bluuebunny/crossref_metadata_2025 huggingface dataset:
Views on the peer review system of biomedical journals: an online survey of academics from high-ranking universities
Authors: Ho Roger Chun-Man , Mak Kwok-Kei , Tao Ren , Lu Yanxia , Day Jeffrey R , Pan Fang
Published: June 2013

Background

Peer review is the major method used by biomedical journals for making the decision of publishing an article. This cross-sectional survey assesses views concerning the review system of biomedical journals among academics globally.

Methods

A total of 28,009 biomedical academics from high-ranking universities listed by the 2009 Times Higher Education Quacquarelli Symonds (THE-QS) World University Rankings were contacted by email between March 2010 and August 2010. 1,340 completed an online survey which focused on their academic background, negative experiences and views on biomedical journal peer review and the results were compared among basic scientists, clinicians and clinician scientists.

Results

Fewer than half of the respondents agreed that the peer review systems of biomedical journals were fair (48.4%), scientific (47.5%), or transparent (25.1%). Nevertheless, 58.2% of the respondents agreed that authors should remain anonymous and 64.4% agreed that reviewers should not be disclosed. Most, (67.7%) agreed to the establishment of an appeal system. The proportion of native English-speaking respondents who agreed that the “peer review system is fair” was significantly higher than for non-native respondents (p = 0.02). Similarly, the proportion of clinicians stating that the “peer review system is fair” was significantly higher than that for basic scientists and clinician-scientists (p = 0.004). For females, (β = −0.1, p = 0.03), the frequency of encountering personal attacks in reviewers’ comments (β = −0.1, p = 0.002) and the frequency of imposition of unnecessary references by reviewers (β = −0.06, p = 0.04) were independently and inversely associated with agreement that “the peer review system is fair”.

Conclusion

Academics are divided on the issue of whether the biomedical journal peer review system is fair, scientific and transparent. A majority of academics agreed with the double-blind peer review and to the establishment of an appeal system. Female academics, experience of personal attacks and imposition of unnecessary references by reviewers were related to disagreement about fairness of the peer review system of biomedical journals.
Primary care Physicians’ perspective on the management of anxiety and depressive disorders: a cross-sectional survey in Emilia Romagna Region
Authors: Casini Federica , Sighinolfi Cecilia , Tedesco Paola , Bandieri Pier Venanzio , Bologna Maria , Colombini Niccolò , Curcetti Clara , Magnani Michele , Morini Mara , Serio Alberto , Tarricone Ilaria , Berardi Domenico , Menchetti Marco
Published: June 2013

Background

Evidences from literature suggest that Primary Care Physicians’ (PCPs) knowledge and attitude about psychological and pharmacological treatments of anxiety and depressive disorders could influence their clinical practice. The aim of the study is double: 1) to assess PCPs’ opinions about antidepressants (ADs) and psychotherapy for the management of anxiety and depressive disorders; 2) to evaluate the influence of PCPs’ gender, age, duration of clinical practice, and office location on their opinions and attitudes.

Methods

This cross-sectional multicentre survey involved 816 PCPs working in four Local Health Units of the Emilia Romagna Region. Participating PCPs were asked to complete a questionnaire during educational meetings between October 2006 and December 2008.

Results

The response rate was 65.1%. Eighty-five percent of PCPs agreed on the effectiveness of ADs for depressive disorder whereas lower agreement emerged for anxiety disorder and on psychotherapy for both anxiety and depression. Forty percent of PCPs reported to feel “very/extremely confident” in recognizing depression and 20.0% felt equally confident in treating it with pharmacotherapy. Considering anxiety disorder, these proportions increased. Female PCPs and those located in the rural/mountain areas reported to adopt more psycho-educational support compared to male and suburban colleagues.

Conclusions

Our results suggest that an effort should be made to better disseminate recent evidences about the management of anxiety and depressive disorders in Primary Care. In particular, the importance of psychological interventions and the role of drugs for anxiety disorder should be addressed.
Dynamically regulated miRNA-mRNA networks revealed by exercise
Authors: Tonevitsky Alexander G , Maltseva Diana V , Abbasi Asghar , Samatov Timur R , Sakharov Dmitry A , Shkurnikov Maxim U , Lebedev Alexey E , Galatenko Vladimir V , Grigoriev Anatoly I , Northoff Hinnak
Published: June 2013

Background

MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and the subsequent recovery period.

Results

Here we monitored the transcriptome changes using microarray analysis of the whole blood of eight highly trained athletes before and after 30 min of moderate exercise followed by 30 min and 60 min of recovery period. We combined expression profiling and bioinformatics and analysed metabolic pathways enriched with differentially expressed mRNAs and mRNAs which are known to be validated targets of differentially expressed miRNAs. Finally we revealed four dynamically regulated networks comprising differentially expressed miRNAs and their known target mRNAs with anti-correlated expression profiles over time. The data suggest that hsa-miR-21-5p regulated TGFBR3, PDGFD and PPM1L mRNAs. Hsa-miR-24-2-5p was likely to be responsible for MYC and KCNJ2 genes and hsa-miR-27a-5p for ST3GAL6. The targets of hsa-miR-181a-5p included ROPN1L and SLC37A3. All these mRNAs are involved in processes highly relevant to exercise response, including immune function, apoptosis, membrane traffic of proteins and transcription regulation.

