bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Metabolic Effects of Hydrogen Sulfide on the Development of Bombyx mori (Lepidoptera: Bombycidae), Using Liquid Chromatography-Mass Spectrometry-Based Metabolomics
Authors: Cao Yu-Yao , Peng Li-Li , Jiang Li , Thakur Kiran , Hu Fei , Tang Shun-Ming , Wei Zhao-Jun
Published: February 2020

Hydrogen sulfide (H2S) is a highly poisonous gas with an unpleasant smell of rotten eggs. Previous studies of H2S have primarily focused on its effects on mammalian nervous and respiratory systems. In this study, silkworm developmental parameters and changes in metabolites in response to H2S exposure were investigated using a hemolymph metabolomic approach, based on liquid chromatography–mass spectrometry (LC-MS). The developmental parameters, body weight, cocoon weight, cocoon shell weight, and cocoon shell ratio, were noticeably increased following H2S exposure, with the greatest effects observed at 7.5-μM H2S. Metabolites upregulated under H2S exposure (7.5 μM) were related to inflammation, and included (6Z, 9Z, 12Z)-octadecatrienoic acid, choline phosphate, and malic acid, while hexadecanoic acid was downregulated. Identified metabolites were involved in biological processes, including pyrimidine, purine, and fatty acid metabolism, which are likely to affect silk gland function. These results demonstrate that H2S is beneficial to silkworm development and alters metabolic pathways related to spinning function and inflammation. The present study provides new information regarding the potential functions of H2S in insects and metabolic pathways related to this phenomenon.
Parent Responses to Their Child's Pain: Systematic Review and Meta-Analysis of Measures
Authors: Harrison Lauren E , Timmers Inge , Heathcote Lauren C , Fisher Emma , Tanna Vivek , Duarte Silva Bans Tom , Simons Laura E
Published: February 2020

Objective

Parent responses can have a major impact on their child’s pain. The purpose of this systematic review is to (a) identify and describe measures assessing pain-related cognitive, affective, and behavioral responses in parents of children with chronic pain and (b) meta-analyze reported correlations between parent constructs and child outcomes (i.e., pain intensity, functional disability, and school functioning). Prospero protocol registration ID: CRD42019125496.

Methods

We conducted a systematic search of studies including a measure of parent/caregiver responses to their child’s chronic pain. Study characteristics and correlations between parent measures and child outcomes were extracted. Data were summarized and meta-analyzed.

Results

Seventy-nine met inclusion criteria using 18 different measures of cognitive/affective (n = 3), behavioral (n = 5), and multidimensional responses (n = 10). Measures were used a median of three times (range 1–48), predominantly completed by mothers (88%), and primarily in mixed pain samples. Psychometrics of measures were generally adequate. Meta-analyses were based on 42 papers across five measures. Results showed that each of the cognitive, affective, and behavioral parent constructs we examined was significantly associated with pain-related functional disability. A small number of measures assessing parent cognitions and affective functioning were associated with higher child pain intensity; however, the majority were not.

Conclusion

Findings demonstrate that there is a wealth of measures available, with adequate reliability overall but a lack of psychometrics on temporal stability. Synthesizing data across studies revealed small effects between parent responses and child functioning, and even smaller and/or absent effects on child pain intensity.
Diabetes-Specific Self-Compassion: A New Measure for Parents of Youth With Type 1 Diabetes
Authors: Tanenbaum Molly L , Adams Rebecca N , Wong Jessie J , Hood Korey K
Published: February 2020

Objective

Given the high daily demands of managing type 1 diabetes (T1D), parents of youth with T1D can experience high levels of emotional distress, burden, and self-criticism, with implications for parent and child well-being and parent self-efficacy for managing diabetes. Diabetes-specific self-compassion (SC), or being kind to oneself when facing challenges related to managing diabetes, may serve as protective for parents. This study aimed to create and assess the psychometric properties of a new tool, the diabetes-specific Self-Compassion Scale (SCS-Dp), to assess diabetes-specific SC in parents of youth with T1D.

Methods

We adapted a parent diabetes-specific SC measure; surveyed parents (N = 198; parent: 88% female; 95% non-Hispanic White; M age = 44 ± 8.9; child: 46% female; M age = 13 ± 3.4, range 2–18 years; 83% insulin pump users; 40% continuous glucose monitor (CGM) users; HbA1c from clinic data available for 76 participants: M HbA1c = 8.1 ± 1.3%) and conducted confirmatory factor analysis, and reliability and construct validity analyses. Validity measures included diabetes distress, diabetes empowerment, diabetes numeracy, and HbA1c.

Results

A bifactor structure provided the best fit, with one general factor and two wording-related group factors (positively and negatively worded items). The final 19-item SCS-Dp demonstrated excellent internal consistency (α =.94; range of item-total correlations: .52–.81) and good construct validity. As predicted, greater SC was associated with lower distress (r = −.68, p < .001) and greater empowerment (r = .43, p < .001) and was not associated with diabetes numeracy (p = .61). Diabetes-specific Self-Compassion Scale was not associated with HbA1c (p = .28).

