bluuebunny/crossref_metadata_2025 huggingface dataset:
Bartonella spp. Antibodies in Forensic Samples from Swedish Heroin Addicts
Authors: McGILL SVENA , HJELM EVA , RAJS JOVAN , LINDQUIST OLLE , FRIMAN GÖRAN
Published: July 2009

Abstract: A high frequency of Bartonella elizabethae seropositivity (39%) was recorded among intravenous heroin addicts in Stockholm, Sweden, who died from a lethal injection. Some of the B. elizabethae‐seropositive individuals also had antibodies to B. henselae Houston‐1, B. grahamii, and B. quintana, but none had antibodies to B. henselae Marseille or B. vinsonii subsp. vinsonii. Hepatitis was a frequent finding but no case had peliosis hepatitis. There was no case of endocarditis, but in three persons active subacute‐to‐chronic myocarditis was found; two of these cases were Bartonella‐positive and HIV‐negative.
Mechanisms to Create a Safe Haven by Members of the Family Anaplasmataceae
Authors: RIKIHISA YASUKO
Published: July 2009

Abstract: Members of the family Anaplasmataceae are obligatory intracellular bacteria with unique host cell specificities. Depending on each bacterial species, granulocytes, platelets, endothelial cells, monocytes, macrophages, red blood cells, and cells of invertebrates are specifically infected. This unique host cell specificity has been the major hurdle to overcome in order to cultivate this group of bacteria. Because these bacteria cannot survive outside host cells, once released from a host cell, they need to rapidly induce signals for their own internalization into another host cell unique to each species. How these bacteria enter and continue to survive and replicate within the host milieu, then exit the host cell is largely unknown. Recently, however, unique strategies employed by some of these bacteria for successful parasitism of mammalian leukocytes have begun to be uncovered. When these bacteria interact with host cells, signals are transduced both inside the host cells and inside the bacteria. These signals disable the alarm system, as well as microbicidal mechanisms, of the leukocytes and condition the host cells to accept these intruders to share space and nutrient resources. Signals transduced inside the bacteria allow them to finely tune their metabolism and physiology in the new host cell environment and to disguise themselves as “insiders” so that their sojourn does not upset the host cell physiology until they have sufficiently multiplied. This paper discusses our recent findings on these topics.
From Genes to Proteins
Authors: RENESTO P. , RAOULT D.
Published: July 2009

Abstract: The availability of the complete genome sequences of several organisms allows the comparative analysis of genomes, a branch of bioinformatics known as genomics. With this approach, much can be learned about the biology of organisms that are difficult to culture, even when few, if any, of their proteins have been isolated and studied directly. We have focused our interest on Rickettsia conorii, an obligate intracellular bacterium responsible for Mediterranean spotted fever, a disease endemic in southern Europe. While bioinformatic annotation of the complete genome of this bacteria has allowed identification of 1,374 genes, a large number of them remain functionally uncharacterized. The final goal of many experiments in molecular biology is to use biological systems to synthesize the protein encoded by the gene being studied. Because three‐dimensional structures are more resilient to evolution and change than amino acid sequences, structure determination of some open reading frames should also exhibit structural similarity to previously described protein families. We have thus initiated a systematic expression and structure determination program for the proteins encoded by rickettsial genes of interest. We have cloned different genes of R. conorii by recombinational cloning (GATEWAY®, Invitrogen) a method that uses in vitro site‐specific recombination to accomplish a directional cloning of PCR products and the subsequent automatic subcloning of the DNA segment into new vector backbones at high efficiency. The constructions in p‐Dest17 yielded several clones able to express recombinant proteins with a C‐terminal histidine tag. Expression of corresponding proteins was then performed using a cell‐free protein expression system (Rapid Translation System, RTS, Roche Diagnostics). The recombinational cloning approach coupled to RTS provides an approach to rapid optimization of protein expression and is very useful to express rickettsial proteins. Moreover, this system is able to overcome some of the limitations encountered with rickettsial proteins highly toxic for E. coli or insect cells.
Phylogenetic Relationships among Ehrlichia ruminantium Isolates
Authors: ALLSOPP M.T. E.P. , VAN HEERDEN H. , STEYN H. C. , ALLSOPP B. A.
Published: July 2009

Abstract: Ehrlichia ruminantium, the causative agent of heartwater, is a tick‐borne pathogen infecting ruminants throughout sub‐Saharan Africa and on some Caribbean islands. The most reliable test for E. ruminantium is PCR‐based, but this gives positive results in some areas free of clinical heartwater and of the known Amblyomma spp. tick vectors. To investigate the molecular basis for this finding we have sequenced and carried out phylogenetic analysis of a range of genes from a number of E. ruminantium isolates. The genes include ribonuclease III and cytochrome c oxidase assembly protein genes (the pCS20 region), groESL, citrate synthase (gltA), and 16S ribosomal RNA. Relationships among major antigenic protein (map1) genes have been exhaustively investigated in a previous study that showed that the genes are variable in length, have non‐synonymous mutations, and show no geographical specificity among isolates. The 16S sequences are highly conserved, except in the V1 loop region. The pCS20, groESL, and gltA genes show only single nucleotide polymorphisms (SNPs) dispersed throughout the sequenced regions. Phylogenetic analysis using pCS20 data differentiates the western African isolates into a single clade, which also includes a southern African isolate. All other southern African isolates and a Caribbean isolate fall into a further clade, which is subdivided into two groups. Sequence variation within this clade is greater than that within the western African clade, suggesting that E. ruminantium originated in southern Africa.
Development of Rickettsia prowazekii DNA Vaccine
Authors: COKER CHRISTOPHER , MAJID MAHREEN , RADULOVIC SUZANA
Published: July 2009

