bluuebunny/crossref_metadata_2025 huggingface dataset:
WegenerNet: A Pioneering High-Resolution Network for Monitoring Weather and Climate
Authors: Kirchengast Gottfried , Kabas Thomas , Leuprecht Armin , Bichler Christoph , Truhetz Heimo
Published: July 2013

The Feldbach region in southeast Austria, characteristic for experiencing a rich variety of weather and climate patterns, has been selected as the focus area for a pioneering weather and climate observation network at very high resolution: The WegenerNet comprises 151 meteorological stations measuring temperature, precipitation, and other parameters, in a tightly spaced grid within an area of about 20 km × 15 km centered near the city of Feldbach (46.93°N, 15.90°E). With its stations about every 2 km2, each with 5-min time sampling, the network provides regular measurements since January 2007, after a pilot phase, until 2010, meanwhile in an operational manner. Quality-controlled station time series and gridded field data (spacing 200 m × 200 m) are available in near–real time (data latency less than 1–2 h) for visualization and download via a data portal (www.wegenernet.org; detailed information is available via www.wegcenter.at/wegenernet).

This paper introduces the WegenerNet from its design and setup via its processing system and data products to showing example results. The latter include extreme weather event examples, climate variability over the 5-yr period from 2007 to 2011, and an example of calibration support to coupled climate–hydrology modeling. The network is set to serve as a long-term monitoring and validation facility for weather and climate research and applications. Uses include validation of nonhydrostatic models operated at 1-km-scale resolution and of statistical downscaling techniques (in particular for precipitation), validation of weather radar and satellite data, study of orography–climate relationships, and many others.
Insulin-like growth factor-1 receptor (IGF1R) as a novel target in chronic lymphocytic leukemia
Authors: Yaktapour Niuscha , Übelhart Rudolf , Schüler Julia , Aumann Konrad , Dierks Christine , Burger Meike , Pfeifer Dietmar , Jumaa Hassan , Veelken Hendrik , Brummer Tilman , Zirlik Katja
Published: July 2013

Key Points

We provide a functional analysis of IGF1R expression in primary human B-CLL. Sorafenib reduces IGF1R expression in B-CLL.
Implications of continued response after autologous stem cell transplantation for multiple myeloma
Authors: Gonsalves Wilson I. , Gertz Morie A. , Dispenzieri Angela , Lacy Martha Q. , Lin Yi , Singh Preet P. , Gupta Vinay , Hayman Suzanne R. , Buadi Francis K. , Dingli David , Kapoor Prashant , McCurdy Arleigh R. , Kumar Shaji K.
Published: July 2013

Key Points

A continued monoclonal protein response after ASCT in the absence of further therapy is prognostic in MM patients.
De novo sequencing and transcriptome analysis of the desert shrub, Ammopiptanthus mongolicus, during cold acclimation using Illumina/Solexa
Authors: Pang Tao , Ye Chu-Yu , Xia Xinli , Yin Weilun
Published: July 2013

Background

Ammopiptanthus mongolicus(Maxim. ex Kom.) Cheng f., an evergreen broadleaf legume shrub, is distributed in Mid-Asia where the temperature can be as low as −30°C during the winter. AlthoughA. mongolicusis an ideal model to study the plant response to cold stress, insufficient genomic resources for this species are available in public databases. To identify genes involved in cold acclimation (a phenomenon experienced by plants after low temperature stress), a high-throughput sequencing technology was applied.

Results

We sequenced cold-treated and control (untreated) samples ofA. mongolicus, and obtained 65,075,656 and 67,287,120 high quality reads, respectively. Afterde novoassembly and quantitative assessment, 82795 all-unigenes were finally generated with an average length of 816 bp. We then obtained functional annotations by aligning all-unigenes with public protein databases including NR, SwissProt, KEGG and COG. Differentially expressed genes (DEGs) were investigated using the RPKM method. Overall, 9309 up-regulated genes and 23419 down-regulated genes were identified. To increase our understanding of these DEGs, we performed GO enrichment and metabolic pathway enrichment analyses. Based on these results, a series of candidate genes involved in cold responsive pathways were selected and discussed. Moreover, we analyzed transcription factors, and found 720 of them are differentially expressed. Finally, 20 of the candidate genes that were up-regulated and known to be associated with cold stress were examined using qRT-PCR.

Conclusions

In this study, we identified a large set of cDNA unigenes fromA. mongolicus. This is the first transcriptome sequencing of this non-model species under cold-acclimation using Illumina/Solexa, a next-generation sequencing technology. We sequenced cold-treated and control (untreated) samples ofA. mongolicusand obtained large numbers of unigenes annotated to public databases. Studies of differentially expressed genes involved in cold-related metabolic pathways and transcription factors facilitate the discovery of cold-resistance genes.
Molecular characterization of hepatitis B virus in liver disease patients and asymptomatic carriers of the virus in Sudan
Authors: Yousif Mukhlid , Mudawi Hatim , Bakhiet Sahar , Glebe Dieter , Kramvis Anna
Published: July 2013

Background

Hepatitis B virus is hyperendemic in Sudan. Our aim was to molecularly characterize hepatitis B virus from Sudanese individuals, with and without liver disease, because genotypes play an important role in clinical manifestation and treatment management.

Methods

Ninety-nine patients - 30 asymptomatic, 42 cirrhotic, 15 with hepatocellular carcinoma, 7 with acute hepatitis and 5 with chronic hepatitis- were enrolled. Sequencing of surface and basic core promoter/precore regions and complete genome were performed.

