bluuebunny/crossref_metadata_2025 huggingface dataset:
Epstein-Barr Virus Downregulates MicroRNA 203 through the Oncoprotein Latent Membrane Protein 1: a Contribution to Increased Tumor Incidence in Epithelial Cells
Authors: Yu Haibo , Lu Jianhong , Zuo Lielian , Yan Qijia , Yu Zhengyuan , Li Xiayu , Huang Jin , Zhao Lian , Tang Hailin , Luo Zhaohui , Liao Qianjin , Zeng Zhaoyang , Zhang Junyi , Li Guiyuan
Published: December 2011

The Epstein-Barr virus (EBV) is highly associated with nasopharyngeal carcinoma (NPC), and it regulates some microRNAs (miRNAs) that are involved in the development of cancer. The role of EBV in the deregulation of cellular miRNAs and how this affects the progression of NPC remain to be investigated. An analysis of the miRNA profile in an EBV-infected cell line revealed that miRNA 203 (miR-203) was downregulated. miR-203 is expressed specifically in epithelial cells. This downregulation of miR-203 was further verified and functionally analyzed. miR-203 was downregulated substantially in epithelial cells and NPC tissues that were latently infected with EBV. Downregulation of miR-203 also occurred during the early stage of EBV infection. Furthermore, the viral oncoprotein, latent membrane protein 1 (LMP1), was responsible for downregulation of miR-203. Removal of the latent EBV genome or suppression of LMP1 resulted in restoration of miR-203 expression. EBV-LMP1 mediated the downregulation of miR-203 at the primary transcript level. E2F3 and CCNG1 were identified as target genes of miR-203. Ectopic expression of miR-203 inhibited EBV-induced S-phase entry and transformation
in vivo
. Overexpression of the targets overcame the effects of miR-203 mimics on the cell cycle, and the expression of target genes in tumor models was inhibited by miR-203. Inhibitors of Jun N-terminal protein kinase (JNK) and NF-κB blocked miR-203 downregulation. These results imply that EBV promotes malignancy by downregulating cellular miR-203, which contributes to the etiology of NPC.
Macrophage Internal HIV-1 Is Protected from Neutralizing Antibodies
Authors: Koppensteiner Herwig , Banning Carina , Schneider Carola , Hohenberg Heinrich , Schindler Michael
Published: December 2011

In macrophages, HIV-1 accumulates in intracellular vesicles designated virus-containing compartments (VCCs). These might play an important role in the constitution of macrophages as viral reservoirs and allow HIV-1 to evade the immune system by sequestration in an internal niche, which is difficult to access from the exterior. However, until now, evidence of whether internal virus accumulations are protected from the host's humoral immune response is still lacking. In order to be able to study the formation and antibody accessibility of VCCs, we generated HIV-1 with green fluorescent protein (GFP)-tagged Gag replicating in primary macrophages. Live-cell observations revealed faint initial cytosolic Gag expression and subsequent large intracellular Gag accumulations which stayed stable over days. Taking advantage of the opportunity to study the accessibility of intracellular VCCs via the cell surface, we demonstrate that macrophage internal HIV-1-containing compartments cannot be targeted by neutralizing antibodies. Furthermore, HIV-1 was efficiently transferred from antibody-treated macrophages to T cells. Three-dimensional reconstruction of electron microscopic slices revealed that Gag accumulations correspond to viral particles within enclosed compartments and convoluted membranes. Thus, although some VCCs were connected to the plasma membrane, the complex membrane architecture of the HIV-1-containing compartment might shield viral particles from neutralizing antibodies. In sum, our study provides evidence that HIV-1 is sequestered into a macrophage internal membranous web, posing an obstacle for the elimination of this viral reservoir.
The Association of Recombination Events in the Founding and Emergence of Subgenogroup Evolutionary Lineages of Human Enterovirus 71
Authors: McWilliam Leitch E. C. , Cabrerizo M. , Cardosa J. , Harvala H. , Ivanova O. E. , Koike S. , Kroes A. C. M. , Lukashev A. , Perera D. , Roivainen M. , Susi P. , Trallero G. , Evans D. J. , Simmonds P.
Published: December 2011

Enterovirus 71 (EV71) is responsible for frequent large-scale outbreaks of hand, foot, and mouth disease worldwide and represent a major etiological agent of severe, sometimes fatal neurological disease. EV71 variants have been classified into three genogroups (GgA, GgB, and GgC), and the latter two are further subdivided into subgenogroups B1 to B5 and C1 to C5. To investigate the dual roles of recombination and evolution in the epidemiology and transmission of EV71 worldwide, we performed a large-scale genetic analysis of isolates (
n
= 308) collected from 19 countries worldwide over a 40-year period. A series of recombination events occurred over this period, which have been identified through incongruities in sequence grouping between the VP1 and 3Dpol regions. Eleven 3Dpol clades were identified, each specific to EV71 and associated with specific subgenogroups but interspersed phylogenetically with clades of coxsackievirus A16 and other EV species A serotypes. The likelihood of recombination increased with VP1 sequence divergence; mean half-lives for EV71 recombinant forms (RFs) of 6 and 9 years for GgB and GgC overlapped with those observed for the EV-B serotypes, echovirus 9 (E9), E30, and E11, respectively (1.3 to 9.8 years). Furthermore, within genogroups, sporadic recombination events occurred, such as the linkage of two B4 variants to RF-W instead of RF-A and of two C4 variants to RF-H. Intriguingly, recombination events occurred as a founding event of most subgenogroups immediately preceding their lineage expansion and global emergence. The possibility that recombination contributed to their subsequent spread through improved fitness requires further biological and immunological characterization.
DNA-Binding Activity of Adeno-Associated Virus Rep Is Required for Inverted Terminal Repeat-Dependent Complex Formation with Herpes Simplex Virus ICP8
Authors: Alex Martin , Weger Stefan , Mietzsch Mario , Slanina Heiko , Cathomen Toni , Heilbronn Regine
Published: December 2011