Abstract: Rickettsia prowazekii, the etiologic agent of louse‐borne typhus, is listed as a category B agent under the select agent list of the United States Centers for Disease Control and Prevention. R. prowazekii was placed on the select agent list due to its potential to cause epidemic, high mortality in untreated and/or misdiagnosed cases, and ease of spread in vulnerable populations. Historically, R. prowazekii vaccines using crude antigen and/or inactivated rickettsia were partially protective but have been accompanied with undesirable toxic reactions and difficulties in standardization. The availability of the genome sequence of R. prowazekii allowed us to select genes that encode proteins with potential in immuno‐protection against this human pathogen. We successfully PCR‐amplified a group of genes involved in invasion (invA), cell division (fts), protein secretion (sec gene family), and virulence (ompA and ompB, virB gene family, cap and tlyA and tlyC). The generated PCR products were cloned into the GatewayTM cloning system and the cloned products will be introduced into Vical VR 1020‐DV and VR 1012‐DV DNA vaccine plasmids. Twenty‐four target genes from R. prowazekii have been PCR amplified, of which fifteen have been introduced into the pENTR/SD/D‐TOPO entry cloning vector.
Evaluation of Topiramate Neuroprotective Effect in Severe TBI Using Microdialysis
Authors: ALVES OSCAR L. , DOYLE AIDEN J. , CLAUSEN TOBIAS , GILMAN CHARLOTTE , BULLOCK ROSS
Published: July 2009

Abstract: Despite recent advances in our understanding of human traumatic brain injury (TBI) pathophysiology, we still need effective neuroprotective agents. The lack of rigorous drug pharmacokinetic studies in the “living” brain is an important cause of neuroprotection trials failure in human TBI research. In the past, several drugs have been labeled as inefficient, and even withdrawn from expensive trials, without knowing their actual penetration in the traumatized human brain. The injured brain is characterized by an increased diffusion distance, due to edema, and reduced blood flow that modulates drug transport across the blood‐brain barrier (BBB). In the study reported in this paper, we used cerebral microdialysis to provide a safe and efficient tool for continuous in vivo evaluation of bioavailability and pharmacologic efficacy of topiramate, a glutamate release inhibitor. Topiramate crossed the BBB in neuroprotective concentrations, and showed a lowering effect on glutamate levels, thereby modifying the natural history of glutamate release after TBI. The use of cerebral microdialysis in phase II drug studies will allow the detection of the appropriate therapeutic window and dosage for the neuroprotective agent. This strategy represents a clear improvement compared to traditional clinical trial design, and will reduce the trial costs.
Why Have So Many Drugs with Stellar Results in Laboratory Stroke Models Failed in Clinical Trials?
Authors: CURRY STEPHEN H.
Published: July 2009

Abstract: The failure, in the clinic, of at least fourteen potential neuroprotective agents expected to aid in recovery from stroke, after studies in animal models had predicted that they would be successful, is examined in relation to principles of extrapolation of data from animals to humans. Allometric scaling of glutamate data, especially duration of elevated glutamate levels in CSF and plasma, is used to support a hypothesis that treatment needs to be extended for the time that glutamate is elevated in the individual patient. According to this scenario, trials should be restricted to patients with progressing stroke and associated elevated glutamate levels, and patients without elevated glutamate might show adverse effects of drug treatment if normal levels of glutamate, which may be associated with neuroprotection, are antagonized.
Estrogen as a Neuroprotective Agent in the Treatment of Spinal Cord Injury
Authors: SRIBNICK ERIC ANTHONY , WINGRAVE JAMES MICHAEL , MATZELLE DEBORAH DENISE , RAY SWAPAN KUMAR , BANIK NAREN LAL
Published: July 2009

Abstract: The following review is a brief discussion about spinal cord injury and the possibility of using estrogen as a neuroprotective agent. There are several pathways by which secondary cell death can occur following spinal cord injury, including infiltration of inflammatory cells, generation of reactive oxygen species, decreases in spinal cord blood flow, and increases in intracellular Ca2+ levels. This secondary damage leads to apoptotic cell death, and the neuroprotective effects of pharmacologic agents have been investigated using experimentally induced spinal cord injury in animals. Currently, only high‐dose methylprednisolone is advocated for the treatment of patients following spinal cord injury. Estrogen has been shown to be neuroprotective in both in vitro and in vivo studies. There are several possible mechanisms of action by which estrogen may attenuate damage following spinal cord injury and improve functional outcome. Estrogen has been shown to have anti‐inflammatory properties. Estrogen levels are correlated with an increase in post‐traumatic blood flow to injured tissue. Estrogen may also upregulate protein levels of anti‐apoptotic Bcl‐2 and may attenuate the post‐traumatic influx of Ca2+.
Mating Attenuates Aging‐Associated Increase of Lipid Peroxidation Activity in C57BL/6J Mice
Authors: OXENKRUG GREGORY F. , REQUINTINA PURA J.
Published: July 2009