Results

The mean ± standard deviation, age was 45.7±14.8 years and the male to female ratio 77:22. The median (interquartile range) of hepatitis B virus DNA and alanine aminotransferase levels were 2.8 (2.2-4.2) log IU/ml and 30 (19–49) IU/L, respectively. Using three genotyping methods, 81/99 (82%) could be genotyped. Forty eight percent of the 99 patients were infected with genotype D and 24% with genotype E, 2% with putative D/E recombinants and 7% with genotype A. Patients infected with genotype E had higher frequency of hepatitis B e antigen-positivity and higher viral loads compared to patients infected with genotype D. Basic core promoter/precore region mutations, including the G1896A in 37% of HBeAg-negative individuals, could account for hepatitis B e antigen-negativity. Pre-S deletion mutants were found in genotypes D and E. Three isolates had the vaccine escape mutant sM133T.

Conclusion

Sudanese hepatitis B virus carriers were mainly infected with genotypes D or E, with patients infected with genotype E having higher HBeAg-positivity and higher viral loads. This is the first study to molecularly characterize hepatitis B virus from liver disease patients in Sudan.
Trends in sugar supply and consumption in Australia: is there an Australian Paradox?
Authors: Rikkers Wavne , Lawrence David , Hafekost Katherine , Mitrou Francis , Zubrick Stephen R
Published: July 2013

Background

High consumption of refined carbohydrate, in particular sugar, has been identified as a possible contributory factor in greater risk of excess weight gain. In spite of data limitations, one recent paper suggests that Australian sugar consumption has decreased over the same time period that obesity has increased, a so called ‘Australian Paradox’. Given the significant public health focus on nutrition, we aimed to estimate Australian sugar supply and consumption over recent decades, to determine whether these data could be used to make any conclusions about sugar’s role in obesity.

Methods

Foods high in sugar were identified. Data relating to sugar supply and consumption from 1988 to 2010 were obtained from multiple sources. Using these data we attempted to generate a time series estimate of sugar in Australia’s food supply.

Results

Australia produces and exports sugar from sugar cane and the sugar in imported foods has received little attention. We were unable to produce a reliable and robust estimate of total sugars in the Australian diet due to data limitations and a lack of current data sources. However, available Import data showed large increases in the volume and value of imported sweetened products between 1988 and 2010 to over 30 grams of sugar per person per day. Value estimates of local production of sweetened products also show substantial increases in this period.

Conclusion

The Australian Paradox assertion is based on incomplete data, as it excludes sugar contained in imported processed foods, which have increased markedly. A major Australian public health target is to improve the quality of the food supply, and actions have been set in terms of achieving broader environmental changes. However, evaluation of progress is hampered by lack of high quality data relating to supply and consumption. We recommend the regular collection of comprehensive food supply statistics, which include both local production and imports. This would provide an inexpensive addition to survey data and could assist in monitoring sugar consumption trends in food supply. Such information would also help inform public health policy.
Bee venom effects on ubiquitin proteasome system in hSOD1G85R-expressing NSC34 motor neuron cells
Authors: Kim Seon Hwy , Jung So Young , Lee Kang-Woo , Lee Sun Hwa , Cai MuDan , Choi Sun-Mi , Yang Eun Jin
Published: July 2013

Background

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from a progressive loss of motor neurons. Familial ALS (fALS) is caused by missense mutations in Cu, Zn-superoxide dismutase 1 (SOD1) that frequently result in the accumulation of mutant protein aggregates that are associated with impairments in the ubiquitin-proteasome system (UPS). UPS impairment has been implicated in many neurological disorders. Bee venom (BV) extracted from honey bees has been used as a traditional medicine for treating inflammatory diseases and has been shown to attenuate the neuroinflammatory events that occur in a symptomatic ALS animal model.

Methods

NSC34 cells were transiently transfected with a WT or G85R hSOD1-GFP construct for 24 hrs and then stimulated with 2.5 μg/ml BV for 24 hrs. To determine whether a SOD1 mutation affects UPS function in NSC34 cells, we examined proteasome activity and performed western blotting and immunofluorescence using specific antibodies, such as anti-misfolded SOD1, anti-ubiquitin, anti-GRP78, anti-LC3, and anti-ISG15 antibodies.

Results

We found that GFP-hSOD1G85R overexpression induced SOD1 inclusions and reduced proteasome activity compared with the overexpression of GFP alone in NSC34 motor neuronal cells. In addition, we also observed that BV treatment restored proteasome activity and reduced the accumulation of ubiquitinated and misfolded SOD1 in GFP-hSOD1G85R-overexpressing NSC34 motor neuronal cells. However, BV treatment did not activate the autophagic pathway in these cells.

Conclusion

Our findings suggest that BV may rescue the impairment of the UPS in ALS models.
Late developing mammary tumors and hyperplasia induced by a low-oncogenic variant of mouse mammary tumor virus (MMTV) express genes identical to those induced by canonical MMTV
Authors: Bruno Robert D , Rosenfield Sonia M , Smith Gilbert H
Published: July 2013

Background

The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes.

Findings

We confirmed the presence of active virus in Mtv-1/NIV infected tissues and using quantitative reverse transcription PCR (qRT-PCR) found that Mtv-1/NIV induced neoplasms (tumors and hyperplasia) commonly expressed the core CIS genes Wnt1, Wnt10b, Rspo2, Fgf3.

