bluuebunny/crossref_metadata_2025 huggingface dataset:
Consumption of reactive halogen species from sea-salt aerosol by secondary organic aerosol: slowing down the bromine explosion
Authors: Buxmann Joelle , Bleicher Sergej , Platt Ulrich , von Glasow Roland , Sommariva Roberto , Held Andreas , Zetzsch Cornelius , Ofner Johannes
Published: July 2015

Environmental context
Secondary organic aerosols together with sea-salt aerosols are a major contribution to global aerosols and influence the release of reactive halogens, which affect air quality and human health. In this study, the loss of reactive halogen species from simulated salt aerosols due to three different types of secondary organic aerosols was quantified in chamber experiments and investigated with the help of a numerical model. The loss rate can be included into chemistry models of the atmosphere and help to quantify the halogen budget in nature.

Abstract
The interaction between secondary organic aerosols (SOAs) and reactive bromine species (e.g. BrO, Br2, HOBr) coexisting in the environment is not well understood and not included in current chemistry models. The present study quantifies the quenching of bromine release from an artificial salt aerosol caused by SOAs from ozonolysis of three precursors (α-pinene, catechol or guaiacol) in a Teflon smog chamber and incorporates it into a chemical box model. The model simulations perform very well for a blank experiment without SOA precursor, capturing BrO formation, as detected by differential optical absorption spectrometry. A first-order BrO loss rate of 0.001s–1 on the surface of SOA represents the overall effective Brx (total inorganic bromine) loss included in the model. Generally, the model agrees with the maximum BrO mixing ratio in time and magnitude, with some disagreements in the exact shape. Formation of reactive OClO was observed in the presence of organics but could not be reproduced by the model. According to current knowledge, most inorganic chlorine would be in the form of HCl in the presence of organics, as predicted by the model. In order to reproduce the net effects of the presence of SOA, the effective uptake coefficients of reactive bromine on the SOA surface are estimated to be 0.01, 0.01 and 0.004 for α-pinene, catechol and guaiacol respectively. The uptake coefficient can now be incorporated into box models and even global models, where sinks for bromine species are thought to be inadequately represented.
Reproductive biology of an endemic amphidromous goby, Cotylopus acutipinnis, from La Réunion Island
Authors: Teichert Nils , Valade Pierre , Fostier Alexis , Grondin Henri , Gaudin Philippe
Published: July 2015

Amphidromous gobies living in the rivers of tropical islands display a high continuous reproductive effort in response to environmental unpredictability. Females are usually able to spawn a large number of eggs over an extended season, which contributes to offset the high larval mortality. The increasing human pressure on the insular aquatic systems threatens these gobies and highlights the urgent need to acquire knowledge on their biology for management purposes. The present study investigated the reproductive traits of the endemic amphidromous goby, Cotylopus acutipinnis, in a river of La Réunion Island. Ovarian histology showed that females were multiple spawners with a group-synchronous ovarian follicle development and an indeterminate fecundity. Females reproduced from 28.6-mm TL and laid their eggs in a unique event (from 3226 to 106840 eggs), with a spawning frequency of ~1 month or less. The drop in reproductive activity coincided with lower water temperatures and a decrease in daylight duration. Evidence suggested that spawning activity was not disturbed by flooding events recorded a few days before sampling. We suggested that the temperature threshold inducing the ovarian growth (18.3°C for C. acutipinnis) could be a determinant factor explaining the specific repartition of gobies throughout the river.
Novel method for shark age estimation using near infrared spectroscopy
Authors: Rigby C. L. , Wedding B. B. , Grauf S. , Simpfendorfer C. A.
Published: July 2015

Accurate age determination is an important component of assessing and managing fish populations, yet traditional ageing using growth bands is time-consuming and has limitations. In the present study, an alternative approach to shark age estimation using near infrared spectroscopy (NIRS) was investigated using two species. The ages of Sphyrna mokarran and Carcharhinus sorrah vertebrae that had been traditionally aged and validated were successfully predicted up to 10 years of age using NIRS. The correlations between the known ages of the vertebrae and their near infrared spectra were strong, with R2 values of 0.89 and 0.84 for S. mokarran and C. sorrah respectively. The major advantage of the NIRS ageing approach was the rapid speed of age estimation, which could enable large numbers of sharks to be aged quickly. This would offer the fisheries management benefit of improving the reliability of age information for stock and risk assessments.
Mitogen-activated protein kinase-activated protein kinase 2 is a critical regulator of pig oocyte meiotic maturation
Authors: Ou Xiang-Hong , Li Sen , Xu Bao-Zeng , Chen Lei-Ning , Jiang Man-Xi , Chen Shao-Qin , Chen Nan-Qiao
Published: July 2015

Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a direct substrate of p38 MAPK, plays key roles in multiple cellular processes. In the present study, we showed that MK2 affected not only cumulus expansion, but also the oocyte meiotic cell cycle in porcine oocytes. Inhibition of MK2 arrested oocytes at the germinal vesicle (GV) stage or the prometaphase I/metaphase I stage. Unlike in mouse oocytes, where phosphorylated (p-) MK2 was localised at the minus end of spindle microtubules and close to the spindle poles, in porcine oocytes p-MK2 was concentrated at the spindle equator and localised at the plus end of spindle microtubules. Knockdown or inhibition of MK2 resulted in spindle defects: spindles were surrounded by irregular chromosome non-disjunction or by chromosomes detached from the spindles. MK2 regulated spindle organisation and chromosome alignment by connecting microtubules with kinetochores. In addition, unlike in mitotic cells and meiotic mouse oocytes, the MK2–p38 MAPK pathway may not play an important role during meiotic cell cycle in porcine oocytes. In conclusion, MK2 is an important regulator of porcine oocyte meiotic maturation.
Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex
Authors: Heddi Brahim , Cheong Vee Vee , Martadinata Herry , Phan Anh Tuân
Published: July 2015

