bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral granulomatosis‐like lesions in liver‐transplanted pediatric patients
Authors: Vivas APM , Bomfin LE , Costa WL , Porta G , Alves FA
Published: June 2013

Objective

This study evaluated oral mucosal lesions in liver‐transplanted children.

Methods

A retrospective study was performed on pediatric patients who underwent liver transplantation between 2002 and 2009, at A.C. Camargo Hospital, Sao Paulo‐SP. Alterations, such as polypoid lesions over the dorsum of the tongue, lip swelling, angular cheilitis, fissures of the lips, mucosal tags, cobblestone appearance, and fissures of the tongue, were considered as orofacial granulomatosis (OFG)‐like lesions. All clinical data were collected from medical records. Descriptive analyses and logistic regression were used to characterize and identify OFG‐like lesion predictors.

Results

Of the 265 transplanted children, 56.6% were female, and 64.1% had biliary atresia. Fourteen patients died as a consequence of the transplantation surgery and were therefore excluded from the analysis related to oral lesions. Hence, among 251 patients, 64 showed OFG‐like lesions. The lesions occurred around 26 months after transplantation, and the only therapy that all the patients were receiving in common was tacrolimus. Furthermore, patients aged 12 months old or less at transplantation presented higher risk to present oral lesions.

Conclusions

This study described specific oral mucosal lesions in liver‐transplanted children. Such lesions have recently been described as a novel entity. Although young age at transplantation has been associated to its development, the etiology of this condition is uncertain.
Association of TLR2, TLR3, TLR4 and CD14 genes polymorphisms with oral cancer risk and survival
Authors: Zeljic K , Supic G , Jovic N , Kozomara R , Brankovic‐Magic M , Obrenovic M , Magic Z
Published: June 2013

Objectives

The aim of this study is to investigate association between polymorphisms in TLR2, TLR3, TLR4 and CD14 genes or their haplotypes with oral squamous cell carcinomas (OSCC) risk and survival.

Methods

The study was conducted on 93 OSCC patients and 104 cancer‐free controls. Polymorphisms were genotyped by real‐time PCR or PCR‐RFLP method.

Results

Significant increase in oral cancer risk was observed in individuals with mutated genotype of TLR3 rs3775291 polymorphism (OR = 1.096, P = 0.036) compared to wild‐type. The heterozygous and mutated genotype of TLR3 rs5743312 polymorphism had worse survival in group of patients with stage III tumours (P = 0.043). Multivariate Cox regression analysis revealed that TLR3 rs5743312 polymorphism could be considered as prognostic marker in advanced III stage OSCC (HR = 2.456, P = 0.007), but not independently of nodal status. TLR3 rs3775291 and rs5743312 polymorphisms were in strong linkage disequilibrium. Haplotype TG was associated with worse prognosis in OSCC patients in comparison with common CG haplotype (HR = 1.717, P = 0.042). Interaction among polymorphisms in TLR2, TLR3 and CD14 genes was observed (P = 0.010).

Conclusions

TLR3 rs5743312 polymorphism could be considered as potential predictor of worse overall survival in advanced oral cancer, but not independently of nodal status. Haplotypes in TLR3 gene might be associated with poor prognosis in OSCC patients.
Assessing Motivations for Suicide Attempts: Development and Psychometric Properties of the Inventory of Motivations for Suicide Attempts
Authors: May Alexis M. , Klonsky E. David
Published: June 2013

This study describes the psychometric properties of the Inventory of Motivations for Suicide Attempts (IMSA). The IMSA was designed to comprehensively assess motivations for suicide emphasized by major theories of suicidality. The IMSA was administered to two samples of recent suicide attempters, undergraduates (n = 66) and outpatients (n = 53). The IMSA exhibited a reliable two‐factor structure in which one factor represented Intrapersonal motivations related to ending emotional pain, and the second represented Interpersonal motivations related to communication or help‐seeking. Convergent validity and divergent validity of IMSA scales were supported by expected patterns of correlations with another measure of suicide motivations. In addition, the IMSA scales displayed clinical utility, in which greater endorsement of intrapersonal motivations was associated with greater intent to die, whereas greater endorsement of interpersonal motivations was associated with less lethal intent and greater likelihood of rescue. Findings suggest the IMSA can be of use for both research and clinical purposes when a comprehensive assessment of suicide motivations is desired.
Region growing by sector analysis for detection of blue‐gray ovoids in basal cell carcinoma
Authors: Pelin Guvenc S. , Leander Robert W. , Kefel Serkan , Rader Ryan K. , Hinton Kristen A. , Stricklin Sherea M. , Stoecker William V.
Published: June 2013

Blue‐gray ovoids (B‐GOs) are critical dermoscopic structures in basal cell carcinomas (BCCs) that pose a challenge for automatic detection. Due to variation in size and color, B‐GOs can be easily mistaken for similar structures in benign lesions. Analysis of these structures could help further accomplish the goal of automatic BCC detection. This study introduces an efficient sector‐based method for segmenting B‐GOs. Four modifications of conventional region‐growing techniques are presented: (i) employing a seed area rather than a seed point, (ii) utilizing fixed control limits determined from the seed area to eliminate re‐calculations of previously‐added regions, (iii) determining region growing criteria using logistic regression, and (iv) area analysis and expansion by sectors. Contact dermoscopy images of 68 confirmed BCCs having B‐GOs were obtained. A total of 24 color features were analyzed for all B‐GO seed areas. Logistic regression analysis determined blue chromaticity, followed by red variance, were the best features for discriminating B‐GO edges from surrounding areas. Segmentation of malignant structures obtained an average Pratt's figure of merit of 0.397. The techniques presented here provide a non‐recursive, sector‐based, region‐growing method applicable to any colored structure appearing in digital images. Further research using these techniques could lead to automatic detection of B‐GOs in BCCs.
Identification of a cyanobacterial CRR6 protein, Slr1097, required for efficient assembly of NDH‐1 complexes in Synechocystis sp. PCC 6803
Authors: Dai Huiling , Zhang Lili , Zhang Jingsong , Mi Hualing , Ogawa Teruo , Ma Weimin
Published: June 2013