Herpes simplex virus (HSV) helper functions for (AAV) replication comprise HSV ICP8 and helicase-primase UL5/UL52/UL8. Here we show that N-terminal amino acids of AAV Rep78 that contact the Rep-binding site within the AAV inverted terminal repeat (ITR) are required for ternary-complex formation with infected-cell protein 8 (ICP8) on AAV single-strand DNA (ssDNA)
in vitro
and for colocalization in nuclear replication domains
in vivo
. Our data suggest that HSV-dependent AAV replication is initiated by Rep contacting the AAV ITR and by cooperative binding of ICP8 on AAV ssDNA.
Stimulation of BK Virus DNA Replication by NFI Family Transcription Factors
Authors: Liang Bo , Tikhanovich Irina , Nasheuer Heinz Peter , Folk William R.
Published: December 2011

BK polyomavirus (BKV) establishes persistent, low-level, and asymptomatic infections in most humans and causes polyomavirus-associated nephropathy (PVAN) and other pathologies in some individuals. The activation of BKV replication following kidney transplantation, leading to viruria, viremia, and, ultimately, PVAN, is associated with immune suppression as well as inflammation and stress from ischemia-reperfusion injury of the allograft, but the stimuli and molecular mechanisms leading to these pathologies are not well defined. The replication of BKV DNA in cell cultures is regulated by the viral noncoding control region (NCCR) comprising the core origin and flanking sequences, to which BKV T antigen (Tag), cellular proteins, and small regulatory RNAs bind. Six nuclear factor I (NFI) binding sites occur in sequences flanking the late side of the core origin (the enhancer) of the archetype virus, and their mutation, either individually orin toto, reduces BKV DNA replication when placed in competition with templates containing intact BKV NCCRs. NFI family members interacted with the helicase domain of BKV Tag in pulldown assays, suggesting that NFI helps recruit Tag to the viral core origin and may modulate its function. However, Tag may not be the sole target of the replication-modulatory activities of NFI: the NFIC/CTF1 isotype stimulates BKV template replicationin vitroat low concentrations of DNA polymerase-α primase (Pol-primase), and the p58 subunit of Pol-primase associates with NFIC/CTF1, suggesting that NFI also recruits Pol-primase to the NCCR. These results suggest that NFI proteins (and the signaling pathways that target them) activate BKV replication and contribute to the consequent pathologies caused by acute infection.
Coordinate Deletion of N-Glycans from the Heptad Repeats of the Fusion F Protein of Newcastle Disease Virus Yields a Hyperfusogenic Virus with Increased Replication, Virulence, and Immunogenicity
Authors: Samal Sweety , Khattar Sunil K. , Kumar Sachin , Collins Peter L. , Samal Siba K.
Published: December 2011

The role of N-linked glycosylation of the Newcastle disease virus (NDV) fusion (F) protein in viral replication and pathogenesis was examined by eliminating potential acceptor sites using a reverse genetics system for the moderately pathogenic strain Beaudette C (BC). The NDV-BC F protein contains six potential acceptor sites for N-linked glycosylation at residues 85, 191, 366, 447, 471, and 541 (sites Ng1 to Ng6, respectively). The sites at Ng2 and Ng5 are present in heptad repeat (HR) domains HR1 and HR2, respectively, and thus might affect fusion. Each N-glycosylation site was eliminated individually by replacing asparagine (N) with glutamine (Q), and a double mutant (Ng2 + 5) involving the two HR domains was also made. Each mutant was successfully recovered by reverse genetics except for the one involving Ng6, which is present in the cytoplasmic domain. All of the F proteins expressed by the recovered mutant viruses were efficiently cleaved and transported to the infected-cell surface. None of the individual mutations affected viral fusogenicity, but the double mutation at Ng2 and Ng5 in HR1 and HR2 increased fusogenicity >12-fold. The single mutations at sites Ng1, Ng2, and Ng5 resulted in modestly reduced multicycle growth
in vitro
. These three single mutations were also the most attenuating in eggs and 1-day-old chicks and were associated with decreased replication and spread in 2-week-old chickens. In contrast, the combination of the mutations at Ng2 and Ng5 yielded a virus that, compared to the BC parent, replicated >100-fold more efficiently
in vitro
, was more virulent in eggs and chicks, replicated more efficiently in chickens with enhanced tropism for the brain and gut, and elicited stronger humoral cell responses. These results illustrate the effects of N-glycosylation of the F protein on NDV pathobiology and suggest that the N-glycans in HR1 and HR2 coordinately downregulate viral fusion and virulence.
A Leucine Zipper Motif of a Tegument Protein Triggers Final Envelopment of Human Cytomegalovirus
Authors: Meissner Christina Sylvia , Suffner Sascha , Schauflinger Martin , von Einem Jens , Bogner Elke
Published: December 2011

