bluuebunny/crossref_metadata_2025 huggingface dataset:
12/15-Lipoxygenase-Dependent Myeloid Production of Interleukin-12 Is Essential for Resistance to Chronic Toxoplasmosis
Authors: Middleton Melissa K. , Zukas Alicia M. , Rubinstein Tanya , Kinder Michelle , Wilson Emma H. , Zhu Peijuan , Blair Ian A. , Hunter Christopher A. , Puré Ellen
Published: October 2009

Interleukin-12 (IL-12) is critical for resistance toToxoplasma gondiiduring both the acute and chronic stages of infection. However, the cellular and molecular pathways that regulate IL-12 production during chronic toxoplasmosis are incompletely defined. We recently discovered that 12/15-lipoxygenase (12/15-LOX), which oxidizes unsaturated lipids in macrophages, is a novel and selective regulator of IL-12 production. We now demonstrate the essential role of this enzyme in the chronic phase of toxoplasmosis. Although 12/15-LOX-deficient mice were resistant to acuteT. gondiiinfection, 80% of 12/15-LOX-deficient mice died during chronic toxoplasmosis, compared to no deaths in wild-type controls. The morbidity of chronically infected 12/15-LOX mice was associated with an increase in brain inflammation and parasite burden. These data suggest that the evolution of the immune response toT. gondiiis accompanied by an increasing requirement for 12/15-LOX-mediated signaling. Consistent with this conclusion, 12/15-LOX activity was enhanced during chronic, but not acute, toxoplasmosis. Furthermore, the enhanced susceptibility of 12/15-LOX-deficient mice to chronic toxoplasmosis was associated with reduced production of IL-12 and gamma interferon (IFN-γ) that was not evident during acute infection. Importantly, ex vivo IFN-γ production by 12/15-LOX-deficient splenocytes could be rescued by the addition of recombinant IL-12. These data establish that 12/15-LOX is a critical mediator of the chronic type 1 inflammatory response and that immune mediators can be subject to distinct cellular and/or molecular mechanisms of regulation at different stages of inflammation.
SuperantigenicStaphylococcus aureusStimulates Production of Interleukin-17 from Memory but Not Naive T Cells
Authors: Islander Ulrika , Andersson Annica , Lindberg Erika , Adlerberth Ingegerd , Wold Agnes E. , Rudin Anna
Published: October 2009

T-helper 17 (Th17) cells are characterized by their production of interleukin-17 (IL-17) and have a role in the protection against infections and in certain inflammatory diseases. Humans who lack Th17 cells are more susceptible toStaphylococcus aureusinfections compared to individuals having Th17 cells.S. aureusis part of the commensal skin microflora and also colonize the infant gut. To investigate whether UV-killedS. aureuswould be more capable of inducing IL-17 than other commensal bacteria, we stimulated mononuclear cells from adults, infants, and newborns with various gram-positive and gram-negative commensal bacteria. IL-17 was produced from adult memory Th17 cells after stimulation with superantigen-producingS. aureusbut not nonsuperantigenicS. aureusor other common commensal gut bacteria. Cells from newborns were poor IL-17 producers after stimulation withS. aureus, whereas in some cases IL-17 was secreted from cells isolated from infants at the age of 4 and 18 months. These results suggest that superantigenicS. aureusare particularly efficient in stimulating IL-17 production and that the cytokine is produced from memory T cells.
A Histidine-to-Arginine Substitution in Panton-Valentine Leukocidin from USA300 Community-Acquired Methicillin-Resistant
Staphylococcus aureus
Does Not Impair Its Leukotoxicity
Authors: Besseyre des Horts Timothée , Dumitrescu Oana , Badiou Cédric , Thomas Damien , Benito Yvonne , Etienne Jerome , Vandenesch François , Lina Gerard
Published: October 2009

Panton-Valentine leukocidin (PVL) is a synergohymenotropic toxin (SHT) produced by
Staphylococcus aureus
. At present, there are conflicting reports on the leukotoxic activity of PVL and its consequent role as a virulence factor in USA300. In this work, we compared the cytolytic effects induced by wild-type PVL and those of PVL harboring a histidine-to-arginine substitution at amino acid 176 in the
S. aureus
USA300 strain. We also investigated the capacity of wild-type and H176R LukS-PV to recruit and form pores with the F components of other SHTs. For this purpose, we assayed polymorphonuclear neutrophils for leukotoxicity after incubation with either culture supernatants from strains bearing different PVL haplotypes or recombinant toxins from different types of SHT. We show here that the H176R variation in the PVL sequence causes no change in leukotoxicity and that the R variant is as efficient as wild-type PVL at inducing pore formation in leukocytes.
Histamine Plays an Essential Regulatory Role in Lung Inflammation and Protective Immunity in the Acute Phase ofMycobacterium tuberculosisInfection
Authors: Carlos D. , Fremond C. , Samarina A. , Vasseur V. , Maillet I. , Ramos S. G. , Erard F. , Quesniaux V. , Ohtsu H. , Silva C. L. , Faccioli L. H. , Ryffel B.
Published: October 2009