Significance

G-quadruplexes (G4) are four-stranded nucleic acid structures implicated in important biological processes. Interaction between G4 and proteins is essential for the cellular functions of G4. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds and unwinds G4 structures. The structure of an 18-aa peptide, identified as the G4-binding domain of RHAU, was solved in the complex with a G4 by NMR spectroscopy. The structure of the complex explains how RHAU specifically recognizes G4 structures and suggests a strategy for G4 recognition by proteins.
Global trends in infectious diseases at the wildlife–livestock interface
Authors: Wiethoelter Anke K. , Beltrán-Alcrudo Daniel , Kock Richard , Mor Siobhan M.
Published: July 2015

Significance

Infectious diseases at the wildlife–livestock interface threaten the health and well-being of wildlife, livestock, and human populations, and contribute to significant economic losses to each sector. No studies have sought to characterize the diseases and animals involved on a global level. Using a scoping review framework we show that 10 diseases—mostly zoonoses—have accounted for half of the published research in this area over the past century. We show that relatively few interfaces can be considered important from a disease ecology perspective. These findings suggest that surveillance and research strategies that target specific wildlife–livestock interfaces may yield the greatest return in investment.
Simple mechanism whereby the F
1
-ATPase motor rotates with near-perfect chemomechanical energy conversion
Authors: Saita Ei-ichiro , Suzuki Toshiharu , Kinosita Kazuhiko , Yoshida Masasuke
Published: July 2015

Significance

ATP synthase produces most of the ATP in respiratory and photosynthetic cells. It is a rotary motor enzyme and its catalytic portion F
1
-ATPase hydrolyzes ATP to drive rotation of the central γ subunit. Efficiency of chemomechanical energy conversion by this motor is always near-perfect under different ATP hydrolysis energy (Δ
G
ATP
) conditions. However, the mechanism for the efficient conversion remains unknown. We measured the torque as a function of rotation angle under different Δ
G
ATP
conditions and estimated mechanical work. The torque profiles show three sawtooth-like repeats during a single ATP hydrolysis. When concentrations of ATP/ADP and P
i
in the environment are changed, the height, and hence the area, of the sawtooth changes accordingly so that mechanical work can always match Δ
G
ATP
.
Evolutionary perspectives on clonal reproduction in vertebrate animals
Authors: Avise John C.
Published: July 2015

A synopsis is provided of different expressions of whole-animal vertebrate clonality (asexual organismal-level reproduction), both in the laboratory and in nature. For vertebrate taxa, such clonal phenomena include the following: human-mediated cloning via artificial nuclear transfer; intergenerational clonality in nature via parthenogenesis and gynogenesis; intergenerational hemiclonality via hybridogenesis and kleptogenesis; intragenerational clonality via polyembryony; and what in effect qualifies as clonal replication via self-fertilization and intense inbreeding by simultaneous hermaphrodites. Each of these clonal or quasi-clonal mechanisms is described, and its evolutionary genetic ramifications are addressed. By affording an atypical vantage on standard vertebrate reproduction, clonality offers fresh perspectives on the evolutionary and ecological significance of recombination-derived genetic variety.
CBR antimicrobials inhibit RNA polymerase via at least two bridge-helix cap-mediated effects on nucleotide addition
Authors: Bae Brian , Nayak Dhananjaya , Ray Ananya , Mustaev Arkady , Landick Robert , Darst Seth A.
Published: July 2015

Significance

The multisubunit RNA polymerases (RNAPs) are complex molecular machines that control catalysis through concerted conformational changes of conserved structural modules surrounding the active site. Central to these modules is the bridge helix (BH). The nature of these conformational changes and their detailed roles in the different steps of the RNAP nucleotide addition cycle are central issues in understanding the structural basis of RNAP catalytic activity. We report crystal structures of
Escherichia coli
RNAP complexes with a class of small molecule inhibitor (CBR inhibitors) and biochemical tests that establish two distinct effects of the inhibitors on the RNAP catalytic site. These results provide insights into the enzyme’s catalytic mechanism.
How clonal are
Neisseria
species? The epidemic clonality model revisited
Authors: Tibayrenc Michel , Ayala Francisco J.
Published: July 2015

