bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of temperature and strain rate on tensile stress–strain and workhardening behaviour of P92 ferritic steel
Authors: Sainath G. , Choudhary B. K. , Christopher J. , Isaac Samuel E. , Mathew M. D.
Published: November 2013

Detailed analysis on true stress σ–true plastic strain ϵ data indicated that the tensile flow and workhardening behaviour of P92 ferritic steel can be described most accurately by the combination of Ludwigson and Hollomon relations at strain rates ranging from 3·16×10−5 to 1·26×10−3 s−1 over the temperature range of 300–923 K. At room and intermediate temperatures, the Ludwigson equation follows the σ– ϵ data closely, whereas at high temperatures, the Ludwigson equation reduces to the Hollomon relation. The variations in σ– ϵ, workhardening parameters and θ– σ with temperature exhibited three distinct temperature regimes. At intermediate temperatures, anomalous variations in σ– ϵ, workhardening parameters and θ– σ with respect to temperature and strain rate have been observed. At high temperatures, the dominance of recovery is reflected in the rapid decrease in flow stress and workhardening parameters associated with Ludwigson/Hollomon relations with increasing temperature and decreasing strain rate.
Exploratory studies of extended storage of apheresis platelets in a platelet additive solution (PAS)
Authors: Slichter Sherrill J. , Corson Jill , Jones Mary Kay , Christoffel Todd , Pellham Esther , Bailey S. Lawrence , Bolgiano Doug
Published: November 2013

Key Points

Extended apheresis platelet storage is dependent on the collection method, storage in a storage solution, and storage bag composition. The lifespan of the platelet is not intrinsic to the cell, and platelet viability is better maintained in vitro than in vivo.
Cell intrinsic and extrinsic factors synergize in mice with haploinsufficiency for Tp53, and two human del(5q) genes, Egr1 and Apc
Authors: Stoddart Angela , Wang Jianghong , Fernald Anthony A. , Karrison Theodore , Anastasi John , Le Beau Michelle M.
Published: November 2013

Key Points

Haploinsufficiency of Egr1, Apc, and Tp53 in mice cooperate to model the pathogenesis of the early stages of t-MN with a del(5q). Exposure of an Apc haploinsufficient BM microenvironment to radiation and/or an alkylating agent accelerates disease development.
RNA-seq reveals the RNA binding proteins, Hfq and RsmA, play various roles in virulence, antibiotic production and genomic flux in Serratia sp. ATCC 39006
Authors: Wilf Nabil M , Reid Adam J , Ramsay Joshua P , Williamson Neil R , Croucher Nicholas J , Gatto Laurent , Hester Svenja S , Goulding David , Barquist Lars , Lilley Kathryn S , Kingsley Robert A , Dougan Gordon , Salmond George PC
Published: November 2013

Background

Serratia sp. ATCC 39006 (S39006) is a Gram-negative enterobacterium that is virulent in plant and animal models. It produces a red-pigmented trypyrrole secondary metabolite, prodigiosin (Pig), and a carbapenem antibiotic (Car), as well as the exoenzymes, pectate lyase and cellulase. Secondary metabolite production in this strain is controlled by a complex regulatory network involving quorum sensing (QS). Hfq and RsmA (two RNA binding proteins and major post-transcriptional regulators of gene expression) play opposing roles in the regulation of several key phenotypes within S39006. Prodigiosin and carbapenem production was abolished, and virulence attenuated, in an S39006 ∆hfq mutant, while the converse was observed in an S39006 rsmA transposon insertion mutant.

Results

In order to define the complete regulon of Hfq and RsmA, deep sequencing of cDNA libraries (RNA-seq) was used to analyse the whole transcriptome of S39006 ∆hfq and rsmA::Tn mutants. Moreover, we investigated global changes in the proteome using an LC-MS/MS approach. Analysis of differential gene expression showed that Hfq and RsmA directly or indirectly regulate (at the level of RNA) 4% and 19% of the genome, respectively, with some correlation between RNA and protein expression. Pathways affected include those involved in antibiotic regulation, virulence, flagella synthesis, and surfactant production. Although Hfq and RsmA are reported to activate flagellum production in E. coli and an adherent-invasive E. coli hfq mutant was shown to have no flagella by electron microscopy, we found that flagellar production was increased in the S39006 rsmA and hfq mutants. Additionally, deletion of rsmA resulted in greater genomic flux with increased activity of two mobile genetic elements. This was confirmed by qPCR and analysis of rsmA culture supernatant revealed the presence of prophage DNA and phage particles. Finally, expression of a hypothetical protein containing DUF364 increased prodigiosin production and was controlled by a putative 5′ cis-acting regulatory RNA element.

Conclusion

Using a combination of transcriptomics and proteomics this study provides a systems-level understanding of Hfq and RsmA regulation and identifies similarities and differences in the regulons of two major regulators. Additionally our study indicates that RsmA regulates both core and variable genome regions and contributes to genome stability.
Does PRP enhance bone integration with grafts, graft substitutes, or implants? A systematic review
Authors: Roffi Alice , Filardo Giuseppe , Kon Elizaveta , Marcacci Maurilio
Published: November 2013

Background

Several bone implants are applied in clinical practice, but none meets the requirements of an ideal implant. Platelet-rich plasma (PRP) is an easy and inexpensive way to obtain growth factors in physiologic proportions that might favour the regenerative process. The aim of this review is to analyse clinical studies in order to investigate the role of PRP in favouring bone integration of graft, graft substitutes, or implants, and to identify the materials for which the additional use of PRP might be associated with superior osseo- and soft tissues integration.

