bluuebunny/crossref_metadata_2025 huggingface dataset:
What shapes adolescents’ diet and physical activity habits in rural Konkan, India? Adolescents’ and caregivers’ perspectives
Authors: Banavali Ulka , Patil Suvarna , Chavan Rupali , Sonawane Swati , Joglekar Charudatta , Fall Caroline , Weller Susie , Kehoe Sarah H , Barker Mary , Hardy-Johnson Polly
Published: July 2020

Objective:

To explore, adolescents’ and caregivers’ perspectives, about shaping of diet and physical activity habits in rural Konkan, India.

Design:

Five focus group discussions (FGD) were conducted with adolescents and two with caregivers. Data were analysed using thematic analysis.

Setting:

FGD were conducted in secondary schools located in remote rural villages in the Ratnagiri district, Konkan region, Maharashtra, India.

Participants:

Forty-eight adolescents were recruited including twenty younger (10–12 years) and twenty-eight older (15–17 years) adolescents. Sixteen caregivers (all mothers) were also recruited.

Results:

Three themes emerged from discussion: (i) adolescents’ and caregivers’ perceptions of the barriers to healthy diet and physical activity, (ii) acceptance of the status quo and (iii) salience of social and economic transition. Adolescents’ basic dietary and physical activity needs were rarely met by the resources available and infrastructure of the villages. There were few opportunities for physical activity, other than performing household chores and walking long distances to school. Adolescents and their caregivers accepted these limitations and their inability to change them. Increased use of digital media and availability of junk foods marked the beginning of a social and economic transition.

Conclusion:

FGD with adolescents and their caregivers provided insights into factors influencing adolescent diet and physical activity in rural India. Scarcity of basic resources limited adolescent diet and opportunities for physical activity. To achieve current nutritional and physical activity recommendations for adolescents requires improved infrastructure in these settings, changes which may accompany the current Indian social and economic transition.
Institutionalization of Ethnocultural Diversity and the Representation of European Muslims
Authors: Aktürk Şener , Katliarou Yury
Published: July 2020

We seek to explain variation in the descriptive representation of Muslim minorities in national legislatures, relying on an original data set that includes 635 seats filled by Muslim-origin MPs in the lower chambers of national parliaments of twenty-six European polities in three legislative cycles between 2007 and 2018. We argue that the image of a polity as a union of multiple ethnocultural groups, reflected in concrete state policies and institutional arrangements, may be conducive to better descriptive representation of Muslim minorities, who were not originally envisioned as one of the communities constituting the nation. The results of multivariate regression analysis provide support for our hypothesis that the extent to which ethnocultural diversity is recognized and institutionalized helps explain variation in the levels of descriptive representation of European Muslims. We supplement our findings with congruence testing in four brief case studies: Belgium, France, the Netherlands, and Bulgaria.
Evaluation of Ionospheric Scintillation in GNSS Radio Occultation Measurements and Simulations
Authors: Ludwig‐Barbosa Vinícius , Sievert Thomas , Rasch Joel , Carlström Anders , Pettersson Mats I. , T. Vu Viet
Published: July 2020

Like any other system relying on transionospheric propagation, Global Navigation Satellite System (GNSS) Radio Occultation (GNSS‐RO) is affected by ionospheric conditions during measurements. Regions of plasma irregularities in F region create abrupt gradients in the distribution of ionized particles. Radio signals propagated through such regions suffer from constructive and destructive contributions in phase and amplitude, known as scintillations. Different approaches have been proposed in order to model and reproduce the wave propagation through ionospheric irregularities. We present simulations considering single‐slope power law model of irregularities integrated with Multiple Phase Screen (MPS) propagation. In this work, the capability of the scintillation model to reproduce features in low‐latitude MetOp measurements in the early hours of DOY 76, 2015 is evaluated. Power spectral density (PSD) analysis, scintillation index, decorrelation time, and standard deviation of neutral bending angle are considered in the comparison between the simulations and RO measurements. The results demonstrate the capability of the simulator to replicate an equivalent error contribution to the neutral bending angle measurement in cases of moderate to strong scintillation.
An Increase in Specific Discharge With Catchment Area Implies That Bedrock Infiltration Feeds Large Rather Than Small Mountain Headwater Streams
Authors: Asano Yuko , Kawasaki Masatoshi , Saito Toshihiro , Haraguchi Ryusei , Takatoku Kae , Saiki Michio , Kimura Kota
Published: July 2020

Mountains are a source of water for downstream areas; thus, it is important to understand the storage and discharge characteristics of steep mountain catchments. Nested catchment studies have indicated that the relation between catchment area and specific discharge during baseflow can represent mesoscale storage and discharge characteristics, but this is poorly understood. We found that baseflow‐specific discharge increased with catchment size in the headwater of the Arakawa River and identified the processes responsible for this spatial pattern. Synoptic discharge measurements obtained in catchment areas of 0.05 to 93.58 km2 showed that specific discharge increased more than threefold with increasing drainage area. Analyses of the spatial variation in precipitation, hydrographs from three continuous gauging stations, and isotopic tracers implied that in this catchment, considerable amounts of water infiltrated in bedrock on hillslopes and did not discharge into small streams, but instead fed surface flow into a larger downstream catchment. A review of previous nested studies demonstrated three spatial patterns for specific discharge: Specific discharge may increase or decrease with catchment area, or it may be independent of area. An increase in specific discharge with area was observed only in catchments with permeable bedrock, which implies that such an increase is a useful indicator of the importance of the bedrock flow path to mountain watershed storage. The pattern of relationships between catchment area and specific discharge can be used to assess the storage and discharge properties of mesoscale catchments when the processes driving each pattern have been clarified.
Predicting Transverse Mixing Efficiency Downstream of a River Confluence
Authors: Pouchoulin S. , Le Coz J. , Mignot E. , Gond L. , Riviere N.
Published: July 2020