The three species
Neisseria meningitidis
,
Neisseria gonorrheae
, and
Neisseria lactamica
are often regarded as highly recombining bacteria.
N
.
meningitidis
has been considered a paradigmatic case of the “semiclonal model” or of “epidemic clonality,” demonstrating occasional bouts of clonal propagation in an otherwise recombining species. In this model, occasional clonality generates linkage disequilibrium in the short term. In the long run, however, the effects of clonality are countered by recombination. We show that many data are at odds with this proposal and that
N
.
meningitidis
fits the criteria that we have proposed for predominant clonal evolution (PCE). We point out that (
i
) the proposed way to distinguish epidemic clonality from PCE may be faulty and (
ii
) the evidence of deep phylogenies by microarrays and whole-genome sequencing is at odds with the predictions of the semiclonal model. Last, we revisit the species status of
N
.
meningitidis
,
N
.
gonorrheae
, and
N
.
lactamica
in the light of the PCE model.
Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the strengthening of labor contractions, produced by hypoxic stresses
Authors: Alotaibi Mohammed , Arrowsmith Sarah , Wray Susan
Published: July 2015

Significance

Parturition requires strong uterine contractions. A longstanding enigma has been how contractions strengthen despite also causing transient ischemia as they occlude uterine blood vessels. Here we demonstrate a hitherto undescribed mechanism whereby in an adaptation at labor, brief hypoxia in uterine muscle, stimulates the contractile activity. We have named this hypoxia-induced force increase, or HIFI. We identify the underlying mechanism, which involves adenosine and prostaglandin and a rise in intracellular calcium, and show it is present in animal and human uterus, but only close to delivery. We speculate that aberrations in this powerful mechanism could underlie contractions being triggered too early (preterm labor) or if HIFI is deficient, weak contractions, and thus poor and unsuccessful term labors.
The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells
Authors: Sunwoo Hongjae , Wu John Y. , Lee Jeannie T.
Published: July 2015

Significance

X-chromosome inactivation (XCI) is initiated by the long noncoding RNA Xist. Here we view Xist RNA and the Xi at 20-nm resolution using STochastic Optical Reconstruction Microscopy (STORM) and observe dynamics at the single-cell level not predicted by epigenomic analysis. Only 50–100 Xist molecules and ∼50 PRC2 foci are observed per Xi, contrasting with the chromosome-wide “coat” observed by deep sequencing and conventional microscopy. Xist knock-off experiments enable visualization of dissociation and relocalization dynamics, and support a functional tethering of Xist and PRC2. Thus, Xist-PRC2 complexes are less numerous than expected, implying that the Xist-PRC2 complexes methylate nucleosomes in a hit-and-run model.
Heterogeneous binding of the SH3 client protein to the DnaK molecular chaperone
Authors: Lee Jung Ho , Zhang Dongyu , Hughes Christopher , Okuno Yusuke , Sekhar Ashok , Cavagnero Silvia
Published: July 2015

Significance

Heat shock protein 70 (Hsp70) molecular chaperones play key roles in protein folding and other cellular processes. The effect of Hsp70 on the conformation of its substrate proteins is still largely unknown. This study unveils, for the first time to our knowledge, the effect of the bacterial Hsp70 chaperone DnaK on the structure of the full-length substrate protein SRC homology 3 domain (SH3). We show that multiple largely unstructured conformations of SH3, distinct from the protein’s unfolded state, interact with DnaK. The bound client protein shares a flexible N terminus and multiple slowly interconverting conformations in different parts of the sequence. In all, there is significant structural and dynamical heterogeneity. This result is important because it reveals that proteins may undergo conformational sampling while chaperone-bound.
Complex dynamics of synergistic coinfections on realistically clustered networks
Authors: Hébert-Dufresne Laurent , Althouse Benjamin M.
Published: July 2015

Significance

Concurrent infection with multiple pathogens is an important factor for human disease. For example, rates ofStreptococcus pneumoniaecarriage (a leading cause of pneumonia) in children under five years can exceed 80%, and coinfection with other respiratory infections (e.g., influenza) can increase mortality drastically; despite this, examination of interacting coinfections on realistic human contact structures remains an understudied problem in epidemiology and network science. Here we show that clustering of contacts, which usually hinders disease spread, can speed up spread of both diseases by keeping synergistic infections together and that a microscopic change in transmission rates can cause a macroscopic change in expected epidemic size, such that clustered networks can sustain diseases that would otherwise die in random networks.
Spontaneous retrotransposon insertion into
TNF
3′UTR causes heart valve disease and chronic polyarthritis
Authors: Lacey Derek , Hickey Peter , Arhatari Benedicta D. , O’Reilly Lorraine A. , Rohrbeck Leona , Kiriazis Helen , Du Xiao-Jun , Bouillet Philippe
Published: July 2015

Significance

Tumor necrosis factor (TNF) is a cytokine involved in a large array of inflammatory diseases such as arthritis and psoriasis. We have found that the insertion of a retrotransposon in the 3′ untranslated region of
Tnf
impairs its normal regulation and causes polyarthritis and heart valve disease. We have identified several CCCH-containing zinc-finger proteins as new regulators of
Tnf
expression, as well as a new regulatory element within the
TNF
3′UTR. Although anti-TNF therapies are successful in controlling some inflammatory diseases, their cost and the development of resistance in some patients show that other treatment options are required. Our findings provide an important foundation toward understanding how
Tnf
expression is regulated and identify potential targets for therapeutic intervention.
Ubl4A is required for insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching
Authors: Zhao Yu , Lin Yuting , Zhang Honghong , Mañas Adriana , Tang Wenwen , Zhang Yuzhu , Wu Dianqing , Lin Anning , Xiang Jialing
Published: July 2015

