bluuebunny/crossref_metadata_2025 huggingface dataset:
Executive deficits in schizophrenia: mediation by processing speed and its relationships with aging
Authors: Thuaire Flavien , Rondepierre Fabien , Vallet Guillaume T. , Jalenques Isabelle , Izaute Marie
Published: August 2020

Background

Executive deficits are a core characteristic of schizophrenia. Yet, the origin of these impairments remains unclear as they may be caused by processing slowing. This issue is of particular interest for aging insofar as cognitive aging is also associated with a decline in executive functioning and a slowing of processing speed. As schizophrenia patients’ life expectancy increases, a better understanding of the origin of older patients’ cognitive deficits becomes essential so that healthcare can be adapted to suit them. This study aims to determine whether processing speed mediates how schizophrenia affects executive functions and whether these relationships are moderated by age.

Methods

Sixty-two schizophrenia patients (27 women) and 62 healthy comparison subjects matched for age (range: 18–76 years), gender and education performed neurocognitive tests to evaluate their executive functions (shifting, updating, inhibition and access) and processing speed.

Results

Processing speed mediated the effect of schizophrenia on the four specific executive functions, and age moderated this mediation for shifting, updating and access, but in different ways. Age moderated the effect of processing speed on shifting, the direct effect of schizophrenia on access, and both the effect of processing speed and the direct effect of schizophrenia on updating.

Conclusions

This research highlights the need to evaluate processing speed routinely during therapeutic follow-up, as it is easy and simple to assess and appears to be at the heart of the cognitive deficits in schizophrenia. Finally, processing speed abilities yield information about the evolution of cognition with aging in schizophrenia.
Theorizing Popular Sovereignty in the Colony: Abul Aʿla Maududi's “Theodemocracy”
Authors: Iqtidar Humeira
Published: August 2020

Abul Aʿla Maududi (1903–1979), the influential Indo-Pakistani Islamist thinker, proposed a detailed vision of what he called “theodemocracy.” This has been seen widely as a theocracy despite Maududi's explicit rejection of the term and its philosophical underpinnings. I suggest here that Maududi's vision of theodemocracy opens up a productive space for reflection on the relationship between popular and state sovereignty. Maududi saw popular sovereignty as an ethical problem; it corrupted the potential for individual moral development that the institutional mechanism of the state could otherwise allow for. Highlighting the complicated relationship of his ideas with colonial rule, and showing that he used the colonial liberal state as both a foiland modelfor his analysis, I argue here that “theodemocracy” was his attempt at divorcing sovereignty from the state. This endeavor generated creative tensions, and forms an important contribution to the global discussion about sovereignty and the state.
STOCHASTIC ORDERING OF LIFETIMES OF PARALLEL AND SERIES SYSTEMS COMPRISING HETEROGENEOUS DEPENDENT COMPONENTS WITH GENERALIZED BIRNBAUM-SAUNDERS DISTRIBUTIONS
Authors: Amiri Mehdi , Balakrishnan Narayanaswamy , Jamalizadeh Ahad
Published: August 2020

In this paper, we discuss stochastic orderings of lifetimes of two heterogeneous parallel and series systems with heterogeneous dependent components having generalized Birnbaum–Saunders distributions. The comparisons presented here are based on the vector majorization of parameters. The ordering results are established in some special cases for the generalized Birnbaum–Saunders distribution based on the multivariate elliptical, normal, t, logistic, and skew-normal kernels. Further, we use these results by considering Archimedean copulas to model the dependence structure among systems with generalized Birnbaum–Saunders components. These results have been used to derive some upper and lower bounds for survival functions of lifetimes of parallel and series systems.
Moral marketplaces: regulating the food markets of late Elizabethan and early Stuart London
Authors: Taverner Charlie
Published: August 2020

This article examines the economic culture of urban food markets in early modern England. It focuses on London between 1590 and 1640 to argue that market regulation, even in fast-growing, commercializing cities, was underpinned by moralized values. It also assesses a largely untapped citywide book of fines, containing payments for regulatory offences. The first section outlines London's market system and regulation, the second looks at enforcement in practice and the third discusses the underlying values. This contributes to our understanding of day-to-day food marketing and proposes that studies of ‘moral economy’ should examine everyday commerce and major cities.
BMI, high-sensitivity C-reactive protein and the conversion from metabolically healthy to unhealthy phenotype in Chinese adults: a cohort study
Authors: Xu Renying , Shen Peixiao , Wu Chunhua , Wan Yanping , Fan Zhuping , Gao Xiang
Published: August 2020

Objective:

We performed the cohort study to evaluate the association between BMI, high-sensitivity C-reactive protein (hs-CRP) and the conversion from metabolically healthy to unhealthy phenotype in Chinese adults.

Design:

Metabolically healthy was defined as participants without history of metabolic diseases and with normal fasting blood glucose level, glycated Hb A1c level, blood pressure, lipid profile, serum uric acid level and liver ultrasonographic findings at baseline. Participants were either classified into normal weight (18·5 ≤ BMI < 24·0 kg/m2) and overweight (BMI ≥ 24·0 kg/m2) based on baseline BMI, or low (<1 mg/l) and high (≥1 mg/l) groups based on baseline hs-CRP. The conversion from metabolically healthy to unhealthy phenotype was deemed if any of the metabolic abnormalities had been confirmed twice or more during 5 years of follow-up.

Results:

Included were 4855 (1942 men and 2913 women, aged 36·0 ± 8·9 years) metabolically healthy Chinese adults. We identified 1692 participants who converted to metabolically unhealthy phenotype during the follow-up. Compared with their counterparts, the adjusted hazards ratio of the conversion was 1·19 (95 % CI 1·07, 1·33) for participants with overweight, while it was 1·15 (95 % CI 1·03, 1·29) for those with high hs-CRP level (≥1 mg/l). Further adjustment of hs-CRP did not materially change the association between BMI and the conversion. However, the association between hs-CRP and the conversion was not significant after further adjustment of BMI. The sensitivity analysis generated similar results to main analysis.

Conclusion:

BMI was associated with the risk of the conversion from metabolically healthy to unhealthy status in Chinese adults.
Status of palliative care education in Mainland China: A systematic review
Authors: Willemsen Antonia M. , Mason Stephen , Zhang Silja , Elsner Frank
Published: August 2020

Objective

China is home to one-fifth of the world's population. In the setting of a growing and aging population as well as the designation of palliative care access as a human right in 2013, the implementation of palliative care in China gains special importance. Palliative care education is an important precondition to ensure a nationwide access to palliative care. This systematic review details the status of under- and postgraduate palliative care education in China, examining both the students’ and physicians’ perception, knowledge, and skills in palliative care, and the available educational interventions and programs.

Method

Four databases were searched in September 2018, using considered search terms. Titles, abstracts, and, if necessary, full texts were scanned to identify publications matching the inclusion criteria.

Results

Nine publications were included. They revealed six findings: palliative care education is lacking in both under- and postgraduate medical education, only a few programs exist. Palliative care as a concept is well known, detailed knowledge, and practical skills are less developed. Chinese physicians consider palliative care an important field to be developed in cancer care, yet the majority of healthcare professionals are not willing to work in palliative care services. Communication should be a main emphasis in palliative care education, especially in undergraduate training. Finally, there is no highly qualified research on under- or postgraduate palliative care education in Mainland China.

Significance of results

These findings suggest that palliative care education in China is in demand and should be systematically integrated into medical education. Further research on the topic is urgently needed.
International vs. area? The disciplinary-politics of knowledge-exchange between IR and Area Studies
Authors: Aris Stephen
Published: August 2020

Within the political-economy of the social sciences, Area Studies (AS) is supposed to supply contextually-informed knowledge on (non-Western) areas to the other social sciences, in exchange for theory to guide further empirical investigations. Based on this assumption, there are regular calls for greater engagement with AS to counteract the shortcomings of International Relations’ (IR) knowledge-base on many areas, perspectives, and practices of the international. However, there has been little work empirically detailing knowledge-exchange practices between IR and AS, so it remains an open question if the relationship functions as an exchange of ‘international’ theory-for-‘area’ empirics. This paper provides a macro-sociological analysis of the practices of IR–AS knowledge-exchange. By focusing on citation practice, it moves beyond accounts that treat the two disciplines as ‘black boxes’, to trace which parts of the ‘dividing discipline’ of IR are active in exchanging knowledge with which ‘area’ scholarships. Hence, it asks: Are there ‘area’ blindspots in IR's knowledge-production? And, what type of IR theory is exported to AS? This analysis informs an assessment of whether AS represents a significant resource for IR in its efforts to, one, better inform its knowledge-production about ‘other’ areas of the international, and two, assert its disciplinary-relevance within the academy.
The GFDL Global Atmospheric Chemistry‐Climate Model AM4.1: Model Description and Simulation Characteristics
Authors: Horowitz Larry W. , Naik Vaishali , Paulot Fabien , Ginoux Paul A. , Dunne John P. , Mao Jingqiu , Schnell Jordan , Chen Xi , He Jian , John Jasmin G. , Lin Meiyun , Lin Pu , Malyshev Sergey , Paynter David , Shevliakova Elena , Zhao Ming
Published: August 2020

We describe the baseline model configuration and simulation characteristics of the Geophysical Fluid Dynamics Laboratory (GFDL)'s Atmosphere Model version 4.1 (AM4.1), which builds on developments at GFDL over 2013–2018 for coupled carbon‐chemistry‐climate simulation as part of the sixth phase of the Coupled Model Intercomparison Project. In contrast with GFDL's AM4.0 development effort, which focused on physical and aerosol interactions and which is used as the atmospheric component of CM4.0, AM4.1 focuses on comprehensiveness of Earth system interactions. Key features of this model include doubled horizontal resolution of the atmosphere (~200 to ~100 km) with revised dynamics and physics from GFDL's previous‐generation AM3 atmospheric chemistry‐climate model. AM4.1 features improved representation of atmospheric chemical composition, including aerosol and aerosol precursor emissions, key land‐atmosphere interactions, comprehensive land‐atmosphere‐ocean cycling of dust and iron, and interactive ocean‐atmosphere cycling of reactive nitrogen. AM4.1 provides vast improvements in fidelity over AM3, captures most of AM4.0's baseline simulations characteristics, and notably improves on AM4.0 in the representation of aerosols over the Southern Ocean, India, and China—even with its interactive chemistry representation—and in its manifestation of sudden stratospheric warmings in the coldest months. Distributions of reactive nitrogen and sulfur species, carbon monoxide, and ozone are all substantially improved over AM3. Fidelity concerns include degradation of upper atmosphere equatorial winds and of aerosols in some regions.
Some Farm Animals Might Have a Sense About Impending Earthquakes
Authors: Learn Joshua
Published: August 2020

Stabled animals seem to grow fidgety in the hours before an earthquake, whereas their free-range counterparts show no discernible difference in behavior.
Storm‐Time Coupling of Equatorial Nighttime F Region Neutral Winds and Plasma Drifts
Authors: Navarro L. A. , Fejer B. G.
Published: August 2020

We used observations from the Peruvian Fabry‐Perot Interferometer network and from the Jicamarca radar to study the coupling of equatorial nighttime thermospheric winds and ionospheric drifts under moderate solar flux conditions. We show that the coupling of the extended quiet time zonal winds and drifts increases from dusk to midnight and is stronger during equinox than during June solstice. After midnight, they are strongly coupled, except during December solstice when the drifts are stronger. The nighttime disturbance zonal winds and drifts, derived by removing the corresponding quiet time values, are westward with peak magnitudes around midnight. They are in close agreement, except at early night when the winds are stronger, and have strongest (weakest) magnitudes during equinox (June solstice). We also present observations showing the strong neutral wind‐plasma drift coupling during the September 2017 and August 2015 large geomagnetic storms. We show that during the early phase of the September 2017 storm there were large and short‐lived, prompt penetration electric field‐driven, correlated oscillations (~1 hr) in the vertical and zonal plasma drifts, and in the zonal and meridional winds. These are the first observations of prompt penetration‐driven equatorial zonal and meridional wind disturbances. In this event, the vertical and zonal drift oscillations were anticorrelated, and the zonal winds followed the zonal drift oscillations with a delay of ~15 min. Our results illustrate the strong coupling of equatorial thermospheric winds and plasma drifts during geomagnetically quiet as well as during short‐lived prompt penetration and long‐lasting disturbance dynamo events.
Australian Rainfall Anomalies in 2018–2019 Linked to Indo‐Pacific Driver Indices Using ERA5 Reanalyses
Authors: Watterson I. G.
Published: August 2020

The 2019 and 2018–2019 periods had record low All‐Australia rainfall in both observations and the ECMWF's Reanalysis 5, or ERA5, data set over 1979–2019. An analysis of the relationships between interannual variability of rainfall and atmospheric circulation, vertically integrated moisture flux, and temperature anomalies using ERA5 alone is undertaken. Both standard driver indices and those that combine the Pacific and Indian Ocean influences are used. Regression fields for low annual Australian rainfall show a widespread negative rainfall anomaly extending into the east Indian Ocean or IND region and a positive anomaly in the western Pacific PAC region. A moisture flux anomaly takes moisture eastwards toward PAC. This pattern largely persists in the four seasons. In March–May 2019 it can be partially linked to a positive Niño 3.4 anomaly and in June–August to a positive Indian Ocean Dipole. For the annual case, the detrended Niño 4 index explains 24% of the 2019 ERA5 Australian rainfall deficit. This rises to 38% for the 2018–2019 deficit (46% for observations), for the Pacific‐Indian Dipole index that combines the PAC and IND regions, whose sea surface temperature anomalies have opposite effects. The correlation of the index with 2‐year rainfall is −0.7. There is much variability, in the Australian monsoon rainfall especially, that is not linked to simple indices, although rainfall is well matched with moisture flux convergence. This extends to the equatorial zone where the climate of the Maritime Continent can be better examined with ERA5's 0.25° data.
New Insights Into Legacy Phosphorus From Fractionation of Streambed Sediment
Authors: Lannergård Emma E. , Agstam‐Norlin Oskar , Huser Brian J. , Sandström Sara , Rakovic Jelena , Futter Martyn N.
Published: August 2020

Streambed and lake sediment was studied in Sävjaån, a eutrophic mesoscale catchment (722 km2) in central Sweden. Triplicate sediment cores from five lakes and nine streams, ranging from headwater to fourth order, were sampled. The sediment was analyzed with a sequential extraction method, where six different phosphorus (P) fractions were measured. The results showed that streambed sediments store considerable amounts of P and in some cases have comparable P contents (g/kg DW) to lake sediment. Land use, soil type, and drainage area (location in the catchment) had a significant effect on the different P fractions found in surficial sediments. Sediment from lakes and forested headwater streams generally had high proportions of organic P and iron bound P. In larger streams located in agricultural areas on clay soils closer to the catchment outlet, with dense sediment and a relatively low proportion of organic matter, P was to a larger extent bound to calcium. Streambed sediment may be an important catchment scale P store and should be considered when modeling catchment P dynamics. The large stores of streambed legacy P should also be considered when performing ditch maintenance to avoid unnecessary mobilization of bioavailable P.
Characterization of FLT3-ITDmut acute myeloid leukemia: molecular profiling of leukemic precursor cells
Authors: Travaglini Serena , Angelini Daniela Francesca , Alfonso Valentina , Guerrera Gisella , Lavorgna Serena , Divona Mariadomenica , Nardozza Anna Maria , Consalvo Maria Irno , Fabiani Emiliano , De Bardi Marco , Neri Benedetta , Forghieri Fabio , Marchesi Francesco , Paterno Giovangiacinto , Cerretti Raffaella , Barragan Eva , Fiori Valentina , Dominici Sabrina , Del Principe Maria Ilaria , Venditti Adriano , Battistini Luca , Arcese William , Lo-Coco Francesco , Voso Maria Teresa , Ottone Tiziana
Published: August 2020

Acute myeloid leukemia (AML) with FLT3-ITD mutations (FLT3-ITDmut) remains a therapeutic challenge, with a still high relapse rate, despite targeted treatment with tyrosine kinase inhibitors. In this disease, the CD34/CD123/CD25/CD99+ leukemic precursor cells (LPCs) phenotype predicts for FLT3-ITD-positivity. The aim of this study was to characterize the distribution of FLT3-ITD mutation in different progenitor cell subsets to shed light on the subclonal architecture of FLT3-ITDmut AML. Using high-speed cell sorting, we sequentially purified LPCs and CD34+ progenitors in samples from patients with FLT3-ITDmut AML (n = 12). A higher FLT3-ITDmut load was observed within CD34/CD123/CD25/CD99+ LPCs, as compared to CD34+ progenitors (CD123+/−,CD25−,CD99low/−) (p = 0.0005) and mononuclear cells (MNCs) (p < 0.0001). This was associated with significantly increased CD99 mean fluorescence intensity in LPCs. Significantly higher FLT3-ITDmut burden was also observed in LPCs of AML patients with a small FLT3-ITDmut clones at diagnosis. On the contrary, the mutation burden of other myeloid genes was similar in MNCs, highly purified LPCs and/or CD34+ progenitors. Treatment with an anti-CD99 mAb was cytotoxic on LPCs in two patients, whereas there was no effect on CD34+ cells from healthy donors. Our study shows that FLT3-ITD mutations occur early in LPCs, which represent the leukemic reservoir. CD99 may represent a new therapeutic target in FLT3-ITDmut AML.
RETRACTED ARTICLE: Origin and cross-species transmission of bat coronaviruses in China
Authors: Latinne Alice , Hu Ben , Olival Kevin J. , Zhu Guangjian , Zhang Libiao , Li Hongying , Chmura Aleksei A. , Field Hume E. , Zambrana-Torrelio Carlos , Epstein Jonathan H. , Li Bei , Zhang Wei , Wang Lin-Fa , Shi Zheng-Li , Daszak Peter
Published: August 2020

Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the evolution and diversification of these coronaviruses remains poorly understood. Here we use a Bayesian statistical framework and a large sequence data set from bat-CoVs (including 630 novel CoV sequences) in China to study their macroevolution, cross-species transmission and dispersal. We find that host-switching occurs more frequently and across more distantly related host taxa in alpha- than beta-CoVs, and is more highly constrained by phylogenetic distance for beta-CoVs. We show that inter-family and -genus switching is most common in Rhinolophidae and the genus Rhinolophus. Our analyses identify the host taxa and geographic regions that define hotspots of CoV evolutionary diversity in China that could help target bat-CoV discovery for proactive zoonotic disease surveillance. Finally, we present a phylogenetic analysis suggesting a likely origin for SARS-CoV-2 in Rhinolophus spp. bats.
Blood substitution therapy rescues the brain of mice from ischemic damage
Authors: Ren Xuefang , Hu Heng , Farooqi Imran , Simpkins James W.
Published: August 2020

Acute stroke causes complex, pathological, and systemic responses that have not been treatable by any single medication. In this study, using a murine transient middle cerebral artery occlusion stroke model, a novel therapeutic strategy is proposed, where blood replacement (BR) robustly reduces infarctions and improves neurological deficits in mice. Our analyses of immune cell subsets suggest that BR therapy substantially decreases neutrophils in blood following a stroke. Electrochemiluminescence detection demonstrates that BR therapy reduces cytokine storm in plasma and ELISA demonstrates reduced levels of matrix metalloproteinase-9 (MMP-9) in the plasma and brains at different time points post-stroke. Further, we have demonstrated that the addition of MMP-9 to the blood diminishes the protective effect of the BR therapy. Our study is the first to show that BR therapy leads to profoundly improved stroke outcomes in mice and that the improved outcomes are mediated via MMP-9. These results offer new insights into the mechanisms of stroke damage.
Ultrafast terahertz magnetometry
Authors: Zhang Wentao , Maldonado Pablo , Jin Zuanming , Seifert Tom S. , Arabski Jacek , Schmerber Guy , Beaurepaire Eric , Bonn Mischa , Kampfrath Tobias , Oppeneer Peter M. , Turchinovich Dmitry
Published: August 2020

A material’s magnetic state and its dynamics are of great fundamental research interest and are also at the core of a wide plethora of modern technologies. However, reliable access to magnetization dynamics in materials and devices on the technologically relevant ultrafast timescale, and under realistic device-operation conditions, remains a challenge. Here, we demonstrate a method of ultrafast terahertz (THz) magnetometry, which gives direct access to the (sub-)picosecond magnetization dynamics even in encapsulated materials or devices in a contact-free fashion, in a fully calibrated manner, and under ambient conditions. As a showcase for this powerful method, we measure the ultrafast magnetization dynamics in a laser-excited encapsulated iron film. Our measurements reveal and disentangle distinct contributions originating from (i) incoherent hot-magnon-driven magnetization quenching and (ii) coherent acoustically-driven modulation of the exchange interaction in iron, paving the way to technologies utilizing ultrafast heat-free control of magnetism. High sensitivity and relative ease of experimental arrangement highlight the promise of ultrafast THz magnetometry for both fundamental studies and the technological applications of magnetism.
Exposure to air pollution and scarlet fever resurgence in China: a six-year surveillance study
Authors: Liu Yonghong , Ding Hui , Chang Shu-ting , Lu Ran , Zhong Hui , Zhao Na , Lin Tzu-Hsuan , Bao Yiming , Yap Liwei , Xu Weijia , Wang Minyi , Li Yuan , Qin Shuwen , Zhao Yu , Geng Xingyi , Wang Supen , Chen Enfu , Yu Zhi , Chan Ta-Chien , Liu Shelan
Published: August 2020

Scarlet fever has resurged in China starting in 2011, and the environment is one of the potential reasons. Nationwide data on 655,039 scarlet fever cases and six air pollutants were retrieved. Exposure risks were evaluated by multivariate distributed lag nonlinear models and a meta-regression model. We show that the average incidence in 2011–2018 was twice that in 2004–2010 [RR = 2.30 (4.40 vs. 1.91), 95% CI: 2.29–2.31; p < 0.001] and generally lower in the summer and winter holiday (p = 0.005). A low to moderate correlation was seen between scarlet fever and monthly NO2 (r = 0.21) and O3 (r = 0.11). A 10 μg/m3 increase of NO2 and O3 was significantly associated with scarlet fever, with a cumulative RR of 1.06 (95% CI: 1.02–1.10) and 1.04 (95% CI: 1.01–1.07), respectively, at a lag of 0 to 15 months. In conclusion, long-term exposure to ambient NO2 and O3 may be associated with an increased risk of scarlet fever incidence, but direct causality is not established.
Cryo-EM structure of trimeric Mycobacterium smegmatis succinate dehydrogenase with a membrane-anchor SdhF
Authors: Gong Hongri , Gao Yan , Zhou Xiaoting , Xiao Yu , Wang Weiwei , Tang Yanting , Zhou Shan , Zhang Yuying , Ji Wenxin , Yu Lu , Tian Changlin , Lam Sin Man , Shui Guanghou , Guddat Luke W. , Wong Luet-Lok , Wang Quan , Rao Zihe
Published: August 2020

Diheme-containing succinate:menaquinone oxidoreductases (Sdh) are widespread in Gram-positive bacteria but little is known about the catalytic mechanisms they employ for succinate oxidation by menaquinone. Here, we present the 2.8 Å cryo-electron microscopy structure of a Mycobacterium smegmatis Sdh, which forms a trimer. We identified the membrane-anchored SdhF as a subunit of the complex. The 3 kDa SdhF forms a single transmembrane helix and this helix plays a role in blocking the canonically proximal quinone-binding site. We also identified two distal quinone-binding sites with bound quinones. One distal binding site is formed by neighboring subunits of the complex. Our structure further reveals the electron/proton transfer pathway for succinate oxidation by menaquinone. Moreover, this study provides further structural insights into the physiological significance of a trimeric respiratory complex II. The structure of the menaquinone binding site could provide a framework for the development of Sdh-selective anti-mycobacterial drugs.
Confinement in crystal lattice alters entire photocycle pathway of the Photoactive Yellow Protein
Authors: Konold Patrick E. , Arik Enis , Weißenborn Jörn , Arents Jos C. , Hellingwerf Klaas J. , van Stokkum Ivo H. M. , Kennis John T. M. , Groot Marie Louise
Published: August 2020

Femtosecond time-resolved crystallography (TRC) on proteins enables resolving the spatial structure of short-lived photocycle intermediates. An open question is whether confinement and lower hydration of the proteins in the crystalline state affect the light-induced structural transformations. Here, we measured the full photocycle dynamics of a signal transduction protein often used as model system in TRC, Photoactive Yellow Protein (PYP), in the crystalline state and compared those to the dynamics in solution, utilizing electronic and vibrational transient absorption measurements from 100 fs over 12 decades in time. We find that the photocycle kinetics and structural dynamics of PYP in the crystalline form deviate from those in solution from the very first steps following photon absorption. This illustrates that ultrafast TRC results cannot be uncritically extrapolated to in vivo function, and that comparative spectroscopic experiments on proteins in crystalline and solution states can help identify structural intermediates under native conditions.
Neural signal analysis with memristor arrays towards high-efficiency brain–machine interfaces
Authors: Liu Zhengwu , Tang Jianshi , Gao Bin , Yao Peng , Li Xinyi , Liu Dingkun , Zhou Ying , Qian He , Hong Bo , Wu Huaqiang
Published: August 2020

Brain-machine interfaces are promising tools to restore lost motor functions and probe brain functional mechanisms. As the number of recording electrodes has been exponentially rising, the signal processing capability of brain–machine interfaces is falling behind. One of the key bottlenecks is that they adopt conventional von Neumann architecture with digital computation that is fundamentally different from the working principle of human brain. In this work, we present a memristor-based neural signal analysis system, where the bio-plausible characteristics of memristors are utilized to analyze signals in the analog domain with high efficiency. As a proof-of-concept demonstration, memristor arrays are used to implement the filtering and identification of epilepsy-related neural signals, achieving a high accuracy of 93.46%. Remarkably, our memristor-based system shows nearly 400× improvements in the power efficiency compared to state-of-the-art complementary metal-oxide-semiconductor systems. This work demonstrates the feasibility of using memristors for high-performance neural signal analysis in next-generation brain–machine interfaces.
A fine resolution dataset of accessibility under different traffic conditions in European cities
Authors: Christodoulou Aris , Dijkstra Lewis , Christidis Panayotis , Bolsi Paolo , Poelman Hugo
Published: August 2020

Urban accessibility and congestion indicators allow us to benchmark cities. If these indicators are also available at a fine resolution, we can compare different neighbourhoods within a city. We present a dataset of different accessibility indicators for all urban areas with more than 250 thousand people in the EU27, the UK, Switzerland and Norway. Each city is analysed by means of a population grid of 500 m by 500 m and represented by a wider area covering both the densely populated urban centre and the commuting zone. To capture congestion, we measure accessibility for each grid cell at different times of the day that correspond to different traffic conditions using the detailed network and congestion information provided by TomTom.
Experimental investigation of the dynamic cavitation behavior and wall static pressure characteristics through convergence-divergence venturis with various divergence angles
Authors: Liu Yinan , Fan Hua , Wu Di , Chen Haijun , Feng Kuolei , Zhao Chaocheng , Wu Dongyin
Published: August 2020

As a highly efficient and energy-saving cavitation method, Venturi cavitation is widely used in many industrial fields. This study synchronously investigated the cavity behavior and its corresponding wall static pressure characteristics in Venturi channels with various divergence angles to research the role of the divergence angle in cavity shape and the wall static pressure oscillation. Five rectangular Venturi channels with different divergence angles (4°, 6°, 8°, 10°, and 12°) were tested at the cavitation number (0.3–1.0). Based on the dynamic behaviour of gas–liquid interface, three cavity shedding types were identified: front shedding (I), central shedding (II) and tail shedding (III). A modified correlation for predicting average cavity length was proposed with the consideration of the effect of the divergence angle. Combined with the wall static pressure characteristics, as the divergence angle increased, the wall static pressure fluctuation in the Venturi became more intense. According to the wall static pressure oscillation characteristics, for the larger divergence angles (θ = 6°, 8°, 10° and 12°), the wall static pressure oscillation frequency was the same as the cavity shedding frequency and increased with the increase of the divergence angle. For smaller divergence angle (θ = 4°), no definite periodicity in pressure oscillation frequency could be observed.
New water-soluble colorimetric pH and metal ione sensor based on graphene quantum dot modified with alizarine red S
Authors: Ahmadi Hassan , Keshipour Sajjad , Ahour Fatemeh
Published: August 2020

A new colorimetric sensor was designed for the screening pH changes in solutions, as well as, detection of some cations. The sensor preparation includes the chemical binding of alizarine red S (ARS) as a sensor of pH and cation to graphene quantum dots (GQD). Loading ARS on GQD led to the formation of water soluble sensor which finally responded to the colorimetric detection of some cations in water. Solubility and stability of the sensor in water indicate that the sensor is an ideal system for the biological and environmental applications. To demonstrate the applicability of the new sensor, the colorimetric responds of sensor were examined for some cations including Fe3+, Co2+, Ca2+, As3+, Cd2+, Hg2+, Pb2+, Sn2+, Al3+, and Cr3+. The colorimetric detections of all the ions were performable individually in a solution. In addition, GQD-ARS as a colorimetric sensor detected Co2+ at pH < 0.6 with limit of quantification 0.08 mM and Fe3+ at 0.6 < pH < 4.0 with limit of quantification 0.03 mM in the mixture of cations.
TRPV4 activates the Cdc42/N-wasp pathway to promote glioblastoma invasion by altering cellular protrusions
Authors: Yang Wei , Wu Peng-fei , Ma Jian-xing , Liao Mao-jun , Xu Lun-shan , Yi Liang
Published: August 2020

The invasion ability of glioblastoma (GBM) causes tumor cells to infiltrate the surrounding brain parenchyma and leads to poor outcomes. Transient receptor potential vanilloid 4 (TRPV4) exhibits a remarkable role in cancer cell motility, but the contribution of TRPV4 to glioblastoma metastasis is not fully understood. Here, we reported that TRPV4 expression was significantly elevated in malignant glioma compared to normal brain and low-grade glioma, and TRPV4 expression was negatively correlated with the prognosis of glioma patients. Functionally, stimulation of TRPV4 promoted glioblastoma cell migration and invasion, and repression of TRPV4 hindered the migration and invasion of glioblastoma cells in vitro. Molecularly, TRPV4 strongly colocalized and interacted with skeletal protein-F-actin at cellular protrusions, and TRPV4 regulated the formation of invadopodia and filopodia in glioblastoma cells. Furthermore, the Cdc42/N-wasp axis mediated the effect of TRPV4-regulated cellular protrusions and invasion. Foremost, TRPV4 inhibitor treatment or downregulation of TRPV4 significantly reduced the invasion-growth of subcutaneously and intracranially transplanted glioblastoma in mice. In conclusion, the TRPV4/Cdc42/wasp signaling axis regulates cellular protrusion formation in glioblastoma cells and influences the invasion-growth phenotype of glioblastoma in vivo. TRPV4 may serve as a prognostic factor and specific therapeutic target for GBM patients.
MRI-based radiomics in breast cancer: feature robustness with respect to inter-observer segmentation variability
Authors: Granzier R. W. Y. , Verbakel N. M. H. , Ibrahim A. , van Timmeren J. E. , van Nijnatten T. J. A. , Leijenaar R. T. H. , Lobbes M. B. I. , Smidt M. L. , Woodruff H. C.
Published: August 2020

Radiomics is an emerging field using the extraction of quantitative features from medical images for tissue characterization. While MRI-based radiomics is still at an early stage, it showed some promising results in studies focusing on breast cancer patients in improving diagnoses and therapy response assessment. Nevertheless, the use of radiomics raises a number of issues regarding feature quantification and robustness. Therefore, our study aim was to determine the robustness of radiomics features extracted by two commonly used radiomics software with respect to variability in manual breast tumor segmentation on MRI. A total of 129 histologically confirmed breast tumors were segmented manually in three dimensions on the first post-contrast T1-weighted MR exam by four observers: a dedicated breast radiologist, a resident, a Ph.D. candidate, and a medical student. Robust features were assessed using the intraclass correlation coefficient (ICC > 0.9). The inter-observer variability was evaluated by the volumetric Dice Similarity Coefficient (DSC). The mean DSC for all tumors was 0.81 (range 0.19–0.96), indicating a good spatial overlap of the segmentations based on observers of varying expertise. In total, 41.6% (552/1328) and 32.8% (273/833) of all RadiomiX and Pyradiomics features, respectively, were identified as robust and were independent of inter-observer manual segmentation variability.
The effects of Piper sarmentosum aqueous extracts on zebrafish (Danio rerio) embryos and caudal fin tissue regeneration
Authors: Zainol Abidin Intan Zarina , Fazry Shazrul , Jamar Nur Hidayah , Ediwar Dyari Herryawan Ryadi , Zainal Ariffin Zaidah , Johari Anis Nabilah , Ashaari Nur Suhanawati , Johari Nor Azfa , Megat Abdul Wahab Rohaya , Zainal Ariffin Shahrul Hisham
Published: August 2020

In Malaysia,Piper sarmentosumor ‘kaduk’ is commonly used in traditional medicines. However, its biological effects including in vivo embryonic toxicity and tissue regenerative properties are relatively unknown. The purpose of this study was to determine zebrafish (Danio rerio) embryo toxicities and caudal fin tissue regeneration in the presence ofP. sarmentosumaqueous extracts. The phytochemical components and antioxidant activity of the extract were studied using GC–MS analysis and DPPH assay, respectively. Embryo toxicity tests involving survival, heartbeat, and morphological analyses were conducted to determineP. sarmentosumextract toxicity (0–60 µg/mL); concentrations of 0–400 µg/mL of the extract were used to study tissue regeneration in the zebrafish caudal fin. The extract contained several phytochemicals with antioxidant activity and exhibited DPPH scavenging activity (IC50 = 50.56 mg/mL). Embryo toxicity assays showed that a concentration of 60 μg/mL showed the highest rates of lethality regardless of exposure time. Slower embryogenesis was observed at 40 µg/mL, with non-viable embryos first detected at 50 µg/mL. Extracts showed significant differences (p < 0.01) for tissue regeneration at all concentrations when compared to non-treated samples. In conclusion,Piper sarmentosumextracts accelerated tissue regeneration, and extract concentrations at 60 µg/mL showed the highest toxicity levels for embryo viability.
The proanthocyanin-related transcription factors MYBC1 and WRKY44 regulate branch points in the kiwifruit anthocyanin pathway
Authors: Peng Yongyan , Thrimawithana Amali H. , Cooney Janine M. , Jensen Dwayne J. , Espley Richard V. , Allan Andrew C.
Published: August 2020

The groups of plant flavonoid metabolites termed anthocyanins and proanthocyanins (PA) are responsible for pigmentation in seeds, flowers and fruits. Anthocyanins and PAs are produced by a pathway of enzymes which are transcriptionally regulated by transcription factors (TFs) that form the MYB-bHLH-WD40 (MBW) complex. In this study, transcriptomic analysis of purple-pigmented kiwifruit skin and flesh tissues identified MYBC1, from subgroup 5 of the R2R3 MYB family, and WRKY44 (highly similar to Arabidopsis TTG2) as candidate activators of the anthocyanin pathway. Transient over-expression of MYBC1 and WRKY44 induced anthocyanin accumulation in tobacco leaves. Dual luciferase promoter activation assays revealed that both MYBC1 and WRKY44 were able to strongly activate the promoters of the kiwifruit F3′H and F3′5′H genes. These enzymes are branch points of the pathway which specifies the type of anthocyanin accumulated. Stable over-expression of MYBC1 and WRKY44 in kiwifruit calli activated the expression of F3′5′H and PA-related biosynthetic genes as well as increasing levels of PAs. These results suggest that while previously characterised anthocyanin activator MYBs regulate the overall anthocyanin biosynthesis pathway, the PA-related TFs, MYBC1 and WRKY44, more specifically regulate key branch points. This adds a layer of regulatory control that potentially balances anthocyanin and PA levels.
Electrowetting-on-dielectric characteristics of ZnO nanorods
Authors: Kim Jae-Hun , Lee Jae-Hyoung , Mirzaei Ali , Kim Hyoun Woo , Tan Boon Teoh , Wu Ping , Kim Sang Sub
Published: August 2020

Herein, we report the electrowetting-on-dielectric (EWOD) characteristics of ZnO nanorods (NRs) prepared via the hydrothermal method with different initial Zn2+ concentrations (0.03, 0.07, and 0.1 M). Diameter of the resultant ZnO NRs were 50, 70 and 85 nm, respectively. Contact angle (CA) measurements showed that the Teflon-coated ZnO NRs with diameters of 85 nm prepared from the 0.1 M solution had the highest CA (137°). During the EWOD studies, on the application of a voltage of 250 V, the water CA decreased to 78°, which demonstrates the potential application of this material in EWOD electronics. Furthermore, we explained the relationship between the applied voltage and CA based on the substrate nanostructures and our newly developed NR-on-film wetting model. In addition, we further validated our model by introducing the homo-composite dielectric structure, which is a composite of thin layered ZnO/Teflon and nano-roded ZnO/Teflon.
The α2 Na+/K+-ATPase isoform mediates LPS-induced neuroinflammation
Authors: Leite J. A. , Isaksen T. J. , Heuck A. , Scavone C. , Lykke-Hartmann K.
Published: August 2020

Na+/K+-ATPase is a transmembrane ion pump that is essential for the maintenance of ion gradients and regulation of multiple cellular functions. Na+/K+-ATPase has been associated with nuclear factor kappa B (NFκB) signalling, a signal associated with lipopolysaccharides (LPSs)-induced immune response in connection with activated Toll-like receptor 4 (TLR4) signalling. However, the contribution of Na+/K+-ATPase to regulating inflammatory responses remains elusive. We report that mice haploinsufficient for the astrocyte-enriched α2Na+/K+-ATPase isoform (α2+/G301R mice) have a reduced proinflammatory response to LPS, accompanied by a reduced hypothermic reaction compared to wild type litter mates. Following intraperitoneal injection of LPS, gene expressions of Tnf-α, Il-1β, and Il-6 was reduced in the hypothalamus and hippocampus from α2+/G301R mice compared to α2+/+ littermates. The α2+/G301R mice experienced increased expression of the gene encoding an antioxidant enzyme, NRF2, in hippocampal astrocytes. Our findings indicate that α2Na+/K+-ATPase haploinsufficiency negatively modulates LPS-induced immune responses, highlighting a rational pharmacological target for reducing LPS-induced inflammation.
Potential mechanisms underlying the association between single nucleotide polymorphism (BRAP and ALDH2) and hypertension among elderly Japanese population
Authors: Shimizu Yuji , Arima Kazuhiko , Noguchi Yuko , Kawashiri Shin-Ya , Yamanashi Hirotomo , Tamai Mami , Nagata Yasuhiro , Maeda Takahiro
Published: August 2020

Minor allele frequency (MAF) of rs3782886 (BRAP) and rs671 (ALDH2) are reported to be inversely associated with blood pressure. Another study revealed that hematopoietic activity which is evaluated by reticulocytes could influenced on hypertension status partly by indicating activity of endothelial maintenance. Therefore, to evaluate the association between genetic factor and hypertension, influence of hematopoietic activity should be considered. A multi-faced analysis was performed in a simple general elderly population model (1,313 older Japanese aged 60–98 years). Participants were stratified by median values of reticulocytes (5.21 × 104 cells/μL for men and 4.65 × 104 cells/μL for women). Independent of known cardiovascular risk factors, MAF of rs3782886 and rs671 are significantly inversely associated with hypertension for participants with high hematopoietic activity (high reticulocytes level) (fully adjusted odds ratio (ORs) were 0.72 (0.55, 0.96) for rs3782886 and 0.72 (0.54, 0.96) for rs671) but not for low reticulocytes count (the corresponding values were 1.05 (0.79, 1.39) and 1.08 (0.81, 1.45), respectively). Hematopoietic activity evaluated by reticulocytes levels could influence on the association between single nucleotide polymorphism (rs3782886 and rs671) and hypertension. Those results were efficient tool to clarify the part of the mechanism that underlying the association between genetic factor and hypertension.
Heterologous expression of high-activity cytochrome P450 in mammalian cells
Authors: Kumondai Masaki , Hishinuma Eiji , Gutiérrez Rico Evelyn Marie , Ito Akio , Nakanishi Yuya , Saigusa Daisuke , Hirasawa Noriyasu , Hiratsuka Masahiro
Published: August 2020

The evaluation of Cytochrome P450 (CYP) enzymatic activity is essential to estimate drug pharmacokinetics. Numerous CYP allelic variants have been identified; the functional characterisation of these variants is required for their application in precision medicine. Results from heterologous expression systems using mammalian cells can be integrated in in vivo studies; however, other systems such as E. coli, bacteria, yeast, and baculoviruses are generally used owing to the difficulty in expressing high CYP levels in mammalian cells. Here, by optimising transfection and supplementing conditions, we developed a heterologous expression system using 293FT cells to evaluate the enzymatic activities of three CYP isoforms (CYP1A2, CYP2C9, and CYP3A4). Moreover, we established co-expression with cytochrome P450 oxidoreductase and cytochrome b5. This expression system would be a potential complementary or beneficial alternative approach for the pharmacokinetic evaluation of clinically used and developing drugs in vitro.
Activation-induced cytidine deaminase overexpression in double-hit lymphoma: potential target for novel anticancer therapy
Authors: Zhang Jingcheng , Shi Yifen , Zhao Mingzhe , Hu Huixian , Huang He
Published: August 2020

Activation-induced cytidine deaminase (AID) is one kind of the mutant enzymes, which target regulating the immunoglobulin (Ig) gene in Burkitt’s lymphoma to initiate class switch recombination (CSR), resulting in c-Myc chromosomal translocation. However, it is not clear that whether AID induces c-Myc/IgH translocation in double-hit lymphoma (DHL) with c-Myc gene translocation. In this study, the AID in DHL tissues and classical diffuse large b-cell lymphoma (DLBCL) tissues were compared. The results suggested that AID is of important value in predicting DHL, stronger CSR of AID was observed in DHL patients, which exhibited AID overexpression and c-Myc gene translocation of DHL after CSR induction. It is concluded that AID directly induces CSR in DHL and may result in c-Myc gene translocation. Targeting AID may be a good treatment regimen for DHL.
Penicillin causes non-allergic anaphylaxis by activating the contact system
Authors: Gao Yuan , Han Yixin , Zhang Xiaoyu , Fei Qiaoling , