bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Augmented Immune Surveillance and Tumor Cell Death by Cytoplasmic Stabilization of p53 as a Chemopreventive Strategy of 3 Promising Medicinal Herbs in Murine 2-Stage Skin Carcinogenesis
Authors: Ali Farrah , Khan Rehan , Khan Abdul Quaiyoom , Lateef Md Abdul , Maqbool Tahir , Sultana Sarwat
Published: December 2013

Cancer is the final outcome of a plethora of events. Targeting the proliferation or inducing programmed cell death in a proliferating population is a major standpoint in the cancer therapy. However, proliferation is regulated by several cellular and immunologic processes. This study reports the inhibition of proliferation by augmenting immune surveillance, silencing acute inflammation, and inducing p53-mediated apoptosis of skin cancer by 3 promising medicinal extracts. We used the well-characterized model for experimental skin carcinogenesis in mice for 32 weeks to study the chemopreventive effect of the methanolic extracts of Trigonella foenumgraecum, Eclipta alba, and Calendula officinalis. All 3 extracts reduced the number, incidence, and multiplicity of tumors, which was confirmed by the pathologic studies that showed regressed tumors. There was a significant reduction in the PCNA+ nuclei in all treatment groups 32 weeks after the initiation. Mechanistic studies revealed that proliferative population in tumors is diminished by the restoration of the endogenous antioxidant defense, inhibition of the stress-related signal-transducing element NFκB, reduction of inflammation, enhancement of immunosurveillance of the genetically mutated cells, along with silencing of the cell cycle progression signals. Finally, all 3 medicinal extracts induced stable expression of p53 within the tumors, confirmed by the CFDA-Cy3 apoptosis assay. Results of our study confirm that these extracts not only limit the rate of proliferation by inhibition of the processes integral to cancer development but also induce stable cytoplasmic expression of p53-mediated apoptosis, leading to fewer and regressed tumors in mice.
Preservation by Neglect in Soviet-Era Town Planning in Tartu, Estonia
Authors: Hess Daniel Baldwin , Hiob Mart
Published: December 2013

In the former Soviet Union, traditional urban districts with pre–World War II housing were considered obsolete and the aim was to demolish them, but in practice they were frequently ignored, because efforts were focused on new housing production in order to address acute housing shortages. Inertial forces stymied plan implementation for older districts during a rich period of plan making while new residential districts were built at a fast pace on virgin land. This research analyzes more than a dozen written planning documents from various periods during the twentieth century for Tartu, Estonia, where, had mid-twentieth century town plans been implemented, entire districts of nineteenth-century and early twentieth-century wooden houses and apartment buildings would have been demolished. Findings suggest that several factors acted in concert to set the conditions for both neglect and preservation of such districts during the second half of the twentieth century that resulted in continuous occupancy of the dwellings and preserved the built form (and the social structure) of the district. These factors include a focus on building new housing and new districts rather than renovating older districts; a lack of resources to renovate older districts; and a lack of resources to implement plans. This synthesis of town planning in Estonia demonstrates how planning ideas have evolved throughout the twentieth century parallel to—but temporally delayed compared to—Western Europe and North America.
Psychological Capital
Authors: Wernsing Tara
Published: December 2013

This study examined measurement invariance of the 12-item psychological capital survey across 12 national cultures (Brazil, China, Germany, India, Italy, Mexico, Poland, South Africa, Sweden, Turkey, the United Kingdom, and the United States), representing a cross-section of all major world cultures corresponding to the GLOBE research project. Analysis of data from 56,363 employees confirms the configural second-order hierarchical factor structure for psychological capital in all national cultures. However, more stringent levels of metric equivalence were supported only with a simplified three-factor structure proposed in this research as a cross-cultural nine-item instrument. Implications for comparing means for psychological capital across national cultures are discussed.
A study on the deep etching and ohmic contact process of 6H-SiC high-temperature pressure sensor
Authors: Tang Fei , Ma Ximin , Wang Xiaohao
Published: December 2013

In all the process steps of manufacturing high-temperature pressure silicon carbide sensors, deep etching and ohmic contact are two crucial processes. Reactive ion etching is used for the deep etching of silicon carbide in our experiment, and the surface has a high quality after etching. Using nickel as the mask material on the C layer by electroplating, the depth of deep etching reaches about 81 µm and the thickness uniformity is fairly good, fluctuating within 200 nm or less. The Ti–TiN–Pt system is proposed for metallization, in which Ti, TiN and Pt are used as the contact layer, the diffusion impervious layer and the lead interaction layer, respectively. The Kelvin test shows that stable ohmic contact is achieved and a specific contact resistivity of 8.42 × 10−4Ω cm2 is detected. The etching depth of 81 µm meets the requirement of forming a sensitive circular membrane, and the metal system of Ti–TiN–Pt ensures reliable connection and stable ohmic contact between the metal and semiconductor at high temperatures.
What makes a good ultrasound report?
Authors: Edwards Hazel , Smith Jane , Weston Michael
Published: December 2013

It is essential for the management of the patient that ultrasound practitioners produce reports based on their examinations that are accurate and clear. Ideally, all reports should attempt to answer the original clinical question. This seems a simple requirement and yet it is not always as easy as it sounds. In this paper, we explore the importance of the report, reasons that give rise to poor report writing and suggest educational resources that are available to improve poor report writing. Common mistakes and language ambiguity are discussed. Finally, we suggest a simple five-point framework, which practitioners may find useful when constructing ultrasound reports.
Sonographer registration in the United Kingdom – a review of the current situation
Authors: Thomson Nigel , Paterson Audrey
Published: December 2013