Despite significant progress in clarifying the subunit compositions and functions of the multiple NADPH dehydrogenase (NDH‐1) complexes in cyanobacteria, the subunit maturation and assembly of their NDH‐1 complexes are poorly understood. By transformation of wild‐type cells with a transposon‐tagged library, we isolated three mutants of Synechocystis sp. PCC 6803 defective in NDH‐1‐mediated cyclic electron transfer and unable to grow under high light conditions. All the mutants were tagged in the same slr1097 gene, encoding an unknown protein that shares significant homology with the Arabidopsis protein chlororespiratory reduction 6 (CRR6). The slr1097 product was localized in the cytoplasm and was required for efficient assembly of NDH‐1 complexes. Analysis of the interaction of Slr1097 with 18 subunits of NDH‐1 complexes using a yeast two‐hybrid system indicated a strong interaction with NdhI but not with other Ndh subunits. Absence of Slr1097 resulted in a significant decrease of NdhI in the cytoplasm, but not of other Ndh subunits including NdhH, NdhK and NdhM; the decrease was more evident in the cytoplasm than in the thylakoid membranes. In the ∆slr1097 mutant, NdhH, NdhI, NdhK and NdhM were hardly detectable in the NDH‐1M complex, whereas almost half the wild‐type levels of these subunits were present in NDH‐1L complex; similar results were observed in the NdhI‐less mutant. These results suggest that Slr1097 is involved in the maturation of NdhI, and that assembly of the NDH‐1M complex is strongly dependent on this factor. Maturation of NdhI appears not to be crucial to assembly of the NDH‐1L complex.
Tunable Gigahertz Oscillators of Gliding Incommensurate Bilayer Graphene Sheets
Authors: Luo Ming , Zhang Zhuhua , Yakobson Boris I.
Published: June 2013

Oscillators composed of incommensurate graphene sheets have been investigated by molecular dynamics simulations. The oscillation frequencies can reach tens of gigahertz range and depend on the surface energy of the bilayer graphene and the oscillatory amplitude. We demonstrate the tunability of such an oscillator in terms of frequency and friction by its varying geometric parameters. Exploration of the damping mechanism by combining the autocorrelation function theory and the direct atomistic simulations reveals that the friction force is proportional to the velocity of oscillatory motion. The results should help optimize the design of graphene-based nanoelectromechanical devices.
Mechanics of Adhered, Pressurized Graphene Blisters
Authors: Boddeti Narasimha G. , Koenig Steven P. , Long Rong , Xiao Jianliang , Bunch J. Scott , Dunn Martin L.
Published: June 2013

We study the mechanics of pressurized graphene membranes using an experimental configuration that allows the determination of the elasticity of graphene and the adhesion energy between a substrate and a graphene (or other two-dimensional solid) membrane. The test consists of a monolayer graphene membrane adhered to a substrate by surface forces. The substrate is patterned with etched microcavities of a prescribed volume and, when they are covered with the graphene monolayer, it traps a fixed number (N) of gas molecules in the microchamber. By lowering the ambient pressure and thus changing the pressure difference across the graphene membrane, the membrane can be made to bulge and delaminate in a stable manner from the substrate. This is in contrast to the more common scenario of a constant pressure membrane blister test, where membrane delamination is unstable, and so this is not an appealing test to determine adhesion energy. Here, we describe the analysis of the membrane/substrate as a thermodynamic system and explore the behavior of the system over representative experimentally accessible geometry and loading parameters. We carry out companion experiments and compare them to the theoretical predictions and then use the theory and experiments together to determine the adhesion energy of graphene/SiO2 interfaces. We find an average adhesion energy of 0.24 J/m2, which is lower but in line with our previously reported values. We assert that this test—which we call the constant N blister test—is a valuable approach to determine the adhesion energy between two-dimensional solid membranes and a substrate, which is an important but not well-understood aspect of behavior. The test also provides valuable information that can serve as the basis for subsequent research to understand the mechanisms contributing to the observed adhesion energy. Finally, we show how, in the limit of a large microcavity, the constant N test approaches the behavior observed in a constant pressure blister test, and we provide an experimental observation that suggests this behavior.
L-A-lus, a New Variant of the L-A Totivirus Found in Wine Yeasts with Klus Killer Toxin-Encoding Mlus Double-Stranded RNA: Possible Role of Killer Toxin-Encoding Satellite RNAs in the Evolution of Their Helper Viruses
Authors: Rodríguez-Cousiño Nieves , Gómez Pilar , Esteban Rosa
Published: June 2013