The course and outcome of infection with mycobacteria are determined by a complex interplay between the immune system of the host and the survival mechanisms developed by the bacilli. Recent data suggest a regulatory role of histamine not only in the innate but also in the adaptive immune response. We used a model of pulmonaryMycobacterium tuberculosisinfection in histamine-deficient mice lacking histidine decarboxylase (HDC−/−), the histamine-synthesizing enzyme. To confirm that mycobacterial infection induced histamine production, we exposed mice toM. tuberculosisand compared responses in C57BL/6 (wild-type) and HDC−/−mice. Histamine levels increased around fivefold above baseline in infected C57BL/6 mice at day 28 of infection, whereas only small amounts were detected in the lungs of infected HDC−/−mice. Blocking histamine production decreased both neutrophil influx into lung tissue and the release of proinflammatory mediators, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), in the acute phase of infection. However, the accumulation and activation of CD4+T cells were augmented in the lungs of infected HDC−/−mice and correlated with a distinct granuloma formation that contained abundant lymphocytic infiltration and reduced numbers of mycobacteria 28 days after infection. Furthermore, the production of IL-12, gamma interferon, and nitric oxide, as well as CD11c+cell influx into the lungs of infected HDC−/−mice, was increased. These findings indicate that histamine produced afterM. tuberculosisinfection may play a regulatory role not only by enhancing the pulmonary neutrophilia and production of IL-6 and TNF-α but also by impairing the protective Th1 response, which ultimately restricts mycobacterial growth.
Evaluating recreational fisheries for an endangered species: a case study of taimen, Hucho taimen, in Mongolia
Authors: Jensen Olaf P. , Gilroy David J. , Hogan Zeb , Allen Brant C. , Hrabik Thomas R. , Weidel Brian C. , Chandra Sudeep , Vander Zanden M. Jake
Published: October 2009

Understanding the tradeoff between exploitation and conservation is difficult in data-poor situations, which are typical for most recreational fisheries, even in developed countries. In a developing country where the target species is endangered, the stakes are higher and the management resources are fewer. We combined a mark–recapture experiment, life history invariants, and meta-analysis to parameterize a delay-difference model for a population of the endangered giant Eurasian trout (taimen, Hucho taimen ) in northern Mongolia. The model allowed us to evaluate the impacts of a recreational fishery for taimen based on a suite of population characteristics including equilibrium abundance, biomass, and mean weight. The Bayesian framework and Monte Carlo simulations combine disparate sources of information while keeping track of uncertainty as it propagates through the model. In the case of taimen in the Eg–Uur watershed, the existing catch–release recreational fishery has likely reduced taimen abundance, biomass, and mean weight by less than 10% compared with levels predicted in the absence of recreational fishing. In comparison, if all taimen caught in this fishery were retained (as they are elsewhere in Mongolia), there is a 57% chance that such harvest levels, if maintained, would lead to the eventual extirpation of the population.
Contribution of three life history types to smolt production in a Chinook salmon (Oncorhynchus tshawytscha) population
Authors: Copeland Timothy , Venditti David A.
Published: October 2009

The most productive juvenile life history in the Pahsimeroi River Chinook salmon ( Oncorhynchus tshawytscha ; Idaho, USA) population (in terms of smolt production) is being eliminated. Length at emigration and survival from spawning areas to Lower Granite Dam within each of three juvenile phenotypes (age-0 smolts, fall parr, age-1 smolts) were influenced by initial cohort abundance. The proportion of age-1 emigrants reaching Lower Granite Dam was dome-shaped with respect to initial cohort abundance. As initial abundance increased, higher proportions of juveniles adopted the age-1 smolt phenotype or emigrated as fall parr. The age-0 smolt phenotype had the highest relative survival, and the fall parr phenotype, the lowest. The contributions of each emigrant type to cohort smolt production varied with circumstances; hence, the full expression of phenotypic diversity is important to the study population. However, there were no records of tagged age-0 smolts surviving to return from the Pacific Ocean. Given the potential productivity of this life history, management and recovery efforts should be directed at the age-0 smolt phenotype.
Benthic bioturbator enhances CH4 fluxes among aquatic compartments and atmosphere in experimental microcosms
Authors: Figueiredo-Barros Marcos Paulo , Caliman Adriano , Leal João J. F. , Bozelli Reinaldo L. , Farjalla Vinicius F. , Esteves Francisco A.
Published: October 2009

We utilized laboratory microcosms to evaluate the effects of a benthic sediment bioturbator ( Heteromastus similis ; Polychaeta; conveyor-belt deposit feeder) on vertical distributions of CH4 in sediment and net CH4 fluxes across sediment–water–air interfaces. The effect of H. similis on sediment CH4 concentration ([CH4]) varied depending on sediment depth and was strongest at higher animal densities. In comparison with defaunated controls, microcosms with the highest density of H. similis exhibited an increase in [CH4] of 3.7-fold, on average, at the sediment surface (0–2 cm), but these concentrations decreased by ~2-fold in deeper sediment layers (2–8 cm). However, irrespective of sediment depth, the density of H. similis resulted in an overall nonlinear reduction of bulk sediment [CH4]. Most of the observed CH4 losses from the sediment were due to CH4 oxidation, but the bioturbatory activities of H. similis also promoted significant increases in [CH4] in both the water column and the microcosm headspace. These results suggest that benthic invertebrates can mediate CH4 turnover between compartments in aquatic ecosystems, with further consequences for the coupling between benthic–pelagic food chains via the methanotrophic-mediated microbial loop, as well as increase CH4 emissions to the atmosphere.
Ancestry, population structure, and conservation genetics of Arctic grayling (Thymallus arcticus) in the upper Missouri River, USA
Authors: Peterson Douglas P. , Ardren William R.
Published: October 2009