Conclusions

Results provide initial evidence of good reliability and validity of the SCS-Dp to assess diabetes-specific SC in parents.
Internal herniation of the caecum and the ascending colon through the foramen of Winslow
Authors: Azer Mina , Lira-Schuldes Alejandro-Daniel , Volkers Hans-Uwe
Published: February 2020

We are reporting a case of internal herniation of the bowel through the foramen of Winslow. This is a very rare condition that prompts an urgent operative intervention due to its potential fatal complications, as it is usually accompanied by bowel strangulation and ischemia. Due to the vague clinical picture, the diagnosis only reached using imaging techniques such as computed tomography or as a surgical surprise during the operation. Key aspects of surgical interventions are hernia reduction, bowel resection in case of non-viable ischemic bowel and the highly debatable recurrence prevention maneouvres.
RAP2.3 negatively regulates nitric oxide biosynthesis and related responses through a rheostat-like mechanism in Arabidopsis
Authors: León José , Costa-Broseta Álvaro , Castillo Mari Cruz
Published: February 2020

Nitric oxide (NO) is sensed through a mechanism involving the degradation of group-VII ERF transcription factors (ERFVIIs) that is mediated by the N-degron pathway. However, the mechanisms regulating NO homeostasis and downstream responses remain mostly unknown. To explore the role of ERFVIIs in regulating NO production and signaling, genome-wide transcriptome analyses were performed on single and multiple erfvii mutants of Arabidopsis following exposure to NO. Transgenic plants overexpressing degradable or non-degradable versions of RAP2.3, one of the five ERFVIIs, were also examined. Enhanced RAP2.3 expression attenuated the changes in the transcriptome upon exposure to NO, and thereby acted as a brake for NO-triggered responses that included the activation of jasmonate and ABA signaling. The expression of non-degradable RAP2.3 attenuated NO biosynthesis in shoots but not in roots, and released the NO-triggered inhibition of hypocotyl and root elongation. In the guard cells of stomata, the control of NO accumulation depended on PRT6-triggered degradation of RAP2.3 more than on RAP2.3 levels. RAP2.3 therefore seemed to work as a molecular rheostat controlling NO homeostasis and signaling. Its function as a brake for NO signaling was released upon NO-triggered PRT6-mediated degradation, thus allowing the inhibition of growth, and the potentiation of jasmonate- and ABA-related signaling.
How does bark contribution to postural control change during tree ontogeny? A study of six Amazonian tree species
Authors: Lehnebach Romain , Alméras Tancrède , Clair Bruno
Published: February 2020

Recent works revealed that bark is able to produce mechanical stress to control the orientation of young tilted stems. Here we report how the potential performance of this function changes with stem size in six Amazonian species with contrasted bark anatomy. The potential performance of the mechanism depends both on the magnitude of bark stress and the relative thickness of the bark. We measured bark longitudinal residual strain and density, and the allometric relationship between bark thickness and stem radius over a gradient of tree sizes. Constant tensile stress was found in species that rely on bark for the control of stem orientation in young stages. Other species had increasing compressive stress, associated with increasing density attributed to the development of sclereids. Compressive stress was also associated with low relative bark thickness. The relative thickness of bark decreased with size in all species, suggesting that a reorientation mechanism based on bark progressively performs less well as the tree grows. However, greater relative thickness was observed in species with more tensile stress, thereby evidencing that this reduction in performance is mitigated in species that rely on bark for reorientation.
Thermal instability of halo gas heated by streaming cosmic rays
Authors: Kempski Philipp , Quataert Eliot
Published: February 2020

Heating of virialized gas by streaming cosmic rays (CRs) may be energetically important in galaxy haloes, groups, and clusters. We present a linear thermal stability analysis of plasmas heated by streaming CRs. We separately treat equilibria with and without background gradients, and with and without gravity. We include both CR streaming and diffusion along the magnetic-field direction. Thermal stability depends strongly on the ratio of CR pressure to gas pressure, which determines whether modes are isobaric or isochoric. Modes with $\boldsymbol {k \cdot B }\ne 0$ are strongly affected by CR diffusion. When the streaming time is shorter than the CR diffusion time, thermally unstable modes (with $\boldsymbol {k \cdot B }\ne 0$) are waves propagating at a speed ∝ the Alfvén speed. Halo gas in photoionization equilibrium is thermally stable independent of CR pressure, while gas in collisional ionization equilibrium is unstable for physically realistic parameters. In gravitationally stratified plasmas, the oscillation frequency of thermally overstable modes can be higher in the presence of CR streaming than the buoyancy/free-fall frequency. This may modify the critical tcool/tff at which multiphase gas is present. The criterion for convective instability of a stratified, CR-heated medium can be written in the familiar Schwarzschild form dseff/dz < 0, where seff is an effective entropy involving the gas and CR pressures. We discuss the implications of our results for the thermal evolution and multiphase structure of galaxy haloes, groups, and clusters.
A detailed study on the reflection component for the black hole candidate MAXI J1836−194
Authors: Dong Yanting , García Javier A , Liu Zhu , Zhao Xueshan , Zheng Xueying , Gou Lijun
Published: February 2020

