bluuebunny/crossref_metadata_2025 huggingface dataset:
A study on emissions improvement of a diesel engine equipped with a mechanical supercharger
Authors: Ishikawa N
Published: January 2012

The engine performance and emissions from a 3 l diesel engine equipped with a mechanical supercharger are investigated experimentally, and the advantages and disadvantages of the mechanical supercharger system are discussed in a comparison with performances and emissions from a corresponding 3 l diesel engine equipped with a turbocharger. An experiment conducted under steady-state conditions shows that the mechanical supercharger delivers higher boost pressures than the turbocharger under steady-state low- and middle-load operating conditions, and that the higher boost pressure allows the application of higher amounts of exhaust gas recirculation (EGR), which leads to lower NOx emissions. In a transient test, the fuel flowrate is increased instantly from a low to high rate at a constant engine speed, and T90, which is the time required for the mechanical supercharger to achieve 90 per cent of the steady-state boost pressure, is found to be considerably shortened as compared to T90 obtained in a similar test with a corresponding turbocharged engine. In addition, the Japanese JE05 test result shows that NOx emission from the 3 l engine equipped with the mechanical supercharger is lower by 50 per cent than the engine with the turbocharger at a common level of soot emissions. However, the fuel consumption rate is worsened by 5.5 per cent due to the drive loses of the supercharger. Further study for reducing the fuel penalty is necessary to apply the mechanical supercharger to practical diesel engine systems.
Stentless pediatric robotic pyeloplasty
Authors: Rodriguez Alejandro R. , Rich Mark A. , Swana Hubert S.
Published: January 2012

Objectives: Open dismembered pyeloplasty remains the standard of care for the correction of ureteropelvic junction obstruction in children. We describe our experience with a tubeless, stentless pediatric robotic pyeloplasty technique.

Methods: Between October 2008 and September 2009, 12 consecutive children underwent robotic dismembered pyeloplasty. Ureteral stents or nephrostomy tubes were not used. Operative time, hospital stay, days of Jackson–Pratt drainage, and complications were analyzed. Postoperative renal ultrasonography was obtained at 4–6 weeks after surgery.

Results: The mean patient age was 9.1 years (3.5–16). The mean operative and console times were 178 (122–250) and 129 (96–193) minutes, respectively. The Jackson–Pratt drain was removed after a mean of 1.8 days (1–4). The mean hospital stay was 2.4 days (1–4.5). There were no complications. Mean follow up was 16 months (12–24 months). All patients had complete resolution of symptoms. Hydronephrosis either completely resolved or significantly decreased in all cases. In cases without complete resolution of hydronephrosis, 99m Tc-MAG-3 diuretic renography showed preservation of renal function without obstruction.

Conclusions: Robot-assisted laparoscopic pyeloplasty can be safely performed without internal indwelling stent drainage. In children, this avoids the need for additional anesthesia and stent-related morbidity.
Meditation for Quality Improvement of Medical Encounters: Single-Intervention, Vedanta-Based Meditation Effects on Vital Signs and Mood Indices
Authors: Srinivasan Jayaram , Breheny Patrick J.
Published: January 2012

A 15-minute, single-intervention, individually guided, Vedanta-based meditation was evaluated for acute effects on vital signs and mood indices. This study included 99 volunteers. Subjects were led in meditations incorporating breathing techniques, relaxation exercises, mental imagery, and silent mantra repetition. Pre- and post-intervention vital signs and mood indices were assessed, including heart rate, respiratory rate, blood pressure, temperature, Beck Depression Inventory (BDI), and Likert scales for mood. The meditation was shown to have statistically significant effects in the immediate improvement of vital signs and mood indices. The most substantial effects occurred for blood pressure, respiratory rate, Beck Depression Inventory, depression, anxiousness, happiness, and peacefulness. Also, males experienced greater physiological benefit whereas females experienced greater psychological benefit. The results of this study could be useful in developing gender-specific meditations to improve vital signs and mood indices in acute settings.
Gain-of-function ADAMTS13 variants that are resistant to autoantibodies against ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura
Authors: Jian Cui , Xiao Juan , Gong Lingjie , Skipwith Christopher G. , Jin Sheng-Yu , Kwaan Hau C. , Zheng X. Long
Published: January 2012

Thrombotic thrombocytopenic purpura (TTP) is primarily caused by immunoglobulin G (IgG) autoantibodies against A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats, 13 (ADAMTS13). Nearly all adult idiopathic TTP patients harbor IgGs, which bind the spacer domain of ADAMTS13, a region critical for recognition and proteolysis of von Willebrand factor (VWF). We hypothesize that a modification of an exosite in the spacer domain may generate ADAMTS13 variants with reduced autoantibody binding while preserving or enhancing specific activity. Site-directed mutagenesis was used to generate a series of ADAMTS13 variants, and their functional properties were assessed. Of 24 novel ADAMTS13 variants, 2 (ie, M4, R660K/F592Y/R568K/Y661F and M5, R660K/F592Y/R568K/Y661F/Y665F) exhibited increased specific activity approximately 4- to 5-fold and approximately 10- to 12-fold cleaving a peptide VWF73 substrate and multimeric VWF, respectively. More interestingly, the gain-of-function ADAMTS13 variants were more resistant to inhibition by anti-ADAMTS13 autoantibodies from patients with acquired idiopathic TTP because of reduced binding by anti-ADAMTS13 IgGs. These results shed more light on the critical role of the exosite in the spacer domain in substrate recognition. Our findings also help understand the pathogenesis of acquired autoimmune TTP. The autoantibody-resistant ADAMTS13 variants may be further developed as a novel therapeutic for acquired TTP with inhibitors.
graphite - a Bioconductor package to convert pathway topology to gene network
Authors: Sales Gabriele , Calura Enrica , Cavalieri Duccio , Romualdi Chiara
Published: January 2012