Significance

The signal-induced Akt membrane recruitment is a crucial step for its activation, but the underlying mechanism is incompletely understood. We show that ubiquitin-like protein 4A (Ubl4A) is required for insulin-induced Akt membrane translocation through direct promotion of actin-related protein 2 and 3 (Arp2/3)-dependent actin branching, thereby ensuring glycogen synthesis for neonatal survival. As a novel Arp2/3-binding protein, Ubl4A may play important roles in the translocation of other actin-binding molecules controlled by a similar mechanism, as well as a broad range of cellular functions related to the actin branching network.
Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium
Authors: Murata Yoji , Kotani Takenori , Supriatna Yana , Kitamura Yasuaki , Imada Shinya , Kawahara Kohichi , Nishio Miki , Daniwijaya Edwin Widyanto , Sadakata Hisanobu , Kusakari Shinya , Mori Munemasa , Kanazawa Yoshitake , Saito Yasuyuki , Okawa Katsuya , Takeda-Morishita Mariko , Okazawa Hideki , Ohnishi Hiroshi , Azuma Takeshi , Suzuki Akira , Matozaki Takashi
Published: July 2015

Significance

Much attention has been recently paid to the role of intestinal epithelial cells in the homeostatic regulation of intestinal immunity. Here we show that ablation of stomach-cancer–associated protein tyrosine phosphatase 1 (SAP-1) markedly increased the severity of colitis in interleukin (IL)-10–deficient mice, suggesting that SAP-1 protects against colitis in a cooperative manner with IL-10. We also identify carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an intestinal microvilli-specific membrane protein, as a dephosphorylation target for SAP-1. Indeed, tyrosine phosphorylation of CEACAM20 promotes the binding of spleen tyrosine kinase (Syk) and activation of nuclear factor-κB (NF-κB), thereby inducing production of chemokines such as IL-8. Thus, we propose a mechanism by SAP-1 and CEACAM20 in the intestinal epithelium for regulation of the intestinal immunity.
Top-down modulation in the infant brain: Learning-induced expectations rapidly affect the sensory cortex at 6 months
Authors: Emberson Lauren L. , Richards John E. , Aslin Richard N.
Published: July 2015

Significance

Although infants are excellent learners, it is unclear whether infants use neural strategies similar to those of adults to track changes in their environment. One adult neural strategy is to use feedback connections to modulate sensory cortices based on their expectations. The current study provides, to our knowledge, the first evidence that the fundamental architecture required for sensory feedback is already in place in infancy. This top-down modulation is especially impressive because the study employs an audiovisual task that requires the flexible use of long-range neural connections, and the infant brain is dominated by short-range neural connections with weak (e.g., unmyelinated) long-range connections. These results suggest that learners can use sophisticated top-down feedback neural strategies from an early age.
Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE
2
RD) for diagnostics
Authors: Inci Fatih , Filippini Chiara , Baday Murat , Ozen Mehmet Ozgun , Calamak Semih , Durmus Naside Gozde , Wang ShuQi , Hanhauser Emily , Hobbs Kristen S. , Juillard Franceline , Kuang Ping Ping , Vetter Michael L. , Carocci Margot , Yamamoto Hidemi S. , Takagi Yuko , Yildiz Umit Hakan , Akin Demir , Wesemann Duane R. , Singhal Amit , Yang Priscilla L. , Nibert Max L. , Fichorova Raina N. , Lau Daryl T.-Y. , Henrich Timothy J. , Kaye Kenneth M. , Schachter Steven C. , Kuritzkes Daniel R. , Steinmetz Lars M. , Gambhir Sanjiv S. , Davis Ronald W. , Demirci Utkan
Published: July 2015

Significance

Biosensing technologies have significant impact on medical diagnostics but difficulties in the handling of complex biospecimens, portability, and nonlinearity in dynamic detection range present considerable technical bottlenecks in their translation into clinical settings. Here, we present the nanoplasmonic electrical field-enhanced resonating device (NE
2
RD) that detects and quantifies multiple biotargets from distinct clinical specimens (i.e., saliva, serum, and whole blood) with a broad linear dynamic range. Unlike conventional platforms, the NE
2
RD does not require lengthy sample-preparation steps, skilled personnel, or expensive infrastructure. Further, as a model clinical validation study, we monitored chemotherapy effects on viral load for coinfected patients on a single platform. Therefore, the portable NE
2
RD can be broadly applied to primary care and point-of-care settings with multiple clinical applications.
Erlotinib protects against LPS-induced Endotoxicity because TLR4 needs EGFR to signal
Authors: De Sarmishtha , Zhou Hao , DeSantis David , Croniger Colleen M. , Li Xiaoxia , Stark George R.
Published: July 2015

Significance

The activation of nuclear factor κB (NFκB) in the normal inflammatory response is rapidly down regulated, whereas constitutive NFκB activation is a hallmark of cancer. We now reveal cross signaling between EGF receptor (EGFR) and Toll-like receptor 4 (TLR4). NFκB activation in response to EGF requires, in addition to EGFR, TLR4 and two downstream proteins. Conversely, EGFR is required for TLR4-mediated activation of NFκB in response to lipopolysaccharide (LPS). The LYN proto-oncogene (LYN) is required for NFκB activation in response to either ligand. In mice, the EGFR inhibitor erlotinib greatly reduces both cytokine expression and endotoxicity in response to LPS, suggesting that EGFR inhibitors may find use in treating septic shock.
Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics
Authors: Kuo Szu-Yu , Castoreno Adam B. , Aldrich Leslie N. , Lassen Kara G. , Goel Gautam , Dančík Vlado , Kuballa Petric , Latorre Isabel , Conway Kara L. , Sarkar Sovan , Maetzel Dorothea , Jaenisch Rudolf , Clemons Paul A. , Schreiber Stuart L. , Shamji Alykhan F. , Xavier Ramnik J.
Published: July 2015