We present a detailed spectral analysis of the black hole candidate MAXI J1836−194. The source was caught in the intermediate state during its 2011 outburst by Suzaku and RXTE. We jointly fit the X-ray data from these two missions using the relxill model to study the reflection component, and a steep inner emissivity profile indicating a compact corona as the primary source is required in order to achieve a good fit. In addition, a reflection model with a lamp-post configuration (relxilllp), which is normally invoked to explain the steep emissivity profile, gives a worse fit and is excluded at 99 per cent confidence level compared to relxill. We also explore the effect of the ionization gradient on the emissivity profile by fitting the data with two relativistic reflection components, and it is found that the inner emissivity flattens. These results may indicate that the ionization state of the disc is not constant. All the models above require a supersolar iron abundance higher than ∼4.5. However, we find that the high-density version of reflionx can describe the same spectra even with solar iron abundance well. A moderate rotating black hole (a* = 0.84–0.94) is consistently obtained by our models, which is in agreement with previously reported values.
A 5° × 5° deep H i survey of the M81 group − II. H i distribution and kinematics of IC 2574 and HIJASS J1021+68
Authors: Sorgho A , Chemin L , Kam Z S , Foster T , Carignan C
Published: February 2020

We analyse the eastern region of a 5° × 5° deep H i survey of the M81 group containing the dwarf galaxy IC 2574 and the H i complex HIJASS J1021+68, located between the dwarf and the M81 system. The data show that IC 2574 has an extended H i envelope that connects to HIJASS J1021+68 in the form of a collection of small clouds, but no evident connection has been found between IC 2574 and the central members of the M81 group. We argue, based on the morphology of the clouds forming HIJASS J1021+68 and its velocity distribution, that the complex is not a dark galaxy as previously suggested, but is instead a complex of clouds either stripped from, or falling on to the primordial H i envelope of IC 2574. We also use the deep H i observations to map the extended H i envelope around IC 2574 and, using a 3D tilted-ring model, we derive the rotation curve of the galaxy to a larger extent than has been done before. Combining the obtained rotation curve to higher resolution curves from the literature, we constrain the galaxy’s dark matter halo parameters.
The complex formed between a synthetic RNA aptamer and the transcription repressor TetR is a structural and functional twin of the operator DNA–TetR regulator complex
Authors: Grau Florian C , Jaeger Jeannine , Groher Florian , Suess Beatrix , Muller Yves A
Published: February 2020

RNAs play major roles in the regulation of gene expression. Hence, designer RNA molecules are increasingly explored as regulatory switches in synthetic biology. Among these, the TetR-binding RNA aptamer was selected by its ability to compete with operator DNA for binding to the bacterial repressor TetR. A fortuitous finding was that induction of TetR by tetracycline abolishes both RNA aptamer and operator DNA binding in TetR. This enabled numerous applications exploiting both the specificity of the RNA aptamer and the efficient gene repressor properties of TetR. Here, we present the crystal structure of the TetR-RNA aptamer complex at 2.7 Å resolution together with a comprehensive characterization of the TetR–RNA aptamer versus TetR–operator DNA interaction using site-directed mutagenesis, size exclusion chromatography, electrophoretic mobility shift assays and isothermal titration calorimetry. The fold of the RNA aptamer bears no resemblance to regular B-DNA, and neither does the thermodynamic characterization of the complex formation reaction. Nevertheless, the functional aptamer-binding epitope of TetR is fully contained within its DNA-binding epitope. In the RNA aptamer complex, TetR adopts the well-characterized DNA-binding-competent conformation of TetR, thus revealing how the synthetic TetR-binding aptamer strikes the chords of the bimodal allosteric behaviour of TetR to function as a synthetic regulator.
Microbiome Restoration by RBX2660 Does Not Preclude Recurrence of Multidrug-Resistant Urinary Tract Infection Following Subsequent Antibiotic Exposure: A Case Report
Authors: Keen Eric C , Tasoff Preston , Hink Tiffany , Reske Kimberly A , Burnham Carey-Ann D , Dantas Gautam , Kwon Jennie H , Dubberke Erik R
Published: February 2020

A 62-year-old woman received RBX2660, an investigational microbiome restoration therapeutic, for recurrent multidrug-resistant (MDR) urinary tract infection (UTI). RBX2660 increased gut microbiome diversity but did not eliminate uropathogen carriage, and MDR UTI recurred after subsequent antibiotic exposure. Thus, restoration of microbiome diversity does not preclude disease recurrence by residual MDR pathogens.
A 72-Year-Old Female With Bow Hunter Syndrome: A Rare Surgical Approach to C4-5 Vertebral Artery Decompression: 2-Dimensional Operative Video
Authors: Gigliotti Michael J , Joseph Jacob , Thompson Byron Gregory , Park Paul
Published: February 2020

Bow hunter syndrome is defined as vertebrobasilar insufficiency due to mechanical occlusion of the vertebral artery during head and neck rotation. In many cases, this is due to osteophyte formation, disc herniation, cervical spondylosis, tendinous bands, or tumors. Symptomatic disease may vary from inducing transient vertigo to posterior circulation stroke. Although digital subtraction angiography is the gold standard in diagnosis, the underlying pathology in bow hunter syndrome may be detected with doppler ultrasound, computed tomography (CT) angiogram, magnetic resonance imaging and angiogram, and diagnostic angiography with dynamic testing. In this case, a 72-yr-old female with a recent right-sided cerebellar stroke underwent operative intervention to decompress the right vertebral artery at C4-C5 in order to relieve symptomatic bow hunter syndrome. Preoperative CT angiogram revealed bilateral significant stenosis of the vertebral arteries at the C4-C5 level with follow-up diagnostic angiogram revealing complete occlusion of the right vertebral artery with the head rotated right (compared to 80% occlusion observed when the patient's head was rotated left). Prior to the procedure, the patient experienced lightheadedness, diaphoresis, dizziness, and a sensation of facial flushing exacerbated by rotating her head to the right. To relieve her symptoms, operative intervention was undertaken. To access the lateral osteophytes originating from the uncovertebral joint, a C4-5 discectomy is utilized. The vertebral artery was decompressed, and a standard anterior cervical fusion was performed. Postoperatively, the patient was stable and was discharged 1 d after surgery. Postoperative imaging showed adequate decompression of the right vertebral artery at the level of C4-5.

