bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing Transition of Care Through the Facilitation of a Pharmacist-Managed Deep Vein Thrombosis Treatment Program
Authors: Davis Kyle A. , Miyares Marta A. , Price-Goodnow Venessa S.
Published: November 2012

A pharmacist-managed deep vein thrombosis (DVT) treatment program was put into operation at Jackson Memorial Hospital in Miami, Florida to provide appropriate transition of care to the outpatient setting for patients diagnosed with DVT. A postgraduate year 1 pharmacy practice resident partnered with a clinical pharmacist to establish and implement the DVT pilot program in the emergency department (ED). Once contacted, the pharmacy resident or the clinical pharmacist communicated with the ED physician and made recommendations regarding appropriate anticoagulation. The pharmacist met with the patient to obtain informed consent and provide counseling regarding the anticoagulants. A timely outpatient appointment at the pharmacy-managed warfarin clinic was arranged for the patient and contact information was exchanged between the patient and the pharmacist. On average, patients enrolled in the DVT program from the ED were released 18.29 hours (±7.06) following the time of arrival. Following release from the hospital, 91% of patients attended their outpatient follow-up appointment at the warfarin clinic. Since the initiation of the DVT program, 1 patient experienced a recurrent DVT and major bleed during their treatment course. Due to successful implementation of this pharmacist-managed DVT program in the ED, the services were subsequently extended to inpatients with DVT.
Embedding a Social Cause in News Features
Authors: Kim Hyo Jung , Oh Hyun Jee , Thorson Esther
Published: November 2012

The current two studies, one testing college students and the other testing adults, showed nearly identical comparative effects of news features about either a nonprofit organization alone or about that same nonprofit but sponsored by a commercial company. There were two exemplars of nonprofit and commercial company pairings, and each was presented as “localized.” That is, the nonprofit and commercial company were located in the same city as the respondents or nonlocalized. Surprisingly, there was almost no indication that the commercial sponsor damaged positive responses, but there was some indication that under the localized condition, there was more negativity toward the commercial sponsorship. The elaboration likelihood model and attribution theory provide theoretical space for understanding these effects.
Measuring science or religion? A measurement analysis of the National Science Foundation sponsored science literacy scale 2006–2010
Authors: Roos J. Micah
Published: November 2012

High scientific literacy is widely considered a public good. Methods of assessing public scientific knowledge or literacy are equally important. In an effort to measure lay scientific literacy in the United States, the National Science Foundation (NSF) science literacy scale has been a part of the last three waves of the General Social Survey. However, there has been debate over the validity of some survey items as indicators of science knowledge. While many researchers treat the NSF science scale as measuring a single dimension, previous work (Bann and Schwerin, 2004; Miller, 1998, 2004) suggests a bidimensional structure. This paper hypothesizes and tests a new measurement model for the NSF science knowledge scale and finds that two items about evolution and the big bang are more measures of a religious belief dimension termed “Young Earth Worldview” than they are measures of scientific knowledge. Results are replicated in seven samples.
Simultaneous energy harvesting and vibration control of structures with tuned mass dampers
Authors: Tang Xiudong , Zuo Lei
Published: November 2012

The vibrations of the tall buildings are serious concerns to both engineers and architects for the protection of the safety of the structure and occupant comfort. In order to mitigate the vibration, different approaches have been proposed, among which tuned mass dampers are one of the most preferable and have been widely used in practice. Instead of dissipating the vibration energy into heat waste via the viscous damping element, this article presents an approach to harvest the vibration energy from tall buildings with tuned mass dampers, by replacing the energy-dissipating element with an electromagnetic harvester. This article demonstrates that vibration mitigation and energy harvesting can be achieved simultaneously by the utilization of an electricity-generating tuned mass damper and relevant algorithms. Based on the proposed switching energy harvesting circuit, three control strategies are investigated in this article, namely, semi-active, self-powered active, and passive-matching regenerative. The functions of the energy harvesting circuit on damping force control and power regulation, as well the effectiveness of the control strategies, are illustrated by simulation. The simultaneous energy harvesting and vibration control are demonstrated, for the first time, by experiment based on a three-story building prototype with the electricity-generating tuned mass damper, which is composed of a rotational brushed direct current motor and rack–pinion mechanism.
Study of open crack in rotor shaft using changes in frequency response function phase
Authors: Rahman Abdul Ghaffar Abdul , Ismail Zubaidah , Noroozi Siamak , Chao Ong Zhi
Published: November 2012