Yeast killer viruses are widely distributed in nature. Several toxins encoded in double-stranded RNA (dsRNA) satellites of the L-A totivirus have been described, including K1, K2, K28, and Klus. The 4.6-kb L-A genome encodes the Gag major structural protein that forms a 39-nm icosahedral virion and Gag-Pol, a minor fusion protein. Gag-Pol has transcriptase and replicase activities responsible for maintenance of L-A (or its satellite RNAs). Recently we reported a new killer toxin, Klus. The L-A virus in Klus strains showed poor hybridization to known L-A probes, suggesting substantial differences in their sequences. Here we report the characterization of this new L-A variant named L-A-lus. At the nucleotide level, L-A and L-A-lus showed only 73% identity, a value that increases to 86% in the amino acid composition of Gag or Gag-Pol. Two regions in their genomes, however, the frameshifting region between Gag and Pol and the encapsidation signal, are 100% identical, implying the importance of these two
cis
signals in the virus life cycle. L-A-lus shows higher resistance than L-A to growth at high temperature or to
in vivo
expression of endo- or exonucleases. L-A-lus also has wider helper activity, being able to maintain not only Mlus but also M1 or a satellite RNA of L-A called X. In a screening of 31 wine strains, we found that none of them had L-A; they carried either L-A-lus or a different L-A variant in K2 strains. Our data show that distinct M killer viruses are specifically associated with L-As with different nucleotide compositions, suggesting coevolution.
Evidence for Coexistence of Distinct Escherichia coli Populations in Various Aquatic Environments and Their Survival in Estuary Water
Authors: Berthe T. , Ratajczak M. , Clermont O. , Denamur E. , Petit F.
Published: June 2013

Escherichia coli
, a commensal bacterium from the intestinal tracts of humans and vertebrate animals, has been used as one of two bacterial indicators of fecal contamination, along with intestinal enterococci, to monitor the microbiological quality of water. However, water environments are now recognized as a secondary habitat where some strains can survive. We investigated the survival of
E. coli
isolates collected from bodies of water in France exhibiting distinct profiles of contamination, defined according to the following criteria: vicinity of the point sources of contamination, land use, hydrology, and physicochemical characteristics of the receiving water. We selected 88
E. coli
strains among a collection of 352 strains to carry out a microcosm experiment in filtered estuarine water for 14 days at 10°C. The relationship between the survival of
E. coli
strains and genotypic and phenotypic characteristics was analyzed. This work showed that distinct
E. coli
survival types, able to survive from between 7 and 14 days to less than 2 days, coexisted in the water.
E. coli
isolates that rapidly lost their culturability were more frequently isolated in water recently contaminated by fecal bacteria of human origin, and most were multiresistant to antibiotics and harbored several virulence factors. In contrast, persistent strains able to survive from 4 to 14 days were more often found in water with low levels of fecal bacteria, belonged mainly to the B1 phylogroup, often harbored only one virulence factor,
kspE
or
ompT
, and were able to grow at 7°C.
Fusion of a Flavin-Based Fluorescent Protein to Hydroxynitrile Lyase from Arabidopsis thaliana Improves Enzyme Stability
Authors: Scholz Kathrin Emmi , Kopka Benita , Wirtz Astrid , Pohl Martina , Jaeger Karl-Erich , Krauss Ulrich
Published: June 2013

Hydroxynitrile lyase from
Arabidopsis thaliana
(
At
HNL) was fused to different fluorescent reporter proteins. Whereas all fusion constructs retained enzymatic activity and fluorescence
in vivo
and
in vitro
, significant differences in activity and pH stability were observed. In particular, flavin-based fluorescent reporter (FbFP) fusions showed almost 2 orders of magnitude-increased half-lives in the weakly acidic pH range compared to findings for the wild-type enzyme. Analysis of the quaternary structure of the respective FbFP-
At
HNL fusion proteins suggested that this increased stability is apparently caused by oligomerization mediated via the FbFP tag. Moreover, the increased stability of the fusion proteins enabled the efficient synthesis of (
R
)-mandelonitrile in an aqueous-organic two-phase system at a pH of <5. Remarkably, (
R
)-mandelonitrile synthesis is not possible using wild-type
At
HNL under the same conditions due to the inherent instability of this enzyme below pH 5. The fusion strategy presented here reveals a surprising means for the stabilization of enzymes and stresses the importance of a thorough
in vitro
characterization of
in vivo
-employed fluorescent fusion proteins.
Biotransformation of Trichoderma spp. and Their Tolerance to Aromatic Amines, a Major Class of Pollutants
Authors: Cocaign Angélique , Bui Linh-Chi , Silar Philippe , Chan Ho Tong Laetitia , Busi Florent , Lamouri Aazdine , Mougin Christian , Rodrigues-Lima Fernando , Dupret Jean-Marie , Dairou Julien
Published: June 2013

Trichoderma
spp. are cosmopolitan soil fungi that are highly resistant to many toxic compounds. Here, we show that
Trichoderma virens
and
T. reesei
are tolerant to aromatic amines (AA), a major class of pollutants including the highly toxic pesticide residue 3,4-dichloroaniline (3,4-DCA). In a previous study, we provided proof-of-concept remediation experiments in which another soil fungus,
Podospora anserina
, detoxifies 3,4-DCA through its arylamine
N
-acetyltransferase (NAT), a xenobiotic-metabolizing enzyme that enables acetyl coenzyme A-dependent detoxification of AA. To assess whether the
N
-acetylation pathway enables AA tolerance in
Trichoderma
spp., we cloned and characterized NATs from
T. virens
and
T. reesei
. We characterized recombinant enzymes by determining their catalytic efficiencies toward several toxic AA. Through a complementary approach, we also demonstrate that both
Trichoderma
species efficiently metabolize 3,4-DCA. Finally, we provide evidence that NAT-independent transformation is solely (in
T. virens
) or mainly (in
T. reesei
) responsible for the observed removal of 3,4-DCA. We conclude that
T. virens
and, to a lesser extent,
T. reesei
likely utilize another, unidentified, metabolic pathway for the detoxification of AA aside from acetylation. This is the first molecular and functional characterization of AA biotransformation in
Trichoderma
spp. Given the potential of
Trichoderma
for cleanup of contaminated soils, these results reveal new possibilities in the fungal remediation of AA-contaminated soil.
Transcriptome Sequencing (RNA-seq) Analysis of the Effects of Metal Nanoparticle Exposure on the Transcriptome of Chlamydomonas reinhardtii
Authors: Simon Dana F. , Domingos Rute F. , Hauser Charles , Hutchins Colin M. , Zerges William , Wilkinson Kevin J.
Published: June 2013