 The authors confirm that they have obtained, prior to submission, a written release from the patient authorizing use of this surgical video to be submitted and published in the journal Operative Neurosurgery, as well as consent to perform the procedure.
Genesis of Recent Mafic Magmatism in the Taupo Volcanic Zone, New Zealand: Insights into the Birth and Death of Very Large Volume Rhyolitic Systems?
Authors: Zellmer Georg F , Kimura Jun-Ichi , Stirling Claudine H , Lube Gert , Shane Phil A , Iizuka Yoshiyuki
Published: February 2020

Mafic magmatism of the rifting Taupo Volcanic Zone (TVZ) of the North Island, New Zealand, is volumetrically minor, but is thought to tap the material that provides the heat source for voluminous rhyolite production through partial melting of the crust, which ultimately results in very large volume explosive eruptions. We have studied the major and trace element chemistry of 14 mafic samples from across the entire TVZ, and the U isotopic composition of whole-rocks, groundmasses and separates of mafic mineral phases from a selection of nine samples (with the remaining five too sparsely phyric for mineral separation). Some minerals yield significant 234U enrichments despite groundmass and whole-rock close to 238U–234U secular equilibrium, pointing to uptake of variably hydrothermally altered antecrystic minerals prior to the eruption of originally sparsely phyric to aphyric mafic magmas. However, incompatible trace element patterns indicate that there are three chemically distinct groups of samples, and that samples may be used to derive primary melt compositions. We employ the latest version of the Arc Basalt Simulator (ABS5) to forward model these compositions, deriving mantle source parameters including mantle fertility, slab liquid flux, mantle volatile content, degree of melting, and P–T conditions of melt segregation. We show that mafic rocks erupted in areas of old, now inactive calderas constitute low-degree, deep melts, whereas those in areas of active caldera-volcanism are high-degree partial melts segregated from a less depleted source at an intermediate depth. Finally, high-Mg basaltic andesites erupted in the SW and NE of the TVZ point to a fertile, shallow mantle source. Our data are consistent with a petrogenetic model in which mantle melting is dominated by decompression, rather than fluid fluxing, and progresses from shallow to deeper levels with time. Melt volumes initially increase to a tipping point, at which large-scale crustal melting and caldera volcanism become prominent, and then decrease owing to progressive depletion of the mantle wedge by melting, resulting in the dearth of heat provided and eventual cessation of very large volume rhyolitic volcanism. ABS5 modelling therefore supports the notion of a direct link between the chemistry of recently erupted mafic magmas and the long-term activity and evolution of rhyolitic volcanism in the TVZ.
Metasomatism and Hydration of the Oceanic Lithosphere: a Case Study of Peridotite Xenoliths from Samoa
Authors: Ashley Aaron Wolfgang , Bizimis Michael , Peslier Anne H , Jackson Matthew , Konter Jasper G
Published: February 2020

Water influences geodynamic processes such as melting, deformation and rheology, yet its distribution in the oceanic upper mantle is primarily known indirectly from melt inclusions and glasses of erupted mantle melts (i.e. mid-ocean ridge and ocean island basalts). To better constrain the mechanisms influencing the distribution of H2O in the mantle, particularly regarding the role of metasomatism, we analyzed 15 peridotite xenoliths from Savai‘i and two dunite xenoliths from Ta‘ū (Samoa) for structural H2O (by polarized Fourier transform infrared spectroscopy), and major and trace element concentrations. Clinopyroxenes from the Ta‘ū dunites show trace element concentrations consistent with equilibration with their host lavas, but lower H2O contents than expected. Savai‘i peridotites are highly depleted harzburgites (melt depletion ≥17 %). They show strong evidence of transient metasomatism by both carbonatite and silicate melts, with highly variable Ti and Zr depletions and light rare earth element enrichments. However, despite metasomatism the H2O concentrations in olivines (0 − 4 ppm H2O) and orthopyroxenes (17 − 89 ppm H2O) are among the lowest reported in oceanic xenoliths, but higher than expected for the estimated degree of depletion. In general, H2O concentrations vary less than those of other incompatible trace elements in these samples. Transects across mineral grains show generally homogeneous distributions of H2O, indicating no significant H2O loss or gain during ascent. Raman spectroscopy on inclusions in minerals shows the presence of CO2 but an absence of molecular H2O. This agrees with the absence of H2O concentration variations between inclusion-rich and -poor domains in minerals. The above data can be explained by transient metasomatism along grain boundaries, now recorded as planes of inclusions within annealed grains. Fast diffusion of hydrogen (but not lithophile elements) from the inclusions into the host mineral phase will simultaneously enrich H2O contents across the grain and lower them in the inclusion-rich domains. The result is highly variable metasomatism recorded in lithophile elements, with smaller magnitude H2O variations that are decoupled from lithophile element metasomatism. Comparison with xenoliths from Hawai‘i shows that evidence for metasomatism from lithophile elements alone does not imply rehydration of the oceanic lithosphere. Instead, H2O concentrations depend on the overall amount of H2O added to the lithosphere through metasomatism, and the proximity of sampled material to areas of melt infiltration in the lithosphere.
Smoking in spondyloarthritis: unravelling the complexities
Authors: Zhao Sizheng Steven , Goodson Nicola J , Robertson Selina , Gaffney Karl
Published: February 2020