Predicting mixing processes, especially transverse mixing, downstream of river confluences, is necessary for assessing and modeling the fate of pollutants transported in river networks, but it is still challenging. Typically, there is a lack of transverse mixing solutions implemented in 1‐D hydrodynamical models widely used in river engineering applications. To investigate the mixing processes developing downstream of a medium‐sized river confluence, three high‐resolution in situ surveys are conducted at the Rhône‐Saône confluence in France, based on geolocated specific conductivity and hydroacoustic measurements. Contrasting mixing situations are observed depending on hydrological conditions. In some cases, the two flows mix slowly due to turbulent shear at their vertical interface. This can be modeled by an analytical solution of the advection‐diffusion equation. In other cases, the waters from one of the two tributaries move under the waters of the other tributary. The induced local circulation enhances transverse mixing but not vertical mixing and the flow remains stratified vertically, which may be missed when surface or satellite images are analyzed qualitatively. Stratification may be predicted by comparing the time scales for shear and density‐driven adjustment. Shear‐dominated transverse mixing of depth‐averaged concentrations can be predicted analytically and implemented in 1‐D hydrodynamical models. However, the initiation of apparently rapid transverse mixing due to density‐driven circulation remains to be better understood and quantified.
Coastal Groundwater Flow at the Nearshore and Embayment Scales: A Field and Modeling Study
Authors: Evans Tyler B. , White Scott M. , Wilson Alicia M.
Published: July 2020

Knowledge of coastal groundwater flow is critical for managing coastal groundwater resources and quantifying submarine groundwater discharge (SGD), but this flow occurs over multiple scales that can be difficult to study in an integrated way. We designed a field and modeling study to investigate groundwater flow and the distribution of salinity during sea level rise in a domain that included beaches, salt marshes and the first major confined aquifer, which reached 10–15 km offshore. Numerical models were based on the flat‐lying, passive margin coastline of North Inlet, SC, and were constrained by field studies including subsurface resistivity surveys and hydraulic head observations. Simulations that included tidal fluctuations showed that the salt marsh generated more than three times as much SGD as the beach and inner shelf, per unit length of coastline. Groundwater exchange between scales was small, suggesting that physical fluxes of groundwater can be considered independently at different scales. However, salinization of the first major confined aquifer occurred by downward transport from overlying aquifers rather than intrusion from the seaward end, suggesting that studies of aquifer salinization should consider multiscale flow. During simulated sea level rise, fresh‐to‐brackish groundwater persisted in the first confined aquifer as far as the seaward end of the overlying confining unit, 10–20 km offshore. Total fluxes of SGD decreased significantly with future sea level rise, dominated by declining SGD in the salt marsh, and portending a marked decline in the flux of nutrients and carbon to estuaries and the coastal ocean.
A New Inverse Modeling Approach for Hydraulic Conductivity Estimation Based on Gaussian Mixtures
Authors: Minutti Carlos , Illman Walter A. , Gomez Susana
Published: July 2020

This study proposes a new inverse algorithm to estimate the hydraulic conductivity (K) distribution based on a Gaussian Mixture Model that significantly reduces the number of parameters to be estimated during the inversion process. Moreover, a new objective function that increases the sensitivity of parameters using the spatial derivatives of hydraulic heads is introduced, and the algorithm is further improved by including a Bayes estimator that takes advantage of different possible solutions. The developed approach is tested through multiple synthetic experiments consisting of 250 randomly generated K fields resulting in different levels of heterogeneity and the use of different number of pumping tests, with a total of 1,000 cases of two‐dimensional configuration. A large number of cases are considered to ensure that our findings and conclusions are not based on a single realization. Results revealed significant improvements to K estimates, computational time, and predictions of independently conducted tests not used in the calibration effort when compared to a geostatistical inverse approach. Overall, our results reveal that the Gaussian Mixture inversion approach is able to achieve similar or higher levels of accuracy using half of the pumping tests and 20% of the computational time compared to a geostatistical inversion approach.
Magnetospheric Multiscale Observation of an Electron Diffusion Region at High Latitudes
Authors: Burkholder B. L. , Nykyri K. , Ma X. , Rice R. , Fuselier S. A. , Trattner K. J. , Pritchard K. R. , Burch J. L. , Petrinec S. M.
Published: July 2020

On 17 October 2016, Magnetospheric Multiscale (MMS) sampled an electron diffusion region (EDR) embedded in an electron‐scale current sheet within a mixed portion of the high‐latitude magnetosheath adjacent to the magnetopause. We analyze the generalized Ohm's law, dissipation, and electron velocity distributions inside the EDR. The velocities, magnetic fields, and densities observed in the magnetosheath and magnetosphere indicate the magnetopause was unstable to the Kelvin‐Helmholtz instability, which can form electron‐scale current sheets. Alternatively, a current sheet was observed in the solar wind at L1 40 min before the MMS observations, which could have been compressed by the bow shock initiating reconnection. Hundreds of keV particles near the EDR may have been locally accelerated.
Comparison of Equilibrium Climate Sensitivity Estimates From Slab Ocean, 150‐Year, and Longer Simulations
Authors: Dunne John P. , Winton Michael , Bacmeister Julio , Danabasoglu Gokhan , Gettelman Andrew , Golaz Jean‐Christophe , Hannay Cecile , Schmidt Gavin A. , Krasting John P. , Leung L. Ruby , Nazarenko Larissa , Sentman Lori T. , Stouffer Ronald J. , Wolfe Jonathan D.
Published: July 2020

