bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced auto-antibody production and Mott cell formation in FcμR-deficient autoimmune mice
Authors: Honjo Kazuhito , Kubagawa Yoshiki , Suzuki Yusuke , Takagi Miyuki , Ohno Hiroshi , Bucy R. Pat , Izui Shozo , Kubagawa Hiromi
Published: July 2014

The IgM-Fc receptor (FcμR) is involved in IgM homeostasis as evidenced by increased pre-immune serum IgM and natural auto-antibodies of both IgM and IgG isotypes in Fcmr-deficient C57BL/6 (B6) mice. To determine the impact of Fcmr-ablation on autoimmunity, we introduced the Fcmr null mutation onto the Fas-deficient autoimmune-prone B6.MRL Faslpr/lpr mouse background (B6/lpr). Both IgM and IgG auto-antibodies against dsDNA or chromatin appeared earlier in FcμR(−) B6/lpr than FcμR(+) B6/lpr mice, but this difference became less pronounced with age. Splenic B2 cells, which were 2-fold elevated in FcμR(+) B6/lpr mice, were reduced to normal B6 levels in FcμR(−) B6/lpr mice, whereas splenic B1 cells were comparable in both groups of B6/lpr mice. By contrast, marginal zone (MZ) B cells were markedly reduced in FcμR(−) B6/lpr mice compared with either FcμR(+) B6/lpr or wild type (WT) B6 mice. This reduction appeared to result from rapid differentiation of MZ B cells into plasma cells in the absence of FcμR, as IgM antibody to a Smith (Sm) antigen, to which MZ B cells are known to preferentially respond, was greatly increased in both groups (B6/lpr and B6) of FcμR(−) mice compared with FcμR(+) B6/lpr or B6 mice. Mott cells, aberrant plasma cells with intra-cytoplasmic inclusions, were also increased in the absence of FcμR. Despite these abnormalities, the severity of renal pathology and function and survival were all indistinguishable between FcμR(−) and FcμR(+) B6/lpr mice. Collectively, these findings suggest that FcμR plays important roles in the regulation of auto-antibody production, Mott cell formation and the differentiation of MZ B cells into plasma cells in B6.MRL Faslpr/lpr mice.
Opinion: uracil DNA glycosylase (UNG) plays distinct and non-canonical roles in somatic hypermutation and class switch recombination
Authors: Yousif Ashraf S. , Stanlie Andre , Begum Nasim A. , Honjo Tasuku
Published: July 2014

Activation-induced cytidine deaminase (AID) is essential to class switch recombination (CSR) and somatic hypermutation (SHM). Uracil DNA glycosylase (UNG), a member of the base excision repair complex, is required for CSR. The role of UNG in CSR and SHM is extremely controversial. AID deficiency in mice abolishes both CSR and SHM, while UNG-deficient mice have drastically reduced CSR but augmented SHM raising a possibility of differential functions of UNG in CSR and SHM. Interestingly, UNG has been associated with a CSR-specific repair adapter protein Brd4, which interacts with acetyl histone 4, γH2AX and 53BP1 to promote non-homologous end joining during CSR. A non-canonical scaffold function of UNG, but not the catalytic activity, can be attributed to the recruitment of essential repair proteins associated with the error-free repair during SHM, and the end joining during CSR.
A dimeric state for PRC2
Authors: Davidovich Chen , Goodrich Karen J. , Gooding Anne R. , Cech Thomas R.
Published: July 2014

Polycomb repressive complex-2 (PRC2) is a histone methyltransferase required for epigenetic silencing during development and cancer. Long non-coding RNAs (lncRNAs) can recruit PRC2 to chromatin. Previous studies identified PRC2 subunits in a complex with the apparent molecular weight of a dimer, which might be accounted for by the incorporation of additional protein subunits or RNA rather than PRC2 dimerization. Here we show that reconstituted human PRC2 is in fact a dimer, using multiple independent approaches including analytical size exclusion chromatography (SEC), SEC combined with multi-angle light scattering and co-immunoprecipitation of differentially tagged subunits. Even though it contains at least two RNA-binding subunits, each PRC2 dimer binds only one RNA molecule. Yet, multiple PRC2 dimers bind a single RNA molecule cooperatively. These observations suggest a model in which the first RNA binding event promotes the recruitment of multiple PRC2 complexes to chromatin, thereby nucleating repression.
Massive Hemorrhage
Authors: Dutton Richard P. , Lee Lorri A. , Stephens Linda S. , Posner Karen L. , Davies Joanna M. , Domino Karen B.
Published: July 2014

Background:

Hemorrhage is a potentially preventable cause of adverse outcomes in surgical and obstetric patients. New understanding of the pathophysiology of hemorrhagic shock, including development of coagulopathy, has led to evolution of recommendations for treatment. However, no recent study has examined the legal outcomes of these claims. The authors reviewed closed anesthesia malpractice claims related to hemorrhage, seeking common factors to guide future management strategies.

Methods:

The authors analyzed 3,211 closed surgical or obstetric anesthesia malpractice claims from 1995 to 2011 in the Anesthesia Closed Claims Project. Claims where patient injury was attributed to hemorrhage were compared with all other surgical and obstetric claims. Risk factors for hemorrhage and coagulopathy, clinical factors, management, and communication issues were abstracted from claim narratives to identify recurrent patterns.