The widespread use of nanoparticles (NPs) raises concern over their potential toxicological effects in humans and ecosystems. Here we used transcriptome sequencing (RNA-seq) to evaluate the effects of exposure to four different metal-based NPs, nano-Ag (nAg), nano-TiO
2
(nTiO
2
), nano-ZnO (nZnO), and CdTe/CdS quantum dots (QDs), in the eukaryotic green alga
Chlamydomonas reinhardtii
. The transcriptome was characterized before and after exposure to each NP type. Specific toxicological effects were inferred from the functions of genes whose transcripts either increased or decreased. Data analysis resulted in important differences and also similarities among the NPs. Elevated levels of transcripts of several marker genes for stress were observed, suggesting that only nZnO caused nonspecific global stress to the cells under environmentally relevant conditions. Genes with photosynthesis-related functions were decreased drastically during exposure to nTiO
2
and slightly during exposures to the other NP types. This pattern suggests either toxicological effects in the chloroplast or effects that mimic a transition from low to high light. nAg exposure dramatically elevated the levels of transcripts encoding known or predicted components of the cell wall and the flagella, suggesting that it damages structures exposed to the external milieu. Exposures to nTiO
2
, nZnO, and QDs elevated the levels of transcripts encoding subunits of the proteasome, suggesting proteasome inhibition, a phenomenon believed to underlie the development and progression of several major diseases, including Alzheimer's disease, and used in chemotherapy against multiple myeloma.
Biodegradation of Endocrine Disruptors in Solid-Liquid Two-Phase Partitioning Systems by Enrichment Cultures
Authors: Villemur Richard , dos Santos Silvia Cristina Cunha , Ouellette Julianne , Juteau Pierre , Lépine François , Déziel Eric
Published: June 2013

Naturally occurring and synthetic estrogens and other molecules from industrial sources strongly contribute to the endocrine disruption of urban wastewater. Because of the presence of these molecules in low but effective concentrations in wastewaters, these endocrine disruptors (EDs) are only partially removed after most wastewater treatments, reflecting the presence of these molecules in rivers in urban areas. The development of a two-phase partitioning bioreactor (TPPB) might be an effective strategy for the removal of EDs from wastewater plant effluents. Here, we describe the establishment of three ED-degrading microbial enrichment cultures adapted to a solid-liquid two-phase partitioning system using Hytrel as the immiscible water phase and loaded with estrone, estradiol, estriol, ethynylestradiol, nonylphenol, and bisphenol A. All molecules except ethynylestradiol were degraded in the enrichment cultures. The bacterial composition of the three enrichment cultures was determined using 16S rRNA gene sequencing and showed sequences affiliated with bacteria associated with the degradation of these compounds, such as
Sphingomonadales
. One
Rhodococcus
isolate capable of degrading estrone, estradiol, and estriol was isolated from one enrichment culture. These results highlight the great potential for the development of TPPB for the degradation of highly diluted EDs in water effluents.
Development of a New Method for Detection and Identification of Oenococcus oeni Bacteriophages Based on Endolysin Gene Sequence and Randomly Amplified Polymorphic DNA
Authors: Doria Francesca , Napoli Chiara , Costantini Antonella , Berta Graziella , Saiz Juan-Carlos , Garcia-Moruno Emilia
Published: June 2013

Malolactic fermentation (MLF) is a biochemical transformation conducted by lactic acid bacteria (LAB) that occurs in wine at the end of alcoholic fermentation.Oenococcus oeniis the main species responsible for MLF in most wines. As in other fermented foods, where bacteriophages represent a potential risk for the fermentative process,O. oenibacteriophages have been reported to be a possible cause of unsuccessful MLF in wine. Thus, preparation of commercial starters that take into account the different sensitivities ofO. oenistrains to different phages would be advisable. However, currently, no methods have been described to identify phages infectingO. oeni. In this study, two factors are addressed: detection and typing of bacteriophages. First, a simple PCR method was devised targeting a conserved region of the endolysin (lys) gene to detect temperateO. oenibacteriophages. For this purpose, 37O. oenistrains isolated from Italian wines during different phases of the vinification process were analyzed by PCR for the presence of thelysgene, and 25 strains gave a band of the expected size (1,160 bp). This is the first method to be developed that allows identification of lysogenicO. oenistrains without the need for time-consuming phage bacterial-lysis induction methods. Moreover, a phylogenetic analysis was conducted to type bacteriophages. After the treatment of bacteria with UV light, lysis was obtained for 15 strains, and the 15 phage DNAs isolated were subjected to two randomly amplified polymorphic DNA (RAPD)-PCRs. By combining the RAPD profiles andlyssequences, 12 differentO. oeniphages were clearly distinguished.
The Plasma Membrane Proton Pump PMA-1 Is Incorporated into Distal Parts of the Hyphae Independently of the Spitzenkörper in Neurospora crassa
Authors: Fajardo-Somera Rosa A. , Bowman Barry , Riquelme Meritxell
Published: June 2013