Conclusions

These results underscore the importance of core CIS gene expression in the early events leading to MMTV-induced mammary tumor initiation regardless of the viral variant.
Prognostic analysis of esophageal cancer in elderly patients: metastatic lymph node ratio versus 2010 AJCC classification by lymph nodes
Authors: Feng Ji-Feng , Huang Ying , Chen Lu , Zhao Qiang
Published: July 2013

Background

Recent studies have proposed a new prognostic factor (metastatic lymph node ratio, or MLNR) for patients with esophageal cancer (EC). However, to the best of our knowledge, there have been no studies conducted to date regarding MLNR in elderly patients. The aim of this study was to determine the prognostic value of MLNR staging compared with the 2010 American Joint Committee on Cancer (AJCC) N staging in elderly patients with EC.

Methods

From January 2001 to December 2009, a retrospective analysis of 132 consecutive patients older than 70 years of age with esophageal squamous cell carcinoma (ESCC) was conducted. Prognostic factors for disease-specific survival were analyzed. Receiver operating characteristic curves were also plotted to verify the accuracy of MLNR staging and N staging for survival prediction.

Results

The disease-specific survival rates of N0, N1, N2 and N3 patients according to the AJCC Cancer Staging Manual Seventh Edition N staging were 65.5%, 42.9%, 22.2% and 0, respectively (N0 vs N1, P = 0.017; N1 vsN2, = 0.050; N2 vs N3, P < 0.001). The disease-specific survival rates of MLNR0, MLNR1, MLNR2 and MLNR3 patients were 65.5%, 45.0%, 21.1% and 0, respectively (MLNR0 vsMLNR1, P = 0.026; MLNR1 vs MLNR2, P = 0.033; MLNR2 vs MLNR3, P = 0.015). The areas under the curve were 0.731 for the 2010 AJCC N staging and 0.737 for the MLNR staging.

Conclusion

MLNR is an independent predictor of survival in elderly patients with ESCC. MLNR staging predicts survival after EC similarly to the 2010 AJCC N classifications and should be considered an alternative to current N staging.
Downlink interference minimization in cooperative cognitive LTE-femtocell networks
Authors: Tao Xin , Zhao Zhifeng , Li Rongpeng , Palicot Jacques , Zhang Honggang
Published: July 2013

Femtocell is considered to be one of the most promising solutions for future indoor wireless communication. Due to the scarcity of spectrum resources, femtocells need to share the spectrum with other networks, which will inevitably bring in severe interference. Therefore, minimizing the cross-tier and co-tier interference while maintaining high system throughput or spectrum efficiency is one of main challenges before largely deploying femtocell networks. In order to effectively mitigate the interference, cognitive radio-enabled techniques can play a key role by providing more secondary spectrum access opportunities, especially in dense femtocells deployment scenarios. Supported by cognitive radio functionality, femtocell users can access and share these licensed spectra including the frequency bands of both macrocells and other licensed systems (e.g., TV white spaces) as long as not causing harmful interference to the coexisting licensed systems. In this paper, based on cognitive sensing, we propose a joint channel assignment and power allocation scheme, aiming to minimize the aggregate interference from multiple femtocells to the licensed users while satisfying the constraints of each femtocell’s capacity and power budget. It is believed that the cooperation among multiple femtocells is quite helpful in mitigating the interference considering the mobility of the licensed users. Specifically, Hungarian algorithm is involved in our scheme to address the co-tier femtocell interference issue. In order to illustrate our scheme more explicitly, we come up with the concepts of Physical Cluster and Virtual Cluster and synthetically apply the related algorithms to reduce the interference step by step. Finally, the performances of employed algorithms are evaluated and analyzed. Numerical results have validated that the proposed scheme is viable and effective in managing the femtocell interference.
Intraperitoneal Administration of AAV9-shRNA Inhibits Target Gene Expression in the Dorsal Root Ganglia of Neonatal Mice
Authors: Machida Akira , Kuwahara Hiroya , Mayra Azat , Kubodera Takayuki , Hirai Takashi , Sunaga Fumiko , Tajiri Mio , Hirai Yukihiko , Shimada Takashi , Mizusawa Hidehiro , Yokota Takanori
Published: July 2013

Background

There is considerable interest in inducing RNA interference (RNAi) in neurons to study gene function and identify new targets for disease intervention. Although short interfering RNAs (siRNAs) have been used to silence genes in neurons, in vivo delivery of RNAi remains a major challenge, especially by systemic administration. We have developed a highly efficient method for in vivo gene silencing in dorsal root ganglia (DRG) by using short hairpin RNA-expressing single-stranded adeno-associated virus 9 (ssAAV9-shRNA).

Results

Intraperitoneal administration of ssAAV9-shRNA to neonatal mice resulted in highly effective and specific silencing of a target gene in DRG. We observed an approximately 80% reduction in target mRNA in the DRG, and 74.7% suppression of the protein was confirmed by Western blot analysis. There were no major side effects, and the suppression effect lasted for more than three months after the injection of ssAAV9-shRNA.

Conclusions

Although we previously showed substantial inhibition of target gene expression in DRG via intrathecal ssAAV9-shRNA administration, here we succeeded in inhibiting target gene expression in DRG neurons via intraperitoneal injection of ssAAV9-shRNA. AAV9-mediated delivery of shRNA will pave the way for creating animal models for investigating the molecular biology of the mechanisms of pain and sensory ganglionopathies.
Electroacupuncture to treat painful diabetic neuropathy: study protocol for a three-armed, randomized, controlled pilot trial
Authors: Lee Seunghoon , Kim Joo-Hee , Shin Kyung-Min , Kim Jung-Eun , Kim Tae-Hun , Kang Kyung-Won , Lee Minhee , Jung So-Young , Shin Mi-Suk , Kim Ae-Ran , Park Hyo-Ju , Hong Kwon-Eui , Choi Sun-Mi
Published: July 2013

Background

The purpose of this study is to conduct a basic analysis of the effectiveness and safety of electroacupuncture in the treatment of painful diabetic neuropathy (PDN) as compared to placebo and usual care and to evaluate the feasibility of large-scale clinical research.

Methods/design

This study is a protocol for a three-armed, randomized, patient-assessor-blinded (to the type of treatment), controlled pilot trial. Forty-five participants with a ≥ six month history of PDN and a mean weekly pain score of ≥ 4 on the 11-point Pain Intensity Numerical Rating Scale (PI-NRS) will be assigned to the electroacupuncture group (n = 15), sham group (n = 15) or usual care group (n = 15). The participants assigned to the electroacupuncture group will receive electroacupuncture (remaining for 30 minutes with a mixed current of 2 Hz/120 Hz and 80% of the bearable intensity) at 12 standard acupuncture points (bilateral ST36, GB39, SP9, SP6, LR3 and GB41) twice per week for eight weeks (a total of 16 sessions) as well as the usual care. The participants in the sham group will receive sham electroacupuncture (no electrical current will be passed to the needle, but the light will be seen, and the sound of the pulse generator will be heard by the participants) at non-acupuncture points as well as the usual care. The participants in the usual care group will not receive electroacupuncture treatment during the study period and will receive only the usual care. The follow-up will be in the 5th, 9th and 17th weeks after random allocation. The PI-NRS score assessed at the ninth week will be the primary outcome measurement used in this study. The Short-Form McGill Pain Questionnaire (SF-MPQ), a sleep disturbance score (11-point Likert scale), the Short-Form 36v2 Health Survey (SF-36), the Beck Depression Inventory (BDI) and the Patient Global Impression of Change (PGIC) will be used as outcome variables to evaluate the effectiveness of the acupuncture. Safety will be assessed at every visit.

Discussion

The result of this trial will provide a basis for the effectiveness and safety of electroacupuncture for PDN.

Trial registration

Clinical Research information Service. Unique identifier:KCT0000466.
Phenotypic and genotypic identification of streptococci and related bacteria isolated from bovine intramammary infections
Authors: Raemy Andreas , Meylan Mireille , Casati Simona , Gaia Valeria , Berchtold Beat , Boss Renate , Wyder Anja , Graber Hans U
Published: July 2013

Background

Streptococcus spp. and other Gram-positive, catalase-negative cocci (PNC) form a large group of microorganisms which can be found in the milk of cows with intramammary infection. The most frequently observed PNC mastitis pathogens (major pathogens) are Streptococcus uberis, Strep. dysgalactiae, and Strep. agalactiae. The remaining PNC include a few minor pathogens and a large nonpathogenic group. Improved methods are needed for the accurate identification and differentiation of PNC.

A total of 151 PNC were collected from cows with intramammary infection and conclusively identified by 16S rRNA sequencing as reference method. Nine phenotypic microbiological tests (alpha-hemolysis, CAMP reaction, esculin hydrolysis, growth on kanamycin esculin azide agar and on sodium chloride agar, inulin fermentation, hippurate hydrolysis, leucine aminopeptidase and pyrrolidonyl peptidase activity), multiplex PCR for the three major pathogens (target genes for Strep. uberis, Strep. dysgalactiae and Strep. agalactiae: pauA, 16S rRNA, and sklA3, respectively), and mass spectroscopy using the matrix-assisted laser desorption ionization-time of flight (MALDI-TOF MS) were evaluated for the diagnosis and discrimination of the three clinically most relevant PNC.

Results

The probability that a strain of Strep. uberis, Strep. dysgalactiae and Strep. agalactiae was correctly identified by combining the results of the 9 phenotypic tests was 92%, 90%, and 100%, respectively. Applying the multiplex PCR, all strains of the three major pathogens were correctly identified and no false positive results occurred. Correct identification was observed for all strains of Strep. uberis and Strep. agalactiae using MALDI-TOF MS. In the case of Strep. dysgalactiae, some variability was observed at the subspecies level, but all strains were allocated to one single cluster.

Conclusions

The results of the present study show that reliable identification of the clinically most relevant PNC (Strep. uberis, Strep. agalactiae and Strep. dysgalactiae) can be obtained by use of a combination of colony morphology, hemolysis type and catalase reaction, and a multiplex PCR with specific primers restricted to these 3 pathogens. The MALDI-TOF MS is a fast method that shows promising results, although identification of Strep. dysgalactiae at the subspecies level is not yet satisfactory.
Effectiveness of green tea mouthwash in postoperative pain control following surgical removal of impacted third molars: double blind randomized clinical trial
Authors: Eshghpour Majid , Mortazavi Hamed , Mohammadzadeh Rezaei Naser , Nejat AmirHossein
Published: July 2013

Background

Pain following surgical removal of impacted molars has remained an important concern among practitioners. Various protocols have been proposed to reduce postoperative pain. However, each one has special side effects and limitations. As green tea possesses anti-inflammatory and antibacterial properties, the aim of the current study was to evaluate the effectiveness of green tea mouthwash in controlling postoperative pain.

Materials and methods

In a study with split-mouth and double blind design, 44 patients in need of bilateral removal of impacted third molars underwent randomized surgical extraction; following one surgery patients rinsed with a green tea mouthwash from the first to seventh postoperative day and after other extraction rinsed with placebo mouthwash in the same duration. Both patients and surgeon were blinded to the type of mouthwash. The predictor variable was type of mouthwash and primary outcome variable was postoperative pain measured by visual analogue scale (VAS) during first week after surgery. In addition, number of analgesics patients used after surgery recorded. To measure the effect of green tea mouthwash, repeated measures test with confidence interval of 95% was performed.

Results

Total of 43 patients with mean age of 24 years underwent total of 86 surgeries. VAS value had no statistically difference prior rinsing among groups (P-value > 0.05). However, the mean value of VAS following rinsing with green tea was statistically lower than placebo in postoperative days of 3–7 (P-value < 0.05). In addition, while rinsing with green tea, patients took significantly lower number of analgesics after surgery (P-value < 0.05). No side effects reported.

Conclusion

Green tea mouthwash could be an appropriate and safe choice to control postoperative pain after third molar surgery.
Health education interventions to raise awareness of rheumatic fever: a systematic review protocol
Authors: Ramsey Laura Susan , Watkins Lauren , Engel Mark Emmanuel
Published: July 2013

Background

There is a significant global health burden associated with acute rheumatic fever (ARF) and rheumatic heart disease (RHD), especially in developing countries. ARF and RHD most often strike children and young adults living in impoverished settings, where unhygienic conditions and lack of awareness and knowledge of streptococcal infection progression are common. Secondary prophylactic measures have been recommended in the past, but primary prevention measures have been gaining more attention from researchers frustrated by the perpetual prevalence of ARF and RHD in developing countries. Health education aims to empower people to take responsibility for their own well-being by gaining control over the underlying factors that influence health. We therefore conducted a review of the current best evidence for the use of health education interventions to increase awareness and knowledge of streptococcal pharyngitis and ARF.

Methods and design

This article describes the protocol for a systematic review of the effectiveness of health education interventions aimed at increasing awareness and knowledge of the symptoms, causes and consequences of streptococcal pharyngitis, rheumatic fever and/or rheumatic heart disease. Studies will be selected in which the effect of an intervention is compared with either a pre-intervention or a control, targeting all possible audience types. Primary and secondary outcomes of interest are pre-specified. Randomized controlled trials, quasi-randomized trials, controlled before–after studies and controlled clinical trials will be considered. We will search several bibliographic databases (for example, PubMed, EMBASE, World Health Organization Library databases, Google Scholar) and search sources for gray literature. We will meta-analyze included studies. We will conduct subgroup analyses according to intervention subtypes: printed versus audiovisual and mass media versus training workshops.

Discussion

This review will provide evidence for the effectiveness of educational components in health promotion interventions in raising public awareness in regard to the symptoms, causes and consequences of streptococcal pharyngitis, ARF and/or RHD. Our results may provide guidance in the development of future intervention studies and programs.
Treatment of Methicillin-resistant Staphylococcus aureus experimental Osteomyelitis with bone-targeted Vancomycin
Authors: Karau Melissa J , Schmidt-Malan Suzannah M , Greenwood-Quaintance Kerryl E , Mandrekar Jayawant , Cai Jian , Pierce William M , Merten Kevyn , Patel Robin
Published: July 2013

Introduction

Methicillin-resistant S. aureus (MRSA) is a common cause of bone and joint infection. BT2-peg2-vancomycin is an investigational bone-targeted formulation of vancomycin which we hypothesized would have increased antimicrobial activity compared to conventional vancomycin in a chronic experimental MRSA osteomyelitis model.

Methods

We tested bone affinity using an hydroxyapatite (HA) binding assay, assessed the in vitro antimicrobial susceptibility of 30 MRSA isolates, and compared vancomycin and BT2-peg2-vancomycin in a rat experimental osteomyelitis model.

Results

Vancomycin did not bind to hydroxyapatite (HA binding index = 0), whereas BT2-peg2-vancomycin showed appreciable binding (HA binding index = 57). The MIC50 was 1 μg/ml and the MIC90 was 2 μg/ml for both vancomycin and BT2-peg2-vancomycin. The MBC90 was 16 and 4 μg/ml for vancomycin and BT2-peg2-vancomycin, respectively. Treatment with 50 mg/kg of vancomycin every 12 hours (median, 4.73 log10 cfu/g), 63.85 mg/kg (equivalent to 50 mg/kg vancomycin) of BT2-peg2-vancomycin every 12 hours (median, 3.93 log10 cfu/g) or 63.85 mg/kg of BT2-peg2-vancomycin once per week (median, 5.00 log10 cfu/g) was more active than no treatment (median, 5.22 log10 cfu/g) (P =0.0481). Treatment with 63.85 mg/kg of BT2-peg2-vancomycin every 12 hours was more active than all other treatment regimens evaluated (P≤0.0150), but was associated with high plasma BT2-peg2-vancomycin levels, decreased animal weight, increased kidney size, creatinine and BUN, and leukocytosis with tubulointerstitial nephritis.

Conclusion

With optimization of pharmacokinetic parameters to prevent toxicity, BT2-peg2-vancomycin may be useful in the treatment of MRSA osteomyelitis.
A compact, in vivo screen of all 6-mers reveals drivers of tissue-specific expression and guides synthetic regulatory element design
Authors: Smith Robin P , Riesenfeld Samantha J , Holloway Alisha K , Li Qiang , Murphy Karl K , Feliciano Natalie M , Orecchia Lorenzo , Oksenberg Nir , Pollard Katherine S , Ahituv Nadav
Published: July 2013

Background

Large-scale annotation efforts have improved our ability to coarsely predict regulatory elements throughout vertebrate genomes. However, it is unclear how complex spatiotemporal patterns of gene expression driven by these elements emerge from the activity of short, transcription factor binding sequences.

Results

We describe a comprehensive promoter extension assay in which the regulatory potential of all 6 base-pair (bp) sequences was tested in the context of a minimal promoter. To enable this large-scale screen, we developed algorithms that use a reverse-complement aware decomposition of the de Bruijn graph to design a library of DNA oligomers incorporating every 6-bp sequence exactly once. Our library multiplexes all 4,096 unique 6-mers into 184 double-stranded 15-bp oligomers, which is sufficiently compact for in vivo testing. We injected each multiplexed construct into zebrafish embryos and scored GFP expression in 15 tissues at two developmental time points. Twenty-seven constructs produced consistent expression patterns, with the majority doing so in only one tissue. Functional sequences are enriched near biologically relevant genes, match motifs for developmental transcription factors, and are required for enhancer activity. By concatenating tissue-specific functional sequences, we generated completely synthetic enhancers for the notochord, epidermis, spinal cord, forebrain and otic lateral line, and show that short regulatory sequences do not always function modularly.

Conclusions

This work introduces a unique in vivo catalog of short, functional regulatory sequences and demonstrates several important principles of regulatory element organization. Furthermore, we provide resources for designing compact, reverse-complement aware k-mer libraries.
Ensuring That Guidelines Help Reduce Patient Harm
Authors: Pronovost Peter J.
Published: July 2013

The most important determinant of whether a hospital dramatically reduces bloodstream infections is whether clinicians believe these infections are their problem and they can solve the problem. If clinicians believe, results will follow.
Lymph Node Evaluation for Colon Cancer in an Era of Quality Guidelines: Who Improves?
Authors: Parsons Helen M. , Begun James W. , Kuntz Karen M. , Tuttle Todd M. , McGovern Patricia M. , Virnig Beth A.
Published: July 2013

The implementation of lymph node evaluation guidelines has been accepted gradually into practice but has been adopted more quickly in the treatment of higher risk patients.
Reading the Past on the Mountainsides of Colombia: Mid-Nineteenth-Century Patriotic Geology, Archaeology, and Historiography
Authors: Appelbaum Nancy P.
Published: July 2013

The mid-nineteenth-century Colombian Chorographic Commission drew on geology, archaeology, and history to project a patriotic past onto the Andean landscape of the young republic then known as New Granada. This geographic expedition, led initially by Agustín Codazzi and Manuel Ancízar, explored and mapped the country from 1850 to 1859. For the commissioners and their associates among the creole elite, the history of past epochs was “written” on the mountainsides for scientific travelers such as themselves to “read.” They portrayed disparate historical and prehistoric events as overlapping and interrelated. The commission’s texts and images linked a catastrophic interpretation of geologic origins to historia patria (patriotic history). The commissioners merged the wars of conquest and independence into a two-act drama enacted on a singular territorial stage. Their reading of geologic, archaeological, and historical evidence endowed the impoverished young Republic of New Granada with a grandiose territory, a great precursor civilization, and a legacy of patriotic resistance to imperialism. Their interpretations, however, would prove controversial. During the second half of the nineteenth century, debates over geology, archaeology, and history reflected conflicting Liberal and Conservative political projects. Moreover, the midcentury intellectuals failed to incorporate contemporaneous indigenous and poor citizens into an imagined national community based on the ideal of a shared historical memory embedded on a readable landscape.
Huarpe Archives in the Argentine Desert: Indigenous Claims and State Construction in Nineteenth-Century Mendoza
Authors: Escolar Diego
Published: July 2013

The narrative of indigenous extinction and the construction of a “white” Argentina entailed an ethnogeographic imaginary by which the territories of the former Spanish colonies were inhabited since the nineteenth century by gauchos or eventually peasants. The population classified as indigenous, in this view, was projected outside the central areas controlled by the nation-state, beyond the frontiers of the Pampas, Patagonia, and the Chaco. Historical writing accepted and contributed to the formation of this image by characterizing the political mobilization of gauchos or peasants (especially in their bellicosity as montoneras — irregular militia units) as a natural reflection of the projects of elites, factions, patrons, or parties. That historiography dismissed as irrelevant any demands stemming from the gauchos and peasantry themselves, such as those based on the long historical experience of indigenous peoples.

Based on documents preserved by inhabitants of the travesía, or the desert, of Guanacache, in the central Cuyo region, the descendants of the Huarpe Indians who were considered extinct in the seventeenth century, this analysis stresses the continuity of indigenous claims and the political strategies of the communities of the countryside during the nineteenth century. While recognizing that other factors were involved in political mobilization, this analysis shows the primary importance of indigenous claims in an area of traditional montonero rebellion and civil conflict, and the active participation of the region in the construction of the state beginning in the 1820s. Indigenous leaders who also served as government officials pressed for institutionalized recognition of indigenous rights. That pressure eventually led to the acceptance of their claims and the maintenance of relative political autonomy until the 1870s.
MRAS GTPase is a novel stemness marker that impacts mouse embryonic stem cell plasticity and Xenopus embryonic cell fate
Authors: Mathieu Marie-Emmanuelle , Faucheux Corinne , Saucourt Claire , Soulet Fabienne , Gauthereau Xavier , Fédou Sandrine , Trouillas Marina , Thézé Nadine , Thiébaud Pierre , Boeuf Hélène
Published: July 2013