Tobacco smoking is a major threat to health. There is no doubt about the need to promote and support cessation at every opportunity. Smoking has a clear role in RA, but what evidence is there that the same relationship exists in SpA? In this review, we examine (the less cited) paradoxes and contradictions in the existing axial SpA (axSpA) and PsA literature; for example, smoking appears to be ‘protective’ for some axSpA manifestations. We also highlight findings from higher quality evidence: smoking is associated with increased risk of PsA and the risk of psoriasis in axSpA. The relationship between smoking and SpA is far from simple. Our aim is to highlight the harms of smoking in SpA and bring attention to inconsistencies in the literature to inform further research.
Metabolism and Effects on Endogenous Metabolism of Paracetamol (Acetaminophen) in a Porcine Model of Liver Failure
Authors: Dargue Rebecca , Zia Rabiya , Lau Chungho , Nicholls Andrew W , Dare Theo O , Lee Karla , Jalan Rajiv , Coen Muireann , Wilson Ian D
Published: February 2020

The metabolic fate, toxicity, and effects on endogenous metabolism of paracetamol (acetaminophen, APAP) in 22 female Landrace cross large white pigs were evaluated in a model of acute liver failure (ALF). Anesthetized pigs were initially dosed at 250 mg/kg via an oroduodenal tube with APAP serum concentrations maintained above 300 mg/l using maintenance doses of 0.5–4 g/h until ALF. Studies were undertaken to determine both the metabolic fate of APAP and its effects on the endogenous metabolic phenotype of ALF in using 1H NMR spectroscopy. Increased concentrations of citrate combined with pre-ALF increases in circulating lactate, pyruvate, and alanine in plasma suggest mitochondrial dysfunction and a switch in hepatic energy metabolism to glycolysis in response to APAP treatment. A specific liquid chromatography-tandem mass spectrometry assay was used to quantify APAP and metabolites. The major circulating and urinary metabolite of APAP was the phenolic glucuronide (APAP-G), followed by p-aminophenol glucuronide (PAP-G) formed from N-deacetylated APAP. The PAP produced by N-deacetylation was the likely cause of the methemoglobinemia and kidney toxicity observed in this, and previous, studies in the pig. The phenolic sulfate of APAP, and the glutathione-derived metabolites of the drug were only found as minor components (with the cysteinyl conjugate detected but not the mercapturate). Given its low sulfation, combined with significant capacity for N-deacetylation the pig may represent a poor translational model for toxicology studies for compounds undergoing significant metabolism by sulfation, or which contain amide bonds which when hydrolyzed to unmask an aniline lead to toxicity. However, the pig may provide a useful model where extensive amide hydrolysis is seen for drugs or environmental chemicals in humans, but not in, eg, the rat and dog which are the preclinical species normally employed for safety assessment.
Identification and Fine Mapping of qSCR4.01, a Novel Major QTL for Resistance to Puccinia polysora in Maize
Authors: Deng Ce , Lv Meng , Li Xueying , Zhao Xiaodi , Li Huimin , Li Zhimin , Tian Zhiqiang , Leonard April , Jaqueth Jennifer , Li Bailin , Hao Junjie , Ding Junqiang
Published: February 2020

Southern corn rust (SCR) is a prevalent foliar disease that can lead to severe yield losses in maize. Growing SCR-resistant varieties is the most effective way to control the disease. To identify major quantitative trait loci (QTLs) for SCR resistance, a recombinant inbred line population derived from a cross between CIMBL83 (resistant) and Lx9801 (susceptible) was analyzed. The resistance to SCR had high heritability within the population, and a major QTL on chromosome 4 (qSCR4.01), which can explain 48 to 65% of the total phenotypic variation, was consistently detected across multiple environments. Using a progeny-based fine-mapping strategy, we delimited qSCR4.01 to an interval of ∼770 kb. In contrast to other major QTLs for SCR resistance previously reported on the short arm of chromosome 10, qSCR4.01 is a novel QTL and, therefore, a desirable source of SCR resistance in maize breeding programs.
Enhanced Resistance toFusarium graminearumin Transgenic Arabidopsis Plants Expressing a Modified Plant Thionin
Authors: Hao Guixia , Bakker Matthew G. , Kim Hye-Seon
Published: February 2020