Results:

Hemorrhage occurred in 141 (4%) claims. Obstetrics accounted for 30% of hemorrhage claims compared with 13% of nonhemorrhage claims (P < 0.001); thoracic or lumbar spine surgery was similarly overrepresented (24 vs. 6%, P < 0.001). Mortality was higher in hemorrhage than nonhemorrhage claims (77 vs. 27%, P < 0.001), and anesthesia care was more often judged to be less than appropriate (55 vs. 38%, P < 0.001). Median payments were higher in hemorrhage versus nonhemorrhage claims ($607,750 vs. $276,000, P < 0.001). Risk factors for hemorrhage and coagulopathy were common, and initiation of transfusion therapy was commonly delayed.

Conclusions:

Hemorrhage is a rare, but serious, cause of anesthesia malpractice claims. Understanding which patients are at risk can aid in patient referral decisions, design of institutional systems for responding to hemorrhage, and education of surgeons, obstetricians, and anesthesiologists.
Thermosipho activus sp. nov., a thermophilic, anaerobic, hydrolytic bacterium isolated from a deep-sea sample
Authors: Podosokorskaya Olga A. , Bonch-Osmolovskaya Elizaveta A. , Godfroy Anne , Gavrilov Sergey N. , Beskorovaynaya Daria A. , Sokolova Tatyana G. , Kolganova Tatyana V. , Toshchakov Stepan V. , Kublanov Ilya V.
Published: July 2014

A novel obligately anaerobic, extremely thermophilic, organotrophic bacterium, strain Rift-s3T, was isolated from a deep-sea sample containingRiftia pachyptilasheath from Guaymas Basin, Gulf of California. Cells of the novel isolate were rods, 0.3–0.8 µm in width and 1.5–10 µm in length, surrounded by a sheath-like structure (toga). Strain Rift-s3Tgrew at temperatures ranging from 44 to 75 °C, at pH 5.5 to 8.0, and with NaCl concentrations of 3 to 60 g l−1. Under optimum conditions (65 °C, pH 6.0, NaCl 25 g l−1), the doubling time was 30 min. The isolate was able to ferment mono-, oligo- and polysaccharides including cellulose, chitin, xylan and pectin, and proteins including β-keratins, casein and gelatin. Acetate, hydrogen and carbon dioxide were the main products of glucose fermentation. The G+C content of the DNA was 30 mol%. Phylogenetic analysis of 16S rRNA gene sequences showed the affiliation of strain Rift-s3Twith the genusThermosipho, withThermosipho atlanticusOb7Tas the closest relative (96.5 % 16S rRNA gene sequence similarity). Based on the phylogenetic analysis and physiological properties of the novel isolate we propose a novel species of the genusThermosipho,Thermosipho activussp. nov., with Rift-s3T( = DSM 26467T = VKM B-2803T) as the type strain.
Streptococcus loxodontisalivarius sp. nov. and Streptococcus saliviloxodontae sp. nov., isolated from oral cavities of elephants
Authors: Saito Masanori , Shinozaki-Kuwahara Noriko , Hirasawa Masatomo , Takada Kazuko
Published: July 2014

Four Gram-stain-positive, catalase-negative, coccoid-shaped organisms were isolated from elephant oral cavities. The isolates were tentatively identified as streptococcal species based on the results of biochemical tests. Comparative 16S rRNA gene sequencing studies confirmed the organisms to be members of the genus

Streptococcus

. Two isolates (NUM 6304T and NUM 6312) were related most closely to

Streptococcus salivarius

with 96.8 % and 93.1 % similarity based on the 16S rRNA gene and the RNA polymerase β subunit encoding gene (rpoB), respectively, and to

Streptococcus vestibularis

with 83.7 % similarity based on the 60 kDa heat-shock protein gene (groEL). The other two isolates (NUM 6306T and NUM 6318) were related most closely to S. vestibularis with 97.0 % and 82.9 % similarity based on the 16S rRNA and groEL genes, respectively, and to S. salivarius with 93.5 % similarity based on the rpoB gene. Based on phylogenetic and phenotypic evidence, these isolates are suggested to represent novel species of the genus

Streptococcus

, for which the names Streptococcus loxodontisalivarius sp. nov. (type strain NUM 6304T = JCM 19287T = DSM 27382T) and Streptococcus saliviloxodontae sp. nov. (type strain NUM 6306T = JCM 19288T = DSM 27513T) are proposed.
Single haplotype assembly of the human genome from a hydatidiform mole
Authors: Steinberg Karyn Meltz , Schneider Valerie A. , Graves-Lindsay Tina A. , Fulton Robert S. , Agarwala Richa , Huddleston John , Shiryev Sergey A. , Morgulis Aleksandr , Surti Urvashi , Warren Wesley C. , Church Deanna M. , Eichler Evan E. , Wilson Richard K.
Published: July 2014