We compare equilibrium climate sensitivity (ECS) estimates from pairs of long (≥800‐year) control and abruptly quadrupled CO2 simulations with shorter (150‐ and 300‐year) coupled atmosphere‐ocean simulations and slab ocean models (SOMs). Consistent with previous work, ECS estimates from shorter coupled simulations based on annual averages for years 1–150 underestimate those from SOM (−8% ± 13%) and long (−14% ± 8%) simulations. Analysis of only years 21–150 improved agreement with SOM (−2% ± 14%) and long (−8% ± 10%) estimates. Use of pentadal averages for years 51–150 results in improved agreement with long simulations (−4% ± 11%). While ECS estimates from current generation U.S. models based on SOM and coupled annual averages of years 1–150 range from 2.6°C to 5.3°C, estimates based longer simulations of the same models range from 3.2°C to 7.0°C. Such variations between methods argues for caution in comparison and interpretation of ECS estimates across models.
Estimating Satellite Orbital Drag During Historical Magnetic Superstorms
Authors: Oliveira Denny M. , Zesta Eftyhia , Hayakawa Hisashi , Bhaskar Ankush
Published: July 2020

Understanding extreme space weather events is of paramount importance in efforts to protect technological systems in space and on the ground. Particularly in the thermosphere, the subsequent extreme magnetic storms can pose serious threats to low Earth orbit (LEO) spacecraft by intensifying errors in orbit predictions. Extreme magnetic storms (minimum Dst ≤ −250 nT) are extremely rare: Only seven events occurred during the era of spacecraft with high‐level accelerometers such as CHAMP (CHAllenge Minisatellite Payload) and GRACE (Gravity Recovery And Climate experiment) and none with minimum Dst ≤ −500 nT, here termed magnetic superstorms. Therefore, current knowledge of thermospheric mass density response to superstorms is very limited. Thus, in order to advance this knowledge, four known magnetic superstorms in history, that is, events occurring before CHAMP's and GRACE's commission times, with complete data sets, are used to empirically estimate density enhancements and subsequent orbital drag. The November 2003 magnetic storm (minimum Dst = −422 nT), the most extreme event observed by both satellites, is used as the benchmark event. Results show that, as expected, orbital degradation is more severe for the most intense storms. Additionally, results clearly point out that the time duration of the storm is strongly associated with storm time orbital drag effects, being as important as or even more important than storm intensity itself. The most extreme storm time decays during CHAMP/GRACE‐like sample satellite orbits estimated for the March 1989 magnetic superstorm show that long‐lasting superstorms can have highly detrimental consequences for the orbital dynamics of satellites in LEO.
Poroelastic Solution for the Nonlinear Injectivity of Subsurface Rocks With Strain‐Induced Permeability Variations
Authors: Zhang Wei , Mehrabian Amin
Published: July 2020

Fluid injection in porous rock occurs in a variety of hydrogeological operations including wastewater disposal, CO2 sequestration, enhanced oil recovery, and geothermal energy extraction. Influx of fluid into the host rock is usually accompanied by induced permeability enhancement due to increased pore fluid pressure and consequent dilation of the pore volume. The effect would, in turn, enhance the well injectivity index. This paper presents an analytical solution to the nonlinear problem of underground fluid injection in a disk‐shaped reservoir while accounting for the induced permeability enhancement. The host rock permeability is considered to depend on the rock total stress and pore fluid pressure. For this purpose, the rock stress is formulated as a nonlocal function of disturbances in the pore fluid pressure using the fundamental solution for a nucleus of strain in an elastic half space. Alongside, the nonlinear fluid transport equation that incorporates stress‐sensitive rock permeability is analytically solved using a perturbation technique. The good match with finite difference solution to the same problem verifies the validity and accuracy of the perturbation solution. Parametric study on a test case problem is conducted to examine the influence of different parameters on well injectivity. Findings reveal the higher vulnerability of shallower host reservoirs to stress‐induced permeability variations. The effect of rock poroelastic properties on fluid transport process is discussed.
Advances in understanding of angioimmunoblastic T-cell lymphoma
Authors: Chiba Shigeru , Sakata-Yanagimoto Mamiko
Published: July 2020

It has been nearly half a century since angioimmunoblastic T-cell lymphoma (AITL) was characterized in the early 1970’s. Our understanding of the disease has dramatically changed due to multiple discoveries and insights. One of the key features of AITL is aberrant immune activity. Although AITL is now understood to be a neoplastic disease, pathologists appreciated that it was an inflammatory condition. The more we understand AITL at cellular and genetic levels, the more we view it as both a neoplastic and an inflammatory disease. Here, we review recent progress in our understanding of AITL, focusing on as yet unsolved questions.
Maternal pre-pregnancy overweight and gestational diabetes and dietary intakes among young adult offspring
Authors: Kaseva Nina , Vääräsmäki Marja , Matinolli Hanna-Maria , Sipola Marika , Tikanmäki Marjaana , Kanerva Noora , Heinonen Kati , Lano Aulikki , Wolke Dieter , Andersson Sture , Järvelin Marjo-Riitta , Räikkönen Katri , Eriksson Johan G. , Männistö Satu , Kajantie Eero
Published: July 2020

Background/Objectives

Maternal pre-pregnancy overweight/obesity and gestational diabetes (GDM) are associated with increased fat deposition in adult offspring. The purpose of this study was to identify if maternal pre-pregnancy overweight (body mass index (BMI) ≥ 25 kg/m2) or GDM are associated with dietary quality or intake in adult offspring.

