bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytoskeleton‐modulating effectors of enteropathogenic and enterohemorrhagic Escherichia coli: a case for EspB as an intrinsically less‐ordered effector
Authors: Hamada Daizo , Hamaguchi Mitsuhide , Suzuki Kayo N. , Sakata Ikuhiro , Yanagihara Itaru
Published: May 2010

Enterohemorrhagic and enteropathogenic Escherichia coli produce various effector proteins that are directly injected into the host‐cell cytosol through the type III secretion system. E. coli secreted protein (Esp)B is one such effector protein, and affects host‐cell morphology by reorganizing actin networks. Unlike most globular proteins that have well‐ordered, rigid structures, the structures of type III secretion system effectors from pathogenic Gram‐negative bacteria, including EspB, are often less well‐ordered. This minireview focuses on the functional relationship between the structural properties of these proteins and their roles in type III secretion system‐associated pathogenesis.
Time Course of Serum S100B Protein and Neuron‐Specific Enolase Levels of a Single Dose of Chlorpyrifos in Rats
Authors: Bozkurt Ayhan , Yardan Turker , Ciftcioglu Engin , Baydin Ahmet , Hakligor Aylin , Bitigic Medine , Bilge Sirri
Published: April 2010

Abstract:  Organophosphate (OP) compounds are a large class of chemicals, many of which are used as pesticides. It is suggested that OPs specifically affect glia and neurons. Effects of acute exposure to chlorpyrifos (CPF), which is a common organophosphorus pesticide used worldwide, on neuron‐specific enolase (NSE) and S100B levels in rat blood during 7 days were assessed. Rats were evaluated either before (0 hr) or 2, 12, 24, 48 and 168 hr (7 days) after injection of CPF (279 mg/kg, s.c.) or vehicle (peanut oil, 2 ml/kg, s.c.) for clinical signs of toxicity. Immediately after the evaluation of toxicity, blood samples were taken for biochemical assays. CPF administration produced decreases in body‐weight and temperature, which were observed for first time at 12 hr after CPF administration and continued for 168 hr (p < 0.05–0.001). Serum S100B and NSE levels were acutely increased 2 hr after CPF administration and remained high at 12 hr (p < 0.01–0.001). NSE and S100B levels were not different in either CPF or vehicle groups at following time points. Serum butyrylcholinesterase (EC 3.1.1.8; BuChE) activity was dramatically reduced at 2 hr after CPF and remained low at each time points during 7 days (p < 0.01–0.001). Our results suggest that the usefulness of serum levels of these glia‐ and neuron‐specific marker proteins in assessing OP toxicity, specifically CPF‐induced toxicity.
Interleukin‐10 gene promoter polymorphism in Polish rheumatoid arthritis patients
Authors: Paradowska‐Gorycka A. , Trefler J. , Maciejewska‐Stelmach J. , Łącki J. K.
Published: May 2010

Interleukin (IL)‐10 is an important multifunctional cytokine with both anti‐inflammatory and immunoregulatory effects in rheumatoid arthritis (RA). In the present study, we evaluated the frequency and potential impact of IL‐10 promoter polymorphisms on susceptibility to and severity of RA in Polish in – patients with a high disease activity (mean DAS 28 C‐reactive protein 5.25). DNA was obtained from 244 RA patients and 106 healthy controls. The −592C/A and −1082G/A IL‐10 gene polymorphisms were amplified by polymerase chain reaction with restriction endonuclease mapping. The frequency of the IL‐10‐592CA, ‐592AA genotypes (respectively: 30% vs 5% and 7% vs 0%) and allele −592A (37% vs 5%) were significantly higher in RA patients as compared with a control group. We did not find any association of the IL‐10‐592C/A genotype distribution with disease parameters, except for an increased ESR (erythrocyte sedimentation rate) in patients with the −592CC genotype as compared with those with −592CA or −592AA genotypes (P = 0.01). The frequency of the IL‐10‐1082GG genotype was lower (P = 0.0001), and that of the IL‐10‐1082GA genotype was higher (P = 0.009) in RA patients comparing with the control group. In RA patients with −1082GA or −1082AA genotypes the time duration of the disease (P = 0.03), Health Assessment Questionnaire (HAQ) Score (P = 0.04) and PLT count (P = 0.001) were significantly increased as compared with subjects with −1082GG genotype. Presented findings indicate that IL‐10‐592C/A and IL‐10‐1082G/A polymorphisms may be considered genetic risk factors for RA susceptibility and severity.
Analysis of peripheral blood T‐cell subsets, natural killer cells and serum levels of cytokines in children with Down syndrome
Authors: Cetiner S. , Demirhan O. , Inal T. C. , Tastemir D. , Sertdemir Y.
Published: May 2010