Conclusions

We have identified metabolic pathways involved in response to exercise and revealed four miRNA-mRNA networks dynamically regulated following exercise. This work is the first study to monitor miRNAs and mRNAs in parallel into the recovery period. The results provide a novel insight into the regulatory role of miRNAs in stress adaptation.
The effects of a histone deacetylase inhibitor on biological behavior of diffuse large B-cell lymphoma cell lines and insights into the underlying mechanisms
Authors: Cai Ying , Cui Wenli , Chen Weixiang , Wei Ping , Chi Yayun , Zhang Ping , Bi Rui , Zhou Xiaoyan
Published: June 2013

Background

Epigenetic control using histone deacetylase (HDAC) inhibitors is a promising therapy for lymphomas. Insights into the anti-proliferative effects of HDAC inhibitors on diffuse large B-cell lymphoma (DLBCL) and further understanding of the underlying mechanisms, which remain unclear to date, are of great importance.

Methods

Three DLBCL cell lines (DoHH2, LY1 and LY8) were used to define the potential epigenetic targets for Trichostatin A (TSA)-mediated anti-proliferative effects via CCK-8 assay. Cell cycle distribution and apoptosis were detected by flow cytometry. We further investigated the underlying molecular mechanisms by examining expression levels of relevant proteins using western blot analysis.

Results

TSA treatment inhibited the growth of all three DLBCL cell lines and enhanced cell cycle arrest and apoptosis. Molecular analysis revealed upregulated acetylation of histone H3, α-tubulin and p53, and dephosphorylation of pAkt with altered expression of its main downstream effectors (p21, p27, cyclin D1 and Bcl-2). HDAC profiling revealed that all three cell lines had varying HDAC1–6 expression levels, with the highest expression of all six isoforms, in DoHH2 cells, which displayed the highest sensitivity to TSA.

Conclusion

Our results demonstrated that the HDAC inhibitor TSA inhibited DLBCL cell growth, and that cell lines with higher expression of HDACs tended to be more sensitive to TSA. Our data also suggested that inhibition of pAkt and activation of p53 pathway are the main molecular events involved in inhibitory effects of TSA.
In vitro susceptibility to quinine and microsatellite variations of the Plasmodium falciparum Na+/H+ exchanger transporter (Pfnhe-1) gene in 393 isolates from Dakar, Senegal
Authors: Pascual Aurélie , Fall Bécaye , Wurtz Nathalie , Fall Mansour , Camara Cheikhou , Nakoulima Aminata , Baret Eric , Diatta Bakary , Fall Khadidiatou Ba , Mbaye Pape Saliou , Diémé Yaya , Bercion Raymond , Bogreau Hervé , Briolant Sébastien , Rogier Christophe , Wade Boubacar , Pradines Bruno
Published: June 2013

Background

Although the World Health Organization recommends replacing quinine (QN) by artesunate due to its increased efficacy and the higher tolerance to the drug in both adults and children, QN remains a first-line treatment for severe malaria, especially in Africa. Investigations of microsatellite Pfnhe-1 ms4760 polymorphisms in culture-adapted isolates from around the world have revealed that an increase in the number of DNNND amino acid motifs was associated with decreased QN susceptibility, whereas an increase in the number of DDNHNDNHNND motifs was associated with increased QN susceptibility.

Methods

In this context, to further analyse associations between Pfnhe-1 ms4760 polymorphisms and QN susceptibility, 393 isolates freshly collected between October 2009 and January 2010 and July 2010 and February 2011, respectively, at the Hôpital Principal de Dakar, Senegal were assessed ex vivo for QN susceptibility, and their genes were amplified and sequenced.

Results

Of the 393 Plasmodium falciparum clinical isolates collected, 145 were successfully cultured. The 145 QN IC50s ranged from 2.1 to 1291 nM, and 17 isolates (11.7%) exceed the QN reduced susceptibility threshold of 611 nM. Among the 393 P. falciparum clinical isolates, 47 different alleles were observed. The three most prevalent profiles were ms4760-1 (no = 72; 18.3%), ms4760-3 (no = 65; 16.5%) and ms4760-7 (no = 40; 10.2%). There were no significant associations observed between QN IC50 values and i) the number of repeats of DNNND in block II (p = 0.0955, Kruskal-Wallis test); ii) the number of repeats of DDNHNDNHNND in block V (p = 0.1455, Kruskal-Wallis test); or iii) ms4760 profiles (p = 0.1809, Kruskal-Wallis test).

Conclusions

Pfnhe-1 ms4760 was highly diverse in parasite isolates from Dakar (47 different profiles). Three profiles (ms4760-1, ms4760-3 and ms4760-7) were predominant. The number of repeats for block II (DNNND) or block V (DDNHNDNHNND) was not significantly associated with QN susceptibility. New studies, and especially in vivo studies, are necessary to confirm the role of Pfnhe-1 ms4760 as a marker of QN resistance.
Programmable nanoengineering templates for fabrication of three-dimensional nanophotonic structures
Authors: Lin Qingfeng , Leung Siu-Fung , Tsui Kwong-Hoi , Hua Bo , Fan Zhiyong
Published: June 2013

Porous anodic alumina membranes (AAMs) have attracted great amount of attention due to their potential application as templates for nanoengineering. Template-guided fabrication and assembly of nanomaterials based on AAMs are cost-effective and scalable methods to program and engineer the shape and morphology of nanostructures and nanomaterials. In this work, perfectly ordered AAMs with the record large pitch up to 3 μm have been fabricated by properly controlling the anodization conditions and utilization of nanoimprint technique. Due to the capability of programmable structural design and fabrication, a variety of nanostructures, including nanopillar arrays, nanotower arrays, and nanocone arrays, have been successfully fabricated using nanoengineered AAM templates. Particularly, amorphous Si nanocones have been fabricated as three-dimensional nanophotonic structures with the characterization of their intriguing optical anti-reflection property. These results directly indicate the potential application of the reported approach for photonics and optoelectronics.
Si-rich Al2O3 films grown by RF magnetron sputtering: structural and photoluminescence properties versus annealing treatment
Authors: Korsunska Nadiia , Khomenkova Larysa , Kolomys Oleksandr , Strelchuk Viktor , Kuchuk Andrian , Kladko Vasyl , Stara Tetyana , Oberemok Oleksandr , Romanyuk Borys , Marie Philippe , Jedrzejewski Jedrzej , Balberg Isaac
Published: June 2013