Most models for fungal growth have proposed a directional traffic of secretory vesicles to the hyphal apex, where they temporarily aggregate at the Spitzenkörper before they fuse with the plasma membrane (PM). The PM H+-translocating ATPase (PMA-1) is delivered via the classical secretory pathway (endoplasmic reticulum [ER] to Golgi) to the cell surface, where it pumps H+out of the cell, generating a large electrochemical gradient that supplies energy to H+-coupled nutrient uptake systems. To characterize the traffic and delivery of PMA-1 during hyphal elongation, we have analyzed by laser scanning confocal microscopy (LSCM) strains ofNeurospora crassaexpressing green fluorescent protein (GFP)-tagged versions of the protein. In conidia, PMA-1-GFP was evenly distributed at the PM. During germination and germ tube elongation, PMA-1-GFP was found all around the conidial PM and extended to the germ tube PM, but fluorescence was less intense or almost absent at the tip. Together, the data indicate that the electrochemical gradient driving apical nutrient uptake is generated from early developmental stages. In mature hyphae, PMA-1-GFP localized at the PM at distal regions (>120 μm) and in completely developed septa, but not at the tip, indicative of a distinct secretory route independent of the Spitzenkörper occurring behind the apex.
Activation of CpxRA in Haemophilus ducreyi Primarily Inhibits the Expression of Its Targets, Including Major Virulence Determinants
Authors: Gangaiah Dharanesh , Zhang Xinjun , Fortney Kate R. , Baker Beth , Liu Yunlong , Munson Robert S. , Spinola Stanley M.
Published: June 2013

Haemophilus ducreyicauses chancroid, a genital ulcer disease that facilitates the transmission of human immunodeficiency virus type 1. In humans,H. ducreyiis surrounded by phagocytes and must adapt to a hostile environment to survive. To sense and respond to environmental cues, bacteria frequently use two-component signal transduction (2CST) systems. The only obvious 2CST system inH. ducreyiis CpxRA; CpxR is a response regulator, and CpxA is a sensor kinase. Previous studies by Hansen and coworkers showed that CpxR directly represses the expression ofdsrA, thelspB-lspA2operon, and theflpoperon, which are required for virulence in humans. They further showed that CpxA functions predominantly as a phosphatasein vitroto maintain the expression of virulence determinants. Since acpxAmutant is avirulent while acpxRmutant is fully virulent in humans, CpxA also likely functions predominantly as a phosphatasein vivo. To better understand the role ofH. ducreyiCpxRA in controlling virulence determinants, here we defined genes potentially regulated by CpxRA by using RNA-Seq. Activation of CpxR by deletion ofcpxArepressed nearly 70% of its targets, including seven established virulence determinants. Inactivation of CpxR by deletion ofcpxRdifferentially regulated few genes and increased the expression of one virulence determinant. We identified a CpxR binding motif that was enriched in downregulated but not upregulated targets. These data reinforce the hypothesis that CpxA phosphatase activity plays a critical role in controllingH. ducreyivirulencein vivo. Characterization of the downregulated genes may offer new insights into pathogenesis.
Role of the Ribosomal P-Site Elements of m
2
G966, m
5
C967, and the S9 C-Terminal Tail in Maintenance of the Reading Frame during Translational Elongation in Escherichia coli
Authors: Arora Smriti , Bhamidimarri Satya Prathyusha , Weber Michael H. W. , Varshney Umesh
Published: June 2013

The ribosomal P-site hosts the peptidyl-tRNAs during translation elongation. Which P-site elements support these tRNA species to maintain codon-anticodon interactions has remained unclear. We investigated the effects of P-site features of methylations of G966, C967, and the conserved C-terminal tail sequence of Ser, Lys, and Arg (SKR) of the S9 ribosomal protein in maintenance of the translational reading frame of an mRNA. We generated
Escherichia coli
strains deleted for the SKR sequence in S9 ribosomal protein, RsmB (which methylates C967), and RsmD (which methylates G966) and used them to translate LacZ from its +1 and −1 out-of-frame constructs. We show that the S9 SKR tail prevents both the +1 and −1 frameshifts and plays a general role in holding the P-site tRNA/peptidyl-tRNA in place. In contrast, the G966 and C967 methylations did not make a direct contribution to the maintenance of the translational frame of an mRNA. However, deletion of
rsmB
in the S9Δ3 background caused significantly increased −1 frameshifting at 37°C. Interestingly, the effects of the deficiency of C967 methylation were annulled when the
E. coli
strain was grown at 30°C, supporting its context-dependent role.
Discovery of Catalases in Members of the Chlamydiales Order
Authors: Rusconi Brigida , Greub Gilbert
Published: June 2013

Catalase is an important virulence factor for survival in macrophages and other phagocytic cells. InChlamydiaceae, no catalase had been described so far. With the sequencing and annotation of the full genomes ofChlamydia-related bacteria, the presence of different catalase-encoding genes has been documented. However, their distribution in theChlamydialesorder and the functionality of these catalases remain unknown. Phylogeny of chlamydial catalases was inferred using MrBayes, maximum likelihood, and maximum parsimony algorithms, allowing the description of three clade 3 and two clade 2 catalases. Only monofunctional catalases were found (no catalase-peroxidase or Mn-catalase). All presented a conserved catalytic domain and tertiary structure. Enzymatic activity of cloned chlamydial catalases was assessed by measuring hydrogen peroxide degradation. The catalases are enzymatically active with different efficiencies. The catalase ofParachlamydia acanthamoebaeis the least efficient of all (its catalytic activity was 2 logs lower than that ofPseudomonas aeruginosa). Based on the phylogenetic analysis, we hypothesize that an ancestral class 2 catalase probably was present in the common ancestor of all currentChlamydialesbut was retained only inCriblamydia sequanensisandNeochlamydia hartmannellae. The catalases of class 3, present inEstrella lausannensisandParachlamydia acanthamoebae, probably were acquired by lateral gene transfer fromRhizobiales, whereas forWaddlia chondrophilathey likely originated fromLegionellalesorActinomycetales. The acquisition of catalases on several occasions in theChlamydialessuggests the importance of this enzyme for the bacteria in their host environment.
Hypovitaminosis D and severe hypocalcaemia: the rebirth of an old disease
Authors: Pedrosa Cristina , Ferraria Nélia , Limbert Catarina , Lopes Lurdes
Published: June 2013

Vitamin D deficiency, once thought to be eradicated, is becoming a frequent occurence in children, caused mainly by dietary insufficiency. The classical manifestation is rickets, but in infants severe hypocalcaemia may present as stridor, tetany, seizures or, rarely, heart disease. Here, we describe four infants who presented with complications of severe hypocalcaemia secondary to nutritional vitamin D deficiency. (1) Female, 4 months old, several spasms. (2) Male, 8 days old, generalised tonic-clonic seizure. (3) Male, 9 months old, tetany. (4) Male, 4 months old, cardiogenic shock. The cases highlight the importance of child vitamin D supplementation from birth and throughout childhood. We also note that the vitamin D state should be evaluated by the 25(OH)-D value and not the 1,25(OH)2-D.
Megacystis microcolon intestinal hypoperistalsis syndrome
Authors: Hiradfar Mehran , Shojaeian Reza , Dehghanian Paria , Hajian Sara
Published: June 2013

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a multisystemic disorder in which impaired intestinal motor activity causes recurrent symptoms of intestinal obstruction in the absence of mechanical occlusion, associated with bladder distention without distal obstruction of the urinary tract. MMIHS and prune belly syndrome may overlap in most of the clinical features and discrimination of these two entities is important because the prognosis, management and consulting with parents are completely different. MMIHS outcome is very poor and in this article we present two neonates with MMIHS that both died in a few days.
Malignant fibrous histiocytoma
Authors: Mohan Ravi Prakash Sasankoti , Verma Sankalp , Siddhu Vivek Kumar , Agarwal Neha
Published: June 2013

Malignant fibrous histiocytoma (MFH) is a type of histiocytoma and is the most common soft tissue sarcoma of late adult life. However, it is relatively uncommon in the head and neck area. It usually occurs/develops in the lower extremities and in the retroperitonium. This tumour is difficult to distinguish histologically from other sarcomas and carcinomas. Surgery is the only treatment option. Prognosis is fairly poor; recurrence and local metastasis are common. In comparison with MFH of the extremities and the trunk, the 5-year survival rate for cases of this tumour in the head and neck is low. It is important to consider MFH in differential diagnosis of head and neck tumours because of its poor prognosis. We report a rare case of MFH in an 11-year-old girl.
Vertebra collapse due to primary amyloidosis causing neurological compromise
Authors: Yoshihara Hiroyuki , Nojiri Kenya , Yabe Mariko , Takahata Takeshi
Published: June 2013

In primary amyloidosis (AL), a fibrillar protein (amyloid light chain) is deposited in many organs; however, it is rare to have involvement of the vertebral bodies. Multiple myeloma is a well-known systemic amyloid disease that frequently has vertebral involvement. However, the pathology of vertebral involvement of these two clinical entities differs significantly. We report a patient with L4 vertebral collapse because of primary AL, causing neurological compromise that improved with surgical treatment. Deposition of amyloid and following demineralisation caused the vertebral collapse. Primary AL needs to be taken into consideration as a cause of pathological vertebral fracture.
Laryngeal leiomyosarcoma masquerading as laryngeal carcinoma
Authors: Singh Lavleen , Mallick Saumyaranjan , Singh Shuchita , Safaya Rajni
Published: June 2013

Laryngeal leiomyosarcoma is an exceedingly rare malignant tumour, with fewer than 50 reported cases in scientific literature. Diagnosis is based on immunohistochemistry, supplemented with ultrastructural studies, if required. It is aggressive and associated with variable survival outcomes. A 63-year-old man presented with hoarseness for 7 months and breathlessness for 3 months. Imaging showed a well-defined 3 cm glottic mass. Total laryngectomy was performed. The histopathological examination showed features of leiomyosarcoma. The index case has been presented owing to its rarity, variable clinical manifestations and diagnostic dilemmas and to stress upon the importance of ancillary techniques for confirmation.
Analysis using histograms of muscle CT images in patients with Duchenne muscular dystrophy
Authors: Nakayama Takahiro , Kuru Satoshi , Kawai Mitsuru
Published: June 2013