Abstract: In the frame of the free‐radical hypothesis of aging and literature data on increased life span of mated animals, we evaluated brain, kidney, and liver lipid peroxidation in C57Bl/6J mice of various ages and compared lipid peroxidation activity in mated and non‐mated mice of both genders. An aging‐associated increase (from 3 to 12 months of age) of lipid peroxidation, as measured by malonaldehyde and 4‐hydroxyalkenals (MDA + HAE) levels, was observed in the liver and kidney, but not in the brain. Tissue MDA + HAE levels were lower in 12‐month old mated mice (housed with animals of opposite gender from three to five months of age) than in 12‐month old non‐mated animals. There were no gender differences in the observed effect. It is suggested that mating might attenuate the increase of lipid peroxidation associated with aging.
Potential Mechanism by Which Resveratrol, a Red Wine Constituent, Protects Neurons
Authors: ZHUANG HEAN , KIM YUN‐SOOK , KOEHLER RAYMOND C. , DORÉ SYLVAIN
Published: July 2009

Abstract: Polyphenolic compounds, such as resveratrol, are naturally present at high concentration in grape skin, seeds, and red wine. Resveratrol is present in cis and trans isoforms and the major trans isomer is the biologically active one. Epidemiologic studies have revealed a reduced incidence of cardiovascular risk associated with consumers of red wine; this has been popularized as the French paradox. Resveratrol has been shown to have significant antioxidant properties in a variety of in vitro and in vivo models. It can reduce ischemic damage in heart ischemia reperfusion injury and also in brain ischemia/reperfusion in rodent models. Due to the high rate of oxygen consumption in the brain, and especially low levels of antioxidant defense enzymes, this organ is particularly susceptible of free radical damage. Most of the protective biological actions associated with resveratrol have been associated with its intrinsic radical scavenger properties. We have investigated the possibility of other indirect pathways by which resveratrol can exert its neuroprotective abilities. We have specifically tested whether heme oxygenase neuroprotective enzyme could be stimulated after resveratrol treatment. Using primary neuronal cultures, resveratrol was able to significantly induce heme oxygenase 1, whereas vehicle control showed no effect. No detectable toxicity was quantified. It is well established that after stroke significant levels of intracellular heme levels increase. The source of free heme comes mainly from several heme‐containing enzymes. Heme (iron‐protoporphyrin IX) is a pro‐oxidant and its rapid degradation by heme oxygenase is believed to be protective. Moreover, the generation of heme metabolites can also have their own intrinsic cellular properties. All together, increased heme oxygenase activity by resveratrol is a unique pathway by which this compound can exert its neuroprotective actions.
A Statistical Approach in Using cDNA Array Analysis to Determine Modest Changes in Gene Expression in Several Brain Regions after Neurotoxic Insult
Authors: DELONGCHAMP ROBERT R. , HARRIS ANGELA J. , BOWYER JOHN F.
Published: July 2009

Abstract: Modest changes in gene expression of three‐fold or less might be expected after mild to moderate neurotoxic exposure to classes of compounds, such as the substituted amphetamines, or at time points that are weeks after more severe neurotoxic exposures. When many genes appear to change expression by less than two‐fold, it is crucial to run several pairs of arrays and use statistical analysis to determine which genes are really changing. This limits the number of genes that have to undergo the time consuming task of performing RT‐PCR to validate change in expression levels. We describe here methods for statistically determining which genes are being expressed above background levels. These methods are used to compare expression differences among the striatum, parietal cortex, posterior lateral amygdaloid nucleus, and substantia nigra brain regions, all of which differ significantly in their gene expression profiles. In these comparisons, it was possible to distinguish differences among hundreds of genes with manageable estimated false discovery rates. The effect of amphetamine treatment on gene expression in posterior lateral amygdaloid nucleus was also evaluated. The expression data indicate that many genes have changed, but in this case it is more difficult to separate affected genes from false positives. The optimum list has 50 genes, of which 32% are expected to be false positives.
A Topographic Study of Minicolumnar Core Width by Lamina Comparison between Autistic Subjects and Controls: Possible Minicolumnar Disruption due to an Anatomical Element In‐Common to Multiple Laminae
Authors: Casanova Manuel F. , El‐Baz Ayman , Vanbogaert Eric , Narahari Praveen , Switala Andrew
Published: July 2009

Radial cell minicolumns are basic cytoarchitectonic motifs of the mammalian neocortex. Recent studies reveal that autism is associated with a “minicolumnopathy” defined by decreased columnar width and both a diminished and disrupted peripheral neuropil compartment. This study further characterizes this cortical deficit by comparing minicolumnar widths across layers. Brains from seven autistic patients and an equal number of age‐matched controls were celloidin embedded, serially sectioned at 200 µm and Nissl stained with gallocyanin. Photomicrograph mosaics of the cortex were analyzed with computerized imaging methods to determine minicolumnar width at nine separate neocortical areas: Brodmann Area's (BA) 3b, 4, 9, 10, 11, 17, 24, 43 and 44. Each area was assessed at supragranular, granular and infragranular levels. Autistic subjects had smaller minicolumns whose dimensions varied according to neocortical area. The greatest difference between autistic and control groups was observed in area 44. The interaction of diagnosis × cortical area × lamina (F16,316 = 1.33; P = 0.175) was not significant. Diminished minicolumnar width across deep and superficial neocortical layers most probably reflects involvement of shared constituents among the different layers. In this article we discuss the possible role of double bouquet and pyramidal cells in the translaminar minicolumnar width narrowing observed in autistic subjects.
Case–control studies on risk factors for chronic obstructive pulmonary disease: how does the sampling of the cases and controls affect the results?
Authors: Sørheim Inga‐Cecilie , Johannessen Ane , Grydeland Thomas Blix , Omenaas Ernst Reidar , Gulsvik Amund , Bakke Per Sigvald
Published: July 2009

Introduction:  Sampling is regarded as crucial to the validity of case–control studies. Ideally, cases and controls should be selected from the same source population, but deviations from this approach are often seen.