The product of the human cytomegalovirus (HCMV) UL71 gene is conserved throughout the herpesvirus family. During HCMV infection, protein pUL71 is required for efficient virion egress and is involved in the final steps of secondary envelopment leading to infectious viral particles. We found strong indications for oligomerization of pUL71 under native conditions when recombinant pUL71 was negatively stained and analyzed by electron microscopy. Oligomerization of pUL71 during infection was further verified by native and reducing polyacrylamide gel electrophoresis (PAGE). By
in silico
analyses of the pUL71 sequence, we noticed a basic leucine zipper (bZIP)-like domain, which might serve as an oligomerization domain. We demonstrated the requirement of the bZIP-like domain for pUL71 oligomerization by coimmunoprecipitation and bimolecular fluorescence complementation using a panel of pUL71 mutants. These studies revealed that the mutation of two leucine residues is sufficient to abrogate oligomerization but that intracellular localization of pUL71 was unaffected. To investigate the relevance of the bZIP domain in the viral context, recombinant viruses carrying mutations identical to those in the panel of pUL71 mutants were generated. bZIP-defective viral mutants showed impaired viral growth, a small-plaque phenotype, and an ultrastructural phenotype similar to that of the previously described UL71 stop mutant virus. The majority of virus particles within the viral assembly compartment exhibited various stages of incomplete envelopment, which is consistent with the growth defect for the bZIP mutants. From these data we conclude that the bZIP-like domain is required for oligomerization of pUL71, which seems to be essential for correct envelopment of HCMV.
Adenovirus E4orf3 Targets Transcriptional Intermediary Factor 1γ for Proteasome-Dependent Degradation during Infection
Authors: Forrester Natalie A. , Patel Rakesh N. , Speiseder Thomas , Groitl Peter , Sedgwick Garry G. , Shimwell Neil J. , Seed Robert I. , Catnaigh Pól Ó , McCabe Christopher J. , Stewart Grant S. , Dobner Thomas , Grand Roger J. A. , Martin Ashley , Turnell Andrew S.
Published: December 2011

The ability of adenovirus early region proteins, E1B-55K and E4orf6, to usurp control of cellular ubiquitin ligases and target proteins for proteasome-dependent degradation during infection is well established. Here we show that the E4 gene product, E4orf3 can, independently of E1B-55K and E4orf6, target the transcriptional corepressor transcriptional intermediary factor 1γ (TIF1γ) for proteasome-mediated degradation during infection. Initial mass spectrometric studies identified TIF1 family members—TIF1α, TIF1β, and TIF1γ—as E1B-55K-binding proteins in both transformed and infected cells, but analyses revealed that, akin to TIF1α, TIF1γ is reorganized in an E4orf3-dependent manner to promyelocytic leukemia protein-containing nuclear tracks during infection. The use of a number of different adenovirus early region mutants identified the specific and sole requirement for E4orf3 in mediating TIF1γ degradation. Further analyses revealed that TIF1γ is targeted for degradation by a number of divergent human adenoviruses, suggesting that the ability of E4orf3 to regulate TIF1γ expression is evolutionarily conserved. We also determined that E4orf3 does not utilize the Cullin-based ubiquitin ligases, CRL2 and CRL5, or the TIF1α ubiquitin ligase in order to promote TIF1γ degradation. Further studies suggested that TIF1γ possesses antiviral activity and limits adenovirus early and late gene product expression during infection. Indeed, TIF1γ knockdown accelerates the adenovirus-mediated degradation of MRE11, while TIF1γ overexpression delays the adenovirus-mediated degradation of MRE11. Taken together, these studies have identified novel adenovirus targets and have established a new role for the E4orf3 protein during infection.
Characterization of the R263K Mutation in HIV-1 Integrase That Confers Low-Level Resistance to the Second-Generation Integrase Strand Transfer Inhibitor Dolutegravir
Authors: Quashie Peter K. , Mesplède Thibault , Han Ying-Shan , Oliveira Maureen , Singhroy Diane N. , Fujiwara Tamio , Underwood Mark R. , Wainberg Mark A.
Published: December 2011

Integrase (IN) strand transfer inhibitors (INSTIs) have been developed to inhibit the ability of HIV-1 integrase to irreversibly link the reverse-transcribed viral DNA to the host genome. INSTIs have proven their high efficiency in inhibiting viral replication
in vitro
and in patients. However, first-generation INSTIs have only a modest genetic barrier to resistance, allowing the virus to escape these powerful drugs through several resistance pathways. Second-generation INSTIs, such as dolutegravir (DTG, S/GSK1349572), have been reported to have a higher resistance barrier, and no novel drug resistance mutation has yet been described for this drug. Therefore, we performed
in vitro
selection experiments with DTG using viruses of subtypes B, C, and A/G and showed that the most common mutation to emerge was R263K. Further analysis by site-directed mutagenesis showed that R263K does confer low-level resistance to DTG and decreased integration in cell culture without altering reverse transcription. Biochemical cell-free assays performed with purified IN enzyme containing R263K confirmed the absence of major resistance against DTG and showed a slight decrease in 3′ processing and strand transfer activities compared to the wild type. Structural modeling suggested and
in vitro
IN-DNA binding assays show that the R263K mutation affects IN-DNA interactions.
Contribution of Intra- and Interhost Dynamics to Norovirus Evolution
Authors: Bull Rowena A. , Eden John-Sebastian , Luciani Fabio , McElroy Kerensa , Rawlinson William D. , White Peter A.
Published: December 2011