Subjects/Methods

Participants (n = 882) from two longitudinal cohort studies (ESTER Maternal Pregnancy Disorders Study and the Arvo Ylppö Longitudinal Study) completed a validated food-frequency questionnaire at a mean age of 24.2 years (SD 1.3). Diet quality was evaluated by a Recommended Finnish Diet Index (RDI). The study sample included offspring of normoglycaemic mothers with pre-pregnancy overweight/obesity (ONO = 155), offspring of mothers with GDM regardless of BMI (OGDM = 190) and offspring of mothers with normal weight and no GDM (controls; n = 537).

Results

Among men, daily energy and macronutrient intakes were similar in ONO and controls. However, after adjusting for current offspring characteristics, including BMI, daily carbohydrate intake relative to total energy intake was higher in ONO-men [2.2 percentages of total energy intake (95% confidence interval 0.4, 4.0)]. In ONO-women, macronutrient intakes relative to total energy intake were similar with controls, while total daily energy intake seemed lower [−587.2 kJ/day (−1192.0, 4.4)]. After adjusting for confounders, this difference was attenuated. Adherence to a healthy diet, as measured by RDI, was similar in ONO and controls [mean difference: men 0.40 (−0.38, 1.18); women 0.25 (−0.50, 1.00)]. In OGDM vs. controls, total energy and macronutrient intakes were similar for both men and women. Also adherence to a healthy diet was similar [RDI: men 0.09 (−0.62, 0.80); women −0.17 (−0.93, 0.59)].

Conclusions

Our study suggested higher daily carbohydrate intake in male offspring exposed to maternal pre-pregnancy overweight/obesity, compared with controls. Prenatal exposure to GDM was not associated with adult offspring dietary intakes.
Phase 1 safety and pharmacodynamic study of lenalidomide combined with everolimus in patients with advanced solid malignancies with efficacy signal in adenoid cystic carcinoma
Authors: Harvey R. Donald , Carthon Bradley C. , Lewis Colleen , Hossain Mohammad S. , Zhang Chao , Chen Zhengjia , Harris Wayne B. , Alese Olatunji B. , Shaib Walid , Bilen Mehmet A. , Lawson David H. , Wu Christina , Steuer Conor E. , El-Rayes Bassel F. , Khuri Fadlo R. , Lonial Sagar , Waller Edmund K. , Ramalingam Suresh S. , Owonikoko Taofeek K.
Published: July 2020

Background

Purpose: The combination of a mammalian target of rapamycin inhibitor and lenalidomide showed enhanced preclinical cytotoxicity. We conducted a phase 1 study in advanced solid tumour patients to assess safety, efficacy and pharmacodynamic (PD) outcomes.

Methods

We employed a 3+3 dose escalation design to establish the safety and recommended phase 2 doses (RP2D) of daily everolimus and lenalidomide in patients with advanced solid tumours. The starting doses were 5 and 10 mg, respectively, with planned escalation to maximum single-agent doses of 10 and 25 mg in the absence of dose-limiting toxicity. PD endpoints of lymphocyte subsets and immune cytokines were assessed in peripheral blood using multiparameter flow cytometry and LUMINEX assay. Efficacy was evaluated by cross-sectional imaging after every two cycles of treatment.

Results

The study enrolled 44 patients, median age of 58 years and 28 males (63.6%). The RP2D was established as 10 and 25 mg daily continuously for everolimus and lenalidomide. Common (>5%) grade ≥3 adverse events included rash (19%), neutropenia (19%), hypokalaemia (11%) and fatigue (9%). Best efficacy outcomes in 36 evaluable patients were partial response in 5 (13.8%), stable disease in 24 (55.8%) and progressive disease in 7 (19.4%) patients. PD assessment revealed significant association of cytokine levels (interleukin-2 (IL2), IL21 and IL17), baseline activated and total CD8+ lymphocytes and change in B cell lymphocytes and activated NK cells with clinical benefit.

Conclusions

The study demonstrated the safety of everolimus and lenalidomide with promising efficacy signal in thyroid and adenoid cystic cancers.

Clinical Trial Registration

NCT01218555
Reflections on the upsurge of virtual cancer conferences during the COVID-19 pandemic
Authors: Speirs Valerie
Published: July 2020

The COVID-19 pandemic resulted in the cancellation or postponement of traditional face-to-face scientific conferences, necessitating a rapid change in the way new discoveries in cancer were shared with the cancer research community. Here I present personal reflections on the upsurge of virtual cancer conferences, discussing their pros and cons in the context of traditional face-to-face deliveries.
Deacetylation of HSD17B10 by SIRT3 regulates cell growth and cell resistance under oxidative and starvation stresses
Authors: Liu Lu , Chen Shuaiyi , Yu Miao , Ge Chenxu , Ren Mengmeng , Liu Boya , Yang Xin , Christian Thomas W. , Hou Ya-Ming , Zou Junhua , Zhu Wei-Guo , Luo Jianyuan
Published: July 2020