Silicon-rich Al2O3 films (Si
x
(Al2O3)1−x
) were co-sputtered from two separate silicon and alumina targets onto a long silicon oxide substrate. The effects of different annealing treatments on the structure and light emission of the films versus x were investigated by means of spectroscopic ellipsometry, X-ray diffraction, micro-Raman scattering, and micro-photoluminescence (PL) methods. The formation of amorphous Si clusters upon the deposition process was found for the films with x ≥ 0.38. The annealing treatment of the films at 1,050°C to 1,150°C results in formation of Si nanocrystallites (Si-ncs). It was observed that their size depends on the type of this treatment. The conventional annealing at 1,150°C for 30 min of the samples with x = 0.5 to 0.68 leads to the formation of Si-ncs with the mean size of about 14 nm, whereas rapid thermal annealing of similar samples at 1,050°C for 1 min showed the presence of Si-ncs with sizes of about 5 nm. Two main broad PL bands were observed in the 500- to 900-nm spectral range with peak positions at 575 to 600 nm and 700 to 750 nm accompanied by near-infrared tail. The low-temperature measurement revealed that the intensity of the main PL band did not change with cooling contrary to the behavior expected for quantum confined Si-ncs. Based on the analysis of PL spectrum, it is supposed that the near-infrared PL component originates from the exciton recombination in the Si-ncs. However, the most intense emission in the visible spectral range is due to either defects in matrix or electron states at the Si-nc/matrix interface.
Strong convergence theorems for three-steps iterations for asymptotically nonexpansive mappings in Banach spaces
Authors: An Cui Yun , Fei Zuo Zhan , Hudzik Henryk
Published: June 2013

We consider the problem of the convergence of the three-steps iterative sequences for asymptotically nonexpansive mappings in a real Banach space. Under suitable conditions, it has been proved that the iterative sequence converges strongly to a fixed point, which is also a solution of certain variational inequality. The results presented in this paper extend and improve some recent results.
Effects of painful stimulation and acupuncture on attention networks in healthy subjects
Authors: Liu Gang , Ma Hui-juan , Hu Pan-pan , Tian Yang-hua , Hu Shen , Fan Jin , Wang Kai
Published: June 2013

Pain is a subjective sensory and emotional experience, and it has been reported that many different brain regions are regulated by pain, and that pain can impact attention. Acupuncture is an important treatment component of Chinese traditional medicine, and has been used for thousands of years to treat a wide variety of conditions. Although several studies have shown that acupuncture improves consciousness, the precise impact of both acupuncture and painful stimulation on attention is unclear. Are all of the attention networks modulated, or do these stimuli act on a specific network? Is the effect of painful stimulation similar to that of acupuncture? We administered the attention network test to 30 participants (15 males) to investigate the relative efficiencies of three independent attention networks (alerting, orienting, and executive control networks) under three conditions: baseline, after painful stimulation, and after acupuncture. The degree of pain experienced was assessed on a horizontally oriented visual analogue scale. The results showed that painful stimulation and acupuncture had similar effects on the orienting and executive control networks; however, there was a significantly different effect between the three conditions on the alerting network. In conclusion, (1) painful stimulation can selectively impact attention; (2) acupuncture can also selectively impact attention; i.e., both have selective influences on the alerting and executive control networks, but not on the orienting network; (3) the effects of acupuncture and painful stimulation are not identical. The mechanisms by which painful stimulation and acupuncture influence attention warrant further research.
Intermediate-risk prostate cancer patients treated with androgen deprivation therapy and a hypofractionated radiation regimen with or without image guided radiotherapy
Authors: Valeriani Maurizio , Bracci Stefano , Osti Mattia Falchetto , Falco Teresa , Agolli Linda , De Sanctis Vitaliana , Enrici Riccardo Maurizi
Published: June 2013

Background

To evaluate the efficacy of hypofractionated radiotherapy (HyRT) with or without image guided radiotherapy (IGRT) in intermediate risk prostate cancer.

Methods

105 patients were treated with HyRT, 43,8 Gy and 54,75 Gy were delivered to the seminal vescicles and to the prostate, respectively; 3,65 Gy/fraction three times weekly. All patients underwent 9 months hormonal therapy. Patient position was verified with daily kV cone beam CT in 69 patients (IGRT group). Acute and late toxicities were evaluated according to RTOG scale. Biochemical relapse was defined using PSA nadir + 2 ng/mL. The data were prospectively collected and retrospectively analyzed to evaluate the efficacy of IGRT.

Results

After a median follow-up of 31 months the actuarial 3-year bNED was 93,7%. During RT, 10.5% and 7.6% of patients developed ≥Grade 2 rectal and urinary toxicities, respectively. The cumulative incidence of ≥Grade 2 late rectal and urinary toxicities at 3 years were 6,9%, and 10,8%, respectively. The incidence of ≥Grade 2 late rectal toxicities was significant reduced in the IGRT group (1,6% vs. 14,5%, p=0,021). Two patients developed Grade 3 urethral obstruction and one patient developed grade 3 rectal bleeding.