An accurate and complete reference human genome sequence assembly is essential for accurately interpreting individual genomes and associating sequence variation with disease phenotypes. While the current reference genome sequence is of very high quality, gaps and misassemblies remain due to biological and technical complexities. Large repetitive sequences and complex allelic diversity are the two main drivers of assembly error. Although increasing the length of sequence reads and library fragments can help overcome these problems, even the longest available reads do not resolve all regions of the human genome. In order to overcome the issue of allelic diversity, we used genomic DNA from an essentially haploid hydatidiform mole, CHM1. We utilized several resources from this DNA including a set of end-sequenced and indexed BAC clones, an optical map, and 100X whole genome shotgun (WGS) sequence coverage using short (lllumina) read pairs. We used the WGS sequence and the GRCh37 reference assembly to create a sequence assembly of the CHM1 genome. We subsequently incorporated 382 finished CHORI-17 BAC clone sequences to generate a second draft assembly, CHM1_1.1 (NCBI AssemblyDB GCA_000306695.2). Analysis of gene and repeat content show this assembly to be of excellent quality and contiguity, and comparisons to ClinVar and the NHGRI GWAS catalog show that the CHM1 genome does not harbor an excess of deleterious alleles. However, comparison to assembly-independent resources, such as BAC clone end sequences and long reads generated by a different sequencing technology (PacBio), indicate misassembled regions. The great majority of these regions is enriched for structural variation and segmental duplication, and can be resolved in the future by sequencing BAC clone tiling paths. This publicly available first generation assembly will be integrated into the Genome Reference Consortium (GRC) curation framework for further improvement, with the ultimate goal being a completely finished gap-free assembly.
The dynamics of sperm cooperation in a competitive environment
Authors: Fisher Heidi S. , Giomi Luca , Hoekstra Hopi E. , Mahadevan L.
Published: July 2014

Sperm cooperation has evolved in a variety of taxa and is often considered a response to sperm competition, yet the benefit of this form of collective movement remains unclear. Here we use fine-scale imaging and a minimal mathematical model to study sperm aggregation in the rodent genusPeromyscus. We demonstrate that as the number of sperm cells in an aggregate increase, the group moves with more persistent linearity but without increasing speed; this benefit, however, is offset in larger aggregates as the geometry of the group forces sperm to swim against one another. The result is a non-monotonic relationship between aggregate size and average velocity with both a theoretically predicted and empirically observed optimum of 6-7 sperm/aggregate. To understand the role of sexual selection in driving these sperm group dynamics, we compared two sister-species with divergent mating systems and find that sperm ofP. maniculatus(highly promiscuous), which have evolved under intense competition, form optimal-sized aggregates more often than sperm ofP. polionotus(strictly monogamous), which lack competition. Our combined mathematical and experimental study of coordinated sperm movement reveals the importance of geometry, motion and group size on sperm velocity and suggests how these physical variables interact with evolutionary selective pressures to regulate cooperation in competitive environments.
(E)-4-[7-(2,3-Dihydrothieno[3,4-b][1,4]dioxin-5-yl)-2,1,3-benzothiadiazol-4-yl]-2-[(neopentylimino)methyl]phenol
Authors: Mitchell Lauren A. , Dinser Jordan A. , Holliday Bradley J.
Published: July 2014

In the title molecule, C24H23N3O3S2, the benzothiadiazole ring system is essentially planar, with an r.m.s. deviation of 0.020 (8) Å. The thiophene and hydroxy-substitiuted rings form dihedral angles of 23.43 (9) and 35.45 (9)°, respectively, with the benzothiadiazole ring system. An intramolecular O—H...N hydrogen bond is observed. In the crystal, weak C—H...O hydrogen bonds and π–π stacking interactions [centroid–centroid distance = 3.880 (3) Å] link molecules into chains along [100]. In addition, there are short S...S contacts [3.532 (3) Å] which link these chains, forming a two-dimensional network parallel to (010).
Allylammonium hydrogen oxalate hemihydrate
Authors: Dziuk Błażej , Zarychta Bartosz , Ejsmont Krzysztof
Published: July 2014

In the title hydrated molecular salt, C3H8N+·C2HO4−·0.5H2O, the water O atom lies on a crystallographic twofold axis. The C=C—C—N torsion angle in the cation is 2.8 (3)° and the dihedral angle between the CO2and CO2H planes in the anion is 1.0 (4)°. In the crystal, the hydrogen oxalate ions are linked by O—H...O hydrogen bonds, generating [010] chains. The allylammonium cations bond to the chains through N—H...O and N—H...(O,O) hydrogen bonds. The water molecule accepts two N—H...O hydrogen bonds and makes two O—H...O hydrogen bonds. Together, the hydrogen bonds generate (100) sheets.
Bis(2-nitrophenyl)methane
Authors: Janzen Daron E. , Crepeau Laura E. , Hageseth Benjamin D. , Wollack James W.
Published: July 2014

In the title compound, C13H10N2O4, the nitro groups are twisted significantly relative to the benzene rings [dihedral angles = 16.64 (18) and 28.02 (11)°]. The benzene groups are nearly perpendicular to each other [dihedral angle = 87.72 (6)°]. Short intermolecular N...O and C...O [2.981 (2) and 3.060 (2) Å, respectively] contacts suggest possible weak π-interactions between nitro groups and between benzene and nitro groups. In addition, there are π–π interactions between one benzene group and an inversion-related equivalent [interplanar separation = 3.494 (2) Å].
How Ebola impacts social dynamics in gorillas: a multistate modelling approach
Authors: Genton Céline , Pierre Amandine , Cristescu Romane , Lévréro Florence , Gatti Sylvain , Pierre Jean‐Sébastien , Ménard Nelly , Le Gouar Pascaline
Published: July 2014

Emerging infectious diseases can induce rapid changes in population dynamics and threaten population persistence. In socially structured populations, the transfers of individuals between social units, for example, from breeding groups to non‐breeding groups, shape population dynamics. We suggest that diseases may affect these crucial transfers.