Norovirus (NoV) is an emerging RNA virus that has been associated with global epidemics of gastroenteritis. Each global epidemic arises with the emergence of novel antigenic variants. While the majority of NoV infections are mild and self-limiting, in the young, elderly, and immunocompromised, severe and prolonged illness can result. As yet, there is no vaccine or therapeutic treatment to prevent or control infection. In order to design effective control strategies, it is important to understand the mechanisms and source of the new antigenic variants. In this study, we used next-generation sequencing (NGS) technology to investigate genetic diversification in three contexts: the impact of a NoV transmission event on viral diversity and the contribution to diversity of intrahost evolution over both a short period of time (10 days), in accordance with a typical acute NoV infection, and a prolonged period of time (288 days), as observed for NoV chronic infections of immunocompromised individuals. Investigations of the transmission event revealed that minor variants at frequencies as low as 0.01% were successfully transmitted, indicating that transmission is an important source of diversity at the interhost level of NoV evolution. Our results also suggest that chronically infected immunocompromised subjects represent a potential reservoir for the emergence of new viral variants. In contrast, in a typical acute NoV infection, the viral population was highly homogenous and relatively stable. These results indicate that the evolution of NoV occurs through multiple mechanisms.
The Amino Acid Linker between the Endonuclease and Helicase Domains of Adeno-Associated Virus Type 5 Rep Plays a Critical Role in DNA-Dependent Oligomerization
Authors: Maggin Jenna E. , James Jeffrey A. , Chappie Joshua S. , Dyda Fred , Hickman Alison Burgess
Published: December 2011

The adeno-associated virus (AAV) genome encodes four Rep proteins, all of which contain an SF3 helicase domain. The larger Rep proteins, Rep78 and Rep68, are required for viral replication, whereas Rep40 and Rep52 are needed to package AAV genomes into preformed capsids; these smaller proteins are missing the site-specific DNA-binding and endonuclease domain found in Rep68/78. Other viral SF3 helicases, such as the simian virus 40 large T antigen and the papillomavirus E1 protein, are active as hexameric assemblies. However, Rep40 and Rep52 have not been observed to form stable oligomers on their own or with DNA, suggesting that important determinants of helicase multimerization lie outside the helicase domain. Here, we report that when the 23-residue linker that connects the endonuclease and helicase domains is appended to the adeno-associated virus type 5 (AAV5) helicase domain, the resulting protein forms discrete complexes on DNA consistent with single or double hexamers. The formation of these complexes does not require the Rep binding site sequence, nor is it nucleotide dependent. These complexes have stimulated ATPase and helicase activities relative to the helicase domain alone, indicating that they are catalytically relevant, a result supported by negative-stain electron microscopy images of hexameric rings. Similarly, the addition of the linker region to the AAV5 Rep endonuclease domain also confers on it the ability to bind and multimerize on nonspecific double-stranded DNA. We conclude that the linker is likely a key contributor to Rep68/78 DNA-dependent oligomerization and may play an important role in mediating Rep68/78's conversion from site-specific DNA binding to nonspecific DNA unwinding.
Vif Proteins of Human and Simian Immunodeficiency Viruses Require Cellular CBFβ To Degrade APOBEC3 Restriction Factors
Authors: Hultquist Judd F. , Binka Mawuena , LaRue Rebecca S. , Simon Viviana , Harris Reuben S.
Published: December 2011

HIV-1 requires the cellular transcription factor CBFβ to stabilize its accessory protein Vif and promote APOBEC3G degradation. Here, we demonstrate that both isoforms of CBFβ allow for increased steady-state levels of Vif, enhanced APOBEC3G degradation, and increased viral infectivity. This conserved functional interaction enhances the steady-state levels of Vif proteins from multiple HIV-1 subtypes and is required for the degradation of all human and rhesus Vif-sensitive APOBEC3 proteins by their respective lentiviral Vif proteins.
Performance evaluation of “ship-in-the-bottle” type heteropoly acid encaged Y-type zeolite as catalyst for oxidative desulfurization
Authors: Wang Han , Wang Rui
Published: December 2011

Clean fuel and clean production technologies, including desulfurization, have become a subject of concern in environmental catalysis studies. One of the most promising desulfurization processes is oxidative desulfurization combined with extraction. Keggin-type heteropoly acids encaged Y-type zeolite were studied as promising catalytic agents for the oxidation of dibenzothiophene with hydrogen peroxide in a normal octane/acetonitrile biphasic system. The key factors affecting the reaction, including the catalyst amount, O/S molar ratio and contact time between oxidant and catalyst, were investigated. The conditions favourable to the reaction were also determined. Moreover, the reused encaged type catalyst exhibited good catalytic activity in recovery experiments and can be effectively applied to diesel oil.
Does the death rate of Hong Kong Chinese change during the lunar ghost month?: Table 1
Authors: Panesar Nirmal S , Graham Colin A
Published: December 2011

Background

Most cultures believe in ghosts and for the Chinese, the seventh lunar month—the ghost month—causes particular concern. ‘The gates of hell’ are open for the first 14 days of the month which allows the restless ghosts of people who were hungry when they died to haunt the living. In this study, it was hypothesised that if the notion that ghosts are out to harm the living could affect the Chinese, this may be reflected in death statistics.

Methods

Because the Chinese believe death is more likely during the ghost month, male and female deaths from all causes and from four common causes of death in the first and second fortnights of the seventh lunar months of 1995–2000 were compared in Hong Kong Chinese. Deaths in two consecutive fortnights 30 days before each year's seventh lunar month were used as controls. Death data were compared using the binomial test with a null hypothesis probability of 0.5 between the first and second fortnights.

Results

There was no difference in male deaths between the first and second fortnights of the control and seventh lunar months. While there were no significant differences in female deaths during the control month periods, fewer women died overall in the first fortnight of the seventh lunar month (p=0.026).

Conclusion

To protect their family, the Chinese women postpone death until after the hungry ghosts have been fed and hopefully banished forever.
Potentially avoidable emergency department attendance: interview study of patients' reasons for attendance
Authors: Agarwal S , Banerjee J , Baker R , Conroy S , Hsu R , Rashid A , Camosso-Stefinovic J , Sinfield P , Habiba M
Published: December 2011

Objectives

To explore the reasons for attendance at the emergency department (ED) by patients who could have been managed in an alternative service and the rate of acute admissions to one acute hospital.