Pluripotent mouse embryonic stem cells (mESCs), maintained in the presence of the leukemia inhibitory factor (LIF) cytokine, provide a powerful model with which to study pluripotency and differentiation programs. Extensive microarray studies on cultured cells have led to the identification of three LIF signatures. Here we focus on muscle ras oncogene homolog (MRAS), which is a small GTPase of the Ras family encoded within the Pluri gene cluster. To characterise the effects of Mras on cell pluripotency and differentiation, we used gain- and loss-of-function strategies in mESCs and in the Xenopus laevis embryo, in which Mras gene structure and protein sequence are conserved. We show that persistent knockdown of Mras in mESCs reduces expression of specific master genes and that MRAS plays a crucial role in the downregulation of OCT4 and NANOG protein levels upon differentiation. In Xenopus, we demonstrate the potential of Mras to modulate cell fate at early steps of development and during neurogenesis. Overexpression of Mras allows gastrula cells to retain responsiveness to fibroblast growth factor (FGF) and activin. Collectively, these results highlight novel conserved and pleiotropic effects of MRAS in stem cells and early steps of development.
Tumor suppressor Nf2 limits expansion of the neural progenitor pool by inhibiting Yap/Taz transcriptional coactivators
Authors: Lavado Alfonso , He Yu , Paré Joshua , Neale Geoffrey , Olson Eric N. , Giovannini Marco , Cao Xinwei
Published: July 2013

Brain development requires a precise balance between expansion of the neural progenitor pool and the production of postmitotic neurons and glia. Disruption of this equilibrium results in a myriad of structural abnormalities and disorders of the nervous system. The molecular mechanism that restricts neural progenitor expansion is poorly understood. Here we show that the tumor suppressor neurofibromatosis 2 (Nf2; merlin) limits the expansion of neural progenitor cells (NPCs) in the mammalian dorsal telencephalon. Nf2 is localized at the apical region of NPCs. In the absence of Nf2, NPCs of the cortical hem, hippocampal primordium and neocortical primordium overexpand, while production of Cajal-Retzius cells and hippocampal neurons decreases, resulting in severe malformation of the hippocampus in adult mice. We further show that Nf2 functions by inhibiting the Yap/Taz transcriptional coactivators, probably through a mechanism that is distinct from the canonical Hippo pathway. Overexpressing human YAP in NPCs causes a hippocampal malformation phenotype that closely resembles that of Nf2 mutants and, importantly, deleting Yap in the Nf2 mutant background largely restores hippocampal development. Our studies uncover Nf2 as an important inhibitor of neural progenitor expansion and establish Yap/Taz as key downstream effectors of Nf2 during brain development.
Behavior of Formate Adsorbed on Cu(110) When Exposed to Hydrogen Gas
Authors: Inoue Kenichiro , Wakabayashi Fumitaka , Domen Kazunari
Published: July 2013

The behavior of formate adsorbed on Cu(110) surface exposed to hydrogen gas was investigated at 300–330 K. Although an exchange reaction from D–COO(a) to H–COO(a) was observed after exposing a DCOO(a)-covered Ni(110) surface to H2 in a previous report, this did not occur with Cu(110). The preadsorbed DCOO(a) desorbed as DCOOH after accepting a hydrogen atom from a gaseous H2 molecule.
Solution-phase Synthesis of Stannite-type Ag2ZnSnS4 Nanoparticles for Application to Photoelectrode Materials
Authors: Sasamura Tetsuya , Osaki Takaaki , Kameyama Tatsuya , Shibayama Tamaki , Kudo Akihiko , Kuwabata Susumu , Torimoto Tsukasa
Published: July 2013

Ag2ZnSnS4 (AZTS) nanoparticles were successfully synthesized at relatively low temperature via thermal reaction of corresponding metal acetates and a sulfur source in a hot oleylamine solution, the purity of the particles being dependent on the amount of metal acetates and the reaction temperature. The obtained pure AZTS particles with size of ca. 15 nm exhibited photoresponse with visible light irradiation similar to that of n-type semiconductors.
An Improved Synthesis of Methyl Protodioscin. II. A Direct E-ring Opening by BF3–Et2O/Ac2O from Dioscin Ester
Authors: Wang Bo , Liu Yang , Liu Xin , Cheng Mao-sheng
Published: July 2013

A direct E-ring opening of dioscin ester by BF3–Et2O/Ac2O was studied, and methyl protodioscin was synthesized from dioscin ester in three steps with a total yield of 44%. The details of the E-ring opening reaction was discussed, and a prominent stability of C16–OAc was obversed.
Synthesis, Structure, and Catalytic Activity of Palladium Complexes Bearing a Tridentate PXP-Pincer Ligand of Heavier Group 14 Element (X = Ge, Sn)
Authors: Takaya Jun , Nakamura Shuhei , Iwasawa Nobuharu
Published: July 2013

An efficient method for the synthesis of tridentate PGeP– and PSnP–palladium complexes is developed. Structural analysis revealed that PSiP-ligand exerts the strongest trans influence and electron donation and that PGeP- and PSnP-ligands provide wider coordination sphere around the palladium. Preliminary studies demonstrated that both PGeP– and PSnP–palladium complexes work as an efficient catalyst for reductive aldol-type reaction, indicating promising utility in synthetic organic chemistry.
Facile Fabrication of Hybrid Hollow Microspheres via in Situ Pickering Miniemulsion Polymerization
Authors: Zhang Jianan , Lin Jizhi , Wu Bo , Yang Beibei , Wu Mingyuan , Yang Wenlong , Wu Qingyun , Yang Jianjun
Published: July 2013

