bluuebunny/crossref_metadata_2025_split huggingface dataset:
RSPO–LGR4 functions via IQGAP1 to potentiate Wnt signaling
Authors: Carmon Kendra S. , Gong Xing , Yi Jing , Thomas Anthony , Liu Qingyun 
Published: March 2014

Significance
R-spondins (RSPOs) and LGR4 emerged as a major ligand–receptor system in the regulation of Wnt signaling as manifested in their pleotropic roles in development and survival of adult stem cells. The mechanism of how RSPO–LGR4 interacts with the Wnt signaling system remains poorly understood. In this work, we describe the identification of IQGAP1 as the first intracellular signaling partner of RSPO–LGR4 and the delineation of IQGAP1’s roles and mechanism in mediating RSPO–LGR4-induced potentiation of Wnt signaling. We also elucidate the relationship between the RSPO–LGR4–IQGAP1 pathway and the function of RSPO–LGR4 in inhibiting RNF43/ZNRF3. The findings uncovered a unique mechanism of RSPO–LGR4 signaling and provide a mechanistic basis for the pleiotropic functions of RSPO–LGR4 signaling in normal and pathological processes.
Hybridization gap and Fano resonance in SmB6
Authors: Rößler Sahana , Jang Tae-Hwan , Kim Dae-Jeong , Tjeng L. H. , Fisk Zachary , Steglich Frank , Wirth Steffen 
Published: March 2014

SignificanceQuantum entanglement may give rise to emerging phenomena and new states of matter. In the intermediate-valence material SmB6, this is realized via hybridization between localized 4fand conduction band states that, at sufficiently low temperatures, results in the screening of the 4flocal moments by the conduction electrons and produces a so-called Kondo resonance in the density of states. The latter is examined by scanning tunneling spectroscopy down to temperatures well below the Kondo temperature. This atomically resolved spectroscopy allows one to distinguish between reconstructed and pristine surfaces and different surface terminations, all of which influence the spectroscopic results. These insights are vital for other, less local spectroscopic tools in the context of possible topologically protected surface states.
Nitrogen isotope fractionation by alternative nitrogenases and past ocean anoxia
Authors: Zhang Xinning , Sigman Daniel M. , Morel François M. M. , Kraepiel Anne M. L. 
Published: March 2014

SignificanceBiological nitrogen fixation is the main route by which nitrogen enters the biosphere. This reaction is catalyzed by nitrogenase, a metalloenzyme that exists in forms containing molybdenum, vanadium, or iron only. The contribution of the “alternative” vanadium and iron-only nitrogenases to nitrogen fixation in the present and the past is unknown. Here we show that the nitrogen isotopic composition (15N to14N ratio) of biomass generated from nitrogen fixation by alternative nitrogenases is significantly and characteristically lower than biomass produced by molybdenum nitrogenases. In light of these results, nitrogen isotope measurements in ancient sediments imply an important role for iron-only nitrogenases in nitrogen fixation within certain anoxic, molybdenum-limited ancient environments.
Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing
Authors: Treutlein Barbara , Gokce Ozgun , Quake Stephen R. , Südhof Thomas C. 
Published: March 2014

Significance
Neurexins are presynaptic cell-adhesion molecules that are essential for synapse formation and synaptic transmission. Extensive alternative splicing of neurexin transcripts may generate thousands of isoforms, but it is unclear how many distinct neurexins are physiologically produced. We used unbiased long-read sequencing of full-length neurexin mRNAs to systematically assess the alternative splicing of neurexins in prefrontal cortex. We identified a novel, abundantly used alternatively spliced exon of neurexins, and found that the different events of alternative splicing of neurexins appear to be independent of each other. Our data suggest that thousands of neurexin isoforms are physiologically generated, consistent with the notion that neurexins represent transsynaptic protein-interaction scaffolds that mediate diverse functions and are regulated by alternative splicing at multiple independent sites.
Rescue Balloon Pulmonary Angioplasty in a Rapidly Deteriorating Chronic Thromboembolic Pulmonary Hypertension Patient with Liver Failure and Refractory Infection
Authors: Tsuji Akihiro , Ogo Takeshi , Demachi Jun , Ono Yusuke , Sanda Yoshihiro , Morita Yoshihiro , Fukuda Tetsuya , Nakanishi Norifumi 
Published: March 2014