17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) plays an important role in mitochondrial fatty acid metabolism and is also involved in mitochondrial tRNA maturation. HSD17B10 missense mutations cause HSD10 mitochondrial disease (HSD10MD). HSD17B10 with mutations identified from cases of HSD10MD show loss of function in dehydrogenase activity and mitochondrial tRNA maturation, resulting in mitochondrial dysfunction. It has also been implicated to play roles in the development of Alzheimer disease (AD) and tumorigenesis. Here, we found that HSD17B10 is a new substrate of NAD-dependent deacetylase Sirtuin 3 (SIRT3). HSD17B10 is acetylated at lysine residues K79, K99 and K105 by the acetyltransferase CBP, and the acetylation is reversed by SIRT3. HSD17B10 acetylation regulates its enzymatic activity and the formation of mitochondrial RNase P. Furthermore, HSD17B10 acetylation regulates the intracellular functions, affecting cell growth and cell resistance in response to stresses. Our results demonstrated that acetylation is an important regulation mechanism for HSD17B10 and may provide insight into interrupting the development of AD.
Catalytically inactive RIP1 and RIP3 deficiency protect against acute ischemic stroke by inhibiting necroptosis and neuroinflammation
Authors: Zhang Yue , Li Ming , Li Xiaoming , Zhang Haiwei , Wang Lingxia , Wu Xiaoxia , Zhang Haibing , Luo Yan
Published: July 2020

Necroptosis, which is mediated by RIP1/RIP3/MLKL (receptor-interacting protein kinase 1/receptor-interacting protein kinase 3/mixed lineage kinase domain-like protein) signaling, is a critical process in the development of acute ischemic stroke. However, it is unclear precisely how necroptosis promotes the pathogenesis of acute ischemic stroke. In this experimental study in mice, we investigated how necroptosis loss-of-function mice, RIP1 kinase-dead mice, RIP3-deficiency mice, and MLKL-deficiency mice could be protected against cerebral injury after acute ischemic stroke. Insoluble RIP1, RIP3, and MLKL were all detected in the infarct area of the study mice, indicating activation of necroptosis. Two types of RIP1 kinase-dead mutant mice (Rip1K45A/K45A or Rip1Δ/Δ) were used to show that catalytically-inactive RIP1 can decrease the infarct volume and improve neurological function after MCAO/R (middle cerebral artery occlusion/reperfusion). Both Rip3−/− mice and Mlkl−/− mice were protected against acute ischemic stroke. In addition, necroptosis loss-of-function mice showed less inflammatory responses in the infarct area. Therefore, necroptosis and its accompanying inflammatory response can lead to acute injury following ischemia stroke. Our study provides new insight into the pathogenetic mechanisms of acute ischemic stroke, and suggests potential therapeutic targets for neuroprotection.
Hsa_circ_0046263 functions as a ceRNA to promote nasopharyngeal carcinoma progression by upregulating IGFBP3
Authors: Yin Li , Chen Jie , Ma Chengxian , Pei Shuai , Du Mingyu , Zhang Yufeng , Feng Yong , Yin Rong , Bian Xiuhua , He Xia , Feng Jifeng
Published: July 2020

Accumulating evidences indicate that circular RNAs (circRNAs), a subclass of noncoding RNAs, play important role in regulating gene expression in eukaryotes. Hsa_circ_0046263 (circ-0046263) was found aberrantly expressed in nasopharyngeal carcinoma (NPC), but its role in tumor growth and metastasis remains largely unclear. Sanger sequencing, RNase R assay, and nucleic acid electrophoresis were conducted to verify the identification of circ-0046263. Nuclear separation and fluorescence in situ hybridization (FISH) assays were used to determine the localization of circ-004263. Dual luciferase reporter and RNA immunoprecipitation (RIP) were employed to confirm the binding of circ-0046263 with miR-133a-5p. Colony formation, proliferation, wound healing, transwell, western blot, and in vivo tumor growth and metastasis assays were performed to assess the roles of circ-0046263, miR-133a-5p, IGFBP3 and their interactions in NPC cells. Circ-0046263 was upregulated in both NPC cell lines and tissues. The in vitro functional studies revealed that knockdown of circ-0046263 inhibited the proliferation, invasion, and migration of NPC cells, whereas its overexpression produced the opposite result. In vivo experiments indicated that knockdown or overexpression of circ-0046263 attenuated or promoted tumor growth and metastasis, respectively. Mechanistically, circ-0046263 could act as a miRNA sponge to absorb miR-133a-5p and upregulate the expression of miRNA downstream target IGFBP3. In addition, miR-133a-5p inhibition or IGFBP3 overexpression could rescue the malignant behavior induced by circ-0046263 silencing. Finally, circ-0046263 plays a tumor-promoting role in NPC to enhance malignant behavior through the miR-133a-5p/IGFBP3 axis, which could be a potential target for NPC therapy.
Nuclear export of chimeric mRNAs depends on an lncRNA-triggered autoregulatory loop in blood malignancies
Authors: Chen Zhen-Hua , Chen Tian-Qi , Zeng Zhan-Cheng , Wang Dan , Han Cai , Sun Yu-Meng , Huang Wei , Sun Lin-Yu , Fang Ke , Chen Yue-Qin , Luo Xue-Qun , Wang Wen-Tao
Published: July 2020