We genotyped Arctic grayling ( Thymallus arcticus ) at 10 microsatellite loci in 18 samples (n = 726) from Montana, Wyoming, and Saskatchewan to determine genetic relationships among native, captive, and naturalized populations in the upper Missouri River basin, to assess patterns in genetic diversity, and to infer recent demographic histories. Substantial genetic subdivision was observed among sample populations (global FST= 0.10). Canadian populations have been isolated from Missouri River populations long enough for mutation to cause genetic differences between regions (mean pairwise FST= 0.18, RST= 0.54). Within the Missouri River basin, most naturalized lacustrine populations traced their ancestry to Red Rock lakes. Two populations in headwater lakes within the Big Hole River watershed appear to be native. We found neither evidence for introgression of Canadian-origin grayling nor any effect of hatchery stocking in native populations. The native fluvial Big Hole River group was genetically distinct and most diverse (HE= 0.89), whereas native Madison River and Red Rock lakes populations exhibited lower genetic diversity (HE= 0.74 and 0.80, respectively) and evidence of recent bottlenecks. The existing Big Hole and Red Rock populations are at low abundance but do not appear to be at immediate risk of inbreeding depression (Ne= 207.7–228.2).
Distribution and identification of proteolytic Bacillus spp. in paddy field soil under rice cultivation
Authors: Watanabe Katsuji , Hayano Koichi
Published: October 2009

Proteolytic bacteria in paddy field soils under rice cultivation were characterized and enumerated using azocoll agar plates. Bacillus spp. were the proteolytic bacteria that were most frequently present, comprising 59% of the isolates. They were always the numerically dominant proteolytic bacteria isolated from three kinds of fertilizer treatments (yearly application of rice-straw compost and chemical fertilizer, yearly application of chemical fertilizer, and no fertilizer application) and at three different stages of rice development (vegetative growth stage, maximal tillering stage, and harvest stage). Of the 411 proteolytic bacteria isolated, 124 isolates had stronger proteolytic activity than others on the basis of gelatin liquefaction tests and most of them were Bacillus spp. (100% in 1989 and 92.4% in 1991). Bacillus subtilis and Bacillus cereus were the main bacteria of this group and Bacillus mycoides, Bacillus licheniformis, and Bacillus megaterium were also present. We conclude that these Bacillus spp. are the primary source of soil protease in these paddy fields.Key words: soil protease, paddy field, proteolytic bacteria, Bacillus spp.
Opsonin-independent adherence and intracellular development of Legionella pneumophila within U-937 cells
Authors: Rodgers Frank G. , Gibson III Frank C.
Published: October 2009

Legionella pneumophila adhered to and multiplied intracellularly in the human histiocytic lymphoma U-937 cell line. The infectious process was evaluated by viable bacterial cell colony counts and documented by transmission and scanning electron microscopy. In the absence of opsonins, wash-resistant bacterial adherence to host cells occurred within 1 h and attachment of 1 or 2 organisms per U-937 host cell involved close surface interactions at the prokaryotic and eukaryotic membranes. Intracellular multiplication of bacteria was maximal by 24 h after inoculation of cell monolayers. Release of L. pneumophila from these cells appeared as a lytic process that resulted in an increase in the numbers of microorganisms in the extracellular fluids and a concomitant decline in the number of intracellular bacteria. The course of cellular infection was completed by 72 h. The cellular and ultrastructural events of L. pneumophila adherence and uptake by U-937 cells in the absence of antibody or complement have been defined. In addition, this work further establishes the U-937 cell as a suitable model for investigating Legionella – host cell interactions.Key words: Legionella, U-937 cells, intracellular replication, opsonin-independent uptake.
FLUCTUATION OF THE MAGNETOCONDUCTIVITY IN POLYCRYSTALLINE Y0.95Tb0.05Ba2Cu3O7-δ SUPERCONDUCTORS
Authors: MENEGOTTO COSTA R. , JURELO A. R. , RIEGEL I. C. , PIMENTAL J. L.
Published: October 2009

The electrical magnetoconductivity near the superconducting transition in granular samples of Y 0.95 Tb 0.05 Ba 2 Cu 3 O 7-δ was experimentally studied. The measurements were performed using low magnetic fields up to 50 Oe, applied parallel to the current. Results showed that the transition proceeds in two stages as seen by the temperature derivative of the resistivity near TC. The analysis of the conductivity in the normal phase has evidenced contributions from Gaussian and critical fluctuations. In the regime of near zero resistance state, the occurrence of a coherence transition was evidenced, which was related to the connective nature of the granular samples. We have obtained the field independent exponents λC = 4.6 ± 1.1 and λC ≅ 6.7 ± 0.7 for fluctuation conductivity in the coherence transition.
A data structure for a sequence of string accesses in external memory
Authors: Ciriani Valentina , Ferragina Paolo , Luccio Fabrizio , Muthukrishnan S.
Published: October 2009

We introduce a new paradigm for querying strings in external memory, suited to the execution of sequences of operations. Formally, given a dictionary of
n
strings
S
1
, …,
S

n

, we aim at supporting a search sequence for
m
not necessarily distinct strings
T
1
,
T
2
, …,
T

m

, as well as inserting and deleting individual strings. The dictionary is stored on disk, where each access to a disk page fetches
B
items, the cost of an operation is the number of pages accessed (I/Os), and efficiency must be attained on entire sequences of string operations rather than on individual ones.