Design

Interview study.

Setting

One acute hospital (University Hospitals of Leicester) in the East Midlands.

Participants

23 patients and/or their carers.

Methods

A purposive sample of patients attending the ED and the linked urgent care centre was identified and recruited. Patients in the sample were approached by a clinician and a researcher and invited to take part in an interview. Patients of different ethnicities and from different age groups, arriving at the ED via different referral routes (self-referral, emergency ambulance, GP referral, out-of-hours services) and attending at different times of the day and night were included. The interviews were recorded and transcribed with the individuals' permission and analysed using the framework analysis approach.

Results

Patients' anxiety or concern about the presenting problem, the range of services available to the ED and the perceived efficacy of these services, patients' perceptions of access to alternative services including general practice and lack of alternative pathways were factors that influenced the decision to use the ED.

Conclusions

Access to general practice, anxiety about the presenting problem, awareness and perceptions of the efficacy of the services available in the ED and lack of alternative pathways are important predictors of attendance rates.
Facet arthrography in an unusual presentation of a lumbar hemorrhagic synovial cyst
Authors: Tofuku Katsuhiro , Koga Hiroaki , Komiya Setsuro
Published: December 2011

An 84-year-old man experienced right buttock pain that radiated gradually to his right lower extremity over a few months before admission. MRI revealed a space occupying intraspinal lesion that was close to the right-sided L4–L5 facet joint and an extraspinal lesion posterior to the right-sided L5 lamina. The lesions appeared as hyperintense areas on T1 weighted images and heterogeneous areas on T2 weighted images. Facet arthrography under CT guidance revealed peripheral infiltration of the contrast medium only in the intraspinal lesion at early stages; subsequently, the contrast medium diffused into the extraspinal lesion, establishing a continuity of the right L4–L5 facet joint with both lesions, which were connected through the interlaminar space. A connection between the intraspinal and extraspinal lesions at the right-sided interlaminar space at the L4–L5 level was clearly noted during intraoperative examination. Histological examination revealed a hemorrhagic synovial cyst.
INFINITESIMAL DEFORMATIONS OF HITCHIN PAIRS AND HITCHIN MAP
Authors: MARTINENGO E.
Published: December 2011

We identify dglas that control infinitesimal deformations of the pairs (manifold, Higgs bundle) and of Hitchin pairs. As a consequence, we recover known descriptions of first order deformations and we refine known results on obstructions. Secondly we prove that the Hitchin map is induced by a natural L∞-morphism and, by standard facts about L∞-algebras, we obtain new conditions on obstructions to deform Hitchin pairs.
VERONESE ARRANGEMENTS OF HYPERPLANES IN REAL PROJECTIVE SPACES
Authors: CHO KOJI , YOSHIDA MASAAKI
Published: December 2011

This paper studies chambers cut out by a special kind of hyperplane arrangements in general position, the Veronese arrangements, in the real projective spaces.
DETECTING COHERENT ENERGY
Authors: MORLEY P. D. , BROWN JERRY W.
Published: December 2011

We apply the mathematics of cognitive radio to a single receiver to obtain a new coherent energy metric. This allows us to derive the time correlation law separating Gaussian colored noise from coherent signal energy.
INFLUENCE OF CHANGING ENVIRONMENT ON SHENNAN-TYPE EVOLUTION OF CULTURAL INNOVATION
Authors: LIMA F. W. S. , STAUFFER DIETRICH
Published: December 2011

The computer simulations of Shennan [S. Shennan, Camb. Archeol. J.11, 5 (2001)] are complemented by assuming the environment to change randomly. For moderate change rates, fitness optimization through evolution is still possible.
CLASS PRESERVING AUTOMORPHISMS OF UNITRIANGULAR GROUPS
Authors: BARDAKOV VALERIY , VESNIN ANDREI , YADAV MANOJ K.
Published: December 2011

Let UTn(K) be a unitriangular group over a field K. We prove that the group of all class preserving automorphisms of UTn(K) is equal to Inn ( UTn(K)) if and only if K is a prime field. Let [Formula: see text], where γ3( UTn(𝔽pm)) denotes the third term of the lower central series of UTn(𝔽pm). We calculate the group of all class preserving automorphisms and class preserving outer automorphisms of [Formula: see text].
CIRCADIAN PHASE RE-SETTING USING NONLINEAR OUTPUT-FEEDBACK CONTROL
Authors: TONTHAT LONG , DING ZHENGTAO
Published: December 2011

Circadian rhythms occupy an important role in daily biological activities of living species. Circadian disorder is a phenomenon of circadian rhythms which occurs when internal rhythms cannot keep up with the changes of external environment rhythms. Changes of environmental rhythms, presented by the change of light/dark cycles or by irregular rhythms, result in phase shifts between internal and external rhythms. The existence of these phase shifts in longer term has negative effect to health. Therefore, in biological study of circadian rhythms, finding a method to recover the shifted phases to their normal rhythms, which is also the treatment of circadian disorder, is an important required task. In this paper, we propose a control design method to reset the circadian phases. The phase restoration is carried out by the synchronization of trajectories generated from a controlled model with the trajectories of a reference system via nonlinear control design using only one measurement. Both reference and controlled systems are based on a given 3rd order model of Neurospora circadian rhythms. The two other unknown states are estimated using a recently developed nonlinear observer for the output-feedback control.
EFFECTIVENESS OF STRETCHING AFTER TRIGGER POINT INJECTIONS
Authors: Emad Mohammad Reza , Roshanzamir Sharareh , Ghasempoor Mohsen Zafar , Sedaghat Shahriar Mirshamsand Parisa
Published: December 2011