We aimed to determine how disturbance by an emerging disease affects demographic rates of gorillas, especially transfer rates within populations and immigration rates into populations.

We compared social dynamics and key demographic parameters in a gorilla population affected by Ebola using a long‐term observation data set including pre‐, during and post‐outbreak periods. We also studied a population of undetermined epidemiological status in order to assess whether this population was affected by the disease. We developed a multistate model that can handle transition between social units while optimizing the number of states.

During the Ebola outbreak, social dynamics displayed increased transfers from a breeding to a non‐breeding status for both males and females. Six years after the outbreak, demographic and most of social dynamics parameters had returned to their initial rates, suggesting a certain resilience in the response to disruption. The formation of breeding groups increased just after Ebola, indicating that environmental conditions were still attractive. However, population recovery was likely delayed because compensatory immigration was probably impeded by the potential impact of Ebola in the surrounding areas. The population of undetermined epidemiological status behaved similarly to the other population before Ebola.

Our results highlight the need to integrate social dynamics in host‐population demographic models to better understand the role of social structure in the sensitivity and the response to disease disturbances.
(Re)Producing Nature in Pyrmont and Ultimo
Authors: TROY LAURENCE
Published: July 2014

Urban political ecology (UPE), as articulated by Heynen et al., is premised on the refusal to ontologically separate nature and society. The urban becomes representative of an unbounded process of ‘urbanisation’, a complex interplay between ecological, political, and economic processes that produce historically and geographically contingent outcomes. Importantly, it advances a historical conception of nature, and problems in and of nature, that necessarily encompasses the socio‐economic conditions of its production. This paper presents research into the formation of urban sustainability policy in Australia that draws on the theoretical insights offered by the UPE approach. Using one of Australia's largest urban regeneration projects as a focus, Pyrmont and Ultimo in Sydney, this paper discusses how the politics and economics of urban change and development framed possibilities of how urban environmental problems were firstly understood and, secondly, how they could be addressed. In doing so, this foreclosed alternative visions of urban policy that do not align with hegemonic forms of socio‐economic regulation.
Body mass estimation in non‐avian bipeds using a theoretical conversion to quadruped stylopodial proportions
Authors: Campione Nicolás E. , Evans David C. , Brown Caleb M. , Carrano Matthew T.
Published: July 2014

Body mass is strongly related to both physiological and ecological properties of living organisms. As a result, generating robust, broadly applicable models for estimating body mass in the fossil record provides the opportunity to reconstruct palaeobiology and investigate evolutionary ecology on a large temporal scale.

A recent study provided strong evidence that the minimum circumference of stylopodial elements (humerus and femur) is conservatively associated with body mass in living quadrupeds. Unfortunately, this model is not directly applicable to extinct bipeds, such as non‐avian dinosaurs.

This study presents a new equation that mathematically corrects the quadruped equation for use in bipeds. It is derived from the systemic difference in the circumference‐to‐area scaling relationship of two circles (hypothetical quadruped) and one circle (hypothetical biped), which represent the cross‐section of the main weight‐bearing limb bones.

When applied to a newly constructed data set of femoral circumferences and body masses in living birds, the new equation reveals errors that are significantly lower than other published equations, but significantly higher than the error inherent in the avian data set. Such errors, however, are expected given the unique overall femoral circumference–body mass scaling relationship found in birds.

Body mass estimates for a sample of bipedal dinosaurs using the new model are consistent with recent estimates based on volumetric life reconstructions, but, in contrast, this equation is simpler to use, with the concomitant potential to provide a wider set of body mass estimates for extinct bipeds.

Although it is evident that no one estimation model is flawless, the combined use of the corrected quadrupedal equations and the previously published quadrupedal equation offer a consistent approach with which to estimate body masses in both quadrupeds and bipeds. These models have implications for conducting large‐scale macroevolutionary analyses of body size throughout the evolutionary history of terrestrial vertebrates, and, in particular, across major changes in body plan, such as the evolution of bipedality in archosaurs and quadrupedality in dinosaurs.
Monitoring of myocardial function by ultrasonic transducers
Authors: ESPINOZA ANDREAS W.
Published: July 2014

Background

The aim of this PhD thesis was to provide a continuous method to monitor myocardial function during cardiac surgery with the superior sensitivity of ultrasonic technique and the continuity of electrocardiographic (ECG) monitoring.

Methods

An ultrasound system with epicardial transducers was provided, presenting real‐time M‐mode LV wall images. In two experimental studies the transducers were tested. Their sensitivity in myocardial function assessment was compared to ECG and hemodynamics during ischemia and hypothermia. In one patient study during off‐pump coronary artery bypass surgery the transducers were used to monitor myocardial function, and an automated analysis algorithm was tested.

Results

In the experimental studies the ultrasound system could detect myocardial dysfunction during ischemia, and diastolic dysfunction during hypothermia. In the patient study the ultrasound signal detected ischemia without concomitant ECG ST‐segment abnormalities or hemodynamic changes. The automated algorithm had equal sensitivity for detection of ischemic myocardial dysfunction as manual off‐line analysis.