We showed that the shape of the thigh CT value histogram, which was reflecting muscle and fat, changed with the disease progression in a patient with Duchenne muscular dystrophy, and this shape of the histogram will employ a new analytical method. CT images of the middle part of the thigh were acquired in a patient with Duchenne muscular dystrophy once a year from 6 to 11 years of age. Regions apparently corresponding to subcutaneous fat, bone and bone marrow were manually excluded, and the CT values were calculated to prepare histograms. His motor disability was also evaluated employing Vignos functional rating scale. A single peak was noted in the muscle CT value range in the histogram at the youngest age. The muscle-to-fat ratio in muscle decreased with the worsening of his disease disability level and the peak of the histogram shifted from the muscle to the fat CT value.
Fracture of temporary femoral haemodialysis catheter: our experience
Authors: Cruz Sanjay D , Gupta Monica , Kaur Ravinder , Gupta Sanjay
Published: June 2013

We report two similar cases of fracture and proximal migration of temporary femoral haemodialysis catheters. The two cases were encountered 6 years apart. These types of occurrences, especially in centres where catheter reuse is practiced, are not uncommon but seldom reported in the literature. Alert dialysis staff on both the occasions took remedial steps in time, which prevented embolisation of the catheters into the inferior vena cava. Both the catheters were removed successfully by the surgical team.
Viral and paraneoplastic encephalitis in a patient with liver transplant with unilateral temporoparietal lobe abnormalities: a diagnostic challenge
Authors: Cheng Christopher K , Siller Keith A
Published: June 2013

We report a patient who recently had a liver transplant presented with increasing confusion and intermittent hallucinations. MRI of the brain revealed diffuse left temporal and parietal lobe swelling with cortical diffusion restriction suggestive of possible infectious aetiology, although stroke was also possible given the presence of left posterior cerebral arteries with fetal origin in the anterior circulation. An EEG demonstrated subclinical seizures, for which he was placed on an antiepileptic medication. Routine laboratory testing, lumbar puncture, serum and cerebrospinal fluid testing for viral and paraneoplastic encephalitis, and brain biopsy were performed on our patient. Our clinical diagnosis was viral encephalitis, and positive N-type voltage-gated calcium channel antibody titres were suggestive of paraneoplastic limbic encephalitis. Treatment with antiviral and antiepileptic medications for subclinical seizures resulted in the improvement of his mental status, language output and motor functioning.
Tuberous sclerosis presenting with spontaneous pneumothorax secondary to lymphangioleiomyomatosis; previously mistaken for asthma
Authors: Gosein Maria Angela , Ameeral Anthony , Konduru Siva Krishna Prasad , Dola Venkata Naga Srinivas
Published: June 2013

A middle-aged female patient, previously diagnosed with asthma, presented with a large spontaneous left pneumothorax. She had a history of nephrectomy for a ruptured renal angiomyolipoma (AML) with a postoperative spontaneous pneumothorax when she was an adolescent. High-resolution CT chest revealed multiple scattered thin-walled lung parenchyma cysts consistent with lymphangioleiomyomatosis (LAM). Hepatic AMLs and adenoma sebaceum skin lesions were also noted, consistent with an overall diagnosis of tuberous sclerosis. Her acute management included lung re-expansion via chest tube insertion, antibiotics for concurrent chest infection, nebulisation and chest physiotherapy. Since discharge, the patient had only occasional shortness of breath, relieved by bronchodilators. She is considering expanded immunisation as well as enrolment in a clinical trial. Her hepatic AMLs will be monitored via ultrasound for growth. LAM treatment is generally aimed at its complications with lung transplantation reserved for severe disease; however, hormonal therapy and the mTOR inhibitor aim at targeting systemic disease.
Clinical scaphoid score (CSS) to identify scaphoid fracture with MRI in patients with normal x-ray after a wrist trauma
Authors: Bergh Torbjørn Hiis , Lindau Tommy , Soldal Lars Atle , Bernardshaw Soosaipillai V , Behzadi Mehdi , Steen Knut , Brudvik Christina
Published: June 2013

Introduction

The aim of this study was to compare a combination of three commonly used tests to identify scaphoid fractures with MRI in patients with normal x-ray after a wrist trauma.

Patients and methods

This prospective MRI study included patients between 18 years and 49 years, who attended the Emergency Department, Bergen, Norway after sustaining an acute wrist trauma within the previous week. Initial x-rays of the wrist were normal. MRI was done within a median of 1 day after the trauma. The study period lasted 1 year. The patients were examined with three commonly used clinical scaphoid tests; tenderness in the anatomical snuffbox with the wrist in ulnar deviation (3 points), tenderness over the scaphoid tubercle (2 points) and pain upon longitudinal compression of the thumb (1 point). The clinical scaphoid score (CSS) is a sum of these points, which was compared with MRI verified fracture of the scaphoid.

Results

We included 154 patients with wrist sprain and normal x-rays; 13 had occult scaphoid fracture. A CSS of 4 or more was the only statistically significant ‘cut-off’ value to identify occult scaphoid fractures (p<0.05). Diagnostic sensitivity increased with more experienced Emergency Department doctors.

Conclusions

If a patient with wrist pain after injury and normal x-ray has a CSS≥4 (pain in the anatomical snuffbox in addition to pain at scaphoid tubercle or longitudinal compression or both) we recommend MRI. A CSS <4 has a negative predictive value of 96%, which makes scaphoid fracture unlikely.
Hepatitis E: the forgotten virus
Authors: Freshwater Dennis A
Published: June 2013

Hepatitis E virus (HEV) has a long military association being first discovered during the Soviet occupation of Afghanistan in the 1980s after an outbreak of unexplained hepatitis at a military camp. HEV is now endemic in the UK, and should be considered in all cases of jaundice. The prevalence is high in certain operational areas (28.5% in Afghanistan), and maintenance of integrity of food and water supplies together with scrupulous attention to environmental hygiene remains paramount. Pregnancy confers a much higher risk of fulminant hepatitis, with a mortality rate of up to 25%. Management is usually symptomatic, but ribavirin can be considered in non-pregnant patients with fulminant hepatitis. This narrative review examines the presentations and management of Hepatitis E in military populations.
The Genetic Theory of Infectious Diseases: A Brief History and Selected Illustrations
Authors: Casanova Jean-Laurent , Abel Laurent
Published: June 2013

Until the mid-nineteenth century, life expectancy at birth averaged 20 years worldwide, owing mostly to childhood fevers. The germ theory of diseases then gradually overcame the belief that diseases were intrinsic. However, around the turn of the twentieth century, asymptomatic infection was discovered to be much more common than clinical disease. Paradoxically, this observation barely challenged the newly developed notion that infectious diseases were fundamentally extrinsic. Moreover, interindividual variability in the course of infection was typically explained by the emerging immunological (or somatic) theory of infectious diseases, best illustrated by the impact of vaccination. This powerful explanation is, however, best applicable to reactivation and secondary infections, particularly in adults; it can less easily account for interindividual variability in the course of primary infection during childhood. Population and clinical geneticists soon proposed a complementary hypothesis, a germline genetic theory of infectious diseases. Over the past century, this idea has gained some support, particularly among clinicians and geneticists, but has also encountered resistance, particularly among microbiologists and immunologists. We present here the genetic theory of infectious diseases and briefly discuss its history and the challenges encountered during its emergence in the context of the apparently competing but actually complementary microbiological and immunological theories. We also illustrate its recent achievements by highlighting inborn errors of immunity underlying eight life-threatening infectious diseases of children and young adults. Finally, we consider the far-reaching biological and clinical implications of the ongoing human genetic dissection of severe infectious diseases.
The Power of Meta-Analysis in Genome-Wide Association Studies
Authors: Panagiotou Orestis A. , Willer Cristen J. , Hirschhorn Joel N. , Ioannidis John P.A.
Published: June 2013

Meta-analysis of multiple genome-wide association (GWA) studies has become common practice over the past few years. The main advantage of this technique is the maximization of power to detect subtle genetic effects for common traits. Moreover, one can use meta-analysis to probe and identify heterogeneity in the effect sizes across the combined studies. In this review, we systematically appraise and evaluate the characteristics of GWA meta-analyses with 10,000 or more subjects published up to June 2012. We provide an overview of the current landscape of variants discovered by GWA meta-analyses, and we discuss and assess with extrapolations from empirical data the value of larger meta-analyses for the discovery of additional genetic associations and new biology in the future. Finally, we discuss some emerging logistical and practical issues related to the conduct of meta-analysis of GWA studies.
Gene Therapy for Blindness
Authors: Sahel José-Alain , Roska Botond
Published: June 2013

Sight-restoring therapy for the visually impaired and blind is a major unmet medical need. Ocular gene therapy is a rational choice for restoring vision or preventing the loss of vision because most blinding diseases originate in cellular components of the eye, a compartment that is optimally suited for the delivery of genes, and many of these diseases have a genetic origin or genetic component. In recent years we have witnessed major advances in the field of ocular gene therapy, and proof-of-concept studies are under way to evaluate the safety and efficacy of human gene therapies. Here we discuss the concepts and recent advances in gene therapy in the retina. Our review discusses traditional approaches such as gene replacement and neuroprotection and also new avenues such as optogenetic therapies. We conjecture that advances in gene therapy in the retina will pave the way for gene therapies in other parts of the brain.
The Genetics of Hair Cell Development and Regeneration
Authors: Groves Andrew K. , Zhang Kaidi D. , Fekete Donna M.
Published: June 2013

Sensory hair cells are exquisitely sensitive vertebrate mechanoreceptors that mediate the senses of hearing and balance. Understanding the factors that regulate the development of these cells is important, not only to increase our understanding of ear development and its functional physiology but also to shed light on how these cells may be replaced therapeutically. In this review, we describe the signals and molecular mechanisms that initiate hair cell development in vertebrates, with particular emphasis on the transcription factor Atoh1, which is both necessary and sufficient for hair cell development. We then discuss recent findings on how microRNAs may modulate the formation and maturation of hair cells. Last, we review recent work on how hair cells are regenerated in many vertebrate groups and the factors that conspire to prevent this regeneration in mammals.
Mechanisms and Functions of Theta Rhythms
Authors: Colgin Laura Lee
Published: June 2013

The theta rhythm is one of the largest and most sinusoidal activity patterns in the brain. Here I survey progress in the field of theta rhythms research. I present arguments supporting the hypothesis that theta rhythms emerge owing to intrinsic cellular properties yet can be entrained by several theta oscillators throughout the brain. I review behavioral correlates of theta rhythms and consider how these correlates inform our understanding of theta rhythms' functions. I discuss recent work suggesting that one function of theta is to package related information within individual theta cycles for more efficient spatial memory processing. Studies examining the role of theta phase precession in spatial memory, particularly sequence retrieval, are also summarized. Additionally, I discuss how interregional coupling of theta rhythms facilitates communication across brain regions. Finally, I conclude by summarizing how theta rhythms may support cognitive operations in the brain, including learning.