bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Asparagine Endopeptidase in Mediating Wild-Type p53 Inactivation of Glioblastoma
Authors: Lin Yingying , Liao Keman , Miao Yifeng , Qian Zhongrun , Fang Zhaoyuan , Yang Xi , Nie Quanmin , Jiang Gan , Liu Jianhua , Yu Yiyi , Wan Jieqing , Zhang Xiaohua , Hu Yaomin , Jiang Jiyao , Qiu Yongming
Published: July 2019

Background

Isocitrate dehydrogenase wild-type (WT) glioblastoma (GBM) accounts for 90% of all GBMs, yet only 27% of isocitrate dehydrogenase WT-GBMs have p53 mutations. However, the tumor surveillance function of WT-p53 in GBM is subverted by mechanisms that are not fully understood.

Methods

We investigated the proteolytic inactivation of WT-p53 by asparaginyl endopeptidase (AEP) and its effects on GBM progression in cancer cells, murine models, and patients’ specimens using biochemical and functional assays. The sera of healthy donors (n = 48) and GBM patients (n = 20) were examined by enzyme-linked immunosorbent assay. Furthermore, effects of AEP inhibitors on GBM progression were evaluated in murine models (n = 6–8 per group). The statistical significance between groups was determined using two-tailed Student t tests.

Results

We demonstrate that AEP binds to and directly cleaves WT-p53, resulting in the inhibition of WT-p53-mediated tumor suppressor function in both tumor cells and stromal cells via extracellular vesicle communication. High expression of uncleavable p53-N311A-mutant rescue AEP-induced tumorigenesis, proliferation, and anti-apoptotic abilities. Knock down or pharmacological inhibition of AEP reduced tumorigenesis and prolonged survival in murine models. However, overexpression of AEP promoted tumorigenesis and shortened the survival time. Moreover, high AEP levels in GBM tissues were associated with a poor prognosis of GBM patients (n = 83; hazard ratio = 3.94, 95% confidence interval = 1.87 to 8.28; P < .001). A correlation was found between high plasma AEP levels and a larger tumor size in GBM patients (r = 0.6, P = .03), which decreased dramatically after surgery.

Conclusions

Our results indicate that AEP promotes GBM progression via inactivation of WT-p53 and may serve as a prognostic and therapeutic target for GBM.
Rare case of bilateral anterolateral and symmetrical bowing of tibia successfully treated with a distal tibial opening wedge osteotomy
Authors: Miranda Margarida , Afonso Carolina , Martins Carla , Carvalho João , Campos Armando
Published: July 2019

The anterolateral bowing of the tibia is closely associated with the development of its pseudarthrosis. Roughly, all deformities are unilateral so the shortening and angulation are easy to identify. We present a 6-year-old boy with an exuberant bilateral anterolateral bowing of tíbia. He has short stature, disturbed gait and callosity at the lateral border of the foot. Deformity was successfully treated by opening wedge tibia osteotomy and filled the remaining gap with structural fibular graft. It was fixed with two crossed K-wires and cast immobilization for 6 weeks. We decided to correct it before skeletal maturity due to the significant disturbance of the gait and esthetic impairment. It was obtained a satisfactory morphological and functional result with a simple and fast technique.
Appendiceal mucocele secondary to torsion in an asymptomatic patient
Authors: Aggarwal Nikhil , Bhargava Aman
Published: July 2019

Torsion of the appendix associated with an appendiceal mucocele is extremely rare with just a few published cases. To our knowledge, we report the first case of appendiceal mucocele secondary to torsion in an asymptomatic patient. In this case, numerous adhesions were found attaching the tip of the appendix mucocele to the peritoneum contributing to torsion as well as a lack of evidence for appendiceal neoplasm. Complications of appendiceal mucocele include obstruction, intussusception and pseudomyxoma peritonei, which has a particularly poor prognosis. Clinicians should, therefore, consider prompt surgical resection for definitive histopathological diagnosis and management.
Autopolyploidization in switchgrass alters phenotype and flowering time via epigenetic and transcription regulation
Authors: Yan Haidong , Bombarely Aureliano , Xu Bin , Wu Bingchao , Frazier Taylor P , Zhang Xinquan , Chen Jing , Chen Peilin , Sun Min , Feng Guangyan , Wang Chengran , Cui Chenming , Li Qi , Zhao Bingyu , Huang Linkai
Published: July 2019

Polyploidization is a significant source of genomic and organism diversification during plant evolution, and leads to substantial alterations in plant phenotypes and natural fitness. To help understand the phenotypic and molecular impacts of autopolyploidization, we conducted epigenetic and full-transcriptomic analyses of a synthesized autopolyploid accession of switchgrass (Panicum virgatum) in order to interpret the molecular and phenotypic changes. We found that mCHH levels were decreased in both genic and transposable element (TE) regions, and that TE methylation near genes was decreased as well. Among 142 differentially expressed genes involved in cell division, cellulose biosynthesis, auxin response, growth, and reproduction processes, 75 of them were modified by 122 differentially methylated regions, 10 miRNAs, and 15 siRNAs. In addition, up-regulated PvTOE1 and suppressed PvFT probably contribute to later flowering time of the autopolyploid. The expression changes were probably associated with modification of nearby methylation sites and siRNAs. We also experimentally demonstrated that expression levels of PvFT and PvTOE1 were regulated by DNA methylation, supporting the link between alterations in methylation induced by polyploidization and the phenotypic changes that were observed. Collectively, our results show epigenetic modifications in synthetic autopolyploid switchgrass for the first time, and support the hypothesis that polyploidization-induced methylation is an important cause of phenotypic alterations and is potentially important for plant evolution and improved fitness.
Axial anatomy of the leaf midrib provides new insights into the hydraulic architecture and cavitation patterns of Acer pseudoplatanus leaves
Authors: Lechthaler Silvia , Colangeli Pierluigi , Gazzabin Moira , Anfodillo Tommaso
Published: July 2019

The structure of leaf veins is typically described by a hierarchical scheme (e.g. midrib, 1st order, 2nd order), which is used to predict variation in conduit diameter from one order to another whilst overlooking possible variation within the same order. We examined whether xylem conduit diameter changes within the same vein order, with resulting consequences for resistance to embolism. We measured the hydraulic diameter (Dh), and number of vessels (VN) along the midrib and petioles of leaves of Acer pseudoplatanus, and estimated the leaf area supplied (Aleaf-sup) at different points of the midrib and how variation in anatomical traits affected embolism resistance. We found that Dh scales with distance from the midrib tip (path length, L) with a power of 0.42, and that VN scales with Aleaf-sup with a power of 0.66. Total conductive area scales isometrically with Aleaf-sup. Embolism events along the midrib occurred first in the basipetal part and then at the leaf tip where vessels are narrower. The distance from the midrib tip is a good predictor of the variation in vessel diameter along the 1st order veins in A. pseudoplatanus leaves and this anatomical pattern seems to have an effect on hydraulic integrity since wider vessels at the leaf base embolize first.
A MIF-like effector suppresses plant immunity and facilitates nematode parasitism by interacting with plant annexins
Authors: Zhao Jianlong , Li Lijuan , Liu Qian , Liu Pei , Li Shuang , Yang Dan , Chen Yongpan , Pagnotta Sophie , Favery Bruno , Abad Pierre , Jian Heng
Published: July 2019

The plant-parasitic nematode Meloidogyne incognita secretes MIF-like proteins into plant tissues, and MiMIF-2 interacts with two plant annexins to suppress plant immune responses and promote parasitism.
Proline oxidation fuels mitochondrial respiration during dark-induced leaf senescence in Arabidopsis thaliana
Authors: Launay Alban , Cabassa-Hourton Cécile , Eubel Holger , Maldiney Régis , Guivarc’h Anne , Crilat Emilie , Planchais Séverine , Lacoste Jérôme , Bordenave-Jacquemin Marianne , Clément Gilles , Richard Luc , Carol Pierre , Braun Hans-Peter , Lebreton Sandrine , Savouré Arnould
Published: July 2019

Oxidation of proline in response to dark-induced senescence in Arabidopsis leaves allows this amino acid to be used as an alternative respiratory substrate and contributes to the production of glutamate and energy that can be used for nutrient remobilization.
The Study of SALL4 Gene and BMI-1 Gene Expression in Acute Myeloid Leukemia Patients
Authors: Swelem Rania Shafik , Elneely Dalia Abdelmoety , Shehata Ahmed Abdel Rahman
Published: July 2019

Background

In acute myeloid leukemia (AML), many genes have been studied as prognostic markers. SALL4 is expressed constitutively in human leukemia cell lines and primary AML cells. BMI-1 is expressed highly in purified hematopoietic stem cells (HSCs), and its expression declines with differentiation.

Objective

To study the expression levels of SALL4 and BMI-1 and their clinical significance in patients with AML.

Methods

The study was performed with 60 patients newly diagnosed with AML and 50 control individuals. SALL4 and BMI-1 expression detection were performed using real-time polymerase chain reaction (PCR).

Results

The expression of SALL4 and BMI-1 was significantly higher in cases of AML and showed a strong association with failure to achieve complete remission (CR) or with relapse (P = .02, P = .03, respectively). In multivariate analysis, these genes were the most powerful independent predictors of poor prognosis (P = .01 for SALL4, P = .02 for BMI-1).

Conclusion

SALL4 and BMI-1 are significant prognostic factors in AML and could be strong targets for novel types of therapy.
The Influence of the Test Operator on the Expressive Power of PDL-like Logics
Authors: Nguyen Linh Anh
Published: July 2019

Berman and Paterson proved that test-free propositional dynamic logic (PDL) is weaker than PDL. One would raise questions: does a similar result also hold for extensions of PDL? For example, is test-free converse-PDL (CPDL) weaker than CPDL? In what circumstances the test operator can be eliminated without reducing the expressive power of a PDL-based logical formalism? These problems have not yet been studied. As the description logics $\mathcal{ALC}_{trans}$ and $\mathcal{ALC}_{reg}$ are, respectively, variants of test-free PDL and PDL, there is a concept of $\mathcal{ALC}_{reg}$ that is not equivalent to any concept of $\mathcal{ALC}_{trans}$. Generalizing this, we prove that there is a concept of $\mathcal{ALC}_{reg}$ that is not equivalent to any concept of the logic that extends $\mathcal{ALC}_{trans}$ with inverse roles, nominals, qualified number restrictions, the universal role and local reflexivity of roles. We also provide some results for the case with RBoxes and TBoxes. One of them states that tests can be eliminated from TBoxes of the deterministic Horn fragment of $\mathcal{ALC}_{reg}$.
The Type II superluminous SN 2008es at late times: near-infrared excess and circumstellar interaction
Authors: Bhirombhakdi Kornpob , Chornock Ryan , Miller Adam A , Filippenko Alexei V , Cenko S Bradley , Smith Nathan
Published: July 2019

SN 2008es is one of the rare cases of a Type II superluminous supernova (SLSN), showing no narrow features in its early-time spectra, and therefore, its powering mechanism is under debate between circumstellar interaction (CSI) and magnetar spin-down. Late-time data are required for better constraints. We present optical and near-infrared (NIR) photometry obtained from Gemini, Keck, and Palomar Observatories from 192 to 554 d after explosion. Only broad H α emission is detected in a Gemini spectrum at 288 d. The line profile exhibits red-wing attenuation relative to the early-time spectrum. In addition to the cooling SN photosphere, an NIR excess with blackbody temperature ∼1500 K and radius ∼1016 cm is observed. This evidence supports dust condensation in the cool dense shell being responsible for the spectral evolution and NIR excess. We favour CSI, with ∼2–3 M⊙ of circumstellar material (CSM) and ∼10–20 M⊙ of ejecta, as the powering mechanism, which still dominates at our late-time epochs. Both models of uniform density and steady wind fit the data equally well, with an effective CSM radius ∼1015 cm, supporting the efficient conversion of shock energy to radiation by CSI. A low amount (≲0.4 M⊙) of 56Ni is possible but cannot be verified yet, since the light curve is dominated by CSI. The magnetar spin-down powering mechanism cannot be ruled out, but is less favoured because it overpredicts the late-time fluxes and may be inconsistent with the presence of dust.
Higher order harmonics in the light curves of eccentric planetary systems
Authors: Penoyre Zephyr , Sandford Emily
Published: July 2019

As a planet orbits, it causes periodic modulations in the light curve of its host star. Due to the combined effects of the planet raising tides on the host star, relativistic beaming of the starlight, and reflection of light off the planet’s surface, these modulations occur at the planet’s orbital frequency, as well as integer multiples of this frequency. In particular, planets on eccentric orbits induce third and higher order harmonics in the stellar light curve which cannot be explained by circular-orbit models. Even at moderate eccentricities, such as those typical of Solar system planets, these harmonics are detectable in current and future photometric data. We present an analysis of the harmonics caused by tides, beaming, and reflection in eccentric planetary systems. We explore the dependence of these signals on the parameters of the system, and we discuss prospects for current and future observations of these signals, particularly by the NASA TESS mission. Finally, we present publicly available code for computation of light curves with tidal, beaming, and reflection signals, oot.
ERQs are the BOSS of quasar samples: the highest velocity [O iii] quasar outflows
Authors: Perrotta S , Hamann F , Zakamska N L , Alexandroff R M , Rupke D , Wylezalek D
Published: July 2019

We investigate extremely red quasars (ERQs), a remarkable population of heavily reddened quasars at redshift z ∼ 2−3 that might be caught during a short-lived ‘blow-out’ phase of quasar/galaxy evolution. We perform a near-IR observational campaign using Keck/NIRSPEC, VLT/X-shooter, and Gemini/GNIRS to measure rest-frame optical spectra of 28 ERQs with median infrared luminosity 〈log L(erg s−1)〉 ∼ 46.2. They exhibit the broadest and most blueshifted [O iii] λ4959,5007 emission lines ever reported, with widths (w90) ranging between 2053 and 7227 km s−1, and maximum outflow speeds (v98) up to 6702 km s−1. ERQs on average have [O iii] outflows velocities about three times larger than those of luminosity-matched blue quasar samples. This discrepancy can be explained by a strong correlation between [O iii] kinematics and i–W3 colour, and not by radio loudness, or higher Eddington ratios. We estimate for these objects that at least 3–5 per cent of their bolometric luminosity is being converted into the kinetic power of the observed wind. Our results reveal that ERQs have the potential to strongly affect the evolution of host galaxies.
BAT AGN Spectroscopic Survey – XVII. The parsec-scale jet properties of the ultrahard X-ray-selected local AGNs
Authors: Baek Junhyun , Chung Aeree , Schawinski Kevin , Oh Kyuseok , Wong O Ivy , Koss Michael , Ricci Claudio , Trakhtenbrot Benny , Smith Krista Lynne , Ueda Yoshihiro
Published: July 2019

We have performed a very long baseline interferometry (VLBI) survey of local (z < 0.05) ultrahard X-ray (14–195 keV) selected active galactic nuclei (AGNs) from the Swift Burst Alert Telescope (BAT) using KVN, KaVA, and VLBA. We first executed fringe surveys of 142 BAT-detected AGNs at 15 or 22 GHz. Based on the result from the fringe surveys and archival data, we find 10/279 nearby AGN (∼4 per cent) VLBI have 22 GHz flux above 30 mJy. This implies that the X-ray AGNs with a bright nuclear jet are not common. Among these 10 radio-bright AGNs, we obtained 22 GHz VLBI imaging data of our own for four targets and reprocessed archival data for six targets. We find that, although our 10 AGNs observed with VLBI span a wide range of pc-scale morphological types, they lie on a tight linear relation between accretion luminosity and nuclear jet luminosity. Our result suggests that a powerful nuclear radio jet correlates with the accretion disc luminosity. We also probed the Fundamental Plane of black hole activity at VLBI scales (e.g. few milliarcsecond). The jet luminosity and size distribution among our sample roughly fit into the proposed AGN evolutionary scenario, finding powerful jets after the blow-out phase based on the Eddington ratio (λEdd)–hydrogen column density (NH) relation. In addition, we find some hints of gas inflow or galaxy–galaxy merger in the majority of our sample. This implies that gas supply via tidal interactions in galactic scale may help the central AGN to launch a powerful parsec-scale jet.
Synchrotron self absorption and the minimum energy of optically thick radio flares from stellar mass black holes
Authors: Fender Rob , Bright Joe
Published: July 2019

We consider the case of radio flares from black hole X-ray binaries in which the flare spectrum evolves from optically thick to optically thin, under the assumption that this is due to decreasing optical depth to synchrotron self absorption. We are able to place upper and lower limits on the size of the emitting region associated with a radio flare, and determine the synchrotron source magnetic field and energy as a function of size. The energy has a clear minimum which occurs close to the condition that the magnetic field derived from synchrotron self absorption equals that calculated from equipartition. This minimum energy estimate is independent of the rise time of the event, and so may be applied to any event for which the peak flux is measured and there is evidence for self-absorption. This is a much more accurate approach to minimum energy estimation than assuming expansion at close to the speed of light. We apply this method to four examples of optically thick radio flares and find that in each case either the filling factor of the synchrotron source is considerably less than unity, or the expansion speed is considerably less than the speed of light. The combination of unity filling factor and expansion speeds close to the speed of light is completely ruled out on energetic grounds for three of the four events we consider. The inferred slowed expansion is consistent with detailed modelling of such events which has been recently reported in the literature. The minimum power requirements associated with the flares are found to be ∼1036 erg s−1, which are easily accomodated in the context of stellar mass black hole accretion at near-Eddington levels, when these flares typically occur. However, the true jet power could still be orders of magnitude higher.
Compositional characterization of V-type candidate asteroids identified using the MOVIS catalogue
Authors: Medeiros H , de León J , Lazzaro D , Popescu M , Lorenzi V , Pinilla-Alonso N , Landsman Z , Rizos J L , Morate D
Published: July 2019

The main objective of this work is to compositionally analyse the visible to near-infrared spectra of a total of six V-type candidates identified using the MOVIS (Y-J) versus (J-Ks) colour–colour plot and located outside the Vesta collisional family. We obtained visible and near-infrared spectra of these asteroids using the 2.54m Isaac Newton Telescope, the 2.5m Nordic Optical Telescope, and the 3.58m Telescopio Nazionale Galileo, all located at the El Roque de Los Muchachos Observatory (La Palma, Spain), as well as the 3.0m NASA Infrared Telescope Facility, located at the Mauna Kea Observatory in Hawaii. We computed several diagnostic spectral parameters (slopes, band centres, band depths, band area ratio, or BAR) and compared them to the ones known for HED meteorites and (4) Vesta. The taxonomic classification confirmed five out of the six candidates as V-types, leading to an identification success rate about 83 per cent. In general, the spectral parameters obtained for the five V-types are in good agreement with those of HED meteorites and (4) Vesta. The exception is asteroid (2452) Lyot, a V-type in the outer belt, located very close to (1459) Magnya, but showing distinct [Wo] and [Fs] molar contents both from Magnya and Vesta, pointing toward a diogenitic compostion. We also studied the dependency of the BAR parameter on the way it is computed (removing or not the continuum), the spectral slope, and the last point used to delimit the right wing of the absorption band at 2 μm.
Relativistic Fe Kα line in the composite X-ray spectra of radio-loud active galactic nuclei
Authors: Hu Jingwei , Liu Zhu , Jin Chichuan , Yuan Weimin
Published: July 2019

While a broad Fe Kα emission line is generally found in the X-ray spectra of radio quiet (RQ) active galactic nuclei (AGNs), this feature, commonly thought to be broadened by the relativistic effects near the central black hole, appears to be rare in their radio loud (RL) counterparts. In this paper, we carry out a detailed study of the ensemble property of the X-ray spectra, focusing on the Fe line, of 97 RL AGNs by applying the spectral stacking method to the spectra obtained with XMM–Newton. For comparison, the same analysis is also performed for 193 RQ AGNs. Both a narrow and a broad component of the Fe Kα line are detected at high significance in the stacked spectra of both samples. The broad lines can be well fitted with relativistically broadened line profiles. Our results suggest that, as in their RQ counterparts, a relativistic Fe line component is commonly present in RL AGNs, though it may not be detected unambiguously in individual objects with spectra of relatively low signal to noise. We try to constrain the average spin of the black holes for both the RL and RQ AGN samples by modelling their composite Fe line spectral profiles with relativistic disc line models. For the RL sample, the average spin is loosely constrained and a wide range is allowed except for very fast spins (<0.78, 90 per cent confidence), while for the RQ sample, it is constrained to be low or moderate (<0.24). We conclude that the more precise measurement of the black hole spins in RL AGNs has to await for the advent of future high-throughput X-ray telescopes.
A physical model for [C ii] line emission from galaxies
Authors: Ferrara A , Vallini L , Pallottini A , Gallerani S , Carniani S , Kohandel M , Decataldo D , Behrens C
Published: July 2019

A tight relation between the [C ii] 158 $\mu$m line luminosity and star formation rate is measured in local galaxies. At high redshift (z > 5), though, a much larger scatter is observed, with a considerable (15–20 per cent) fraction of the outliers being [C ii]-deficient. Moreover, the [C ii] surface brightness ($\Sigma_{\rm [C\, \small {II}]}$) of these sources is systematically lower than expected from the local relation. To clarify the origin of such [C ii]-deficiency, we have developed an analytical model that fits local [C ii] data and has been validated against radiative transfer simulations performed with cloudy. The model predicts an overall increase of $\Sigma_{\rm [C\, \small {II}]}$ with ΣSFR. However, for ΣSFR ${\gtrsim} 1 \, \mathrm{M}_\odot \,{\rm yr}^{-1}\,{\rm kpc}^{-2}$, $\Sigma_{\rm [C\, \small {II}]}$ saturates. We conclude that underluminous [C ii] systems can result from a combination of three factors: (a) large upward deviations from the Kennicutt–Schmidt relation (κs ≫ 1), parametrized by the ‘burstiness’ parameter κs; (b) low metallicity; (c) low gas density, at least for the most extreme sources (e.g. CR7). Observations of [C ii] emission alone cannot break the degeneracy among the above three parameters; this requires additional information coming from other emission lines (e.g. [O iii]88 $\mu$m, C iii]1909 Å, CO lines). Simple formulae are given to interpret available data for low- and high-z galaxies.
Fast radio burst dispersion measures and rotation measures and the origin of intergalactic magnetic fields
Authors: Hackstein S , Brüggen M , Vazza F , Gaensler B M , Heesen V
Published: July 2019

We investigate the possibility of measuring intergalactic magnetic fields using the dispersion measures and rotation measures of fast radio bursts. With Bayesian methods, we produce probability density functions for values of these measures. We distinguish between contributions from the intergalactic medium, the host galaxy, and the local environment of the progenitor. To this end, we use constrained, magnetohydrodynamic simulations of the local Universe to compute lines-of-sight integrals from the position of the Milky Way. In particular, we differentiate between predominantly astrophysical and primordial origins of magnetic fields in the intergalactic medium. We test different possible types of host galaxies and probe different distribution functions of fast radio burst progenitor locations inside the host galaxy. Under the assumption that fast radio bursts are produced by magnetars, we use analytic predictions to account for the contribution of the local environment. We find that less than 100 fast radio bursts from magnetars in stellar-wind environments hosted by starburst dwarf galaxies at redshift z ≳ 0.5 suffice to discriminate between predominantly primordial and astrophysical origins of intergalactic magnetic fields. However, this requires the contribution of the Milky Way to be removed with a precision of ≈1 rad m−2. We show the potential existence of a subset of fast radio bursts whose rotation measures carry information on the strength of the intergalactic magnetic field and its origins.
Generation of a caged lentiviral vector through an unnatural amino acid for photo-switchable transduction
Authors: Wang Yan , Li Shuai , Tian Zhenyu , Sun Jiaqi , Liang Shuobin , Zhang Bo , Bai Lu , Zhang Yuanjie , Zhou Xueying , Xiao Sulong , Zhang Qiang , Zhang Lihe , Zhang Chuanling , Zhou Demin
Published: July 2019

Application of viral vectors in gene delivery is attracting widespread attention but is hampered by the absence of control over transduction, which may lead to non-selective transduction with adverse side effects. To overcome some of these limitations, we proposed an unnatural amino acid aided caging–uncaging strategy for controlling the transduction capability of a viral vector. In this proof-of-principle study, we first expanded the genetic code of the lentiviral vector to incorporate an azido-containing unnatural amino acid (Nϵ-2-azidoethyloxycarbonyl-l-lysine, NAEK) site specifically within a lentiviral envelope protein. Screening of the resultant vectors indicated that NAEK incorporation at Y77 and Y116 was capable of inactivating viral transduction upon click conjugation with a photo-cleavable chemical molecule (T1). Exposure of the chimeric viral vector (Y77-T1) to UVA light subsequently removed the photo-caging group and restored the transduction capability of lentiviral vector both in vitro and in vivo. Our results indicate that the use of the photo-uncage activation procedure can reverse deactivated lentiviral vectors and thus enable regulation of viral transduction in a switchable manner. The methods presented here may be a general approach for generating various switchable vectors that respond to different stimulations and adapt to different viral vectors.
Targeted short read sequencing and assembly of re-arrangements and candidate gene loci provide megabase diplotypes
Authors: Shin GiWon , Greer Stephanie U , Xia Li C , Lee HoJoon , Zhou Jun , Boles T Christian , Ji Hanlee P
Published: July 2019

The human genome is composed of two haplotypes, otherwise called diplotypes, which denote phased polymorphisms and structural variations (SVs) that are derived from both parents. Diplotypes place genetic variants in the context of cis-related variants from a diploid genome. As a result, they provide valuable information about hereditary transmission, context of SV, regulation of gene expression and other features which are informative for understanding human genetics. Successful diplotyping with short read whole genome sequencing generally requires either a large population or parent-child trio samples. To overcome these limitations, we developed a targeted sequencing method for generating megabase (Mb)-scale haplotypes with short reads. One selects specific 0.1–0.2 Mb high molecular weight DNA targets with custom-designed Cas9–guide RNA complexes followed by sequencing with barcoded linked reads. To test this approach, we designed three assays, targeting the BRCA1 gene, the entire 4-Mb major histocompatibility complex locus and 18 well-characterized SVs, respectively. Using an integrated alignment- and assembly-based approach, we generated comprehensive variant diplotypes spanning the entirety of the targeted loci and characterized SVs with exact breakpoints. Our results were comparable in quality to long read sequencing.
Malaria.tools—comparative genomic and transcriptomic database for Plasmodium species
Authors: Tan Qiao Wen , Mutwil Marek
Published: July 2019

Malaria is a tropical parasitic disease caused by the Plasmodium genus, which resulted in an estimated 219 million cases of malaria and 435 000 malaria-related deaths in 2017. Despite the availability of the Plasmodium falciparum genome since 2002, 74% of the genes remain uncharacterized. To remedy this paucity of functional information, we used transcriptomic data to build gene co-expression networks for two Plasmodium species (P. falciparum and P. berghei), and included genomic data of four other Plasmodium species, P. yoelii, P. knowlesi, P. vivax and P. cynomolgi, as well as two non-Plasmodium species from the Apicomplexa, Toxoplasma gondii and Theileria parva. The genomic and transcriptomic data were incorporated into the resulting database, malaria.tools, which is preloaded with tools that allow the identification and cross-species comparison of co-expressed gene neighbourhoods, clusters and life stage-specific expression, thus providing sophisticated tools to predict gene function. Moreover, we exemplify how the tools can be used to easily identify genes relevant for pathogenicity and various life stages of the malaria parasite. The database is freely available at www.malaria.tools.
Engineering DNA recognition and allosteric response properties of TetR family proteins by using a module-swapping strategy
Authors: Dimas Rey P , Jordan Benjamin R , Jiang Xian-Li , Martini Catherine , Glavy Joseph S , Patterson Dustin P , Morcos Faruck , Chan Clement T Y
Published: July 2019

The development of synthetic biological systems requires modular biomolecular components to flexibly alter response pathways. In previous studies, we have established a module-swapping design principle to engineer allosteric response and DNA recognition properties among regulators in the LacI family, in which the engineered regulators served as effective components for implementing new cellular behavior. Here we introduced this protein engineering strategy to two regulators in the TetR family: TetR (UniProt Accession ID: P04483) and MphR (Q9EVJ6). The TetR DNA-binding module and the MphR ligand-binding module were used to create the TetR-MphR. This resulting hybrid regulator possesses DNA-binding properties of TetR and ligand response properties of MphR, which is able to control gene expression in response to a molecular signal in cells. Furthermore, we studied molecular interactions between the TetR DNA-binding module and MphR ligand-binding module by using mutant analysis. Together, we demonstrated that TetR family regulators contain discrete and functional modules that can be used to build biological components with novel properties. This work highlights the utility of rational design as a means of creating modular parts for cell engineering and introduces new possibilities in rewiring cellular response pathways.
Determinants of change in arterial stiffness over 5 years in early chronic kidney disease
Authors: McIntyre Natasha J , Shardlow Adam , Fluck Richard J , McIntyre Christopher W , Taal Maarten W
Published: July 2019

Background

Arterial stiffness (AS) is an established and potentially modifiable risk factor for cardiovascular disease associated with chronic kidney disease (CKD). There have been few studies to evaluate the progression of AS over time or factors that contribute to this, particularly in early CKD. We therefore investigated AS over 5 years in an elderly population with CKD Stage 3 cared for in primary care.

Methods

A total of 1741 persons with an estimated glomerular filtration rate of 30–59 mL/min/1.73 m2 underwent detailed clinical and biochemical assessment at baseline and Years 1 and 5. Carotid to femoral pulse wave velocity (PWV) was measured to assess AS using a Vicorder device.

Results

970 participants had PWV assessments at baseline and 5 years. PWV increased significantly by a mean of 1.1 m/s (from 9.7 ± 1.9 to 10.8 ± 2.1 m/s). Multivariable linear regression analysis identified the following independent determinants of ΔPWV at Year 5: baseline age, diabetes status, baseline systolic blood pressure (SBP) and diastolic blood pressure, baseline PWV, ΔPWV at 1 year, ΔSBP over 5 years and Δserum bicarbonate over 5 years (R2 = 0.38 for the equation).

Conclusions

We observed a clinically significant increase in PWV over 5 years in a cohort with early CKD despite reasonably well-controlled hypertension. Measures of BP were identified as the most important modifiable determinant of ΔPWV, suggesting that interventions to prevent arterial disease should focus on improved control of BP, particularly in those who evidence an early increase in PWV. These hypotheses should now be tested in prospective trials.
Changes in China’s lakes: climate and human impacts
Authors: Tao Shengli , Fang Jingyun , Ma Suhui , Cai Qiong , Xiong Xinyu , Tian Di , Zhao Xia , Fang Leqi , Zhang Heng , Zhu Jiangling , Zhao Shuqing
Published: July 2019

Lakes have played a critical role in providing water and ecosystem services for people and other organisms in China for millennia. However, accelerating climate change and economic boom have resulted in unprecedented changes in these valuable lakes. Using Landsat images covering the entity of the country, we explored the changes in China’s lakes and the associated driving forces over the last 30 years (i.e. mid-1980s to 2015). We discovered that China’s lakes have changed with divergent regional trends: in the sparsely populated Tibetan Plateau, lakes are abundant and the lake area has increased dramatically from 38 596 to 46 831 km2 (i.e. increased by 8235 km2, or 21.3%), whereas, in the densely populated northern and eastern regions, lakes are relatively scarce and the lake area has decreased from 36 659 to 33 657 km2 (i.e. decreased by 3002 km2, or 8.2%). In particular, severe lake decreases occurred in the Mongolia-Xinjiang Plateau and the Eastern Plain (−2151 km2). Statistical analyses indicated that climate was the most important factor controlling lake changes in the Tibetan Plateau, the Yun-Gui Plateau and the Northeast Plain. However, the strength of climatic control on lake changes was low in the Eastern Plain and the Mongolia-Xinjiang Plateau, where human activities, e.g. impoldering, irrigation and mining, have caused serious impacts on lakes. Further lake changes will exacerbate regional imbalances between lake resources and population distribution, and thus may increase the risk of water-resource crises in China.
Effects of oats on gastrointestinal health as assessed by in vitro, animal, and human studies
Authors: Korczak Renee , Kocher Megan , Swanson Kelly S
Published: July 2019

Oats are uniquely nutritious, owing to their composition of bioactive compounds, lipids, and β-glucan. Scientific research has established that oats can improve diet quality, reduce cholesterol, regulate satiety, and protect against carcinogenesis in the colon; however, determining the effects of oats on gastrointestinal health and the gut microbiome is a newer, evolving area of research. To better understand the effects of oats on gastrointestinal health in humans, a literature review with predefined search criteria was conducted using the PubMed database and keywords for common gastrointestinal health outcomes. Moreover, to examine the gastrointestinal effects of oats across the scientific spectrum, a similar search strategy was executed to identify animal studies. In vitro studies were identified from the reference lists of human and animal studies. A total of 8 human studies, 19 animal studies, and 5 in vitro studies met the inclusion criteria for this review. The evidence in humans shows beneficial effects of oats on gastrointestinal health, with supportive evidence provided by in vitro and animal studies. The effective dose of oats varies by type, although an amount providing 2.5 to 2.9 g of β-glucan per day was shown to decrease fecal pH and alter fecal bacteria. For oat bran, 40 to 100 g/d was shown to increase fecal bacterial mass and short-chain fatty acids in humans. Differences in study design, methodology, and type of oats tested make valid comparisons difficult. The identification of best practices for the design of oat studies should be a priority in future research, as the findings will be useful for determining how oats influence specific indices of gastrointestinal health, including the composition of the human gut microbiome.
KOOLS–IFU: Kyoto Okayama Optical Low-dispersion Spectrograph with optical-fiber Integral Field Unit
Authors: Matsubayashi Kazuya , Ohta Kouji , Iwamuro Fumihide , Iwata Ikuru , Kambe Eiji , Tsutsui Hironori , Izumiura Hideyuki , Yoshida Michitoshi , Hattori Takashi
Published: July 2019

Observations of transient objects, such as short gamma-ray bursts and electromagnetic counterparts of gravitational wave sources, require prompt spectroscopy. To carry out prompt spectroscopy, we have developed an optical-fiber integral field unit (IFU) and connected it with an existing optical spectrograph, KOOLS. KOOLS–IFU was mounted on the Okayama Astrophysical Observatory 188 cm telescope. The fiber core and cladding diameters of the fiber bundle are 100 μm and 125 μm, respectively, and 127 fibers are hexagonally close-packed in the sleeve of the two-dimensional fiber array. We conducted test observations to measure the KOOLS–IFU performance and obtained the following conclusions: (1) the spatial sampling is ${2{^{\prime\prime}_{.}}34}$$\, \pm \,$${0{^{\prime\prime}_{.}}05}$ per fiber, and the total field of view is ${30{^{\prime\prime}_{.}}4}$$\, \pm \,$${0{^{\prime\prime}_{.}}65}$ with 127 fibers; (2) the observable wavelength and the spectral resolving power of the grisms of KOOLS are 4030–7310 Å and 400–600, 5020–8830 Å and 600–900, 4160–6000 Å and 1000–1200, and 6150–7930 Å and 1800–2400, respectively; and (3) the estimated limiting magnitude is 18.2–18.7 AB mag during 30 min exposure under optimal conditions.
Chloroplast-Localized Protoporphyrinogen IX Oxidase1 Is Involved in the Mitotic Cell Cycle in Arabidopsis
Authors: Li Jialong , Zhang Fan , Li Yuhong , Yang Weicai , Lin Rongcheng
Published: July 2019

Protoporphyrinogen IX oxidase1 (PPO1) catalyzes the oxidation of protoporphyrinogen IX to form protoporphyrin IX in the plastid tetrapyrrole biosynthesis pathway and is also essential for plastid RNA editing in Arabidopsis thaliana. The Arabidopsis ppo1-1 mutation was previously shown to be seedling lethal; however, in this study, we showed that the heterozygous ppo1-1/+ mutant exhibited reproductive growth defects characterized by reduced silique length and seed set, as well as aborted pollen development. In this mutant, the second mitotic division was blocked during male gametogenesis, whereas female gametogenesis was impaired at the one-nucleate stage. Before perishing at the seedling stage, the homozygous ppo1-1 mutant displayed reduced hypocotyl and root length, increased levels of reactive oxygen species accumulation and elevated cell death, especially under light conditions. Wild-type seedlings treated with acifluorfen, a PPO1 inhibitor, showed similar phenotypes to the ppo1-1 mutants, and both plants possessed a high proportion of 2C nuclei and a low proportion of 8C nuclei compared with the untreated wild type. Genome-wide RNA-seq analysis showed that a number of genes, including cell cycle-related genes, were differentially regulated by PPO1. Consistently, PPO1 was highly expressed in the pollen, anther, pistil and root apical meristem cells actively undergoing cell division. Our study reveals a role for PPO1 involved in the mitotic cell cycle during gametogenesis and seedling development.
CYP712K4 Catalyzes the C-29 Oxidation of Friedelin in the Maytenus ilicifolia Quinone Methide Triterpenoid Biosynthesis Pathway
Authors: Bicalho Keylla U , Santoni Mariana M , Arendt Philipp , Zanelli Cleslei F , Furlan Maysa , Goossens Alain , Pollier Jacob
Published: July 2019

The native Brazilian plant Maytenus ilicifolia accumulates a set of quinone methide triterpenoids with important pharmacological properties, of which maytenin, pristimerin and celastrol accumulate exclusively in the root bark of this medicinal plant. The first committed step in the quinone methide triterpenoid biosynthesis is the cyclization of 2,3-oxidosqualene to friedelin, catalyzed by the oxidosqualene cyclase friedelin synthase (FRS). In this study, we produced heterologous friedelin by the expression of M. ilicifolia FRS in Nicotiana benthamiana leaves and in a Saccharomyces cerevisiae strain engineered using CRISPR/Cas9. Furthermore, friedelin-producing N. benthamiana leaves and S. cerevisiae cells were used for the characterization of CYP712K4, a cytochrome P450 from M. ilicifolia that catalyzes the oxidation of friedelin at the C-29 position, leading to maytenoic acid, an intermediate of the quinone methide triterpenoid biosynthesis pathway. Maytenoic acid produced in N. benthamiana leaves was purified and its structure was confirmed using high-resolution mass spectrometry and nuclear magnetic resonance analysis. The three-step oxidation of friedelin to maytenoic acid by CYP712K4 can be considered as the second step of the quinone methide triterpenoid biosynthesis pathway, and may form the basis for further discovery of the pathway and heterologous production of friedelanes and ultimately quinone methide triterpenoids.
CFM9, a Mitochondrial CRM Protein, Is Crucial for Mitochondrial Intron Splicing, Mitochondria Function and Arabidopsis Growth and Stress Responses
Authors: Lee Kwanuk , Park Su Jung , Park Youn-Il , Kang Hunseung
Published: July 2019

Although the importance of chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins has been established for chloroplast RNA metabolism and plant development, the functional role of CRM proteins in mitochondria remains largely unknown. Here, we investigated the role of a mitochondria-targeted CRM protein (At3g27550), named CFM9, in Arabidopsis thaliana. Confocal analysis revealed that CFM9 is localized in mitochondria. The cfm9 mutant exhibited delayed seed germination, retarded growth and shorter height compared with the wild type under normal conditions. The growth-defect phenotypes were more manifested upon high salinity, dehydration or ABA application. Complementation lines expressing CFM9 in the mutant background fully recovered the wild-type phenotypes. Notably, the mutant had abnormal mitochondria, increased hydrogen peroxide and reduced respiration activity, implying that CFM9 is indispensable for normal mitochondrial function. More important, the splicing of many intron-containing genes in mitochondria was defective in the mutant, suggesting that CFM9 plays a crucial role in the splicing of mitochondrial introns. Collectively, our results provide clear evidence emphasizing that CFM9 is an essential factor in the splicing of mitochondrial introns, which is crucial for mitochondrial biogenesis and function and the growth and development of Arabidopsis.
Response Regulators 9 and 10 Negatively Regulate Salinity Tolerance in Rice
Authors: Wang Wei-Chen , Lin Te-Che , Kieber Joseph , Tsai Yu-Chang
Published: July 2019

Cytokinins are involved in the regulation of many plant growth and development processes, and function in response to abiotic stress. Cytokinin signaling is similar to the prokaryotic two-component signaling systems and includes the transcriptional upregulation of type-A response regulators (RRs), which in turn act to inhibit cytokinin signal response via negative feedback. Cytokinin signaling consists of several gene families and only a handful full of genes is studied. In this study, we demonstrated the function of two highly identical type-A RR genes from rice, OsRR9 and OsRR10, which are induced by cytokinin and only OsRR10 repressed by salinity stress in rice. Loss-of-function mutations give rise to mutant genes, osrr9/osrr10, which have higher salinity tolerance than wild type rice seedlings. The transcriptomic analysis uncovered several ion transporter genes, which were upregulated in response to salt stress in the osrr9/osrr10 mutants relative to the wild type seedlings. These include high-affinity potassium transporters, such as OsHKT1;1, OsHKT1;3 and OsHKT2;1, which play an important role in sodium and potassium homeostasis. In addition, disruption of the genes OsRR9 and OsRR10 also affects the expression of multiple genes related to photosynthesis, transcription and phytohormone signaling. Taken together, these results suggest that the genes OsRR9 and OsRR10 function as negative regulators in response to salinity in rice.
Men, Chronic Pain, and Prescription Pain Medication Use: The Role of Gender Role Beliefs in a Longitudinal Moderated Mediation Model
Authors: Daheim Jacob , Kim Shin Ye , Neduvelil Ashley , Nguyen Nguyen P
Published: July 2019

Objective

Although past research has established that men with chronic pain are more likely to misuse prescription pain medications in a myriad of ways compared with women, little is known about men’s medication use in the context of their gender role beliefs. The aim of the present study was to examine the role of men’s domestic gender role beliefs on their use of prescription pain medication for chronic pain.

Methods

Using a nationally representative data set with 304 men with chronic pain, this study examined a longitudinal moderated mediation model in which pain interference mediates the longitudinal relationship between somatic amplification and prescription pain medication use, with domestic gender role beliefs as a moderator of the aforementioned mediated relationship.

Results

Results indicated a significant moderated mediation model in which pain interference fully mediated the relationship between somatic amplification and prescription pain medication use, with men’s domestic gender role beliefs moderating this mediated relationship. Specifically, domestic gender role beliefs moderated the relationship between pain interference and prescription pain medication use. Men with higher levels of traditional domestic gender role beliefs strengthened the mediated relationship, contributing to increased prescription pain medication use.

Conclusions

These findings suggest that although men’s perceptions of somatic stimuli through its perceived interference contribute to their medication use, the extent to which they consume prescription pain medication depends on their beliefs in domestic gender roles during chronic pain.