In recent years, significant efforts have been devoted to developing non-destructive techniques for damage identification in structures. This study investigated the effects of cracks and damages on the integrity of structures, with a view to detect, quantify, and determine their extents and locations. Previous works have used parameters, such as, changes in natural frequencies and mode shapes, as detectors. However, such parameters are not sensitive enough to detect early defects. In this paper, phase measurements are sought. Measurements of the acceleration frequency responses at different points on each rotor shaft were taken using a multi-channel frequency analyzer. The damage detection schemes used in this study depended on the changes in the phase of the measured acceleration frequency response functions. To study the changes of phases, it was interpreted in phase spectrum and Nyquist plot. Nyquist plot was used as it includes both real and imaginary parts of the amplitude and this was used to study phase shifts due to the presence of crack. The changes in phase depended on crack depth and how close the crack is to that mode shape node. Meanwhile, the changes in phase of lower eigenvectors were observed clearly. Thus, first mode shape was helpful in identifying the location of the crack. The vibration behavior of the rotor shaft was shown to be very sensitive to the crack depth, crack location and mode number. It is concluded that changes in phase as a function of crack depths and locations can be effective in crack detection methodology.
Efficacy of the I Can Control Asthma and Nutrition Now (ICAN) Pilot Program on Health Outcomes in High School Students With Asthma
Authors: Kouba Joanne , Velsor-Friedrich Barbarba , Militello Lisa , Harrison Patrick R. , Becklenberg Amy , White Barb , Surya Shruti , Ahmed Avais
Published: November 2012

Asthma is the most prevalent chronic illness in childhood affecting 7 million youth. Many youth with asthma face another risk factor in obesity. Obesity, in turn, increases disorders such as asthma. Studies have recommended that asthma programs also address weight management in youth. Taking this into consideration, the I Can Control Asthma and Nutrition Now (ICAN) program is an innovative school-based program composed of (1) nutrition and weight management education, (2) asthma education, and (3) monthly reenforcement visits. This pilot study tested the initial effectiveness of the ICAN pilot program on a variety of asthma and nutrition outcomes in 25 urban minority students with asthma. Over the course of the pilot program, significant increases in asthma knowledge, asthma self-efficacy, asthma quality of life, asthma self-care, nutrition knowledge, nutrition self-efficacy, and asthma control were observed. The ICAN program has demonstrated promising preliminary results in improving nutrition and asthma health outcomes with urban minority high school students.
Renal Choriocarcinoma
Authors: Vereczkey Ildikó , Csernák Erzsébet , Olasz Judit , Küronya Zsófia , Szentirmay Zoltán , Tóth Erika
Published: November 2012

Choriocarcinoma is a rare, highly malignant trophoblastic tumor with gestational or, rarely, germ cell origin. Primary extragenital localization is extremely rare. This report describes a choriocarcinoma case clinically mimicking a primary renal cell carcinoma with multiplex pulmonary metastases. Differentiation from a sarcomatoid renal cell carcinoma with trophoblastic differentiation and identification of the exact origin, namely gestational or germ cell origin by molecular genetic methods is of great importance as it helps determine the prognosis and the most effective therapy of the disease. The Investigator Hexaplex ESS Kit was used for DNA polymorphism studies. This showed foreign alleles in the tumor DNA that confirmed the presence of paternal DNA and the gestational origin of the tumor.
Application of edible coating and acidic washing for extending the storage life of mushrooms (Agaricus bisporus)
Authors: Sedaghat Naser , Zahedi Younes
Published: November 2012

Hydrocolloid-based materials have been extensively used to coat fruit and vegetables to prolong shelf-life. The effects of different concentrations of acidic washing (acetic, ascorbic, citric and malic acids) followed by coating with gum arabic (GA), carboxymethyl cellulose and emulsified gum arabic (EGA) were evaluated on the weight loss (WL), firmness and color of mushroom. The WL of the uncoated mushrooms was significantly ( p < 0.05) greater than that of the coated ones, and the minimum WL was obtained with EGA coating. The mushrooms washed with malic and ascorbic acids showed minimum and maximum of WL, respectively. Loss in firmness of the EGA-coated mushrooms was by 21% (the minimum of loss), while loss value of the uncoated ones was by 39% (the maximum of loss). Firmness of mushrooms was not influenced by the acid type. Concentration of the acid significantly ( p < 0.05) influenced the firmness of mushrooms, and at the lowest concentration of acid (1%), the mushrooms tissue was firmest. The L* value of the mushrooms coated with GA was higher than that of others. A significant ( p < 0.05) decrease in L* value and a significant ( p < 0.05) increase in a* and b* values occurred in the mushrooms washed with acetic acid. Overall, washing with 1% citric or malic acid followed by coating with EGA resulted in minimum decrease in WL and firmness of the mushrooms.
Musical Sound Quality Impairments in Cochlear Implant (CI) Users as a Function of Limited High-Frequency Perception
Authors: Roy Alexis T. , Jiradejvong Patpong , Carver Courtney , Limb Charles J.
Published: November 2012