Our approach relies on a novel and conceptually simple self-adjusting data structure (SASL) based on skip lists, that is also interesting
per se
. The search for the whole sequence
T
1
,
T
2
, …,
T

m

can be done in an expected number of I/Os:

O
(∑

j
=1

m

|
T

j

|/
B
+ ∑

i
=1

n
n

(
n

i

log

B

m
/
n

i

)),

where each
T

j

may or may not be present in the dictionary, and
n

i

is the number of times
S

i

is queried (i.e., the number of
T

j

s equal to
S

i

). Moreover, inserting or deleting a string
S

i

takes an expected amortized number
O
(|
S

i

|/
B
+ log

B

n
) of I/Os. The term ∑

j
=1

m

|
T
j
|/
B
in the search formula is a lower bound for reading the input, and the term ∑

i
=1

n

n

i

log

B

m
/
n

i

(entropy of the query sequence) is a standard information-theoretic lower bound. We regard this result as the
static optimality theorem for external-memory string access
, as compared to Sleator and Tarjan's classical theorem for numerical dictionaries [Sleator and Tarjan 1985]. Finally, we reformulate the search bound if a cache is available, taking advantage of common prefixes among the strings examined in the search.
Algorithmic aspects of bandwidth trading
Authors: Bhatia Randeep , Chuzhoy Julia , Freund Ari , Naor Joseph (Seffi)
Published: October 2009

We study algorithmic problems that are motivated by bandwidth trading in next-generation networks. Typically, bandwidth trading involves sellers (e.g., network operators) interested in selling bandwidth pipes that offer to buyers a guaranteed level of service for a specified time interval. The buyers (e.g., bandwidth brokers) are looking to procure bandwidth pipes to satisfy the reservation requests of end-users (e.g., Internet subscribers). Depending on what is available in the bandwidth exchange, the goal of a buyer is to either spend the least amount of money so as to satisfy all the reservations made by its customers, or to maximize its revenue from whatever reservations can be satisfied.

We model this as a real-time nonpreemptive scheduling problem in which machine types correspond to bandwidth pipes and jobs correspond to end-user reservation requests. Each job specifies a time interval during which it must be processed, and a set of machine types on which it can be executed. If necessary, multiple machines of a given type may be allocated, but each must be paid for. Finally, each job has associated with it a revenue, which is realized if the job is scheduled on some machine.

There are two versions of the problem that we consider. In the cost minimization version, the goal is to minimize the total cost incurred for scheduling all jobs, and in the revenue maximization version the goal is to maximize the revenue of the jobs that are scheduled for processing on a given set of machines. We consider several variants of the problems that arise in practical scenarios, and provide constant factor approximations.
Revascularization for Coronary Artery Disease: Stents Versus Bypass Surgery
Authors: King Spencer B. , Marshall John Jeffrey , Tummala Pradyumna E.
Published: October 2009

Coronary artery disease (CAD) is one manifestation of ischemic heart disease, which is the leading cause of mortality in the world. In addition to preventive medical therapy and lifestyle changes, consideration of revascularization of obstructed arteries to reduce ischemia, alleviate angina, and improve quality of life is a mainstay of current practice. However, the benefits of different methods of revascularization in particular patient populations are debated. Percutaneous coronary intervention (PCI), which involves placement of intracoronary stents in most patients, is a less invasive procedure than coronary artery bypass graft (CABG) surgery. Although it is generally accepted that patients with single-vessel obstructive CAD are best treated with PCI, patients with multivessel CAD have a higher ischemia burden, a greater risk for developing recurrent ischemic events, and a higher mortality. It is in this patient population where the debate over revascularization with stents versus surgery continues.
Trigona corvina: An Ecological Study Based on Unusual Nest Structure and Pollen Analysis
Authors: Roubik David W. , Moreno Patiño J. Enrique
Published: October 2009

We found that the nest ofTrigona corvina(Apidae; Meliponini) consists mainly of pollen exines from bee excrement, forming a scutellum shield encasing the colony. A 20-year-old nest (1980–2000) from a lowland Panama forested habitat was sawed in half longitudinally, and a 95 cm transect was systematically sampled each 5 cm. Samples subjected to detailed pollen analysis held 72 botanical species belonging to 65 genera in 41 families. Over 90% of scutellum pollen volume was Cecropiaceae and Arecaceae, among grains. Potentially the oldest samples, in the middle of the nest, indicate that Mimosoideae, Euphorbiaceae, and Bombacaceae (now Malvaceae) were lost when Africanized honey bee competitors colonized Panama in 1984.Cecropiadeposited in the nest increased markedly after landscape-level vegetation disturbance. Pollen fromCavanillesiademonstrated that the foraging range encompassed 3  and perhaps 500 plant species.Trigona corvinaprimarily foraged on plants with large inflorescences, consistent with foraging theory considering their aggressive behavior.
Phase Transition in Dynamical Systems: Defining Classes of Universality for Two‐Dimensional Hamiltonian Mappings via Critical Exponents
Authors: Leonel Edson D.
Published: October 2009

A phase transition from integrability to nonintegrability in two‐dimensional Hamiltonian mappings is described and characterized in terms of scaling arguments. The mappings considered produce a mixed structure in the phase space in the sense that, depending on the combination of the
control parameters and initial conditions, KAM islands which are surrounded by chaotic seas that
are limited by invariant tori are observed. Some dynamical properties for the largest component of
the chaotic sea are obtained and described in terms of the control parameters. The average value
and the deviation of the average value for chaotic components of a dynamical variable are described
in terms of scaling laws, therefore critical exponents characterizing a scaling function that describes
a phase transition are obtained and then classes of universality are characterized. The three models
considered are: The Fermi‐Ulam accelerator model, a periodically corrugate waveguide, and variant of
the standard nontwist map.
Serotonin 5- Receptor Function as a Contributing Factor to Both Neuropsychiatric and Cardiovascular Diseases
Authors: Nichols Charles D.
Published: October 2009