Significance

Given the importance of autophagy in a number of human diseases, we have identified small-molecule modulators of autophagy that affect disease-associated phenotypes in relevant cell types. BRD5631 and related compounds can serve as tools for studying how autophagy regulates immune pathways, and for evaluating the therapeutic potential of modulating autophagy in a variety of disease contexts. Deeper investigation into their mechanisms of action may reveal proteins and pathways that could serve as relevant targets for future therapeutic discovery.
Hybrid integral-differential simulator of EM force interactions/scenario-assessment tool with pre-computed influence matrix in applications to ITER
Authors: Rozov V. , Alekseev A.
Published: July 2015

A necessity to address a wide spectrum of engineering problems in ITER determined the need for efficient tools for modeling of the magnetic environment and force interactions between the main components of the magnet system. The assessment of the operating window for the machine, determined by the electro-magnetic (EM) forces, and the check of feasibility of particular scenarios play an important role for ensuring the safety of exploitation. Such analysis-powered prevention of damages forms an element of the Machine Operations and Investment Protection strategy. The corresponding analysis is a necessary step in preparation of the commissioning, which finalizes the construction phase. It shall be supported by the development of the efficient and robust simulators and multi-physics/multi-system integration of models. The developed numerical model of interactions in the ITER magnetic system, based on the use of pre-computed influence matrices, facilitated immediate and complete assessment and systematic specification of EM loads on magnets in all foreseen operating regimes, their maximum values, envelopes and the most critical scenarios. The common principles of interaction in typical bilateral configurations have been generalized for asymmetry conditions, inspired by the plasma and by the hardware, including asymmetric plasma event and magnetic system fault cases. The specification of loads is supported by the technology of functional approximation of nodal and distributed data by continuous patterns/analytical interpolants. The global model of interactions together with the mesh-independent analytical format of output provides the source of self-consistent and transferable data on the spatial distribution of the system of forces for assessments of structural performance of the components, assemblies and supporting structures. The numerical model used is fully parametrized, which makes it very suitable for multi-variant and sensitivity studies (positioning, off-normal events, asymmetry, etc). The obtained results and matrices form a basis for a relatively simple and robust force processor as a specialized module of a global simulator for diagnostic, operational instrumentation, monitoring and control, as well as a scenario assessment tool. This paper gives an overview of the model, applied technique, assessed problems and obtained qualitative and quantitative results.
Genome Sequence and Architecture of the Tobacco Downy Mildew Pathogen Peronospora tabacina
Authors: Derevnina Lida , Chin-Wo-Reyes Sebastian , Martin Frank , Wood Kelsey , Froenicke Lutz , Spring Otmar , Michelmore Richard
Published: July 2015

Peronospora tabacina is an obligate biotrophic oomycete that causes blue mold or downy mildew on tobacco (Nicotiana tabacum). It is an economically important disease occurring frequently in tobacco-growing regions worldwide. We sequenced and characterized the genomes of two P. tabacina isolates and mined them for pathogenicity-related proteins and effector-encoding genes. De novo assembly of the genomes using Illumina reads resulted in 4,016 (63.1 Mb, N50 = 79 kb) and 3,245 (55.3 Mb, N50 = 61 kb) scaffolds for isolates 968-J2 and 968-S26, respectively, with an estimated genome size of 68 Mb. The mitochondrial genome has a similar size (approximately 43 kb) and structure to those of other oomycetes, plus several minor unique features. Repetitive elements, primarily retrotransposons, make up approximately 24% of the nuclear genome. Approximately 18,000 protein-coding gene models were predicted. Mining the secretome revealed approximately 120 candidate RxLR, six CRN (candidate effectors that elicit crinkling and necrosis), and 61 WY domain–containing proteins. Candidate RxLR effectors were shown to be predominantly undergoing diversifying selection, with approximately 57% located in variable gene-sparse regions of the genome. Aligning the P. tabacina genome to Hyaloperonospora arabidopsidis and Phytophthora spp. revealed a high level of synteny. Blocks of synteny show gene inversions and instances of expansion in intergenic regions. Extensive rearrangements of the gene-rich genomic regions do not appear to have occurred during the evolution of these highly variable pathogens. These assemblies provide the basis for studies of virulence in this and other downy mildew pathogens.
Rapid Quantitative Assessment of Rhizoctonia Resistance in Roots of Selected Wheat and Barley Genotypes
Authors: Okubara Patricia A. , Leston Natalie , Micknass Ute , Kogel Karl-Heinz , Imani Jafargholi
Published: July 2015