Objective:  Our objective was to examine how exposure–disease relationships in a study on chronic obstructive pulmonary disease (COPD) were affected by the sampling sources of cases and controls.

Methods:  A Norwegian case–control study on COPD including 1909 subjects used three sources of recruitment for cases (general population, hospital registry and volunteers) and two sources for controls (general population and volunteers). This resulted in six sampling combinations of cases and controls (groups A–F). We examined how the risk factors gender, age, smoking, educational level and comorbidity were associated with COPD in these six sampling groups.

Results:  Several exposure–disease associations were dependent on variation in sampling source, thereby demonstrating the possibility of selection bias. The theoretically most ideal sampling group is likely group A, where both cases and controls are recruited from a general population. When using group A as a reference, the groups containing either voluntary controls and/or hospital‐based cases deviated the most, suggesting higher susceptibility to selection bias in these groups.

Conclusion:  Recruitment from several sources made our study design vulnerable to selection bias. Our findings should bring about increased awareness to the sampling process, and encourage sampling of cases and controls from the same source population in future studies.

Please cite this paper as: Sørheim I‐C, Johannessen A, Grydeland TB, Omenaas ER, Gulsvik A and Bakke PS. Case–control studies on risk factors for COPD: how does the sampling of the cases and controls affect the results? The Clinical Respiratory Journal 2010; 4: 89–96.
Response to Comment by Poinar
et al
. on “DNA from Pre-Clovis Human Coprolites in Oregon, North America”
Authors: Gilbert M. Thomas P. , Jenkins Dennis L. , Higham Thomas F. G. , Rasmussen Morten , Malmström Helena , Svensson Emma M. , Sanchez Juan J. , Cummings Linda Scott , Yohe Robert M. , Hofreiter Michael , Götherström Anders , Willerslev Eske
Published: July 2009

The arguments of Poinar
et al
. neither challenge our conclusions nor would contribute to the verification of our data. We counter their questions about the authenticity of our ancient DNA results and the reliability of the radiocarbon data and stand by the conclusion that our data provide strong evidence of pre-Clovis Native Americans.
Manganese- and Iron-Dependent Marine Methane Oxidation
Authors: Beal Emily J. , House Christopher H. , Orphan Victoria J.
Published: July 2009

Electrons Accepted Here

Methane is produced in large quantities in marine sediments during the breakdown of organic matter. Methane is a powerful greenhouse gas that plays a large role in the regulation of climate. Methane is also an energy source for the abundant anaerobic methanotrophs that consume most of it before it ever reaches the atmosphere. The anaerobic oxidation of methane in marine systems depends on the presence of sulfate, which acts as an electron acceptor and is often considered essential for the reaction to proceed.

Beal
et al.

(p.
184
) report that anaerobic methane oxidation in marine sediments can be facilitated by iron and manganese, as well as by sulfate. Thus, anaerobic methane oxidation using iron and manganese could have been an important methane sink, and energy source, for the early biosphere.
How Did the Turtle Get Its Shell?
Authors: Rieppel Olivier
Published: July 2009

Details of embryonic skeletal and muscular organization provide evidence for the evolution of the turtle shell.
Researchers Generally Happy With Final Stem Cell Rules
Authors: Holden Constance
Published: July 2009

The final guidelines on research with human embryonic stem cells issued on Monday by the National Institutes of Health set out criteria for determining which ES cell lines can be used in federally funded experiments and give NIH discretion to approve old lines that don't meet stringent modern ethical requirements.
Hughes's Tjian Holds to a ‘Global’ Standard of Merit
Authors: Kaiser Jocelyn
Published: July 2009

Biochemist Robert Tjian, 59, took the helm of the Howard Hughes Medical Institute in April at a challenging time, after its endowment, which had stood at $17.5 billion last August, had been battered by the economic recession. On 25 June, Tjian spoke with
Science
; his comments have been edited for brevity and clarity.
Resignations Highlight Disagreement On Vaccines in Autism Group
Authors: Stokstad Erik
Published: July 2009

A prominent member of the science advisory board for Autism Speaks, the largest private funder of autism research, resigned last week citing his disagreement with efforts to study vaccines as a possible cause of autism.
Evaluation of the Specificity of Pneumococcal Polysaccharide Enzyme-Linked Immunosorbent Assay and the Effect of Serum Adsorption Based on Standard Pneumococcal Serogroup- or Serotype-Specific Rabbit Antisera
Authors: Slotved Hans-Christian , Guttmann Christina , Pedersen Charlotte Demuth , Jacobsen Jasper Neergaard , Krogfelt Karen Angeliki
Published: July 2009