The fungal pathogen Fusarium graminearum causes Fusarium head blight (FHB) on wheat, barley, and other grains. FHB results in yield reductions and contaminates grain with trichothecene mycotoxins, which threaten food safety and food security. Innovative mechanisms for controlling FHB are urgently needed. We have previously shown that transgenic tobacco and citrus plants expressing a modified thionin (Mthionin) exhibited enhanced resistance toward several bacterial pathogens. The aim of this study was to investigate whether overexpression of Mthionin could be similarly efficacious against F. graminearum, and whether transgenic expression of Mthionin impacts the plant microbiome. Transgenic Arabidopsis plants expressing Mthionin were generated and confirmed. When challenged with F. graminearum, Mthionin-expressing plants showed less disease and fungal biomass in both leaves and inflorescences compared with control plants. When infiltrated into leaves, macroconidia of F. graminearum germinated at lower rates and produced less hyphal growth in Arabidopsis leaves expressing Mthionin. Moreover, marker genes related to defense signaling pathways were expressed at significantly higher levels after F. graminearum infection in Mthionin transgenic Arabidopsis plants. However, Mthionin expression did not appreciably alter the overall microbiome associated with transgenic plants grown under controlled conditions; across leaves and roots of Mthionin-expressing and control transgenic plants, only a few bacterial and fungal taxa differed, and differences between Mthionin transformants were of similar magnitude compared with control plants. In sum, our data indicate that Mthionin is a promising candidate to produce transgenic crops for reducing FHB severity and ultimately mycotoxin contamination.
Prenatal exposure of staphylococcal enterotoxin B attenuates the development and function of blood regulatory T cells to repeated staphylococcal enterotoxin B exposure in adult offspring rats
Authors: Gao Shu-xian , Sun Jing , Li Hui-hui , Chen Jie , Kashif Mohsin Raza , Zhou Ping , Wei Li , Zheng Qing-wei , Wu Li-gao , Guan Jun-chang
Published: February 2020

Introduction. Staphylococcal enterotoxin B (SEB) is an extensively studied super-antigen. A previous study by us suggested that SEB exposure during pregnancy could alter the percentage of CD4+ and CD8+ T cells in the peripheral blood of neonatal offspring rats.

Aim. It is unknown whether SEB exposure during pregnancy can influence the development of regulatory T cells (Tregs) in the peripheral blood of neonatal offspring rats.

Methodology. Pregnant rats at gestational day 16 were intravenously injected with 15 µg SEB. Peripheral blood was acquired from neonatal offspring rats on days 1, 3 and 5 after delivery and from adult offspring rats for determination of Treg number by cytometry, cytokines by ELISA, and FoxP3 expression by real-time PCR and western blot.

Results. SEB given to pregnant rats significantly increased the absolute number of Tregs and the expression levels of FoxP3, IL-10 and TGF-β (P<0.05, P<0.01) in the peripheral blood of not only neonatal but also adult offspring rats. Furthermore, repeated SEB exposure in adult offspring rats significantly decreased the absolute number of Tregs (P<0.01), and the expression levels of FoxP3, IL-10 and TGF-β (P<0.05, P<0.01) in their peripheral blood.

Conclusion. Prenatal SEB exposure attenuates the development and function of Tregs to repeated SEB exposure in the peripheral blood of adult offspring rats.
Anti-cancer Drug Synergy Prediction in Understudied Tissues using Transfer Learning
Authors: Kim Yejin , Zheng Shuyu , Tang Jing , Zheng W. Jim , Li Zhao , Jiang Xiaoqian
Published: February 2020

Motivation

Exploring an exponentially increasing yet more promising space, high-throughput combinatorial drug screening has advantages in identifying cancer treatment options with higher efficacy without degradation in terms of safety. A key challenge is that accumulated number of observations in in-vitro drug responses varies greatly among different cancer types, where some tissues (such as bone and prostate) are understudied than the others. Thus, we aim to develop a drug synergy prediction model for understudied data-poor tissues as overcoming data scarcity problem.

Results

We collected a comprehensive set of genetic, molecular, phenotypic features for cancer cell lines from six different databases. We developed a drug synergy prediction model based on deep neural networks to integrate multi-modal input and utilize transfer learning from data-rich tissues to data-poor tissues. We showed improved accuracy in predicting drug synergy in understudied tissues without enough drug combination screening data nor after-treatment transcriptome. Our synergy prediction model can be used to rank synergistic drug combinations in understudied tissues and thus help prioritizing future in-vitro experiments.

Availability and Implementation

Our algorithm will be publicly available viahttps://github.com/yejinjkim/drug-synergy-prediction
A New Model to Determine the Personal Reference Interval of Tests in Laboratory Medicine: A Preliminary Study
Authors: Coskun Abdurrahman , serteser Mustafa , Cavusoglu Coskun , Kilercik Meltem , Unsal Ibrahim
Published: February 2020

“The authors have withdrawn this manuscript because they discovered errors in the equations that no longer support the findings given in the paper. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.”
Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group
Authors: Gorbalenya Alexander E. , Baker Susan C. , Baric Ralph S. , de Groot Raoul J. , Drosten Christian , Gulyaeva Anastasia A. , Haagmans Bart L. , Lauber Chris , Leontovich Andrey M , Neuman Benjamin W. , Penzar Dmitry , Perlman Stanley , Poon Leo L.M. , Samborskiy Dmitry , Sidorov Igor A. , Sola Isabel , Ziebuhr John
Published: February 2020

The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of theCoronaviridaefamily, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the speciesSevere acute respiratory syndrome-related coronavirusand designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.
Eicosanoid Inflammatory Mediators Are Robustly Associated with Blood Pressure in the General Population
Authors: Palmu Joonatan , Watrous Jeramie D. , Mercader Kysha , Havulinna Aki S. , Lagerborg Kim A. , Salosensaari Aaro , Inouye Mike , Larson Martin G. , Rong Jian , Vasan Ramachandran S. , Lahti Leo , Andres Allen , Cheng Susan , Jousilahti Pekka , Salomaa Veikko , Jain Mohit , Niiranen Teemu J.
Published: February 2020

Epidemiological and animal studies have associated systemic inflammation with blood pressure (BP). However, the mechanistic factors linking inflammation and BP remain unknown. Fatty acid derived eicosanoids serve as mediators of inflammation and have been suggested to also regulate renal vascular tone, peripheral resistance, renin-angiotensin system, and endothelial function. We therefore hypothesize that specific pro- and anti-inflammatory eicosanoids are linked with BP. We studied a population sample of 8099 FINRISK 2002 participants randomly drawn from the Finnish population register (53% women, mean age 48±13 years) and, for external validation, a sample of 2859 Framingham Heart Study (FHS) Offspring study participants (55% women, mean age 66±9 years). Using non-targeted liquid chromatography-mass spectrometry, we profiled 545 distinct high-quality eicosanoids and related oxylipin mediators in plasma. Adjusting for conventional hypertension risk factors, we observed 187 (34%) metabolites that were significantly associated with systolic BP (P < Bonferroni-corrected threshold of 0.05/545). We used forward selection linear regression modeling in FINRISK to define a general formula for individual eicosanoid risk score. Individuals of the top risk score quartile in FINRISK had a 9.0 mmHg (95% CI 8.0-10.1) higher systolic BP compared with individuals in the lowest quartile in fully adjusted models. Observed metabolite associations were consistent across FINRISK and FHS. In conclusion, plasma eicosanoids demonstrate strong associations with BP in the general population. As eicosanoid compounds affect numerous physiological processes that are central to BP regulation, they may offer new insights regarding pathogenesis of hypertension, as well as serve as potential targets for therapeutic intervention.
The parotid secretory protein BPIFA2 is a salivary surfactant that affects LPS action
Authors: Nandula Seshagiri R. , Huxford Ian , Wheeler Thomas T. , Aparicio Conrado , Gorr Sven-Ulrik
Published: February 2020

Saliva plays important roles in the mastication, swallowing and digestion of food, speech and lubrication of oral mucosa, antimicrobial and anti-inflammatory activity and control of body temperature in grooming animals. The salivary protein BPIFA2 (BPI fold containing family A member 2; former names: Parotid Secretory Protein, PSP, SPLUNC2, C20orf70) is related to lipid-binding and LPS-binding proteins expressed in mucosa. Indeed, BPIFA2 binds LPS but the physiological role of BPIFA2 remains to be determined. To address this question,Bpifa2knockout (Bpifa2tm1(KOMP)Vlcg) (KO) mice were phenotyped with a special emphasis on saliva and salivary glands. Saliva collected from KO mice was less able to spread on a hydrophobic surface than wild-type saliva and the surface tension of KO saliva was close to that of water. These data suggest that BPIFA2 is a salivary surfactant that is mainly responsible for the low surface tension of mouse saliva. The reduced surfactant activity of KO saliva did not affect consumption of dry food or grooming, but saliva from KO mice contained less LPS than wild-type saliva. Indeed, mice lacking BPIFA2 responded to ingested LPS with an increased stool frequency, suggesting that BPIFA2 plays a role in the solubilization and activity of ingested LPS. Consistent with these findings, BPIFA2-depleted mice also showed increased insulin secretion and metabolomic changes that were consistent with a mild endotoxemia. These results support the distal physiological function of a salivary protein and reinforce the connection between oral biology and systemic disease.
Rapid Prototyping of Wireframe Scaffolded DNA Origami using ATHENA
Authors: Jun Hyungmin , Wang Xiao , Bricker William P. , Jackson Steve , Bathe Mark
Published: February 2020

Wireframe DNA origami assemblies can now be programmed automatically from the “top-down” using simple wireframe target geometries, or meshes, in 2D and 3D geometries using either rigid, six-helix bundle (6HB) or more compliant, two-helix bundle (2HB or DX) edges. While these assemblies have numerous applications in nanoscale materials fabrication due to their nanoscale spatial addressability and high degree of customization, no easy-to-use graphical user interface software yet exists to deploy these algorithmic approaches within a single, stand-alone interface. Here, we present ATHENA, an open-source software package with a graphical user interface that automatically renders single-stranded DNA scaffold routing and staple strand sequences for any target wireframe DNA origami in 2D or 3D using 2HB or 6HB edges. ATHENA enables external editing of sequences using the popular tool caDNAno, demonstrated here using asymmetric nanoscale positioning of gold nanoparticles, as well as atomic-level models for molecular dynamics, coarse-grained dynamics, or other computational chemistry simulation approaches. We anticipate ATHENA will significantly reduce the barrier for non-specialists to perform wireframe DNA origami sequence design and fabrication for custom applications in materials science, nanotechnology, therapeutics, and other areas.
Nyctinastic thallus movement in the liverwortMarchantia polymorphais regulated by a circadian clock
Authors: Lagercrantz Ulf , Billhardt Anja , Rousku Sabine N. , Eklund D. Magnus
Published: February 2020

The circadian clock coordinates an organism’s growth, development and physiology with environmental factors. One illuminating example is the rhythmic growth of hypocotyls and cotyledons inArabidopsis thaliana. Such daily oscillations in leaf position are often referred to as sleep movements or nyctinasty. Here, we report that plantlets of the liverwortMarchantia polymorphashow analogous rhythmic movements of thallus lobes, and that the circadian clock controls this rhythm, with auxin a likely meditator. The mechanisms of this circadian clock are partly conserved as compared to angiosperms, with homologs to the core clock genesPRR,RVEandTOC1forming a core transcriptional feedback loop also inM. polymorpha.
Pathogen community composition and co-infection patterns in a wild community of rodents
Authors: Abbate Jessica L. , Galan Maxime , Razzauti Maria , Sironen Tarja , Voutilainen Liina , Henttonen Heikki , Gasqui Patrick , Cosson Jean-François , Charbonnel Nathalie
Published: February 2020

Rodents are major reservoirs of pathogens that can cause disease in humans and livestock. It is therefore important to know what pathogens naturally circulate in rodent populations, and to understand the factors that may influence their distribution in the wild. Here, we describe the occurrence and distribution patterns of a range of endemic and zoonotic pathogens circulating among rodent communities in northern France. The community sample consisted of 713 rodents, including 11 host species from diverse habitats. Rodents were screened for virus exposure (hantaviruses, cowpox virus, Lymphocytic choriomeningitis virus, Tick-borne encephalitis virus) using antibody assays. Bacterial communities were characterized using 16S rRNA amplicon sequencing of splenic samples. Multiple correspondence (MCA), multiple regression and association screening (SCN) analyses were used to determine the degree to which extrinsic factors (study year and site; host habitat, species, sex and age class) contributed to pathogen community structure, and to identify patterns of associations between pathogens within hosts. We found a rich diversity of bacterial genera, with 36 known or suspected to be pathogenic. We revealed that host species is the most important determinant of pathogen community composition, and that hosts that share habitats can have very different pathogen communities. Pathogen diversity and co-infection rates also vary among host species. Aggregation of pathogens responsible for zoonotic diseases suggests that some rodent species may be more important for transmission risk than others. Moreover, we detected positive associations between several pathogens, includingBartonella,Mycoplasmaspecies, Cowpox virus (CPXV) and hantaviruses, and these patterns were generally specific to particular host species. Altogether, our results suggest that host and pathogen specificity is the most important driver of pathogen community structure, and that interspecific pathogen-pathogen associations also depend on host species.
SpliceViNCI: Visualizing the splicing of non-canonical introns through recurrent neural networks
Authors: Dutta Aparajita , Singh Kusum Kumari , Anand Ashish
Published: February 2020

Most of the current computational models for splice junction prediction are based on the identification of canonical splice junctions. However, it is observed that the junctions lacking the consensus dimersGTandAGalso undergo splicing. Identification of such splice junctions, called the non-canonical splice junctions, is also essentially important for a comprehensive understanding of the splicing phenomenon. This work focuses on the identification of non-canonical splice junctions through the application of a bidirectional long short-term memory (BLSTM) network. Furthermore, we apply a back-propagation based (integrated gradient) and a perturbation based (occlusion) visualization techniques to extract the non-canonical splicing features learned by the model. The features obtained are validated with the existing knowledge from the literature. Integrated gradient extracts features that comprise contiguous nucleotides, whereas occlusion extracts features that are individual nucleotides distributed across the sequence.
Septins coordinate cell wall integrity and lipid metabolism in a sphingolipid-dependent process
Authors: Mela Alexander , Momany Michelle
Published: February 2020

During normal development and response to environmental stress, fungi must coordinate synthesis of the cell wall and plasma membrane. Septins, small cytoskeletal GTPases, colocalize with membrane sterol-rich regions and facilitate recruitment of cell wall synthases during dynamic wall remodeling. In this study we show that null mutants missing anAspergillus nidulanscore septin present in hexamers and octamers (ΔaspAcdc11, ΔaspBcdc3, or ΔaspCcdc12) are sensitive to multiple cell wall-disturbing agents known to activate the cell wall integrity MAPK pathway and that this sensitivity can be remediated by osmotic support. The null mutant missing the octamer-exclusive core septin (ΔaspDcdc10) showed similar osmotic-remedial sensitivity, but only to a single cell wall-disturbing agent and the null mutant missing the noncore septin (ΔaspE) showed very mild osmotic-remedial sensitivity to a different single agent. Representative core septin null mutants showed changes in cell wall polysaccharide composition, organization, and chitin synthase localization. Double mutant analysis withΔmpkAsuggested core septins interact with the cell wall integrity pathway. Null mutants missing any of the five septins were resistant to ergosterol-disrupting agents. The ΔaspAcdc11, ΔaspBcdc3, and ΔaspCcdc12mutants showed increased sensitivity to sphingolipid-disrupting agents that was remediated by addition of exogenous phytosphingosine. Representative core septins were mislocalized after treatment with sphingolipid-disrupting agents, but not after treatment with ergosterol-disrupting agents. When challenged with both sphingolipid-disturbing and cell wall-disturbing agents in combination, remediation of the lipid defect restored proper growth to ΔaspAcdc11, ΔaspBcdc3, and ΔaspCcdc12, but remediation of the cell wall defect did not. Our data suggest that the core hexamer and octamer septins are involved in cell wall integrity signaling with the noncore septin playing a minor role; that all five septins are involved in monitoring ergosterol metabolism; that the hexamer septins are required for sphingolipid metabolism; and that septins require sphingolipids to coordinate the cell wall integrity response.