Conclusions

HyRT represents a well-tolerated treatment able to achieve a high bNED. The use of daily IGRT is beneficial for reducing the incidence of late toxicities.
Strontium enhances osseointegration of calcium phosphate cement: a histomorphometric pilot study in ovariectomized rats
Authors: Baier Martin , Staudt Patric , Klein Roman , Sommer Ulrike , Wenz Robert , Grafe Ingo , Meeder Peter Jürgen , Nawroth Peter P , Kasperk Christian
Published: June 2013

Background

Calcium phosphate cements are used frequently in orthopedic and dental surgeries. Strontium-containing drugs serve as systemic osteoblast-activating medication in various clinical settings promoting mechanical stability of the osteoporotic bone.

Methods

Strontium-containing calcium phosphate cement (SPC) and calcium phosphate cement (CPC) were compared regarding their local and systemic effects on bone tissue in a standard animal model for osteoporotic bone. A bone defect was created in the distal femoral metaphysis of 60 ovariectomized Sprague-Dawley rats. CPC and SPC were used to fill the defects in 30 rats in each group. Local effects were assessed by histomorphometry at the implant site. Systemic effects were assessed by bone mineral density (BMD) measurements at the contralateral femur and the spine.

Results

Faster osseointegration and more new bone formation were found for SPC as compared to CPC implant sites. SPC implants exhibited more cracks than CPC implants, allowing more bone formation within the implant. Contralateral femur BMD and spine BMD did not differ significantly between the groups.

Conclusions

The addition of strontium to calcium phosphate stimulates bone formation in and around the implant. Systemic release of strontium from the SPC implants did not lead to sufficiently high serum strontium levels to induce significant systemic effects on bone mass in this rat model.
Monitoring of brain oxygen saturation (INVOS) in a protocol to direct blood transfusions during cardiac surgery: a prospective randomized clinical trial
Authors: Vretzakis George , Georgopoulou Stavroula , Stamoulis Konstantinos , Tassoudis Vassilios , Mikroulis Dimitrios , Giannoukas Athanasios , Tsilimingas Nikolaos , Karanikolas Menelaos
Published: June 2013

Background

Blood transfusions are common in cardiac surgery, but have been associated with increased morbidity and long-term mortality. Efforts to reduce blood product use during cardiac surgery include fluid restriction to minimize hemodilution, and protocols to guide transfusion decisions. INVOS is a modality that monitors brain tissue oxygen saturation, and could be useful in guiding decisions to transfuse. However, the role of INVOS (brain tissue oxygen saturation) as part of an algorithm to direct blood transfusions during cardiac surgery has not been evaluated. This study was conducted to investigate the value of INVOS as part of a protocol for blood transfusions during cardiac surgery.

Methods

Prospective, randomized, blinded clinical trial, on 150 (75 per group) elective cardiac surgery patients. The study was approved by the Institution Ethics committee and all patients gave written informed consent. Data were initially analyzed based on “intention to treat”, but subsequently were also analyzed “per protocol”.

Results

When protocol was strictly followed (“per protocol analysis”), compared to the control group, significantly fewer patients monitored with INVOS received any blood transfusions (46 of 70 patients in INVOS group vs. 55 of 67 patients in the control group, p = 0.029). Similarly, patients monitored with INVOS received significantly fewer units of red blood cell transfusions intraoperatively (0.20 ± 0.50 vs. 0.52 ± 0.88, p = 0.008) and overall during hospital stay (1.31 ± 1.20 vs. 1.82 ± 1.46, p = 0.024). When data from all patients (including patient with protocol violation) were analyzed together (“intention to treat analysis”), the observed reduction of blood transfusions in the INVOS group was still significant (51 of 75 patients transfused in the INVOS group vs. 63 of 75 patients transfused in the control group, p = 0.021), but the overall number of units transfused per patient did not differ significantly between the groups (1.55 ± 1.97 vs. 1.84 ± 1.41, p = 0.288).

Conclusions

Our data suggest that INVOS could be a useful tool as part of an algorithm to guide decisions for blood transfusion in cardiac surgery. Additional data from rigorous, well designed studies are needed to further evaluate the role of INVOS in guiding blood transfusions in cardiac surgery, and circumvent the limitations of this study.

Trial registration

ClinicalTrials.gov: NCT00879463
Glomus tumor of uncertain malignant potential arising in the bronchus
Authors: Zhu Ya-Zhen , Li Wei-Ping , Wang Zhi-Yuan , Yang Hai-Feng , He Qing-Lian , Zhu Hong-Guang , Zheng Guang-Juan
Published: June 2013

Glomus tumor is usually a small, benign tumor and typically occurs in the dermis or subcutis or soft tissue of the extremities and rarely in the visceral locations. Its occurrence in the main bronchus is extremely rare. The current case reported a 30-year-old woman with dyspnea on exertion and hemoptysis, she had a glomus tumor which has large size, deep location and exhibits an infiltrative margin as well as increased atypical mitotic figures. These characteristics suggest malignant behavior. However, there is little data regarding glomus tumors arising in the bronchus, the need for caution in diagnosing this case as a malignant glomus tumor must be highlighted. Therefore, the diagnosis of bronchial glomus tumor of uncertain malignant potential was favored. To the best of our knowledge, both the type and the location of this glomus tumor are extremely rare. Accumulation of more cases are needed to clarify their diagnosis and significance since there is little data regarding glomus tumors arising in the bronchus.
Ixodid ticks of traditionally managed cattle in central Nigeria: where Rhipicephalus (Boophilus) microplus does not dare (yet?)
Authors: Lorusso Vincenzo , Picozzi Kim , de Bronsvoort Barend MC , Majekodunmi Ayodele , Dongkum Charles , Balak Gyang , Igweh Augustine , Welburn Susan C
Published: June 2013

Background

Ticks and tick-borne diseases (TBDs) undermine cattle fitness and productivity in the whole of sub-Saharan Africa, including Nigeria. The aim of this study was to document the composition of tick species, assessing the burden of infestation, in traditionally managed cattle in an area of central Nigeria where acaricides have not been used historically.