Background

Gene set analysis is moving towards considering pathway topology as a crucial feature. Pathway elements are complex entities such as protein complexes, gene family members and chemical compounds. The conversion of pathway topology to a gene/protein networks (where nodes are a simple element like a gene/protein) is a critical and challenging task that enables topology-based gene set analyses.

Unfortunately, currently available R/Bioconductor packages provide pathway networks only from single databases. They do not propagate signals through chemical compounds and do not differentiate between complexes and gene families.

Results

Here we present , a Bioconductor package addressing these issues. Pathway information from four different databases is interpreted following specific biologically-driven rules that allow the reconstruction of gene-gene networks taking into account protein complexes, gene families and sensibly removing chemical compounds from the final graphs. The resulting networks represent a uniform resource for pathway analyses. Indeed, graphite provides easy access to three recently proposed topological methods. The package is available as part of the Bioconductor software suite.

Conclusions

is an innovative package able to gather and make easily available the contents of the four major pathway databases. In the field of topological analysis acts as a provider of biological information by reducing the pathway complexity considering the biological meaning of the pathway elements.
Gene duplication and an accelerated evolutionary rate in 11S globulin genes are associated with higher protein synthesis in dicots as compared to monocots
Authors: Li Chun , Li Meng , Dunwell Jim M , Zhang Yuan-Ming
Published: January 2012

Background

Seed storage proteins are a major source of dietary protein, and the content of such proteins determines both the quantity and quality of crop yield. Significantly, examination of the protein content in the seeds of crop plants shows a distinct difference between monocots and dicots. Thus, it is expected that there are different evolutionary patterns in the genes underlying protein synthesis in the seeds of these two groups of plants.

Results

Gene duplication, evolutionary rate and positive selection of a major gene family of seed storage proteins (the 11S globulin genes), were compared in dicots and monocots. The results, obtained from five species in each group, show more gene duplications, a higher evolutionary rate and positive selections of this gene family in dicots, which are rich in 11S globulins, but not in the monocots.

Conclusion

Our findings provide evidence to support the suggestion that gene duplication and an accelerated evolutionary rate may be associated with higher protein synthesis in dicots as compared to monocots.
Xanthomonas oryzae pv oryzae triggers immediate transcriptomic modulations in rice
Authors: Grewal Rumdeep K , Gupta Sumanti , Das Sampa
Published: January 2012

Background

Xanthomonas oryzaepvoryzaeis a devastating pathogen of rice and has been extensively studied as a model pathogen of monocotyledons. Expressional studies in both the contenders have been undertaken in past to understand the molecular mechanism underlying the compatible and incompatible interactions in the pathosystem. Continuous update on database and gene annotations necessitates constant updating on the roles of the new entities as well as reinterpretation of regulations of the previous ones. Moreover the past endeavors have addressed the middle or late defense responses of the rice plant whereas in the present study an attempt has been made to investigate the early defense responses taking place immediately after inoculation.

Results

Microarray was used to study the transcriptional modulations in eighteen days old rice seedling leaves of both susceptible and resistant genotypes one hour after inoculation. In resistant plants as compared to susceptible ones 274 genes were found to be differentially expressed. Annotations could be assigned to 112 up- and 73 down-regulated transcripts and gene interaction maps were generated for 86 transcripts. Expressional data and interaction maps were used to develop a hypothetical scheme of the molecular events taking place during early defense response. Network analysis with the differential transcripts showed up-regulation of major clusters of cell signaling proteins and transcription factors while growth and basal metabolic components were largely found to be down-regulated.

Conclusions

This study provides an understanding of the early defense signaling in rice cells. Components of the calcium and lipid signaling as well as MAPK cascade were modulated, by signals from surface receptors and cytosolic R-proteins, to arouse jasmonic acid and ethylene signaling and suppress auxin signaling through various transcription factors. Abscisic acid modulation was also evident through the expression regulation of transcription factors involved with its functions. Moreover adjustments in expression levels of components of primary as well as secondary metabolism, protein trafficking and turnout were apparent, highlighting the complexity of defense response.
Improvement of maternal Aboriginality in NSW birth data
Authors: Xu Fenglian , Sullivan Elizabeth A , Madden Richard C , Black Deborah , Jackson Pulver Lisa R
Published: January 2012

Background

The Indigenous population of Australia was estimated as 2.5% and under-reported. The aim of this study is to improve statistical ascertainment of Aboriginal women giving birth in New South Wales.