Worldwide,
Streptococcus pneumoniae
(pneumococcus) is a major cause of morbidity and mortality, especially in infants and elderly people. Pneumococcal capsular polysaccharides are well characterized, and more than 90 different serotypes have been identified. Serotype-specific antibodies against the capsular polysaccharide are produced during infection. Detection of antibodies against pneumococci by enzyme-linked immunosorbent assay (ELISA) is performed according to WHO guidelines, using antigens provided by ATCC. However, testing the ELISA for specificity is challenging due to the difficulty in obtaining human naïve serum with pneumococcal antibodies as well as human serum with antibodies against a single serotype. The application of well-defined serotype-specific sera produced in animals to evaluate the specificity of the ATCC antigens and the effect of adsorption with cell wall and 22F polysaccharides has not been performed before, to our knowledge. In this study, the specificity of ATCC antigens (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) was tested by using commercial serotype-, serogroup-, and pool-specific pneumococcal rabbit antisera.
Assessment ofMycobacterium tuberculosisOmpATb as a Novel Antigen for the Diagnosis of Bovine Tuberculosis
Authors: Schiller Irene , Vordermeier H. Martin , Waters W. Ray , Palmer Mitchell , Thacker Tyler , Whelan Adam , Hardegger Roland , Marg-Haufe Beatrice , Raeber Alex , Oesch Bruno
Published: July 2009

In the search for better tools to control bovine tuberculosis, the development of diagnostic tests with improved specificity and sensitivity has a high priority. We chose to search for novel immunodiagnostic reagents. In this study, Rv0899 (outer membrane protein A ofMycobacterium tuberculosis[OmpATb]) was evaluated as a stimulation antigen in a gamma interferon (IFN-γ) release assay to diagnose bovine tuberculosis. OmpATb induced IFN-γ responses in cattle experimentally infected withM. bovisas early and as persistently as ESAT-6 and CFP-10, the current lead diagnostic antigens. In naturally infected cattle, OmpATb stimulated IFN-γ production in 22 of 26 animals (85%). Importantly, OmpATb detected a portion ofM. bovis-infected cattle which did not respond to ESAT-6 and CFP-10 (five of six cattle). The combined diagnostic sensitivity of OmpATb, ESAT-6, and CFP-10 for a preselected group consisting of naturally infected cattle with an overrepresentation of ESAT-6/CFP-10 nonresponders was 96% (25 of 26 animals). The specificity of OmpATb for uninfected cattle was 100% (27 cattle were tested; 12 of them gave false-positive results with tuberculins). In summary, our results indicate that OmpATb has the potential to enhance the sensitivity of previously described diagnostic tests based on ESAT-6 and CFP-10 and that the combined use of OmpATb, ESAT-6, CFP-10, and other proteins may achieve at least equal sensitivity to that obtained with purified protein derivative, but at a higher specificity. Further studies evaluating the diagnostic performance of OmpATb in combination with other proteins are ongoing.
Vesicular Stomatitis Virus Induces Apoptosis Primarily through Bak Rather than Bax by Inactivating Mcl-1 and Bcl-X
L
Authors: Pearce Alicia F. , Lyles Douglas S.
Published: July 2009

Vesicular stomatitis virus (VSV) induces apoptosis via the mitochondrial pathway. The mitochondrial pathway is regulated by the Bcl-2 family of proteins, which consists of both pro- and antiapoptotic members. To determine the relative importance of the multidomain proapoptotic Bcl-2 family members Bak and Bax, HeLa cells were transfected with Bak and/or Bax small interfering RNA (siRNA) and subsequently infected with recombinant wild-type VSV. Our results showed that Bak is more important than Bax for the induction of apoptosis in this system. Bak is regulated by two antiapoptotic Bcl-2 proteins, Mcl-1, which is rapidly turned over, and Bcl-X
L
, which is relatively stable. Inhibition of host gene expression by the VSV M protein resulted in the degradation of Mcl-1 but not Bcl-X
L
. However, inactivation of both Mcl-1 and Bcl-X
L
was required for cells to undergo apoptosis. While inactivation of Mcl-1 was due to inhibition of its expression, inactivation of Bcl-X
L
indicates a role for one or more BH3-only Bcl-2 family members. VSV-induced apoptosis was inhibited by transfection with siRNA against Bid, a BH3-only protein that is normally activated by the cleavage of caspase-8, the initiator caspase associated with the death receptor pathway. Similarly, treatment with an inhibitor of caspase-8 inhibited VSV-induced apoptosis. These results indicate a role for cross talk from the death receptor pathway in the activation of the mitochondrial pathway by VSV.
The Linear Plasmid Prophage Vp58.5 of
Vibrio parahaemolyticus
Is Closely Related to the Integrating Phage VHML and Constitutes a New Incompatibility Group of Telomere Phages
Authors: Zabala Beatriz , Hammerl Jens A. , Espejo Romilio T. , Hertwig Stefan
Published: July 2009

Vibrio parahaemolyticus
O3:K6 pandemic strains recovered in Chile frequently possess a 42-kb plasmid which is the prophage of a myovirus. We studied the prototype phage VP58.5 and show that it does not integrate into the host cell chromosome but replicates as a linear plasmid (Vp58.5) with covalently closed ends (telomeres). The Vp58.5 replicon coexists with other plasmid prophages (N15, PY54, and ΦKO2) in the same cell and thus belongs to a new incompatibility group of telomere phages. We determined the complete nucleotide sequence (42,612 nucleotides) of the VP58.5 phage DNA and compared it with that of the plasmid prophage. The two molecules share the same nucleotide sequence but are 35% circularly permuted to each other. In contrast to the hairpin ends of the plasmid, VP58.5 phage DNA contains 5′-protruding ends. The VP58.5 sequence is 92% identical to the sequence of phage VHML, which was reported to integrate into the host chromosome. However, the gene order and termini of the phage DNAs are different. The VHML genome exhibits the same gene order as does the Vp58.5 plasmid. VHML phage DNA has been reported to contain terminal inverted repeats. This repetitive sequence is similar to the telomere resolution site (
telRL
) of VP58.5 which, after processing by the phage protelomerase, forms the hairpin ends of the Vp58.5 prophage. It is discussed why these closely related phages may be so different in terms of their genome ends and their lifestyle.
A 49-Kilodalton Isoform of the Adenovirus Type 5 Early Region 1B 55-Kilodalton Protein Is Sufficient To Support Virus Replication
Authors: Kindsmüller Kathrin , Schreiner Sabrina , Leinenkugel Florian , Groitl Peter , Kremmer Elisabeth , Dobner Thomas
Published: July 2009