Methods

The study was carried out in September 2010 in 9 villages belonging to three neighbouring local government areas in Plateau State, Nigeria. In each village all visible adult ticks were collected from at least 15 cattle (mean number = 25). Collected ticks were preserved in 70% ethanol to be counted and morphologically identified to the species level.

Results

A total of 5011 ixodid ticks (1935 males and 3076 females) were collected from 228 cattle, comprising 14 calves, 33 juveniles, and 181 adults. Three tick genera (i.e., Amblyomma, Hyalomma, and Rhipicephalus, including the Boophilus sub-genus) and 11 species were identified. The most prevalent species was Rhipicephalus (Boophilus) decoloratus (41.4%), followed by Rhipicephalus (Boophilus) annulatus (15.4%), Rhipicephalus guilhoni (12.0%), Rhipicephalus (Boophilus) geigyi (7.6%), Hyalomma truncatum (7.4%), Amblyomma variegatum (6.3%), Rhipicephalus simus Group (4.0%), Rhipicephalus turanicus (1.2%), Rhipicephalus sanguineus (0.3%), Hyalomma rufipes (0.2%), and Rhipicephalus lunulatus (n = 1). Mean tick loads recorded were relatively high (22 ± 1.4), in spite of the practice of hand removal of ticks traditionally undertaken by the Fulani pastoralists in the area. Calves bore a significantly lower tick burden than adults (p = 0.004). Rhipicephalus (Boophilus) microplus was not found in the area, suggesting that the eastbound expansion of this tick species in West Africa, has not yet reached central Nigeria.

Conclusions

This study ascertained the presence of a broad variety of cattle tick species, most of which are of veterinary importance. The presence of each tick species is correlated with the potential occurrence of tick-borne pathogens and suggestions for tick control in the area are considered. Results should assist the diagnosis of related TBDs in cattle as well as the strategic planning of cost-effective tick control.
A novel methyl-binding domain protein enrichment method for identifying genome-wide tissue-specific DNA methylation from nanogram DNA samples
Authors: Oliver Verity F , Wan Jun , Agarwal Saurabh , Zack Donald J , Qian Jiang , Merbs Shannath L
Published: June 2013

Background

Growing evidence suggests that DNA methylation plays a role in tissue-specific differentiation. Current approaches to methylome analysis using enrichment with the methyl-binding domain protein (MBD) are restricted to large (≥1 μg) DNA samples, limiting the analysis of small tissue samples. Here we present a technique that enables characterization of genome-wide tissue-specific methylation patterns from nanogram quantities of DNA.

Results

We have developed a methodology utilizing MBD2b/MBD3L1 enrichment for methylated DNA, kinase pre-treated ligation-mediated PCR amplification (MeKL) and hybridization to the comprehensive high-throughput array for relative methylation (CHARM) customized tiling arrays, which we termed MeKL-chip. Kinase modification in combination with the addition of PEG has increased ligation-mediated PCR amplification over 20-fold, enabling >400-fold amplification of starting DNA. We have shown that MeKL-chip can be applied to as little as 20 ng of DNA, enabling comprehensive analysis of small DNA samples. Applying MeKL-chip to the mouse retina (a limited tissue source) and brain, 2,498 tissue-specific differentially methylated regions (T-DMRs) were characterized. The top five T-DMRs (Rgs20, Hes2, Nfic, Cckbr and Six3os1) were validated by pyrosequencing.

Conclusions

MeKL-chip enables genome-wide methylation analysis of nanogram quantities of DNA with a wide range of observed-to-expected CpG ratios due to the binding properties of the MBD2b/MBD3L1 protein complex. This methodology enabled the first analysis of genome-wide methylation in the mouse retina, characterizing novel T-DMRs.
The diagnosis of food allergy: protocol for a systematic review
Authors: Soares‐Weiser Karla , Panesar Sukhmeet S , Rader Tamara , Takwoingi Yemisi , Werfel Thomas , Muraro Antonella , Hoffmann‐Sommergruber Karin , Roberts Graham , Sheikh Aziz ,   the EAACI Food Allergy and Anaphylaxis Group
Published: June 2013

Background

The literature on diagnostic tests for food allergy currently lacks clear consensus regarding the accuracy and safety of different investigative approaches. The European Academy of Allergy and Clinical Immunology is in the process of developing its Guideline for Food Allergy and Anaphylaxis, and this systematic review is one of seven inter‐linked evidence syntheses that are being undertaken in order to provide a state‐of‐the‐art synopsis of the current evidence base in relation to epidemiology, prevention, diagnosis and clinical management, and impact on quality of life, which will be used to inform the formulation of clinical recommendations. The aim of this systematic review will be to assess the diagnostic accuracy of tests aimed at supporting the clinical diagnosis of IgE‐mediated food allergy.