There is no statutory registration as a sonographer available in the United Kingdom (UK) and the titles of ‘sonographer’ and ‘ultrasonographer’ are not legally protected. The majority of sonographers are statutorily registered with the Health and Care Professions Council or Nursing and Midwifery Council as they have a professional background as a radiographer, clinical scientist, nurse, physiotherapist or midwife that allows this, but this registration is not as a sonographer. For otherwise well-qualified and experienced sonographers, statutory registration is impossible to achieve at the present time and they have no statutory regulatory home. This can lead to problems for the sonographers themselves, for the patients and public in terms of protection and for employers when selecting staff. This paper discusses the complex registration situation for sonographers in the UK and includes reference to the alternative voluntary registers and their possible accreditation by the Professional Standards Authority.
The management of ultrasound equipment at Sheffield Teaching Hospitals NHS Foundation Trust
Authors: Verma PK , Peacock M
Published: December 2013

Management of ultrasound equipment at Sheffield Teaching Hospitals NHS Foundation Trust is described. The organisation and input of various stakeholders and their involvement with ultrasound equipment management and scientific ultrasound is discussed. Two important stakeholders are the Medical Equipment Management Group and the Radiation Safety Steering Committee. The Medical Equipment Management Group has a specific sub-group, the Ultrasound sub-group, and its role is to coordinate the purchase, replacement and quality assurance of ultrasound equipment in the Trust. The Radiation Safety Steering Committee has a non-ionising radiation representative and the role of this committee is to provide corporate assurance that any health and safety issues arising from the use of radiation to either patients, members of the public or staff within the Trust are being effectively managed. The Ultrasound sub-group of the Medical Equipment Management Group has successfully brought together management of all ultrasound equipment within the Trust and is in the process of fulfilling the quality assurance and training milestones set out by the Medical Equipment Management Group. Advice from the Radiation Safety Steering Committee has helped to increase awareness of ultrasound safety and good scanning practice, especially in the case of neonatal ultrasound imaging, within the Trust. In addition, the RSSC has given advice on clinical pathways for patients undergoing ionising radiation imaging while being treated by extra-corporeal shockwave lithotripsy.
Ultrasound quality assurance and equipment governance
Authors: Russell Stephen
Published: December 2013

A case is presented to show the importance of good governance of ultrasound medical imaging equipment. Issues relating to the large numbers and diverse range of users and equipment are identified. Based on experience gained over 25 years, supporting upwards of 1000 systems, discussions consider why and how the testing of ultrasound systems should be approached by both the medical physics expert and end user. The management of the process is presented in the context of professional guidance and monitoring organisations’ standards are considered to give a suggested best practice.
Enacting identity in microblogging through ambient affiliation
Authors: Zappavigna Michele
Published: December 2013

This article explores how we use social media to construe identities and align with others into communities of shared values. The focus is on how ‘users of language perform their identities within uses of language’: How do personae using the microblogging service Twitter perform relational identities as they enact discourse fellowships? Addressing this question means understanding how personae enter into ambient affiliation. Such affiliation is ambient in the sense that social media users may not be interacting directly, but instead participating in mass performances of hashtagging or contributing to iterations of Internet memes. This article will consider three key bonds ( self-deprecation, frazzle and addiction) using both a 100 million-word corpus of posts and a smaller specialized corpus collected by capturing the entire Twitter stream of a particular user.
Urticaria
Authors: Simon Chantal
Published: December 2013

The term urticaria refers to a vascular reaction of the upper dermis marked by the transient appearance of slightly elevated patches (weals), that are redder or paler than the surrounding skin and often accompanied by severe itching. It is commonly referred to as hives, or nettle rash (the word urticarial comes from the Latin, urticus, meaning nettle). This article explores the causes of urticaria and its management in general practice.
Tolcapone addition improves Parkinson’s disease associated nonmotor symptoms
Authors: Müller Thomas ,   for the TANIMOS Study Investigators
Published: December 2013

Background:

Addition of catechol-O-methyltransferase inhibitors to a conventional levodopa/dopadecarboxylase inhibitor regimen improves motor symptoms in patients with Parkinson’s disease. Optimizing dopamine substitution is also beneficial for nonmotor features.

Objectives:

To investigate the efficacy of supplemental tolcapone intake on nonmotor symptoms.

Design/methods:

A total of 125 levodopa-treated patients additionally took tolcapone in this observational trial. Initially and following 4 weeks of tolcapone intake, the neurologist scored with Unified Parkinson’s Disease Rating Scale parts I, II, IV, the nonmotor symptoms scale for Parkinson’s disease and recorded the off time. The patients rated themselves with the EuroQuol, its visual analogue scale and the nonmotor screening questionnaire. Caregivers reported the daily duration of care giving.

Results:

All scores improved except for Unified Parkinson’s Disease Rating Scale part IV and domains 4, 5 and 8 of the nonmotor symptoms scale for Parkinson’s disease.