Methods

This study was based on linked birth data from the Midwives Data Collection (MDC) and the Registry of Births Deaths and Marriages (RBDM) of New South Wales (NSW). Data linkage was performed by the Centre for Health Record Linkage (CHeReL) for births in NSW for the period January 2001 to December 2005. The accuracy of maternal Aboriginal status in the MDC and RBDM was assessed by consistency, sensitivity and specificity. A new statistical variable, ASV, or Aboriginal Statistical Variable, was constructed based on Indigenous identification in both datasets. The ASV was assessed by comparing numbers and percentages of births to Aboriginal mothers with the estimates by capture-recapture analysis.

Results

Maternal Aboriginal status was under-ascertained in both the MDC and RBDM. The ASV significantly increased ascertainment of Aboriginal women giving birth and decreased the number of missing cases. The proportion of births to Aboriginal mothers in the non-registered birth group was significantly higher than in the registered group.

Conclusions

Linking birth data collections is a feasible method to improve the statistical ascertainment of Aboriginal women giving birth in NSW. This has ramifications for the ascertainment of babies of Aboriginal mothers and the targeting of appropriate services in pregnancy and early childhood.
VIP in construction: systematic development and evaluation of a multifaceted health programme aiming to improve physical activity levels and dietary patterns among construction workers
Authors: Viester Laura , Verhagen Evert ALM , Proper Karin I , van Dongen Johanna M , Bongers Paulien M , van der Beek Allard J
Published: January 2012

Background

The prevalence of both overweight and musculoskeletal disorders (MSD) in the construction industry is high. Many interventions in the occupational setting aim at the prevention and reduction of these health problems, but it is still unclear how these programmes should be designed. To determine the effectiveness of interventions on these health outcomes randomised controlled trials (RCTs) are needed. The aim of this study is to systematically develop a tailored intervention for prevention and reduction of overweight and MSD among construction workers and to describe the evaluation study regarding its (cost-)effectiveness.

Methods/Design

The Intervention Mapping (IM) protocol was applied to develop and implement a tailored programme aimed at the prevention and reduction of overweight and MSD. The (cost-) effectiveness of the intervention programme will be evaluated using an RCT. Furthermore, a process evaluation will be conducted. The research population will consist of blue collar workers of a large construction company in the Netherlands.

Intervention

The intervention programme will be aimed at improving (vigorous) physical activity levels and healthy dietary behaviour and will consist of tailored information, face-to-face and telephone counselling, training instruction (a fitness "card" to be used for exercises), and materials designed for the intervention (overview of the company health promoting facilities, waist circumference measuring tape, pedometer, BMI card, calorie guide, recipes, and knowledge test).

Main study parameters/endpoints

The intervention effect on body weight and waist circumference (primary outcome measures), as well as on lifestyle behaviour, MSD, fitness, CVD risk indicators, and work-related outcomes (i.e. productivity, sick leave) (secondary outcome measures) will be assessed.

Discussion

The development of the VIP in construction intervention led to a health programme tailored to the needs of construction workers. This programme, if proven effective, can be directly implemented.

Trial registration

Netherlands Trial Register (NTR):NTR2095
Molecular relationship between field and vaccine strain of measles virus and its persistence in Pakistan
Authors: Shah Masaud , Shams Sulaiman , Rahman Ziaur
Published: January 2012

Background

Countrywide 5.9 million, 0-11 Month old children are immunized annually by EPI (Expended Program on Immunization) against 8 vaccine preventable diseases including measles and so on. Unfortunately the basic immunity centers are not uniform throughout the country. Each center provides services to about 27000 people which is inadequate. The purpose of this study was to explore the development of EPI Pakistan in terms of immunization of measles.

Methods

Nucleotide sequences were analyzed by neighbor joining method (bootstrap test) using Bio- edit and MEGA-5 software to find evolutionary relationship between wild type measles strain and vaccine strain (Edmonston strain) used in Pakistan. For statistical analysis of data SPSS 16 was used.

Results

Currently 1.3 vaccinators are working at each U C (union council) which according to national EPI policy should be at least 2. About 56% and 44% children of age 0-11 months did not received second dose of measles in the last two years respectively. Out of these 4231 cases which were reported last year, 1370 have received their first dose of measles vaccine.

Conclusion

Seroconversion and seroprevalence study of the vaccine and field strain of measles virus is needed to confirm whether its failure is due to service unavailability or vaccine in-affectivity.
Facile synthesis of uniform large-sized InP nanocrystal quantum dots using tris(tert-butyldimethylsilyl)phosphine
Authors: Joung SoMyoung , Yoon Sungwoo , Han Chang-Soo , Kim Youngjo , Jeong Sohee
Published: January 2012

Colloidal III-V semiconductor nanocrystal quantum dots [NQDs] have attracted interest because they have reduced toxicity compared with II-VI compounds. However, the study and application of III-V semiconductor nanocrystals are limited by difficulties in their synthesis. In particular, it is difficult to control nucleation because the molecular bonds in III-V semiconductors are highly covalent. A synthetic approach of InP NQDs was presented using newly synthesized organometallic phosphorus [P] precursors with different functional moieties while preserving the P-Si bond. Introducing bulky side chains in our study improved the stability while facilitating InP formation with strong confinement at a readily low temperature regime (210°C to 300°C). Further shell coating with ZnS resulted in highly luminescent core-shell materials. The design and synthesis of P precursors for high-quality InP NQDs were conducted for the first time, and we were able to control the nucleation by varying the reactivity of P precursors, therefore achieving uniform large-sized InP NQDs. This opens the way for the large-scale production of high-quality Cd-free nanocrystal quantum dots.
Neuroprotective function for ramified microglia in hippocampal excitotoxicity
Authors: Vinet Jonathan , van Weering Hilmar RJ , Heinrich Annette , Kälin Roland E , Wegner Anja , Brouwer Nieske , Heppner Frank L , van Rooijen Nico , Boddeke Hendrikus WGM , Biber Knut
Published: January 2012