Pulmonary endarterectomy (PEA) is the standard therapy for chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) is an alternative therapy for such patients. Here we report the case of a 60‐year‐old woman who presented with severe CTEPH resulting in low cardiac output and liver failure. Her clinical status rapidly deteriorated after she developed a respiratory infection that was refractory to antibiotic treatment. PEA was risky because of her unstable hemodynamics, uncontrolled infection, and liver failure with jaundice. We thus performed rescue BPA. After 3 BPA procedures, her cardiac symptoms improved from World Health Organization functional class IV to II, and her jaundice resolved. The day after her final BPA procedure, her hemodynamics dramatically improved, and she continued to show improvement 3 months later. We thus suggest that BPA is a good treatment option in CTEPH patients with rapidly deteriorating heart failure and uncontrolled comorbidities.
Hydrogen peroxide thermochemical oscillator as driver for primordial RNA replication
Authors: Ball Rowena , Brindley John 
Published: March 2014

AbstractThis paper presents and tests a previously unrecognised mechanism for driving a replicating molecular system on the prebiotic earth. It is proposed that cell-free RNA replication in the primordial soup may have been driven by self-sustained oscillatory thermochemical reactions. To test this hypothesis a well-characterised hydrogen peroxide oscillator was chosen as the driver and complementary RNA strands with known association and melting kinetics were used as the substrate. An open flow system model for the self-consistent, coupled evolution of the temperature and concentrations in a simple autocatalytic scheme is solved numerically, and it is shown that thermochemical cycling drives replication of the RNA strands. For the (justifiably realistic) values of parameters chosen for the simulated example system, the mean amount of replicant produced at steady state is 6.56 times the input amount, given a constant supply of substrate species. The spontaneous onset of sustained thermochemical oscillations via slowly drifting parameters is demonstrated, and a scheme is given for prebiotic production of complementary RNA strands on rock surfaces.
Metabolic free energy and biological codes: a ‘Data Rate Theorem’ aging model
Authors: Wallace Rodrick 
Published: March 2014

AbstractThe living state is cognitive at every scale and level of organization. Since it is possible to associate a broad class of cognitive processes with ‘dual’ information sources, many pathologies can be addressed using statistical models based on the Shannon Coding, the Shannon-McMillan Source Coding, the Rate Distortion, and the Data Rate Theorems, as these impose powerful necessary condition constraints on information generation and exchange, and on system control. Deterministic-but-for-error biological codes do not directly invoke cognition, although they may be essential subcomponents within larger cognitive processes. A formal argument, however, places such codes within a similar framework, with metabolic free energy serving as a ‘control signal’ stabilizing biochemical code-and-translator dynamics in the presence of noise. Demand beyond available energy supply then expresses itself in punctuated destabilization of the coding channel, affecting a spectrum of essential biological functions. Aging, normal or prematurely driven by psychosocial or environmental stressors, must eventually interfere with the routine operation of such mechanisms, triggering chronic diseases associated with senescence. Amyloid fibril formation, intrinsically disordered protein logic gates, and cell surface glycan/lectin ‘kelp bed’ logic gates are reviewed from this perspective. The results, however, generalize beyond coding machineries having easily recognizable symmetry modes, and strip a full layer of mathematical complication from the study of phase transitions in nonequilibrium biological systems.
Structural characterization and comparison of the large subunits of IPM isomerase and homoaconitase fromMethanococcus jannaschii
Authors: Lee Eun Hye , Lee Kitaik , Hwang Kwang Yeon 
Published: March 2014

The aconitase family of proteins includes three classes of hydro-lyase enzymes: aconitases, homoaconitases and isopropylmalate (IPM) isomerases. They have a common Fe–S cluster-binding site and catalyze the isomerization of specific substrates by sequential dehydration and hydration. The archaeonMethanococcus jannaschiicontains two aconitase family proteins, IPM isomerase and homoaconitase, which have 50% sequence identity. These two enzymes are heterodimeric proteins composed of large and small subunits encoded by separate genes. Although structures have been reported for the small subunits of the two enzymes, the first structures of oxidized and reduced forms of the large subunit of IPM isomerase (ox-MJ0499 and red-MJ0499, respectively) fromM. jannaschiiare reported here at 1.8 and 2.7 Å resolution, respectively, together with the structure of the large subunit of homoaconitase (MJ1003) at 2.5 Å resolution. The structures of both proteins have unbound Fe–S clusters and contain a fourth cysteine in the active site. The active site of MJ1003 is homologous to that of aconitase, whereas MJ0499 has significant structural distortion at the active site compared with aconitase. In addition, significant large conformational changes were observed in the active site of red-MJ0499 when compared with ox-MJ0499. The active sites of the two proteins adopt two different states before changing to the Fe–S cluster-bound `activated' state observed in aconitase. MJ1003 has an `open' active site, which forms an active pocket for the cluster, while ox-MJ0499 has a `closed' active site, with four cysteines in disulfide bonds. These data will be helpful in understanding the biochemical mechanism of clustering of the Fe–S protein family.
The structures of cytosolic and plastid-located glutamine synthetases fromMedicago truncatulareveal a common and dynamic architecture
Authors: Torreira Eva , Seabra Ana Rita , Marriott Hazel , Zhou Min , Llorca Óscar , Robinson Carol V. , Carvalho Helena G. , Fernández-Tornero Carlos , Pereira Pedro José Barbosa 
Published: March 2014

The first step of nitrogen assimilation in higher plants, the energy-driven incorporation of ammonia into glutamate, is catalyzed by glutamine synthetase. This central process yields the readily metabolizable glutamine, which in turn is at the basis of all subsequent biosynthesis of nitrogenous compounds. The essential role performed by glutamine synthetase makes it a prime target for herbicidal compounds, but also a suitable intervention point for the improvement of crop yields. Although the majority of crop plants are dicotyledonous, little is known about the structural organization of glutamine synthetase in these organisms and about the functional differences between the different isoforms. Here, the structural characterization of two glutamine synthetase isoforms from the model legumeMedicago truncatulais reported: the crystallographic structure of cytoplasmic GSII-1a and an electron cryomicroscopy reconstruction of plastid-located GSII-2a. Together, these structural models unveil a decameric organization of dicotyledonous glutamine synthetase, with two pentameric rings weakly connected by inter-ring loops. Moreover, rearrangement of these dynamic loops changes the relative orientation of the rings, suggesting a zipper-like mechanism for their assembly into a decameric enzyme. Finally, the atomic structure ofM. truncatulaGSII-1a provides important insights into the structural determinants of herbicide resistance in this family of enzymes, opening new avenues for the development of herbicide-resistant plants.
Pregnancy and childbirth outcomes among adolescent mothers: a World Health Organization multicountry study
Authors: Ganchimeg T , Ota E , Morisaki N , Laopaiboon M , Lumbiganon P , Zhang J , Yamdamsuren B , Temmerman M , Say L , Tunçalp Ö , Vogel JP , Souza JP , Mori R ,   on behalf of the WHO Multicountry Survey on Maternal Newborn Health Research Network
Published: March 2014

ObjectiveTo investigate the risk of adverse pregnancy outcomes among adolescents in 29 countries.DesignSecondary analysis using facility‐based cross‐sectional data of the World Health Organization Multicountry Survey on Maternal and Newborn Health.SettingTwenty‐nine countries in Africa, Latin America, Asia and the Middle East.PopulationWomen admitted for delivery in 359 health facilities during 2–4 months between 2010 and 2011.MethodsMultilevel logistic regression models were used to estimate the association between young maternal age and adverse pregnancy outcomes.Main outcome measuresRisk of adverse pregnancy outcomes among adolescent mothers.ResultsA total of 124 446 mothers aged ≤24 years and their infants were analysed. Compared with mothers aged 20–24 years, adolescent mothers aged 10–19 years had higher risks of eclampsia, puerperal endometritis, systemic infections, low birthweight, preterm delivery and severe neonatal conditions. The increased risk of intra‐hospital early neonatal death among infants born to adolescent mothers was reduced and statistically insignificant after adjustment for gestational age and birthweight, in addition to maternal characteristics, mode of delivery and congenital malformation. The coverage of prophylactic uterotonics, prophylactic antibiotics for caesarean section and antenatal corticosteroids for preterm delivery at 26–34 weeks was significantly lower among adolescent mothers.ConclusionsAdolescent pregnancy was associated with higher risks of adverse pregnancy outcomes. Pregnancy prevention strategies and the improvement of healthcare interventions are crucial to reduce adverse pregnancy outcomes among adolescent women in low‐ and middle‐income countries.
Dating of Seals Produced with Stamp‐Pad Ink Using Gas Chromatography Method
Authors: Li Biao 
Published: March 2014

AbstractSeals are often placed on important documents, and determining the date when a seal was affixed can be important to assess the authenticity of a document. In this study, thirty‐seven different brands of stamp‐pad inks and three different types of paper were used to make diachronic samples of the seals. The volatile components of stamp‐pad ink were determined, and the stamp‐pad ink was classified by gas chromatography with a flame ionization detector. Calibration curves were created to show the relationship between the content of volatile stamp‐pad ink components and the age of stamp‐pad ink entries stored under natural aging,UV‐induced aging, and heating aging conditions. The experimental results showed thatGCwas useful in the analysis of stamp‐pad ink and applicable for determining the relative age of stamp‐pad ink entries in some cases where the seal was placed on the document within 3 months.
Field Study on the Attraction and Development of Insects on Human Meconium and Breast‐fed‐Infant Feces
Authors: De Jong Grant D. 
Published: March 2014

AbstractUrogenital myiasis of newborn infants, although rare, is usually considered to indicate neglect due to attraction of flies to feces; however, infant feces have not been determined to attract insects. Human meconium and breast‐fed‐infant feces were used to determine attractiveness to insects and to examine subsequent colonization and growth patterns of insect larvae. Despite small amounts of fecal material present, adults of Lucilia sericata arrived at breast‐fed‐infant feces within five minutes; insects were rarely observed on meconium. Oviposition and growth of L. sericata larvae occurred only on breast‐fed‐infant feces; however, the larvae did not progress beyond the second instar. These data suggest that urogenital myiasis by L. sericata in newborn human infants within the first few days postpartum would not be expected, but desiccation and depletion of infested feces may provide a possible pathway for urogenital myiasis in older newborn infants.
A Comparison of the Effectiveness of Swabbing and Flossing as a Means of Recovering Spermatozoa from the Oral Cavity
Authors: Roberts Katherine A. , Johnson Donald J. , Cruz Sherillelynn , Simpson Heather , Safer Alan 
Published: March 2014

AbstractThis study examined whether flossing the teeth is a more effective collection method in recovering spermatozoa than conventional swabbing techniques. It was hypothesized that inclusion of flossing as a collection method would extend the recovery of spermatozoa to longer postcoital intervals (PCIs). Eighteen individuals provided 174 oral cavity samples. Successful recovery of spermatozoa was assessed with respect to the collection method and reported activity in the oral cavity during the PCI. Samples were subjected to a differential extraction procedure prior to microscopic evaluation of the extracted pellet. The results indicate that swabbing is more effective than flossing when the PCI falls within 1.5–12 h. However, spermatozoa were recovered from seven floss samples where the corresponding swabs gave negative results. When combining the results from the two collection methods, the percentage of subjects from whom spermatozoa are recovered increases for each PCI beyond the 0‐h interval.
Enhanced UV‐B radiation during pupal stage reduce body mass and fat content, while increasing deformities, mortality and cell death in female adults of solitary bee Osmia bicornis
Authors: Wasielewski Oskar , Wojciechowicz Tatiana , Giejdasz Karol , Krishnan Natraj 
Published: March 2014

AbstractThe effects of enhanced UV‐B radiation on the oogenesis and morpho‐anatomical characteristics of the European solitary red mason bee Osmia bicornis L. (Hymenoptera: Megachilidae) were tested under laboratory conditions. Cocooned females in the pupal stage were exposed directly to different doses (0, 9.24, 12.32, and 24.64 kJ/m2/d) of artificial UV‐B. Our experiments revealed that enhanced UV‐B radiation can reduce body mass and fat body content, cause deformities and increase mortality. Following UV exposure at all 3 different doses, the body mass of bees was all significantly reduced compared to the control, with the highest UV dose causing the largest reduction. Similarly, following UV‐B radiation, in treated groups the fat body index decreased and the fat body index was the lowest in the group receiving the highest dose of UV radiation. Mortality and morphological deformities, between untreated and exposed females varied considerably and increased with the dose of UV‐B radiation. Morphological deformities were mainly manifested in the wings and mouthparts, and occurred more frequently with an increased dose of UV. Cell death was quantified by the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (DNA fragmentation) during early stages of oogenesis of O. bicornis females. The bees, after UV‐B exposure exhibited more germarium cells with fragmented DNA. The TUNEL test indicated that in germarium, low doses of UV‐B poorly induced the cell death during early development. However, exposure to moderate UV‐B dose increased programmed cell death. In females treated with the highest dose of UV‐B the vast majority of germarium cells were TUNEL‐positive.
Cardiac dosimetry for adjuvant left‐sided breast radiotherapy: Patterns with 2D‐ versus 3D‐era planning and correlates of coronary dose with maximum depth of myocardial exposure
Authors: Graham PH 
Published: March 2014

AbstractIntroductionThe purpose of this study was to evaluate the cardiac dosimetry delivered before and after routine 3D CT whole‐breast radiotherapy planning, including cardiac contouring and the relevance of a 15‐mm maximum myocardial depth (MMD) planning tolerance threshold.MethodsThe PULp FICTion study permitted cardiac dosimetry comparisons for 140 patients (70 in the ‘before‐contouring era’ (BC) and 70 in the ‘post‐contouring era’ (PC) ). Comparisons were made of MMD and dosimetry for whole heart, anterior myocardium and left anterior descending (LAD)/coronary artery (overall, superior and inferior) by contouring era.ResultsThe MMD mean was 15.6 mm (range 1–40). If the internal mammary chain (IMC) was treated, the MMD increased from 15 to 27.7 mm (P < 0.0001). Excluding IMC patients revealed no difference in MMD between conservation and mastectomy (14.9 vs 17.4, P = 0.3), boost and no boost (14.5 vs 15.5, P = 0.41) or BC and PC (15.7 vs 14.5. P = 0.33) and no differences related to treating clinician, anthracycline use or age. Only in potentially low‐risk patients defined as not requiring IMC or boost treatment was there a difference in MMD by era, with 17.7 mm (1–40) in the BC era and 13.9 mm (1–31) mm in the PC era (P = 0.013). Inferior LAD mean doses increased from 49% to 84% of the prescribed breast dose when MMD was >15 mm, and the proportion of patients with a mean dose <40% of the prescribed breast dose fell from 48% to 8%.ConclusionChanges in cardiac dosimetry associated with routine cardiac contouring have initially been minor and restricted to low‐risk patients. A 15‐mm MMD reasonably represents a transition from low mean distal LAD doses to substantial doses.
Accelerated microglial pathology is associated with Aβ plaques in mouse models of Alzheimer's disease
Authors: Baron Rona , Babcock Alicia A. , Nemirovsky Anna , Finsen Bente , Monsonego Alon 
Published: March 2014

SummaryMicroglia integrate within the neural tissue with a distinct ramified morphology through which they scan the surrounding neuronal network. Here, we used a digital tool for the quantitative morphometric characterization of fine cortical microglial structures in mice, and the changes they undergo with aging and in Alzheimer's‐like disease. We show that, compared with microglia in young mice, microglia in old mice are less ramified and possess fewer branches and fine processes along with a slightly increased proinflammatory cytokine expression. A similar microglial pathology appeared 6–12 months earlier in mouse models of Alzheimer's disease (AD), along with a significant increase in brain parenchyma lacking coverage by microglial processes. We further demonstrate that microglia near amyloid plaques acquire unique activated phenotypes with impaired process complexity. We thus show that along with a chronic proinflammatory reaction in the brain, aging causes a significant reduction in the capacity of microglia to scan their environment. This type of pathology is markedly accelerated in mouse models of AD, resulting in a severe microglial process deficiency, and possibly contributing to enhanced cognitive decline.