg also activate β-catenin, experiments were designed to determine whether URG7 blocked apoptosis via activation of β-catenin. Both HBxAg and URG7 activated fragments of the β-catenin promoter, and also promoted expression of β-catenin target genes. Hence, URG7 inhibits TNFα-mediated killing by blocking one or more caspases in the apoptotic pathway and by activating phosphoinositol 3-kinase and β-catenin, thereby overriding the apoptotic signalling of TNFα. This suggests that URG7 helps to protect virus-infected hepatocytes during chronic hepatitis B virus infection.
Demographic risk factors for classical and atypical scrapie in Great Britain
Authors: Green Darren M. , del Rio Vilas Victor J. , Birch Colin P. D. , Johnson Jethro , Kiss Istvan Z. , McCarthy Noel D. , Kao Rowland R.
Published: November 2007

Following the bovine spongiform encephalopathy (BSE) crisis, the European Union has introduced policies for eradicating transmissible spongiform encephalopathies (TSEs), including scrapie, from large ruminants. However, recent European Union surveillance has identified a novel prion disease, ‘atypical’ scrapie, substantially different from classical scrapie. It is unknown whether atypical scrapie is naturally transmissible or zoonotic, like BSE. Furthermore, cases have occurred in scrapie-resistant genotypes that are targets for selection in legislated selective breeding programmes. Here, the first epidemiological study of British cases of atypical scrapie is described, focusing on the demographics and trading patterns of farms and using databases of recorded livestock movements. Triplet comparisons found that farms with atypical scrapie stock more sheep than those of the general, non-affected population. They also move larger numbers of animals than control farms, but similar numbers to farms reporting classical scrapie. Whilst there is weak evidence of association through sheep trading of farms reporting classical scrapie, atypical scrapie shows no such evidence, being well-distributed across regions of Great Britain and through the sheep-trading network. Thus, although cases are few in number so far, our study suggests that, should natural transmission of atypical scrapie be occurring at all, it is doing so slowly.