bluuebunny/crossref_metadata_2025 huggingface dataset:
GLP‐1 (9–36) Amide, Cleavage Product of GLP‐1 (7–36) Amide, Is a Glucoregulatory Peptide
Authors: Elahi Dariush , Egan Josephine M. , Shannon Richard P. , Meneilly Graydon S. , Khatri Ashok , Habener Joel F. , Andersen Dana K.
Published: April 2008

Objective: Glucagon‐like peptide‐1 (GLP‐1) (7–36) amide is a glucoregulatory hormone with insulinotropic and insulinomimetic actions. We determined whether the insulinomimetic effects of GLP‐1 are mediated through its principal metabolite, GLP‐1 (9–36) amide (GLP‐1m).

Methods and Procedures: Glucose turnover during two, 2‐h, euglycemic clamps was measured in 12 lean and 12 obese (BMI <25 or >30 kg/m2) male and female subject volunteers with normal oral glucose tolerance test. Saline or GLP‐1m were infused from 0 to 60 min in each study. Additionally, seven lean and six obese subjects underwent a third clamp in which the GLP‐1 receptor (GLP‐1R) antagonist, exendin (9–39) amide was infused from −60 to 60 min with GLP‐1m from 0 to 60 min.

Results: No glucose infusion was required in lean subjects to sustain euglycemia (glucose clamp) during saline or GLP‐1m infusions. However, in obese subjects glucose infusion was necessary during GLP‐1m infusion alone in order to compensate for a marked (>50%) inhibition of hepatic glucose production (HGP). Plasma insulin levels remained constant in lean subjects but rose significantly in obese subjects after termination of the peptide infusions. During GLP‐1R blockade, infusion of glucose was immediately required upon starting GLP‐1m infusions in all subjects due to a more dramatic reduction in HGP, as well as a delayed and modest insulinotropic response.

Discussion: We conclude that GLP‐1m potently inhibits HGP and is a weak insulinotropic agent. These properties are particularly apparent and pronounced in obese but only become apparent in lean subjects during GLP‐1 (7–36) receptor blockade. These previously unrecognized antidiabetogenic actions of GLP‐1m may have therapeutic usefulness.
Body Fat and Mobility Are Explained by Common Genetic and Environmental Influences in Older Women
Authors: Ortega‐Alonso Alfredo , Sipilä Sarianna , Kujala Urho M. , Kaprio Jaakko , Rantanen Taina
Published: April 2008

In older adults, mobility limitations often coexist with overweight or obesity, suggesting that similar factors may underlie both traits. This study examined the extent to which genetic and environmental influences explain the association between adiposity and mobility in older women. Body fat percentage (bioimpedance test), walking speed over 10 m, and distance walked in a 6‐min test were evaluated in 92 monozygotic (MZ) and 104 dizygotic (DZ) pairs of twin sisters reared together, aged 63–76 years. Genetic and environmental influences on each trait were estimated using age‐adjusted multivariate genetic modeling. The analyses showed that the means (and s.d.) for body fat percentage, walking speed, and walking endurance were 33.2 ± 7.3%, 1.7 ± 0.3 m/s and 529.7 ± 75.4 m, respectively. The phenotypic correlation between adiposity and walking speed was −0.32 and between adiposity and endurance it was −0.33. Genetic influences explained 80% of the association between adiposity and speed, and 65% of adiposity and walking endurance. Cross‐trait genetic influences accounted for 12% of the variability in adiposity, 56% in walking speed, and 34% in endurance. Trait‐specific genetic influences were also detected for adiposity (54%) and walking endurance (13%), but not speed. In conclusion, among community‐living older women, an inverse association was found between adiposity and mobility that was mostly due to the effect of shared genes. This result suggests that the identification of genetic variants for body fat metabolism may also provide understanding of the development of mobility limitations in older women.
Maternal and Paternal Controlling Feeding Practices: Reliability and Relationships With BMI
Authors: Haycraft Emma L. , Blissett Jacqueline M.
Published: April 2008

Objective: This study aimed to examine the interrelationships between mothers' and fathers' reports on the child‐feeding questionnaire (CFQ), the BMI of parents and their children, and observations of parents' controlling feeding practices at mealtimes.

Methods and Procedures: Twenty‐three mothers and twenty‐three fathers of children aged between 18 and 67 months reported on their child‐feeding practices, on their child's height and weight, and were observed during a normal family mealtime at home.

Results: No associations were found between mothers' reported and observed feeding practices. Fathers' reported pressure to eat and restriction were associated with more controlling observed mealtime feeding practices. Mothers and fathers did not significantly differ in their reported or observed child‐feeding practices. Children's BMI was not related to maternal or paternal reported or observed feeding practices. More mealtime pressure was observed in parents with a higher BMI.