Conclusion:

This trial demonstrates that tolcapone addition may improve nonmotor features.
Tumor heterogeneity in the clinic: is it a real problem?
Authors: Janku Filip
Published: December 2013

Tumor heterogeneity is one of the major problems limiting the efficacy of targeted therapies and compromising treatment outcomes. A better understanding of tumor biology has advanced our knowledge of the molecular landscape of cancer to an unprecedented level. However, most patients with advanced cancers treated with appropriately selected targeted therapies become resistant to the therapy, ultimately developing disease progression and succumbing to metastatic disease. Multiple factors account for therapeutic failures, which include cancer cells accumulating new molecular aberrations as a consequence of tumor progression and selection pressure of cancer therapies. Therefore, single agent targeted therapies, often administered in advanced stages, are unlikely to have a sufficiently lethal effect in most cancers. Finally, the molecular profile of cancer can change over time, which we are not able to monitor with existing strategies using tumor tissue biopsies as the gold standard for molecular diagnostics. Novel technologies focusing on testing low-risk, easily obtainable material, such as molecular cell-free DNA from plasma, can fill that gap and allow personalized therapy to be delivered in real time.
Phantom-based quality assurance measurements in B-mode ultrasound
Authors: Mannila Vilma , Sipilä Outi
Published: December 2013

Background

Recommended phantom-based quality assurance measurements in B-mode ultrasound (US) may be tedious. For the purpose of cost-effective US quality assurance it is important to evaluate measurements that effectively reflect the quality of US scanner.

Purpose

To find out which recommended phantom-based quality assurance measurements are effective in detecting dead or weak transducer elements or channels in US scanners when visual image analysis and manual measurements are used.

Material and Methods

Altogether 66 transducers from 33 US scanners were measured using a general purpose phantom and a transducer tester. The measurements were divided into two groups. Group I consisted of phantom-based uniformity measurement, imaging the air with a clean transducer (air image) and measuring the transducer with the transducer tester, and group II of phantom-based measurements of depth of penetration, beam profile, near field, axial and lateral resolution, and vertical and horizontal distance accuracy. The group II measurements were compared to group I measurements.

Results

With group I measurements, the results with 20% of the transducers were found defective. With 35% of the transducers the results were considered defective in group II measurements. Concurrent flaws in both groups were found with 11% of the transducers.

Conclusion

Phantom-based measurements of depth of penetration, beam profile, near field, axial and lateral resolution, and vertical and horizontal distance accuracy did not consistently detect dead or weak transducer elements or channels in US scanners.
Imaging findings for malignancy-mimicking nodular fasciitis of the breast and a review of previous imaging studies
Authors: Son Youn Mi , Nahm Ji Hae , Moon Hee Jung , Kim Min Jung , Kim Eun-Kyung
Published: December 2013

We report a case of nodular fasciitis of the breast mimicking malignant tumor. A 41-year-old female patient with a palpable mass in the upper center of the left breast present for 1 week visited our hospital. A mammogram showed an oval isodense with a partially indistinct margin. Ultrasonography demonstrated a hypoechoic mass, 8 × 11 mm in size. Breast cancer could not be excluded based on mammographic and ultrasonographic (US) findings. A core needle biopsy and excisional biopsy were performed. Histopathologic examination revealed a diagnosis of nodular fasciitis of the breast. The mammographic and US findings of nodular fasciitis in the breast is reviewed.
The Anatomic Pattern of Injuries in Acute Inversion Ankle Sprains
Authors: Khor Yuet Peng , Tan Ken Jin
Published: December 2013

Background:

There are little data on the incidence and patterns of injuries seen on magnetic resonance imaging (MRI) in acute inversion ankle sprains. This study may help in the understanding of the pathomechanics, natural history, and outcomes of this common injury.

Study Design:

Case series; Level of evidence, 4.

Methods:

From June 2011 to June 2013, a total of 64 consecutive patients had MRI of the ankle performed for acute inversion injury to the ankle. All injuries/pathologies reported were recorded.

Results:

Only 22% of patients had isolated lateral ligament complex injuries. Twenty-two percent of patients had other pathologies but no lateral ligament injury, and 53% had lateral ligament injuries in combination with other pathologies or injuries. The most common associated finding with lateral ligament injuries was bone bruising (76%) followed by deltoid ligament injury (50%). The overall incidence of bone bruising was 50%. Thirty percent of ankles had tendon pathology, 27% had deltoid ligament injury, and 22% had occult fractures.

Conclusion:

Isolated lateral ligament ankle injury is not as common as is believed. The pattern of injury seems complex, and most patients appear to have more injuries than expected. MRI reveals additional information that may have significance in terms of diagnosis, treatment, and prognosis in this common injury.
Monoclonal antibody targeting of IL-3 receptor α with CSL362 effectively depletes CML progenitor and stem cells
Authors: Nievergall Eva , Ramshaw Hayley S. , Yong Agnes S. M. , Biondo Mark , Busfield Samantha J. , Vairo Gino , Lopez Angel F. , Hughes Timothy P. , White Deborah L. , Hiwase Devendra K.
Published: December 2013