Aberrant chromosomal translocations leading to tumorigenesis have been ascribed to the heterogeneously oncogenic functions. However, how fusion transcripts exporting remains to be declared. Here, we showed that the nuclear speckle-specific long noncoding RNA MALAT1 controls chimeric mRNA export processes and regulates myeloid progenitor cell differentiation in malignant hematopoiesis. We demonstrated that MALAT1 regulates chimeric mRNAs export in an m6A-dependent manner and thus controls hematopoietic cell differentiation. Specifically, reducing MALAT1 or m6A methyltransferases and the ‘reader’ YTHDC1 result in the universal retention of distinct oncogenic gene mRNAs in nucleus. Mechanically, MALAT1 hijacks both the chimeric mRNAs and fusion proteins in nuclear speckles during chromosomal translocations and mediates the colocalization of oncogenic fusion proteins with METTL14. MALAT1 and fusion protein complexes serve as a functional loading bridge for the interaction of chimeric mRNA and METTL14. This study demonstrated a universal mechanism of chimeric mRNA transport that involves lncRNA-fusion protein-m6A autoregulatory loop for controlling myeloid cell differentiation. Targeting the lncRNA-triggered autoregulatory loop to disrupt chimeric mRNA transport might represent a new common paradigm for treating blood malignancies.
Advancing theoretical understanding and practical performance of signal processing for nonlinear optical communications through machine learning
Authors: Fan Qirui , Zhou Gai , Gui Tao , Lu Chao , Lau Alan Pak Tao
Published: July 2020

In long-haul optical communication systems, compensating nonlinear effects through digital signal processing (DSP) is difficult due to intractable interactions between Kerr nonlinearity, chromatic dispersion (CD) and amplified spontaneous emission (ASE) noise from inline amplifiers. Optimizing the standard digital back propagation (DBP) as a deep neural network (DNN) with interleaving linear and nonlinear operations for fiber nonlinearity compensation was shown to improve transmission performance in idealized simulation environments. Here, we extend such concepts to practical single-channel and polarization division multiplexed wavelength division multiplexed experiments. We show improved performance compared to state-of-the-art DSP algorithms and additionally, the optimized DNN-based DBP parameters exhibit a mathematical structure which guides us to further analyze the noise statistics of fiber nonlinearity compensation. This machine learning-inspired analysis reveals that ASE noise and incomplete CD compensation of the Kerr nonlinear term produce extra distortions that accumulates along the DBP stages. Therefore, the best DSP should balance between suppressing these distortions and inverting the fiber propagation effects, and such trade-off shifts across different DBP stages in a quantifiable manner. Instead of the common ‘black-box’ approach to intractable problems, our work shows how machine learning can be a complementary tool to human analytical thinking and help advance theoretical understandings in disciplines such as optics.
Photodegradable branched polyethylenes from carbon monoxide copolymerization under benign conditions
Authors: Morgen Tobias O. , Baur Maximilian , Göttker-Schnetmann Inigo , Mecking Stefan
Published: July 2020

Small amounts of in-chain keto groups render polyethylene (PE) photodegradable, a desirable feature in view of environmental plastics pollution. Free-radical copolymerization of CO and ethylene is challenging due to the formation of stable acyl radicals which hinders further chain growth. Here, we report that copolymerization to polyethylenes with desirable low ketone content is enabled in dimethyl carbonate organic solvent or under aqueous conditions at comparatively moderate pressures <350 atm that compare favorable to typical ethylene polymerization at 2000 atm. Hereby, thermoplastic processable materials can be obtained as demonstrated by injection molding and tensile testing. Colloidally stable dipersions from aqueous polymerizations form continuous thin films upon drying at ambient conditions. Extensive spectroscopic investigation including 13C labeling provides an understanding of the branching microstructures associated with keto groups. Exposure of injection molded materials or thin films to simulated sunlight under sea-like conditions results in photodegradation.
Author Correction: Combined ground and aerial measurements resolve vent-specific gas fluxes from a multi-vent volcanic system
Authors: Pering T. D. , Liu E. J. , Wood K. , Wilkes T. C. , Aiuppa A. , Tamburello G. , Bitetto M. , Richardson T. , McGonigle A. J. S.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A picture of pseudogap phase related to charge fluxes
Authors: Chen Xi , Dong Jiahao , Li Xin
Published: July 2020

Recently, charge density fluctuations or charge fluxes attract strong interests in understanding the unconventional superconductivity. In this paper, a new emergent configuration in cuprates is identified by density functional theory simulations, called the charge pseudoplane, which exhibits the property of confining the dynamic charge fluxes for higher superconducting transition temperatures. It further redefines the fundamental collective excitation in cuprates as pQon with the momentum-dependent and ultrafast localization-delocalization duality. It is shown that both pseudogap and superconducting phases can be born from and intertwined through the charge flux confinement property of the charge pseudoplane region. Our experimental simulations based on the new picture provide good agreements with previous angle resolved photoemission spectroscopy and scanning tunneling microscopy results. Our work thus opens a new perspective into the origin of the pseudogap phase and other related phases in cuprates, and further provides a critical descriptor to search and design higher temperature superconductors.
Live imaging and functional changes of the inner ear in an animal model of Meniere’s disease
Authors: Kakigi Akinobu , Egami Naoya , Uehara Natsumi , Fujita Takeshi , Nibu Ken-ichi , Yamashita Shinji , Yamasoba Tatsuya
Published: July 2020

The symptoms of Meniere’s disease (MD) are generally considered to be related to endolymphatic hydrops (EH). There are many recent reports supporting the possibility that vasopressin (VP) is closely linked to the formation of EH in Meniere’s disease. Based on this, we developed a clinically relevant animal model of Meniere’s disease in which a VP type 2 receptor agonist was administered after electrocauterization of the endolymphatic sac. We report live imaging of the internal structure, and functional changes of the inner ear after electrocauterization of the endolymphatic sac and administration of a VP type 2 receptor agonist. In this model, the development of EH was visualized in vivo using optical coherence tomography, there was no rupture of Reissner’s membrane, and low-tone hearing loss and vertiginous attacks were observed. This study suggested that acute attacks are caused by the abrupt development of EH. This is the first report of live imaging of the development of EH induced by the administration of a VP type 2 receptor agonist.
Gene expression profiling of glioblastoma cell lines depending on TP53 status after tumor-treating fields (TTFields) treatment
Authors: Lee Yeon-Joo , Seo Hyun Wook , Baek Jeong-Hwa , Lim Sun Ha , Hwang Sang-Gu , Kim Eun Ho
Published: July 2020

Glioblastoma is frequently associated with TP53 mutation, which is linked to a worse prognosis and response to conventional treatments (chemoradiotherapy). Therefore, targeting TP53 is a promising strategy to overcome this poor therapeutic response. Tumor-treating fields (TTFields) are a recently approved treatment for newly diagnosed glioblastoma, which involves direct application of low-intensity, intermediate-frequency alternating electric fields to the tumor, thereby offering a local tumor-killing effect. However, the influence of TP53 mutation status on the effectiveness of TTFields is controversial. Here, we identified the key gene signatures and pathways associated with TTFields in four glioblastoma cell lines varying in TP53 mutation status using gene profiling and functional annotation. Overall, genes associated with the cell cycle, cell death, and immune response were significantly altered by TTFields regardless of TP53 status. TTFields appeared to exert enhanced anti-cancer effects by altering the immune system in the inflammatory environment and regulating cell cycle- and cell death-related genes, but the precise genes influenced vary according to TP53 status. These results should facilitate detailed mechanistic studies on the molecular basis of TTFields to further develop this modality as combination therapy, which can improve the therapeutic effect and minimize side effects of chemoradiotherapy.
Old African fossils provide new evidence for the origin of the American crocodiles
Authors: Delfino Massimo , Iurino Dawid A. , Mercurio Bruno , Piras Paolo , Rook Lorenzo , Sardella Raffaele
Published: July 2020

Molecular and morphological phylogenies concur in indicating that the African lineages formerly referred to Crocodylus niloticus are the sister taxon the four Neotropical crocodiles (Crocodylus intermedius, C. moreleti, C. acutus and C. rhombifer), implying a transoceanic dispersal from Africa to America. So far the fossil record did not contribute to identify a possible African forerunner of the Neotropical species but, curiously, the oldest remains referred to the African C. niloticus are Quaternary in age, whereas the oldest American fossils of Crocodylus are older, being dated to the early Pliocene, suggesting that another species could be involved. We re-described, also thanks to CT imaging, the only well-preserved topotipic skull of Crocodylus checchiai Maccagno, 1947 from the late Miocene (Messinian) African site of As Sahabi in Libya. As previously suggested on the basis of late Miocene material from Tanzania, C. checchiai is a valid, diagnosable species. According to our phylogenetic analyses, C. checchiai is related to the Neotropical taxa and could be even located at the base of their radiation, therefore representing the missing link between the African and the American lineages.
Stabilization of ferulic acid in topical gel formulation via nanoencapsulation and pH optimization
Authors: Das Surajit , Wong Annie B. H.
Published: July 2020

Ferulic acid is a potent anti-oxidant with scientifically proven skin care efficacies. However, instability of this active in the skin care products restricted its wide application in beauty and skin care industries. This study aimed to stabilize ferulic acid in topical hydrogel formulation via nanoencapsulation technique. Ferulic acid loaded nanocapsules were prepared via high pressure homogenization method and physicochemically characterized. Mean particle size of ferulic acid loaded nanocapsules was < 300 nm. TEM and SEM images exhibited spherical particles with smooth surface. DSC and XRD results indicated that ferulic acid was completely dissolved in the lipid matrix of the nanocapsules and remained in amorphous form. Two types of hydrogel formulations containing ferulic acid loaded nanocapsules were prepared: Gel A with pH higher and Gel B with pH lower than pKa of ferulic acid. Cross-polarized microscopic image of the gel formulations did not show presence of any un-encapsulated and un-dissolved crystal. Gel B showed slower and controlled release of ferulic acid than Gel A. Ferulic acid permeation through skin mimic from the gel formulation demonstrated controlled permeation. Color stability of the gel and chemical stability of ferulic acid were very good in Gel B, while poor in Gel A (although significantly better than the gel with un-encapsulated ferulic acid). The result clearly indicates that together with nanoencapsulation, low pH (less than pKa of ferulic acid) of the hydrogel was crucial for both product appearance and chemical stability of ferulic acid. In fact, it has been proved that skin care product with low pH is good for skin as it can maintain skin homeostasis and microbiome. Furthermore, the permeation result suggests that ferulic acid may penetrate into deep skin layers and at the same time avoid systemic circulation. Overall, this low pH hydrogel formulation containing nanoencapsulated ferulic acid demonstrates great promise for commercialization.
Brown adipose tissue ameliorates autoimmune arthritis via inhibition of Th17 cells
Authors: Moon Jeonghyeon , Kim Dasom , Kim Eun Kyung , Lee Seon-yeong , Na Hyun Sik , Kim Gyoung Nyun , Lee Aram , Jung KyungAh , Choi Jeong Won , Park Sung-Hwan , Roh Sangho , Cho Mi-La
Published: July 2020

The functions of adipose tissue are associated with autoimmune diseases, such as rheumatoid arthritis (RA). Some studies have shown that the three compositions of adipose tissue (white, brown, and beige) have different functions. Brown adipose tissue (BAT) is known to secrete several factors that differ from those in white adipose tissue. This suggests that BAT might have potential positive advantages in the physiology of autoimmune diseases. We compared the functions of collagen-induced arthritis mice-derived BAT (CIA BAT) with normal mice-derived BAT. DBA/1J mice (6–7 weeks of age) were immunized by intradermal injection at the base of the tail with 100 μg of bovine type II collagen (CII) emulsified in complete Freund’s adjuvant. Immunized mice then received booster immunizations by intraperitoneal injection with 100 μg of CII in incomplete Freund’s adjuvant. We transplanted CIA BAT and normal BAT into CIA recipient mice. After transplantation, we measured the functions of CIA BAT and normal BAT in mice. Normal BAT-transplanted mice showed significantly lower scores of bone damage, inflammation, and cartilage damage. The proinflammatory cytokines in normal BAT-transplanted mice, such as IL-12, IL-17, IL-6, and tumor necrosis factor-α (TNF-α), tended to decrease. Microarray analysis showed that the PI3K-AKT signaling pathway and IL-17 levels of CIA BAT tissues were significantly higher than those of normal BAT tissues. These results suggest that the transplantation of normal brown fat may have a therapeutic effect in RA patients.
Antibacterial and antifungal activity of crude and freeze-dried bacteriocin-like inhibitory substance produced by Pediococcus pentosaceus
Authors: de Souza de Azevedo Pamela Oliveira , Mendonça Carlos Miguel Nóbrega , Moreno Ana Carolina Ramos , Bueno Antonio Vinicius Iank , de Almeida Sonia Regina Yokomizo , Seibert Liane , Converti Attilio , Watanabe Ii-Sei , Gierus Martin , de Souza Oliveira Ricardo Pinheiro
Published: July 2020

Pediococcus pentosaceus LBM 18 has shown potential as producer of an antibacterial and antifungal bacteriocin-like inhibitory substance (BLIS). BLIS inhibited the growth of spoilage bacteria belonging to Lactobacillus, Enterococcus and Listeria genera with higher activity than Nisaplin used as control. It gave rise to inhibition halos with diameters from 9.70 to 20.00 mm, with Lactobacillus sakei being the most sensitive strain (13.50–20.00 mm). It also effectively suppressed the growth of fungi isolated from corn grain silage for up to 25 days and impaired morphology of colonies by likely affecting fungal membranes. These results point out that P. pentosaceus BLIS may be used as a new promising alternative to conventional antibacterial and antifungal substances, with potential applications in agriculture and food industry as a natural bio-controlling agent. Moreover, cytotoxicity and cell death induction tests demonstrated cytotoxicity and toxicity of BLIS to human colon adenocarcinoma Caco-2cells but not to peripheral blood mononuclear cells, with suggests possible applications of BLIS also in medical-pharmaceutical applications.
Application of next generation sequencing (NGS) for descriptive analysis of 30 genomes of Leishmania infantum isolates in Middle-North Brazil
Authors: Carvalho Kátia Silene Sousa , da Silva Júnior Wilson José , da Silveira Regueira Neto Marcos , Silva Vladimir Costa , de Sá Leitão Paiva Júnior Sérgio , Balbino Valdir Queiroz , Costa Dorcas Lamounier , Costa Carlos Henrique Nery
Published: July 2020

Visceral leishmaniasis (VL) is a life-threatening disease caused by the protozoa Leishmania donovani and L. infantum. Likely, L. infantum was introduced in the New World by the Iberic colonizers. Due to recent introduction, the genetic diversity is low. Access to genomic information through the sequencing of Leishmania isolates allows the characterization of populations through the identification and analysis of variations. Population structure information may reveal important data on disease dynamics. Aiming to describe the genetic diversity of L. infantum from the Middle-North, Brazil, next generation sequencing of 30 Leishmania isolates obtained in the city of Teresina, from where the disease dispersed, was performed. The variations were categorized accordingly to the genome region and impact and provided the basis for chromosomal ploidy and population structure analysis. The results showed low diversity between the isolates and the Iberic reference genome JPCM5. Most variations were seen in non-coding regions, with modifying impact. The ploidy number analysis showed aneuploid profile. The population structure analysis revealed the presence of two L. infantum populations identified in Teresina. Further population genetics studies with a larger number of isolates should be performed in order to identify the genetic background associated with virulence and parasite ecology.
Hemisphere-specific, differential effects of lateralized, occipital–parietal α- versus γ-tACS on endogenous but not exogenous visual-spatial attention
Authors: Kasten Florian H. , Wendeln Tea , Stecher Heiko I. , Herrmann Christoph S.
Published: July 2020

Orienting spatial attention has been associated with interhemispheric asymmetry of power in the α- and γ-band. Specifically, increased α-power has been linked to the inhibition of unattended sensory streams (e.g. the unattended visual field), while increased γ-power is associated with active sensory processing. Here, we aimed to differentially modulate endogenous and exogenous visual-spatial attention using transcranial alternating current stimulation (tACS). In a single-blind, within-subject design, participants performed several blocks of a spatial cueing task comprised of endogenous and exogenous cues while receiving lateralized α- or γ-tACS or no stimulation over left or right occipital-parietal areas. We found a significant, differential effect of α- and γ-tACS on endogenous (top-down) spatial attention but not on exogenous (bottom-up) attention. The effect was specific to tACS applied to the left hemisphere and driven by a modulation of attentional disengagement and re-orientation as measured during invalid trials. Our results indicate a causal role of α-/γ-oscillations for top-down (endogenous) attention. They may further suggest a left hemispheric dominance in controlling interhemispheric α-/γ-power asymmetry. The absence of an effect on exogenous attention may be indicative of a differential role of α-/γ-oscillations during different attention types or spatially distinct attentional subsystems.