Methods

A search on PubMed database was performed considering the literature from 2000 to 2012, using the following string: ("Bone Substitutes"[Mesh] OR "Bone Transplantation"[Mesh] OR "Bone Regeneration"[Mesh] OR "Osseointegration"[Mesh]) AND ("Blood Platelets"[Mesh] OR "Platelet-Rich Plasma"[Mesh]). After abstracts screening, the full-texts of selected papers were analyzed and the papers found from the reference lists were also considered. The search focused on clinical applications documented in studies in the English language: levels of evidence included in the literature analysis were I, II and III.

Results

Literature analysis showed 83 papers that fulfilled the inclusion criteria: 26 randomized controlled trials (RCT), 14 comparative studies, 29 case series, and 14 case reports. Several implant materials were identified: 24 papers on autologous bone, 6 on freeze-dried bone allograft (FDBA), 16 on bovine porous bone mineral (BPBM), 9 on β-tricalcium phosphate (β-TCP), 4 on hydroxyapatite (HA), 2 on titanium (Ti), 1 on natural coral, 1 on collagen sponge, 1 on medical-grade calcium sulphate hemihydrate (MGCSH), 1 on bioactive glass (BG) and 18 on a combination of biomaterials. Only 4 papers were related to the orthopaedic field, whereas the majority belonged to clinical applications in oral/maxillofacial surgery.

Conclusions

The systematic research showed a growing interest in this approach for bone implant integration, with an increasing number of studies published over time. However, knowledge on this topic is still preliminary, with the presence mainly of low quality studies. Many aspects still have to be understood, such as the biomaterials that can benefit most from PRP and the best protocol for PRP both for production and application.
Danggui-Jakyak-San ameliorates memory impairment and increase neurogenesis induced by transient forebrain ischemia in mice
Authors: Song Mi Deok , Kim Dong Hyun , Kim Jong Min , Lee Hyung Eun , Park Se Jin , Ryu Jong Hoon , Lew Jae Hwan
Published: November 2013

Background

Danggui-Jakyak-San (DJS), a traditional herbal prescription, has been used to treat insufficient blood supplies. Recently, regenerative medication for the treatment of cerebral ischemia has drawn the attention of many researchers.

Methods

In this study, we examined whether DJS exerts a neuronal regenerative effect in the hippocampus of a transient forebrain ischemia mice model. Transient forebrain ischemia was induced by bilateral common carotid artery occlusion (BCCAO). Animals were divided into three groups (sham, BCCAO + vehicle, and BCCAO + DJS). To test the effect of DJS on learning and memory, Morris water maze or passive avoidance test was conducted. To test neuroprotective and neurogenic effect, immunohistochemistry and Western blot analysis were used. Statistical significance was analyzed with Studentt-test, one-way or two-way analysis of variance.

Results

We found that the administration of DJS ameliorated ischemia-induced spatial memory impairment in the Morris water maze task. Moreover, Akt/glycogen synthase kinase-3β (GSK3β)/β-catenin signaling was increased by DJS, which would be one possible mechanism of DJS for neurogenesis in the hippocampal dentate gyrus region.

Conclusions

These results suggest that DJS is a possible candidate for the treatment of ischemia-induced neuronal degeneration.
The predictability of claim-data-based comorbidity-adjusted models could be improved by using medication data
Authors: Bang Ji Hwan , Hwang Soo-Hee , Lee Eun-Jung , Kim Yoon
Published: November 2013

Background

Recently, claim-data-based comorbidity-adjusted methods such as the Charlson index and the Elixhauser comorbidity measures have been widely used among researchers. At the same time, there have been an increasing number of attempts to improve the predictability of comorbidity-adjusted models. We tried to improve the predictability of models using the Charlson and Elixhauser indices by using medication data; specifically, we used medication data to estimate omitted comorbidities in the claim data.

Methods

We selected twelve major diseases (other than malignancies) that caused large numbers of in-hospital mortalities during 2008 in hospitals with 700 or more beds in South Korea. Then, we constructed prediction models for in-hospital mortality using the Charlson index and Elixhauser comorbidity measures, respectively. Inferring missed comorbidities using medication data, we built enhanced Charlson and Elixhauser comorbidity-measures-based prediction models, which included comorbidities inferred from medication data. We then compared the c-statistics of each model.

Results

247,712 admission cases were enrolled. 55 generic drugs were used to infer 8 out of 17 Charlson comorbidities, and 106 generic drugs were used to infer 14 out of 31 Elixhauser comorbidities. Before the inclusion of comorbidities inferred from medication data, the c-statistics of models using the Charlson index were 0.633-0.882 and those of the Elixhauser index were 0.699-0.917. After the inclusion of comorbidities inferred from medication data, 9 of 12 models using the Charlson index and all of the models using the Elixhauser comorbidity measures were improved in predictability but, the differences were relatively small.

Conclusion

Prediction models using Charlson index or Elixhauser comorbidity measures might be improved by including comorbidities inferred from medication data.
Estimating the parasitaemia of Plasmodium falciparum: experience from a national EQA scheme
Authors: Manser Monika , Olufsen Catherine , Andrews Nick , Chiodini Peter L
Published: November 2013

Background

To examine performance of the identification and estimation of percentage parasitaemia of Plasmodium falciparum in stained blood films distributed in the UK National External Quality Assessment Scheme (UKNEQAS) Blood Parasitology Scheme.

Methods

Analysis of performance for the diagnosis and estimation of the percentage parasitaemia of P. falciparum in Giemsa-stained thin blood films was made over a 15-year period to look for trends in performance.

Results

An average of 25% of participants failed to estimate the percentage parasitaemia, 17% overestimated and 8% underestimated, whilst 5% misidentified the malaria species present.

Conclusions

Although the results achieved by participants for other blood parasites have shown an overall improvement, the level of performance for estimation of the parasitaemia of P. falciparum remains unchanged over 15 years. Possible reasons include incorrect calculation, not examining the correct part of the film and not examining an adequate number of microscope fields.
Novices may be trained to screen for abdominal aortic aneurysms using ultrasound
Authors: Nguyen Anh TV , Hill Geraldine B , Versteeg Matthew PT , Thomson Ian A , van Rij Andre M
Published: November 2013

Background

Highly trained vascular sonographers make up a significant cost of abdominal aortic aneurysm (AAA) ultrasound screening. However, they are over-trained for this very limited task. Others have reported that health workers (e.g. emergency room staff and nurses) with far less training may be able to perform these scans. The national AAA screening programme in the UK uses staff with limited training. Whether individuals without a health professional qualification could be trained to perform the scan accurately to improve cost-effectiveness is not known. We aimed to investigate whether a short, well-supervised course in ultrasonography could train novices to detect AAA for screening purposes.

Methods

Three novices were trained by an experienced sonographer for 15 days to perform abdominal aortic ultrasound examinations and detect AAA using a portable ultrasound system. The examination included four anterior-posterior aortic measurements: a maximal diameter in the coronal plane and three diameters of the suprarenal, mid and distal infrarenal aorta in the transverse plane. The novices independently scanned 215 subjects following training; experienced sonographers repeated the measurements on the same subject in the same session. Using Bland-Altman plots and CUSUM analysis, the novices’ and experienced sonographers’ accuracy and efficiency measurements were compared. Factors influencing performance were recorded.

Results

The novices measured the maximal coronal aortic diameter accurately, to within 0.46-0.52 cm of the true diameter; 85-97% of their coronal measurements were within 0.5 cm of the assessors; kappa statistic and Bland-Altman plots show a high agreement with the assessor’s measurements. However, the novices’ measurements of the three diameters in the transverse plane were outside clinically acceptable limits. Assuming a referral policy for a second scan for scans recorded as 'difficult’, only one novice missed a 3.13 cm aneurysm.

A CUSUM quality improvement analysis demonstrated substantial improvements in the scanning efficiency of the novices with continued scanning experience.

Conclusion

This study showed that novices could be trained to screen for AAA over 15 days. However, the need for continuing quality improvement is critical, especially in more technically demanding cases. Measuring the maximal infrarenal diameter instead of specific segmental diameters may be more appropriate for AAA screening using novices.
Widening disparity in the geographic distribution of pediatricians in Japan
Authors: Sasaki Hiromasa , Otsubo Tetsuya , Imanaka Yuichi
Published: November 2013

Background

The shortage of physicians in Japan is a serious concern, particularly in specialties like pediatrics. The purpose of this study was to investigate recent changes in the geographic distribution of pediatricians and the factors underlying this change.

Methods

We investigated the numerical changes in the pediatrician workforce (2002 to 2007) per 100,000 of the population under the age of 15 years in 369 secondary medical areas throughout Japan, using attributive variables such as population size, social and economic status, and pediatric service delivery. We performed principal component analysis and multiple regression analysis.

Results

We obtained two principal components: one that reflected the degree of urbanization and another that reflected the volume of pediatric service delivery. Only the first component score was positively correlated with an increased pediatrician workforce per 100,000 of the population under the age of 15 years. We classified the secondary medical areas into four groups using component scores. The increase in pediatrician workforce during this period was primarily absorbed into the two groups with higher levels of urbanization, whereas the two rural groups exhibited little increase. Pediatricians aged 50 to 59 years increased in all four groups, whereas pediatricians aged 30 to 39 years decreased in the two rural groups and increased in the two urban groups.

Conclusions

The trends of the pediatrician workforce increase generally kept pace with urbanization, but were not associated with the original pediatrician workforce supply. The geographic distribution of pediatricians showed rapid concentration in urban areas. This trend was particularly pronounced among female pediatricians and those aged 30 to 39 years. Given that aging pediatricians in rural areas are not being replaced by younger doctors, these areas will likely face new crises when senior physicians retire.
The arrestin-domain containing protein AdcA is a response element to stress
Authors: Habourdin Clémence , Klein Gérard , Araki Tsuyoshi , Williams Jeffrey G , Aubry Laurence
Published: November 2013

Background

Cell behaviour is tightly determined by sensing and integration of extracellular changes through membrane detectors such as receptors and transporters and activation of downstream signalling cascades. Arrestin proteins act as scaffolds at the plasma membrane and along the endocytic pathway, where they regulate the activity and the fate of some of these detectors. Members of the arrestin clan are widely present from unicellular to metazoa, with roles in signal transduction and metabolism. As a soil amoeba, Dictyostelium is frequently confronted with environmental changes likely to compromise survival. Here, we investigated whether the recently described arrestin-related protein AdcA is part of the cell response to stresses.

Results

Our data provide evidence that AdcA responds to a variety of stresses including hyperosmolarity by a transient phosphorylation. Analysis in different mutant backgrounds revealed that AdcA phosphorylation involves pathways other than the DokA and cGMP-dependent osmostress pathways, respectively known to regulate PKA and STATc, key actors in the cellular response to conditions of hyperosmolarity. Interestingly, however, both AdcA and STATc are sensitive to changes in the F-actin polymerization status, suggesting a common primary sensor/trigger and linking the stress-sensitive kinase responsive for AdcA phosphorylation to the actin cytoskeleton. We also show that STATc-dependent transcriptional activity is involved for the timely dephosphorylation of AdcA in cells under stress.

Conclusion

Under osmotic stress, AdcA undergoes a phosphorylation-dephosphorylation cycle involving a stress-sensitive kinase and the transcription regulator STATc. This transient post-transcriptional modification may allow a regulation of AdcA function possibly to optimize the cellular stress response.
Fabrication of nanowire network AAO and its application in SERS
Authors: Jiwei Qi , Yudong Li , Ming Yang , Qiang Wu , Zongqiang Chen , Jingyang Peng , Yue Liu , Wudeng Wang , Xuanyi Yu , Qian Sun , Jingjun Xu
Published: November 2013

In this paper, nanowire network anodized aluminum oxide (AAO) was fabricated by just adding a simple film-eroding process after the production of porous AAO. After depositing 50 nm of Au onto the surface, nanowire network AAO can be used as ultrasensitive and high reproducibility surface-enhanced Raman scattering (SERS) substrate. The average Raman enhancement factor of the nanowire network AAO SERS substrate can reach 5.93 × 106, which is about 14% larger than that of commercial Klarite® substrates. Simultaneously, the relative standard deviations in the SERS intensities are limited to approximately 7%. All of the results indicate that our large-area low-cost high-performance nanowire structure AAO SERS substrates have a great advantage in chemical/biological sensing applications.
Application of p-regularity theory to nonlinear boundary value problems
Authors: Grzegorczyk Wiesław , Medak Beata , Tret’yakov Alexey A
Published: November 2013

The paper studies the question of solution existence to a nonlinear equation in the degenerate case. This question is studied for three particular boundary value problems for ordinary and partial second-order differential equations. The so-called p-regularity theory is applied to these purposes as an effective apparatus to investigate many nonlinear mathematical, physical and numerical problems. All results obtained in the paper are based on the constructions of this theory whose basic concepts were described by Tret’yakov. We recall the main definitions and theorems of p-regularity theory and illustrate the results by examples including singular boundary value problems. In the first and second ones, the description of solutions by a tangent cone at an initial point are given. In the third example, we formulate a sufficient condition for p-regularity (

p
=
2

), which can be tested using the notion of resultant.

MSC: 47J05, 34B15, 34B16.
Fourier-Hankel solution of the Robin problem for the Helmholtz equation in supershaped annular domains
Authors: Caratelli Diego , Gielis Johan , Tavkhelidze Ilia , Ricci Paolo E
Published: November 2013

The Robin problem for the Helmholtz equation in normal-polar annuli is addressed by using a suitable Fourier-Hankel series technique. Attention is in particular focused on the wide class of domains whose boundaries are defined by the so-called superformula introduced by Gielis. A dedicated numerical procedure based on the computer algebra system Mathematica© is developed in order to validate the proposed methodology. In this way, highly accurate approximations of the solution, featuring properties similar to the classical ones, are obtained.
Prevention of Decline in Cognition after Stroke Trial (PODCAST): a study protocol for a factorial randomised controlled trial of intensive versus guideline lowering of blood pressure and lipids
Authors: Blackburn Daniel J , Krishnan Kailash , Fox Lydia , Ballard Clive , Burns Alistair , Ford Gary A , Mant Jonathan , Passmore Peter , Pocock Stuart , Reckless John , Sprigg Nikola , Stewart Rob , Wardlaw Joanna , Bath Philip MW
Published: November 2013

Background

Stroke is a common cause of cognitive impairment and dementia. However, effective strategies for reducing the risk of post-stroke dementia remain undefined. Potential strategies include intensive lowering of blood pressure and/or lipids.

Methods/Design

Design: multi-centre prospective randomised open-label blinded-endpoint controlled partial-factorial phase IV trial in secondary and primary care.

Participants: 100 participants from 30 UK Stroke Research Network sites who are post- ischemic stroke or intracerebral haemorrhage by three to seven months.

Interventions - all patients (1:1): intensive versus guideline blood pressure lowering (target systolic < 125 mmHg versus < 140 mmHg).

Interventions - ischemic stroke (1:1): intensive versus guideline lipid lowering (target low density lipoprotein-cholesterol (LDL-c) < 1.4 mmol/l versus < 3 mmol/l).

Hypotheses: does ‘intensive’ blood pressure lowering therapy and/or ‘intensive’ lipid control reduce cognitive decline and dementia in people with ischemic stroke; and does ‘intensive’ blood pressure lowering therapy reduce cognitive decline and dementia in patients with hemorrhagic stroke.

Primary outcome: Addenbrooke’s Cognitive Examination-Revised.

Secondary outcomes: feasibility of recruitment and retention of participants, tolerability and safety of the interventions, achieving and maintaining the blood pressure and lipid targets, maintaining differences in systolic blood pressure (> 10 mmHg) and low density lipoprotein-cholesterol (> 1 mmol/l) between the treatment groups, and performing clinic and telephone follow-up of cognition measures.

Randomisation: using stratification, minimization and simple randomization.

Blinding: participants receive open-label management. Cognition is assessed both unblinded (in clinic) and blinded (by telephone) to treatment. Adjudication of events (dementia, vascular, serious adverse events) is blinded to management.

Discussion

The PODCAST trial is ongoing with 78 patients recruited to date from 22 sites. Outcomes of cognitive impairment and dementia are accruing.

Trial registration

ISRCTN85562386
Drosophila melanogaster as a model organism for Alzheimer’s disease
Authors: Prüßing Katja , Voigt Aaron , Schulz Jörg B
Published: November 2013

Drosophila melanogaster provides an important resource for in vivo modifier screens of neurodegenerative diseases. To study the underlying pathogenesis of Alzheimer’s disease, fly models that address Tau or amyloid toxicity have been developed. Overexpression of human wild-type or mutant Tau causes age-dependent neurodegeneration, axonal transport defects and early death. Large-scale screens utilizing a neurodegenerative phenotype induced by eye-specific overexpression of human Tau have identified several kinases and phosphatases, apoptotic regulators and cytoskeleton proteins as determinants of Tau toxicity in vivo. The APP ortholog of Drosophila (dAPPl) shares the characteristic domains with vertebrate APP family members, but does not contain the human Aβ42 domain. To circumvent this drawback, researches have developed strategies by either direct secretion of human Aβ42 or triple transgenic flies expressing human APP, β-secretase and Drosophila γ-secretase presenilin (dPsn). Here, we provide a brief overview of how fly models of AD have contributed to our knowledge of the pathomechanisms of disease.
Heat shock factor 1 over-expression protects against exposure of hydrophobic residues on mutant SOD1 and early mortality in a mouse model of amyotrophic lateral sclerosis
Authors: Lin Pei-Yi , Simon Sharotka M , Koh Won Kyun , Folorunso Oluwarotimi , Umbaugh C Samuel , Pierce Anson
Published: November 2013

Background

Mutations in the Cu/Zn superoxide dismutase gene (SOD1) are responsible for 20% of familial forms of amyotrophic lateral sclerosis (ALS), and mutant SOD1 has been shown to have increased surface hydrophobicityin vitro. Mutant SOD1 may adopt a complex array of conformations with varying toxicityin vivo. We have used a novel florescence-based proteomic assay using 4,4’-bis-1-anilinonaphthalene-8-sulfonate (bisANS) to assess the surface hydrophobicity, and thereby distinguish between different conformations, of SOD1and other proteinsin situ.

Results

Covalent bisANS labeling of spinal cord extracts revealed that alterations in surface hydrophobicity of H46R/H48Q mutations in SOD1 provoke formation of high molecular weight SOD1 species with lowered solubility, likely due to increased exposure of hydrophobic surfaces. BisANS was docked on the H46R/H48Q SOD1 structure at the disordered copper binding and electrostatic loops of mutant SOD1, but not non-mutant WT SOD1. 16 non-SOD1 proteins were also identified that exhibited altered surface hydrophobicity in the H46R/H48Q mutant mouse model of ALS, including proteins involved in energy metabolism, cytoskeleton, signaling, and protein quality control. Heat shock proteins (HSPs) were also enriched in the detergent-insoluble fractions with SOD1. Given that chaperones recognize proteins with exposed hydrophobic surfaces as substrates and the importance of protein homeostasis in ALS, we crossed SOD1 H46R/H48Q mutant mice with mice over-expressing the heat shock factor 1 (HSF1) transcription factor. Here we showed that HSF1 over-expression in H46R/H48Q ALS mice enhanced proteostasis as evidenced by increased expression of HSPs in motor neurons and astrocytes and increased solubility of mutant SOD1. HSF1 over-expression significantly reduced body weight loss, delayed ALS disease onset, decreases cases of early disease, and increased survival for the 25thpercentile in an H46R/H48Q SOD1 background. HSF1 overexpression did not affect macroautophagy in the ALS background, but was associated with maintenance of carboxyl terminus of Hsp70 interacting protein (CHIP) expression which declined in H46R/H48Q mice.

Conclusion

Our results uncover the potential importance of changes in protein surface hydrophobicity of SOD1 and other non-SOD1 proteins in ALS, and how strategies that activate HSF1 are valid therapies for ALS and other age-associated proteinopathies.
Karyotype and cytogenetic mapping of 9 classes of repetitive DNAs in the genome of the naked catfish Mystus bocourti (Siluriformes, Bagridae)
Authors: Supiwong Weerayuth , Liehr Thomas , Cioffi Marcelo B , Chaveerach Arunrat , Kosyakova Nadezda , Pinthong Krit , Tanee Tawatchai , Tanomtong Alongklod
Published: November 2013

Background

In the present study, conventional and molecular cytogenetic studies were performed in the naked catfish Mystus bocourti (Siluriformes, Bagridae). Besides the conventional Giemsa staining, fluorescence in situ hybridization (FISH) using nine classes of repetitive DNAs namely 5S and 18S rDNAs, U2 snRNA, the microsatellites (CA)15 and (GA)15, telomeric repeats, and the retrotransposable elements Rex1, 3 and 6. was also performed.

Results

M. bocourti had 2n = 56 chromosomes with a karyotype composed by 11 m + 11 sm + 6 st/a and a fundamental number (NF) equal to 100 in both sexes. Heteromorphic sex chromosome cannot be identified. The U2 snRNA, 5S and 18S rDNA were present in only one pair of chromosomes but none of them in a syntenic position. Microsatellites (CA)15 and (GA)15 showed hybridization signals at subtelomeric regions of all chromosomes with a stronger accumulation into one specific chromosomal pair. FISH with the telomeric probe revealed hybridization signals on each telomere of all chromosomes and interstitial telomeric sites (ITS) were not detected. The retrotransposable elements Rex1, 3 and 6 were generally spread throughout the genome.

Conclusions

In general, the repetitive sequences were not randomly distributed in the genome, suggesting a pattern of compartmentalization on the heterochromatic region of the chromosomes. Little is known about the structure and organization of bagrid genomes and the knowledge of the chromosomal distribution of repetitive DNA sequences in M. bocourti represents the first step for achieving an integrated view of their genomes.
Identification of Streptococcus parasanguinis DNA contamination in human buccal DNA samples
Authors: Mahfuz Istiak , Cheng Wei , White Stefan J
Published: November 2013

Background

The use of buccal swabs in clinical and scientific studies is a very popular method of collecting DNA, due to its non-invasive nature of collection. However, contamination of the DNA sample may interfere with analysis.

Findings

Here we report the finding of Streptococcus parasanguinis bacterial DNA contamination in human buccal DNA samples, which led to preferential amplification of bacterial sequence with PCR primers designed against human sequence.

Conclusion

Contamination of buccal-derived DNA with bacterial DNA can be significant, and may influence downstream genetic analysis. One needs to be aware of possible bacterial contamination when interpreting abnormal findings following PCR amplification of buccal swab DNA samples.
Population and growth of queen conch (Lobatus gigas Linnaeus, 1758) in the Sapodilla Cayes Marine Reserve of Belize
Authors: Chan Isani , Tseng Li-Chun , Dahms Hans-Uwe , Hwang Jiang-Shiou
Published: November 2013

Background

The conservation effectiveness of marine protected areas is of substantial dispute. In the Belize Barrier Reef, there are several zones with increasing human activity and harvesting of overexploited species. Marine protected areas are designed to protect endangered species and increase the population size of exploited species. The present study investigated the population and morphological characteristics of Lobatus gigas (Linnaeus, 1758) in the Sapodilla Cayes Marine Reserve (SCMR) at the southernmost tip of the Belize Barrier Reef to estimate the effectiveness of the marine protected area.

Results

A total of 693 L. gigas conches were counted over the 7,200 m2 from 36 transect lines. The densities of juveniles and adult conches in the conservation zone were substantially higher (20.13 and 2.88 individuals/100 m2, respectively) than in the general use zone (5.29 juveniles and 0.58 adults individuals/100 m2). The shell length of adult individuals ranged from 14.4 to 18.5 cm in the conservation zone and from 14.6 to 18.1 cm in the general use zone. A comparison of shell length of juveniles and adults showed no significant differences between the conservation zone (11.39 ± 1.46 cm) and general use zone (11.62 ± 1.24 cm). There was a significant positive correlation for shell length with lip thickness in the conservation zone (Pearson's correlation, r = 0.729, p < 0.001) and general use zone (Pearson's correlation, r = 0.613, p = 0.02).

Conclusions

The function and effectiveness of marine protected areas are discussed using the results of the present study that identifies the primary objective which is to ensure a continuous recruitment of valuable targeted species by the protection of spawning stock biomass that is important for the management of marine protected areas in an environmentally sensitive ecosystem.
The vertebrate taxonomy ontology: a framework for reasoning across model organism and species phenotypes
Authors: Midford Peter E , Dececchi Thomas Alex , Balhoff James P , Dahdul Wasila M , Ibrahim Nizar , Lapp Hilmar , Lundberg John G , Mabee Paula M , Sereno Paul C , Westerfield Monte , Vision Todd J , Blackburn David C
Published: November 2013

Background

A hierarchical taxonomy of organisms is a prerequisite for semantic integration of biodiversity data. Ideally, there would be a single, expansive, authoritative taxonomy that includes extinct and extant taxa, information on synonyms and common names, and monophyletic supraspecific taxa that reflect our current understanding of phylogenetic relationships.

Description

As a step towards development of such a resource, and to enable large-scale integration of phenotypic data across vertebrates, we created the Vertebrate Taxonomy Ontology (VTO), a semantically defined taxonomic resource derived from the integration of existing taxonomic compilations, and freely distributed under a Creative Commons Zero (CC0) public domain waiver. The VTO includes both extant and extinct vertebrates and currently contains 106,947 taxonomic terms, 22 taxonomic ranks, 104,736 synonyms, and 162,400 cross-references to other taxonomic resources. Key challenges in constructing the VTO included (1) extracting and merging names, synonyms, and identifiers from heterogeneous sources; (2) structuring hierarchies of terms based on evolutionary relationships and the principle of monophyly; and (3) automating this process as much as possible to accommodate updates in source taxonomies.

Conclusions

The VTO is the primary source of taxonomic information used by the Phenoscape Knowledgebase (http://phenoscape.org/), which integrates genetic and evolutionary phenotype data across both model and non-model vertebrates. The VTO is useful for inferring phenotypic changes on the vertebrate tree of life, which enables queries for candidate genes for various episodes in vertebrate evolution.
Genomic analysis reveals key aspects of prokaryotic symbiosis in the phototrophic consortium “Chlorochromatium aggregatum”
Authors: Liu Zhenfeng , Müller Johannes , Li Tao , Alvey Richard M , Vogl Kajetan , Frigaard Niels-Ulrik , Rockwell Nathan C , Boyd Eric S , Tomsho Lynn P , Schuster Stephan C , Henke Petra , Rohde Manfred , Overmann Jörg , Bryant Donald A
Published: November 2013

Background

‘Chlorochromatium aggregatum’ is a phototrophic consortium, a symbiosis that may represent the highest degree of mutual interdependence between two unrelated bacteria not associated with a eukaryotic host. ‘Chlorochromatium aggregatum’ is a motile, barrel-shaped aggregate formed from a single cell of ‘Candidatus Symbiobacter mobilis”, a polarly flagellated, non-pigmented, heterotrophic bacterium, which is surrounded by approximately 15 epibiont cells of Chlorobium chlorochromatii, a non-motile photolithoautotrophic green sulfur bacterium.

Results

We analyzed the complete genome sequences of both organisms to understand the basis for this symbiosis. Chl. chlorochromatii has acquired relatively few symbiosis-specific genes; most acquired genes are predicted to modify the cell wall or function in cell-cell adhesion. In striking contrast, ‘Ca. S. mobilis’ appears to have undergone massive gene loss, is probably no longer capable of independent growth, and thus may only reproduce when consortia divide. A detailed model for the energetic and metabolic bases of the dependency of ‘Ca. S. mobilis’ on Chl. chlorochromatii is described.

Conclusions

Genomic analyses suggest that three types of interactions lead to a highly sophisticated relationship between these two organisms. Firstly, extensive metabolic exchange, involving carbon, nitrogen, and sulfur sources as well as vitamins, occurs from the epibiont to the central bacterium. Secondly, ‘Ca. S. mobilis’ can sense and move towards light and sulfide, resources that only directly benefit the epibiont. Thirdly, electron cycling mechanisms, particularly those mediated by quinones and potentially involving shared protonmotive force, could provide an important basis for energy exchange in this and other symbiotic relationships.
Polysome profiling reveals translational control of gene expression in the human malaria parasite Plasmodium falciparum
Authors: Bunnik Evelien M , Chung Duk-Won Doug , Hamilton Michael , Ponts Nadia , Saraf Anita , Prudhomme Jacques , Florens Laurence , Le Roch Karine G
Published: November 2013

Background

In eukaryotic organisms, gene expression is regulated at multiple levels during the processes of transcription and translation. The absence of a tight regulatory network for transcription in the human malaria parasite suggests that gene expression may largely be controlled at post-transcriptional and translational levels.

Results

In this study, we compare steady-state mRNA and polysome-associated mRNA levels of Plasmodium falciparum at different time points during its asexual cell cycle. For more than 30% of its genes, we observe a delay in peak transcript abundance in the polysomal fraction as compared to the steady-state mRNA fraction, suggestive of strong translational control. Our data show that key regulatory mechanisms could include inhibitory activity of upstream open reading frames and translational repression of the major virulence gene family by intronic transcripts. In addition, we observe polysomal mRNA-specific alternative splicing events and widespread transcription of non-coding transcripts.

Conclusions

These different layers of translational regulation are likely to contribute to a complex network that controls gene expression in this eukaryotic pathogen. Disrupting the mechanisms involved in such translational control could provide novel anti-malarial strategies.
An ethics safe harbor for international genomics research?
Authors: Dove Edward S , Knoppers Bartha M , Zawati Ma’n H
Published: November 2013

Background

Genomics research is becoming increasingly globally connected and collaborative, contesting traditional ethical and legal boundaries between global and local research practice. As well, global data-driven genomics research holds great promise for health discoveries. Yet, paradoxically, current research ethics review systems around the world challenge potential improvements in human health from such research and thus undermine respect for research participants. Case reports illustrate that the current system is costly, fragmented, inefficient, inadequate, and inconsistent. There is an urgent need to improve the governance system of ethics review to enable secure and seamless genomic and clinical data sharing across jurisdictions.

Discussion

Building on the international privacy 'safe harbor’ model that was developed following the adoption of the European Privacy Directive, we propose an international infrastructure. The goal is to create a streamlined and harmonized ethics governance system for international, data-driven genomics research projects. The proposed 'Safe Harbor Framework for International Ethics Equivalency’ would consist in part of an agency supporting an International Federation for Ethics Review (IFER), formed by a voluntary agreement among countries, granting agencies, philanthropies, institutions, and healthcare, patient advocacy, and research organizations. IFER would be both a central ethics review body and also a forum for review and follow-up of policies concerning ethics norms for international genomics research projects. It would be built on five principle elements: (1) registration; (2) compliance review; (3) recognition; (4) monitoring and enforcement; and (5) public participation.

A Safe Harbor Framework for International Ethics Equivalency would create many benefits for researchers, countries, and the general public, and may eventually have application beyond genomics to other areas of biomedical research that increasingly engage in secondary use of data and present only negligible risks. Among the benefits, research participants and patients would have uniform adequate protection, while researchers would be ensured expert ethics review with a reduction in cost, time, administrative hassle, and redundant regulatory hurdles. Most importantly, society would enjoy the maximization of the potential benefits of genomics research.
Conical faults apparent in a 3D seismic image
Authors: Hale Dave , Groshong Richard H.
Published: November 2013

Map-scale geologic faults with a conical shape are apparent in a public-domain 3D seismic image of block F3 in the Dutch sector of the North Sea. These cone-shaped normal faults exist among many polygonal normal faults in fine-grained clay sediments. The conical faults were discovered using new algorithms for seismic image processing, but they are apparent without that processing. They appear circular in horizontal image slices and have an inverted-V shape in vertical sections for any azimuth through their vertical axes of symmetry. They form horsts bounded by planar strata above and below, with maximum throws of about 35 m roughly halfway between their bases and tops. The bases are up to 1 km wide, and dips of the conical faults are in the range 35º–38º. Because polygonal faults exist elsewhere at or near the seafloor with dips of about 60º, most such faults likely formed close to the depositional interface; the much lower dips of deeply buried faults, such as the faults observed here, are likely due to vertical compaction. We inferred that polygonal and conical fault geometries result from a uniform radial extension stress caused by volumetric contraction, analogous to the formation of mudcracks. Cone-shaped faults have been observed in laboratory experiments on rocks and ceramics, where the conical geometry results from uniaxial compression. In the subsurface, the formation of conical faults implies that stresses and sediments were exceptionally homogeneous. The cone shape suggests a pointlike heterogeneity near the depositional surface, which served as a trigger for downward propagation of the faults, rather unlike the random, in-plane propagation and linking inferred by others for polygonal faults.
Neural Input Is Critical for Arcuate Hypothalamic Neurons to Mount Intracellular Signaling Responses to Systemic Insulin and Deoxyglucose Challenges in Male Rats: Implications for Communication Within Feeding and Metabolic Control Networks
Authors: Khan Arshad M. , Walker Ellen M. , Dominguez Nicole , Watts Alan G.
Published: November 2013

The hypothalamic arcuate nucleus (ARH) controls rat feeding behavior in part through peptidergic neurons projecting to the hypothalamic paraventricular nucleus (PVH). Hindbrain catecholaminergic (CA) neurons innervate both the PVH and ARH, and ablation of CA afferents to PVH neuroendocrine neurons prevents them from mounting cellular responses to systemic metabolic challenges such as insulin or 2-deoxy-d-glucose (2-DG). Here, we asked whether ablating CA afferents also limits their ARH responses to the same challenges or alters ARH connectivity with the PVH. We examined ARH neurons for three features: (1) CA afferents, visualized by dopamine-β-hydroxylase (DBH)– immunoreactivity; (2) activation by systemic metabolic challenge, as measured by increased numbers of neurons immunoreactive (ir) for phosphorylated ERK1/2 (pERK1/2); and (3) density of PVH-targeted axons immunoreactive for the feeding control peptides Agouti-related peptide and α-melanocyte-stimulating hormone (αMSH). Loss of PVH DBH immunoreactivity resulted in concomitant ARH reductions of DBH-ir and pERK1/2-ir neurons in the medial ARH, where AgRP neurons are enriched. In contrast, pERK1/2 immunoreactivity after systemic metabolic challenge was absent in αMSH-ir ARH neurons. Yet surprisingly, axonal αMSH immunoreactivity in the PVH was markedly increased in CA-ablated animals. These results indicate that (1) intrinsic ARH activity is insufficient to recruit pERK1/2-ir ARH neurons during systemic metabolic challenges (rather, hindbrain-originating CA neurons are required); and (2) rats may compensate for a loss of CA innervation to the ARH and PVH by increased expression of αMSH. These findings highlight the existence of a hierarchical dependence for ARH responses to neural and humoral signals that influence feeding behavior and metabolism.
Vulnerability of the Neural Circuitry Underlying Sexual Behavior to Chronic Adult Exposure to Oral Bisphenol A in Male Mice
Authors: Picot Marie , Naulé Lydie , Marie-Luce Clarisse , Martini Mariangela , Raskin Kalina , Grange-Messent Valérie , Franceschini Isabelle , Keller Matthieu , Mhaouty-Kodja Sakina
Published: November 2013

There are human reproduction concerns associated with extensive use of bisphenol A (BPA)-containing plastic and, in particular, the leaching of BPA into food and beverages. In this context, it remains unclear whether and how exposure to BPA interferes with the developmental organization and adult activation of male sexual behavior by testosterone. We evaluated the developmental and adult exposure to oral BPA at doses equivalent to the no-observed-adverse-effect-level (5 mg/kg body weight per day) and tolerable daily intake (TDI) (50 μg/kg body weight per day) on mouse sexual behavior and the potential mechanisms underlying BPA effects. Adult exposure to BPA reduced sexual motivation and performance at TDI dose only. Exposed males took longer to initiate mating and reach ejaculation despite normal olfactory chemoinvestigation. This deficiency was not restored by sexual experience and was associated with unchanged circulating levels of testosterone. By contrast, developmental exposure to BPA at TDI or no-observed-adverse-effect-level dose did not reduce sexual behavior or alter the neuroanatomical organization of the preoptic area. Disrupting the neural androgen receptor resulted in behavioral and neuroanatomical effects similar to those induced by adult exposure to TDI dose. Moreover, adult exposure of mutant males to BPA at TDI dose did not trigger additional alteration of sexual behavior, suggesting that BPA and neural androgen receptor mutation share a common mechanism of action. This shows, for the first time, that the neural circuitry underlying male sexual behavior is vulnerable to chronic adult exposure to low dose of BPA and suggests that BPA could act in vivo as an antiandrogenic compound.