Methods

The following databases from inception to September 30, 2012 will be searched for studies of diagnostic tests: Cochrane Library (Wiley&Sons); MEDLINE (OVID); Embase (OVID); CINAHL (Ebscohost); ISI Web of Science (Thomson Web of Knowledge); TRIP Database (web http://www.tripdatabase.com); and ClinicalTrials.gov (NIH web). These database searches will be supplemented by contacting an international panel of experts. Studies evaluating APT, SPT, specific‐IgE, and component specific‐IgE in participants of any age with suspected food allergy will be included. The reference standard will be DBPCFC in at least 50% of the participants. Studies will be quality assessed by using the QUADAS‐2 instrument. We will report summary statistics such as sensitivity, specificity, and/or likelihood ratios. We will use the hierarchical summary ROC (HSROC) model to summarize the accuracy of each test and to compare the accuracy of two or more tests.

Discussion

Decisions on which tests to use need to be guided by availability of tests, populations being cared for, risks, financial considerations and test properties. This review will examine papers from around the world, covering children and adults with suspected food allergy in varying populations and concentrated on four type of tests: APT, SPT, specific‐IgEs, and component specific‐IgEs.
Habitat selection by bluetongue lizards (Tiliqua, Scincidae) in tropical Australia: a study using GPS telemetry
Authors: Price-Rees Samantha J , Brown Gregory P , Shine Richard
Published: June 2013

Background

Emerging global positioning system (GPS) technologies can clarify movement patterns of free-ranging animals in far more detail than has been possible with previous methods. We conducted long-term (mean, 65 days; maximum, 221 days) GPS radio-tracking of 41 northern bluetongue lizards (Tiliqua scincoides intermedia) and 8 centralian bluetongue lizards (T. multifasciata) at two study sites in northwestern Australia, close to the border between Western Australia and the Northern Territory.

Results

Individuals of both species spent long periods within small and distinctive habitat patches, interspersed with longer directional relocations from one patch to the next. Our sampling showed that these patches of core activity differed significantly from the surrounding landscape in several respects. The patches provided relatively shaded, cool, and damp conditions, with higher grass and more leaf-litter cover. The location of these patches in the landscape is probably determined by drainage patterns, soil moisture-holding ability, and stochastic recruitment of shade trees.

Conclusions

These scattered patches provide a critically important habitat for lizards (and probably, other taxa) within this hot dry landscape. Future conservation and management strategies need to prioritize the retention of such sites, at a spatial scale that allows animals to move between them.
The plasticity of the grapevine berry transcriptome
Authors: Dal Santo Silvia , Tornielli Giovanni Battista , Zenoni Sara , Fasoli Marianna , Farina Lorenzo , Anesi Andrea , Guzzo Flavia , Delledonne Massimo , Pezzotti Mario
Published: June 2013

Background

Phenotypic plasticity refers to the range of phenotypes a single genotype can express as a function of its environment. These phenotypic variations are attributable to the effect of the environment on the expression and function of genes influencing plastic traits. We investigated phenotypic plasticity in grapevine by comparing the berry transcriptome in a single clone of the vegetatively-propagated common grapevine species Vitis vinifera cultivar Corvina through 3 consecutive growth years cultivated in 11 different vineyards in the Verona area of Italy.

Results

Most of the berry transcriptome clustered by year of growth rather than common environmental conditions or viticulture practices, and transcripts related to secondary metabolism showed high sensitivity towards different climates, as confirmed also by metabolomic data obtained from the same samples. When analyzed in 11 vineyards during 1 growth year, the environmentally-sensitive berry transcriptome comprised 5% of protein-coding genes and 18% of the transcripts modulated during berry development. Plastic genes were particularly enriched in ontology categories such as transcription factors, translation, transport, and secondary metabolism. Specific plastic transcripts were associated with groups of vineyards sharing common viticulture practices or environmental conditions, and plastic transcriptome reprogramming was more intense in the year characterized by extreme weather conditions. We also identified a set of genes that lacked plasticity, showing either constitutive expression or similar modulation in all berries.

Conclusions

Our data reveal candidate genes potentially responsible for the phenotypic plasticity of grapevine and provide the first step towards the characterization of grapevine transcriptome plasticity under different agricultural systems.
Platelet-rich plasma preparation for regenerative medicine: optimization and quantification of cytokines and growth factors
Authors: Amable Paola Romina , Carias Rosana Bizon Vieira , Teixeira Marcus Vinicius Telles , da Cruz Pacheco Ítalo , Corrêa do Amaral Ronaldo José Farias , Granjeiro José Mauro , Borojevic Radovan
Published: June 2013

Introduction

Platelet-rich plasma (PRP) is nowadays widely applied in different clinical scenarios, such as orthopedics, ophthalmology and healing therapies, as a growth factor pool for improving tissue regeneration. Studies into its clinical efficiency are not conclusive and one of the main reasons for this is that different PRP preparations are used, eliciting different responses that cannot be compared. Platelet quantification and the growth factor content definition must be defined in order to understand molecular mechanisms behind PRP regenerative strength. Standardization of PRP preparations is thus urgently needed.

Methods

PRP was prepared by centrifugation varying the relative centrifugal force, temperature, and time. Having quantified platelet recovery and yield, the two-step procedure that rendered the highest output was chosen and further analyzed. Cytokine content was determined in different fractions obtained throughout the whole centrifugation procedure.