There are high levels of comorbidity between neuropsychiatric and cardiovascular disorders. A key molecule central to both cognitive and cardiovascular function is the molecule serotonin. In the brain, serotonin modulates neuronal activity and is actively involved in mediating many cognitive functions and behaviors. In the periphery, serotonin is involved in vasoconstriction, inflammation, and cell growth, among other processes. It is hypothesized that one component of the serotonin system, the receptor, is a common and contributing factor underlying aspects of the comorbidity between neuropsychiatric and cardiovascular disorders. Within the brain this receptor participates in processes such as cognition and working memory, been implicated in effective disorders such as schizophrenia, and mediate the primary effects of hallucinogenic drugs. In the periphery, receptors have been linked to vasoconstriction and hypertension, and to inflammatory processes that can lead to atherosclerosis.
Nasolabial Cyst
Authors: Sahin Caner
Published: October 2009

Nasolabial cyst is a rare nonodontogenics, soft-tissue cyst occurring in the sublabial area and anterior maxillary region. The patient usually presents with a slowly enlarging asymptomatic swelling. They are usually diagnosed in early stages because of cosmetic problems. In our paper we report anasolabial cystof a 53-year-old man and discuss the diagnosis, differential diagnosis, and treatment in the light of the literature.
Nonexistence and Radial Symmetry of Positive Solutions of Semilinear Elliptic Systems
Authors: Zhang Zhengce , Zhu Liping
Published: October 2009

Nonexistence and radial symmetry of positive solutions for a class of semilinear elliptic systems are considered via the method of moving spheres.
Integrating Diverse Information to Gain More Insight into Microarray Analysis
Authors: Loganantharaj Raja , Chung Jun
Published: October 2009

Microarray technology provides an opportunity to view transcriptions at genomic level under different conditions controlled by an experiment. From an array experiment using a human cancer cell line that is engineered to differ in expression of tumor antigen, integrinα6β4, few hundreds of differentially expressed genes are selected and are clustered using one of several standard algorithms. The set of genes in a cluster is expected to have similar expression patterns and are most likely to be coregulated and thereby expected to have similar function. The highly expressed set of upregulated genes become candidates for further evaluation as potential biomarkers. Besides these benefits, microarray experiment by itself does not help us to understand or discover potential pathways or to identify important set of genes for potential drug targets. In this paper we discuss about integrating protein‐to‐protein interaction information, pathway information with array expression data set to identify a set of “important” genes, and potential signal transduction networks that help to target and reverse the oncogenic phenotype induced by tumor antigen such as integrinα6β4. We will illustrate the proposed method with our recent microarray experiment conducted for identifying transcriptional targets of integrinα6β4 for cancer progression.
MicroRNA Implications across Neurodevelopment and Neuropathology
Authors: Martino Sabata , di Girolamo Ilaria , Orlacchio Antonio , Datti Alessandro , Orlacchio Aldo
Published: October 2009

MicroRNAs (miRNAs) have rapidly emerged as biologically important mediators of posttranscriptional and epigenetic regulation in both plants and animals. miRNAs function through a variety of mechanisms including mRNA degradation and translational repression; additionally, miRNAs may guide gene expression by serving as transcription factors. miRNAs are highly expressed in human brain. Tissue and cell type‐specific enrichments of certain miRNAs within the nervous system argue for a biological significance during neurodevelopmental stages. On the other hand, a large number of studies have reported links between alterations of miRNA homeostasis and pathologic conditions such as cancer, heart diseases, and neurodegeneration. Thus, profiles of distinct or aberrant miRNA signatures have most recently surged as one of the most fascinating interests in current biology. Here, the most recent insights into the involvement of miRNAs in the biology of the nervous system and the occurrence of neuropathological disorders are reviewed and discussed.
Treatment Strategy According to Findings on Pressure-Flow Study for Women with Decreased Urinary Flow Rate
Authors: Tanaka Yoshinori , Masumori Naoya , Tsukamoto Taiji , Furuya Seiji , Furuya Ryoji , Ogura Hiroshi
Published: October 2009

Purpose. In women who reported a weak urinary stream, the efficacy of treatment chosen according to the urodynamic findings on pressure-flow study was prospectively evaluated.Materials and Methods. Twelve female patients with maximum flow rates of 10 mL/sec or lower were analyzed in the present study. At baseline, all underwent pressure-flow study to determine the degree of bladder outlet obstruction (BOO) and status of detrusor contractility on Schäfer's diagram. Distigmine bromide, 10 mg/d, was given to the patients with detrusor underactivity (DUA) defined as weak/very weak contractility, whereas urethral dilatation was performed using a metal sound for those with BOO (linear passive urethral resistance relation 2–6). Treatment efficacy was evaluated using the International Prostate Symptom Score (IPSS), uroflowmetry, and measurement of postvoid residual urine volume. Some patients underwent pressure-flow study after treatment.Results. Urethral dilatation was performed for six patients with BOO, while distigmine bromide was given to the remaining six showing DUA without BOO. IPSS, QOL index, and the urinary flow rate were significantly improved in both groups after treatment. All four of the patients with BOO and one of the three with DUA but no BOO who underwent pressure-flow study after treatment showed decreased degrees of BOO and increased detrusor contractility, respectively.Conclusions. Both BOO and DUA cause a decreased urinary flow rate in women. In the short-term, urethral dilatation and distigmine bromide are efficacious for female patients with BOO and those with DUA, respectively.
Novel miR390‐Dependent Transacting siRNA Precursors in Plants Revealed by a PCR‐Based Experimental Approach and Database Analysis
Authors: Krasnikova M. S. , Milyutina I. A. , Bobrova V. K. , Ozerova L. V. , Troitsky A. V. , Solovyev A. G. , Morozov S. Y.
Published: October 2009