Background

Most of the known functions of microglia, including neurotoxic and neuroprotective properties, are attributed to morphologically-activated microglia. Resting, ramified microglia are suggested to primarily monitor their environment including synapses. Here, we show an active protective role of ramified microglia in excitotoxicity-induced neurodegeneration.

Methods

Mouse organotypic hippocampal slice cultures were treated with N-methyl-D-aspartic acid (NMDA) to induce excitotoxic neuronal cell death. This procedure was performed in slices containing resting microglia or slices that were chemically or genetically depleted of their endogenous microglia.

Results

Treatment of mouse organotypic hippocampal slice cultures with 10-50 μM N-methyl-D-aspartic acid (NMDA) induced region-specific excitotoxic neuronal cell death with CA1 neurons being most vulnerable, whereas CA3 and DG neurons were affected less. Ablation of ramified microglia severely enhanced NMDA-induced neuronal cell death in the CA3 and DG region rendering them almost as sensitive as CA1 neurons. Replenishment of microglia-free slices with microglia restored the original resistance of CA3 and DG neurons towards NMDA.

Conclusions

Our data strongly suggest that ramified microglia not only screen their microenvironment but additionally protect hippocampal neurons under pathological conditions. Morphological activation of ramified microglia is thus not required to influence neuronal survival.
Gaming control using a wearable and wireless EEG-based brain-computer interface device with novel dry foam-based sensors
Authors: Liao Lun-De , Chen Chi-Yu , Wang I-Jan , Chen Sheng-Fu , Li Shih-Yu , Chen Bo-Wei , Chang Jyh-Yeong , Lin Chin-Teng
Published: January 2012

A brain-computer interface (BCI) is a communication system that can help users interact with the outside environment by translating brain signals into machine commands. The use of electroencephalographic (EEG) signals has become the most common approach for a BCI because of their usability and strong reliability. Many EEG-based BCI devices have been developed with traditional wet- or micro-electro-mechanical-system (MEMS)-type EEG sensors. However, those traditional sensors have uncomfortable disadvantage and require conductive gel and skin preparation on the part of the user. Therefore, acquiring the EEG signals in a comfortable and convenient manner is an important factor that should be incorporated into a novel BCI device. In the present study, a wearable, wireless and portable EEG-based BCI device with dry foam-based EEG sensors was developed and was demonstrated using a gaming control application. The dry EEG sensors operated without conductive gel; however, they were able to provide good conductivity and were able to acquire EEG signals effectively by adapting to irregular skin surfaces and by maintaining proper skin-sensor impedance on the forehead site. We have also demonstrated a real-time cognitive stage detection application of gaming control using the proposed portable device. The results of the present study indicate that using this portable EEG-based BCI device to conveniently and effectively control the outside world provides an approach for researching rehabilitation engineering.
Medical ethnobotany of the Albanian Alps in Kosovo
Authors: Mustafa Behxhet , Hajdari Avni , Krasniqi Feriz , Hoxha Esat , Ademi Hatixhe , Quave Cassandra L , Pieroni Andrea
Published: January 2012

Background

Ethnobotanical studies are crucial in South-Eastern Europe for fostering local development and also for investigating the dynamics of Traditional Environmental Knowledge (TEK) related to plants in one of the most crucial European hotspots for biocultural diversity. The current medico-ethnobotanical survey was conducted in rural alpine communities in Kosovo. The aims of the study were twofold: 1) to document the state of TEK of medicinal plants in these communities; 2) to compare these findings with that of similar field studies previously conducted among local populations inhabiting the Montenegrin and Albanian side of the same Alpine range.

Methods

Field research was conducted in 36 villages on the Kosovar side of the Albanian Alps. Snowball sampling techniques were used to recruit 91 elderly informants (≥ 50 years-old) for participation in semi-structured interviews and structured surveys regarding the use of the local flora for medicinal and food purposes. Standard ethnobotanical methods were employed and prior informed consent was obtained for all study participants.

Results and Conclusion

The uses of 98 plants species belonging to 39 families were recorded; the most quoted botanical families were Rosaceae, Asteraceae, and Lamiaceae. Mainly decoctions and infusions were quoted as folk medicinal preparations and the most common uses referred to gastrointestinal and respiratory disorders, as well as illnesses of the uro-genital system. Among the most uncommon medicinal taxa quoted by the informants, Carduus nutansL.,Echinops bannaticusRochel ex Schrad., andOrlaya grandifloraHoffm. may merit phytochemical and phytopharmacological investigations.