The purpose of this study was to (a) apply the musical sound quality assessment method, Cochlear Implant-MUltiple Stimulus with Hidden Reference and Anchor (CI-MUSHRA), to quantify musical sound quality deficits in CI (cochlear implant) users with respect to high-frequency loss, and (b) assess possible correlations between CI-MUSHRA performance and self-reported musical sound quality, as assessed by more traditional rating scales. Five versions of real-world musical stimuli were created: 8-,4-, and 2-kHz low-pass-filtered (LPF) versions with increasing high-frequency removal, a composite stimulus containing a 1-kHz LPF-filtered version and white noise (“anchor”), and an unaltered version (“hidden reference”). Using the CI-MUSHRA methodology, these versions were simultaneously presented to participants in addition to a labeled reference. Participants listened to all versions and provided ratings based on a 100-point scale that reflected perceived sound quality difference among the versions. A total of 25 musical stimuli were tested. As comparison measures, participants completed four Visual Analogue Scales (VAS) to assess musical sound quality. Overall, compared to normal hearing (NH) listeners, CI users demonstrated an impaired ability to discriminate between unaltered and altered musical stimuli with variable amounts of high-frequency information removed. Performance using CI-MUSHRA to evaluate this parameter did not correlate to measurements of musical sound quality, as assessed by VAS. This study identified high-frequency loss as one acoustic parameter contributing to overall CI-mediated musical sound quality limitations. CI-MUSHRA provided a quantitative assessment of musical sound quality. This method offers the potential to quantify CI impairments of many different acoustic parameters related to musical sound quality in the future.
Effects of Bandwidth, Compression Speed, and Gain at High Frequencies on Preferences for Amplified Music
Authors: Moore Brian C. J.
Published: November 2012

This article reviews a series of studies on the factors influencing sound quality preferences, mostly for jazz and classical music stimuli. The data were obtained using ratings of individual stimuli or using the method of paired comparisons. For normal-hearing participants, the highest ratings of sound quality were obtained when the reproduction bandwidth was wide (55 to 16000 Hz) and ripples in the frequency response were small (less than ± 5 dB). For hearing-impaired participants listening via a simulated five-channel compression hearing aid with gains set using the CAM2 fitting method, preferences for upper cutoff frequency varied across participants: Some preferred a 7.5- or 10-kHz upper cutoff frequency over a 5-kHz cutoff frequency, and some showed the opposite preference. Preferences for a higher upper cutoff frequency were associated with a shallow high-frequency slope of the audiogram. A subsequent study comparing the CAM2 and NAL-NL2 fitting methods, with gains slightly reduced for participants who were not experienced hearing aid users, showed a consistent preference for CAM2. Since the two methods differ mainly in the gain applied for frequencies above 4 kHz (CAM2 recommending higher gain than NAL-NL2), these results suggest that extending the upper cutoff frequency is beneficial. A system for reducing “overshoot” effects produced by compression gave small but significant benefits for sound quality of a percussion instrument (xylophone). For a high-input level (80 dB SPL), slow compression was preferred over fast compression.
Pilot Study of a Statewide Initiative to Enhance Depression Care Among Older Home Care Patients
Authors: Delaney Colleen , Fortinsky Richard , Mills Dana , Doonan Lorraine , Grimes Rita , Rosenberg Suzanne , Pearson Terra-Lee , Bruce Martha L.
Published: November 2012

Late-life depression is prevalent in home care. This pilot study, part of a statewide initiative to enhance depression care, evaluated the influence of a 2-hour depression screening and intervention workshop on home care professionals’ knowledge, self-efficacy, and attitudes related to depression in older home care patients. A pretest, posttest design was used to evaluate the effects of the workshop with 280 home care professionals from 7 home care agencies. Following the depression workshop, participants’ knowledge levels in evidence-based screening and care for depressed older adults was significantly increased, t(280) = 16.49, p<.001. A significant increase in confidence and attitude ratings were found (p<.001). Findings from this pilot study support broader dissemination throughout Connecticut home care agencies.
An Exploration of Recidivism and the Officer Shuffle in Police Sexual Violence
Authors: Rabe-Hemp Cara E. , Braithwaite Jeremy
Published: November 2012

By examining a decade of newspapers accounts in the Midwest, the current study explores the nature of repeat or recidivist police sexual violence (PSV) in comparison to first-time offending in the characteristics of the offenders, nature of the PSV acts, and the departments and criminal justice system response. Results show that more than 41% of PSV cases are committed by recidivist officers who averaged 4 victims each over a 3-year span of offending. The idea of the officer shuffle is explored in the context of sexual offending by police, indicating that a minority of officers move across jurisdictions maintaining police certification despite allegations of violence and misconduct. Implications explore how policy changes, such as a national reporting system for police sexual offending, would impact problem-prone PSV offending.
Intelligence-Led Policing
Authors: Darroch Steve , Mazerolle Lorraine
Published: November 2012

The capacity of police organizations to adopt innovative practices is poorly understood. This article compares and contrasts the uptake of one particular innovation: intelligence-led policing (ILP), in New Zealand, using a survey of 286 officers and 32 depth interviews to explore police attitudes and perceptions of the organizational factors influencing the adoption of ILP. We found that leadership and effective use of technology were critical to initiating and sustaining innovation. We conclude with a discussion of how police departments might best plan for and execute the adoption of new, innovative approaches to crime control.
Being business-like while pursuing a social mission: Acknowledging the inherent tensions in US nonprofit organizing
Authors: Sanders Matthew L. , McClellan John G.
Published: November 2012