Results

Our method showed reproducibility when applied to different blood donors. We recovered 46.9 to 69.5% of total initial platelets and the procedure resulted in a 5.4-fold to 7.3-fold increase in platelet concentration (1.4 × 106 to 1.9 × 106 platelets/μl). Platelets were highly purified, because only <0.3% from the initial red blood cells and leukocytes was present in the final PRP preparation. We also quantified growth factors, cytokines and chemokines secreted by the concentrated platelets after activation with calcium and calcium/thrombin. High concentrations of platelet-derived growth factor, endothelial growth factor and transforming growth factor (TGF) were secreted, together with the anti-inflammatory and proinflammatory cytokines interleukin (IL)-4, IL-8, IL-13, IL-17, tumor necrosis factor (TNF)-α and interferon (IFN)-α. No cytokines were secreted before platelet activation. TGF-β3 and IFNγ were not detected in any studied fraction. Clots obtained after platelet coagulation retained a high concentration of several growth factors, including platelet-derived growth factor and TGF.

Conclusions

Our study resulted in a consistent PRP preparation method that yielded a cytokine and growth factor pool from different donors with high reproducibility. These findings support the use of PRP in therapies aiming for tissue regeneration, and its content characterization will allow us to understand and improve the clinical outcomes.
Retinoic acid, acting as a highly specific IgA isotype switch factor, cooperates with TGF-β1 to enhance the overall IgA response
Authors: Seo Goo-Young , Jang Young-Saeng , Kim Hyun-A , Lee Mi-Ra , Park Mi-Hee , Park Seok-Rae , Lee Jeong-Min , Choe Jongseon , Kim Pyeung-Hyeun
Published: June 2013

The present study demonstrates that RA has activity of an IgA switch factor and is more specific than TGF-β1. RA independently caused only IgA switching, whereas TGF-β1 caused IgA and IgG2b switching. We found that RA increased IgA production and that this was a result of its ability to increase the frequency of IgA-secreting B cell clones. Increased IgA production was accompanied by an increase of GLTα. RA activity was abrogated by an antagonist of the RAR. Additionally, RA affected intestinal IgA production in mice. Surprisingly, RA, in combination with TGF-β1, notably enhanced not only IgA production and GLTα expression but also CCR9 and α4β7 expression on B cells. These results suggest that RA selectively induces IgA isotype switching through RAR and that RA and TGF-β have important effects on the overall gut IgA antibody response.
Stretch-free migration imaging condition
Authors: Zhu Xinfa , McMechan George A.
Published: June 2013

Prestack migration has angle-dependent wavelet stretch effects, which lowers the image resolution at large reflection angles. Most current stretch correction methods operate on the migrated images. We develop a new stretch-free imaging condition, which does a shrink-and-shift operation on the extracted propagation wavelet after extrapolation, but before the imaging condition is applied. The algorithm is illustrated with the excitation amplitude imaging condition; the new images show successful stretch corrections over wide angle apertures, and preserve amplitude and phase.
Epigenetic Modifications During Sex Change Repress Gonadotropin Stimulation of Cyp19a1a in a Teleost Ricefield Eel (Monopterus albus)
Authors: Zhang Yang , Zhang Shen , Liu Zhixin , Zhang Lihong , Zhang Weimin
Published: June 2013

In vertebrates, cytochrome P450 aromatase, encoded by cyp19a1, converts androgens to estrogens and plays important roles in gonadal differentiation and development. The present study examines whether epigenetic mechanisms are involved in cyp19a1a expression and subsequent gonadal development in the hermaphroditic ricefield eel. The expression of the ricefield eel cyp19a1a was stimulated by gonadotropin via the cAMP pathway in the ovary but not the ovotestis or testis. The CpG within the cAMP response element (CRE) of the cyp19a1a promoter was hypermethylated in the ovotestis and testis compared with the ovary. The methylation levels of CpG sites around CRE in the distal region (region II) and around steroidogenic factor 1/adrenal 4 binding protein sites and TATA box in the proximal region (region I) were inversely correlated with cyp19a1a expression during the natural sex change from female to male. In vitro DNA methylation decreased the basal and forskolin-induced activities of cyp19a1a promoter. Chromatin immunoprecipitation assays indicated that histone 3 (Lys9) in both regions I and II of the cyp19a1a promoter were deacetylated and trimethylated in the testis, and in contrast to the ovary, phosphorylated CRE-binding protein failed to bind to these regions. Lastly, the DNA methylation inhibitor 5-aza-2′-deoxycytidine reversed the natural sex change of ricefield eels. These results suggested that epigenetic mechanisms involving DNA methylation and histone deacetylation and methylation may abrogate the stimulation of cyp19a1a by gonadotropins in a male-specific fashion. This may be a mechanism widely used to drive natural sex change in teleosts as well as gonadal differentiation in other vertebrates.
The Two Kisspeptin Neuronal Populations Are Differentially Organized and Activated by Estradiol in Mice
Authors: Brock Olivier , Bakker Julie
Published: June 2013