Rhizoctonia solani AG8, causal agent of Rhizoctonia root rot and bare patch in dryland cereal production systems of the Pacific Northwest United States and Australia, reduces yields in a wide range of crops. Disease is not consistently controlled by available management practices, so genetic resistance would be a desirable resource for growers. In this report, we describe three rapid and low-cost assays for R. solani AG8 resistance in wheat and barley, with the view of facilitating screens for genetic resistance in these hosts. The first assay uses 50-ml conical centrifuge tubes containing soil infested with R. solani AG8 on a substrate of ground oats. The second assay uses roots of 3-day-old seedlings directly coated with infested ground oats, followed by incubation in plastic dishes. The third assay, suitable for barley, uses whole infested oat kernels in 50-ml tubes. Symptoms are quantified on the bases of root fresh weight and total root length at 7 and 3 days for the tube and coating assays, respectively. Each of the assays show the same disease differential between susceptible and partially resistant wheat genotypes. The assays can be conducted in the laboratory, growth chamber, or greenhouse.
Real-time Three-dimensional Echocardiographic Assessment of Rheumatic Mitral Valve Stenosis
Authors: Essandoh Michael
Published: July 2015

Supplemental Digital Content is available in the text.
Not All Hip Dysplasias are the Same: Preoperative CT Version Study and the Need for Reverse Bernese Periacetabular Osteotomy
Authors: Thawrani Dinesh P. , Feldman David S. , Sala Debra A.
Published: July 2015

Background:

Dysplastic hip may present with acetabular retroversion with or without femoral retroversion. This retroversion, if not accounted for when performing a periacetabular osteotomy (PAO), will lead to anterior hip pain and early osteoarthritis. A reverse PAO involves anteverting the acetabulum while still obtaining lateral coverage. The purpose of this study was to investigate the relationship between rotational malalignment of acetabulum and femur on 2-dimensional computed tomographic (CT) scans of hips that underwent Bernese PAO and its role in the surgical decision making.

Methods:

This retrospective, case-control study examined and compared preoperative 2-dimensional CT scans of hips that underwent reverse PAO to the hips that underwent traditional PAO.

Results:

Twelve hips underwent reverse PAO from 2005 to 2010. Twelve hips were randomly selected from a cohort of 52 hips that underwent traditional PAO during same time period. Hips that underwent reverse PAO showed crossover sign on preoperative radiographs, but not on postoperative radiographs. Crossover sign was negative preoperatively and postoperatively on hips that underwent traditional PAO. The 2 groups were similar in regards to preoperative lateral center-edge angle, acetabular index, and anterior center-edge angle on plain radiographs and showed significant improvement after surgery.

On preoperative CT scans both acetabulae and femurs were retroverted in reverse PAO group. Comparison of the 2 groups demonstrated that acetabular version (16.5±4.9 degrees vs. 25.3±5.6 degrees, P=0.001), femoral version (12.8±10.4 degrees vs. 31.9±8 degrees, P<0.001), and McKibbins Instability Index (29.3±11.9 degrees vs. 57.1±9.8 degrees, P<0.001) were significantly lower for the reverse PAO than the traditional PAO group. Anterior Acetabular Sector Angle (determines anterior coverage) was significantly higher in reverse PAO group, 53.1±13.7 degrees versus 39.7±10.4 degrees (P=0.013).

Conclusions:

Retroverted acetabulae seem to be associated with reduced femoral version. Given that retroverted acetabulum and retroverted femur have additive effect and increase chances of anterior hip pain, preoperative identification of correct acetabular, and femoral version by CT scan or MRI is necessary to determine which hip need reverse PAO as opposed to traditional PAO.

Level of Evidence:

Level III—Therapeutic.
Abdominal X‐ray in Pediatric Acute Severe Colitis and Radiographic Predictors of Response to Intravenous Steroids
Authors: Livshits Alina , Fisher Drora , Hadas Irith , Bdolah‐Abram Tali , Mack David , Hyams Jeffrey , Crandall Wallace , Griffiths Anne M. , Turner Dan
Published: July 2015

Background:

Abdominal x‐ray (AXR) can identify complications in acute severe colitis (ASC) and may assist in selecting high‐risk children for early aggressive treatment. We aimed to describe AXR findings in pediatric ASC and to explore radiological predictors of response to intravenous corticosteroid (IVCS) therapy.

Methods:

A total of 56 children with ASC were included in a multicenter, retrospective 1‐year cohort study (41% boys, mean age 12.1 ± 4.2). Radiographs of responders to IVCS and those requiring second‐line salvage therapy by discharge were analyzed independently by 2 blinded radiologists.

Results:

A total of 33 responders to IVCS were compared with 23 nonresponders. The day‐3 Pediatric Ulcerative Colitis Activity Index (PUCAI) score was significantly higher in nonresponders (63 ± 16 vs 46 ± 21, P = 0.001). The mean transverse colon luminal diameter was 30 ± 16 mm in responders and 38 ± 16 mm in nonresponders (P = 0.94). The upper range of transverse colonic diameter in children <12 years was ∼40 mm, whereas in older children it was 60 mm as accepted in adults. Ulcerations and megacolon seen on AXR were associated with nonresponse to IVCS (P = 0.006 and 0.064, respectively).

Conclusions:

The presence of mucosal ulcerations and megacolon on AXR could be considered in the risk stratification of children with ASC for early aggressive treatment, together with the previously known day‐3 and day‐5 Pediatric Ulcerative Colitis Activity Index scores, albumin, and C‐reactive protein.
Unintended Adverse Effects of Enteral Nutrition Support
Authors: Pahsini Karoline , Marinschek Sabine , Khan Zahra , Dunitz‐Scheer Marguerite , Scheer Peter Jaron
Published: July 2015

Objectives:

The present study highlights the occurrence of unintended adverse effects of enteral nutrition in infancy and childhood, as viewed and reported from a parental perspective.