Discussion: Fathers' self‐reports of their mealtime practices are reliable. Mothers' feeding practices may differ when fathers are present and further work should examine mothers at mealtimes with and without fathers. Although children's BMI was not related to parents' use of reported or observed control, parents with a higher BMI were more controlling, highlighting the importance of considering parents' own weight in future studies.
Nuclear Astrophysics Before 1957
Authors: Salpeter Edwin E.
Published: April 2008

I discuss especially my summer with Willy Fowler at Kellogg Radiation Laboratory in 1951, where I did my ‘triple alpha’ work. I also go back even earlier to Arthur Eddington and Hans Bethe. The 1953 summer school in Ann Arbor only gets a mention.
Solar Neutrinos: Models, Observations and New Opportunities
Authors: Haxton W. C.
Published: April 2008

I discuss the development and resolution of the solar neutrino problem, as well as opportunities now open to us to extend our knowledge of main-sequence stellar evolution and neutrino astrophysics.
New and Old in the Southern Question
Authors: Bevilacqua Piero
Published: April 2008

The southern question has been posed at the key moments in the history of the Italian state. Today we face a moment of comparable importance which urges that the southern question be re-thought. It is not an unchanging question, yet it concerns issues fundamental to the state and has been treated by the country's greatest intellectuals as a national issue. The meridionalisti have been Italy's critical conscience yet, at the same time, stereotypes of a uniformly backward South have taken hold. The post-war intervention in the Mezzogiorno should not be seen through such stereotypes as a wholly negative experience. Its successes and failures fit into an Italian pattern of state-led modernization and it cannot be understood in isolation from the Italian state's weaknesses. Today, a new pact between the weakest and strongest sectors is essential. The South's economic and political leadership will be a central object of study if intellectuals are to help inform new policy.
ITALIAN IDENTITY: CATHOLIC RESPONSES TO SECULARIST DEFINITIONS, c.1910–48
Authors: Logan Oliver
Published: April 2008

In united Italy, assertions by Catholic militants about their nation's true identity have been bound up with polemic against secularist forces and with claims about the position due to the Church in Italian society. They have insisted that Italy's authentic traditions are Catholic and that her true greatness resides in her being the heart of Christian civilization. Hostile or threatening ideologies, e.g. idealist philosophy and Communism, have been stigmatized as alien to Italian tradition. In the face of Fascism, with which the ‘Catholic world's’ relations were ambivalent, there was a major ideological campaign to assert a Catholic definition of the keyword romanità. The way in which Catholic theoreticians have defined the ‘nation’ in organicist terms have been linked to strategies of ideological defence against state forms, whether liberal or Fascist, perceived to be overweening.
De Gasperi and Togliatti: political leadership and personality cults in post-war Italy
Authors: Marsili Marzia
Published: April 2008

After twenty years of Fascism, political leaders were faced with the need to rediscover or invent new ways of relating to the mass public and, in the first place, to distance themselves from the type of relationship consolidated under Fascism. This article is based on an examination of the representations of De Gasperi and Togliatti in illustrated weeklies and in the satirical press, as well as their more or less hagiographical biographies. From the sources it emerges that, in the case of the Christian Democrat leader, the hypothesis that there was a personality cult is hard to sustain. By contrast, in the case of Togliatti, it does seem possible to argue that there were manifestations of a genuine cult, but these were set within the context of an institutional charisma.
Leptin affects endocardial cushion formation by modulating EMT and migration via Akt signaling cascades
Authors: Nath Anjali K. , Brown Rachel M. , Michaud Michael , Sierra-Honigmann M. Rocio , Snyder Michael , Madri Joseph A.
Published: April 2008

Blood circulation is dependent on heart valves to direct blood flow through the heart and great vessels. Valve development relies on epithelial to mesenchymal transition (EMT), a central feature of embryonic development and metastatic cancer. Abnormal EMT and remodeling contribute to the etiology of several congenital heart defects. Leptin and its receptor were detected in the mouse embryonic heart. Using an ex vivo model of cardiac EMT, the inhibition of leptin results in a signal transducer and activator of transcription 3 and Snail/vascular endothelial cadherin–independent decrease in EMT and migration. Our data suggest that an Akt signaling pathway underlies the observed phenotype. Furthermore, loss of leptin phenocopied the functional inhibition of αvβ3 integrin receptor and resulted in decreased αvβ3 integrin and matrix metalloprotease 2, suggesting that the leptin signaling pathway is involved in adhesion and migration processes. This study adds leptin to the repertoire of factors that mediate EMT and, for the first time, demonstrates a role for the interleukin 6 family in embryonic EMT.
DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement
Authors: Jang Chang-Young , Wong Jim , Coppinger Judith A. , Seki Akiko , Yates John R. , Fang Guowei
Published: April 2008

Dynamic turnover of the spindle is a driving force for chromosome congression and segregation in mitosis. Through a functional genomic analysis, we identify DDA3 as a previously unknown regulator of spindle dynamics that is essential for mitotic progression. DDA3 depletion results in a high frequency of unaligned chromosomes, a substantial reduction in tension across sister kinetochores at metaphase, and a decrease in the velocity of chromosome segregation at anaphase. DDA3 associates with the mitotic spindle and controls microtubule (MT) dynamics. Mechanistically, DDA3 interacts with the MT depolymerase Kif2a in an MT-dependent manner and recruits Kif2a to the mitotic spindle and spindle poles. Depletion of DDA3 increases the steady-state levels of spindle MTs by reducing the turnover rate of the mitotic spindle and by increasing the rate of MT polymerization, which phenocopies the effects of partial knockdown of Kif2a. Thus, DDA3 represents a new class of MT-destabilizing protein that controls spindle dynamics and mitotic progression by regulating MT depolymerases.
Weighted projective spaces and minimal nilpotent orbits
Authors: Rossi Carlo
Published: April 2008

We investigate (twisted) rings of differential operators on the resolution of singularities of an irreducible component

X
¯

\overline X

of

O
¯

m
i
n

∩

n

+

\overline O_{\mathrm {min}}\cap \mathfrak n_+

(where

O
¯

m
i
n

\overline O_{\mathrm {min}}

is the (Zariski) closure of the minimal nilpotent orbit of

s
p

2
n

\mathfrak {sp}_{2n}

and

n

+

\mathfrak n_+

is the Borel subalgebra of

s
p

2
n

\mathfrak {sp}_{2n}

) using toric geometry, and show that they are homomorphic images of a certain family of associative subalgebras of

U
(

s
p

2
n

)

U(\mathfrak {sp}_{2n})

, which contains the maximal parabolic subalgebra

p

\mathfrak p

determining

O
¯

min

\overline O_{\min }

. Further, using Fourier transforms on Weyl algebras, we show that (twisted) rings of well-suited weighted projective spaces are obtained from the same family of subalgebras. Finally, we investigate this family of subalgebras from the representation-theoretical point of view and, among other things, rediscover in a different framework irreducible highest weight modules for the UEA of

s
p

2
n

\mathfrak {sp}_{2n}

.
Validation of the Berlin Questionnaire and American Society of Anesthesiologists Checklist as Screening Tools for Obstructive Sleep Apnea in Surgical Patients
Authors: Chung Frances , Yegneswaran Balaji , Liao Pu , Chung Sharon A. , Vairavanathan Santhira , Islam Sazzadul , Khajehdehi Ali , Shapiro Colin M.
Published: April 2008

Background

Because of the high prevalence of obstructive sleep apnea (OSA) and its adverse impact on perioperative outcome, a practical screening tool for surgical patients is required. This study was conducted to validate the Berlin questionnaire and the American Society of Anesthesiologists (ASA) checklist in surgical patients and to compare them with the STOP questionnaire.

Methods

After hospital ethics approval, preoperative patients aged 18 yr or older and without previously diagnosed OSA were recruited. The scores from the Berlin questionnaire, ASA checklist, and STOP questionnaire were evaluated versus the apnea-hypopnea index from in-laboratory polysomnography. The perioperative data were collected through chart review.

Results

Of 2,467 screened patients, 33, 27, and 28% were respectively classified as being at high risk of OSA by the Berlin questionnaire, ASA checklist, and STOP questionnaire. The performance of the screening tools was evaluated in 177 patients who underwent polysomnography. The sensitivities of the Berlin questionnaire, ASA checklist, and STOP questionnaire were 68.9-87.2, 72.1-87.2, and 65.6-79.5% at different apnea-hypopnea index cutoffs. There was no significant difference between the three screening tools in the predictive parameters. The patients with an apnea-hypopnea index greater than 5 and the patients identified as being at high risk of OSA by the STOP questionnaire or ASA checklist had a significantly increased incidence of postoperative complications.

Conclusions

Similar to the STOP questionnaire, the Berlin questionnaire and ASA checklist demonstrated a moderately high level of sensitivity for OSA screening. The STOP questionnaire and the ASA checklist were able to identify the patients who were likely to develop postoperative complications.
PrP genotypes of free-ranging wapiti (Cervus elaphus nelsoni) with chronic wasting disease
Authors: Perucchini Matteo , Griffin Karen , Miller Michael W. , Goldmann Wilfred
Published: April 2008

Variation in PrP prion gene sequence appears to modulate susceptibility to chronic wasting disease (CWD), a naturally occurring prion disease affecting four North American species of the family Cervidae. Wapiti (Cervus elaphus nelsoni) PrP is polymorphic at codon 132 [methionine (M) or leucine (L)]. We genotyped 171 samples, collected between 2002 and 2005 from CWD-infected and uninfected wapiti from three free-ranging populations in Colorado, USA, to study influences of PrP polymorphisms on CWD susceptibility further. Overall genotype frequencies for 124 apparently uninfected animals were 65.3 % MM132, 32.3 % ML132 and 2.4 % LL132; for 47 CWD-infected animals, these frequencies were 70.2 % MM132, 27.7 % ML132 and 2.1 % LL132. Surprisingly, our data revealed that, among recent (approx. 2002–2005) CWD cases detected in free-ranging Colorado wapiti, the three PrP codon 132 genotypes were represented in proportion to their abundance in sampled populations (P≥0.24) and all three genotypes showed equivalent susceptibility to infection.
Activation of sterol regulatory element-binding protein 1c and fatty acid synthase transcription by hepatitis C virus non-structural protein 2
Authors: Oem Jae-Ku , Jackel-Cram Candice , Li Yi-Ping , Zhou Yan , Zhong Jin , Shimano Hitoshi , Babiuk Lorne A. , Liu Qiang
Published: April 2008

Transcriptional factor sterol regulatory element-binding protein 1c (SREBP-1c) activates the transcription of lipogenic genes, including fatty acid synthase (FAS). Hepatitis C virus (HCV) infection is often associated with lipid accumulation within the liver, known as steatosis in the clinic. The molecular mechanisms of HCV-associated steatosis are not well characterized. Here, we showed that HCV non-structural protein 2 (NS2) activated SREBP-1c transcription in human hepatic Huh-7 cells as measured by using a human SREBP-1c promoter–luciferase reporter plasmid. We further showed that sterol regulatory element (SRE) and liver X receptor element (LXRE) in the SREBP-1c promoter were involved in SREBP-1c activation by HCV NS2. Furthermore, expression of HCV NS2 resulted in the upregulation of FAS transcription. We also showed that FAS upregulation by HCV NS2 was SREBP-1-dependent since deleting the SRE sequence in a FAS promoter and expressing a dominant-negative SREBP-1 abrogated FAS promoter upregulation by HCV NS2. Taken together, our results suggest that HCV NS2 can upregulate the transcription of SREBP-1c and FAS, and thus is probably a contributing factor for HCV-associated steatosis.
Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein tyrosine kinase Syk
Authors: Inubushi Sachiko , Nagano-Fujii Motoko , Kitayama Kikumi , Tanaka Motofumi , An Chunying , Yokozaki Hiroshi , Yamamura Hirohei , Nuriya Hideko , Kohara Michinori , Sada Kiyonao , Hotta Hak
Published: April 2008

Hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma. However, the precise mechanism underlying the carcinogenesis is yet to be elucidated. It has recently been reported that Syk, a non-receptor protein tyrosine kinase, functions as a potent tumour suppressor in human breast carcinoma. This study first examined the possible effect of HCV infection on expression of Sykin vivo. Immunohistochemical analysis revealed that endogenous Syk, which otherwise was expressed diffusely in the cytoplasm of normal hepatocytes, was localized near the cell membrane with a patchy pattern in HCV-infected hepatocytes. The possible interaction between HCV proteins and Syk in human hepatoma-derived Huh-7 cells was then examined. Immunoprecipitation analysis revealed that NS5A interacted strongly with Syk. Deletion-mutation analysis revealed that an N-terminal portion of NS5A (aa 1–175) was involved in the physical interaction with Syk. Anin vitrokinase assay demonstrated that NS5A inhibited the enzymic activity of Syk and that, in addition to the N-terminal 175 residues, a central portion of NS5A (aa 237–302) was required for inhibition of Syk. Moreover, Syk-mediated phosphorylation of phospholipase C-γ1 was downregulated by NS5A. An interaction of NS5A with Syk was also detected in Huh-7.5 cells harbouring an HCV RNA replicon or infected with HCV. In conclusion, these results demonstrated that NS5A interacts with Syk resulting in negative regulation of its kinase activity. The results indicate that NS5A may be involved in the carcinogenesis of hepatocytes through the suppression of Syk kinase activities.
Endoplasmic reticulum chaperones participate in human cytomegalovirus US2-mediated degradation of class I major histocompatibility complex molecules
Authors: Oresic Kristina , Tortorella Domenico
Published: April 2008

Inhibition of cell-surface expression of major histocompatibility complex class I molecules by human cytomegalovirus (HCMV, aβ-herpesvirus) promotes escape from recognition by CD8+cytotoxic T cells. The HCMV US2 and US11 gene products induce class I downregulation during the early phase of HCMV infection by facilitating the degradation of class I heavy chains. The HCMV proteins promote the transport of the class I heavy chains across the endoplasmic reticulum (ER) membrane into the cytosol by a process referred to as ‘dislocation’, which is then followed by proteasome degradation. This process has striking similarities to the degradation of misfolded ER proteins mediated by ER quality control. Even though the major steps of the dislocation reaction have been characterized, the cellular proteins, specifically the ER chaperones involved in targeting class I for dislocation, have not been fully delineated. To elucidate the chaperones involved in HCMV-mediated class I dislocation, we utilized a chimeric class I heavy chain with an affinity tag at its carboxy terminus. Interestingly, US2 but not US11 continued to target the class I chimera for destruction, suggesting a structural limitation for US11-mediated degradation. Association studies in US2 cells and in cells that express a US2 mutant, US2–186HA, revealed that class I specifically interacts with calnexin, BiP and calreticulin. These findings demonstrate that US2-mediated class I destruction utilizes specific chaperones to facilitate class I dislocation. The data suggest a more general model in which the chaperones that mediate protein folding may also function during ER quality control to eliminate aberrant ER proteins.
Mouse cytomegalovirus inhibits beta interferon (IFN-β) gene expression and controls activation pathways of the IFN-β enhanceosome
Authors: Le Vu Thuy Khanh , Trilling Mirko , Zimmermann Albert , Hengel Hartmut
Published: April 2008

We have investigated beta interferon (IFN-β) and IFN-α4 gene expression and activation of related transcription factors in mouse cytomegalovirus (MCMV)-infected fibroblasts. mRNA analysis demonstrated an initial phase of IFN gene induction upon MCMV infection, which was followed by a sustained MCMV-mediated simultaneous downregulation of IFN-β and IFN-α4 gene expression. The induction of IFN transcription resulted from the activation of the components of the IFN-β enhanceosome, i.e. IFN regulatory factor (IRF) 3, nuclear factor (NF)-κB, activating transcription factor (ATF)-2 and c-Jun. Activation of the transcription factors occurred rapidly and in a sequential order upon infection, but only lasted a while. As a consequence, IFN-α/β gene expression became undetectable 6 h post-infection and throughout the MCMV replication cycle. This effect is based on an active interference since restimulation of IFN gene induction by further external stimuli (e.g. Sendai virus infection) was completely abolished. This inhibition required MCMV gene expression and was not observed in cells infected with UV-inactivated MCMV virions. The efficiency of inhibition is achieved by a concerted blockade of IκBα degradation and a lack of nuclear accumulation of IRF3 and ATF-2/c-Jun. Using an MCMV mutant lacking pM27, a signal transducer and activator of transcription (STAT) 2-specific inhibitor of Jak/STAT signalling, we found that the initial phase of IFN induction and the subsequent inhibition does not depend on the positive-IFN feedback loop. Our findings indicate that the MCMV-mediated downregulation of IFN transcription in fibroblasts relies on a large arsenal of inhibitory mechanisms targeting each pathway that contributes to the multiprotein enhanceosome complex.
Complete genome sequence analysis of Seneca Valley virus-001, a novel oncolytic picornavirus
Authors: Hales Laura M. , Knowles Nick J. , Reddy P. Seshidar , Xu Ling , Hay Carl , Hallenbeck Paul L.
Published: April 2008