TAS loci in plant genomes encode transacting small interfering RNAs (ta‐siRNAs) that regulate expression of a number of genes. The function of TAS3 precursor in Arabidopsis thaliana is controlled by two miR390 target sites flanking two ta‐siARF sequences targeting mRNAs of ARF transcription factors. Cleavage of the 3′‐miR390‐site initiates ta‐siRNAs biogenesis. Here we describe the new method for identification of plant ta‐siRNA precursors based on PCR with oligodeoxyribonucleotide primers mimicking miR390. The method was found to be efficient for dicotiledonous plants, cycads, and mosses. Based on sequences of amplified loci and a database analysis, a novel type of miR390‐dependent TAS sequences was identified in dicots. These TAS loci are characterized by a smaller distance between miR390 sites compared to TAS3, a single copy of ta‐siARF, and a sequence conservation pattern pointing to the possibility that processing of novel TAS‐like locus is initiated by cleavage of the 5′‐terminal miR390 target site.
Pharmacologic inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes
Authors: Mumenthaler Shannon M. , Ng Patricia Y.B. , Hodge Amanda , Bearss David , Berk Gregory , Kanekal Sarath , Redkar Sanjeev , Taverna Pietro , Agus David B. , Jain Anjali
Published: October 2009

The serine/threonine family of Pim kinases function as oncogenes and have been implicated in prostate cancer progression, particularly in hormone-refractory prostate disease, as a result of their antiapoptotic function. In this study, we used a pharmacologic inhibitor targeting the Pim family members, SGI-1776, to determine whether modulation of Pim kinase activity could alter prostate cancer cell survival and modulate chemotherapy resistance. Extensive biochemical characterization of SGI-1776 confirmed its specificity for the three isoforms of the Pim family. Treatment of prostate cancer cells with SGI-1776 resulted in a dose-dependent reduction in phosphorylation of known Pim kinase substrates that are involved in cell cycle progression and apoptosis (p21Cip1/WAF1 and Bad). Consequently, SGI-1776 compromised overall cell viability by inducing G1 cell cycle arrest and triggering apoptosis. Overexpression of recombinant Pim-1 markedly increased sensitivity of SGI-1776–mediated prostate cancer cell apoptosis and p21Cip1/WAF1 phosphorylation inhibition, reinforcing the specificity of SGI-1776. An additional cytotoxic effect was observed when SGI-1776 was combined with taxane-based chemotherapy agents. SGI-1776 was able to reduce cell viability in a multidrug resistance 1 protein–based taxane-refractory prostate cancer cell line. In addition, SGI-1776 treatment was able to resensitize chemoresistant cells to taxane-based therapies by inhibiting multidrug resistance 1 activity and inducing apoptosis. These findings support the idea that inhibiting Pim kinases, in combination with a chemotherapeutic agent, could play an important role in prostate cancer treatment by targeting the clinical problem of chemoresistance. [Mol Cancer Ther 2009;8(10):2882–93]
Meconium Periorchitis: A Rare Cause of Fetal Scrotal Cyst – MRI and Pathologic Appearance
Authors: Cesca Eleonora , Midrio Paola , Tregnaghi Alberto , Alaggio Rita , Bitetti Stefania , Gamba Piergiorgio
Published: October 2009

A case of meconium periorchitis detected by fetal MRI and misdiagnosed during pregnancy as inguinoscrotal hernia is reported for the first time. A full-term black boy presented at birth with an asymptomatic, ‘stony-hard’, scrotal mass suggestive of an in utero testicular torsion or testicular/paratesticular tumor. Early surgical treatment resulted in the removal of paratesticular yellowish amorphous material. Histology was consistent with the diagnosis of meconium periorchitis, a rare and benign condition resulting from healed intrauterine bowel perforation.
Increased Fetal Nuchal Translucency as a Sole Clue in the Prenatal Diagnosis of a Fetus with Trisomy 13
Authors: Ki Kyung-Do , Kim So-Ra , Lee Woo-In
Published: October 2009

Trisomy 13 is a fatal chromosomal abnormality. A body of literature supports the assessment of fetal nuchal translucency as an adjunct in the prenatal diagnosis of trisomy 13. Over 90% of affected fetuses are readily diagnosed by ultrasound, as they present typical sonographic features; however, there is no consensus regarding trisomy 13 showing normal second trimester sonographic findings. We report an interesting case of trisomy 13, demonstrating increased nuchal translucency as an apparently isolated prenatal sonographic finding.
Fetal Cardiac Troponin T as a Marker of Poor Prognosis in Nonimmune Hydrops Fetalis
Authors: Nomura Roseli Mieko Yamamoto , Brizot Maria de Lourdes , Liao Adolfo Wenjaw , Andrade Joelma Queiroz , Zugaib Marcelo
Published: October 2009