Methods:

Quantitative analysis of a standardized questionnaire, filled out online by parents of enterally fed children. The questions focused on the nutritive and nonnutritive adverse effects, and other medical and biometric data. Data were collected from January 1, 2009 to December 31, 2013.

Results:

The study cohort consisted of 425 infants and children with different underlying medical conditions and an average age of 2.17 (median = 1.63) years. Nasogastric tubes were used in 44.2% of all the patients, and 55.8% of the children were fed by percutaneous endoscopic gastrostomy tube. Nearly all of the children have been tube‐fed since birth. A total of 56.0% of all tube‐fed children showed regular gagging and retching episodes, 50.0% vomited frequently, 14.8% experienced nausea, 7.5% experienced extreme nervous perspiration during the feeding, 45.2% showed loss of appetite, 5.2% experienced local granulation tissue, and 1.9% had other skin irritations. No significant correlations could be found between age, sex, medical diagnoses, type of feeding tube, feeding schedules (bolus or continuous), and parental and child's behavior regarding the feeding situation and duration of tube feeding.

Conclusions:

Enteral nutrition affects the child and the whole family system on more than just nutritional level. It is suggested that children and their families should be followed‐up by health professionals periodically for nutritional optimization, growth documentation, and other aspects of tube management.
DRESS Syndrome or Hematologic Malignancy?
Authors: Besli Gulser Esen , Yildirim Sema , Yilmaz Kutluhan , Yuksel Elif
Published: July 2015

Drug reaction with eosinophilia and systemic symptom (DRESS) is a serious idiosyncratic drug reaction. It is characterized by skin eruption, fever, hematologic abnormalities, and multi-organ involvement. Diagnosis is challenging because of the wide clinical spectrum. Its association with aromatic antiepileptic drugs, such as phenytoin, phenobarbital, and carbamazepine, has been well described in adults. There are few reports of DRESS syndrome in children, and knowledge about the relationship between new antiepileptic drugs such as oxcarbazepine and this syndrome is limited. The DRESS syndrome is a challenging entity and probably underdiagnosed because many of its clinical findings can mimic those of other serious systemic disorders such as infections and hematologic disorders. Virus reactivation and use of some drugs together with suspected drugs, such as amoxicillin, can trigger the symptoms of DRESS syndrome. This is a case report of a 4-year-old boy with oxcarbazepine-induced DRESS syndrome possibly triggered by amoxicillin; hematologic malignancy was included in the differential diagnosis.
Variation in Computed Tomography Use for Evaluation of Head Injury in a Pediatric Emergency Department
Authors: Miescier Michael J. , Dudley Nanette C. , Kadish Howard A. , Mundorff Michael B. , Corneli Howard M.
Published: July 2015

Objectives

Recent research has shown significant variation in rates of computed tomography (CT) use among pediatric hospital emergency departments (ED) for evaluation of head injured children. We examined the rates of CT use by individual ED attending physicians for evaluation of head injured children in a pediatric hospital ED.

Methods

We used an administrative database to identify children younger than 18 years evaluated for head injury from January 2011 through March 2013 at our children's hospital ED, staffed by pediatric emergency medicine (PEM) fellowship trained physicians and pediatricians. We excluded encounters with trauma team activation or previous head CT performed elsewhere. We excluded physicians whose patient volume was less than 1 standard deviation below the group mean.

Results

After exclusions, we evaluated 5340 encounters for head injury by 27 ED attending physicians. For individual physicians, CT rates ranged from 12.4% to 37.3%, with a mean group rate of 28.4%. Individual PEM physician CT rates ranged from 18.9% to 37.3%, versus 12.4% to 31.8% for pediatricians. Of the 1518 encounters in which CT was done, 128 (8.4%) had a traumatic brain injury on CT, and 125 (8.2%) had a simple skull fracture without traumatic brain injury on CT. Patient factors associated with CT use included age younger than 2 years, higher triage acuity, arrival time of 10:00 pm to 6:00 am, hospital admission, and evaluation by a PEM physician.

Conclusions

Physicians at our pediatric hospital ED varied in the use of CT for the evaluation of head-injured children.
The evolution within us
Authors: Cobey Sarah , Wilson Patrick , Matsen Frederick A.
Published: July 2015

The B-cell immune response is a remarkable evolutionary system found in jawed vertebrates. B-cell receptors, the membrane-bound form of antibodies, are capable of evolving high affinity to almost any foreign protein. High germline diversity and rapid evolution upon encounter with antigen explain the general adaptability of B-cell populations, but the dynamics of repertoires are less well understood. These dynamics are scientifically and clinically important. After highlighting the remarkable characteristics of naive and experienced B-cell repertoires, especially biased usage of genes encoding the B-cell receptors, we contrast methods of sequence analysis and their attempts to explain patterns of B-cell evolution. These phylogenetic approaches are currently unlinked to explicit models of B-cell competition, which analyse repertoire evolution at the level of phenotype, the affinities and specificities to particular antigenic sites. The models, in turn, suggest how chance, infection history and other factors contribute to different patterns of immunodominance and protection between people. Challenges in rational vaccine design, specifically vaccines to induce broadly neutralizing antibodies to HIV, underscore critical gaps in our understanding of B cells' evolutionary and ecological dynamics.
The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains
Authors: Collins Andrew M. , Wang Yan , Roskin Krishna M. , Marquis Christopher P. , Jackson Katherine J. L.
Published: July 2015