The objective of this study was to evaluate the relationship between humoral and cell‐mediated immune response parameters and impairment of immune functions in children with Down syndrome (DS). The patient group was consisted of cytogenetically documented 32 children with DS. Lymphocyte subsets and natural killer cells were counted by flow‐cytometry system. Levels of interleukin (IL)‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10 and tumour necrosis factor‐alpha (TNF‐α) were detected by enzyme‐linked immunosorbent assay method. Serum IgG, IgM, IgA levels were measured by turbidimetric methods. The percentage of CD8+ lymphocytes and CD56+ cells of patients with DS were significantly higher, whereas CD20+ lymphocytes were lower than that of controls (P < 0.05). The percentage of CD2 and CD4 levels and CD4/CD8 ratio of patients with DS and normal controls were similar (P > 0.05). Levels of IL‐4 and IL‐10 were significantly increased, but IL‐6 and TNF‐α levels were decreased in children with DS (P < 0.05). Levels of other studied cytokines between patients with DS and controls were not statistically different (P > 0.05, for all). Serum IgG, IgM and IgA levels were found to be similar between the groups (P > 0.05). It has been known that IL‐4 and IL‐10 are anti‐inflammatory molecules which inhibit the synthesis of proinflammatory cytokines such as IL‐6 and TNF‐α. In this study, levels of IL‐4 and IL‐10 were significantly increased, but IL‐6 and TNF‐α levels were decreased in children with DS. These results may suggest that continuing anti‐inflammatory state in DS and this process may explain the cause of recurrent infection of the disease. On the other hand, in contrast to the low percentage of CD20+ cells, high percentage of CD8+ and CD56+ cells were found. Our findings may demonstrate that the cell‐mediated and humoral immune system parameters in children with DS were altered according to healthy children.
Vascular endothelial growth factor +405 G/C,−460 T/C and −2578 A/C polymorphisms are not associated with insulin resistance in polycystic ovary syndrome
Authors: Vural P. , Küskü‐Kiraz Z. , Doğru‐Abbasoğlu S. , Çil E. , Karadağ B. , Uysal M.
Published: May 2010

Insulin resistance (IR) and pancreatic β‐cell dysfunction are usual comorbidities in polycystic ovary syndrome (PCOS). Vascular endothelial growth factor (VEGF) is known to play an important role in the pathogenesis of PCOS. This study examined firstly the possible association of common +405 G/C,−460 T/C and −2578 A/C polymorphisms of VEGF gene with fasting glucose, fasting insulin and the indices of IR [glucose/insulin ratio (GIR), homoeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI)] in 137 patients with PCOS. None of the studied polymorphisms were found to affect IR indices significantly. However, there was a trend towards higher HOMA in +405 G and −460 T allele carriers in comparison with homozygotes +405 CC and −460 CC, respectively. With regard to −2578 A/C polymorphism, although not significant, in −2578 C carriers HOMA was lower, and GIR was higher in comparison with −2578 AA genotype. Alteration of QUICKI between genotypes was minimal and varied from 4% to 7%. Because of the relatively small sample size, more studies with greater number of cases are necessary to confirm our observations before any statement can be made about the relationship between VEGF gene polymorphism and IR parameters in PCOS.
Genetic polymorphisms of the T‐cell coreceptors CD28 and CTLA‐4 in Afro‐ and Euro‐Brazilians
Authors: Pincerati M. R. , Dalla‐Costa R. , Pavoni D. P. , Petzl‐Erler M. L.
Published: May 2010

CD28 and cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) are two receptors that have complementary functions in control of T‐cell activation. Polymorphisms of their genes, CD28 and CTLA4, might confer differential susceptibility to diseases resulting from unbalanced or inefficient immune responses. Thus far, little is known about the CD28 polymorphism in populations and even for CTLA4 just one or two single nucleotide polymorphisms (SNPs) are usually analysed. To assess the allelic and haplotypic diversity and linkage disequilibrium in the Brazilian population, two samples differing according to predominant ancestry – African or European – have been analysed for seven SNPs, CD28 −372(G>A), and int3 17(T>C); CTLA4 −1722(T>C), −1577(G>A) −318(C>T), 49(A>G), 6230(G>A) also named CT60, and three microsatellites, CD28 (CAA)n, CTLA4 (AT)n and D2S72 (CA)n. The two population strata show little differentiation, the only significant differences being the allele frequencies of the CTLA4 −1577(G>A) SNP and the CTLA4 (AT)n microsatellite (P = 0.018 and P = 0.007, respectively). Linkage disequilibrium is high, especially between the CTLA4 polymorphisms. However, low r2 values indicate that none of the markers is a tag SNP in these populations. These results provide valuable information for optimal selection of markers for use in future association studies. We conclude that disease association studies and functional studies addressing the possible consequences of polymorphisms of the 2q33 genomic region should consider haplotypic data besides analysis of individual polymorphisms.
The polymorphism of human leucocyte antigen‐G gene in a healthy population of Iran
Authors: Rahimi R. , Zavaran Hosseini A. , Yari F.
Published: May 2010

Human leucocyte antigen‐G (HLA‐G) is a non‐classical HLA class I molecule that unlike the classical HLA, has low polymorphism. This molecule, initially, found on invasive trophoblast cells and is postulated to have mediatory role in maternal–fetal interface. So far 43 alleles of HLA‐G gene have been found. Studies on alleles of HLA‐G gene could be useful in understanding the genetic variants of HLA‐G alleles in Iranian population. The goal of this research was to determine the polymorphism of HLA‐G gene in a healthy population of Iran. Genomic DNA was isolated from the whole blood of 102 randomly selected, healthy, unrelated Iranian individuals using salting‐out technique followed by polymerase chain reaction (PCR) amplification of the exons 2 and 3 of HLA‐G gene. For the performance of PCR–restriction fragment length polymorphism method, the PCR products were digested with several restriction enzymes and the resulted fragments were analysed using gel electrophoresis. The obtained results indicated nine alleles of HLA‐G in Iranian individuals including G*01011 (4%), G*01012 (29.86%), G*01013 (10.8%), G*01015 (1.47%), G*01017 (1.96%), G*01018 (2.45%), G*01041 (29.4%), G*01043 (1.96%) and the null allele G* 0105N (18.1%). According to this study, in the Iranian subjects the most incident alleles were G*01012 and G*01041. The results for the frequency of G*01012 showed some similarity with Caucasians (36.3%).
Delayed Selfing in an Alpine BiennialGentianopsis paludosa(Gentianaceae) in the Qinghai‐Tibetan Plateau
Authors: Duan Yuan‐Wen , Dafni Amots , Hou Qin‐Zheng , He Ya‐Ping , Liu Jian‐Quan
Published: April 2010

