bluuebunny/crossref_metadata_2025 huggingface dataset:
Tightening of DNA knots by supercoiling facilitates their unknotting by type II DNA topoisomerases
Authors: Witz Guillaume , Dietler Giovanni , Stasiak Andrzej
Published: February 2011

Using numerical simulations, we compare properties of knotted DNA molecules that are either torsionally relaxed or supercoiled. We observe that DNA supercoiling tightens knotted portions of DNA molecules and accentuates the difference in curvature between knotted and unknotted regions. The increased curvature of knotted regions is expected to make them preferential substrates of type IIA topoisomerases because various earlier experiments have concluded that type IIA DNA topoisomerases preferentially interact with highly curved DNA regions. The supercoiling-induced tightening of DNA knots observed here shows that torsional tension in DNA may serve to expose DNA knots to the unknotting action of type IIA topoisomerases, and thus explains how these topoisomerases could maintain a low knotting equilibrium in vivo, even for long DNA molecules.
X-ray crystal structures elucidate the nucleotidyl transfer reaction of transcript initiation using two nucleotides
Authors: Gleghorn Michael L. , Davydova Elena K. , Basu Ritwika , Rothman-Denes Lucia B. , Murakami Katsuhiko S.
Published: February 2011

We have determined the X-ray crystal structures of the pre- and postcatalytic forms of the initiation complex of bacteriophage N4 RNA polymerase that provide the complete set of atomic images depicting the process of transcript initiation by a single-subunit RNA polymerase. As observed during T7 RNA polymerase transcript elongation, substrate loading for the initiation process also drives a conformational change of the O helix, but only the correct base pairing between the +2 substrate and DNA base is able to complete the O-helix conformational transition. Substrate binding also facilitates catalytic metal binding that leads to alignment of the reactive groups of substrates for the nucleotidyl transfer reaction. Although all nucleic acid polymerases use two divalent metals for catalysis, they differ in the requirements and the timing of binding of each metal. In the case of bacteriophage RNA polymerase, we propose that catalytic metal binding is the last step before the nucleotidyl transfer reaction.
Development of an artificial cell, from self-organization to computation and self-reproduction
Authors: Noireaux Vincent , Maeda Yusuke T. , Libchaber Albert
Published: February 2011

This article describes the state and the development of an artificial cell project. We discuss the experimental constraints to synthesize the most elementary cell-sized compartment that can self-reproduce using synthetic genetic information. The original idea was to program a phospholipid vesicle with DNA. Based on this idea, it was shown that in vitro gene expression could be carried out inside cell-sized synthetic vesicles. It was also shown that a couple of genes could be expressed for a few days inside the vesicles once the exchanges of nutrients with the outside environment were adequately introduced. The development of a cell-free transcription/translation toolbox allows the expression of a large number of genes with multiple transcription factors. As a result, the development of a synthetic DNA program is becoming one of the main hurdles. We discuss the various possibilities to enrich and to replicate this program. Defining a program for self-reproduction remains a difficult question as nongenetic processes, such as molecular self-organization, play an essential and complementary role. The synthesis of a stable compartment with an active interface, one of the critical bottlenecks in the synthesis of artificial cell, depends on the properties of phospholipid membranes. The problem of a self-replicating artificial cell is a long-lasting goal that might imply evolution experiments.
Prion-like propagation of mutant superoxide dismutase-1 misfolding in neuronal cells
Authors: Münch Christian , O’Brien John , Bertolotti Anne
Published: February 2011

Deposition of proteins of aberrant conformation is the hallmark of many neurodegenerative diseases. Misfolding of the normally globular mutant superoxide dismutase-1 (SOD1) is a central, early, but poorly understood event in the pathogenic cascade leading to familial forms of ALS. Here we report that aggregates composed of an ALS-causing SOD1 mutant penetrate inside cells by macropinocytosis and rapidly exit the macropinocytic compartment to nucleate aggregation of the cytosolic, otherwise soluble, mutant SOD1 protein. Once initiated, mutant SOD1 aggregation is self-perpetuating. Mutant SOD1 aggregates transfer from cell to cell with remarkable efficiency, a process that does not require contacts between cells but depends on the extracellular release of aggregates. This study reveals that SOD1 aggregates, propagate in a prion-like manner in neuronal cells and sheds light on the mechanisms underlying aggregate uptake and cell-to-cell transfer.
Transmembrane orientation and possible role of the fusogenic peptide from parainfluenza virus 5 (PIV5) in promoting fusion
Authors: Donald Jason E. , Zhang Yao , Fiorin Giacomo , Carnevale Vincenzo , Slochower David R. , Gai Feng , Klein Michael L. , DeGrado William F.
Published: February 2011

Membrane fusion is required for diverse biological functions ranging from viral infection to neurotransmitter release. Fusogenic proteins increase the intrinsically slow rate of fusion by coupling energetically downhill conformational changes of the protein to kinetically unfavorable fusion of the membrane–phospholipid bilayers. Class I viral fusogenic proteins have an N-terminal hydrophobic fusion peptide (FP) domain, important for interaction with the target membrane, plus a C-terminal transmembrane (C-term-TM) helical membrane anchor. The role of the water-soluble regions of fusogenic proteins has been extensively studied, but the contributions of the membrane-interacting FP and C-term-TM peptides are less well characterized. Typically, FPs are thought to bind to membranes at an angle that allows helix penetration but not traversal of the lipid bilayer. Here, we show that the FP from the paramyxovirus parainfluenza virus 5 fusogenic protein, F, forms an N-terminal TM helix, which self-associates into a hexameric bundle. This FP also interacts strongly with the C-term-TM helix. Thus, the fusogenic F protein resembles SNARE proteins involved in vesicle fusion by having water-soluble coiled coils that zipper during fusion and TM helices in both membranes. By analogy to mechanosensitive channels, the force associated with zippering of the water-soluble coiled-coil domain is expected to lead to tilting of the FP helices, promoting interaction with the C-term-TM helices. The energetically unfavorable dehydration of lipid headgroups of opposing bilayers is compensated by thermodynamically favorable interactions between the FP and C-term-TM helices as the coiled coils zipper into the membrane phase, leading to a pore lined by both lipid and protein.
Broadly neutralizing DNA vaccine with specific mutation alters the antigenicity and sugar-binding activities of influenza hemagglutinin
Authors: Chen Ming-Wei , Liao Hsin-Yu , Huang Yaoxing , Jan Jia-Tsrong , Huang Chih-Cheng , Ren Chien-Tai , Wu Chung-Yi , Cheng Ting-Jen Rachel , Ho David D. , Wong Chi-Huey
Published: February 2011

The rapid genetic drift of influenza virus hemagglutinin is an obstacle to vaccine efficacy. Previously, we found that the consensus hemagglutinin DNA vaccine (pCHA5) can only elicit moderate neutralization activities toward the H5N1 clade 2.1 and clade 2.3 viruses. Two approaches were thus taken to improve the protection broadness of CHA5. The first one was to include certain surface amino acids that are characteristic of clade 2.3 viruses to improve the protection profiles. When we immunized mice with CHA5 harboring individual mutations, the antibodies elicited by CHA5 containing P157S elicited higher neutralizing activity against the clade 2.3 viruses. Likewise, the viruses pseudotyped with hemagglutinin containing 157S became more susceptible to neutralization. The second approach was to update the consensus sequence with more recent H5N1 strains, generating a second-generation DNA vaccine pCHA5II. We showed that pCHA5II was able to elicit higher cross-neutralization activities against all H5N1 viruses. Comparison of the neutralization profiles of CHA5 and CHA5II, and the animal challenge studies, revealed that CHA5II induced the broadest protection profile. We concluded that CHA5II combined with electroporation delivery is a promising strategy to induce antibodies with broad cross-reactivities against divergent H5N1 influenza viruses.
Human transcriptome array for high-throughput clinical studies
Authors: Xu Weihong , Seok Junhee , Mindrinos Michael N. , Schweitzer Anthony C. , Jiang Hui , Wilhelmy Julie , Clark Tyson A. , Kapur Karen , Xing Yi , Faham Malek , Storey John D. , Moldawer Lyle L. , Maier Ronald V. , Tompkins Ronald G. , Wong Wing Hung , Davis Ronald W. , Xiao Wenzhong ,   the Inflammation and Host Response to Injury Large-Scale Collaborative Research Program, Toner Mehmet , Warren Shaw , Schoenfeld David A. , Rahme Laurence G. , McDonald-Smith Grace P. , Hayden Douglas L. , Mason Philip H. , Fagan Shawn , Yu Yong-Ming , Cobb J. Perren , Remick Daniel G. , Mannick John A. , Lederer James A. , Gamelli Richard L. , Silver Geoffrey M. , West Michael A. , Shapiro Michael B. , Smith Richard D. , Camp David G. , Qian Weijun , Tibshirani Robert , Lowry Stephen F. , Calvano Steven E. , Chaudry Irshad , Cohen Mitchell , Moore Ernest E. , Johnson Jeffrey L. , Baker Henry V. , Efron Philip A. , Balis Ulysses G. J. , Billiar Timothy R. , Ochoa Juan B. , Sperry Jason , Miller-Graziano Carol L. , De Asit K. , Bankey Paul E. , Herndon David N. , Finnerty Celeste C. , Jeschke Marc G. , Minei Joseph P. , Arnoldo Brett D. , Hunt John L. , Horton Jureta , Brownstein Bernard H. , Freeman Bradley , Nathens Avery B. , Cuschieri Joseph , Gibran Nicole , Klein Matthew , O'Keefe Grant , Altstein Lily , Gao Hong , Harbrecht Brian G. , Hennessy Laura , Honari Shari E. , McKinley Bruce A. , Moore Frederick A. , Wispelwey Bram
Published: February 2011

A 6.9 million-feature oligonucleotide array of the human transcriptome [Glue Grant human transcriptome (GG-H array)] has been developed for high-throughput and cost-effective analyses in clinical studies. This array allows comprehensive examination of gene expression and genome-wide identification of alternative splicing as well as detection of coding SNPs and noncoding transcripts. The performance of the array was examined and compared with mRNA sequencing (RNA-Seq) results over multiple independent replicates of liver and muscle samples. Compared with RNA-Seq of 46 million uniquely mappable reads per replicate, the GG-H array is highly reproducible in estimating gene and exon abundance. Although both platforms detect similar expression changes at the gene level, the GG-H array is more sensitive at the exon level. Deeper sequencing is required to adequately cover low-abundance transcripts. The array has been implemented in a multicenter clinical program and has generated high-quality, reproducible data. Considering the clinical trial requirements of cost, sample availability, and throughput, the GG-H array has a wide range of applications. An emerging approach for large-scale clinical genomic studies is to first use RNA-Seq to the sufficient depth for the discovery of transcriptome elements relevant to the disease process followed by high-throughput and reliable screening of these elements on thousands of patient samples using custom-designed arrays.
Regulatory T-cell expansion during chronic viral infection is dependent on endogenous retroviral superantigens
Authors: Punkosdy George A. , Blain Melissa , Glass Deborah D. , Lozano Mary M. , O'Mara Leigh , Dudley Jaquelin P. , Ahmed Rafi , Shevach Ethan M.
Published: February 2011

Regulatory T cells (Treg) play critical roles in the modulation of immune responses to infectious agents. Further understanding of the factors that control Treg activation and expansion in response to pathogens is needed to manipulate Treg function in acute and chronic infections. Here we show that chronic, but not acute, infection of mice with lymphocytic choriomeningitis virus results in a marked expansion of Foxp3+Treg that is dependent on retroviral superantigen (sag) genes encoded in the mouse genome. Sag-dependent Treg expansion was MHC class II dependent, CD4 independent, and required dendritic cells. Thus, one unique mechanism by which certain infectious agents evade host immune responses may be mediated by endogenous Sag-dependent activation and expansion of Treg.
Dynamics of the folded and unfolded villin headpiece (HP35) measured with ultrafast 2D IR vibrational echo spectroscopy
Authors: Chung Jean K. , Thielges Megan C. , Fayer Michael D.
Published: February 2011

A series of two-dimensional infrared vibrational echo experiments performed on nitrile-labeled villin headpiece [HP35-(CN)2] is described. HP35 is a small peptide composed of three alpha helices in the folded configuration. The dynamics of the folded HP35-(CN)2are compared to that of the guanidine-induced unfolded peptide, as well as the nitrile-functionalized phenylalanine (PheCN), which is used to differentiate the peptide dynamic contributions to the observables from those of the water solvent. Because the viscosity of solvent has a significant effect on fast dynamics, the viscosity of the solvent is held constant by adding glycerol. For the folded peptide, the addition of glycerol to the water solvent causes observable slowing of the peptide’s dynamics. Holding the viscosity constant as GuHCl is added, the dynamics of unfolded peptide are much faster than those of the folded peptide, and they are very similar to that of PheCN. These observations indicate that the local environment of the nitrile in the unfolded peptide resembles that of PheCN, and the dynamics probed by the CN are dominated by the fluctuations of the solvent molecules, in contrast to the observations on the folded peptide.
Tem1 localization to the spindle pole bodies is essential for mitotic exit and impairs spindle checkpoint function
Authors: Valerio-Santiago Mauricio , Monje-Casas Fernando
Published: February 2011

The mitotic exit network (MEN) is a signaling cascade that triggers inactivation of the mitotic cyclin-dependent kinases and exit from mitosis. The GTPase Tem1 localizes on the spindle pole bodies (SPBs) and initiates MEN signaling. Tem1 activity is inhibited until anaphase by Bfa1-Bub2. These proteins are also part of the spindle position checkpoint (SPOC), a surveillance mechanism that restrains mitotic exit until the spindle is correctly positioned. Here, we show that regulation of Tem1 localization is essential for the proper function of the MEN and the SPOC. We demonstrate that the dynamics of Tem1 loading onto SPBs determine the recruitment of other MEN components to this structure, and reevaluate the interdependence in the localization of Tem1, Bfa1, and Bub2. We also find that removal of Tem1 from the SPBs is critical for the SPOC to impede cell cycle progression. Finally, we demonstrate for the first time that localization of Tem1 to the SPBs is a requirement for mitotic exit.
Voltage- and temperature-dependent activation of TRPV3 channels is potentiated by receptor-mediated PI(4,5)P2 hydrolysis
Authors: Doerner Julia F. , Hatt Hanns , Ramsey I. Scott
Published: February 2011

TRPV3 is a thermosensitive channel that is robustly expressed in skin keratinocytes and activated by innocuous thermal heating, membrane depolarization, and chemical agonists such as 2-aminoethyoxy diphenylborinate, carvacrol, and camphor. TRPV3 modulates sensory thermotransduction, hair growth, and susceptibility to dermatitis in rodents, but the molecular mechanisms responsible for controlling TRPV3 channel activity in keratinocytes remain elusive. We show here that receptor-mediated breakdown of the membrane lipid phosphatidylinositol (4,5) bisphosphate (PI(4,5)P2) regulates the activity of both native TRPV3 channels in primary human skin keratinocytes and expressed TRPV3 in a HEK-293–derived cell line stably expressing muscarinic M1-type acetylcholine receptors. Stimulation of PI(4,5)P2 hydrolysis or pharmacological inhibition of PI 4 kinase to block PI(4,5)P2 synthesis potentiates TRPV3 currents by causing a negative shift in the voltage dependence of channel opening, increasing the proportion of voltage-independent current and causing thermal activation to occur at cooler temperatures. The activity of single TRPV3 channels in excised patches is potentiated by PI(4,5)P2 depletion and selectively decreased by PI(4,5)P2 compared with related phosphatidylinositol phosphates. Neutralizing mutations of basic residues in the TRP domain abrogate the effect of PI(4,5)P2 on channel function, suggesting that PI(4,5)P2 directly interacts with a specific protein motif to reduce TRPV3 channel open probability. PI(4,5)P2-dependent modulation of TRPV3 activity represents an attractive mechanism for acute regulation of keratinocyte signaling cascades that control cell proliferation and the release of autocrine and paracrine factors.
Cross-platform comparison of microarray data using order restricted inference
Authors: Klinglmueller Florian , Tuechler Thomas , Posch Martin
Published: February 2011

Motivation: Titration experiments measuring the gene expression from two different tissues, along with total RNA mixtures of the pure samples, are frequently used for quality evaluation of microarray technologies. Such a design implies that the true mRNA expression of each gene, is either constant or follows a monotonic trend between the mixtures, applying itself to the use of order restricted inference procedures. Exploiting only the postulated monotonicity of titration designs, we propose three statistical analysis methods for the validation of high-throughput genetic data and corresponding preprocessing techniques.

Results: Our methods allow for inference of accuracy, repeatability and cross-platform agreement, with minimal required assumptions regarding the underlying data generating process. Therefore, they are readily applicable to all sorts of genetic high-throughput data independent of the degree of preprocessing. An application to the EMERALD dataset was used to demonstrate how our methods provide a rich spectrum of easily interpretable quality metrics and allow the comparison of different microarray technologies and normalization methods. The results are on par with previous work, but provide additional new insights that cast doubt on the utility of popular preprocessing techniques, specifically concerning the EMERALD projects dataset.

Availability: All datasets are available on EBI's ArrayExpress web site http://www.ebi.ac.uk/microarray-as/ae/) under accession numbers E-TABM-536, E-TABM-554 and E-TABM-555. Source code implemented in C and R is available at: http://statistics.msi.meduniwien.ac.at/float/cross_platform/.

Methods for testing and variance decomposition have been made available in the R-package orQA, which can be downloaded and installed from CRAN http://cran.r-project.org.

Contact:  martin.posch.mail@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Bases adjacent to mononucleotide repeats show an increased single nucleotide polymorphism frequency in the human genome
Authors: Siddle K. J. , Goodship J. A. , Keavney B. , Santibanez-Koref M. F.
Published: February 2011

Mononucleotide repeats (MNRs) are abundant in eukaryotic genomes and exhibit a high degree of length variability due to insertion and deletion events. However, the relationship between these repeats and mutation rates in surrounding sequences has not been systematically investigated. We have analyzed the frequency of single nucleotide polymorphisms (SNPs) at positions close to and within MNRs in the human genome. Overall, we find a 2- to 4-fold increase in the SNP frequency at positions immediately adjacent to the boundaries of MNRs, relative to that at more distant bases. This relationship exhibits a strong asymmetry between 3′ and 5′ ends of repeat tracts and is dependent upon the repeat motif, length and orientation of surrounding repeats. Our analysis suggests that the incorporation or exclusion of bases adjacent to the boundary of the repeat through substitutions, in which these nucleotides mutate towards or away from the base present within the repeat, respectively, may be another mechanism by which MNRs expand and contract in the human genome.

Contact:  kjsiddle@pasteur.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Automated analysis of biological oscillator models using mode decomposition
Authors: Konopka Tomasz
Published: February 2011

Motivation: Oscillating signals produced by biological systems have shapes, described by their Fourier spectra, that can potentially reveal the mechanisms that generate them. Extracting this information from measured signals is interesting for the validation of theoretical models, discovery and classification of interaction types, and for optimal experiment design.

Results: An automated workflow is described for the analysis of oscillating signals. A software package is developed to match signal shapes to hundreds of a priori viable model structures defined by a class of first-order differential equations. The package computes parameter values for each model by exploiting the mode decomposition of oscillating signals and formulating the matching problem in terms of systems of simultaneous polynomial equations. On the basis of the computed parameter values, the software returns a list of models consistent with the data. In validation tests with synthetic datasets, it not only shortlists those model structures used to generate the data but also shows that excellent fits can sometimes be achieved with alternative equations. The listing of all consistent equations is indicative of how further invalidation might be achieved with additional information. When applied to data from a microarray experiment on mice, the procedure finds several candidate model structures to describe interactions related to the circadian rhythm. This shows that experimental data on oscillators is indeed rich in information about gene regulation mechanisms.

Availability: The software package is available at http://babylone.ulb.ac.be/autoosc/.

Contact:  tkonopka@ulb.ac.be

Supplementary information:  Supplementary data are available at Bioinformatics online.
Network clustering: probing biological heterogeneity by sparse graphical models
Authors: Mukherjee Sach , Hill Steven M.
Published: February 2011

Motivation: Networks and pathways are important in describing the collective biological function of molecular players such as genes or proteins. In many areas of biology, for example in cancer studies, available data may harbour undiscovered subtypes which differ in terms of network phenotype. That is, samples may be heterogeneous with respect to underlying molecular networks. This motivates a need for unsupervised methods capable of discovering such subtypes and elucidating the corresponding network structures.

Results: We exploit recent results in sparse graphical model learning to put forward a ‘network clustering’ approach in which data are partitioned into subsets that show evidence of underlying, subset-level network structure. This allows us to simultaneously learn subset-specific networks and corresponding subset membership under challenging small-sample conditions. We illustrate this approach on synthetic and proteomic data.

Availability:  go.warwick.ac.uk/sachmukherjee/networkclustering

Contact:  s.n.mukherjee@warwick.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
eGOB: eukaryotic Gene Order Browser
Authors: López Marcela Dávila , Samuelsson Tore
Published: February 2011

Summary: A large number of genomes have been sequenced, allowing a range of comparative studies. Here, we present the eukaryotic Gene Order Browser with information on the order of protein and non-coding RNA (ncRNA) genes of 74 different eukaryotic species. The browser is able to display a gene of interest together with its genomic context in all species where that gene is present. Thereby, questions related to the evolution of gene organization and non-random gene order may be examined. The browser also provides access to data collected on pairs of adjacent genes that are evolutionarily conserved.

Availability: eGOB as well as underlying data are freely available at http://egob.biomedicine.gu.se

Supplementary information:  Supplementary data are available at Bioinformatics online.

Contact:  tore.samuelsson@medkem.gu.se
Topological entropy of DNA sequences
Authors: Koslicki David
Published: February 2011

Motivation: Topological entropy has been one of the most difficult to implement of all the entropy-theoretic notions. This is primarily due to finite sample effects and high-dimensionality problems. In particular, topological entropy has been implemented in previous literature to conclude that entropy of exons is higher than of introns, thus implying that exons are more ‘random’ than introns.

Results: We define a new approximation to topological entropy free from the aforementioned difficulties. We compute its expected value and apply this definition to the intron and exon regions of the human genome to observe that as expected, the entropy of introns are significantly higher than that of exons. We also find that introns are less random than expected: their entropy is lower than the computed expected value. We also observe the perplexing phenomena that introns on chromosome Y have atypically low and bimodal entropy, possibly corresponding to random sequences (high entropy) and sequences that posses hidden structure or function (low entropy).

Availability: A Mathematica implementation is available at http://www.math.psu.edu/koslicki/entropy.nb

Contact:  koslicki@math.psu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Spatial and temporal variability in the structure of aggregations of Antarctic krill (Euphausia superba) around South Georgia, 1997–1999
Authors: Cox Martin J. , Watkins Jonathan L. , Reid Keith , Brierley Andrew S.
Published: February 2011

Cox, M. J., Watkins, J. L., Reid, K., and Brierley, A. S. 2011. Spatial and temporal variability in the structure of aggregations of Antarctic krill (Euphausia superba) around South Georgia, 1997–1999. – ICES Journal of Marine Science, 68: . Antarctic krill are important in the South Georgia (54°S 35°W) marine ecosystem. They form aggregations that vary widely in packing density (<1 to 1000 s of individuals m−3), length (tens to thousands of metres), and height (tens of metres). Acoustic surveys are often used to estimate krill biomass and provide data that give insight into aggregation structure. Using dual-frequency (38 and 120 kHz) acoustic data collected during six surveys conducted around South Georgia during the 1997, 1998, and 1999 austral summers, we isolated 2990 aggregations by applying the Shoal Analysis and Patch Estimation System algorithm in Echoview and a krill-length-dependent acoustic identifier (ΔSv120–38). Multivariate cluster (partition) analysis was applied to metrics from each of the aggregations, resulting in three aggregation types with an overall proportional split of 0.28:0.28:0.44. Types 1 and 3 had low mean densities (<2 g m−3), whereas Type 2 had a mean density of 94 g m−3. Intersurvey differences were found between the effort-corrected numbers of aggregation types (p = 2.5e−6), and between on- and off-continental shelf areas (p = 1.5e−7), with a greater number of Type 2 aggregations being found on-shelf. The findings suggest intersurvey variation in krill catchability, with krill being more likely to be caught on-shelf.
Recognizing Red Flags in General Practice
Authors: Schroeder Knut , Chan Wai-Sun , Fahey Tom
Published: February 2011

Being able to sort the majority of patients who have self-limiting and benign medical conditions from those who need more urgent investigation or referral because they may have a potentially serious underlying disorder remains a key challenge for GPs. This can be a difficult task, given the wide range of medical problems in general practice and the time constraints under which GPs often have to work. Searching for alarm symptoms, signs or diagnostic tests—or ‘red flags’—can help with ‘ruling in’ and ‘ruling out’ serious diagnoses, such as cancer, myocardial infarction or stroke. This article discusses the usefulness—and limitations—of red flags in clinical practice.
Copper Supplementation Improves Functional Activities of Daily Living in Adults With Copper Deficiency
Authors: Prodan Calin I , Rabadi Meheroz , Vincent Andrea S , Cowan Linda D
Published: February 2011

Objective:

Neurologic manifestations of copper deficiency in adults are increasingly recognized. We sought to determine if copper supplementation over a period of 12 months would improve functional activities of daily living (ADLs) in patients with copper deficiency.

Methods:

We studied 15 consecutively diagnosed patients with copper deficiency that received 12 months of copper supplementation. Functional ADLs were evaluated by the Barthel Index (BI), administered at the time of diagnosis and repeated after 12 months of copper supplementation.

Results:

BI scores were significantly higher after 12 months of continued supplementation when compared with initial scores [(mean ± SD), 74 ± 11.7 versus 83 ± 13.2, P = 0.007, paired t-test]. A significant inverse linear correlation between the duration of symptoms before treatment and the change in the BI scores was noted (P = 0.005).

Conclusions:

Early initiation and sustained supplementation with copper for at least 12 months may improve functional ADLs in patients with copper deficiency.
Hyperalgesia After Volar Wrist Tattoo: A Case of Complex Regional Pain Syndrome?
Authors: Morte Paul D , Magee Larry M
Published: February 2011

Hyperalgesia after a volar wrist tattoo with features consistent with complex regional pain syndrome and a brief literature review is presented. This is the first case of disseminated hyperalgesia reported from a tattoo. It could be related to the increased pain associated with wrist tattooing and the proximity to the palmar cutaneous branch of the median nerve. The response to prednisone was robust. Further cases may appear considering popularization of wrist tattoos by celebrities.
Effects of 3-4 Diaminopyridine (DAP) in Motor Neuron Diseases
Authors: Bertorini Tulio E , Rashed Hani , Zeno Mitzi , Tolley Elizabeth A , Igarashi Masanori , Li Yingjun D
Published: February 2011

Objective:

To study the safety of 3-4 diaminopyridine (DAP) in patients with motor neuron diseases and to examine its efficacy in reducing muscle fatigue and weakness and in improving objective parameters of muscle function.

Design:

Assessments of safety included a questionnaire of symptoms, clinical examination, blood testing, and electrocardiography at each visit; efficacy was assessed by subjective scores of fatigue and weakness; an Amyotrophic Lateral Sclerosis Functional Rating Scale and functional ability scores, including timed verbal scores; manual muscle testing; grip dynamometry; pulmonary function tests; timed functional tests; and electrophysiological studies.

Participants:

Thirteen subjects with amyotrophic lateral sclerosis and seven subjects with only a lower motor neuron syndrome.

Main Outcomes:

Assess tolerability of DAP and determine if there was symptomatic improvement of muscle fatigue.

Secondary Outcome:

To determine the effects of DAP on objective parameters of muscle function.

Results:

The drug was well tolerated with only four subjects reporting tingling of lips and fingers during the active drug period. The subjective scores for fatigue and weakness showed a mild improvement after 4 weeks on DAP compared with placebo. A significant benefit of DAP was also demonstrated in the timed verbal scores.

Conclusion:

3-4 DAP appeared to be safe and produced subjective benefit in motor neuron diseases. The drug could be added for symptomatic treatment in these diseases. Larger studies are necessary to demonstrate efficacy.
Posterior Reversible Encephalopathy Syndrome Resulting From Guillain-Barré-Like Syndrome Secondary to West Nile Virus Infection
Authors: Abraham Alon , Ziv Sari , Drory Vivian E
Published: February 2011

A 67-year-old woman developed hypertension, drowsiness, hemianopia, ascending flaccid tetraparesis, and areflexia. Nerve conduction studies revealed a demyelinating polyneuropathy. Brain magnetic resonance imaging demonstrated hyperintense white matter lesions. IgM antibodies against West Nile virus were positive. She was treated for hypertension and with intravenous immunoglobulins and recovered completely within 2 months. To our knowledge, this is the first case in which West Nile virus infection presented as posterior reversible encephalopathy syndrome associated with Guillain-Barré-like syndrome.
Comparison of Sudomotor and Sensory Nerve Testing in Painful Sensory Neuropathies
Authors: Killian James M , Smyth Shane , Guerra Rudy , Adhikari Ishan , Harati Yadollah
Published: February 2011

Objective:

To compare results of quantitative sudomotor axon reflex testing (QSART), dorsal sural, and sural sensory nerve testing in patients with painful sensory neuropathy (PSN).

Methods:

Fifty-six patients with symptoms and neurologic examinations consistent with PSN who had both autonomic and nerve conduction studies were identified from 376 patients with a clinical diagnosis of painful neuropathy. Cases were clinically categorized as large-fiber or small-fiber neuropathies by described criteria. The results of sural, dorsal sural, and QSART tests were then analyzed in relationship to these two clinical groups.

Results:

Evidence of unmyelinated fiber abnormalities by QSART was noted in 85% of clinical large-fiber and 69% of clinical small-fiber groups. Dorsal sural potentials were absent in all the large-fiber group but also in 52% of clinically classified small-fiber neuropathies. When QSART and dorsal sural abnormalities were combined, the identification of abnormalities in all the cases of PSN was 89% with 75% of cases (42) showing mixed large and small fiber abnormalities, 14% unmyelinated sensory fiber abnormalities (by QSART), and 11% normal studies.

Conclusion:

This study demonstrates the value of combining both QSART and dorsal sural sensory testing in verifying the diagnosis of PSN. The majority of cases demonstrate involvement of unmyelinated C fibers as well as large/medium myelinated fibers, thereby separating mixed large- and small-fiber sensory neuropathies from those cases classified by clinical criteria solely as small-fiber neuropathy.
Delayed Cervicobulbar Neuronopathy and Myokymia After Head and Neck Radiotherapy for Nasopharyngeal Carcinoma: A Case Report
Authors: Rison Richard A , Beydoun Said R
Published: February 2011

Introduction:

Delayed progressive cervicobulbar palsy with secondary lingual, facial, and neck myokymia after radiation therapy to the head and neck is a known but rare event with few reported case descriptions.

Case Presentation:

We report a case with a video description of a young Asian woman who developed progressive dysarthria and dysphagia after approximately 1 year after radiation treatment for nasopharyngeal carcinoma. Her symptoms, clinical, and electromyographic findings are discussed and were felt to be secondary to a cervicobulbar neuronopathy secondary to the previous radiation she received. A brief literature review was performed and pathophysiological mechanisms and treatment options are discussed.

Conclusion:

Delayed progressive cervicobulbar neuronopathy with myokymia is an uncommon complication of radiotherapy for nasopharyngeal carcinoma. Clinicians should be aware of this entity to prevent misdiagnosis with other neuromuscular and nonneuromuscular diseases.
Herpes Zoster With Motor Involvement: Discordance Between the Distribution of Skin Rash and Localization of Peripheral Nervous System Dysfunction
Authors: Alshekhlee Amer , Tay Edward , Buczek Marek , Shakir Zaid A , Katirji Bashar
Published: February 2011

Herpes zoster viral infection (shingles) frequently appears in the thoracic dermatomes with no detectable weakness. We describe three patients who exhibited classic symptoms of herpes zoster infection of the upper limb with various neuropathic findings, including multiple mononeuropathies, radiculopathy, and brachial plexopathy. The distribution of weakness and electrodiagnostic findings was not limited to the involved dermatomes. Furthermore, the electrodiagnostic studies in one patient show evidence of acquired demyelination; hence, the infectious process may include the axon and/or the myelin sheath of the peripheral nerves. In the upper limb, we suggest that a mismatch between the distribution of the vesicular herpetic rash and weakness, as corroborated by the clinical examination and the electrodiagnostic studies, may occur.
Desulfovibrio arcticus sp. nov., a psychrotolerant sulfate-reducing bacterium from a cryopeg
Authors: Pecheritsyna Svetlana A. , Rivkina Elizaveta M. , Akimov Vladimir N. , Shcherbakova Viktoria A.
Published: February 2011

A psychrotolerant sulfate-reducing bacterium, designated B15T, was isolated from supercooled water brine from within permafrost of the Varandey Peninsula, on the southern coast of the Barents Sea. Cells were Gram-negative, motile vibrions (3.0–4.0×0.4–0.5 µm) with a single polar flagellum. The isolate was positive for desulfoviridin as a bisulfite reductase. Strain B15Tgrew at −2 to 28 °C (optimum 24 °C) and with 0–2.0 % NaCl (optimum 0.2 %). The isolate used H2plus acetate, formate, ethanol, lactate, pyruvate and choline as electron donors and used sulfate, sulfite, thiosulfate, elemental sulfur, DMSO and Fe3+as electron acceptors. Pyruvate and lactate were not fermented in the absence of sulfate. The G+C content of genomic DNA was 55.2 mol%. Analysis of the 16S rRNA gene sequence showed that the isolate belonged to the genusDesulfovibrio. Its closest relatives wereDesulfovibrio idahonensisCY1T(98.8 % 16S rRNA gene sequence similarity) andDesulfovibrio mexicanusLup1T(96.5 %). On the basis of genotypic, phenotypic and phylogenetic characteristics, the isolate represents a novel species, for which the nameDesulfovibrio arcticussp. nov. is proposed; the type strain is B15T( = VKM B-2367T = DSM 21064T).
Phenotypic variability and phylogenetic relationships of the genera Tolypothrix and Calothrix (Nostocales, Cyanobacteria) from running water
Authors: Berrendero Esther , Perona Elvira , Mateo Pilar
Published: February 2011

The taxonomy of heterocystous cyanobacteria belonging to the genera Calothrix and Tolypothrix has long been a matter of debate, but their phylogenetic relationships are still not well understood. Our aim was to compare the phylogeny and morphology of members of these genera, which exhibit basal–apical polarity. A phylogeny was reconstructed on the basis of 16S rRNA gene sequences and compared with the morphological characterization of new isolates and environmental samples. Strains isolated from several rivers and streams showed a high degree of tapering when they were cultured in a nutrient-rich medium. However, clear differences were apparent when they were transferred to a nutrient-poor medium. Some strains showed a low degree of tapering and other morphological features corresponding to the genus Tolypothrix, such as false branching, whereas others maintained the morphological characteristics of the genus Calothrix. Phylogenetic analysis was congruent with the phenotypic characterization, in which the strains and environmental samples of the Tolypothrix and Calothrix morphotypes could be clearly separated. Isolates with a low degree of tapering and natural samples of Tolypothrix distorta were grouped in the same cluster, but strains of the genus Calothrix fell into well separated clades. Results from this study showed that representatives of the genus Tolypothrix share most morphological and developmental properties and a high degree of 16S rRNA gene sequence similarity. However, although similar and sometimes overlapping morphologies may occur in isolates of the genus Calothrix, these morphotypes may be distinguished on the basis of their clear genetic divergence.
Laceyella sediminis sp. nov., a thermophilic bacterium isolated from a hot spring
Authors: Chen Jiu-Jiu , Lin Lian-Bing , Zhang Lan-Lan , Zhang Jin , Tang Shu-Kun , Wei Yun-Lin , Li Wen-Jun
Published: February 2011

A thermophilic bacterium, designated strain RHA1T, was isolated from a sediment sample collected from a hot spring in Tengchong county, Yunnan province, south-west China, and was characterized by using a polyphasic approach. Based on its phenotypic and phylogenetic characteristics, strain RHA1T was affiliated to the genus Laceyella. The strain formed white aerial and yellow–white substrate mycelia, bearing single endospores on short sporophores. The cell-wall peptidoglycan contained meso-diaminopimelic acid. Whole-cell hydrolysates contained ribose and glucose. The major fatty acids were iso-C15 : 0 (62.39 %) and anteiso-C15 : 0 (17.55 %). The predominant menaquinone was MK-9. The G+C content of the genomic DNA of strain RHA1T was 47.9 mol%. Based on DNA–DNA hybridization data, chemotaxonomic characteristics and differential physiological properties, strain RHA1T is considered to represent a novel species of the genus Laceyella, for which the name Laceyella sediminis sp. nov. is proposed; the type strain is RHA1T ( = DSM 45263T = CCTCC AA 208058T).
Maritalea porphyrae sp. nov., isolated from a red alga (Porphyra yezoensis), and transfer of Zhangella mobilis to Maritalea mobilis comb. nov.
Authors: Fukui Youhei , Abe Mahiko , Kobayashi Masahiro , Ishihara Kenji , Oikawa Hiroshi , Yano Yutaka , Satomi Masataka
Published: February 2011

Three Gram-negative, motile, aerobic bacteria were isolated from cultures of the marine red alga Porphyra yezoensis. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the novel strains were closely related to Maritalea myrionectae CL-SK30T (97.9 % 16S rRNA gene sequence similarity) and Zhangella mobilis E6T (96.2 %). 16S rRNA gene sequence similarity between Z. mobilis E6T and M. myrionectae CL-SK30T was 97.9 %. The DNA G+C contents of the isolates (49.4–50.0 mol%) were similar to those of M. myrionectae DSM 19524T (52.3 mol%) and Z. mobilis JCM 15144T (50.3 mol%). From these results, it was difficult to differentiate the genus Zhangella from the genus Maritalea. DNA–DNA hybridization demonstrated that the isolates belonged to a single species. The isolates could also be distinguished from M. myrionectae and Z. mobilis on the basis of chemotaxonomic and phenotypic features, including fatty acid composition (particularly C16 : 1ω7c), growth with 6–9 % (w/v) NaCl, carbon utilization, oxidation patterns and so on. A novel species of the genus Maritalea is proposed to accommodate the three isolates, with the name Maritalea porphyrae sp. nov. The type strain is LCM-3T ( = LMG 25872T = NBRC 107169T). Furthermore, it is proposed that Zhangella mobilis should be transferred from the genus Zhangella to the genus Maritalea, with the name Maritalea mobilis comb. nov. (type strain E6T = CGMCC 1.7002T = JCM 15144T).
Psychrobacter sanguinis sp. nov., recovered from four clinical specimens over a 4-year period
Authors: Wirth Samantha E. , Ayala-del-Río Héctor L. , Cole Jocelyn A. , Kohlerschmidt Donna J. , Musser Kimberlee A. , Sepúlveda-Torres Lycely del C. , Thompson Lisa M. , Wolfgang William J.
Published: February 2011

An analysis of 16S rRNA gene sequences from archived clinical reference specimens identified a novel species of the genus Psychrobacter, of which four strains have been independently isolated from human blood. On the basis of 16S rRNA gene sequence similarity, the closest relatives with validly published names were Psychrobacter arenosus R7T (98.7 %), P. pulmonis CECT 5989T (97.7 %), P. faecalis Iso-46T (97.6 %) and P. lutiphocae IMMIB L-1110T (97.2 %). Maximum-likelihood phylogenetic analysis of 16S rRNA gene sequences showed that the isolates belonged to the genus Psychrobacter and were members of a cluster associated with Psychrobacter sp. PRwf-1, isolated from a silk snapper fish. DNA–DNA relatedness and partial 23S rRNA gene sequences also supported the finding that the isolates belonged to a species distinct from its closest phylogenetic neighbours. The predominant cellular fatty acids were C18 : 1ω9c, C16 : 0, summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH), summed feature 5 (C18 : 2ω6,9c and/or anteiso-C18 : 0) and C18 : 0. Biochemical and morphological analysis further supported the assignment of the four isolates to a novel species. The name Psychrobacter sanguinis sp. nov. is proposed. The type strain is 13983T ( = DSM 23635T = CCUG 59771T).
Mucilaginibacter angelicae sp. nov., isolated from the rhizosphere of Angelica polymorpha Maxim
Authors: Kim Byung-Chun , Poo Haryoung , Lee Kang Hyun , Kim Mi Na , Kwon O-Yu , Shin Kee-Sun
Published: February 2011

A Gram-negative-staining, non-motile rod, designated GG-w14T, was isolated from the rhizosphere of Angelica polymorpha Maxim. Phylogenetic analysis of 16S rRNA gene sequences revealed that the isolate belonged to the genus Mucilaginibacter and exhibited 93.9–97.4 % 16S rRNA gene sequence similarity with recognized members of the genus Mucilaginibacter (closest relative Mucilaginibacter gossypii Gh-67T). DNA–DNA relatedness between strain GG-w14T and M. gossypii KCTC 22380T was <41 %. Strain GG-w14T grew at 4–35 °C, at pH 5.0–8.0 and with 0–1 % (w/v) NaCl. The isolate hydrolysed casein, CM-cellulose and starch and contained menaquinone 7 as the major menaquinone. The major cellular fatty acids were summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH; 39.9 %), iso-C15 : 0 (24.2 %) and iso-C17 : 0 3-OH (12.4 %). The DNA G+C content was 42.5 mol%. These data suggest that strain GG-w14T should be considered as a representative of a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter angelicae sp. nov. is proposed. The type strain is GG-w14T ( = KCTC 23250T = NCAIM B 02415T).
Amycolatopsis salitolerans sp. nov., a filamentous actinomycete isolated from a hypersaline habitat
Authors: Guan Tong-Wei , Xia Zhan-Feng , Tang Shu-Kun , Wu Nan , Chen Zheng-Jun , Huang Ying , Ruan Ji-Sheng , Li Wen-Jun , Zhang Li-Li
Published: February 2011

A novel actinomycete strain, designated TRM F103T, was isolated from a hypersaline habitat of the Tarim basin in Xinjiang province, north-west China. Phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate belonged to the genus Amycolatopsis and was most closely related to Amycolatopsis halophila YIM 93223T (99.3 % 16S rRNA gene sequence similarity). However, DNA–DNA relatedness between these two strains, based on triplicate experiments, was only 31.6 %. The isolate contained meso-diaminopimelic acid and ribose, glucose and galactose as the major whole-cell sugars. The predominant menaquinone was MK-8(H4). The major fatty acids were iso-C16 : 0 and C16 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine and glucosamine-containing phospholipids. The G+C content of the genomic DNA was 66.4 mol%. The phenotypic data clearly distinguished the isolate from its closest relatives. The combined phylogenetic, chemotaxonomic and phenotypic data indicate that the isolate represents a novel species of the genus Amycolatopsis. The proposed name is Amycolatopsis salitolerans sp. nov., with TRM F103T ( = JCM 15899T = CCTCC AB 208326T) as the type strain.