In rodents, kisspeptin-expressing neurons are localized in 2 hypothalamic brain nuclei (anteroventral periventricular nucleus/periventricular nucleus continuum [AVPv/PeN] and arcuate nucleus [ARC]) and modulated by sex steroids. By using wild-type (WT) and aromatase knockout (ArKO) mice (which cannot convert testosterone into estradiol) and immunohistochemistry, we observed that WT females showed a continuous increase in kisspeptin peptide expression in the ARC across postnatal ages (postnatal day 5 [P5] to P25), whereas WT males did not show any expression before P25. Kisspeptin peptide expression was also present in ArKO females but did not increase over this early postnatal period, suggesting that kisspeptin peptide expression in the ARC is organized by estradiol-dependent and -independent mechanisms. We also compared kisspeptin peptide expression between groups of adult male and female mice that were left gonadally intact or gonadectomized and treated or not with estradiol (E2) or DHT. In the ARC, kisspeptin peptide expression decreased after gonadectomy but was completely rescued by either E2 or DHT treatment in each sex/genotype. However, kisspeptin peptide expression was lower in ArKO compared with WT subjects. In the AVPv/PeN, ArKO females showed a male-typical kisspeptin peptide expression, and adult E2 treatment partially restored kisspeptin peptide expression. Finally, we showed that, after E2 treatment of WT and ArKO mice between either P5 and P15 or P15 and P25, AVPv/PeN kisspeptin peptide expression could be still masculinized at P5, but was feminized from P15 onward. In conclusion, the 2 kisspeptin neuronal populations (AVPv/PeN vs ARC) seem to be differentially organized and activated by E2.
Predisposition to apoptosis in keratin 8-null liver is related to inactivation of NF-κB and SAPKs but not decreased c-Flip
Authors: Lee Jongeun , Jang Kwi-Hoon , Kim Hakhyun , Lim Younglan , Kim Sujin , Yoon Han-Na , Chung In Kwon , Roth Jürgen , Ku Nam-On
Published: June 2013

Keratin 8 and 18 (K8/K18) are major intermediate filament proteins of liver hepatocytes. They provide mechanical and nonmechanical stability, thereby protecting cells from stress. Hence, K8-null mice are highly sensitive to Fas-mediated liver cell apoptosis. However, the role of c-Flip protein in K8-null related susceptibility to liver injury is controversial. Here we analyzed c-Flip protein expression in various K8 or K18 null/mutant transgenic livers and show that they are similar in all analyzed transgenic livers and that previously reported c-Flip protein changes are due to antibody cross-reaction with mouse K18. Furthermore, analysis of various apoptosis- or cell survival-related proteins demonstrated that inhibition of phosphorylation of NF-κB and various stress activated protein kinases (SAPKs), such as p38 MAPK, p44/42 MAPK and JNK1/2, is related to the higher sensitivity of K8-null hepatocytes whose nuclear NF-κB is rapidly depleted through Fas-mediated apoptosis. Notably, we found that NF-κB and the studied protein kinases are associated with the K8/K18 complex and are released upon phosphorylation. Therefore, interaction of keratins with cell survival-related protein kinases and transcription factors is another important factor for hepatocyte survival.
Effect of tubulex swabs on post-extraction wound healing
Authors: Szyszkowska Anna , Rahnama Mansur , Jakiel Joanna , Puławska Marta , Szczerba Joanna , Jenda Dagmara
Published: June 2013

Socket healing after tooth extraction is a multistage process, often complicated by pain and inflammatory complications. To prevent complications in healing, many preparations of disinfecting, soothing and supporting the healing process activity are used. The effect of Tubulex swabs on wound healing was evaluated. Tubulex are sterile swabs, moistened with Tubulicid Blue, which contains benzalkonium chloride, amphoteric-2, disodium edetate dehydrate and phosphate buffer saline, giving it disinfectant and soothing properties. A positive effect of the use of Tubulex on the healing of post-extraction wounds has been proved.
Influence of fluphenazine dihydrochloride on model dipalmitoylphosphatidylcholine membranes and human genotoxically damaged lymphocyte cultures
Authors: Petrus Joanna , Czarnik-Matusewicz Bogusława , Jaszczyszyn Agata , Gąsiorowski Kazimierz , Cieślik-Boczula Katarzyna , Wesołowska Olga , Michalak Krystyna , Świątek Piotr , Malinka Wiesław
Published: June 2013

The membrane interactions can play a vital role in chemosensitizing activity of fluphenazine dihydrochloride, an inhibitor of P-glycoprotein transport function. In in vitro testings of the influence of fluphenazine dihydrochloride on model dipalmitoylphosphatidylcholine membranes and on human lymphocyte cultures, genotoxically damaged by benzo[a]pyrene, differential scanning calorimetry and rhodamine 123 retention test were applied. The results of both testings shown that the membrane interactions of fluphenazine dihydrochloride in model membrane structure and the chemosensitizing effect of this compound in examined human lymphocyte cultures, depend on its concentration in a sample.
Genetics in Endocrinology: Autosomal dominant osteopetrosis revisited: lessons from recent studies
Authors: Bollerslev Jens , Henriksen Kim , Frost Nielsen Morten , Brixen Kim , Van Hul Wim
Published: June 2013

Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the first propeller ofLRP5, a region of importance for binding inhibitory proteins. Thereby, ADO1 cannot be regarded as a classical form of osteopetrosis but must now be considered a disease of LRP5 activation. ADO (Albers-Schönberg disease, or previously ADO2) is characterized by increased number of osteoclasts and a defect in the chloride transport system (ClC-7) of importance for acidification of the resorption lacuna (a form of Chloride Channel 7 Deficiency Osteopetrosis).Ex vivostudies of osteoclasts from ADO have shown that cells do form normally but have reduced resorption capacity and an expanded life span. Bone formation seems normal despite decreased osteoclast function. Uncoupling of formation from resorption makes ADO of interest for new strategies for treatment of osteoporosis. Recent studies have integrated bone metabolism in whole-body energy homeostasis. Patients with ADO may have decreased insulin levels indicating importance beyond bone metabolism. There seems to be a paradigm shift in the treatment of osteoporosis. Targeting ClC-7 might introduce a new principle of dual action. Drugs affecting ClC-7 could be antiresorptive, still allowing ongoing bone formation. Inversely, drugs affecting the inhibitory site of LRP5 might stimulate bone formation and inhibit resorption. Thereby, these studies have highlighted several intriguing treatment possibilities, employing novel modes of action, which could provide benefits to the treatment of osteoporosis.