Conclusions

The provided ultrasound system could give continuous real‐time monitoring of myocardial function, and detect myocardial dysfunction with superior sensitivity than ECG or hemodynamic monitoring. This could be used for improved monitoring of myocardial function during cardiac surgery.
Champions of the Movement or Fair‐weather Heroes? Individualization and the (A)politics of Local Food
Authors: Busa Julianne H. , Garder Rebekah
Published: July 2014

We ask to what degree consumers who act out movement practices (eg local food consumption) may do so without regard for larger environmental and social justice implications, and how focus on individual concerns reflects the partial (but increasing) neoliberalization and depoliticization of the alternative food movement. Coupling narratives from five citizen‐consumers with analysis of organizational discourse from a major food movement organization in Massachusetts’ Pioneer Valley, we examine the interplay of individual and collective identity to point to places where modified discourse and movement tactics may produce more fruitful outcomes (eg greater community food security). Ultimately, we argue that individualistic interpretations of alternative food are reinforced by organizational campaigns that shape collective identity, casting “buying local” as a heroic act, thereby re‐casting others as anti‐heroes. Counteracting individualization with a new politics of possibility should be prioritized, as citizen‐consumers will inevitably determine future landscapes of food, environmental sustainability and social justice.
Patient representatives' contributions to the benefit–risk assessment tasks of the European Medicines Agency scientific committees
Authors: Bernabe Rosemarie D. L. C. , van Thiel Ghislaine J. M. W. , van Delden Johannes
Published: July 2014

In the European Medicines Agency (EMA), the involvement of patients has been increasingly recognized as valuable and necessary. Specifically in scientific committees, patients through patient representatives are actively involved in deliberations and decision making processes. These scientific committees are meant to ensure that licensed medicines have a positive benefit–risk ratio in favour of the patients and users. To investigate what the contributions are of patient representatives in benefit–risk assessment, we interviewed 15 scientific committee members, 10 of whom are/were EU‐state regulatory representatives and five are/were patient representatives. We asked the participants questions related to the benefit–risk assessment tasks of their committees, the connection between patient representatives and the patient perspective, and the contribution of patient representatives in the various benefit–risk assessments tasks. We found that the contribution of patient representatives benefit–risk assessment may be a variable of the benefits and the risks involved in the drug such that the necessity of their contribution is strongly felt when both benefits and risks are high, when benefits are almost equal or are equal to risks and when both benefits and risks are low. In terms of the various benefit–risk tasks, patient representatives contribute to benefit–risk analysis by providing criteria that help define the benefit–risk picture. In benefit–risk evaluation, patient representatives aid in providing a specific basis for the values and weights given to specific benefits and risks and in decision making, they provide what may be a crucial patient perspective in terms of the acceptability of risks. Hence, patient representatives provide a specific expertise in these scientific committees.
Chromosome Band 7q34 Deletions Resulting in KIAA1549‐BRAF and FAM131B‐BRAF Fusions in Pediatric Low‐Grade Gliomas
Authors: Roth Jacquelyn J. , Santi Mariarita , Pollock Avrum N. , Harding Brian N. , Rorke‐Adams Lucy B. , Tooke Laura S. , Biegel Jaclyn A.
Published: July 2014

The majority of pediatric low‐grade gliomas (LGGs) are characterized by constitutive activation of the mitogen‐activated protein kinase (MAPK) pathway through various mechanisms including BRAF mutations, inactivation of NF1, and KIAA1549‐BRAF and FAM131B‐BRAF fusions. The KIAA1549‐BRAF fusion typically results from a 2.0 Mb tandem duplication in chromosome band 7q34. In the present study, single nucleotide polymorphism (SNP)‐based array analysis of three LGGs demonstrated deletions in 7q34 that resulted in a BRAF fusion. Case 1 was likely a pilocytic astrocytoma (PA) with three deletions in 7q33q34 and an exon 15‐9 KIAA1549‐BRAF fusion. SNP array analysis of case 2, a possible dysembryoplastic neuroepithelial tumor (DNT), revealed a 2.6 Mb deletion, which included the 5′ end of BRAF and extended to the 3′ end of FAM131B. In case 3, deletions involving BRAF and FAM131B were observed in both a primary and a recurrent PA. RNA‐based sequence analysis of cases 2 and 3 confirmed a fusion between FAM131B exon 2 and BRAF exon 9. The presence of fusion transcripts in these three LGGs highlights the utility of SNP array analysis to identify deletions that are suggestive of fusion proteins. BRAF fusions can result from multiple non‐overlapping deletions, suggesting various complex mechanisms of formation.
Epigenetic deregulation of Ellis Van Creveld confers robust Hedgehog signaling in adult T‐cell leukemia
Authors: Takahashi Ryutaro , Yamagishi Makoto , Nakano Kazumi , Yamochi Toshiko , Yamochi Tadanori , Fujikawa Dai , Nakashima Makoto , Tanaka Yuetsu , Uchimaru Kaoru , Utsunomiya Atae , Watanabe Toshiki
Published: July 2014

