bluuebunny/crossref_metadata_2025 huggingface dataset:
CME: Hyperthyreose bei Thyreoiditiden
Authors: Slahor Lea
Published: October 2018

Zusammenfassung. Eine Hyperthyreose resultiert entweder aus Steigerung der Synthese und Sekretion von Schilddrüsenhormonen oder aus deren Freisetzung bei der Destruktion von Schilddrüsengewebe, wie auch durch übermässige exogene Levothyroxin-Gabe. Der Begriff «Thyreoiditis» umfasst eine heterogene Gruppe von Schilddrüsenentzündungen, die durch Parenchymdestruktion zur unregulierten Freisetzung von Schilddrüsenhormonen («Freisetzungs-Hyperthyreose») führen. Diese seltenere Hyperthyreose-Ursache muss differenzialdiagnostisch erkannt werden, da primär eine symptomatische Therapie im Vordergrund steht. Bedingt durch die Pathophysiologie ist eine thyreostatische Therapie unwirksam. Der typische triphasische Verlauf der Funktionslage rechtfertigt ein exspektatives Vorgehen, insbesondere während der ersten selbstlimitierenden hyperthyreoten Phase. Nach der folgenden, meist passageren hypothyreoten Funktionslage wird innerhalb eines Jahres wieder eine euthyreote Funktionslage erreicht. Doch kann eine permanente Hypothyreose resultieren, was die Notwendigkeit regelmässiger Kontrollen verdeutlicht und bei Bedarf eine Levothyroxin-Therapie erfordert.
Infrasonic Early Warning System for Explosive Eruptions
Authors: Ripepe M. , Marchetti E. , Delle Donne D. , Genco R. , Innocenti L. , Lacanna G. , Valade S.
Published: October 2018

Explosive volcanic eruptions can eject large amounts of ash into the atmosphere, posing a serious threat to populations living near the volcano. The abrupt occurrence of such events requires a rapid response and proper volcanic hazard evaluation. Current monitoring procedures still require human intervention, which often results in significant delays between the occurrence of an eruption and notifications being dispatched. We show how dedicated infrasound array processing can be used to detect and notify the authorities, automatically and in real time, of the onset of explosive eruptions. Conceptually, our method relies on the strong coupling between infrasound and the explosive process, and it is not based on probabilistic considerations but on the ability infrasound has to detect the early stage of the explosive phase. This procedure has been tested for the last 8 years, and it is currently applied to issue early warnings for explosive eruptions at Etna Volcano. We show that the system is able to provide a prealert ~1 hr before the eruption, and it has a 96.6% success rate, with only 1.7% false positive alerts and no false negative alerts. This is, to our knowledge, the first example of an operational early warning system totally based on an unsupervised algorithm that provides automatic notifications of eruptions to a government agency. We show that the same early warning concept might be applicable to arrays at large distances (>500 km), suggesting that infrasound could be successfully used to issue automatic notifications of ongoing eruptions at regional to global scales.
Quantification of Ocean Mass Change Using Gravity Recovery and Climate Experiment, Satellite Altimeter, and Argo Floats Observations
Authors: Chen Jianli , Tapley Byron , Save Himanshu , Tamisiea Mark E. , Bettadpur Srinivas , Ries John
Published: October 2018

We analyze global mean ocean mass (GMOM) change over the 12‐year period (January 2005 to December 2016) using three different Gravity Recovery and Climate Experiment (GRACE) RL05 monthly time‐variable gravity solutions and compare GRACE results with independent observations from satellite altimeter and Argo floats (i.e., Altimeter‐Argo). The new results from both GRACE and Altimeter‐Argo show substantially larger GMOM rates than previous estimates, attributed to increased ice losses over land in recent years. Altimeter measurements show an average sea level rise rate of 3.87 ± 0.16 mm/year over the 12‐year period, with 1.12 ± 0.08 mm/year driven by steric effect based on Argo observations. GRACE‐observed ocean mass change agrees well with Altimeter‐Argo estimates at seasonal time scales, but notable discrepancies exist at long‐term time scales. GRACE‐estimated GMOM rates, ranging from 2.17 ± 0.12 to 2.39 ± 0.12 mm/year, are notably smaller than the Altimeter‐Argo estimate of 2.75 ± 0.18 mm/year. However, when GRACE degree‐2 zonal terms are retained (instead of being replaced by satellite laser ranging measurements), the forward modeled GRACE GMOM rate is 2.70 ± 0.16 mm/year, consistent with the Altimeter‐Argo estimate. Accurate quantification of GMOM change using GRACE is challenging and relies on accurate correction for contributions from geocenter motion and Earth oblateness change using independent observations and the Glacial Isostatic Adjustment effect using model predictions. Our analysis indicates that long‐term geocenter motion alone may contribute ~0.3 mm/year to GRACE GMOM rates, and different data processing methods have notable effect on GRACE GMOM estimates.
On the Dynamic Fragmentation and Lubrication of Coseismic Landslides
Authors: Zhao Tao , Crosta Giovanni Battista
Published: October 2018

The three‐dimensional discrete element method has been employed to analyze the dynamic fragmentation and lubrication mechanisms of coseismic Tangjiashan landslide induced by the 2008 Ms 8.0 Wenchuan earthquake. The numerical results show that the internal rock damage occurs and propagates gradually along the basal failure plane due to seismic shaking. At the peak seismic shaking, a sudden increase of tensile and shear stresses can lead to the complete breakage of basal bonds. This is associated with a sudden relief of overburden stress and rapid decrease of basal stress ratio. Thus, the slope fails as a whole and moves quickly downslope. In this process, several large transversal cracks develop at the middle and upper rear regions, disintegrating the slope mass into several large blocks. During landslide propagation, the thickness of basal fragmented layer increases progressively due to intense shearing, and the basal stress ratio reduces accordingly from 0.68 to 0.28. The reduction of landslide basal stress ratio occurs when the strong basal resistance is overcome by seismic‐ and gravity‐induced shear forces together with intense particle rearrangements. It can be quantified by vibrational and rotational granular temperatures of the basal shear layer, with the peak values of 35.2 and 11.6 m2/s2, respectively. The widespread internal slope fragmentation and subsequent lubrication have been identified as the key mechanisms governing landslide motion, which appear to be the intrinsic features of landslide irrespective of its triggering mechanism. The seismic shaking is more relevant to the detachment than to the spreading of landslide mass.
On the Physics of the Inner‐Core Wobble; Corrections to “Dynamics of the Inner‐Core Wobble Under Mantle‐Inner‐Core Gravitational Interactions” by B. F. Chao
Authors: Rochester M. G. , Crossley D. J. , Chao B. F.
Published: October 2018

The original paper by Chao (2017, https://doi.org/10.1002/2017JB014405), denoted C17, derived the period of the Earth's free inner‐core wobble (ICW) with a result which was both retrograde and substantially longer than the prograde period derived by previous authors. Here we correct major errors in C17, bringing the result into better agreement with previous derivations, and clarify the role of the various torques on the Earth's inner core (IC) as presented in C17. One serious discrepancy was the magnitude of
, the zonal quadrupole of the mantle mass distribution, which is incorrectly evaluated in C17, with a value too large compared to those that have been previously well established for a hydrostatic Earth model. Moreover, an error in the kinematics of the ICW in C17 leads to a wrong sign for the gravitational torque exerted by the mantle on the IC. The combination of these errors led to the erroneous conclusion that the ICW is retrograde, with a much longer period (−15.6 yr) compared to previous derivations, which showed it to be prograde with a period of about +7 yr. In correcting C17, we elucidate the complete torque balance involved in the ICW.
Sensitivity of the Amazonian Convective Diurnal Cycle to Its Environment in Observations and Reanalysis
Authors: Itterly Kyle F. , Taylor Patrick C. , Dodson Jason Brant
Published: October 2018

Atmospheric model parameterizations of tropical deep convection struggle to reproduce the observed diurnal variability of convection in the Amazon leading to climatological biases in the energy budget and water cycle. To identify the physical process contributions to these biases, we analyze the relationships between the convective diurnal cycle and atmosphere state variables relevant to convection in the Amazon using satellite observations and reanalysis data sets for wet and dry seasons between 2002 and 2016 and two Green Ocean Amazon periods. The analysis first stratifies the diurnal cycle into convective and nonconvective days using a daily maximum rain rate threshold of 0.5 mm/hr. Second, the population of days is constrained by requiring reanalysis and observations to agree on the occurrence of convective rain rates, controlling for frequency‐dependent biases in convection. The model‐generated precipitation phase in Modern‐Era Retrospective Analysis for Research and Applications‐2 is closer to observations than ERA during 2002–2016, which exhibits a systematic noontime bias and exaggerated diurnal amplitude. Despite the systematic noontime precipitation bias, ERA produces better agreement with Green Ocean Amazon observations due to the frequent midmorning arrival of the coastal front acting to shift the observed diurnal cycle closer to noon. Model disagreement between middle‐tropospheric vertical velocity is largest overnight during the dissipation stage of convection, acting to sustain biases through radiative effects. Specifically, the slower dissipation of convection in Modern‐Era Retrospective Analysis for Research and Applications‐2 acts to reduce morning surface fluxes and increase convective inhibition, whereas enhanced nocturnal midtropospheric subsidence and higher boundary layer humidity in ERA reduce morning convective inhibition leading to an earlier initiation of afternoon deep convection.
The Relative Influence of Storm and Landscape Characteristics on Shallow Groundwater Responses in Forested Headwater Catchments
Authors: Singh Nitin K. , Emanuel Ryan E. , Nippgen Fabian , McGlynn Brian L. , Miniat Chelcy F.
Published: October 2018

Shallow groundwater responses to rainfall in forested headwaters can be highly variable, but their relative strengths of influences remain poorly understood. We investigated the roles of storms and landscape characteristics on short‐term, shallow groundwater responses to rainfall in forested headwater catchments. We used field observations of shallow groundwater combined with random forest modeling to identify the factors that affect shallow groundwater responses and the relative influences of key response drivers. We found that the rainfall thresholds required for groundwater responses were only met by the largest quartile of events, suggesting that most events contributed to unsaturated soil storage or were lost to evaporation. Significantly higher rainfall thresholds and longer response times for south facing catchments as opposed to north facing catchments highlighted the role of insolation in setting antecedent conditions that influenced the groundwater response. During storms, there were significantly larger increases in water table height in catchments dominated by coniferous forests compared to deciduous forests, indicating that local spatial characteristics of hillslopes could be more important factors for groundwater response than catchment wetness. The random‐forest analysis revealed that total rainfall amount had the greatest influence on most groundwater responses, but the relative influence of topography and local antecedent wetness was more pronounced as events progressed, indicating a shift in hydrological processes during different stages of the groundwater response. These results have implications for our understanding of runoff generation processes, including processes that determine hydrologic connectivity between stream and hillslopes.
YAP1 enhances NF-κB-dependent and independent effects on clock-mediated unfolded protein responses and autophagy in sarcoma
Authors: Rivera-Reyes Adrian , Ye Shuai , E. Marino Gloria , Egolf Shaun , E. Ciotti Gabrielle , Chor Susan , Liu Ying , Posimo Jessica M. , Park Paul M. C. , Pak Koreana , Babichev Yael , Sostre-Colón Jaimarie , Tameire Feven , Leli Nektaria Maria , Koumenis Constantinos , C. Brady Donita , Mancuso Anthony , Weber Kristy , Gladdy Rebecca , Qi Jun , Eisinger-Mathason T. S. Karin
Published: October 2018

Terminal differentiation opposes proliferation in the vast majority of tissue types. As a result, loss of lineage differentiation is a hallmark of aggressive cancers, including soft tissue sarcomas (STS). Consistent with these observations, undifferentiated pleomorphic sarcoma (UPS), an STS subtype devoid of lineage markers, is among the most lethal sarcomas in adults. Though tissue-specific features are lost in these mesenchymal tumors they are most commonly diagnosed in skeletal muscle, and are thought to develop from transformed muscle progenitor cells. We have found that a combination of HDAC (Vorinostat) and BET bromodomain (JQ1) inhibition partially restores differentiation to skeletal muscle UPS cells and tissues, enforcing a myoblast-like identity. Importantly, differentiation is partially contingent upon downregulation of the Hippo pathway transcriptional effector Yes-associated protein 1 (YAP1) and nuclear factor (NF)-κB. Previously, we observed that Vorinostat/JQ1 inactivates YAP1 and restores oscillation of NF-κB in differentiating myoblasts. These effects correlate with reduced tumorigenesis, and enhanced differentiation. However, the mechanisms by which the Hippo/NF-κB axis impact differentiation remained unknown. Here, we report that YAP1 and NF-κB activity suppress circadian clock function, inhibiting differentiation and promoting proliferation. In most tissues, clock activation is antagonized by the unfolded protein response (UPR). However, skeletal muscle differentiation requires both Clock and UPR activity, suggesting the molecular link between them is unique in muscle. In skeletal muscle-derived UPS, we observed that YAP1 suppresses PERK and ATF6-mediated UPR target expression as well as clock genes. These pathways govern metabolic processes, including autophagy, and their disruption shifts metabolism toward cancer cell-associated glycolysis and hyper-proliferation. Treatment with Vorinostat/JQ1 inhibited glycolysis/MTOR signaling, activated the clock, and upregulated the UPR and autophagy via inhibition of YAP1/NF-κB. These findings support the use of epigenetic modulators to treat human UPS. In addition, we identify specific autophagy, UPR, and muscle differentiation-associated genes as potential biomarkers of treatment efficacy and differentiation.
PEGylated liposome-encapsulated rhenium-188 radiopharmaceutical inhibits proliferation and epithelial–mesenchymal transition of human head and neck cancer cells in vivo with repeated therapy
Authors: Chang Chun-Yuan , Chen Chao-Cheng , Lin Liang-Ting , Chang Chih-Hsien , Chen Liang-Cheng , Wang Hsin-Ell , Lee Te-Wei , Lee Yi-Jang
Published: October 2018

Human head and neck squamous cell carcinoma (HNSCC) is usually treated with chemoradiotherapy, but the therapeutic efficacy could be hampered by intrinsic radioresistance and early relapse. Repeated administrations of rhenium-188 (188Re)-conjugated radiopharmaceutical has been reported to escalate the radiation doses for better control of advanced human cancers. Here we found that high dosage of 188Re-liposome, the liposome-encapsulated 188Re nanoparticles exhibited significant killing effects on HNSCC FaDu cells and SAS cells but not on OECM-1 cells. To investigate the biological and pharmaceutical responses of high 188Re-liposomal dosage in vivo, repeated doses of 188Re-liposome was injected into the orthotopic tumor model. FaDu cells harboring luciferase reporter genes were implanted in the buccal positions of nude mice followed by intravenous injection of 188Re-liposome. The Cerenkov luminescence imaging (CLI) was performed to demonstrate an increased accumulation of 188Re-liposome in the tumor lesion of nude mice with repeated doses compared to a single dose. Repeated doses also enhanced tumor growth delay and elongated the survival of tumor-bearing mice. These observations were associated with significant loss of Ki-67 proliferative marker and epithelial–mesenchymal transition (EMT) markers in excised tumor cells. The body weights of mice were not significantly changed using different doses of 188Re-liposome, yet repeated doses led to lower blood counts than a single dose. Furthermore, the pharmacokinetic analysis showed that the internal circulation of repeated 188Re-liposomal therapy was elongated. The biodistribution analysis also demonstrated that accumulations of 188Re-liposome in tumor lesions and bone marrow were increased using repeated doses. The absorbed dose of repeated doses over a single dose was about twofold estimated for a 1 g tumor. Together, these data suggest that the radiopharmacotherapy of 188Re-liposome can enhance tumor suppression, survival extension, and internal circulation without acute toxicity using repeated administrations.
High precision FRET studies reveal reversible transitions in nucleosomes between microseconds and minutes
Authors: Gansen Alexander , Felekyan Suren , Kühnemuth Ralf , Lehmann Kathrin , Tóth Katalin , Seidel Claus A. M. , Langowski Jörg
Published: October 2018

Nucleosomes play a dual role in compacting the genome and regulating the access to DNA. To unravel the underlying mechanism, we study fluorescently labeled mononucleosomes by multi-parameter FRET measurements and characterize their structural and dynamic heterogeneity upon NaCl-induced destabilization. Species-selective fluorescence lifetime analysis and dynamic photon distribution analysis reveal intermediates during nucleosome opening and lead to a coherent structural and kinetic model. In dynamic octasomes and hexasomes the interface between the H2A-H2B dimers and the (H3-H4)2 tetramer opens asymmetrically by an angle of ≈20° on a 50 and 15 µs time scale, respectively. This is followed by a slower stepwise release of the dimers coupled with DNA unwrapping. A mutation (H2A-R81A) at the interface between H2A and H3 facilitates initial opening, confirming the central role of the dimer:tetramer interface for nucleosome stability. Partially opened states such as those described here might serve as convenient nucleation sites for DNA-recognizing proteins.
Structural basis of Gip1 for cytosolic sequestration of G protein in wide-range chemotaxis
Authors: Miyagawa Takero , Koteishi Hiroyasu , Kamimura Yoichiro , Miyanaga Yukihiro , Takeshita Kohei , Nakagawa Atsushi , Ueda Masahiro
Published: October 2018

G protein interacting protein 1 (Gip1) binds and sequesters heterotrimeric G proteins in the cytosolic pool, thus regulating G protein-coupled receptor (GPCR) signalling for eukaryotic chemotaxis. Here, we report the underlying structural basis of Gip1 function. The crystal structure reveals that the region of Gip1 that binds to the G protein has a cylinder-like fold with a central hydrophobic cavity composed of six α-helices. Mutagenesis and biochemical analyses indicate that the hydrophobic cavity and the hydrogen bond network at the entrance of the cavity are essential for complex formation with the geranylgeranyl modification on the Gγ subunit. Mutations of the cavity impair G protein sequestration and translocation to the membrane from the cytosol upon receptor stimulation, leading to defects in chemotaxis at higher chemoattractant concentrations. These results demonstrate that the Gip1-dependent regulation of G protein shuttling ensures wide-range gradient sensing in eukaryotic chemotaxis.
IMP2ART systematic review of education for healthcare professionals implementing supported self-management for asthma
Authors: McCleary Nicola , Andrews Amanda , Buelo Audrey , Captieux Mireille , Morrow Susan , Wiener-Ogilvie Sharon , Fletcher Monica , Steed Liz , Taylor Stephanie J. C. , Pinnock Hilary
Published: October 2018

Despite a robust evidence base for its effectiveness, implementation of supported self-management for asthma is suboptimal. Professional education is an implementation strategy with proven effectiveness, though the specific features linked with effectiveness are often unclear. We performed a systematic review of randomised controlled trials and controlled clinical trials (published from 1990 and updated to May 2017 using forward citation searching) to determine the effectiveness of professional education on asthma self-management support and identify features of effective initiatives. Primary outcomes reflected professional behaviour change (provision of asthma action plans) and patient outcomes (asthma control; unscheduled care). Data were coded using the Effective Practice and Organisation of Care Taxonomy, the Theoretical Domains Framework (TDF), and Bloom’s Taxonomy and synthesised narratively. Of 15,637 articles identified, 18 (reporting 15 studies including 21 educational initiatives) met inclusion criteria. Risk of bias was high for five studies, and unclear for 10. Three of 6 initiatives improved action plan provision; 1/2 improved asthma control; and 2/7 reduced unscheduled care. Compared to ineffective initiatives, effective initiatives were more often coded as being guideline-based; involving local opinion leaders; including inter-professional education; and addressing the TDF domains ‘social influences’; ‘environmental context and resources’; ‘behavioural regulation’; ‘beliefs about consequences’; and ‘social/professional role and identity’. Findings should be interpreted cautiously as many strategies were specified infrequently. However, identified features warrant further investigation as part of implementation strategies aiming to improve the provision of supported self-management for asthma.
Tuning quantum channels to maximize polarization entanglement for telecom photon pairs
Authors: Jones Daniel E. , Kirby Brian T. , Brodsky Michael
Published: October 2018

Quantum networks entangle remote nodes by distributing quantum states, which inevitably suffer from decoherence while traversing quantum channels. Pertinent decoherence mechanisms govern the reach, quality, and rate of distributed entanglement. Hence recognizing, understanding, and modeling those mechanisms is a crucial step in building quantum networks. Here, we study real-life fiber-optic quantum channels that partially filter individual modes of transmitted polarization-entangled states and are capable of introducing dephasing. First, we theoretically model and experimentally demonstrate the combined effect of two independent and arbitrarily oriented polarization-dependent loss elements experienced by each photon of an entangled photon pair. Then, we showcase the compensation of lost entanglement by properly adjusting the channels’ properties and discuss the resulting tradeoff between the entanglement quality and rate. Our results provide insights into the robustness of fiber-optic quantum channels, thus taking an important step toward the realization of quantum networks.
Establishing grading indices of available soil potassium on paddy soils in Hubei province, China
Authors: Li Xiaokun , Zhang Yangyang , Wang Weini , Khan Muhammad Rizwan , Cong Rihuan , Lu Jianwei
Published: October 2018