Background: One of the causes of musculoskeletal pain is trigger points. Trigger point injection is one of the acceptable methods to inactivate the trigger points and provide symptomatic relief. The goal of our study was to compare the effectiveness of the injection without muscle stretching versus stretching immediately after injection of methylprednisolon in the treatment of trigger points. Methods: Seventy patients with pain in the gluteal muscles due to trigger points were recruited after explanation regarding their treatment method. A written consent was collected from the patients prior to their participation in the study. The patients had two office visits and two phone follow-ups. All the patients were treated with injections of Lidocaine and Methylprednisolon. In group (A), injection was administered without stretching. In group (B), stretching of the muscle was performed immediately after the injection. The evaluation tools were Numeric Pain Intensity Scale (NPS), Visual Analogue Scale (VAS) and Brief Pain Inventory Scale (BPI). Results: Results from VAS showed significant difference between the two groups after one month. Significant difference was seen between groups, one month and two months after the injection according to NRS. However, no significant difference was detected between two groups in BPI, except in mood. Conclusion: This study, based upon follow-ups in two months upon injection, highlights the effectiveness of muscle stretching immediately after the injection in the treatment of symptomatic gluteal trigger points.
PERCENT OF BODY WEIGHT CARRIED BY SECONDARY SCHOOL STUDENTS IN THEIR BAGS IN A NIGERIAN SCHOOL
Authors: Johnson Olubusola Esther , Adeniji Oluwatoyin Adenike , Mbada Chidozie Emmanuel , Obembe Adebimpe Olayinka , Akosile Christopher Olusanjo
Published: December 2011

Purpose: This study reports percent of bodyweight represented by school bags carried by students in Nigeria. Method: 381 secondary school students were randomly selected in this cross-sectional study. Informed consent and assents were obtained. Weights, heights and backpack weights (BPWT) were measured by blinded researchers. Data was analyzed using descriptive statistics, independent t-test, Chi square and odds ratio, at 0.05 α-level. Results: The mean age, height weight and BMI of participants were 14.01±2.17 years, 1.56±0.11 m, 46.19±9.65 kg, 18.89±3.12 kg/m2, respectively. Average total weight of bags carried by participants was 4.48 kg, relative BPWT was 10.16%, and 65% carried bags on their back. There was no significant association between BPWT and back pain (X2= 0.106. p = 0.744). The relative risks [odds ratio (OR) and 95% confidence interval (CI)] of developing back pain among those that carry normal BPWT compared with those who carry above normal BPWT to school was (OR 0.805; CI 0.478–1.355), (OR 0.733; CI 0.295–1.817) and (OR 0.883; CI 0.454–1.718) for total, junior and senior secondary schools participants, respectively. Conclusion: Percent of body weights represented by the weights of bags carried by students in a Nigerian school fell between the recommended 10–15%. A 10% relative weight is recommended for secondary school students in Nigeria.
CONCENTRATION ON CIRCLES FOR NONLINEAR SCHRÖDINGER–POISSON SYSTEMS WITH UNBOUNDED POTENTIALS VANISHING AT INFINITY
Authors: BONHEURE DENIS , DI COSMO JONATHAN , MERCURI CARLO
Published: December 2011

The present paper is devoted to weighted nonlinear Schrödinger–Poisson systems with potentials possibly unbounded and vanishing at infinity. Using a purely variational approach, we prove the existence of solutions concentrating on a circle.
A NEW METABOLOMICS ANALYSIS TECHNIQUE: STEADY-STATE METABOLIC NETWORK DYNAMICS ANALYSIS
Authors: CAKMAK ALI , QI XINJIAN , CICEK A. ERCUMENT , BEDERMAN ILYA , HENDERSON LEIGH , DRUMM MITCHELL , OZSOYOGLU GULTEKIN
Published: December 2011

With the recent advances in experimental technologies, such as gas chromatography and mass spectrometry, the number of metabolites that can be measured in biofluids of individuals has markedly increased. Given a set of such measurements, a very common task encountered by biologists is to identify the metabolic mechanisms that lead to changes in the concentrations of given metabolites and interpret the metabolic consequences of the observed changes in terms of physiological problems, nutritional deficiencies, or diseases. In this paper, we present the steady-state metabolic network dynamics analysis (SMDA) approach in detail, together with its application in a cystic fibrosis study. We also present a computational performance evaluation of the SMDA tool against a mammalian metabolic network database. The query output space of the SMDA tool is exponentially large in the number of reactions of the network. However, (i) larger numbers of observations exponentially reduce the output size, and (ii) exploratory search and browsing of the query output space is provided to allow users to search for what they are looking for.
GENERATION OF SYNTHETIC DATA AND EXPERIMENTAL DESIGNS IN EVALUATING INTERACTIONS FOR ASSOCIATION STUDIES
Authors: CHEN YIXUAN , LI JING
Published: December 2011

Complex diseases, by definition, involve multiple factors, including gene–gene interactions and gene–environment interactions. Researchers commonly rely on simulated data to evaluate their approaches for detecting high-order interactions in disease gene mapping. A publicly available simulation program to generate samples involving complex genetic and environmental interactions is of great interest to the community. We have developed a software package named gs1.0, which has been widely used since its publication. In this article, we present an upgraded version gs2.0, which not only inherits its capacity to generate realistic genotype data but also provides great functionality and flexibility to simulate various interaction models. In addition to a standalone version, a user-friendly web server () has been set up to help users to build complex interaction models. Furthermore, by utilizing three three-locus models as an example, we have shown how realistic model parameters can be chosen in generating simulated data.
A FAST METHOD FOR LARGE-SCALE MULTICHROMOSOMAL BREAKPOINT MEDIAN PROBLEMS
Authors: Boyd Sylvia , Haghighi Maryam
Published: December 2011

We provide a computationally realistic mathematical framework for the NP-hard problem of the multichromosomal breakpoint median for linear genomes that can be used in constructing phylogenies. A novel approach is provided that can handle signed, unsigned, and partially signed cases of the multichromosomal breakpoint median problem. Our method provides an avenue for incorporating biological assumptions (whenever available) such as the number of chromosomes in the ancestor, and thus it can be tailored to obtain a more biologically relevant picture of the median. We demonstrate the usefulness of our method by performing an empirical study on both simulated and real data with a comparison to other methods.
A BIT-PARALLEL DYNAMIC PROGRAMMING ALGORITHM SUITABLE FOR DNA SEQUENCE ALIGNMENT
Authors: KIMURA KOUICHI , KOIKE ASAKO , NAKAI KENTA
Published: December 2011

Myers' elegant and powerful bit-parallel dynamic programming algorithm for approximate string matching has a restriction that the query length should be within the word size of the computer, typically 64. We propose a modification of Myers' algorithm, in which the modification has a restriction not on the query length but on the maximum number of mismatches (substitutions, insertions, or deletions), which should be less than half of the word size. The time complexity is O(m log |Σ|), where m is the query length and |Σ| is the size of the alphabet Σ. Thus, it is particularly suited for sequences on a small alphabet such as DNA sequences. In particular, it is useful in quickly extending a large number of seed alignments against a reference genome for high-throughput short-read data produced by next-generation DNA sequencers.
A major prolactin-binding complex on human milk fat globule membranes contains cyclophilins A and B: the complex is not the prolactin receptor
Authors: Lorenson Mary Y. , Ueda Eric K. , Chen KuanHui E. , Walker Ameae M.
Published: December 2011

Prolactin (PRL) in milk influences maturation of gastrointestinal epithelium and development of both the hypothalamo-pituitary and immune systems of offspring. Here, we demonstrate that most PRL in human milk is part of a novel, high-affinity, multicomponent binding complex found on the milk fat globule membrane and not in whey. To examine properties of the complex, a sensitive ELISA was developed such that human PRL (hPRL) binding to the complex was measured by loss of hPRL detectability; thus, as much as 50 ng of hPRL was undetectable in the presence of 10 μl of human milk. Using the same methodology, no comparable complex formation was observed with human serum or amniotic fluid. hPRL complexation in milk was rapid, time dependent, and cooperative. Antibodies to or competitors of the hPRL receptor (placental lactogen and growth hormone) showed the hPRL receptor was not involved in the complex. However, hPRL complexation was antagonized by cyclosporine A and anti-cyclophilins. The complex was very stable, resisting dissociation in SDS, urea, and dithiothreitol. Western analysis revealed an ∼75-kDa complex that included hPRL, cyclophilins A and B, and a 16-kDa cyclophilin A. Compared with noncomplexed hPRL, complexed hPRL in whole milk showed similar activation of STAT5 but markedly delayed activation of ERK. Alteration of signaling suggests that complex formation may alter hPRL biological activity. This is the first report of a unique, multicomponent, high-capacity milk fat reservoir of hPRL; all other analyses of milk PRL have utilized defatted milk.
Activation of TRPA1 by luminal stimuli induces EP4-mediated anion secretion in human and rat colon
Authors: Kaji Izumi , Yasuoka Yukiko , Karaki Shin-ichiro , Kuwahara Atsukazu
Published: December 2011

In gastrointestinal (GI) physiology, anion and fluid secretion is an important function for host defense and is induced by changes in the luminal environment. The transient receptor potential A1 (TRPA1) channel is considered to be a chemosensor in several sensory tissues. Although the function of TRPA1 has been studied in GI motility, its contribution to the transepithelial ion transport system has rarely been discussed. In the present study, we investigated the secretory effect of the potential TRPA1 agonist allyl isothiocyanate (AITC) in rat and human colon using an Ussing chamber. The mucosal application of AITC (10−6-10−3 M) induced Cl− and HCO3− secretion in a concentration-dependent manner, whereas the serosal application induced a significantly weaker effect. AITC-evoked anion secretion was attenuated by tissue pretreatment with piroxicam and prostaglandin (PG) E2; however, this secretion was not affected by TTX, atropine, or extracellular Ca2+ depletion. These experiments indicate that TRPA1 activation induces anion secretion through PG synthesis, independent of neural pathways in the colon. Further analysis also indicates that AITC-evoked anion secretion is mediated mainly by the EP4 receptor subtype. The magnitude of the secretory response exhibited segmental heterogeneity in rat colon. Real-time PCR analysis showed the segmental difference was corresponding to the differential expression of EP4 receptor and cyclooxygenase-1 and -2. In addition, RT-PCR, in situ hybridization, and immunohistochemical studies showed TRPA1 expression in the colonic epithelia. Therefore, we conclude that the activation of TRPA1 in colonic epithelial cells is likely involved in the host defense mechanism through rapid anion secretion.
Fish oil prevents high-saturated fat diet-induced impairments in adiponectin and insulin response in rodent soleus muscle
Authors: Tishinsky Justine M. , Gulli Roberto A. , Mullen Kerry L. , Dyck David J. , Robinson Lindsay E.
Published: December 2011

High saturated fatty acid (SFA) diets contribute to the development of insulin resistance, whereas fish oil-derived n-3 polyunsaturated fatty acids (PUFA) increase the secretion of adiponectin (Ad), an adipocyte-derived protein that stimulates fatty acid oxidation (FAO) and improves skeletal muscle insulin response. We sought to determine whether fish oil could prevent and/or restore high SFA diet-induced impairments in Ad and insulin response in soleus muscle. Sprague-Dawley rats were fed 1) a low-fat control diet (CON group), 2) high-SFA diet (SFA group), or 3) high SFA with n-3 PUFA diet (SFA/n-3 PUFA group). At 4 wk, CON and SFA/n-3 PUFA animals were terminated, and SFA animals were either terminated or fed SFA or SFA/n-3 PUFA for an additional 2 or 4 wk. The effect of diet on Ad-stimulated FAO, insulin-stimulated glucose transport, and expression of Ad, insulin and inflammatory signaling proteins was determined in the soleus muscle. Ad stimulated FAO in CON and 4 wk SFA/n-3 PUFA (+36%, +39%, respectively P ≤ 0.05) only. Insulin increased glucose transport in CON, 4 wk SFA/n-3 PUFA, and 4 wk SFA + 4 wk SFA/n-3 PUFA (+82%, +33%, +25%, respectively P ≤ 0.05); this effect was lost in all other groups. TLR4 expression was increased with 4 wk of SFA feeding (+24%, P ≤ 0.05), and this was prevented in 4 wk SFA/n-3 PUFA. Suppressor of cytokine signaling-3 expression was increased in SFA and SFA/n-3 PUFA (+33 and +18%, respectively, P ≤ 0.05). Our results demonstrate that fish oil can prevent high SFA diet-induced impairments in both Ad and insulin response in soleus muscle.
Medial prefrontal cortex endocannabinoid system modulates baroreflex activity through CB1receptors
Authors: Ferreira-Junior Nilson C. , Fedoce Alessandra G. , Alves Fernando H. F. , Corrêa Fernando M. A. , Resstel Leonardo B. M.
Published: December 2011

Neural reflex mechanisms, such as the baroreflex, are involved in the regulation of cardiovascular system activity. Previous results from our group (Resstel LB, Correa FM. Medial prefrontal cortex NMDA receptors and nitric oxide modulate the parasympathetic component of the baroreflex. Eur J Neurosci 23: 481–488, 2006) have shown that glutamatergic synapses in the ventral portion of the medial prefrontal cortex (vMPFC) modulate baroreflex activity. Moreover, glutamatergic neurotransmission in the vMPFC can be modulated by the endocannabinoids system (eCBs), particularly the endocannabinoid anandamide, through presynaptic CB1receptor activation. Therefore, in the present study, we investigated eCBs receptors that are present in the vMPFC, and more specifically whether CB1receptors modulate baroreflex activity. We found that bilateral microinjection of the CB1receptor antagonist AM251 (100 or 300 pmol/200 nl) into the vMPFC increased baroreflex activity in unanesthetized rats. Moreover, bilateral microinjection of either the anandamide transporter inhibitor AM404 (100 pmol/200 nl) or the inhibitor of the enzyme fatty acid amide hydrolase that degrades anandamide, URB597 (100 pmol/200 nl), into the MPFC decreased baroreflex activity. Finally, pretreatment of the vMPFC with an ineffective dose of AM251 (10 pmol/200 nl) was able to block baroreflex effects of both AM404 and URB597. Taken together, our results support the view that the eCBs in the vMPFC is involved in the modulation of baroreflex activity through the activation of CB1receptors, which modulate local glutamate release.
Chronic intermittent hypoxia alters glutamatergic control of sympathetic and respiratory activities in the commissural NTS of rats
Authors: Costa-Silva João H. , Zoccal Daniel B. , Machado Benedito H.
Published: December 2011

Sympathetic overactivity and altered respiratory control are commonly observed after chronic intermittent hypoxia (CIH) exposure. However, the central mechanisms underlying such neurovegetative dysfunctions remain unclear. Herein, we hypothesized that CIH (6% O2every 9 min, 8 h/day, 10 days) in juvenile rats alters glutamatergic transmission in the commissural nucleus tractus solitarius (cNTS), a pivotal site for integration of peripheral chemoreceptor inputs. Using an in situ working heart-brain stem preparation, we found that l-glutamate microinjections (1, 3, and 10 mM) into the cNTS of control rats ( n = 8) evoked increases in thoracic sympathetic nerve (tSN) and central vagus nerve (cVN) activities combined with inhibition of phrenic nerve (PN) activity. Besides, the ionotropic glutamatergic receptor antagonism with kynurenic acid (KYN; 250 mM) in the cNTS of control group ( n = 7) increased PN burst duration and frequency. In the CIH group ( n = 10), the magnitude of l-glutamate-induced cVN excitation was smaller, and the PN inhibitory response was blunted ( P < 0.05). In addition, KYN microinjections into the cNTS of CIH rats ( n = 9) did not alter PN burst duration and produced smaller increases in its frequency compared with controls. Moreover, KYN microinjections into the cNTS attenuated the sympathoexcitatory response to peripheral chemoreflex activation in control but not in CIH rats ( P < 0.05). These functional CIH-induced alterations were accompanied by a significant 10% increase of N-methyl-D-aspartate receptor 1 (NMDAR1) and glutamate receptor 2/3 (GluR2/3) receptor subunit density in the cNTS ( n = 3–8, P < 0.05), evaluated by Western blot analysis. These data indicate that glutamatergic transmission is altered in the cNTS of CIH rats and may contribute to the sympathetic and respiratory changes observed in this experimental model.