The adenovirus type 5 (Ad5) early region 1B 55-kDa (E1B-55K) protein is a multifunctional regulator of cell-cycle-independent virus replication that participates in many processes required for maximal virus production. As part of a study of E1B-55K function, we generated the Ad5 mutant H5
pm
4133, carrying stop codons after the second and seventh codons of the E1B reading frame, thereby eliminating synthesis of the full-length 55K product and its smaller derivatives. Unexpectedly, phenotypic studies revealed that H5
pm
4133 fully exhibits the characteristics of wild-type (wt) Ad5 in all assays tested. Immunoblot analyses demonstrated that H5
pm
4133 and wt Ad5 produce very low levels of two distinct polypeptides in the 48- to 49-kDa range, which lack the amino-terminal region but contain segments from the central and carboxy-terminal part of the 55K protein. Genetic and biochemical studies with different Ad5 mutants show that at least one of these isoforms consists of two closely migrating polypeptides of 433 amino acid residues (433R) and 422R, which are produced by translation initiation at two downstream AUG codons of the 55K reading frame. Significantly, a virus mutant producing low levels of the 433R isoform alone replicated to levels comparable to those of wt Ad5, demonstrating that this polypeptide provides essentially all functions of E1B-55K required to promote maximal virus growth in human tumor cells. Altogether, these results extend previous findings that the wt Ad5 E1B region encodes a series of smaller isoforms of E1B-55K and demonstrate that very low levels of at least one of these novel proteins (E1B-433R) are sufficient for a productive infection.
A One-Plasmid System To Generate Influenza Virus in Cultured Chicken Cells for Potential Use in Influenza Vaccine
Authors: Zhang Xiangmin , Kong Wei , Ashraf Shamaila , Curtiss Roy
Published: July 2009

Influenza virus has a set of ribonucleoproteins (RNPs) consisting of viral RNAs, influenza virus polymerase subunits, and nucleoprotein. Intracellular reconstitution of the whole set of RNPs via plasmid transfection results in the generation of influenza virus. By the use of reverse genetics and dual promoters, we constructed a 23.6-kb eight-unit plasmid that contains all the required constituents to generate influenza virus in chicken cells. Our “one-plasmid” system generated higher titers of influenza virus in chicken cells than the “eight-plasmid” system, enabling a simpler approach for generating vaccine seeds. Our study identified plasmid size as a potential limiting factor affecting transfection efficiency and hence the influenza viral yield from chicken cells.
Dynamic Host Energetics and Cytoskeletal Proteomes in Human Immunodeficiency Virus Type 1-Infected Human Primary CD4 Cells: Analysis by Multiplexed Label-Free Mass Spectrometry
Authors: Chan Eric Y. , Sutton Jennifer N. , Jacobs Jon M. , Bondarenko Andrey , Smith Richard D. , Katze Michael G.
Published: July 2009

We report on a proteomic analysis of ex vivo human immunodeficiency virus (HIV) type 1 infection in human primary CD4 cells by shotgun liquid chromatography-tandem mass spectrometry analysis, revealing two distinct proteomic profiles at two phases of virus replication. Relative to mock-infected cells, 168 signature proteins exhibited abundance changes at the first sign of Gag p24 production (8 h postinfection [p.i.]) or the peak of virus replication (24 h p.i.); interestingly, most of the changes were exclusive to only one phase of virus replication. Based on characterization by functional ontology and known human-HIV protein interactions, we observed the enrichment for protein abundance increases pertaining to protein synthesis and nucleasomal reorganization amid an otherwise placid cellular proteome at the first sign of HIV replication. In contrast, we observed indications of decreased protein turnover, concomitant with heightened DNA repair activities and preludes to apoptosis, in the presence of robust virus replication. We also observed hints of disruptions in protein and small molecule trafficking. Our label-free proteomic strategy allowed us to perform multiplexed comparisons—we buttressed our detection specificity with the use of a reverse transcriptase inhibitor as a counterscreen, enabling highlighting of cellular protein abundance changes unique to robust virus replication as opposed to viral entry. In conjunction with complementary high-throughput screens for cellular partners of HIV, we put forth a model pinpointing specific rerouting of cellular biosynthetic, energetic, and trafficking pathways as HIV replication accelerates in human primary CD4 cells.
Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets
Authors: Koning Fransje A. , Newman Edmund N. C. , Kim Eun-Young , Kunstman Kevin J. , Wolinsky Steven M. , Malim Michael H.
Published: July 2009