Delayed selfing could provide ovules with an opportunity to be fertilized as a means of “pollination assurance” before the flowers wilt. It could, thus, be regarded as an adaptation to unpredictable pollinator environments. Within the alpine biennialGentianopsis paludosa,the showy flowers and herkogamy at the early stage of a flower's life cycle may favor outcrossing. As the flower ages, anthers contact the central stigma due to the elongation of all filaments, resulting in autonomous selfing. Flower visitors are extremely rare in a high altitude population; and examination of the mating system indicates thatG. paludosais self‐pollinated under natural conditions in this population. While at the lower altitude, the bumblebee visitation rate is relatively high but possibly unreliable. Stigma receptivity is the highest on the third day of anthesis, and decreases thereafter. Pollen viability is the highest when flowers open, and gradually decreases later. Self‐pollination ofG. paludosaoccurs at the late stage of a flower's lifecycle when stigma receptivity and pollen viability have both decreased, suggesting delayed selfing and assurance of seed production. This delayed selfing could assure seed production under the constraints of pollinator scarcity, but ensure outcrossing when pollinators were available. Such a flexible pollination mechanism is highly adaptive in the alpine environment of the Qinghai‐Tibetan Plateau.
Role of Ca2+ on Growth of Brassica campestris L. and B. juncea (L.) Czern & Coss under Na+ Stress
Authors: Badr‐uz‐Zaman  , Salim M. , Asghar Rehana
Published: May 2010

Root and shoot growth of Brassica campestris L. and B. juncea increased significantly (P < 0.01) with enhanced Ca2+ treatment along with 60 mM NaCl in the root medium. The maximum fresh mass of shoot and root in B. juncea was recorded at 10 mM Ca2+ concentration. The relative growth rate of shoot of both species reached its maximum at 8 mM of Ca2+ concentration. Average rate of Ca2+ intake (ÎCa) was higher in B. juncea than B. campestris. In B. juncea, the average transport of Ca2+ to shoot increased by 19%, 38%, 119%, 125% and 169% compared with the control. Furthermore specific utilization rate of Ca2+ was higher in B. juncea than B. campestris. In B. campestris it increased by 9%, 32%, 41% and 59% at 4, 6, 8, and 10 mM of calcium in comparison to 2 mM Ca2+ treatment. At 4, 6, 8 and 10 mM of Ca2+ application, the increase in the leaf area ratio was 10, 17, 23 and 30%, respectively. In the shoot and root portions of B. campestris and B. juncea, Ca2+ had a linear relationship with potassium and sulfur, whereas it was in antagonism with sodium ion.
Neuroprotective effects of Lepidium meyenii (Maca)
Authors: Pino‐Figueroa Alejandro , Nguyen Diane , Maher Timothy J.
Published: April 2010

The neuroprotective activity of the plant Lepidium meyenii (Maca) was studied in two experimental models: in vitro and in vivo. Crayfish neurons were pretreated with vehicle or the pentane extract from Maca, subjected to H2O2, and their viability determined microscopically and chemically. A significant concentration‐neuroprotective effect relationship was demonstrated. The pentane extract was then administered intravenously to rats prior to and following middle cerebral artery occlusion. While infarct volumes were decreased for the lower dose, higher doses increased infarct volumes compared to controls. These results suggest a potential application of Maca as a neuroprotectant.
Effects of histone deacetylase inhibitor Trichostatin A on epigenetic changes and transcriptional activation of Bdnf promoter 1 by rat hippocampal neurons
Authors: Tian Feng , Marini Ann M. , Lipsky Robert H.
Published: April 2010

Histone acetylation/deacetylation is a central mechanism for regulating transcription through chromatin remodeling. The brain‐derived neurotrophic factor gene (Bdnf) is regulated in part through chromatin remodeling. An inhibitor of histone deacetylase (HDAC) activity, Trichostatin A (TSA), has differential effects on two activation dependent regions of the Bdnf gene physically linked to transcription sites for exons 1 and 4. We determined that TSA treatment of cultures of hippocampal neurons produced a stronger response at promoter 1. Transcriptional activation of promoter 1 correlated with increased occupancy of the promoter by acetylated histones (H3AcK9/K14). TSA treatment also produced a time‐dependent increase in the level of H3AcK9 and H3AcK14 protein and Hdac1 mRNA levels and HDAC1 protein levels. Taken together, these findings suggest that inhibition of HDAC activity by TSA activates Bdnf transcription and a compensatory change in HDAC1 expression in neurons. This response may reflect a genome‐wide change in gene expression.
Posttreatment with uridine and melatonin following traumatic brain injury reduces edema in various brain regions in rats
Authors: Kabadi Shruti V. , Maher Timothy J.
Published: April 2010