Key Points

IL-3 receptor α (CD123) expression is elevated in CML progenitor and stem cells compared with healthy donors. CD123 monoclonal antibody targeting represents a novel, potentially clinically relevant approach to deplete CML progenitor and stem cells.
AZD1208, a potent and selective pan-Pim kinase inhibitor, demonstrates efficacy in preclinical models of acute myeloid leukemia
Authors: Keeton Erika K. , McEachern Kristen , Dillman Keith S. , Palakurthi Sangeetha , Cao Yichen , Grondine Michael R. , Kaur Surinder , Wang Suping , Chen Yuching , Wu Allan , Shen Minhui , Gibbons Francis D. , Lamb Michelle L. , Zheng Xiaolan , Stone Richard M. , DeAngelo Daniel J. , Platanias Leonidas C. , Dakin Les A. , Chen Huawei , Lyne Paul D. , Huszar Dennis
Published: December 2013

Key Points

AZD1208 is a selective pan-Pim kinase inhibitor with efficacy in AML cells, xenografts, and Flt3-internal tandem duplication or Flt3 wild-type patient samples. AML cell growth inhibition is associated with suppression of p70S6K, 4EBP1 phosphorylation, and messenger RNA translation.
How we treat higher-risk myelodysplastic syndromes
Authors: Sekeres Mikkael A. , Cutler Corey
Published: December 2013

Higher-risk myelodysplastic syndromes (MDS) are defined by patients who fall into higher-risk group categories in the original or revised International Prognostic Scoring System. Survival for these patients is dismal, and treatment should be initiated rapidly. Standard therapies include the hypomethylating agents azacitidine and decitabine, which should be administered for a minimum of 6 cycles, and continued for as long as a patient is responding. Once a drug fails in one of these patients, further treatment options are limited, median survival is <6 months, and consideration should be given to clinical trials. Higher-risk eligible patients should be offered consultation to discuss hematopoietic stem cell transplantation close to the time of diagnosis, depending on patient goals of therapy, with consideration given to proceeding to transplantation soon after an optimal donor is located. In the interim period before transplantation, hypomethylating agent therapy, induction chemotherapy, or enrollment in a clinical trial should be considered to prevent disease progression, although the optimal pretransplantation therapy is unknown.
Plasma CXCL9 elevations correlate with chronic GVHD diagnosis
Authors: Kitko Carrie L. , Levine John E. , Storer Barry E. , Chai Xiaoyu , Fox David A. , Braun Thomas M. , Couriel Daniel R. , Martin Paul J. , Flowers Mary E. , Hansen John A. , Chang Lawrence , Conlon Megan , Fiema Bryan J. , Morgan Rachel , Pongtornpipat Prae , Lamiman Kelly , Ferrara James L. M. , Lee Stephanie J. , Paczesny Sophie
Published: December 2013

Key Points

Plasma concentrations of CXCL9 are elevated at the onset of cGVHD diagnosis, but not in patients with cGVHD for more than 3 months. Plasma concentrations of CXCL9 are impacted by immunosuppressive therapy.
Meta-analysis methods for combining multiple expression profiles: comparisons, statistical characterization and an application guideline
Authors: Chang Lun-Ching , Lin Hui-Min , Sibille Etienne , Tseng George C
Published: December 2013

Background

As high-throughput genomic technologies become accurate and affordable, an increasing number of data sets have been accumulated in the public domain and genomic information integration and meta-analysis have become routine in biomedical research. In this paper, we focus on microarray meta-analysis, where multiple microarray studies with relevant biological hypotheses are combined in order to improve candidate marker detection. Many methods have been developed and applied in the literature, but their performance and properties have only been minimally investigated. There is currently no clear conclusion or guideline as to the proper choice of a meta-analysis method given an application; the decision essentially requires both statistical and biological considerations.

Results

We performed 12 microarray meta-analysis methods for combining multiple simulated expression profiles, and such methods can be categorized for different hypothesis setting purposes: (1)HSA: DE genes with non-zero effect sizes in all studies, (2)HSB: DE genes with non-zero effect sizes in one or more studies and (3)HSr: DE gene with non-zero effect in "majority" of studies. We then performed a comprehensive comparative analysis through six large-scale real applications using four quantitative statistical evaluation criteria: detection capability, biological association, stability and robustness. We elucidated hypothesis settings behind the methods and further apply multi-dimensional scaling (MDS) and an entropy measure to characterize the meta-analysis methods and data structure, respectively.

Conclusions

The aggregated results from the simulation study categorized the 12 methods into three hypothesis settings (HSA,HSB, andHSr). Evaluation in real data and results from MDS and entropy analyses provided an insightful and practical guideline to the choice of the most suitable method in a given application. All source files for simulation and real data are available on the author’s publication website.
A genome-wide scan for signatures of differential artificial selection in ten cattle breeds
Authors: Rothammer Sophie , Seichter Doris , Förster Martin , Medugorac Ivica
Published: December 2013

Background

Since the times of domestication, cattle have been continually shaped by the influence of humans. Relatively recent history, including breed formation and the still enduring enormous improvement of economically important traits, is expected to have left distinctive footprints of selection within the genome. The purpose of this study was to map genome-wide selection signatures in ten cattle breeds and thus improve the understanding of the genome response to strong artificial selection and support the identification of the underlying genetic variants of favoured phenotypes. We analysed 47,651 single nucleotide polymorphisms (SNP) using Cross Population Extended Haplotype Homozygosity (XP-EHH).

Results

We set the significance thresholds using the maximum XP-EHH values of two essentially artificially unselected breeds and found up to 229 selection signatures per breed. Through a confirmation process we verified selection for three distinct phenotypes typical for one breed (polledness in Galloway, double muscling in Blanc-Bleu Belge and red coat colour in Red Holstein cattle). Moreover, we detected six genes strongly associated with known QTL for beef or dairy traits (TG, ABCG2, DGAT1, GH1, GHRand the Casein Cluster) within selection signatures of at least one breed. A literature search for genes lying in outstanding signatures revealed further promising candidate genes. However, in concordance with previous genome-wide studies, we also detected a substantial number of signatures without any yet known gene content.

Conclusions

These results show the power of XP-EHH analyses in cattle to discover promising candidate genes and raise the hope of identifying phenotypically important variants in the near future. The finding of plausible functional candidates in some short signatures supports this hope. For instance,MAP2K6is the only annotated gene of two signatures detected in Galloway and Gelbvieh cattle and is already known to be associated with carcass weight, back fat thickness and marbling score in Korean beef cattle. Based on the confirmation process and literature search we deduce that XP-EHH is able to uncover numerous artificial selection targets in subpopulations of domesticated animals.
Enhancing effect of lysine combined with other compounds on cephamycin C production in Streptomyces clavuligerus
Authors: Leite Carla A , Cavallieri André P , Araujo Maria L G C
Published: December 2013

Background

Lysine plays an important role in Streptomyces clavuligerus metabolism; it takes part in its catabolism, via cadaverine, and in its secondary metabolism, in which lysine is converted via 1-piperideine-6-carboxylate to alpha-aminoadipic acid, a beta-lactam antibiotic precursor. The role of lysine as an enhancer of cephamycin C production, when added to production medium at concentrations above 50 mmol l-1, has already been reported in the literature, with some studies attributing a positive influence to multifunctional diamines, among other compounds. However, there is a lack of research on the combined effect of these compounds on antibiotic production.

Results

Results from experimental design-based tests were used to conduct response surface-based optimization studies in order to investigate the synergistic effect of combining lysine with cadaverine, putrescine, 1,3-diaminopropane, or alpha-aminoadipic acid on cephamycin C volumetric production. Lysine combined with cadaverine influenced production positively, but only at low lysine concentrations. On the whole, higher putrescine concentrations (0.4 g l-1) affected negatively cephamycin C volumetric production. In comparison to culture media containing only lysine as additive, combinations of this amino acid with alpha-aminoadipic acid or 1,3-diaminopropane increased cephamycin C production by more than 100%.

Conclusion

This study demonstrated that different combinations of lysine with diamines or lysine with alpha-aminoadipic acid engender significant differences with respect to antibiotic volumetric production, with emphasis on the benefits observed for lysine combined with alpha-aminoadipic acid or 1,3-diaminopropane. This increase is explained by mathematical models and demonstrated by means of bioreactor cultivations. Moreover, it is consistent with the positive influence of these compounds on lysine conversion to alpha-aminoadipic acid, a limiting step in cephamycin C production.
Commensal Streptococcus agalactiaeisolated from patients seen at University Hospital of Londrina, Paraná, Brazil: capsular types, genotyping, antimicrobial susceptibility and virulence determinants
Authors: Otaguiri Eliane Saori , Morguette Ana Elisa Belotto , Tavares Eliandro Reis , dos Santos Pollyanna Myrella Capela , Morey Alexandre Tadachi , Cardoso Juscélio Donizete , Perugini Márcia Regina Eches , Yamauchi Lucy Megumi , Yamada-Ogatta Sueli Fumie
Published: December 2013

Background

Streptococcus agalactiae or Group B Streptococci (GBS) have the ability to access various host sites, which reflects its adaptability to different environments during the course of infection. This adaptation is due to the expression of virulence factors that are involved with survival, invasion and bacterial persistence in the host. This study aimed to characterize GBS isolates from women of reproductive age seen at University Hospital of Londrina, according to capsular typing, genetic relatedness, antimicrobial susceptibility profile and occurrence of virulence determinants.

Results

A total of 83 GBS isolates were enrolled in this study. Capsular types Ia (42.2%), II (10.8%), III (14.5%) and V (30.1%) were identified in most GBS. One isolate each was classified as type IX and non-typeable.

A total of 15 multiple locus variable number of tandem repeat analysis (MLVA) types were identified among the isolates, seven were singletons and eight were represented by more than four isolates. All isolates were susceptible to penicillin, ampicillin, cefepime, cefotaxime, chloramphenicol, levofloxacin and vancomycin. Resistance to erythromycin and clindamycin was observed in 19.3 and 13.3% of isolates, respectively. All isolates resistant to clindamycin were simultaneously resistant to erythromycin and were distributed in the capsular types III and V. One isolate showed the constitutive macrolide-lincosamide-streptogramin B (cMLSB) phenotype and ten showed the inducible MLSB (iMLSB) phenotype. The mechanism of resistance to erythromycin and clindamycin more prevalent among these isolates was mediated by the gene ermA, alone or in combination with the gene ermB. The isolates displaying resistance only to erythromycin belonged to capsular type Ia, and showed the M phenotype, which was mediated by the mefA/E gene. All isolates harbored the gene hylB and at least one pilus variant, PI-1, PI-2a or PI-2b. Although cylE was observed in all GBS, four isolates were classified as gamma-hemolytic and carotenoid pigment non-producers.

Conclusions

Our results indicate the potential virulence of commensal GBS isolates, reinforcing the need for continued screening for this bacterium to prevent infections. The distribution of capsular and pili antigens, and MLVA profiles was also identified, which may contribute to the development of new strategies for the prevention and treatment of GBS infection.
Global RNA sequencing reveals that genotype-dependent allele-specific expression contributes to differential expression in rice F1 hybrids
Authors: Song Gaoyuan , Guo Zhibin , Liu Zhenwei , Cheng Qin , Qu Xuefeng , Chen Rong , Jiang Daiming , Liu Chuan , Wang Wei , Sun Yunfang , Zhang Liping , Zhu Yingguo , Yang Daichang
Published: December 2013

Background

Extensive studies on heterosis in plants using transcriptome analysis have identified differentially expressed genes (DEGs) in F1 hybrids. However, it is not clear why yield in heterozygotes is superior to that of the homozygous parents or how DEGs are produced. Global allele-specific expression analysis in hybrid rice has the potential to answer these questions.

Results

We report a genome-wide allele-specific expression analysis using RNA-sequencing technology of 3,637–3,824 genes from three rice F1 hybrids. Of the expressed genes, 3.7% exhibited an unexpected type of monoallelic expression and 23.8% showed preferential allelic expression that was genotype-dependent in reciprocal crosses. Those genes exhibiting allele-specific expression comprised 42.4% of the genes differentially expressed between F1 hybrids and their parents. Allele-specific expression accounted for 79.8% of the genes displaying more than a 10-fold expression level difference between an F1 and its parents, and almost all (97.3%) of the genes expressed in F1, but non-expressed in one parent. Significant allelic complementary effects were detected in the F1 hybrids of rice.

Conclusions

Analysis of the allelic expression profiles of genes at the critical stage for highest biomass production from the leaves of three different rice F1 hybrids identified genotype-dependent allele-specific expression genes. A cis-regulatory mechanism was identified that contributes to allele-specific expression, leading to differential gene expression and allelic complementary effects in F1 hybrids.
Transcriptional profiling reveals molecular signatures associated with HIV permissiveness in Th1Th17 cells and identifies Peroxisome Proliferator-Activated Receptor Gammaas an intrinsic negative regulator of viral replication
Authors: Bernier Annie , Cleret-Buhot Aurélie , Zhang Yuwei , Goulet Jean-Philippe , Monteiro Patricia , Gosselin Annie , DaFonseca Sandrina , Wacleche Vanessa Sue , Jenabian Mohammad-Ali , Routy Jean-Pierre , Tremblay Cécile , Ancuta Petronela
Published: December 2013

Background

We previously demonstrated that primary Th1Th17 cells are highly permissive to HIV-1, whereas Th1 cells are relatively resistant. Molecular mechanisms underlying these differences remain unknown.

Results

Exposure to replication competent and single-round VSV-G pseudotyped HIV strains provide evidence that superior HIV replication in Th1Th17vs.Th1 cells was regulated by mechanisms located at entry and post-entry levels. Genome-wide transcriptional profiling identified transcripts upregulated (n = 264) and downregulated (n = 235) in Th1Th17vs.Th1 cells (p-value < 0.05; fold change cut-off 1.3).Gene Set Enrichment Analysisrevealed pathways enriched in Th1Th17 (nuclear receptors, trafficking, p38/MAPK, NF-κB, p53/Ras, IL-23)vs.Th1 cells (proteasome, interferon α/β). Differentially expressed genes were classified into biological categories usingGene Ontology. Th1Th17 cells expressed typical Th17 markers (IL-17A/F, IL-22, CCL20, RORC, IL-26, IL-23R, CCR6) and transcripts functionally linked to regulating cell trafficking (CEACAM1, MCAM), activation (CD28, CD40LG, TNFSF13B, TNFSF25, PTPN13, MAP3K4, LTB, CTSH), transcription (PPARγ, RUNX1, ATF5, ARNTL), apoptosis (FASLG), and HIV infection (CXCR6, FURIN). Differential expression of CXCR6, PPARγ, ARNTL, PTPN13, MAP3K4, CTSH, SERPINB6, PTK2, and ISG20 was validated by RT-PCR, flow cytometry and/or confocal microscopy. The nuclear receptor PPARγ was preferentially expressed by Th1Th17 cells. PPARγ RNA interference significantly increased HIV replication at levels post-entry and prior HIV-DNA integration. Finally, the activation of PPARγ pathwayviathe agonist Rosiglitazone induced the nuclear translocation of PPARγ and a robust inhibition of viral replication.

Conclusions

Thus, transcriptional profiling in Th1Th17vs. Th1 cells demonstrated that HIV permissiveness is associated with a superior state of cellular activation and limited antiviral properties and identified PPARγ as an intrinsic negative regulator of viral replication. Therefore, triggering PPARγ pathwayvianon-toxic agonists may contribute to limiting covert HIV replication and disease progression during antiretroviral treatment.
Activation of Cyclin-Dependent Kinase 5 Mediates Orofacial Mechanical Hyperalgesia
Authors: Prochazkova Michaela , Terse Anita , Amin Niranjana D , Hall Bradford , Utreras Elias , Pant Harish C , Kulkami Ashok B
Published: December 2013

Background

Cyclin-dependent kinase 5 (Cdk5) is a unique member of the serine/threonine kinase family. This kinase plays an important role in neuronal development, and deregulation of its activity leads to neurodegenerative disorders. Cdk5 also serves an important function in the regulation of nociceptive signaling. Our previous studies revealed that the expression of Cdk5 and its activator, p35, is upregulated in nociceptive neurons during peripheral inflammation. The aim of the present study was to characterize the involvement of Cdk5 in orofacial pain. Since mechanical hyperalgesia is the distinctive sign of many orofacial pain conditions, we adapted an existing orofacial stimulation test to assess the behavioral responses to mechanical stimulation in the trigeminal region of the transgenic mice with either reduced or increased Cdk5 activity.

Results

Mice overexpressing or lacking p35, an activator of Cdk5, showed altered phenotype in response to noxious mechanical stimulation in the trigeminal area. Mice with increased Cdk5 activity displayed aversive behavior to mechanical stimulation as indicated by a significant decrease in reward licking events and licking time. The number of reward licking/facial contact events was significantly decreased in these mice as the mechanical intensity increased. By contrast, mice deficient in Cdk5 activity displayed mechanical hypoalgesia.

Conclusions

Collectively, our findings demonstrate for the first time the important role of Cdk5 in orofacial mechanical nociception. Modulation of Cdk5 activity in primary sensory neurons makes it an attractive potential target for the development of novel analgesics that could be used to treat multiple orofacial pain conditions.
Identification of crop cultivars with consistently high lignocellulosic sugar release requires the use of appropriate statistical design and modelling
Authors: Oakey Helena , Shafiei Reza , Comadran Jordi , Uzrek Nicola , Cullis Brian , Gomez Leonardo D , Whitehead Caragh , McQueen-Mason Simon J , Waugh Robbie , Halpin Claire
Published: December 2013

Background

In this study, a multi-parent population of barley cultivars was grown in the field for two consecutive years and then straw saccharification (sugar release by enzymes) was subsequently analysed in the laboratory to identify the cultivars with the highest consistent sugar yield. This experiment was used to assess the benefit of accounting for both the multi-phase and multi-environment aspects of large-scale phenotyping experiments with field-grown germplasm through sound statistical design and analysis.

Results

Complementary designs at both the field and laboratory phases of the experiment ensured that non-genetic sources of variation could be separated from the genetic variation of cultivars, which was the main target of the study. The field phase included biological replication and plot randomisation. The laboratory phase employed re-randomisation and technical replication of samples within a batch, with a subset of cultivars chosen as duplicates that were randomly allocated across batches. The resulting data was analysed using a linear mixed model that incorporated field and laboratory variation and a cultivar by trial interaction, and ensured that the cultivar means were more accurately represented than if the non-genetic variation was ignored. The heritability detected was more than doubled in each year of the trial by accounting for the non-genetic variation in the analysis, clearly showing the benefit of this design and approach.

Conclusions

The importance of accounting for both field and laboratory variation, as well as the cultivar by trial interaction, by fitting a single statistical model (multi-environment trial, MET, model), was evidenced by the changes in list of the top 40 cultivars showing the highest sugar yields. Failure to account for this interaction resulted in only eight cultivars that were consistently in the top 40 in different years. The correspondence between the rankings of cultivars was much higher at 25 in the MET model. This approach is suited to any multi-phase and multi-environment population-based genetic experiment.
Membranous nephropathy with acquired factor V inhibitor: a case report
Authors: Kitamura Shinji , Misawa Mahito , Namba Sayaka , Tsuji Kenji , Torigoe Rikako , Shima Midori , Makino Hirofumi
Published: December 2013

Background

Membranous nephropathy is one of the most common causes of nephrotic syndrome in adults. In contrast, acquired factor V inhibitor is a rare bleeding disorder.

Case presentation

A 62-year-old Asian man with a history of cerebral hemorrhage, purpura, eosinophilia and hyper immunoglobulin E syndrome developed proteinuria. The bleeding disorder was diagnosed with acquired factor V inhibitors. A renal biopsy revealed that he suffered from membranous nephropathy with glomerular endothelial damage which is reported to be involved in another factor disorder. After the steroid administration, the coagulation test and proteinuria were improved.

Conclusions

The presence of factor V inhibitors may have been involved in the development of membranous nephropathy.
Dual potential of microalgae as a sustainable biofuel feedstock and animal feed
Authors: Lum Krystal K , Kim Jonggun , Lei Xin Gen
Published: December 2013

The rise in global population has led to explorations of alternative sources of energy and food. Because corn and soybean are staple food crops for humans, their common use as the main source of dietary energy and protein for food-producing animals directly competes with their allocation for human consumption. Alternatively, de-fatted marine microalgal biomass generated from the potential biofuel production may be a viable replacement of corn and soybean meal due to their high levels of protein, relatively well-balanced amino acid profiles, and rich contents of minerals and vitamins, along with unique bioactive compounds. Although the full-fatted (intact) microalgae represent the main source of omega-3 (n-3) polyunsaturated fatty acids including docohexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the de-fatted microalgal biomass may still contain good amounts of these components for enriching DHA/EPA in eggs, meats, and milk. This review is written to highlight the necessity and potential of using the de-fatted microalgal biomass as a new generation of animal feed in helping address the global energy, food, and environmental issues. Nutritional feasibility and limitation of the biomass as the new feed ingredient for simple-stomached species are elaborated. Potential applications of the biomass for generating value-added animal products are also explored.
Adaptation to mTOR kinase inhibitors by amplification of eIF4E to maintain cap-dependent translation
Authors: Cope Claire L , Gilley Rebecca , Balmanno Kathryn , Sale Matthew J. , Howarth Karen D. , Hampson Mark , Smith Paul D , Guichard Sylvie M , Cook Simon J
Published: December 2013

The mechanistic target of rapamycin (mTOR) protein kinase coordinates responses to nutrients and growth factors and is an anti-cancer drug target. To anticipate how cells will respond and adapt to chronic mTORC1 and mTORC2 inhibition we have generated SW620 colon cancer cells with acquired resistance to the ATP-competitive mTOR kinase inhibitor AZD8055 (SW620:8055R). AZD8055 inhibited mTORC1 and mTORC2 signalling and caused a switch from cap-dependent to IRES-dependent translation in parental SW620 cells. In contrast, SW620:8055R cells exhibited a loss of S6K signalling, an increase in expression of the eukaryotic translation initiation factor eIF4E and increased cap-dependent mRNA translation. As a result the expression of CCND1 and MCL1, proteins encoded by eIF4E-sensitive and capdependent transcripts, was refractory to AZD8055 in SW620:8055R cells. RNAimediated knockdown of eIF4E reversed acquired resistance to AZD8055 in SW620:8055R cells; furthermore increased expression of eIF4E was sufficient to reduce sensitivity to AZD8055 in a heterologous cell system. Finally, whilst the combination of MEK1/2 inhibitors with mTOR inhibitors is an attractive rational drug combination, SW620:8055R cells were actually cross-resistant to the MEK1/2 inhibitor selumetinib. These results exemplify the convergence of ERK1/2 and mTOR signalling at eIF4E and the key role of eIF4E downstream of mTOR in maintaining cell proliferation. They also have important implications for therapeutic strategies based around mTOR and MEK1/2-ERK1/2.
Temperature during embryonic development has persistent effects on metabolic enzymes in the muscle of zebrafish
Authors: Schnurr Meghan E. , Yin Yi , Scott Graham R.
Published: December 2013

Global warming is intensifying interest in the physiological consequences of temperature change in ectotherms, but we still have a relatively poor understanding of the effects of temperature on early life stages. This study determined how embryonic temperature (TE) affects development and the activity of metabolic enzymes in the swimming muscle of zebrafish. Embryos developed successfully to hatching (survival ≥ 88%) from 22°C to 32°C, but suffered sharp increases in mortality outside of this range. Embryos that were incubated until hatching at a control TE (27°C) or near the extremes for successful development (22°C or 32°C) were next raised to adulthood under control conditions at 27°C. Growth trajectories after hatching were altered in the 22°C and 32°C TE groups compared to 27°C TE controls, but growth slowed after 3 months of age in all groups. Maximal enzyme activities of cytochrome c oxidase (COX), citrate synthase (CS), hydroxyacyl-coA dehydrogenase (HOAD), pyruvate kinase (PK), and lactate dehydrogenase (LDH) were measured across a range of assay temperatures (22°C, 27°C, 32°C, 36°C) in adults from each TE group that were acclimated to 27°C or 32°C. Substrate affinities (Km) were also determined for COX and LDH. In adult fish acclimated to 27°C, COX and PK activities were higher in 22°C and 32°C TE groups than in 27°C TE controls, and the temperature optimum for COX activity was higher in the 32°C TE group than in the 22°C TE group. Warm acclimation reduced COX, CS, and/or PK activities in the 22°C and 32°C TE groups, possibly to compensate for thermal effects on molecular activity. This response did not occur in the 27°C TE controls, which instead increased LDH and HOAD activities. Warm acclimation also increased thermal sensitivity (Q10) of HOAD to cool temperatures across all TE groups. We conclude that the temperature experienced during early development can have a persistent impact on energy metabolism pathways and acclimation capacity in later life.
Blood feeding induces hemocyte proliferation and activation in the African malaria mosquito, Anopheles gambiae Giles
Authors: Bryant William B. , Michel Kristin
Published: December 2013

Malaria is a global public health problem especially in sub-Saharan Africa, where the mosquito Anopheles gambiae Giles serves as the major vector for the protozoan Plasmodium falciparum Welch. One determinant of malaria vector competence is the mosquito's immune system. Hemocytes are a critical component as they produce soluble immune factors that either support or prevent malaria parasite development. However, despite their importance in vector competence, understanding of their basic biology is just developing. Applying novel technologies to the study of mosquito hemocytes, we investigated the effect of blood meal on hemocyte population dynamics, DNA replication, and cell cycle progression. In contrast to prevailing published work, data presented here demonstrate that hemocytes in adult mosquitoes continue to undergo low basal levels of replication. In addition, blood ingestion caused significant changes in hemocytes with 24 h. Hemocytes displayed an increase in cell number, size, granularity, and Ras-MAPK signaling as well as altered cell surface moieties. As these changes are well-known markers of immune cell activation in mammals and Drosophila melanogaster Meig., we further investigated if a blood meal changes the expression of hemocyte-derived immune factors. Indeed, hemocytes 24 h post blood meal displayed higher levels of critical components of the complement and melanization immune reactions in mosquitoes. Taken together, this study demonstrates that the normal physiological process of a blood meal activates the innate immune response in mosquitoes. This process is likely in part regulated by Ras-MAPK signaling, highlighting a novel mechanistic link between blood feeding and immunity.