Objective: Severe fetal anemia and cardiac compromise are important causes of nonimmune hydrops fetalis, and fetal recovery also depends on the degree of fetal heart compromise. The aim of this study was to report the fetal cardiac troponin T (cTnT) levels in cases of nonimmune fetal hydrops. Methods: Fetal cTnT was analyzed on 7 occasions in 5 cases of nonimmune fetal hydrops (twice in 2 cases). Results: In 3 of 4 fetuses in which intrauterine death occurred, fetal cTnT levels were increased. The only fetus that survived in this series showed decreased levels of cTnT before birth. Conclusion: Fetal cTnT levels may be a marker of fetal prognosis in cases of fetal hydrops.
Reverse Twin-Twin Transfusion Syndrome after Fetoscopic Laser Photocoagulation of Chorionic Anastomoses: A Case Report
Authors: Wataganara Tuangsit , Chanprapaph Pharuhas , Chuangsuwanich Tuenjai , Kanokpongsakdi Sujin , Chuenwattana Prakong , Titapant Vitaya
Published: October 2009

A case of severe twin-twin transfusion syndrome (TTTS) which developed at menstrual age of 17 weeks underwent a fetoscopic laser ablation of the anastomosing vessels. The vascular equator of the anastomoses was noticed to be deviated due to marginal cord insertion of the recipient fetus. The procedure was accomplished uneventfully. However, the recipient fetus died 6 h after the procedure. After the pregnancy was terminated, the donor was found to be counterintuitively plethoric, and the recipient was pale. Similar appearances were noted on the placental territories of each fetus. This is consistent with reverse TTTS. Dye injection study and microscopic examination revealed a residual deep vein-vein anastomosis. This subchorionic vascular connection is still a challenge to coagulate with current placental surgery techniques. To the best of our knowledge, this is the first confirmed case of reverse TTTS as a cause of fetal loss following laser photocoagulation. This report also discusses the technical considerations in the complicated case of in utero placental surgery for TTTS.
Prognostic Role of Tumor-Head Volume Ratio in Fetal Sacrococcygeal Teratoma
Authors: Sy Edgar D. , Filly Roy A. , Cheong Mei-Leng , Clifton Matthew S. , Cortes Raul A. , Ohashi Shinsuke , Takifuji Katsunari , Ventura Denise Estefan , Grethel Erich J. , Wagner Amy J. , Gress Elizabeth A. , Ball Robert H. , Lee Hanmin , Harrison Michael R.
Published: October 2009

Objective: To evaluate the ability of a tumor-head volume ratio to predict outcome and incidence of hydrops in fetuses with sacrococcygeal teratoma. Methods: Seventy-one sonograms were reviewed retrospectively from 28 fetuses with sacrococcygeal teratoma managed in our institution. Head volume (HV) and total tumor volume were calculated from sonograms. Amount of cystic tumor was estimated to determine solid tumor volume (STV) for the STV/HV ratio. Results: Twenty percent of sonograms with STV/HV <1 and 97.3% with STV/HV >1 were associated with 1 or more abnormal sonographic signs (p = 0.000). Overall mortality was 11/27 (41%). There was no mortality in fetuses with a ratio of <1, while 11/18 (61%) of fetuses with ratio >1 died (p = 0.003). Conclusion: The STV/HV ratio may be used to identify fetuses with a high risk of a poor outcome due to high-output cardiac failure and hydrops, and may help guide management.
Sp1 Specifically Binds to an Evolutionarily Conserved DNA Segment within a Region Necessary for Podocyte-Specific Expression of Nephrin
Authors: Beltcheva Olga , Hjorleifsdottir Eyrun Edda , Kontusaari Sirpa , Tryggvason Karl
Published: October 2009

We have analyzed a conserved 237-bp segment located in a 1.9-kb upstream region of the nephrin gene, previously shown to contain kidney specific enhancer element(s). Electromobility shift assay was used to identify a 20-nucleotide region specifically recognized and bound by protein factors in nuclear extracts from immortalized podocyte and human embryonic kidney cell lines. The region was further narrowed down by competition assays to a stretch of 6 consecutive guanines, which are conserved at this location in multiple species. Introduction of mutations in this sequence abolished all protein binding activity whereas mutations in the flanking nucleotides did not. By means of gel supershift and chromatin immunoprecipitation assays we have shown that the protein factor from podocyte nuclear extracts able to recognize and bind the target sequence is the Sp1 zinc-finger protein.
BMP-7 Blocks the Cyclosporine-A-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells
Authors: Xu Yanfang , Wan Jianxin , Jiang Dewen , Wu Xiaonan
Published: October 2009

Aims: The nephrotoxic side effects of cyclosporine A (CsA) are partly due to induction of the epithelial-to-mesenchymal transition (EMT), possibly through upregulation of connective tissue growth factor (CTGF). Bone morphogenetic protein (BMP-7) has been reported to protect against and reverse renal injury via its renotropic and antifibrotic effects. We therefore designed a method to investigate the mechanism by which BMP-7 inhibits CSA-induced EMT in cultured human renal proximal tubular epithelial (HK-2) cells and whether BMP-7 can antagonize CsA-induced profibrogenic effects. Methods: Cultured HK-2 cells were treated with CsA or a combination of CsA and BMP-7 for 72 h. Morphological changes were assessed by phase-contrast microscopy. The expression of α-smooth muscle actin (α-SMA), E-cadherin, collagen type I and CTGF was analyzed by immunofluorescence, RT-PCR, and Western blot. Additionally, the effect of CTGF silencing on CsA-mediated gene expression was assessed. Results: CsA-induced EMT was associated with decreased expression of E-cadherin, increased expression of α-SMA, collagen type I and CTGF, and loss of epithelial morphology. BMP-7 inhibited these effects in a dose-dependent manner. Using siRNA, CTGF knock-down also attenuated EMT-associated phenotypic changes induced by CsA. Conclusion: These data suggest that BMP-7 can block CsA-induced EMT by downregulating the expression of CTGF, a downstream mediator of EMT.
Vitamin B6 Metabolism in Chronic Kidney Disease – Relation to Transsulfuration, Advanced Glycation and Cardiovascular Disease
Authors: Busch Martin , Göbert Andrea , Franke Sybille , Ott Undine , Gerth Jens , Müller Andreas , Stein Günter , Bitsch Roland , Wolf Gunter
Published: October 2009