Traumatic brain injury (TBI) is a major health problem and a significant cause of death, disability, and neurobehavioral deficits. We investigated the effect of posttreatment with uridine and melatonin, separate and in combination, on edema in various brain regions following TBI via lateral fluid percussion. Uridine (16 and 32 mg/kg, i.p.) and melatonin (200 mg/kg, i.p.), individually reduced edema in impacted striatum versus TBI. Combination treatment of uridine (32) and melatonin (200) decreased edema in impacted as well as non‐impacted hippocampus (75.7 ± 0.5% and 75.4 ± 0.3%) and striatum (69.7 ± 1.2% and 72.6 ± 0.5%) respectively, as compared to the group that received vehicle following TBI. Combination of uridine (16) and melatonin (200) attenuated edema levels in impacted hippocampus (76.6 ± 0.4%) and striatum (71.7 ± 0.5% and 74 ± 0.3%, respectively). Combination of uridine and melatonin may be a possible treatment strategy for the damage caused by TBI and its neuroprotective potential needs to be evaluated further.
Effects of pegaptanib injections on intraocular pressure with and without anterior chamber paracentesis: A Prospective Study
Authors: Knip Maria M. , Välimäki Juha
Published: May 2010

Purpose:  To investigate how prophylactic anterior chamber paracentesis affects the intraocular pressure (IOP) after intravitreal pegaptanib injections.

Methods:  In this prospective study, 41 eyes of 41 patients receiving intravitreal pegaptanib injections were randomly assigned either to receive anterior chamber paracentesis prior to the injection (Group A, 20 patients, n = 35 injections) or not (Group B, 21 patients, n = 38 injections). IOP was measured before the pegaptanib injection (T0) and 2 min (T1), 30 min (T2) and 1 week (T3) after the injection. A four‐point scale was used to evaluate the subjective pain experienced during the procedure.

Results:  The mean IOP at T1 was 15.3 ± 7.5 mmHg in group A and 47.1 ± 24.1 mmHg in group B (difference −31.85 mmHg, 95% Confidence interval −40.13 to −23.56; p < 0.0001). In 45% of the injections without paracentesis, IOP was higher than 50 mmHg 2 min after the pegaptanib injection. No significant difference in IOP was observed at T0, T2 and T3 between the two study groups. The mean pain scores did not differ significantly (0.97 in group A versus 1.32 in group B; p = 0.08).

Conclusions:  The results suggest that prophylactic anterior chamber paracentesis helps to prevent the high postoperative IOP spike without causing patients any additional pain.
Prevalence and correlates of shoulder pain and stiffness in a population‐based study: the North West Adelaide Health Study
Authors: HILL Catherine L. , GILL Tiffany K. , SHANAHAN E.M. , TAYLOR Anne W.
Published: April 2010

Aim:  To determine the prevalence, correlates and impact of shoulder pain in a population‐based sample.

Methods:  The North West Adelaide Health Study is a representative longitudinal cohort study of people aged 18 years and over. The original sample was randomly selected and recruited by telephone interview. Overall, 3206 participants returned to the clinic during the second stage (2004–2006) and were asked to report whether they had pain, aching or stiffness on most days in either of their shoulders. Data was also collected on body mass index; shoulder range of motion, lifestyle and socioeconomic factors; the Shoulder Pain and Disability Index and the Medical Outcomes Study Short Form 36 (SF36) was used.

Results:  Overall, 22.3% of participants indicated that they had pain, aching or stiffness in either of their shoulders. Women, those aged 50 years and over, current smokers and those classified as obese were all significantly more likely to report shoulder pain. Respondents with shoulder pain scored lower on all domains of the SF36. In those with shoulder symptoms, women had more severe pain and worse shoulder function than men, and older people had worse shoulder function than younger people.

Conclusion:  Shoulder pain affects almost a quarter of people in the Australian community, with a significant detrimental impact on health‐related quality of life and physical functioning.
Pathogenesis, diagnosis and treatment of neuromyelitis optica: Changing concept of an old disease
Authors: Illes Zsolt
Published: April 2010

The concept of neuromyelitis optica (NMO) has changed considerably during the past few years. The identification of autoantibodies in the sera generated against the water channel aquaporin 4 (AQP4) has increased the specificity of diagnosis and modified guidelines. A pathogenic role of anti‐AQP4 antibodies has recently been indicated; they evoke the pathological and clinical hallmarks of the disease on transfer and cause necrosis of astrocytes expressing AQP4. The diagnosis of NMO is based on clinical, neuroimaging and serological criteria. Early therapy preventing relapses is mandatory, because neurological impairment accumulated during relapses is the main cause of permanent disability. In a number of cases defined as NMO spectrum diseases, the clinical manifestation is spatially limited. Such events of separate myelitis or relapsing/bilateral optic neuritis challenge diagnosis and might delay proper therapy. Here, current concepts of diagnosis and treatment of NMO and NMO spectrum diseases are summarized. Diagnostic and treatment decisions in different clinical situations are shown by discussion of cases. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759‐1961.2010.00011.x, 2010)
λ‐Interferons and the single nucleotide polymorphisms: A milestone to tailor‐made therapy for chronic hepatitis C
Authors: Tanaka Yasuhito , Nishida Nao , Sugiyama Masaya , Tokunaga Katsushi , Mizokami Masashi
Published: May 2010

Type III interferons (IFN) (IFN‐λ1, ‐λ2, ‐λ3/interleukin [IL]‐29, ‐28A, ‐28B) are cytokines with type I IFN‐like antiviral activities. Most cells have expressed both type I and III IFN following Toll‐like receptor (TLR) stimulation or viral infection, whereas the ability of cells to respond to IFN‐λ was restricted to a specific subset of cells. It was reported that signal transduction pathway of IFN‐λ was similar to that of IFN‐α/β although a receptor adapted by IFN‐λ were distinct from that of IFN‐α/β. However, the clinical significance and the role of each IFN‐λ were unclear. Recent genome‐wide association studies (GWAS) of the human whole genome revealed several single nucleotide polymorphism sites (SNP) strongly associated with the response to pegylated IFN‐α (PEG‐IFN) plus ribavirin (RBV) treatment in chronic hepatitis C patients. The SNP, which are located near theIL‐28Bgene of chromosome 19, were discovered simultaneously by three independent studies opening a new prospective in hepatitis C research. The present review highlights significant insights that can be derived from the GWAS approach, and summarizes current knowledge ofin vitroandin vivostudy on the role of IFN‐λ in antiviral effect.
Anatomical background and generalized detectability in tomosynthesis and cone‐beam CT
Authors: Gang G. J. , Tward D. J. , Lee J. , Siewerdsen J. H.
Published: April 2010

Purpose:

Anatomical background presents a major impediment to detectability in 2D radiography as well as 3D tomosynthesis and cone‐beam CT (CBCT). This article incorporates theoretical and experimental analysis of anatomical background “noise” in cascaded systems analysis of 2D and 3D imaging performance to yield “generalized” metrics of noise‐equivalent quanta (NEQ) and detectability index as a function of the orbital extent of the (circular arc) source‐detector orbit.

Methods:

A physical phantom was designed based on principles of fractal self‐similarity to exhibit power‐law spectral density comparable to various anatomical sites (e.g., breast and lung). Background power spectra were computed as a function of source‐detector orbital extent, including tomosynthesis and CBCT ( to 360°) under two acquisition schemes: (1) Constant angular separation between projections (variable dose) and (2) constant total number of projections (constant dose). The resulting was incorporated in the generalized NEQ, and detectability index was computed from 3D cascaded systems analysis for a variety of imaging tasks.

Results:

The phantom yielded power‐law spectra within the expected spatial frequency range, quantifying the dependence of clutter magnitude and correlation with increasing tomosynthesis angle. Incorporation of in the 3D NEQ provided a useful framework for analyzing the tradeoffs among anatomical, quantum, and electronic noise with dose and orbital extent. Distinct implications are posed for breast and chest tomosynthesis imaging system design—applications varying significantly in and , and imaging task and, therefore, in optimal selection of orbital extent, number of projections, and dose. For example, low‐frequency tasks (e.g., soft‐tissue masses or nodules) tend to benefit from larger orbital extent and more fully 3D tomographic imaging, whereas high‐frequency tasks (e.g., microcalcifications) require careful, application‐specific selection of orbital extent and number of projections to minimize negative effects of quantum and electronic noise.

Conclusions:

The complex tradeoffs among anatomical background, quantum noise, and electronic noise in projection imaging, tomosynthesis, and CBCT can be described by generalized cascaded systems analysis, providing a useful framework for system design and optimization.
A comparative study on the risk of second primary cancers in out‐of‐field organs associated with radiotherapy of localized prostate carcinoma using Monte Carlo‐based accelerator and patient models
Authors: Bednarz Bryan , Athar Basit , Xu X. George
Published: April 2010

Purpose:

A physician's decision regarding an ideal treatment approach (i.e., radiation, surgery, and/or hormonal) for prostate carcinoma is traditionally based on a variety of metrics. One of these metrics is the risk of radiation‐induced second primary cancer following radiation treatments. The aim of this study was to investigate the significance of second cancer risks in out‐of‐field organs from 3D‐CRT and IMRT treatments of prostate carcinoma compared to baseline cancer risks in these organs.

Methods:

Monte Carlo simulations were performed using a detailed medical linear accelerator model and an anatomically realistic adult male whole‐body phantom. A four‐field box treatment, a four‐field box treatment plus a six‐field boost, and a seven‐field IMRT treatment were simulated. Using BEIR VII risk models, the age‐dependent lifetime attributable risks to various organs outside the primary beam with a known predilection for cancer were calculated using organ‐averaged equivalent doses.

Results:

The four‐field box treatment had the lowest treatment‐related second primary cancer risks to organs outside the primary beam ranging from to depending on the patients age at exposure and second primary cancer site. The risks to organs outside the primary beam from the four‐field box and six‐field boost and the seven‐field IMRT were nearly equivalent. The risks from the four‐field box and six‐field boost ranged from to , and from the seven‐field IMRT ranged from to . The second cancer risks in all organs considered from each plan were below the baseline risks.

Conclusions:

The treatment‐related second cancer risks in organs outside the primary beam due to 3D‐CRT and IMRT is small. New risk assessment techniques need to be investigated to address the concern of radiation‐induced second cancers from prostate treatments, particularly focusing on risks to organs inside the primary beam.
Imaging performance of a hybrid x‐ray computed tomography‐fluorescence molecular tomography system using priors
Authors: Ale Angelique , Schulz Ralf B. , Sarantopoulos Athanasios , Ntziachristos Vasilis
Published: April 2010

Purpose:

The performance is studied of two newly introduced and previously suggested methods that incorporate priors into inversion schemes associated with data from a recently developed hybrid x‐ray computed tomography and fluorescence molecular tomography system, the latter based on CCD camera photon detection. The unique data set studied attains accurately registered data of high spatially sampled photon fields propagating through tissue along 360° projections.

Methods:

Approaches that incorporate structural prior information were included in the inverse problem by adding a penalty term to the minimization function utilized for image reconstructions. Results were compared as to their performance with simulated and experimental data from a lung inflammation animal model and against the inversions achieved when not using priors.

Results:

The importance of using priors over stand‐alone inversions is also showcased with high spatial sampling simulated and experimental data. The approach of optimal performance in resolving fluorescent biodistribution in small animals is also discussed.

Conclusions:

Inclusion of prior information from x‐ray CT data in the reconstruction of the fluorescence biodistribution leads to improved agreement between the reconstruction and validation images for both simulated and experimental data.
Absorption spectra time evolution of EBT‐2 model GAFCHROMIC™ film
Authors: Devic Slobodan , Aldelaijan Saad , Mohammed Huriyyah , Tomic Nada , Liang Li‐Heng , DeBlois Francois , Seuntjens Jan
Published: April 2010

Purpose: One of the major drawbacks of the current radiochromic film dosimetry protocols is the postirradiation waiting time. In this article, the authors study the postirradiation time evolution of the absorption spectrum of radiochromic EBT‐2 GAFCHROMIC™ film model.

Methods: Postirradiation scanning times range from 3 min to 5 days and a dose range extends from 0 to 6 Gy. The authors compare the results of absorption spectra measurements for the latest GAFCHROMIC™ EBT‐2 film model to the absorption spectra of the previous EBT GAFCHROMIC™ film model. The authors also describe a method that can establish the time error constraints on the postirradiation scanning time that will still provide an acceptable dose error for clinical applications if the protocol employing the shorter postirradiation scanning time is implemented in the clinic.

Results: The two film models experience the very same dose change in net absorbance with sensitivity of the latest EBT‐2 model GAFCHROMIC™ film being slightly lower than its predecessor. The authors show that for two postirradiation scanning times of 30 min and 24 h, the 1% dose error can be achieved if the scanning time window is less than ±5 min and ±2 h, respectively.

Conclusions: By comparing the resultant change in net absorbance between the latest EBT‐2 and previous EBT GAFCHROMIC™ film models, the authors conclude that the addition of the yellow marker dye to the sensitive layer does not affect dosimetric properties of the latest film model. The authors also describe a procedure by which one can establish an acceptable time window around chosen postirradiation scanning time protocol that would provide an acceptable dose error for practical purposes.
Dosimetric evaluation of a novel polymer gel dosimeter for proton therapy
Authors: Zeidan O. A. , Sriprisan S. I. , Lopatiuk‐Tirpak O. , Kupelian P. A. , Meeks S. L. , Hsi W. C. , Li Z. , Palta J. R. , Maryanski M. J.
Published: April 2010

Purpose:

The aim of this study is to evaluate the dosimetric performance of a newly developed proton‐sensitive polymer gel formulation for proton therapy dosimetry.

Methods:

Using passive scattered modulated and nonmodulated proton beams, the dose response of the gel was assessed. A next‐generation optical CT scanner is used as the readout mechanism of the radiation‐induced absorbance in the gel medium. Comparison of relative dose profiles in the gel to ion chamber profiles in water is performed. A simple and easily reproducible calibration protocol is established for routine gel batch calibrations. Relative stopping power ratio measurement of the gel medium was performed to ensure accurate water‐equivalent depth dose scaling. Measured dose distributions in the gel were compared to treatment planning system for benchmark irradiations and quality of agreement is assessed using clinically relevant gamma index criteria.

Results:

The dosimetric response of the gel was mapped up to 600 cGy using an electron‐based calibration technique. Excellent dosimetric agreement is observed between ion chamber data and gel. The most notable result of this work is the fact that this gel has no observed dose quenching in the Bragg peak region. Quantitative dose distribution comparisons to treatment planning system calculations show that most of the gel dose maps pass the 3%/3 mm gamma criterion.

Conclusions:

This study shows that the new proton‐sensitive gel dosimeter is capable of reproducing ion chamber dose data for modulated and nonmodulated Bragg peak beams with different clinical beam energies. The findings suggest that the gel dosimeter can be used as QA tool for millimeter range verification of proton beam deliveries in the dosimeter medium.
Dose and detectability for a cone‐beam C‐arm CT system revisited
Authors: Ganguly Arundhuti , Yoon Sungwon , Fahrig Rebecca
Published: April 2010

Purpose:

The authors had previously published measurements of the detectability of disk‐shaped contrast objects in images obtained from a C‐arm CT system. A simple approach based on Rose's criterion was used to scale the date, assuming the threshold for the smallest diameter detected should be inversely proportional to. A more detailed analysis based on recent theoretical modeling of C‐arm CT images is presented in this work.

Methods:

The signal and noise propagations in a C‐arm based CT system have been formulated by other authors using cascaded systems analysis. They established a relationship between detectability and the noise equivalent quanta. Based on this model, the authors obtained a relation between x‐ray dose and the diameter of the smallest disks detected. A closed form solution was established by assuming no rebinning and no resampling of data, with low additive noise and using a ramp filter. For the case when no such assumptions were made, a numerically calculated solution using previously reported imaging and reconstruction parameters was obtained. The detection probabilities for a range of dose and kVp values had been measured previously. These probabilities were normalized to a single dose of 56.6 mGy using the Rose‐criteria‐based relation to obtain a universal curve. Normalizations based on the new numerically calculated relationship were compared to the measured results.

Results:

The theoretical and numerical calculations have similar results and predict the detected diameter size to be inversely proportional to and , respectively. The normalized experimental curves and the associated universal plot using the new relation were not significantly different from those obtained using the Rose‐criterion‐based normalization.

Conclusions:

From numerical simulations, the authors found that the diameter of detected disks depends inversely on the cube root of the dose. For observer studies for disks larger than 4 mm, the cube root as well as square root relations appear to give similar results when used for normalization.
Adaptive Evolution ofEscherichia coliK-12 MG1655 during Growth on a Nonnative Carbon Source,l-1,2-Propanediol
Authors: Lee Dae-Hee , Palsson Bernhard Ø.
Published: May 2010

Laboratory adaptive evolution studies can provide key information to address a wide range of issues in evolutionary biology. Such studies have been limited thus far by the inability of workers to readily detect mutations in evolved microbial strains on a genome scale. This limitation has now been overcome by recently developed genome sequencing technology that allows workers to identify all accumulated mutations that appear during laboratory adaptive evolution. In this study, we evolvedEscherichia coliK-12 MG1655 with a nonnative carbon source,l-1,2-propanediol (l-1,2-PDO), for ∼700 generations. We found that (i) experimental evolution ofE. colifor ∼700 generations in 1,2-PDO-supplemented minimal medium resulted in acquisition of the ability to usel-1,2-PDO as a sole carbon and energy source so that the organism changed from an organism that did not grow at all initially to an organism that had a growth rate of 0.35 h−1; (ii) six mutations detected by whole-genome resequencing accumulated in the evolvedE. colimutant over the course of adaptive evolution onl-1,2-PDO; (iii) five of the six mutations were within coding regions, and IS5was inserted between twofucregulons; (iv) two major mutations (mutations infucOand its promoter) involved inl-1,2-PDO catabolism appeared early during adaptive evolution; and (v) multiple defined knock-in mutant strains with all of the mutations had growth rates essentially matching that of the evolved strain. These results provide insight into the genetic basis underlying microbial evolution for growth on a nonnative substrate.
Iron-Dependent Remodeling of Fungal Metabolic Pathways Associated with Ferrichrome Biosynthesis
Authors: Mercier Alexandre , Labbé Simon
Published: May 2010

The fission yeast
Schizosaccharomyces pombe
excretes and accumulates the hydroxamate-type siderophore ferrichrome. The
sib1

+

and
sib2

+

genes encode, respectively, a siderophore synthetase and an
l
-ornithine N
5
-oxygenase that participate in ferrichrome biosynthesis. In the present report, we demonstrate that
sib1

+

and
sib2

+

are repressed by the GATA-type transcriptional repressor Fep1 in response to high levels of iron. We further found that the loss of Fep1 results in increased ferrichrome production. We showed that a
sib1Δ sib2Δ
mutant strain exhibits a severe growth defect on iron-poor media. We determined that two metabolic pathways are involved in biosynthesis of ornithine, an obligatory precursor of ferrichrome. Ornithine is produced by hydrolysis of arginine by the Car1 and Car3 proteins. Although
car3

+

was constitutively expressed,
car1

+

transcription levels were repressed upon exposure to iron, with a concomitant decrease of Car1 arginase activity. Ornithine is also generated by transformation of glutamate, which itself is produced by two separate biosynthetic pathways which are transcriptionally regulated by iron in an opposite fashion. In one pathway, the glutamate dehydrogenase Gdh1, which produces glutamate from 2-ketoglutarate, was repressed under iron-replete conditions in a Fep1-dependent manner. The other pathway involves two coupled enzymes, glutamine synthetase Gln1 and Fe-S cluster-containing glutamate synthase Glt1, which were both repressed under iron-limiting conditions but were expressed under iron-replete conditions. Collectively, these results indicate that under conditions of iron deprivation, yeast remodels metabolic pathways linked to ferrichrome synthesis in order to limit iron utilization without compromising siderophore production and its ability to sequester iron from the environment.
Improvement of the Representation of Bifidobacteria in Fecal Microbiota Metagenomic Libraries by Application of thecpn60Universal Primer Cocktail
Authors: Hill Janet E. , Fernando W. M. Ursla , Zello Gordon A. , Tyler Robert T. , Dahl Wendy J. , Van Kessel Andrew G.
Published: May 2010

Actinobacteria, particularly bifidobacteria, are widely observed to be underrepresented in metagenomic studies of microbial communities. We have compared human fecal microbiota clone libraries based on 16S rRNA andcpn60PCR products. Taxonomic profiles were similar except that thecpn60libraries contained large numbers of bifidobacterial sequences.
Gene Expression in Proliferating Cells of the Dinoflagellate
Alexandrium catenella
(Dinophyceae)
Authors: Toulza Eve , Shin Mi-Sun , Blanc Guillaume , Audic Stéphane , Laabir Mohamed , Collos Yves , Claverie Jean-Michel , Grzebyk Daniel
Published: May 2010

Understanding the conditions leading to harmful algal blooms, especially those produced by toxic dinoflagellate species, is important for environmental and health safety. In addition to investigations into the environmental conditions necessary for the formation of toxic blooms, we postulate that investigating gene expression in proliferating cells is essential for understanding bloom dynamics. Expressed sequence tags were produced from cultured cells of the toxic dinoflagellate
Alexandrium catenella
sampled during the initiation phase of growth using Sanger's method and by 454 pyrosequencing. A significant proportion of identified genes (ca. 25%) represented enzymes and proteins that participate in a variety of cellular regulatory mechanisms that may characterize proliferating cells, e.g., control of the cell cycle and division, regulation of transcription, translation and posttranslational protein modifications, signaling, intracellular trafficking, and transport. All of the several genes selected for gene expression assays due to their involvement in metabolism and the cell cycle were overexpressed during exponential growth. These data will be useful for investigating the mechanisms underlying growth and toxin production in toxic
Alexandrium
species and for studying and monitoring the development of toxic blooms.
Characterization of Strains unlike
Mesorhizobium loti
That Nodulate
Lotus
spp. in Saline Soils of Granada, Spain
Authors: Lorite María J. , Muñoz Socorro , Olivares José , Soto María J. , Sanjuán Juan
Published: May 2010