Soil testing is an important diagnostic tool for assessing crop-available soil potassium (K) and hence making appropriate fertilizer recommendation. This study was aimed at correlating grain yield response data to soil-test K extracted with ammonium acetate (NH4OAc), cold nitric acid (HNO3), sodium tetraphenylboron (NaTPB) and boiling HNO3 solution, based on 54 field trials conducted during 2011 to 2015 across 15 counties in Hubei province, China. The specific objectives were to establish abundance and deficiency indices of available soil-K (ASK) for rice (Oryza sativa L.) and make accurate K fertilizer recommendations. Potassium extracted with NaTPB and boiling HNO3 was 1.47 times and 3.61 times higher respectively than that extracted with cold HNO3, while K extracted with cold HNO3 was 1.32 times higher than that extracted with NH4OAc. There were significant logarithmic relationships between crop response and soil-test K. The R2 values for cold HNO3-K and NaTPB-K methods were much higher than for NH4OAc-K method. In order to calibrate the application, the abundance and deficiency indices of ASK categorized by cold HNO3-K in low, medium, high and very high ranges were <50 mg kg−1, 50 to 100 mg kg−1, 100 to 200 mg kg−1 and >200 mg kg−1 respectively, and that defined by NaTPB-K were <60 mg kg−1, 60 to 150 mg kg−1, 150 to 330 mg kg−1 and >330 mg kg−1, respectively. These values could be used to evaluate soil K supplying capacity and make appropriate K fertilizer recommendations for rice.
Pelvic and hypogastric nerves are injured in a rat prostatectomy model, contributing to development of stress urinary incontinence
Authors: Hehemann Marah , Choe Shawn , Kalmanek Elizabeth , Harrington Daniel , Stupp Samuel I. , McVary Kevin T. , Podlasek Carol A.
Published: October 2018

Urinary incontinence affects 40% of elderly men, is common in diabetic patients and in men treated for prostate cancer, with a prevalence of up to 44%. Seventy-two percent of prostatectomy patients develop stress urinary incontinence (SUI) in the first week after surgery and individuals who do not recover within 6 months generally do no regain function without intervention. Incontinence has a profound impact on patient quality of life and a critical unmet need exists to develop novel and less invasive SUI treatments. During prostatectomy, the cavernous nerve (CN), which provides innervation to the penis, undergoes crush, tension, and resection injury, resulting in downstream penile remodeling and erectile dysfunction in up to 85% of patients. There are other nerves that form part of the major pelvic ganglion (MPG), including the hypogastric (HYG, sympathetic) and pelvic (PN, parasympathetic) nerves, which provide innervation to the bladder and urethra. We examine if HYG and PNs are injured during prostatectomy contributing to SUI, and if Sonic hedgehog (SHH) regulatory mechanisms are active in the PN and HYG nerves. CN, PN, HYG and ancillary (ANC) of uninjured, sham and CN crush/MPG tension injured (prostatectomy model) adult Sprague Dawley rats (n = 37) were examined for apoptosis, sonic hedgehog (SHH) pathway, and intrinsic and extrinsic apoptotic mechanisms. Fluorogold tracing from the urethra/bladder was performed. PN and HYG response to SHH protein was examined in organ culture. TUNEL, immunohistochemical analysis for caspase-3 cleaved, -8, -9, SHH, Patched and Smoothened (SHH receptors), and neurite formation, were examined. Florogold positive neurons in the MPG were reduced with CN crush. Apoptosis increased in glial cells of the PN and HYG after CN crush. Caspase 9 was abundant in glial cells (intrinsic), while caspase-8 was not observed. SHH and its receptors were abundant in neurons and glia of the PN and HYG. SHH treatment increased neurite formation. PN and HYG injury occur concomitant with CN injury during prostatectomy, likely contributing to SUI. PN and HYG response to SHH treatment indicates an avenue for intervention to promote regeneration and prevent SUI.
Transposable Element Expression in Acute Myeloid Leukemia Transcriptome and Prognosis
Authors: Colombo Anthony R. , Triche Timothy , Ramsingh Giridharan
Published: October 2018

Over half of the human genome is comprised of transposable elements (TE). Despite large-scale studies of the transcriptome in cancer, a comprehensive look at TE expression and its relationship to various mutations or prognosis has not been performed. We characterized the expression of TE in 178 adult acute myeloid leukemia (AML) patients using transcriptome data from The Cancer Genome Atlas. We characterized mutation specific dysregulation of TE expression using a multivariate linear model. We identified distinct patterns of TE expression associated with specific mutations and transcriptional networks. Genes regulating methylation was not associated with significant change in TE expression. Using an unpenalized cox regression analysis we identified a TE expression signature that predicted prognosis in AML. We identified 14 candidate prognostic TE transcripts (TEP) that classified AML as high/low-risk and this was independent of mutation-based and coding-gene expression based risk-stratification. TEP was able to predict prognosis in independent cohorts of 284 pediatric AML patients and 19 relapsed adult AML patients. This first comprehensive study of TE expression in AML demonstrates that TE expression can serve as a biomarker for prognosis in AML, and provides novel insights into the biology of AML. Studies characterizing its role in other cancers are warranted.
Drought-induced susceptibility for Cenangium ferruginosum leads to progression of Cenangium-dieback disease in Pinus koraiensis
Authors: Ryu Minji , Mishra Ratnesh Chandra , Jeon Junhyun , Lee Sun Keun , Bae Hanhong
Published: October 2018

Recently, the occurrence of “Cenangium-dieback” has been frequent and devastating. Cenangium-dieback is caused by an endophytic fungus Cenangium ferruginosum in stressed pine trees. Progression of the disease in terms of molecular interaction between host and pathogen is not well studied and there is a need to develop preventive strategies. Thus, we simulated disease conditions and studied the associated transcriptomics, metabolomics, and hormonal changes. Pinus koraiensis seedlings inoculated with C. ferruginosum were analyzed both under drought and well-watered conditions. Transcriptomic analysis suggested decreased expression of defense-related genes in C. ferruginosum-infected seedlings experiencing water-deficit. Further, metabolomic analysis indicated a decrease in the key antimicrobial terpenoids, flavonoids, and phenolic acids. Hormonal analysis revealed a drought-induced accumulation of abscisic acid and a corresponding decline in the defense-associated jasmonic acid levels. Pathogen-associated changes were also studied by treating C. ferruginosum with metabolic extracts from pine seedlings (with and without drought) and polyethylene glycol to simulate the effects of direct drought. From RNA sequencing and metabolomic analysis it was determined that drought did not directly induce pathogenicity of C. ferruginosum. Collectively, we propose that drought weakens pine immunity, which facilitates increased C. ferruginosum growth and results in conversion of the endophyte into the phytopathogen causing dieback.
Strategic single point mutation yields a solvent- and salt-stable transaminase from Virgibacillus sp. in soluble form
Authors: Guidi Benedetta , Planchestainer Matteo , Contente Martina Letizia , Laurenzi Tommaso , Eberini Ivano , Gourlay Louise J. , Romano Diego , Paradisi Francesca , Molinari Francesco
Published: October 2018

A new transaminase (VbTA) was identified from the genome of the halotolerant marine bacterium Virgibacillus 21D. Following heterologous expression in Escherichia coli, it was located entirely in the insoluble fraction. After a single mutation, identified via sequence homology analyses, the VbTA T16F mutant was successfully expressed in soluble form and characterised. VbTA T16F showed high stability towards polar organic solvents and salt exposure, accepting mainly hydrophobic aromatic amine and carbonyl substrates. The 2.0 Å resolution crystal structure of VbTA T16F is here reported, and together with computational calculations, revealed that this mutation is crucial for correct dimerisation and thus correct folding, leading to soluble protein expression.
The Arabidopsis-Trichoderma interaction reveals that the fungal growth medium is an important factor in plant growth induction
Authors: González-Pérez Enrique , Ortega-Amaro María Azucena , Salazar-Badillo Fatima Berenice , Bautista Elihú , Douterlungne David , Jiménez-Bremont Juan Francisco
Published: October 2018

Trichoderma spp colonizes the plant rhizosphere and provides pathogen resistance, abiotic stress tolerance, and enhance growth and development. We evaluated the Arabidopsis-Trichoderma interaction using a split system in which Trichoderma atroviride and Trichoderma virens were grown on PDA or MS medium. Arabidopsis growth was significantly increased at 3 and 5 days post-inoculation with both Trichoderma species, when the fungal strains were grown on PDA in split interaction. The analysis of DR5:uidA reporter line revealed a greater auxin accumulation in root tips when the fungi were grown on PDA in a split interaction. The root hair-defective phenotype of Arabidopsis rhd6 mutant was reverted with both Trichoderma species, even in split interactions. At 12 °C, Trichoderma species in split interactions were able to mitigate the effects of cold stress on the plant, and also Trichoderma induced the AtERD14 expression, a cold related gene. Volatile organic compounds analysis revealed that Trichoderma strains produce mainly sesquiterpenes, and that the type and abundance of these compounds was dependent on the fungal strain and the culture medium. Our results show that fungal nutrition is an important factor in plant growth in a split interaction.
Classification of marine microdebris: A review and case study on fish from the Great Barrier Reef, Australia
Authors: Kroon Frederieke J. , Motti Cherie E. , Jensen Lene H. , Berry Kathryn L. E.
Published: October 2018

Marine debris, and in particular plastic pollution, is ubiquitous throughout global marine environments. Here, we present a classification of marine microdebris (i.e. debris between 0.1 μm and <5 mm) tailored to represent synthetic, semi-synthetic and naturally-derived items. The specific aim of this classification is to introduce a level of consistency in the higher-level characterisation of marine microdebris, thereby improving the overall reporting on marine microdebris contamination. We first conducted an extensive literature review on the accumulation of ingested debris in fish to identify discrepancies in marine microdebris reporting as a basis for the new classification. The review reveals the diverse nature of ingested marine microdebris, including items that are non-plastic but often incorrectly reported on as microplastics. We then applied our classification to a case study on wild-caught juvenile coral trout, Plectropomus spp., from the Great Barrier Reef World Heritage Area, Australia. This first report on accumulation of ingested marine debris in commercial fish on the reef demonstrates a high frequency of occurrence and a prevalence of semi-synthetic and naturally-derived fibres. Based on our findings, we offer recommendations on potential improvements for the classification presented, ultimately contributing to a more realistic assessment of the ecological risks of marine microdebris.
Seismic Detection of a Magma Reservoir beneath Turtle Island of Taiwan by S-Wave Shadows and Reflections
Authors: Lin Cheng-Horng , Lai Ya-Chuan , Shih Min-Hung , Pu Hsin-Chieh , Lee Shiann-Jong
Published: October 2018

Although surface geology, eruption information and clustering seismicity all suggest Turtle Island (Kueishantao) of northern Taiwan is an active volcano, there was no direct evidence to conclude that magma reservoirs exist beneath it. Even less evidence is available to determine their spatial configuration. If the magma reservoirs are filled by liquids and melt, S-waves are totally reflected and leave behind a shadow, like when passing through the Earth’s outer core. We detect both these S-wave shadows and strong reflections from the surface using earthquakes at different depths and azimuths. These observations identify a km-scale molten-filled volume located beneath Turtle Island. The magmatic nature of the reservoir is supported by the onset of non-double-couple earthquakes with strong CLVD (Compensated Linear Vector Dipole) and ISO (Isotropic) components, which show a tensor crack compatible with some volume changes within the reservoir. Combining these results with two independent 3-D velocity models and aeromagnetic anomalies recorded in Taiwan, a partially-molten ~19% low-velocity volume is estimated in the mid-crust (13–23 km), with spatial uncertainties of ~3 km. The elongated direction approximately follows the strike of the Okinawa trough, indicating that the source of the magma reservoir might be a back-arc opening.
On the detection of carbon fibre storage contamination and its effect on the fibre–matrix interface
Authors: Li Quanxiang , Woodhead Andrea L. , Church Jeffrey S. , Naebe Minoo
Published: October 2018

Contamination caused by inappropriate carbon fibre (CF) storage may have an impact on their end use in reinforced composite materials. Due to the chemical complexity of CFs it is not easy to detect potential contaminants, especially at the early stage during manufacturing and handling. In this paper, X-ray Photoelectron Spectroscopy (XPS), Fourier Transform Infrared (FTIR) spectroscopy and Surface Energy Analysis (IGC-SEA) were used to assess the surfaces of CFs stored in polyolefin zip-lock bags for possible contamination. Only after over 2 months in-bag storage, was XPS capable of detecting a minor increase in nitrogen on the CF surface while FTIR revealed the presence of fatty acid amides and fatty acids, both associated with the storage media. However neither of these techniques were sensitive enough to show significant evolution of the amount of contamination as a function of storage time. In contrast, IGC-SEA distinguished surface energy differences between CFs before and after storage. These differences were found to change as a function of storage time, which were attributed to increases in contamination amounts. Single fibre fragmentation tests indicated that the surface contamination had potential to disrupt the fibre-matrix interface. These findings provide a new method for assessing the surface contamination of CFs with potential application to other materials.
In Silico Study Reveals How E64 Approaches, Binds to, and Inhibits Falcipain-2 of Plasmodium falciparum that Causes Malaria in Humans
Authors: Salawu Emmanuel Oluwatobi
Published: October 2018

Plasmodium falciparum malaria, which degrades haemoglobin through falcipain-2 (FP2), is a serious disease killing 445 thousand people annually. Since the P. falciparum’s survival in humans depends on its ability to degrade human’s haemoglobin, stoppage or hindrance of FP2 has antimalarial effects. Therefore, we studied the atomic details of how E64 approaches, binds to, and inhibits FP2. We found that E64 (1) gradually approaches FP2 by first interacting with FP2’s D170 and Q171 or N81, N77, and K76; (2) binds FP2 tightly (ΔGbinding = −12.2 ± 1.1 kJ/mol); and (3) persistently blocks access to FP2’s catalytic residues regardless of whether or not E64 has already been able to form a covalent bond with FP2’s C42. Furthermore, the results suggest that S41, D234, D170, N38, N173, and L172 (which are located in or near the FP2’s catalytic site’s binding pocket) contribute the most towards the favourable binding of E64 to FP2. Their in silico mutations adversely affect E64-FP2 binding affinity with D234L/A, N173L/A, W43F/A, D234L/A, H174F/A, and N38L/A having the most significant adverse effects on E64-FP2 binding and interactions. The findings presented in this article, which has antimalarial implications, suggest that hydrogen bonding and electrostatic interactions play important roles in E64-FP2 binding, and that a potential FP2-blocking E64-based/E64-like antimalarial drug should be capable of being both hydrogen-bond donor and acceptor, and/or have the ability to favourably interact with polar amino acids (such as S41, S149, N38, N173, N77, Q171) and with charged amino acids (such as D234, D170, H174) of FP2. The abilities to favourably interact with ASN, ASP, and SER appears to be important characteristics that such potential drug should have.
Chelating agent-assisted in situ LDH growth on the surface of magnesium alloy
Authors: Shulha T. N. , Serdechnova M. , Lamaka S. V. , Wieland D. C. F. , Lapko K. N. , Zheludkevich M. L.
Published: October 2018

In situformation of layered double hydroxides (LDH) on metallic surfaces has recently been considered a promising approach for protective conversion surface treatments for Al and Mg alloys. In the case of Mg-based substrates, the formation of LDH on the metal surface is normally performed in autoclave at high temperature (between 130 and 170 °C) and elevated pressure conditions. This hampers the industrial application of MgAl LDH to magnesium substrates. In this paper, the growth of MgAl LDH conversion coating directly on magnesium alloy AZ91 at ambient conditions (25 °C) or elevated temperatures is reported in carbonate free electrolyte for the first time. The direct LDH synthesis on Mg alloys is enabled by the presence of organic chelating agents (NTA and EDTA), which control the amount of free and/or hydroxyl bound Mg2+and Al3+in the solution. The application of the chelating agents help overcoming the typical technological limitations of direct LDH synthesis on Mg alloys. The selection of chelators and the optimization of the LDH treatment process are supported by the analysis of the thermodynamic chemical equilibria.
Controlling Fano resonances in multilayer dielectric gratings towards optical bistable devices
Authors: Hoang Thu Trang , Ngo Quang Minh , Vu Dinh Lam , Nguyen Hieu P. T.
Published: October 2018

The spectral properties of Fano resonance generated in multilayer dielectric gratings (MDGs) are reported and numerically investigated in this paper. We examine the MDG consisting of numerous identically alternative chalcogenide glass (As2S3) and silica (SiO2) multilayers with several grating widths inscribed through the structure, emphasizing quality (Q) and asymmetric (q) factors. Manipulation of Fano lineshape and its linear characteristics can be achieved by tailoring the layers’ amount and grating widths so that the proposed structure can be applicable for several optical applications. Moreover, we demonstrate the switching/bistability behaviors of the MDG at Fano resonance which provide a significant switching intensity reduction compared to the established Lorentzian resonant structures.
Direct quantitative material decomposition employing grating-based X-ray phase-contrast CT
Authors: Braig Eva , Böhm Jessica , Dierolf Martin , Jud Christoph , Günther Benedikt , Mechlem Korbinian , Allner Sebastian , Sellerer Thorsten , Achterhold Klaus , Gleich Bernhard , Noël Peter , Pfeiffer Daniela , Rummeny Ernst , Herzen Julia , Pfeiffer Franz
Published: October 2018

Dual-energy CT has opened up a new level of quantitative X-ray imaging for many diagnostic applications. The energy dependence of the X-ray attenuation is the key to quantitative material decomposition of the volume under investigation. This material decomposition allows the calculation of virtual native images in contrast enhanced angiography, virtual monoenergetic images for beam-hardening artifact reduction and quantitative material maps, among others. These visualizations have been proven beneficial for various diagnostic questions. Here, we demonstrate a new method of ‘virtual dual-energy CT’ employing grating-based phase-contrast for quantitative material decomposition. Analogue to the measurement at two different energies, the applied phase-contrast measurement approach yields dual information in form of a phase-shift and an attenuation image. Based on these two image channels, all known dual-energy applications can be demonstrated with our technique. While still in a preclinical state, the method features the important advantages of direct access to the electron density via the phase image, simultaneous availability of the conventional attenuation image at the full energy spectrum and therefore inherently registered image channels. The transfer of this signal extraction approach to phase-contrast data multiplies the diagnostic information gained within a single CT acquisition. The method is demonstrated with a phantom consisting of exemplary solid and fluid materials as well as a chicken heart with an iodine filled tube simulating a vessel. For this first demonstration all measurements have been conducted at a compact laser-undulator synchrotron X-ray source with a tunable X-ray energy and a narrow spectral bandwidth, to validate the quantitativeness of the processing approach.
Untargeted metabolomics reveals transformation pathways and metabolic response of the earthworm Perionyx excavatus after exposure to triphenyl phosphate
Authors: Wang Lei , Huang Xulei , Laserna Anna Karen Carrasco , Li Sam Fong Yau
Published: October 2018

Triphenyl phosphate (TPHP) is one of the most highly utilized organophosphorus flame retardants, and has been frequently detected in various environmental matrices, including soil. So far, limited information is known regarding the potential toxicity of TPHP to the earthworm-soil ecosystem. We investigated the metabolism of TPHP and the perturbation of the endogenous metabolome in the earthworm, Perionyx excavatus, using gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole time-of-flight (LC-QTOF)-based untargeted metabolomics approach after acute exposure to TPHP for one and two days through a filter paper contact test, as well as after chronic exposure for 28 days in a soil microcosm experiment. TPHP showed low bioaccumulation potential in the earthworm-soil ecosystem at concentrations of 10 mg/kg and 50 mg/kg. Identified phase I metabolites include diphenyl phosphate, mono-hydroxylated and di-hydroxylated TPHP. Two groups of phase II metabolites, thiol conjugates (including mercaptolactic acid, cysteine, cysteinylglycine, and mercaptoethanol conjugates) and glucoside conjugates (including glucoside, glucoside-phosphate, and C14H19O10P conjugates), were putatively identified. Only acute TPHP exposure caused significant perturbations of the endogenous metabolome in earthworms, featuring fluctuations in amino acids, glucose, inosine and phospholipids. These results reveal novel phase II metabolism and toxicity of TPHP in P. excavatus.