Background: Vitamin deficiency is common in chronic kidney disease (CKD). Data on B6 supply and possible relationships to cardiovascular events (CVE) in CKD are rare. Pyridoxamine exerts inhibitory effects on the formation of advanced glycation endproducts (AGE) implicated in the pathogenesis of CKD and atherosclerosis. Methods: In 48 CKD patients at stage 2–4, 72 hemodialysis patients (HD), 38 renal transplant recipients (RTR) and 141 healthy controls (mean age 58 ± 13, 61 ± 12, 50 ± 12 and 54 ± 16 years, respectively), plasma and red blood cell (RBC) concentrations of pyridoxal-5′-phosphate (PLP), pyridoxal (PL), 4-pyridoxic acid (PA), pyridoxamine-5′-phosphate (PMP) and of the AGE pentosidine were measured by high-performance liquid chromatography, NΕ-(carboxymethyl)lysine and imidazolone by an ELISA, and total homocysteine and cystathionine by gas chromatography-mass spectrometry. Results: Despite routine low-dose vitamin supplementation in HD, plasma PLP was decreased in HD (79 ± 69 nmol/l) compared with CKD stage 2–4 patients (497 ± 944 nmol/l), RTR (416 ± 604 nmol/l) and controls (159 ± 230 nmol/l; p < 0.001). Plasma PA was significantly increased in HD (11,667 ± 17,871 nmol/l) in comparison with CKD stage 2–4 (435 ± 441 nmol/l), RTR (583 ± 668 nmol/l) and controls (46 ± 49 nmol/l; p < 0.001). B6 forms were significantly affected by renal function (R = 0.792, p < 0.001 for CKD stage 2–4). There was no relation of vitamers with a history of CVE. Relationships between B6 forms and AGE (RBC-PMP with pentosidine in CKD stage 2–4: R = –0.351, p < 0.05) were found. Conclusion: HD patients showed a deficiency in PLP in plasma but not in RBC. Prospective trials are needed to elucidate the potential role of elevated PA on cardiovascular and renal outcome in CKD. Vitamin B6 supplementation might be successful in preventing AGE-related pathologies.
Vulvar Mucinous Adenocarcinoma Associated with Crohn’s Disease: Report of Two Cases
Authors: Matsuo Koji , Chi Dennis S. , Eno Michele L. , Im Dwight D. , Rosenshein Neil B.
Published: October 2009

Background: Rectovaginal fistula in long-standing Crohn’s disease is possibly associated with malignant transformation to mucinous adenocarcinoma of the vagina. However, there have been no previously reported cases documenting vulvar cancer in association with rectovaginal fistula in Crohn’s disease. We report 2 cases of vulvar mucinous adenocarcinoma associated with Crohn’s disease. Both showed vulvar symptoms after the development of rectovaginal fistula. Case 1: A 48-year-old woman, with a 30-year history of Crohn’s disease including a rectovaginal fistula, developed persistent pyoderma gangrenosum. Further workup revealed metastatic vulvar mucinous adenocarcinoma. Case 2: A 37-year-old woman with long-standing Crohn’s disease including numerous episodes of perianal or rectovaginal fistulas complained of a vulvar mass suspicious for an abscess. Biopsy showed mucinous adenocarcinoma. Conclusion: Vulvar lesions or symptoms in the setting of rectovaginal fistula in Crohn’s disease are an important clinical feature and the possible development of vulvar cancer should be considered.
Genetic Association of a Cathepsin D Polymorphism and Sporadic Creutzfeldt-Jakob Disease
Authors: Jeong Byung-Hoon , Lee Kyung-Hee , Lee Yun-Jung , Yun Jisuk , Park Young-Jae , Bae Yoonsang , Kim Young-Hoon , Cho Young-Sook , Choi Eun-Kyoung , Carp Richard I. , Kim Yong-Sun
Published: October 2009

Background: Cathepsin D is the most abundant lysosomal and endosomal aspartyl protease; it shows beta and gamma secretase activity in vitro by cleaving the amyloid precursor protein into amyloid beta protein. In recent studies, cathepsin D was co-localized with PrPSc, the disease-associated form of the prion disease, and abnormal expression of cathepsin D correlated with tissue damage in brains of sporadic Creutzfeldt-Jakob disease (CJD). Objective: To investigate whether a polymorphism at position 224, C224T, on exon 2 of the cathepsin D gene (CTSD) is associated with sporadic CJD in the Korean population. Methods: We compared the genotype and allele frequencies at this polymorphism site in 172 sporadic CJD patients with those in 197 healthy Koreans. Results and Conclusion: Our study does not show a significant difference in genotype (p = 0.901) and allele (p = 0.509) frequencies of CTSD C224T between sporadic CJD patients and normal controls. This was the first genetic association study of CTSD in a sporadic CJD population.