Lotus
species are forage legumes with potential as pastures in low-fertility and environmentally constrained soils, owing to their high persistence and yield under those conditions. The aim of this work was the characterization of phenetic and genetic diversity of salt-tolerant bacteria able to establish efficient symbiosis with
Lotus
spp. A total of 180 isolates able to nodulate
Lotus corniculatus
and
Lotus tenuis
from two locations in Granada, Spain, were characterized. Molecular identification of the isolates was performed by repetitive extragenic palindromic PCR (REP-PCR) and 16S rRNA,
atpD
, and
recA
gene sequence analyses, showing the presence of bacteria related to different species of the genus
Mesorhizobium
:
Mesorhizobium tarimense
/
Mesorhizobium tianshanense
,
Mesorhizobium chacoense
/
Mesorhizobium albiziae
, and the recently described species,
Mesorhizobium alhagi
. No
Mesorhizobium loti
-like bacteria were found, although most isolates carried
nodC
and
nifH
symbiotic genes closely related to those of
M. loti
, considered the type species of bacteria nodulating
Lotus
, and other
Lotus
rhizobia. A significant portion of the isolates showed both high salt tolerance and good symbiotic performance with
L. corniculatus
, and many behaved like salt-dependent bacteria, showing faster growth and better symbiotic performance when media were supplemented with Na or Ca salts.
An Old Yellow Enzyme Gene Controls the Branch Point between
Aspergillus fumigatus
and
Claviceps purpurea
Ergot Alkaloid Pathways
Authors: Coyle Christine M. , Cheng Johnathan Z. , O'Connor Sarah E. , Panaccione Daniel G.
Published: May 2010

Ergot fungi in the genus
Claviceps
and several related fungal groups in the family Clavicipitaceae produce toxic ergot alkaloids. These fungi produce a variety of ergot alkaloids, including clavines as well as lysergic acid derivatives. Ergot alkaloids are also produced by the distantly related, opportunistic human pathogen
Aspergillus fumigatus
. However, this fungus produces festuclavine and fumigaclavines A, B, and C, which collectively differ from clavines of clavicipitaceous fungi in saturation of the last assembled of four rings in the ergoline ring structure. The two lineages are hypothesized to share early steps of the ergot alkaloid pathway before diverging at some point after the synthesis of the tricyclic intermediate chanoclavine-I. Disruption of
easA
, a gene predicted to encode a flavin-dependent oxidoreductase of the old yellow enzyme class, in
A. fumigatus
led to accumulation of chanoclavine-I and chanoclavine-I-aldehyde. Complementation of the
A. fumigatus easA
mutant with a wild-type allele from the same fungus restored the wild-type profile of ergot alkaloids. These data demonstrate that the product of
A. fumigatus easA
is required for incorporation of chanoclavine-I-aldehyde into more-complex ergot alkaloids, presumably by reducing the double bond conjugated to the aldehyde group, thus facilitating ring closure. Augmentation of the
A. fumigatus easA
mutant with a homologue of
easA
from
Claviceps purpurea
resulted in accumulation of ergot alkaloids typical of clavicipitaceous fungi (agroclavine, setoclavine, and its diastereoisomer isosetoclavine). These data indicate that functional differences in the
easA
-encoded old yellow enzymes of
A. fumigatus
and
C. purpurea
result in divergence of their respective ergot alkaloid pathways.
Diverse Bacteria Inhabit Living Hyphae of Phylogenetically Diverse Fungal Endophytes
Authors: Hoffman Michele T. , Arnold A. Elizabeth
Published: April 2010

Both the establishment and outcomes of plant-fungus symbioses can be influenced by abiotic factors, the interplay of fungal and plant genotypes, and additional microbes associated with fungal mycelia. Recently bacterial endosymbionts were documented in soilborne Glomeromycota and Mucoromycotina and in at least one species each of mycorrhizal Basidiomycota and Ascomycota. Here we show for the first time that phylogenetically diverse endohyphal bacteria occur in living hyphae of diverse foliar endophytes, including representatives of four classes of Ascomycota. We examined 414 isolates of endophytic fungi, isolated from photosynthetic tissues of six species of cupressaceous trees in five biogeographic provinces, for endohyphal bacteria using microscopy and molecular techniques. Viable bacteria were observed within living hyphae of endophytic Pezizomycetes, Dothideomycetes, Eurotiomycetes, and Sordariomycetes from all tree species and biotic regions surveyed. A focus on 29 fungus/bacterium associations revealed that bacterial and fungal phylogenies were incongruent with each other and with taxonomic relationships of host plants. Overall, eight families and 15 distinct genotypes of endohyphal bacteria were recovered; most were members of the
Proteobacteria
, but a small number of
Bacillaceae
also were found, including one that appears to occur as an endophyte of plants. Frequent loss of bacteria following subculturing suggests a facultative association. Our study recovered distinct lineages of endohyphal bacteria relative to previous studies, is the first to document their occurrence in foliar endophytes representing four of the most species-rich classes of fungi, and highlights for the first time their diversity and phylogenetic relationships with regard both to the endophytes they inhabit and the plants in which these endophyte-bacterium symbiota occur.