The complete genome sequence of Seneca Valley virus-001 (SVV-001), a small RNA virus, was determined and was shown to have typical picornavirus features. The 7280 nt long genome was predicted to contain a 5′ untranslated region (UTR) of 666 nt, followed by a single long open reading frame consisting of 6543 nt, which encodes a 2181 aa polyprotein. This polyprotein could potentially be cleaved into 12 polypeptides in the standard picornavirus L-4-3-4 layout. A 3′ UTR of 71 nt was followed by a poly(A) tail of unknown length. Comparisons with other picornaviruses showed that the P1, 2C, 3C and 3D polypeptides of SVV-001 were related most closely to those of the cardioviruses, although they were not related as closely to those of encephalomyocarditis virus and Theiler's murine encephalomyelitis virus as the latter were to each other. Most other regions of the polyprotein differed considerably from those of all other known picornaviruses. SVV-001 contains elements of an internal ribosome entry site reminiscent of that found in hepatitis C virus and a number of genetically diverse picornaviruses. SVV-001 is a novel picornavirus and it is proposed that it be classified as the prototype species in a novel genus named ‘Senecavirus’.
Analysis of the genome of Spodoptera frugiperda nucleopolyhedrovirus (SfMNPV-19) and of the high genomic heterogeneity in group II nucleopolyhedroviruses
Authors: Wolff José Luiz Caldas , Valicente Fernando Hercos , Martins Renata , Oliveira Juliana Velasco de Castro , Zanotto Paolo Marinho de Andrade
Published: April 2008

The genome of the most virulent among 22 Brazilian geographical isolates of Spodoptera frugiperda nucleopolyhedrovirus, isolate 19 (SfMNPV-19), was completely sequenced and shown to comprise 132 565 bp and 141 open reading frames (ORFs). A total of 11 ORFs with no homology to genes in the GenBank database were found. Of those, four had typical baculovirus promoter motifs and polyadenylation sites. Computer-simulated restriction enzyme cleavage patterns of SfMNPV-19 were compared with published physical maps of other SfMNPV isolates. Differences were observed in terms of the restriction profiles and genome size. Comparison of SfMNPV-19 with the sequence of the SfMNPV isolate 3AP2 indicated that they differed due to a 1427 bp deletion, as well as by a series of smaller deletions and point mutations. The majority of genes of SfMNPV-19 were conserved in the closely related Spodoptera exigua NPV (SeMNPV) and Agrotis segetum NPV (AgseMNPV-A), but a few regions experienced major changes and rearrangements. Synthenic maps for the genomes of group II NPVs revealed that gene collinearity was observed only within certain clusters. Analysis of the dynamics of gene gain and loss along the phylogenetic tree of the NPVs showed that group II had only five defining genes and supported the hypothesis that these viruses form ten highly divergent ancient lineages. Crucially, more than 60 % of the gene gain events followed a power-law relation to genetic distance among baculoviruses, indicative of temporal organization in the gene accretion process.
Genomic characterizations of bat coronaviruses (1A, 1B and HKU8) and evidence for co-infections in Miniopterus bats
Authors: Chu D. K. W. , Peiris J. S. M. , Chen H. , Guan Y. , Poon L. L. M.
Published: April 2008

We previously reported the detection of bat coronaviruses (bat CoVs 1A, 1B, HKU7, HKU8 and bat-severe acute respiratory syndrome coronavirus) in Miniopterus spp. that cohabit a cave in Hong Kong. Here, we report the full genomic sequences of bat CoVs 1A, 1B and HKU8. Bat CoVs 1A and 1B, which are commonly found in the Miniopterus, are phylogenetically closely related. Using species-specific RT-PCR assays, bat CoVs 1A and 1B were confirmed to have distinct host specificities to Miniopterus
magnater and Miniopterus
pusillus, respectively. Interestingly, co-infections of bat CoVs 1B and HKU8 in M. pusillus are detected in seven of 38 virus-positive specimens collected from 2004 to 2006. These findings highlight that co-infections of some coronaviruses might be common events in nature. The biological basis for the host restriction of bat coronaviruses, however, is yet to be determined.
Bombyx mori nucleopolyhedrovirus ORF56 encodes an occlusion-derived virus protein and is not essential for budded virus production
Authors: Xu Hai-Jun , Yang Zhang-Nv , Zhao Jin-Fang , Tian Cai-Hong , Ge Jun-Qing , Tang Xu-Dong , Bao Yan-Yuan , Zhang Chuan-Xi
Published: April 2008

Bombyx mori nucleopolyhedrovirus ORF56 (Bm56) is a baculovirus core gene that is highly conserved in all baculoviruses that have had their genomes sequenced to date. Its transcripts in BmNPV-infected cells could be detected from 12 h post-infection (p.i.) and the encoded protein could be detected at 16 h p.i. by using a polyclonal antibody against glutathione S-transferase–Bm56 fusion protein. Western blot analysis showed that Bm56 is a structural component of the occlusion-derived virus nucleocapsid. Subsequent confocal microscopy revealed that Bm56 was distributed in the outer nuclear membrane and the intranuclear region of infected cells. To investigate the role of Bm56 in virus replication, a Bm56-knockout bacmid of BmNPV was constructed via homologous recombination in Escherichia coli. The Bm56 deletion had no effect on budded virus (BV) production in cultured cells; however, the deletion affected occlusion-body morphogenesis. A larval bioassay demonstrated that the Bm56 deletion did not reduce infectivity, whereas it resulted in a 50 % lethal time that was 16–18 h longer than that of the wild-type bacmid at every dose used in this study. These results indicate that Bm56 facilitates efficient virus production in vivo; however, it is not essential for BV production in vitro.
Antibodies against Epstein–Barr virus gp78 antigen: a novel marker for serological diagnosis of nasopharyngeal carcinoma detected by xMAP technology
Authors: Gu Ai-Di , Xie Yan-Bo , Mo Hao-Yuan , Jia Wei-Hua , Li Miao-Yan , Li Ming , Chen Li-Zhen , Feng Qi-Sheng , Liu Quentin , Qian Chao-Nan , Zeng Yi-Xin
Published: April 2008

Immunoglobulin (Ig) A and/or IgG reactivities to several Epstein–Barr virus (EBV) antigens have been used to facilitate diagnosis of nasopharyngeal carcinoma (NPC). However, antibodies against gp78, an EBV membrane glycoprotein, have not been examined to this day. In this study, we utilized Luminex multi-analyte profiling (xMAP) technology to analyse antibody responses to a synthetic peptide of gp78 in sera samples from 95 NPC patients and 91 healthy controls. Our results showed the sensitivity and specificity of IgA-gp78 for NPC diagnosis were 79 and 71 %, respectively, while those of IgG-gp78 were 74 and 73 %, respectively. The IgA and IgG responses to different EBV antigens were not identical within an individual and IgA-gp78 and IgG-gp78 could be complementary to antibodies against viral capsid antigen (VCA), the diffused early antigen (EA-D) and the nuclear antigen EBNA1 for NPC diagnosis. When the six EBV parameters for NPC prediction, i.e. IgA-gp78, IgG-gp78, IgA-VCA, IgA-EBNA1, IgA-EA-D and IgG-EA-D, are combined, the combined predictors were able to reach overall sensitivity and specificity of 91 and 95 %, respectively. Thus, simultaneous detection of these EBV serological markers could improve the predictive values of NPC using xMAP technology.
Prospects for the use of differentiation‐modulating agents as adjuvant of photodynamic therapy for proliferative dermatoses
Authors: AKILOV Oleg E. , KOSAKA Sachiko , MAYTIN Edward V. , HASAN Tayyaba
Published: April 2008

Current interest in photodynamic therapy (PDT) in dermatology stems from its recognized success in dermatological oncology, straightforward approach, easy accessibility and low cost. PDT is a photochemistry‐based modality in which a light‐activated photosensitizer (PS) destroys tissue through oxygen‐dependent and ‐independent mechanisms. Although PDT has been used in dermatology for several decades, its application has still not extended significantly into the routine management of neoplastic and proliferative dermatoses because of continuing issues with the selectivity of the PS for affected tissues. This review analyzes prospects for optimization of PDT for the management of dermatoses with defects in keratinocyte proliferation/differentiation, and discusses the use of differentiating agents that redirect metabolic utilization within cells and lead to high levels of PS accumulation.
Case of hypereosinophilic syndrome with cutaneous necrotizing vasculitis
Authors: HAYASHI Masahiro , KAWAGUCHI Masakazu , MITSUHASHI Yoshihiko , SUZUKI Tamio
Published: April 2008

A 25‐year‐old male presented with pruritic papules over his trunk and extremities. The pruritic eruption had appeared on the arms 5 months before and gradually spread over the trunk. Blood tests showed a white blood cell count of 13 760/µL with 42.2% eosinophils. A skin biopsy from the leg revealed necrotizing vasculitis in the upper dermis with prominent eosinophil infiltration in the dermis and subcutis. Liver dysfunction in accordance with eosinophilia was also seen. The underlying disorder causing the eosinophilia was not detected. We diagnosed this case as hypereosinophilic syndrome. Although systemic corticosteroid therapy using prednisolone was effective, the symptoms recurred during a reduction of prednisolone. The addition of cyclosporine resulted in improvement of his symptoms. Both drugs were successfully tapered without relapsing symptoms. Hypereosinophilic syndrome with cutaneous necrotizing vasculitis is a rare condition, and this case suggests that cyclosporine may be a useful therapeutic adjunct in facilitating steroid tapering.
Chronic idiopathic macrocheilia associated with simple lip enlargement and salivary gland hyperplasia
Authors: PARK Hyun Sun , PARK Eun Sang , PARK Kyung Chan , CHO Kwang Hyun , YOUN Sang Woong
Published: April 2008

Chronic macrocheilia is a relatively rare condition of chronic lip enlargement. It can be cosmetically and functionally problematic, and often poses a diagnostic and therapeutic challenge to clinicians especially when its etiology is unclear. We describe a 40‐year‐old Korean man who presented with a 4‐year history of lower lip swelling and was diagnosed as having chronic idiopathic macrocheilia after excluding other disease entities based on histopathological and clinical findings. We believe that the present case has a unique clinico‐histopathological feature that differentiates it from other cases of chronic cheilitis, namely, simple lip swelling showing minor salivary gland hyperplasia only, suggesting the possibility of a new disease entity.
Childhood and adolescent predictors of early and middle adulthood alcohol use and problem drinking: the Columbia County Longitudinal Study
Authors: Dubow Eric F. , Boxer Paul , Huesmann L. Rowell
Published: April 2008

Aims  To examine the role of individually and contextually based factors measured during childhood and adolescence in predicting alcohol use and abuse measured during early and middle adulthood.

Design  Initial sample of 856 individuals first interviewed at age 8 with follow‐up interviews at 19 (n = 427), 30 (n = 409), and 48 (n = 523).

Participants  Individuals enrolled in 3rd‐grade classes in Columbia County, NY, in 1960 (49% female; > 90% Caucasian; primarily working‐class families), who were re‐sampled in 1970 (51% female), 1981 (52% female) and 2000 (49% female).

Measurements  Parent reports of negative family interaction and socio‐economic status when the child was 8 years old; IQ test at age 8; peer nominations of aggression, popularity and behavioral inhibition at ages 8 and 19; self‐report of depression and educational attainment at age 19; self‐report of alcohol use and problem drinking at ages 30 and 48.

Findings  Path models showed that the effects of childhood individual variables (e.g. aggression, popularity, behavioral inhibition) on adulthood alcohol use and abuse generally were mediated by the same behavioral variables in adolescence. Specifically, both for males and for females, lower levels of behavioral inhibition and higher levels of aggression predicted adulthood alcohol variables. Childhood contextual variables (family socio‐economic status and negative family interaction) were relatively weak predictors of adulthood alcohol use and abuse.

Conclusions  Alcohol use and abuse in adulthood, when considered in a long‐term developmental–contextual framework, appear to be consistent with a general deviance model of problem behavior whereby individually based factors from childhood and late adolescence predict long‐term indices of adulthood alcohol use and abuse.
Adolescent risk factors for adult alcohol use and abuse: stability and change of predictive value across early and middle adulthood
Authors: Merline Alicia , Jager Justin , Schulenberg John E.
Published: April 2008

Aims  To examine age‐18 risk factors for alcohol use and heavy drinking during early (ages 22 and 26) and middle (age 35) adulthood, and for symptoms of alcohol use disorders (AUDs) in middle adulthood.

Design  Nationally representative samples of US adolescents in their senior year of secondary school (age 18) were followed into middle adulthood. Structural equation models estimated the associations between age‐18 characteristics and current drinking and heavy drinking at ages 22, 26 and 35 and symptoms of AUDs at age 35.

Participants  The sample consisted of 21 137 respondents from 11 senior year cohorts (1976–86) from the Monitoring the Future study.

Findings  Many predictor variables had stable associations with alcohol use over time, although their ability to explain variance in alcohol use declined with increasing time lags. Being white predicted alcohol use, but not symptoms of AUDs. Parental drinking, risk taking and use of cigarettes and marijuana predicted heavy drinking to age 35. Planning to attend college predicted more heavy drinking at age 22 and less frequent heavy drinking by mid‐life. High school theft and property damage predicted later AUD symptoms. Most associations were invariant across gender, with variations typically taking the form of stronger associations between predictors and alcohol use for men. Invariance in findings across cohorts indicates that results reflect general developmental trends rather than specific historically bounded ones.

Conclusions  Many adolescent individual and contextual characteristics remain important predictors of adult alcohol use and abuse, and their predictive impact varies as a function of age and type of alcohol outcome. These associations are largely equivalent across gender and cohort, thus reflecting robust developmental linkages.
Anticipating problem alcohol use developmentally from childhood into middle adulthood: what have we learned?
Authors: ZUCKER ROBERT A.
Published: April 2008

This commentary reviews and comments on six major longitudinal studies from the United States, Great Britain and Finland, that test predictive models of drinking and problem drinking behavior across a developmental span of one to two generations. The large Ns, in two instances involving population samples, and the broad and study‐overlapping variable domains make this collection of studies unique and of special interest vis‐à‐vis the issue of cross‐study replicability of findings. Significant cross‐study commonalities are noted, involving the strong cross‐study replicability of an undercontrol/externalizing domain as both a childhood and adolescent predictor of problem drinking outcomes in early to middle adulthood, the relative autostability of heavy and problem use of alcohol over intervals of time as long as a generation, the utility of early drinking behavior as an index for later drinking outcomes, the relative parallelism (with some exceptions) of male and female findings, albeit with greater predictability of male over female drinking outcomes and the relatively tighter relational networks of drinking and other behavioral characteristics for males. This impressive group of quasi‐replications also points the field to address several next‐step questions, including: (i) the need to parse the undercontrol/externalizing domain to identify those subcomponential process characteristics that are causal to heavy and problem drinking outcomes; (ii) the need to develop models that will handle more effectively the uneven relationships of negative activity to drinking outcomes, in some instances operating protectively, in other instances operating as risk factors; (iii) the need for more carefully articulated, theoretically driven process models that will specify the ordering, developmental saliency and mediational properties of risk and protective factors as they come on line; and (iv) the need for more developmental testing of trait/context interaction models of problem drinking development.
Stau1 negatively regulates myogenic differentiation in C2C12 cells
Authors: Yamaguchi Yukio , Oohinata Remi , Naiki Takahiro , Irie Kenji
Published: April 2008

Sequential expression of myogenic regulatory factors (MRFs) such as MyoD and myogenin drives myogenic differentiation. Besides transcriptional activation of MRFs, this process is also coordinated by post‐transcriptional regulation; MyoD and myogenin mRNAs are stabilized by RNA‐binding protein HuR. Stau1 is known to regulate mRNA stability in a complex with Upf1, which is termed Stau1‐mediated mRNA decay (SMD). We describe here that Stau1 is involved in the regulation of myogenesis. We found that knockdown of Stau1 promotes myogenesis including the expression of a muscle‐specific marker protein, myoglobin, in C2C12 myoblasts. MyoD induces myogenin expression in response to induction of myogenesis, which is a key step to start myogenesis. The level of MyoD protein was not affected when Stau1 was depleted by siRNA, whereas the levels of myogenin mRNA and protein were increased in Stau1‐knockdown cells. Interestingly, myogenin promoter activity was also increased in Stau1‐knockdown cells in the absence of induction of myogenesis. Furthermore, Stau1‐knockdown cells spontaneously progressed myogenesis including the expression of muscle‐specific protein. Although Stau1 is involved in mRNA decay together with Upf1, Upf1‐knockdown did not affect progression of myogenesis. Our results suggest that Stau1 negatively regulates myogenesis in C2C12 myoblasts through a mechanism that is different from SMD.
Schizosaccharomyces pombe Snf2SR, a novel SNF2 family protein, interacts with Ran GTPase and modulates both RanGEF and RanGAP activities
Authors: Ohba Tomoyuki , Nishijima Hitoshi , Nishitani Hideo , Nishimoto Takeharu
Published: April 2008

Snf2SR, a suppressor of rna1ts, which is a temperature‐sensitive mutation in Schizosaccharomyces pombe RanGAP (GTPase activating protein), possesses both the SNF2 and the helicase domains conserved in the chromatin remodeling SNF2 ATPase/helicase protein family. We have now clarified a function of Snf2SR. Snf2SR indeed showed DNA‐stimulated ATPase activity, proving that it is a member of the SNF2 ATPase/helicase family. Consistent with this role, Snf2SR was localized in the nucleus and cell fractionation analysis revealed that Snf2SR was tightly associated with the nuclear matrix. The disruption of snf2SR+ was detrimental for a cell proliferation of S. pombe. Snf2SR that did not enhance RanGAP activity by itself, but abolished histone‐H3‐mediated RanGAP inhibition, as previously reported for the histone H3 methyltransferase, Clr4, another rna1ts suppressor. In contrast to Clr4, Snf2SR directly bound to the GDP‐bound form of the S. pombe Ran homologue Spi1 and enhanced the nucleotide exchange activity of Pim1, the S. pombe RanGEF (guanine nucleotide exchange factor). Over‐expression of Spi1‐G18V, a Ran GTPase mutant fixed in the GTP‐bound form, was lethal to S. pombe Δsnf2SR. Together, our results indicate that Snf2SR is involved in the Ran GTPase cycle in vivo.
Multiple Roles for the Endocannabinoid System During the Earliest Stages of Life: Pre‐ and Postnatal Development
Authors: Fride E.
Published: April 2008

The endocannabinoid system, including its receptors (CB1 and CB2), endogenous ligands (‘endocannabinoids’), synthesising and degrading enzymes, as well as transporter molecules, has been detected from the earliest stages of embryonic development and throughout pre‐ and postnatal development. In addition, the endocannabinoids, notably 2‐arachidonyl glycerol, are also present in maternal milk. During three distinct developmental stages (i.e. embryonic implantation, prenatal brain development and postnatal suckling), the endocannabinoid system appears to play an essential role for development and survival. Thus, during early pregnancy, successful embryonic passage through the oviduct and implantation into the uterus both require critical enzymatic control of optimal anandamide levels at the appropriate times and sites. During foetal life, the cannabinoid CB1 receptor plays a major role in brain development, regulating neural progenitor differentiation into neurones and glia and guiding axonal migration and synaptogenesis. Postnatally, CB1 receptor blockade interferes with the initiation of milk suckling in mouse pups, by inducing oral motor weakness, which exposes a critical role for CB1 receptors in the initiation of milk suckling by neonates, possibly by interfering with innervation of the tongue muscles. Manipulating the endocannabinoid system by pre‐ and/or postnatal administration of cannabinoids or maternal marijuana consumption, has significant, yet subtle effects on the offspring. Thus, alterations in the dopamine, GABA and endocannabioid systems have been reported while enhanced drug seeking behaviour and impaired executive (prefrontal cortical) function have also been observed. The relatively mild nature of the disruptive effects of prenatal cannabinoids may be understood in the framework of the intricate timing requirements and frequently biphasic effects of the (endo)cannabinoids. In conclusion, the endocannabinoid system plays several key roles in pre‐ and postnatal development. Future studies should further clarify the mechanisms involved and provide a better understanding of the adverse effects of prenatal exposure, in order to design strategies for the treatment of conditions such as infertility, mental retardation and failure‐to‐thrive.
Endocannabinoids and the Brain Immune System: New Neurones at the Horizon?
Authors: Wolf S. A. , Ullrich O.
Published: April 2008

Whereas, in most brain compartments, neuronal cell renewal during early life is replaced by synaptic plasticity and the potentiation of existing pathways and connections, neurogenesis in the hippocampus occurs throughout adulthood. Neuronal progenitor cells in the dentate gyrus of the hippocampus are thought to be the gatekeepers of memory. Neural progenitor cell proliferation and differentiation depends on their intrinsic properties and local environment and is down‐regulated in conditions associated with brain inflammation. Conversely, newly‐formed neurones can survive despite chronic inflammation and, moreover, specifically arise within an inflammatory environment. Since the endocannabinoid system controls immune responses via multiple cellular and molecular targets and influences cell proliferation, fate decision and cell survival in the central nervous system, we summarise how neurogenesis might be regulated by brain cannabinoids, either directly or indirectly via the immune system. This review presents clear evidence that the cannabinoid system influences adult neurogensis. However, there is considerable variability with regard to the strain, model and methods utilised and therefore it is difficult to compare studies investigating the cannabinoid system. As a result, it remains far from clear exactly how endocannabinoids regulate neurogenesis.