One of the hallmarks of cancer, global gene expression alteration, is closely associated with the development and malignant characteristics associated with adult T‐cell leukemia (ATL) as well as other cancers. Here, we show that aberrant overexpression of the Ellis Van Creveld (EVC) family is responsible for cellular Hedgehog (HH) activation, which provides the pro‐survival ability of ATL cells. Using microarray, quantitative RT‐PCR and immunohistochemistry we have demonstrated that EVC is significantly upregulated in ATL and human T‐cell leukemia virus type I (HTLV‐1)‐infected cells. Epigenetic marks, including histone H3 acetylation and Lys4 trimethylation, are specifically accumulated at the EVC locus in ATL samples. The HTLV‐1 Tax participates in the coordination of EVC expression in an epigenetic fashion. The treatment of shRNA targeting EVC, as well as the transcription factors for HH signaling, diminishes the HH activation and leads to apoptotic death in ATL cell lines. We also showed that a HH signaling inhibitor, GANT61, induces strong apoptosis in the established ATL cell lines and patient‐derived primary ATL cells. Therefore, our data indicate that HH activation is involved in the regulation of leukemic cell survival. The epigenetically deregulated EVC appears to play an important role for HH activation. The possible use of EVC as a specific cell marker and a novel drug target for HTLV‐1‐infected T‐cells is implicated by these findings. The HH inhibitors are suggested as drug candidates for ATL therapy. Our findings also suggest chromatin rearrangement associated with active histone markers in ATL.
Design, Synthesis, and Preliminary Activity Evaluation of Novel Pyrimidine Derivatives as Acid Pump Antagonists
Authors: Song Weiguo , Zhang Xiaopan , Li Shutao , Xu Wenfang
Published: July 2014

Acid‐related diseases of the upper gastrointestinal tract, especially gastroesophageal reflux disease (GERD), remain a widespread problem worldwide. In this paper, we reported the design, synthesis, and preliminary gastric antisecretory activity evaluation of novel pyrimidine derivatives as acid pump antagonists. The gastric antisecretory activity assay results showed that all compounds displayed potent gastric antisecretory activity when gastric secretion was stimulated by histamine. The most potent compound5gexhibited even similar gastric antisecretory activity compared with the control revaprazan, and the relative inhibition rate was 93.0%, which was worthy of further investigation.
Self‐concept of left‐behind children in China: a systematic review of the literature
Authors: Wang X. , Ling L. , Su H. , Cheng J. , Jin L. , Sun Y‐H.
Published: July 2014

The aim of our study was to systematically review studies which had compared self‐concept in left‐behind children with the general population of children in China. Relevant studies about self‐concept of left‐behind children in China published from 2004 to 2014 were sought by searching online databases including Chinese Biological Medicine Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Vip Database, PubMed Database, Google Scholar and Web of Science. The methodological quality of the articles was assessed by using Newcastle‐Ottawa Scale (NOS). Poled effect size and associated 95% confidence interval (CI) were calculated using the random effects model. Cochrane's Q was used to test for heterogeneity and I2 index was used to determine the degree of heterogeneity. Nineteen studies involving 7758 left‐behind children met the inclusion criteria and 15 studies were included in a meta‐analysis. The results indicated that left‐behind group had a lower score of self‐concept and more psychological problems than the control group. The factors associated with self‐concept in left‐behind children were gender, age, grade and the relationships with parents, guardians and teachers. Left‐behind children had lower self‐concept and more mental health problems compared with the general population of children. The development of self‐concept may be an important channel for promoting mental health of left‐behind children.
Supporting parents following childhood traumatic brain injury: a qualitative study to examine information and emotional support needs across key care transitions
Authors: Kirk S. , Fallon D. , Fraser C. , Robinson G. , Vassallo G.
Published: July 2014

Introduction

Traumatic brain injury (TBI) is the leading cause of death and acquired disability in childhood. Research has demonstrated that TBI can lead to long‐term physical, cognitive, emotional and behavioural difficulties for children and parental stress. Less is known about how parents experience a childhood brain injury and their information and support needs. This study aimed to examine parents' experiences and support needs following a childhood TBI from the time of the accident to their child's discharge home.

Methods

Qualitative semi‐structured interviews were conducted with 29 parents/carers of children who had experienced a severe TBI. Participants were recruited from one children's tertiary centre in the UK. Data were analysed using the Framework approach.

Results

Parents had unmet information and emotional support needs across the care trajectory from the time of the accident to their child's return home. Information needs related to the impact of the TBI on their child; current and future treatment/rehabilitation plans; helping their child and managing their behaviour; accessing services/support. They lacked information and support for care transitions. In different settings parents faced particular barriers to having their information needs met. Parents' felt they needed emotional support in coming to terms with witnessing the accident and the loss of their former child. Lack of community support related not only to service availability but to a general lack of understanding of the impact of TBI on children, particularly when this was invisible. Overall parents felt unsupported in coping with children's behavioural and psychological difficulties.

Discussion

Taking a holistic approach to examining parents' experiences and support needs has enabled their changing needs to be highlighted across key care transitions within hospital and community settings and the service implications identified. Improvements in care co‐ordination across care transitions are needed to ensure continuity of care and integration of support.
Measuring maternal responsiveness in a community‐based sample of slow‐to‐talk toddlers: a cross‐sectional study
Authors: Down K. , Levickis P. , Hudson S. , Nicholls R. , Wake M.
Published: July 2014

Background

Maternal responsiveness is important in early language development, but its measurement by direct observation has to date been unrealistic in community settings because of training and time constraints. We report on the development and cross‐sectional comparison of a global rating of maternal responsiveness against a detailed measure of responsiveness at age 24 months.