Nonprofit organizations face an increasing expectation to be more business-like. Although scholars have theoretically explored this phenomenon and studied its influence in various contexts, there has been little empirical examination of the ways in which nonprofit practitioners themselves describe and make sense of their organizations and their work as business-like. Specifically, scholars have not explored the ways in which nonprofit practitioners communicatively reconcile the inherent tensions between being business-like and the pursuit of a social mission. Based on findings from an eight-month ethnographic field study of a US nonprofit organization, this article describes the sophisticated ways in which nonprofit practitioners understand, define and negotiate the need to be business-like within the nonprofit context and the central role of communication in that process. Additionally, critical assessment of these findings reveals the political qualities of talking about nonprofit organizing as being business-like, leading to potential transformative redefinitions of the business-like imperative that acknowledge rather than suppress conflicts inherent in the practice of nonprofit organizing.
The stressed subject: Lack, empowerment and liberation
Authors: Driver Michaela
Published: November 2012

The study develops a psychoanalytic perspective on the stressed subject at work. Its focus is on how this subject is continually reconstructed at the interstice of a lack of having and a lack of being. Drawing on the analysis of empirical material consisting of 52 narratives of stress, it examines how individuals construct selves by drawing on stress discourse in both alienating and liberating ways. Specifically, it examines how stress is an imaginary construction of the self and how this subjugates individuals to the power of the imaginary. It also examines how such constructions are invariably disrupted by unconscious desire and how narrating one’s stress provides opportunities to experience empowerment and liberation. Implications of this perspective for our understanding of the stressed subject are discussed.
Revisiting the inclusion-moderation thesis in the context of decentralized institutions
Authors: Buehler Michael
Published: November 2012

Institutions figure prominently in explanations for why radical parties forego their agendas and subject themselves to democratic principles when included in politics. Analyzing the Prosperous Justice Party’s political trajectory across Indonesia’s multi-level government structures between 1999 and 2009, I show that the Islamist party has gradually adopted more moderate behavior not only in national politics, where institutional incentives are conducive to moderation, but also in local politics, where institutional incentives for moderation are weaker. The absence of a strong pattern of invariant association between institutional incentives and the moderation of party behavior points to the importance of party internal mechanisms in moderation processes. Based on primary sources and in-depth interviews with party members, I argue that socio-structural factors shape a party's internal power dynamics and thereby its long-term capacity to adopt more moderate behavior.
From rupture to resonance: Uncertainty and scholarship in Fine Art research degrees
Authors: Simmons Beverley , Holbrook Allyson
Published: November 2012

This article focuses on the phenomenon of ‘rupture’ identified in student narratives of uncertainty and scholarship experienced during the course of Fine Art research degrees in two Australian universities. Rupture captures the phenomenon of severe disruption or discontinuity in existing knowledge and typically signifies epistemological rift for the students. On one level candidates become anxious and directionless; on another they adapt and resolve the challenges they face. All candidates enter research degrees ready to be challenged, but can soon become overwhelmed by what they perceive as chaos in their thinking, combined with organizational hurdles and, in the disciplinary area of fine art, an unfamiliar and newly evolving community of practice. They identify struggle as a crucial stage in their scholarly development, knowledge construction and the advancement of research and art making in their discipline area. This article advances a perspective on the roles of challenge and adaptivity in knowledge production that further informs the literature on the supervision needs of new researchers.
Obtaining surrogate consent for a minimal-risk research study in the intensive care unit setting
Authors: Larkin Mary E , Beauharnais Catherine C , Magyar Kendra , Macey Laurel , Grennan Kerry B , Boykin Emily E , Russell Steven J
Published: November 2012

Background

Obtaining surrogate consent for clinical research studies conducted in the intensive care unit (ICU) setting is logistically challenging.

Purpose

To determine whether differences in proportions consenting to trial enrollment existed among patients eligible to consent directly versus those requiring surrogate decision makers in a minimal-risk study to evaluate the accuracy of continuous glucose monitoring in the ICU setting.

Methods

Low initial enrollment rates prompted a detailed tracking of the screening and consent process. We analyzed the subset of eligible patients identified during a single year to document whether they were approached about trial enrollment, whether they consented or declined, the reasons for declining, and the method of consent (self or surrogate). The proportion of participants who consented and the reasons for declining were compared for self-consenting and surrogate-consenting participants.

Results

Of the 3041 patients screened, one-third (n = 982) were eligible; 119 of the 982 were approached regarding enrollment. Absence of a surrogate accounted for the majority of eligible patients (726; 84%) not approached. The most common reasons for refusal in the self versus surrogate groups included feeling overwhelmed (13% vs 24%), fear of discomfort (22% vs 12%), and fear of risk (7% vs 4%). Of the 57 eligible patients capable of consenting directly, 11 (19%) enrolled versus 12 (19%) of the 62 who required surrogate consent. When recruitment hours were expanded to include evening time, more eligible patients or their surrogates could be approached than during the day-shift hours alone. Consent was obtained for a larger proportion of potential participants with a history of diabetes (40%) than for those without a history of diabetes (14%).

Limitations

The findings are from a subset of the entire study sample; data were available only for participants who could be approached, who may have differed from those who could not be approached.

Conclusions

Surrogate and self-consent rates were similar. Surrogate unavailability was a major barrier to enrollment; overlap of staffing with usual visiting hours should be considered when planning trials in the ICU.
Role of SOX17 in hematopoietic development from human embryonic stem cells
Authors: Nakajima-Takagi Yaeko , Osawa Mitsujiro , Oshima Motohiko , Takagi Haruna , Miyagi Satoru , Endoh Mitsuhiro , Endo Takaho A. , Takayama Naoya , Eto Koji , Toyoda Tetsuro , Koseki Haruhiko , Nakauchi Hiromitsu , Iwama Atsushi
Published: November 2012

To search for genes that promote hematopoietic development from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), we overexpressed several known hematopoietic regulator genes in hESC/iPSC-derived CD34+CD43− endothelial cells (ECs) enriched in hemogenic endothelium (HE). Among the genes tested, only Sox17, a gene encoding a transcription factor of the SOX family, promoted cell growth and supported expansion of CD34+CD43+CD45−/low cells expressing the HE marker VE-cadherin. SOX17 was expressed at high levels in CD34+CD43− ECs compared with low levels in CD34+CD43+CD45− pre-hematopoietic progenitor cells (pre-HPCs) and CD34+CD43+CD45+ HPCs. Sox17-overexpressing cells formed semiadherent cell aggregates and generated few hematopoietic progenies. However, they retained hemogenic potential and gave rise to hematopoietic progenies on inactivation of Sox17. Global gene-expression analyses revealed that the CD34+CD43+CD45−/low cells expanded on overexpression of Sox17 are HE-like cells developmentally placed between ECs and pre-HPCs. Sox17 overexpression also reprogrammed both pre-HPCs and HPCs into HE-like cells. Genome-wide mapping of Sox17-binding sites revealed that Sox17 activates the transcription of key regulator genes for vasculogenesis, hematopoiesis, and erythrocyte differentiation directly. Depletion of SOX17 in CD34+CD43− ECs severely compromised their hemogenic activity. These findings suggest that SOX17 plays a key role in priming hemogenic potential in ECs, thereby regulating hematopoietic development from hESCs/iPSCs.
Activated protein C ameliorates Bacillus anthracis lethal toxin-induced lethal pathogenesis in rats
Authors: Kau Jyh-Hwa , Shih Yung-Luen , Lien Te-Sheng , Lee Chin-Cheng , Huang Hsin-Hsien , Lin Hung-Chi , Sun Der-Shan , Chang Hsin-Hou
Published: November 2012

Background

Lethal toxin (LT) is a major virulence factor of Bacillus anthracis. Sprague Dawley rats manifest pronounced lung edema and shock after LT treatments, resulting in high mortality. The heart failure that is induced by LT has been suggested to be a principal mechanism of lung edema and mortality in rodents. Since LT-induced death occurs more rapidly in rats than in mice, suggesting that other mechanisms in addition to the heart dysfunction may be contributed to the fast progression of LT-induced pathogenesis in rats. Coagulopathy may contribute to circulatory failure and lung injury. However, the effect of LT on coagulation-induced lung dysfunction is unclear.

Methods

To investigate the involvement of coagulopathy in LT-mediated pathogenesis, the mortality, lung histology and coagulant levels of LT-treated rats were examined. The effects of activated protein C (aPC) on LT-mediated pathogenesis were also evaluated.

Results

Fibrin depositions were detected in the lungs of LT-treated rats, indicating that coagulation was activated. Increased levels of plasma D-dimer and thrombomodulin, and the ameliorative effect of aPC further suggested that the activation of coagulation-fibrinolysis pathways plays a role in LT-mediated pathogenesis in rats. Reduced mortality was associated with decreased plasma levels of D-dimer and thrombomodulin following aPC treatments in rats with LT-mediated pathogenesis.

Conclusions

These findings suggest that the activation of coagulation in lung tissue contributes to mortality in LT-mediated pathogenesis in rats. In addition, anticoagulant aPC may help to develop a feasible therapeutic strategy.
SNF8, a member of the ESCRT-II complex, interacts with TRPC6 and enhances its channel activity
Authors: Carrasquillo Robert , Tian Dequan , Krishna Sneha , Pollak Martin R , Greka Anna , Schlöndorff Johannes
Published: November 2012

Background

Transient receptor potential canonical (TRPC) channels are non-selective cation channels involved in receptor-mediated calcium signaling in diverse cells and tissues. The canonical transient receptor potential 6 (TRPC6) has been implicated in several pathological processes, including focal segmental glomerulosclerosis (FSGS), cardiac hypertrophy, and pulmonary hypertension. The two large cytoplasmic segments of the cation channel play a critical role in the proper regulation of channel activity, and are involved in several protein-protein interactions.

Results

Here we report that SNF8, a component of the endosomal sorting complex for transport-II (ESCRT-II) complex, interacts with TRPC6. The interaction was initially observed in a yeast two-hybrid screen using the amino-terminal cytoplasmic domain of TRPC6 as bait, and confirmed by co-immunoprecipitation from eukaryotic cell extracts. The amino-terminal 107 amino acids are necessary and sufficient for the interaction. Overexpression of SNF8 enhances both wild-type and gain-of-function mutant TRPC6-mediated whole-cell currents in HEK293T cells. Furthermore, activation of NFAT-mediated transcription by gain-of-function mutants is enhanced by overexpression of SNF8, and partially inhibited by RNAi mediated knockdown of SNF8. Although the ESCRT-II complex functions in the endocytosis and lysosomal degradation of transmembrane proteins, SNF8 overexpression does not alter the amount of TRPC6 present on the cell surface.

Conclusion

SNF8 is novel binding partner of TRPC6, binding to the amino-terminal cytoplasmic domain of the channel. Modulating SNF8 expression levels alters the TRPC6 channel current and can modulate activation of NFAT-mediated transcription downstream of gain-of-function mutant TRPC6. Taken together, these results identify SNF8 as a novel regulator of TRPC6.
Transcriptional and metabolomic analysis of Ascophyllum nodosum mediated freezing tolerance in Arabidopsis thaliana
Authors: Nair Prasanth , Kandasamy Saveetha , Zhang Junzeng , Ji Xiuhong , Kirby Chris , Benkel Bernhard , Hodges Mark D , Critchley Alan T , Hiltz David , Prithiviraj Balakrishnan
Published: November 2012

Background

We have previously shown that lipophilic components (LPC) of the brown seaweed Ascophyllum nodosum (ANE) improved freezing tolerance in Arabidopsis thaliana. However, the mechanism(s) of this induced freezing stress tolerance is largely unknown. Here, we investigated LPC induced changes in the transcriptome and metabolome of A. thaliana undergoing freezing stress.

Results

Gene expression studies revealed that the accumulation of proline was mediated by an increase in the expression of the proline synthesis genes P5CS1 and P5CS2 and a marginal reduction in the expression of the proline dehydrogenase (ProDH) gene. Moreover, LPC application significantly increased the concentration of total soluble sugars in the cytosol in response to freezing stress. Arabidopsis sfr4 mutant plants, defective in the accumulation of free sugars, treated with LPC, exhibited freezing sensitivity similar to that of untreated controls. The 1H NMR metabolite profile of LPC-treated Arabidopsis plants exposed to freezing stress revealed a spectrum dominated by chemical shifts (δ) representing soluble sugars, sugar alcohols, organic acids and lipophilic components like fatty acids, as compared to control plants. Additionally, 2D NMR spectra suggested an increase in the degree of unsaturation of fatty acids in LPC treated plants under freezing stress. These results were supported by global transcriptome analysis. Transcriptome analysis revealed that LPC treatment altered the expression of 1113 genes (5%) in comparison with untreated plants. A total of 463 genes (2%) were up regulated while 650 genes (3%) were down regulated.

Conclusion

Taken together, the results of the experiments presented in this paper provide evidence to support LPC mediated freezing tolerance enhancement through a combination of the priming of plants for the increased accumulation of osmoprotectants and alteration of cellular fatty acid composition.
Genome sequence of the necrotrophic fungus Penicillium digitatum, the main postharvest pathogen of citrus
Authors: Marcet-Houben Marina , Ballester Ana-Rosa , de la Fuente Beatriz , Harries Eleonora , Marcos Jose F , González-Candelas Luis , Gabaldón Toni
Published: November 2012

Background

Penicillium digitatum is a fungal necrotroph causing a common citrus postharvest disease known as green mold. In order to gain insight into the genetic bases of its virulence mechanisms and its high degree of host-specificity, the genomes of two P. digitatum strains that differ in their antifungal resistance traits have been sequenced and compared with those of 28 other Pezizomycotina.

Results

The two sequenced genomes are highly similar, but important differences between them include the presence of a unique gene cluster in the resistant strain, and mutations previously shown to confer fungicide resistance. The two strains, which were isolated in Spain, and another isolated in China have identical mitochondrial genome sequences suggesting a recent worldwide expansion of the species. Comparison with the closely-related but non-phytopathogenic P. chrysogenum reveals a much smaller gene content in P. digitatum, consistent with a more specialized lifestyle. We show that large regions of the P. chrysogenum genome, including entire supercontigs, are absent from P. digitatum, and that this is the result of large gene family expansions rather than acquisition through horizontal gene transfer. Our analysis of the P. digitatum genome is indicative of heterothallic sexual reproduction and reveals the molecular basis for the inability of this species to assimilate nitrate or produce the metabolites patulin and penicillin. Finally, we identify the predicted secretome, which provides a first approximation to the protein repertoire used during invasive growth.

Conclusions

The complete genome of P. digitatum, the first of a phytopathogenic Penicillium species, is a valuable tool for understanding the virulence mechanisms and host-specificity of this economically important pest.
De novo characterization of the Chinese fir (Cunninghamia lanceolata) transcriptome and analysis of candidate genes involved in cellulose and lignin biosynthesis
Authors: Huang Hua-Hong , Xu Li-Li , Tong Zai-Kang , Lin Er-Pei , Liu Qing-Po , Cheng Long-Jun , Zhu Mu-Yuan
Published: November 2012

Background

Chinese fir (Cunninghamia lanceolata) is an important timber species that accounts for 20–30% of the total commercial timber production in China. However, the available genomic information of Chinese fir is limited, and this severely encumbers functional genomic analysis and molecular breeding in Chinese fir. Recently, major advances in transcriptome sequencing have provided fast and cost-effective approaches to generate large expression datasets that have proven to be powerful tools to profile the transcriptomes of non-model organisms with undetermined genomes.

Results

In this study, the transcriptomes of nine tissues from Chinese fir were analyzed using the Illumina HiSeq™ 2000 sequencing platform. Approximately 40 million paired-end reads were obtained, generating 3.62 gigabase pairs of sequencing data. These reads were assembled into 83,248 unique sequences (i.e. Unigenes) with an average length of 449 bp, amounting to 37.40 Mb. A total of 73,779 Unigenes were supported by more than 5 reads, 42,663 (57.83%) had homologs in the NCBI non-redundant and Swiss-Prot protein databases, corresponding to 27,224 unique protein entries. Of these Unigenes, 16,750 were assigned to Gene Ontology classes, and 14,877 were clustered into orthologous groups. A total of 21,689 (29.40%) were mapped to 119 pathways by BLAST comparison against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The majority of the genes encoding the enzymes in the biosynthetic pathways of cellulose and lignin were identified in the Unigene dataset by targeted searches of their annotations. And a number of candidate Chinese fir genes in the two metabolic pathways were discovered firstly. Eighteen genes related to cellulose and lignin biosynthesis were cloned for experimental validating of transcriptome data. Overall 49 Unigenes, covering different regions of these selected genes, were found by alignment. Their expression patterns in different tissues were analyzed by qRT-PCR to explore their putative functions.

Conclusions

A substantial fraction of transcript sequences was obtained from the deep sequencing of Chinese fir. The assembled Unigene dataset was used to discover candidate genes of cellulose and lignin biosynthesis. This transcriptome dataset will provide a comprehensive sequence resource for molecular genetics research of C. lanceolata.
Population and sex differences in Drosophila melanogaster brain gene expression
Authors: Catalán Ana , Hutter Stephan , Parsch John
Published: November 2012

Background

Changes in gene regulation are thought to be crucial for the adaptation of organisms to their environment. Transcriptome analyses can be used to identify candidate genes for ecological adaptation, but can be complicated by variation in gene expression between tissues, sexes, or individuals. Here we use high-throughput RNA sequencing of a singleDrosophila melanogastertissue to detect brain-specific differences in gene expression between the sexes and between two populations, one from the ancestral species range in sub-Saharan Africa and one from the recently colonized species range in Europe.

Results

Relatively few genes (<100) displayed sexually dimorphic expression in the brain, but there was an enrichment of sex-biased genes, especially male-biased genes, on the X chromosome. Over 340 genes differed in brain expression between flies from the African and European populations, with the inter-population divergence being highly correlated between males and females. The differentially expressed genes included those involved in stress response, olfaction, and detoxification. Expression differences were associated with transposable element insertions at two genes implicated in insecticide resistance (Cyp6g1andCHKov1).

Conclusions

Analysis of the brain transcriptome revealed many genes differing in expression between populations that were not detected in previous studies using whole flies. There was little evidence for sex-specific regulatory adaptation in the brain, as most expression differences between populations were observed in both males and females. The enrichment of genes with sexually dimorphic expression on the X chromosome is consistent with dosage compensation mechanisms affecting sex-biased expression in somatic tissues.
Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine
Authors: Franceschini Alessia , Nair Asha , Bele Tanja , van den Maagdenberg Arn MJM , Nistri Andrea , Fabbretti Elsa
Published: November 2012

Background

Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT) or knock-in (KI) mice expressing the Cacna1a gene mutation (R192Q) found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined.

Results

KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells) strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed.

Conclusions

Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons.
Comparison between the recovery time of alfentanil and fentanyl in balanced propofol sedation for gastrointestinal and colonoscopy: a prospective, randomized study
Authors: Ho Wai-Meng , Yen Chia-Ming , Lan Chin-Hung , Lin Chung-Yi , Yong Su-Boon , Hwang Kai-Lin , Chou Ming-Chih
Published: November 2012

Background

There is increasing interest in balanced propofol sedation (BPS) titrated to moderate sedation (conscious sedation) for endoscopic procedures. However, few controlled studies on BPS targeted to deep sedation for diagnostic endoscopy were found. Alfentanil, a rapid and short-acting synthetic analog of fentanyl, appears to offer clinically significant advantages over fentanyl during outpatient anesthesia.

It is reasonable to hypothesize that low dose of alfentanil used in BPS might also result in more rapid recovery as compared with fentanyl.

Methods

A prospective, randomized and double-blinded clinical trial of alfentanil, midazolam and propofol versus fentanyl, midazolam and propofol in 272 outpatients undergoing diagnostic esophagogastroduodenal endoscopy (EGD) and colonoscopy for health examination were enrolled. Randomization was achieved by using the computer-generated random sequence. Each combination regimen was titrated to deep sedation. The recovery time, patient satisfaction, safety and the efficacy and cost benefit between groups were compared.

Results

260 participants were analyzed, 129 in alfentanil group and 131 in fentanyl group. There is no significant difference in sex, age, body weight, BMI and ASA distribution between two groups. Also, there is no significant difference in recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between two groups. Though deep sedation was targeted, all cardiopulmonary complications were minor and transient (10.8%, 28/260). No serious adverse events including the use of flumazenil, assisted ventilation, permanent injury or death, and temporary or permanent interruption of procedure were found in both groups. However, fentanyl is New Taiwan Dollar (NT$) 103 (approximate US$ 4) cheaper than alfentanil, leading to a significant difference in total cost between two groups.

Conclusions

This randomized, double-blinded clinical trial showed that there is no significant difference in the recovery time, satisfaction score from patients, propofol consumption, awake time from sedation, and sedation-related cardiopulmonary complications between the two most common sedation regimens for EGD and colonoscopy in our hospital. However, fentanyl is NT$103 (US$ 4) cheaper than alfentanil in each case.

Trial registration

Institutional Review Board of Buddhist Tzu Chi General Hospital (IRB097-18) and Chinese Clinical Trial Registry (ChiCTR-TRC-12002575)
Community faecal carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceaein french children
Authors: Birgy André , Cohen Robert , Levy Corinne , Bidet Philippe , Courroux Céline , Benani Mohamed , Thollot Franck , Bingen Edouard
Published: November 2012

Background

The increasing incidence of community acquired infection due to Extended-Spectrum Beta-Lactamase (ESBL) -Producing Enterobacteriaceae represent a great concern because there are few therapeutic alternatives. The fecal flora of children in the community can represent a reservoir for ESBLs genes which are located on highly transmissible plasmids and the spread of these genes among bacterial pathogens is concerning. Because intestinal carriage is a key factor in the epidemiology of ESBL-producing Enterobacteriaceae, the study of the prevalence of these resistant bacteria and risk factors in young children is of particular interest.

Methods

We assessed the prevalence and risk factors of community-acquired faecal carriage of extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae in children aged from 6 to 24 months, by means of rectal swabbing in community pediatric practices. Child’s lifestyle and risk factors for carriage of resistant bacteria were noted.

Results

Among the 411 children enrolled, 4.6% carried ESBL-producing Enterobacteriaceae. CTX-M-1, CTX-M-15 and CTX-M-14 were the predominant ESBLs. The 18 E. coli isolates were genetically heterogeneous. Recent third-generation oral-cephalosporin exposure was associated with a higher risk of ESBL carriage (AOR=3.52, 95% CI[1.06-11.66], p=0.04).

Conclusions

The carriage rate of ESBL-producing Enterobacteriacae in young children in the French community setting is noteworthy, underlining the importance of this population as a reservoir. Exposure to third-generation oral cephalosporins was associated with a significant risk of ESBL carriage in our study. Because of the significant public health implications including the treatment of community-acquired urinary tract infections, the spread of organisms producing ESBLs in the community merits close monitoring with enhanced efforts for surveillance.
Adult siblings with homozygous G6PC3 mutations expand our understanding of the severe congenital neutropenia type 4 (SCN4) phenotype
Authors: Fernandez Bridget A , Green Jane S , Bursey Ford , Barrett Brendan , MacMillan Andrée , McColl Sarah , Fernandez Sara , Rahman Proton , Mahoney Krista , Pereira Sergio L , Scherer Stephen W , Boycott Kym M , Woods Michael O ,   FORGE Canada Consortium
Published: November 2012

Background

Severe congenital neutropenia type 4 (SCN4) is an autosomal recessive disorder caused by mutations in the third subunit of the enzyme glucose-6-phosphatase (G6PC3). Its core features are congenital neutropenia and a prominent venous skin pattern, and affected individuals have variable birth defects. Oculocutaneous albinism type 4 (OCA4) is caused by autosomal recessive mutations in SLC45A2.

Methods

We report a sister and brother from Newfoundland, Canada with complex phenotypes. The sister was previously reported by Cullinane et al., 2011. We performed homozygosity mapping, next generation sequencing and conventional Sanger sequencing to identify mutations that cause the phenotype in this family. We have also summarized clinical data from 49 previously reported SCN4 cases with overlapping phenotypes and interpret the medical histories of these siblings in the context of the literature.

Results

The siblings’ phenotype is due in part to a homozygous mutation in G6PC3, [c.829C > T, p.Gln277X]. Their ages are 38 and 37 years respectively and they are the oldest SCN4 patients published to date. Both presented with congenital neutropenia and later developed Crohn disease. We suggest that the latter is a previously unrecognized SCN4 manifestation and that not all affected individuals have an intellectual disability. The sister also has a homozygous mutation in SLC45A2, which explains her severe oculocutaneous hypopigmentation. Her brother carried one SLC45A2 mutation and was diagnosed with “partial OCA” in childhood.

Conclusions

This family highlights that apparently novel syndromes can in fact be caused by two known autosomal recessive disorders.