Human APOBEC3 enzymes are cellular DNA cytidine deaminases that inhibit and/or mutate a variety of retroviruses, retrotransposons, and DNA viruses. Here, we report a detailed examination of human
APOBEC3
gene expression, focusing on APOBEC3G (A3G) and APOBEC3F (A3F), which are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection but are suppressed by HIV-1 Vif. A3G and A3F are expressed widely in hematopoietic cell populations, including T cells, B cells, and myeloid cells, as well as in tissues where mRNA levels broadly correlate with the lymphoid cell content (gonadal tissues are exceptions). By measuring mRNA copy numbers, we find that
A3G
mRNA is ∼10-fold more abundant than
A3F
mRNA, implying that A3G is the more significant anti-HIV-1 factor in vivo.
A3G
and
A3F
levels also vary between donors, and these differences are sustained over 12 months. Responses to T-cell activation or cytokines reveal that
A3G
and
A3F
mRNA levels are induced ∼10-fold in macrophages and dendritic cells (DCs) by alpha interferon (IFN-α) and ∼4-fold in naïve CD4
+
T cells. However, immunoblotting revealed that A3G protein levels are induced by IFN-α in macrophages and DCs but not in T cells. In contrast, T-cell activation and IFN-γ had a minimal impact on
A3G
or
A3F
expression. Finally, we noted that
A3A
mRNA expression and protein expression are exquisitely sensitive to IFN-α induction in CD4
+
T cells, macrophages, and DCs but not to T-cell activation or other cytokines. Given that A3A does not affect HIV-1 infection, these observations imply that this protein may participate in early antiviral innate immune responses.
Depositional systems and seismic stratigraphy of a Quaternary basin: north Okanagan Valley, British Columbia
Authors: Vanderburgh S. , Roberts M. C.
Published: July 2009

Seismic and core data from north Okanagan Valley, a deep (~700 m of fill), elongate (~3 km wide by 45 km long) basin located in the Cordillera of south-central British Columbia, reveal a thick sequence of fine and coarse elastics. The architecture of the basin fill was delineated using 16 km of high-resolution, reflection seismic profiles, and 30 lithologic logs. Using a depositional systems approach, four systems were identified: subglacial fluvial, glaciolacustrine, alluvial fan, and channel. The subglacial fluvial system consists of a basal suite of compact, stratified to poorly stratified coarse clastics deposited beneath glacial ice under high hydrostatic pressure. Older sediments were almost completely excavated from the basin fill during periods of maximum subglacial flow during Late Wisconsinan glaciation. One of the outcomes of this study is that it lends support to the notion that Late Wisconsinan glaciers were capable of almost totally eroding older Pleistocene basin deposits while depositing thick sequences of subglacial fluvial sediments. During deglaciation, the basin was occupied by a lake in which laminated silt and clay were deposited (glaciolacustrine system). The wedge-shaped alluvial fan system interfingers with the finer clastics of the basin fill. Incised into the upper part of the basin fill are channel sediments forming the channel depositional system. Two stages in the evolution of the north Okanagan basin were identified: in the first stage (~10 ka), lake sediments were rapidly accumulating coeval with the formation of alluvial fans and fan deltas; the second stage shows the present-day architecture of the basin fill.
GENERATION OF HOMOGENEOUS GRANULAR PACKINGS: CONTACT DYNAMICS SIMULATIONS AT CONSTANT PRESSURE USING FULLY PERIODIC BOUNDARIES
Authors: SHAEBANI M. REZA , UNGER TAMÁS , KERTÉSZ JÁNOS
Published: July 2009

The contact dynamics (CD) method is an efficient simulation technique of dense granular media where unilateral and frictional contact problems for a large number of rigid bodies have to be solved. In this paper, we present a modified version of the CD to generate homogeneous random packings of rigid grains. CD simulations are performed at constant external pressure, which allows the variation of the size of a periodically repeated cell. We follow the concept of the Andersen dynamics and show how it can be applied within the framework of the CD method. The main challenge here is to handle the interparticle interactions properly, which are based on constraint forces in CD. We implement the proposed algorithm, perform test simulations, and investigate the properties of the final packings.
LANGLANDS DUALITY IN LIOUVILLE-$H^3_+$ WZNW CORRESPONDENCE
Authors: GIRIBET GASTON , NAKAYAMA YU , NICOLÁS LORENA
Published: July 2009

We show a physical realization of the Langlands duality in correlation functions of [Formula: see text] WZNW model. We derive a dual version of the Stoyanovky–Riabult–Teschner (SRT) formula that relates the correlation function of the [Formula: see text] WZNW and the dual Liouville theory to investigate the level duality k - 2 → (k - 2)-1 in the WZNW correlation functions. Then, we show that such a dual version of the [Formula: see text]-Liouville relation can be interpreted as a particular case of a biparametric family of nonrational conformal field theories (CFT's) based on the Liouville correlation functions, which was recently proposed by Ribault. We study symmetries of these new nonrational CFT's and compute correlation functions explicitly by using the free field realization to see how a generalized Langlands duality manifests itself in this framework. Finally, we suggest an interpretation of the SRT formula as realizing the Drinfeld–Sokolov Hamiltonian reduction. Again, the Hamiltonian reduction reveals the Langlands duality in the [Formula: see text] WZNW model. Our new identity for the correlation functions of [Formula: see text] WZNW model may yield a first step to understand quantum geometric Langlands correspondence yet to be formulated mathematically.
Chapter 1 Physics Goal of BES-III
Authors: Ma Jian-Ping
Published: July 2009