The human and mouse antibody repertoires are formed by identical processes, but like all small animals, mice only have sufficient lymphocytes to express a small part of the potential antibody repertoire. In this study, we determined how the heavy chain repertoires of two mouse strains are generated. Analysis of IgM- and IgG-associated VDJ rearrangements generated by high-throughput sequencing confirmed the presence of 99 functional immunoglobulin heavy chain variable (IGHV) genes in the C57BL/6 genome, and inferred the presence of 164 IGHV genes in the BALB/c genome. Remarkably, only five IGHV sequences were common to both strains. Compared with humans, little N nucleotide addition was seen in the junctions of mouse VDJ genes. Germline human IgG-associated IGHV genes are rare, but many murine IgG-associated IGHV genes were unmutated. Together these results suggest that the expressed mouse repertoire is more germline-focused than the human repertoire. The apparently divergent germline repertoires of the mouse strains are discussed with reference to reports that inbred mouse strains carry blocks of genes derived from each of the three subspecies of the house mouse. We hypothesize that the germline genes of BALB/c and C57BL/6 mice may originally have evolved to generate distinct germline-focused antibody repertoires in the different mouse subspecies.
Ageing of the B-cell repertoire
Authors: Martin Victoria , Wu Yu-Chang (Bryan) , Kipling David , Dunn-Walters Deborah
Published: July 2015

Older people are more susceptible to infection, less responsive to vaccination and have a more inflammatory immune environment. Using spectratype analysis, we have previously shown that the B-cell repertoire of older people shows evidence of inappropriate clonal expansions in the absence of challenge, and that this loss of B-cell diversity correlates with poor health. Studies on response to vaccination, using both spectratyping and high-throughput sequencing of the repertoire, indicate that older responses to challenge are lacking in magnitude and/or delayed significantly. Also that some of the biologically significant differences may be in different classes of antibody. We have also previously shown that normal young B-cell repertoires can vary between different phenotypic subsets of B cells. In this paper, we present an analysis of immunoglobulin repertoire in different subclasses of antibody in five different populations of B cell, and show how the repertoire in these different groups changes with age. Although some age-related repertoire differences occur in naive cells, before exogenous antigen exposure, we see indications that there is a general dysregulation of the selective forces that shape memory B-cell populations in older people.
The mutation patterns in B-cell immunoglobulin receptors reflect the influence of selection acting at multiple time-scales
Authors: Yaari Gur , Benichou Jennifer I. C. , Vander Heiden Jason A. , Kleinstein Steven H. , Louzoun Yoram
Published: July 2015

During the several-week course of an immune response, B cells undergo a process of clonal expansion, somatic hypermutation of the immunoglobulin (Ig) genes and affinity-dependent selection. Over a lifetime, each B cell may participate in multiple rounds of affinity maturation as part of different immune responses. These two time-scales for selection are apparent in the structure of B-cell lineage trees, which often contain a ‘trunk’ consisting of mutations that are shared across all members of a clone, and several branches that form a ‘canopy’ consisting of mutations that are shared by a subset of clone members. The influence of affinity maturation on the B-cell population can be inferred by analysing the pattern of somatic mutations in the Ig. While global analysis of mutation patterns has shown evidence of strong selection pressures shaping the B-cell population, the effect of different time-scales of selection and diversification has not yet been studied. Analysis of B cells from blood samples of three healthy individuals identifies a range of clone sizes with lineage trees that can contain long trunks and canopies indicating the significant diversity introduced by the affinity maturation process. We here show that observed mutation patterns in the framework regions (FWRs) are determined by an almost purely purifying selection on both short and long time-scales. By contrast, complementarity determining regions (CDRs) are affected by a combination of purifying and antigen-driven positive selection on the short term, which leads to a net positive selection in the long term. In both the FWRs and CDRs, long-term selection is strongly dependent on the heavy chain variable gene family.
The challenges of modelling antibody repertoire dynamics in HIV infection
Authors: Luo Shishi , Perelson Alan S.
Published: July 2015

Antibody affinity maturation by somatic hypermutation of B-cell immunoglobulin variable region genes has been studied for decades in various model systems using well-defined antigens. While much is known about the molecular details of the process, our understanding of the selective forces that generate affinity maturation are less well developed, particularly in the case of a co-evolving pathogen such as HIV. Despite this gap in understanding, high-throughput antibody sequence data are increasingly being collected to investigate the evolutionary trajectories of antibody lineages in HIV-infected individuals. Here, we review what is known in controlled experimental systems about the mechanisms underlying antibody selection and compare this to the observed temporal patterns of antibody evolution in HIV infection. We describe how our current understanding of antibody selection mechanisms leaves questions about antibody dynamics in HIV infection unanswered. Without a mechanistic understanding of antibody selection in the context of a co-evolving viral population, modelling and analysis of antibody sequences in HIV-infected individuals will be limited in their interpretation and predictive ability.