Comparison of the data with other ethnobotanical field studies recently conducted on the Albanian and Montenegrin sides of the same Alps has shown a remarkable link between the medical ethnobotany of Montenegrin and Kosovar side of the Albanian Alps. Moreover, folk uses of the most quoted wild medicinal taxa recorded in Kosovo often include those recorded both in Albania and in Montenegro, thus suggesting a hybrid character of the Kosovar local plant knowledge. This may be also explained with the fact that Montenegro and Kosovo, despite their differences in the ethnic composition, have shared a common history during the last Century.
ATP-dependent chromatin remodeling in the DNA-damage response
Authors: Lans Hannes , Marteijn Jurgen A , Vermeulen Wim
Published: January 2012

The integrity of DNA is continuously challenged by metabolism-derived and environmental genotoxic agents that cause a variety of DNA lesions, including base alterations and breaks. DNA damage interferes with vital processes such as transcription and replication, and if not repaired properly, can ultimately lead to premature aging and cancer. Multiple DNA pathways signaling for DNA repair and DNA damage collectively safeguard the integrity of DNA. Chromatin plays a pivotal role in regulating DNA-associated processes, and is itself subject to regulation by the DNA-damage response. Chromatin influences access to DNA, and often serves as a docking or signaling site for repair and signaling proteins. Its structure can be adapted by post-translational histone modifications and nucleosome remodeling, catalyzed by the activity of ATP-dependent chromatin-remodeling complexes. In recent years, accumulating evidence has suggested that ATP-dependent chromatin-remodeling complexes play important, although poorly characterized, roles in facilitating the effectiveness of the DNA-damage response. In this review, we summarize the current knowledge on the involvement of ATP-dependent chromatin remodeling in three major DNA repair pathways: nucleotide excision repair, homologous recombination, and non-homologous end-joining. This shows that a surprisingly large number of different remodeling complexes display pleiotropic functions during different stages of the DNA-damage response. Moreover, several complexes seem to have multiple functions, and are implicated in various mechanistically distinct repair pathways.
Extracellular nicotinamide phosphoribosyltransferase (NAMPT/visfatin) inhibits insulin-like growth factor-1 signaling and proteoglycan synthesis in human articular chondrocytes
Authors: Yammani Raghunatha R , Loeser Richard F
Published: January 2012

Introduction

Obesity is one of the major risk factors for the development of osteoarthritis (OA). Although the mechanical factors appear to be critical, recent studies have suggested a role for adipokines in cartilage degradation. Chondrocytes from osteoarthritic cartilage respond poorly to insulin-like growth factor-1 (IGF-1) and the molecular mechanism(s) involved is not clearly understood. The purpose of the present study was to determine the role of extracellular nicotinamide phosphoribosyltransferase (eNAMPT/visfatin), a newly described adipokine, in regulating IGF-1 function in chondrocytes.

Methods

Human articular chondrocytes isolated from normal ankle cartilage were pretreated with eNAMPT (0.1 to 5.0 μg/ml) overnight followed by stimulation with IGF-1 (50 ng/ml) for 24 hours, and proteoglycan synthesis was measured by [35S]sulfate incorporation. Chondrocytes were pretreated with eNAMPT overnight followed by IGF-1 for 10 minutes, and the cell lysates were immunoblotted for various signaling proteins that are activated by IGF-1 using phosphospecific antibodies. In addition, chondrocytes were pretreated with mitogen-activated protein kinase kinase inhibitor (U0126) prior to stimulation with eNAMPT and IGF-1.

Results

Pretreatment of chondrocytes with eNAMPT inhibited IGF-1-stimulated proteoglycan synthesis in a dose-dependent manner. Treatment of chondrocytes with eNAMPT inhibited IGF-1-induced phosphorylation of signaling molecules, including insulin receptor substrate-1 and AKT. Interestingly, pretreatment of chondrocytes with eNAMPT did not inhibit IGF-1-mediated phosphorylation of the IGF-1 receptor; however, it stimulated a sustained phosphorylation of the extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway. Inhibition of the ERK/MAPK signaling pathway restored IGF-1-mediated insulin receptor substrate-1 and AKT phosphorylation.

Conclusions

Our study demonstrates that eNAMPT/visfatin inhibits IGF-1 function in articular chondrocytes by activating the ERK/MAPK pathway independent of the IGF-1 receptor. Since eNAMPT levels are elevated in the synovial fluid of OA patients, the signaling pathway activated by eNAMPT could contribute to IGF-1 resistance in OA.
SpliceGrapher: detecting patterns of alternative splicing from RNA-Seq data in the context of gene models and EST data
Authors: Rogers Mark F , Thomas Julie , Reddy Anireddy SN , Ben-Hur Asa
Published: January 2012

We propose a method for predicting splice graphs that enhances curated gene models using evidence from RNA-Seq and EST alignments. Results obtained using RNA-Seq experiments in Arabidopsis thaliana show that predictions made by our SpliceGrapher method are more consistent with current gene models than predictions made by TAU and Cufflinks. Furthermore, analysis of plant and human data indicates that the machine learning approach used by SpliceGrapher is useful for discriminating between real and spurious splice sites, and can improve the reliability of detection of alternative splicing. SpliceGrapher is available for download at http://SpliceGrapher.sf.net.
Editorial: T cell memory, bone marrow, and aging: the good news
Authors: Effros Rita B
Published: January 2012