The Standard Model (SM) has been successful at describing all relevant experimental phenomena and, thus, has been generally accepted as the fundamental theory of elementary particle physics. Despite its success, the SM leaves many unanswered questions. These can be classified into two main categories: one for subjects related to possible new physics at unexplored energy scales and the other for nonperturbertive physics, mostly related to Quantum Chromodynamics…
Chapter 12 Two-Photon Physics
Authors: Bian Jian-Ming , Bytev Vladimir , Chen Ying , Jin Hong-Ying , Jin Shan , Qin Hu , Shen Xiao-Yan , Wu Ning , Xu Guo-Fa , Zhang Zhen-Xia , Zhao Qiang , Zhemchugov Alexey , Zheng Han-Qing , Zhu Shi-Lin , Zou Bing-Song
Published: July 2009

The following sections are included:

Introduction

Experimental Status of Two-Photon Processes

Measurement of Two-Photon Processes at BES-III

Summary
Chapter 23 Hadronic D(DS) Decays
Authors: Wu Yue-Liang , Zhong Ming
Published: July 2009

The following sections are included:

Present Status and Implication for QCD

Theoretical Review

Two-Body Decays

Three-Body Decays
Correlation of cardiac performance with cellular energetic components in the oxygen-deprived turtle heart
Authors: Stecyk Jonathan A. W. , Bock Christian , Overgaard Johannes , Wang Tobias , Farrell Anthony P. , Pörtner Hans-O.
Published: July 2009

The relationship between cardiac energy metabolism and the depression of myocardial performance during oxygen deprivation has remained enigmatic. Here, we combine in vivo31P-NMR spectroscopy and MRI to provide the first temporal profile of in vivo cardiac energetics and cardiac performance of an anoxia-tolerant vertebrate, the freshwater turtle ( Trachemys scripta) during long-term anoxia exposure (∼3 h at 21°C and 11 days at 5°C). During anoxia, phosphocreatine (PCr), unbound levels of inorganic phosphate (effective Pi2−), intracellular pH (pHi), and free energy of ATP hydrolysis (dG/dξ) exhibited asymptotic patterns of change, indicating that turtle myocardial high-energy phosphate metabolism and energetic state are reset to new, reduced steady states during long-term anoxia exposure. At 21°C, anoxia caused a reduction in pHifrom 7.40 to 7.01, a 69% decrease in PCr and a doubling of effective Pi2−. ATP content remained unchanged, but the free energy of ATP hydrolysis (dG/dξ) decreased from −59.6 to −52.5 kJ/mol. Even so, none of these cellular changes correlated with the anoxic depression of cardiac performance, suggesting that autonomic cardiac regulation may override putative cellular feedback mechanisms. In contrast, during anoxia at 5°C, when autonomic cardiac control is severely blunted, the decrease of pHifrom 7.66 to 7.12, 1.9-fold increase of effective Pi2−, and 6.4 kJ/mol decrease of dG/dξ from −53.8 to −47.4 kJ/mol were significantly correlated to the anoxic depression of cardiac performance. Our results provide the first evidence for a close, long-term coordination of functional cardiac changes with cellular energy status in a vertebrate, with a potential for autonomic control to override these immediate relationships.
Cell biology and physiology of the uroepithelium
Authors: Khandelwal Puneet , Abraham Soman N. , Apodaca Gerard
Published: July 2009

The uroepithelium sits at the interface between the urinary space and underlying tissues, where it forms a high-resistance barrier to ion, solute, and water flux, as well as pathogens. However, the uroepithelium is not simply a passive barrier; it can modulate the composition of the urine, and it functions as an integral part of a sensory web in which it receives, amplifies, and transmits information about its external milieu to the underlying nervous and muscular systems. This review examines our understanding of uroepithelial regeneration and how specializations of the outermost umbrella cell layer, including tight junctions, surface uroplakins, and dynamic apical membrane exocytosis/endocytosis, contribute to barrier function and how they are co-opted by uropathogenic bacteria to infect the uroepithelium. Furthermore, we discuss the presence and possible functions of aquaporins, urea transporters, and multiple ion channels in the uroepithelium. Finally, we describe potential mechanisms by which the uroepithelium can transmit information about the urinary space to the other tissues in the bladder proper.
Optical Imaging of Contextual Interactions in V1 of the Behaving Monkey
Authors: Kinoshita Masaharu , Gilbert Charles D. , Das Aniruddha
Published: July 2009

Interactions in primary visual cortex (V1) between simple visual elements such as short bar segments are believed to underlie our ability to easily integrate contours and segment surfaces. We used intrinsic signal optical imaging in alert fixating macaques to measure the strength and cortical distribution of V1 interactions among collinear bars. A single short bar stimulus produced a broad-peaked hill of activation (the optical point spread) covering multiple orientation hypercolumns in V1. Flanking the bar stimulus with a pair of identical collinear bars led to a strong nonlinear suppression in the optical signal. This nonlinearity was strongest over the center bar region, with a spatial distribution that cannot be explained by a simple gain control. It was a function of the relative orientation and separation of the bar stimuli in a manner tuned sharply for collinearity, being strongest for immediately adjacent bars lying on a smooth contour. These results suggest intracortical interactions playing a major role in determining V1 activation by smooth extended contours. Our finding that the interaction is primarily suppressive when imaged optically, which presumably reflects the combined inhibitory and excitatory inputs, suggests a complex interplay between these cortical inputs leading to the collinear facilitation seen in the spiking response of V1 neurons. This disjuncture between the facilitation seen in spiking and the suppression in imaging also suggests that cortical representations of complex stimuli involve interactions that need to be studied over extended networks and may be hard to deduce from the responses of individual neurons.