Methods

The community‐based sample comprised 246 toddlers and their mothers, identified as being slow‐to‐talk at age 18 months within the Let's Learn Language population‐based randomized controlled trial. At age 24 months, mother–child dyads were videotaped during 15 minutes of free‐play and children undertook a standardized language assessment. Videos were blindly rated on both the new global measure, comprising a single rating of responsiveness on a five‐point Likert scale, and a detailed rating of responsiveness known to predict language outcomes, comprising a sum of specific maternal responsive behaviours.

Results

The global rating scale required relatively little training and ratings could be conducted in real time. The global and detailed ratings of maternal responsiveness showed moderate correlation (r = 0.44; P < 0.001). Small positive correlations were found between the global rating and expressive (r = 0.23; P < 0.001), receptive (r = 0.28, P < 0.001) and total language (r = 0.28; P < 0.001) at age 24 months.

Conclusion

The global rating scale was efficient and moderately effective as a measure of maternal responsiveness. It is possible that, combined with other risk measures including concurrent language skills, it could strengthen prediction of which children will and will not go on to experience lasting language difficulties.
Modulation of the kallikrein/kinin system by the angiotensin-converting enzyme inhibitor alleviates experimental autoimmune encephalomyelitis
Authors: Uzawa A , Mori M , Taniguchi J , Kuwabara S
Published: July 2014

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Bradykinin is the end-product of the kallikrein/kinin system, which has been recognized as an endogenous target for combating CNS inflammation. Angiotensin-converting enzyme (ACE) inhibitors influence the kallikrein/kinin system and reportedly have immunomodulatory characteristics. The objectives of this study were to determine whether bradykinin is involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and whether bradykinin control by the ACE inhibitor could be a therapeutic target in MS. The ACE inhibitor enalapril (1·0 or 0·2 mg/kg/day) was administered orally to EAE mice and the serum levels of bradykinin and cytokines in EAE mice were analysed. As a result, the administration of enalapril increased serum bradykinin levels, decreased the clinical and pathological severity of EAE and attenuated interleukin-17-positive cell invasion into the CNS. Additionally, bradykinin receptor antagonist administration reduced the favourable effects of enalapril. Our results suggest that bradykinin is involved in the pathomechanism underlying CNS inflammation in EAE, possibly through inhibiting cell migration into CNS. Control of the kallikrein/kinin system using ACE inhibitors could be a potential therapeutic strategy in MS.
HIF1A as a major vascular endothelial growth factor regulator: do its polymorphisms have an association with age‐related macular degeneration?
Authors: Okur Volkan , Cetin Ozan , Cetin Ebru , Tepeli Emre , Bulgu Yunus , Yildirim Cem
Published: July 2014

Background

To investigate the association between age‐related macular degeneration (AMD) and the polymorphisms of HIF1A, a major vascular epithelial growth factor regulator under hypoxic conditions. The associations of AMD and polymorphisms of genes CFH, SKIV2L and MYRIP were also studied.

Design

Prospective study.

Participants

Eighty‐seven AMD patients and 80 healthy subjects admitted to the Department of Ophthalmology at Pamukkale University Hospital, Denizli, Turkey, were included: 45 (52%) had wet type AMD, and 42 (48%) had dry type AMD.

Methods

Polymorphisms rs1061170 (CFH), rs429608 (SKIV2L), rs2679798 (MYRIP) and both rs11549465 and rs11549467 (HIF1A) were investigated in DNA isolated from peripheral blood samples of the cases and controls by dye‐termination DNA sequencing.

Main Outcome Measures

Genotype distribution of rs1061170 (CFH), rs429608 (SKIV2L), rs2679798 (MYRIP) and both rs11549465 and rs11549467 (HIF1A) in AMD cases and healthy controls; association between genotypes and AMD subtypes.

Results

Given the significant difference between the mean age of case and control groups (72.13 ± 5.77 vs. 62.80 ± 5.22, respectively) (P = .000), subsequent analyses were adjusted for age. We found that having at least one C allele for polymorphism rs1061170 increases AMD risk independent of age (OR = 2.42, 95% confidence interval [CI], 1.22–4.81). The ancestral T allele for polymorphism rs1061170 has a protective effect for AMD (OR = 0.53, 95% CI, 0.34–0.83). No statistically significant difference for distributions of other single nucleotide polymorphisms (SNPs) emerged between patients and healthy subjects.

Conclusions

No associations appeared between HIF1A SNPs and AMD, which were studied here for the first time; however, polymorphism rs1061170 of the CFH gene is associated with AMD in our population.
Evaluation of the macular choroidal thickness using spectral optical coherence tomography in patients with obstructive sleep apnoea syndrome
Authors: Bayhan Hasan A , Aslan Bayhan Seray , İntepe Yavuz S , Muhafiz Ersin , Gürdal Canan
Published: July 2014

Background

To assess the choroidal thickness (CT) in patients with obstructive sleep apnoea syndrome (OSAS) and healthy controls.

Design

Prospective, cross‐sectional study

Participants

Ninety‐two eyes of 92 patients with OSAS and 32 eyes of 32 aged and body mass index‐matched healthy subjects were enrolled.

Methods

OSAS patients were further divided into mild, moderate and severe OSAS groups according to their apnoea hypopnea index (AHI) values. The macular CT and peripapillary retinal nerve fibre layer (RNFL) thickness measurements of the subjects were obtained using spectral domain optical coherence tomography (RTVue‐100, Optovue). The CT and RNFL thickness measurements of the groups were compared, and correlations among the AHI values and these measurements were calculated.

Main Outcome Measures

Choroidal thickness.

Results

There were no significant differences in subfoveal and temporal CT measurements of the groups. A pairwise comparison between the groups revealed that severe OSAS group has significantly thinner CT than mild OSAS group at 3.0 mm nasal to the fovea. Also, compared with severe OSAS group, the CT measurements at 1.5 mm and 3.0 mm nasal to the fovea were significantly thicker in control eyes (both, P < 0.05). There were weak negative correlations between the nasal CT measurements and AHI in the OSAS group (nasal 1.5 mm, P = 0.002, r = −0.358; nasal 3.0 mm, P = 0.004, r = −0.336). Compared with controls, severe OSAS group had significantly thinner nasal and superior RNFL thickness measurement.

Conclusions

Sleep apnoea patients had choroidal structural alterations that may have significance on the pathophysiology of the ophthalmic disorders associated with OSAS.
Improving Environmental and Social Targeting through Adaptive Management in Mexico's Payments for Hydrological Services Program
Authors: SIMS KATHARINE R. E. , ALIX‐GARCIA JENNIFER M. , SHAPIRO‐GARZA ELIZABETH , FINE LEAH R. , RADELOFF VOLKER C. , ARONSON GLEN , CASTILLO SELENE , RAMIREZ‐REYES CARLOS , YAÑEZ‐PAGANS PATRICIA
Published: July 2014

Natural resource managers are often expected to achieve both environmental protection and economic development even when there are fundamental trade‐offs between these goals. Adaptive management provides a theoretical structure for program administrators to balance social priorities in the presence of trade‐offs and to improve conservation targeting. We used the case of Mexico's federal Payments for Hydrological Services program (PSAH) to illustrate the importance of adaptive management for improving program targeting. We documented adaptive elements of PSAH and corresponding changes in program eligibility and selection criteria. To evaluate whether these changes resulted in enrollment of lands of high environmental and social priority, we compared the environmental and social characteristics of the areas enrolled in the program with the characteristics of all forested areas in Mexico, all areas eligible for the program, and all areas submitted for application to the program. The program successfully enrolled areas of both high ecological and social priority, and over time, adaptive changes in the program's criteria for eligibility and selection led to increased enrollment of land scoring high on both dimensions. Three factors facilitated adaptive management in Mexico and are likely to be generally important for conservation managers: a supportive political environment, including financial backing and encouragement to experiment from the federal government; availability of relatively good social and environmental data; and active participation in the review process by stakeholders and outside evaluators.

Mejorando los Objetivos Ambiental y Social Mediante el Manejo Adaptativo en el Programa de Pagos por Servicios Hidrológicos en México
Clinical usefulness of a short‐type, prototype single‐balloon enteroscope for endoscopic retrograde cholangiopancreatography in patients with altered gastrointestinal anatomy: Preliminary experiences
Authors: Kawamura Takuji , Uno Koji , Suzuki Azumi , Mandai Koichiro , Nakase Kojiro , Tanaka Kiyohito , Yasuda Kenjiro
Published: July 2014

Background and Aim

A limited number of endoscopic retrograde cholangiopancreatography (ERCP) accessories are compatible with the conventional single‐balloon enteroscope (SBE) because of the latter's dimensions. The aim of the present study was to assess the utility of a prototype SBE that has a shorter working length and a wider channel than the conventional SBE.

Methods

ERCP procedures carried out between January 2012 and July 2013 using the short SBE prototype were reconstructions such as Billroth II (B‐II), post‐gastrectomy with Roux‐en‐Y (RY‐G), and post‐choledochojejunostomy with Roux‐en‐Y (RY‐CJ). We retrospectively analyzed the rate of reaching the blind end of the intestine, the diagnostic success rate, the interventional success rate, and the frequency of related complications.

Results

Twenty‐seven ERCP procedures on 18 patients analyzed comprised two B‐II, 15 RY‐G, and 10 RY‐CJ reconstructions. With a mean procedure time of 56 min (range 40–150 min), the rate of reaching the blind end, the diagnostic success rate, and the interventional success rate were 24/27 (89%), 20/27 (74%), and 19/27 (70%), respectively. There were no major ERCP‐related complications in any patient.

Conclusions

The prototype short‐type SBE appears safe and effective for use in ERCP, and is compatible with conventional endoscopy accessories.
Neonatal imitation predicts how infants engage with faces
Authors: Paukner Annika , Simpson Elizabeth A. , Ferrari Pier F. , Mrozek Timothy , Suomi Stephen J.
Published: July 2014

In human infants, neonatal imitation and preferences for eyes are both associated with later social and communicative skills, yet the relationship between these abilities remains unexplored. Here we investigated whether neonatal imitation predicts facial viewing patterns in infant rhesus macaques. We first assessed infant macaques for lipsmacking (a core affiliative gesture) and tongue protrusion imitation in the first week of life. When infants were 10–28 days old, we presented them with an animated macaque avatar displaying a still face followed by lipsmacking or tongue protrusion movements. Using eye tracking technology, we found that macaque infants generally looked equally at the eyes and mouth during gesture presentation, but only lipsmacking‐imitators showed significantly more looking at the eyes of the neutral still face. These results suggest that neonatal imitation performance may be an early measure of social attention biases and might potentially facilitate the identification of infants at risk for atypical social development.