Discussion on the accumulating evidence that bone marrow in old age is not simply the place where immune cells are generated but the where certain memory cells selectively return to provide a set of distinct immune functions during old age.
Donor-derived, tolerogenic dendritic cells suppress immune rejection in the indirect allosensitization-dominant setting of corneal transplantation
Authors: Hattori Takaaki , Saban Daniel R , Emami-naeini Parisa , Chauhan Sunil K , Funaki Toshinari , Ueno Hiroki , Dana Reza
Published: January 2012

Significant interest has been focused on the use of ex vivo-manipulated DCs to optimally induce transplant tolerance and promote allograft survival. Although it is understood that donor-derived, tolerogenic DCs suppress the direct pathway of allosensitization, whether such DCs can similarly suppress the indirect pathway remains unclear. We therefore used the murine model of corneal transplantation to address this, as these allografts are rejected in an indirect pathway-dominant manner. Interestingly, recipients administered with donor bone marrow-derived DCregs, generated via culturing with GM-CSF, IL-10, and TGF-β1, significantly prolonged survival of corneal allografts. Correspondingly, these recipients demonstrated a potent reduction in the frequency of indirectly allosensitized T cells, as determined by ELISPOT. Examination of DCregs relative to mDCs or iDCs showed a resistance to up-regulation of MHC-II and costimulatory molecules, as well as an impaired capacity to stimulate MLRs. In vivo, DCreg administration in corneal-allografted recipients led to inhibition of CD4+IFN-γ+ T cell frequencies and an associated increase in Foxp3 expression in the Treg compartment. We conclude that donor-derived, tolerogenic DCs significantly suppress the indirect pathway, thereby identifying a novel regulatory mechanism for these cells in transplantation.
Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis
Authors: Brunet Salut , Labopin Myriam , Esteve Jordi , Cornelissen Jan , Socié Gerard , Iori Anna P. , Verdonck Leo F. , Volin Liisa , Gratwohl Alois , Sierra Jorge , Mohty Mohamad , Rocha Vanderson
Published: January 2012

Purpose

Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain.

Patients and Methods

We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning.

Results

Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 × 109/L; P < .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; ± standard deviation) was higher (30% ± 5% v 16% ± 5%; P = .006) and leukemia-free survival (LFS) lower (58% ± 5% v 71% ± 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR.

Conclusion

FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.
Phase I Trial of Anti-CS1 Monoclonal Antibody Elotuzumab in Combination With Bortezomib in the Treatment of Relapsed/Refractory Multiple Myeloma
Authors: Jakubowiak Andrzej J. , Benson Don M. , Bensinger William , Siegel David S.D. , Zimmerman Todd M. , Mohrbacher Ann , Richardson Paul G. , Afar Daniel E.H. , Singhal Anil K. , Anderson Kenneth C.
Published: January 2012

Purpose

To evaluate the maximum-tolerated dose (MTD), safety, and efficacy of elotuzumab in combination with bortezomib in patients with relapsed or relapsed and refractory multiple myeloma (MM).

Patients and Methods

Elotuzumab (2.5, 5.0, 10, or 20 mg/kg intravenously [IV]) and bortezomib (1.3 mg/m2 IV) were administered on days 1 and 11 and days 1, 4, 8, and 11, respectively, in 21-day cycles by using a 3 + 3 dose-escalation design. Patients with stable disease or better after four cycles could continue treatment until disease progression or unexpected toxicity. Responses were assessed during each cycle by using European Group for Blood and Marrow Transplantation (EBMT) criteria.

Results

Twenty-eight patients with a median of two prior therapies were enrolled; three patients each received 2.5, 5.0, and 10 mg/kg of elotuzumab and 19 received 20 mg/kg (six during dose escalation and 13 during an expansion phase). No dose-limiting toxicities were observed during cycle 1 of the dose-escalation phase, and the MTD was not reached up to the maximum planned dose of 20 mg/kg. The most frequent grade 3 to 4 adverse events (AEs) were lymphopenia (25%) and fatigue (14%). Two elotuzumab-related serious AEs of chest pain and gastroenteritis occurred in one patient. An objective response (a partial response or better) was observed in 13 (48%) of 27 evaluable patients and in two (67%) of three patients refractory to bortezomib. Median time to progression was 9.46 months.

Conclusion

The combination of elotuzumab and bortezomib was generally well-tolerated and showed encouraging activity in patients with relapsed/refractory MM.
Age-Related Prognostic Impact of Different Types of DNMT3A Mutations in Adults With Primary Cytogenetically Normal Acute Myeloid Leukemia
Authors: Marcucci Guido , Metzeler Klaus H. , Schwind Sebastian , Becker Heiko , Maharry Kati , Mrózek Krzysztof , Radmacher Michael D. , Kohlschmidt Jessica , Nicolet Deedra , Whitman Susan P. , Wu Yue-Zhong , Powell Bayard L. , Carter Thomas H. , Kolitz Jonathan E. , Wetzler Meir , Carroll Andrew J. , Baer Maria R. , Moore Joseph O. , Caligiuri Michael A. , Larson Richard A. , Bloomfield Clara D.
Published: January 2012

Purpose

To determine the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene- and microRNA-expression signatures in primary cytogenetically normal acute myeloid leukemia (CN-AML).

Patients and Methods

Four hundred fifteen previously untreated adults were analyzed for DNMT3A mutations and established prognostic gene mutations and expression markers. Gene- and microRNA-expression profiles were derived using microarrays.

Results

Younger (< 60 years; n = 181) and older (≥ 60 years; n = 234) patients had similar frequencies of DNMT3A mutations (35.3% v 33.3%). Missense mutations affecting arginine codon 882 (R882-DNMT3A) were more common (n = 92; 62%) than those affecting other codons (non–R882-DNMT3A). DNMT3A-mutated patients did not differ regarding complete remission rate, but had shorter disease-free survival (DFS; P = .03) and, by trend, overall survival (OS; P = .07) than DNMT3A–wild-type patients. In multivariable analyses, DNMT3A mutations remained associated with shorter DFS (P = .01), but not with shorter OS. When analyzed separately, the two DNMT3A mutation types had different significance by age group. Younger patients with non–R882-DNMT3A mutations had shorter DFS (P = .002) and OS (P = .02), whereas older patients with R882-DNMT3A mutations had shorter DFS (P = .005) and OS (P = .002) after adjustment for other clinical and molecular prognosticators. Gene- and microRNA-expression signatures did not accurately predict DNMT3A mutational status.

Conclusion

DNMT3A mutations are frequent in CN-AML, and their clinical significance seems to be age dependent. DNMT3A-R882 mutations are associated with adverse prognosis in older patients, and non–R882-DNMT3A mutations are associated with adverse prognosis in younger patients. Low accuracy of gene- and microRNA-expression signatures in predicting DNMT3A mutation status suggested that the role of these mutations in AML remains to be elucidated.
Ndel1-derived peptides modulate bidirectional transport of injected beads in the squid giant axon
Authors: Segal Michal , Soifer Ilya , Petzold Heike , Howard Jonathon , Elbaum Michael , Reiner Orly
Published: January 2012

Bidirectional transport is a key issue in cellular biology. It requires coordination between microtubule-associated molecular motors that work in opposing directions. The major retrograde and anterograde motors involved in bidirectional transport are cytoplasmic dynein and conventional kinesin, respectively. It is clear that failures in molecular motor activity bear severe consequences, especially in the nervous system. Neuronal migration may be impaired during brain development, and impaired molecular motor activity in the adult is one of the hallmarks of neurodegenerative diseases leading to neuronal cell death. The mechanisms that regulate or coordinate kinesin and dynein activity to generate bidirectional transport of the same cargo are of utmost importance. We examined how Ndel1, a cytoplasmic dynein binding protein, may regulate non-vesicular bidirectional transport. Soluble Ndel1 protein, Ndel1-derived peptides or control proteins were mixed with fluorescent beads, injected into the squid giant axon, and the bead movements were recorded using time-lapse microscopy. Automated tracking allowed for extraction and unbiased analysis of a large data set. Beads moved in both directions with a clear bias to the anterograde direction. Velocities were distributed over a broad range and were typically slower than those associated with fast vesicle transport. Ironically, the main effect of Ndel1 and its derived peptides was an enhancement of anterograde motion. We propose that they may function primarily by inhibition of dynein-dependent resistance, which suggests that both dynein and kinesin motors may remain engaged with microtubules during bidirectional transport.
Avian SERPINB11 gene: a marker for ovarian endometrioid cancer in chickens
Authors: Lim Whasun , Kim Ji-Hye , Ahn Suzie E , Jeong Wooyoung , Kim Jinyoung , Bazer Fuller W , Han Jae Yong , Song Gwonhwa
Published: January 2012

As serine and cysteine proteinase inhibitors, serpins, such as SERPINB5, cause ovarian, colorectal and pancreatic adenocarcinomas. We identified SERPINB11 as a novel estrogen-induced gene in chickens during oviduct development. The chicken is a unique animal model for research on human ovarian cancer, because it spontaneously develops epithelial cell-derived ovarian cancer as in women. Therefore, this study investigated the expression pattern, CpG methylation status, and miRNA regulation of the SERPINB11 gene in normal and cancerous ovaries from chickens. Our results indicate that SERPINB11 is most abundant in the glandular epithelium of endometrioid adenocarcinoma of cancerous, but not normal, ovaries of hens. In addition, bisulfite sequencing revealed that about 30% of −110 CpG sites are methylated in ovarian cancer cells, whereas −110 CpG sites are demethylated in normal ovarian cells. Next, we determined whether miR-1582 influences SERPINB11 expression via its 3′UTR and found that it does not directly target the 3′UTR of SERPINB11 mRNA. Therefore, it is unlikely that post-transcriptional regulation influences SERPINB11 expression in the chicken ovary. On the other hand, in human ovarian cancer cells such as OVCAR-3, SKOV-3 and PA-1 cells, immunoreactive SERPINB11 protein was predominant in the cytoplasm and had a similar expression pattern to that in chicken ovarian cancer cells. Collectively, these results suggest that SERPINB11 is a biomarker for chicken ovarian endometrioid carcinoma that could be used for diagnosis and monitoring effects of therapies for the disease in women.
A 5′-terminal phosphate is required for stable ternary complex formation and translation of leaderless mRNA in Escherichia coli
Authors: Giliberti Jacqueline , O'Donnell Sean , Van Etten William J. , Janssen Gary R.
Published: January 2012

The bacteriophage λ's cI mRNA was utilized to examine the importance of the 5′-terminal phosphate on expression of leadered and leaderless mRNA in Escherichia coli. A hammerhead ribozyme was used to produce leadered and leaderless mRNAs, in vivo and in vitro, that contain a 5′-hydroxyl. Although these mRNAs may not occur naturally in the bacterial cell, they allow for the study of the importance of the 5′-phosphorylation state in ribosome binding and translation of leadered and leaderless mRNAs. Analyses with mRNAs containing either a 5′-phosphate or a 5′-hydroxyl indicate that leaderless cI mRNA requires a 5′-phosphate for stable ribosome binding in vitro as well as expression in vivo. Ribosome-binding assays show that 30S subunits and 70S ribosomes do not bind as strongly to 5′-hydroxyl as they do to 5′-phosphate containing leaderless mRNA and the tRNA-dependent ternary complex is less stable. Additionally, filter-binding assays revealed that the 70S ternary complex formed with a leaderless mRNA containing a 5′-hydroxyl has a dissociation rate (koff) that is 4.5-fold higher compared with the complex formed with a 5′-phosphate leaderless mRNA. Fusion to a lacZ reporter gene revealed that leaderless cI mRNA expression with a 5′-hydroxyl was >100-fold lower than the equivalent mRNA with a 5′-phosphate. These data indicate that a 5′-phosphate is an important feature of leaderless mRNA for stable ribosome binding and expression.
Widespread RNA 3′-end oligouridylation in mammals
Authors: Choi Yun S. , Patena Weronika , Leavitt Andrew D. , McManus Michael T.
Published: January 2012

Nontemplated 3′-end oligouridylation of RNA occurs in many species, including humans. Unlike the familiar phenomenon of polyadenylation, nontemplated addition of uridines to RNA is poorly characterized in higher eukaryotes. Recent studies have reported nontemplated 3′-end oligouridylation of small RNAs and mRNAs. Oligouridylation is involved in many aspects of microRNA biology from biogenesis to turnover of the mature species, and it may also mark long mRNAs for degradation by promoting decapping of the protective 5′-cap structure. To determine the prevalence of oligouridylation in higher eukaryotes, we used next-generation sequencing technology to deeply examine the population of small RNAs in human cells. Our data revealed widespread nontemplated nucleotide addition to the 3′ ends of many classes of RNA, with short stretches of uridine being the most frequently added nucleotide.
Characterization of Attenuated Total Reflection Infrared Spectral Intensity Variations of Immature and Mature Cotton Fibers by Two-Dimensional Correlation Analysis
Authors: Liu Yongliang , Thibodeaux Devron , Gamble Gary
Published: January 2012

Two-dimensional (2D) correlation analysis was applied to characterize the attenuated total reflection (ATR) spectral intensity fluctuations of immature and mature cotton fibers. Prior to 2D analysis, the spectra were leveled to zero at the peak intensity of 1800 cm−1 and then were normalized at the peak intensity of 660 cm−1 to subjectively correct the variations resulting from ATR sampling. Next, normalized spectra were subjected to principal component analysis (PCA), and two clusters of immature and mature fibers were confirmed on the basis of the first principal component (PC1) negative and positive scores, respectively. The normalized spectra clearly demonstrated the intensity increase or decrease of the bands ascribed to different C–O confirmations of primary alcohols in the 1050–950 cm−1 region, which was not apparent from raw ATR spectra. The PC1 increasing-induced 2D correlation analysis revealed remarkable differences between the immature and mature fibers. Of interest were that: (1) Both intensity increase of two bands at 968 and 956 cm−1 and the shifting of 968 cm−1 in immature fibers to 956 cm−1 in mature fibers, together with the intensity decreasing and shifting of the 1048 and 1042 cm−1 bands, are the characteristics of cotton fiber development and maturation. (2) Intensities of most bands in the 1800–1200 cm−1 region decreased with the fiber growth, suggesting they are from either noncellulosic components or CH and OH fractions in amorphous celluloses. (3) The reverse sequence of intensity variations of the bands in the 1100–1000 cm−1 and 1000–900 cm−1 region of asynchronous spectra indicated a different mechanism of compositional and structural changes in developing cotton fibers at different growth stages.
In Situ High-Pressure and High-Temperature Experiments on n-Heptane
Authors: Qiao Erwei , Zheng Haifei , Long Changxing
Published: January 2012

The Raman spectroscopy of n-heptane was investigated in a moissanite anvil cell at ambient temperatures and a diamond anvil cell under pressures of up to ∼2000 MPa and at temperature range from 298 to 588 K. The results show that at room temperature the vibration modes, assigned to the symmetric and antisymmetric stretching of CH3 and CH2 stretching, shifted to higher frequency according to quasi-linearity with increasing pressure, and a liquid–solid phase transition occurred at near 1150 MPa. The high-temperature solidus line of n-heptane follows a quadratic function of P = 0.00737 T 2 + 5.27977 T – 1195.76556. Upon phase change, fitting the experimental data obtained in the temperature range of 183∼412 K to the Clausius–Clapeyron equation allows one to define the thermodynamic parameters of n-heptane of d P/d T = 0.01474 T + 5.27977.