Hybrid hollow microspheres have been fabricated successfully via miniemulsion polymerization using the in situ formed and modified nanosilica particles as Pickering emulsifier. The hydrolysis and condensation reactions of tetraethoxysilane (TEOS) take place to form nanosilica particles which are then partially modified by oil-soluble 3-(trimethoxysilyl)propyl methacrylate (MPS) at the oil/water interface under basic conditions. After the miniemulsification process, Pickering miniemulsions were stabilized by the in situ nanosilica particles. Hybrid hollow microspheres are obtained with silica nanoparticles closely packed on the surface of polymer microspheres. The results showed that both the weight ratios of TEOS/styrene and MPS/TEOS have great effects on the production of stable Pickering emulsion and then the morphologies of the obtained hybrid microspheres.
A Study on the Relationship between the Twisted π-Conjugate System of 1,5-Diaryl-1,5-diazapenta-1,3-dienes and Their Photophysical Properties
Authors: Kamimura Akio , Matsu Hideki , Suzukawa Hiroyuki , Sato Eisuke , Sumimoto Michinori , Uno Hidemitsu
Published: July 2013

One-pot treatment of commercially available 1,3,3-tributoxy-2-cyanopropene with 2 equivalents of primary aromatic amines readily afforded 1,5-diaryl-1,5-diaza-3-cyanopenta-1,3-dienes. UV properties varied as steric size of the ortho-substituent in the N-aryl units increased. X-ray crystallographic analyses indicated preferable conformation of these compounds, and the twist angles between 1,5-diazapentadiene and aromatic units were measured. The relationship between the twisted angles and UV absorptions was rationalized by MO calculation, and the UV peak wavelengths are useful for the estimation of the twisted angles. A novel tetracoordinate diaryl-1,5-diazapentadiene was prepared. UV spectrum for its lithium complex in CHCl3 supported that the complex had a twisted conformation of the aryl units because the two etharial oxygen atoms coordinated to lithium cation.
Amino Acid Ionic Liquid as an Efficient Cosolvent of Dimethyl Sulfoxide to Realize Cellulose Dissolution at Room Temperature
Authors: Ohira Kazutaka , Yoshida Kohei , Hayase Shuichi , Itoh Toshiyuki
Published: July 2013

A mixture of dimethyl sulfoxide (DMSO) and N,N-diethyl-N-(2-methoxyethyl)-N-methylammonium alanine ([N221ME][Ala]) dissolved cellulose at rt; the solubility of cellulose depended on the content of the ionic liquid in DMSO and reached 23 wt % (vs. solvent) in a 1:1 mixture. The solution coagulated in water or ethanol to obtain a transparent regenerated cellulose in quantitative yield.
Deposition of ZnO Particles by Photocatalytic Reaction
Authors: Nagaya Satoshi , Nishikiori Hiromasa
Published: July 2013

Zinc oxide (ZnO) particles were deposited on a very thin titanium dioxide film by a photocatalytic reaction. The particles were formed in an aqueous solution of 0.10 mol dm−3 zinc nitrate at 343 K. The particles consisted of crystals with 0.20–1.0 µm-sized hexagonal columns. A photocurrent was observed in the electrodes containing such ZnO crystals during light irradiation.
Pertussis: novas estratégias de vacinação para prevenção de uma antiga doença
Authors: Bricks Lucia Ferro
Published: July 2013

Introdução: A despeito das elevadas coberturas vacinais, a pertussis persiste como importante causa de hospitalizações e mortes em lactentes, sendo necessárias novas estratégias de vacinação parao controle da doença. Objetivos: Descrever as recentes mudanças na epidemiologia da coqueluche, analisar as principais fontes de transmissão para lactentes, os fatores envolvidos no ressurgimento da doença e as publicações sobre uso de vacinas acelulares em adolescentes e adultos. Métodos: Foram identificados e analisados os artigos publicados no PUBMED e SCIELO, assim como as informações disponíveis nos sites oficiais da OMS, OPAS, CDC, ECDC e do Ministério da Saúde do Brasil, de 01/01/2003 a 31/12/2012. Conclusões: A reemergência da pertussis foi constatada em países que adotam diferentes vacinas e esquemas de imunização. As mais relevantes fontes de pertussis para lactentes, o grupo de mais alto risco para complicações e mortes, são os contatos domiciliares, especialmente, as mães. A proteção oferecida por infecção natural ou por vacinas é limitada. As vacinas Tdap e Tdap-IPV são seguras e imunogênicas, e dados limitados demonstraram que essas vacinas conferem proteção direta e indireta, com efetividade de, aproximadamente 80%, durante 5 anos. É necessário melhorar a educação sobre os benefícios da vacinação de adolescentes e adultos e aprimorar a vigilância da pertussis nesses grupos com maior utilização novos recursos laboratoriais (PCR e sorologia) a fim de identificar o intervalo ideal para administrar as doses de reforço e as melhores estratégias de vacinação para reduzir o número de mortes em lactentes.
"My Dear Comrade Frederickus": Walt Whitman and Fred Gray
Authors: Blalock Stephanie M.
Published: July 2013

Offers detailed biographical information (and two photographs) of Whitman’s close friend, Fred Gray, and examines the nature of what Whitman called the “Fred Gray Association,” “a circle of New York comrades,” some of them “highly literate and upwardly mobile,” who frequented Pfaff’s beer hall and had “ties to the nearby New York Hospital”; traces Whitman’s continuing associations with Gray and his associates throughout the poet’s life.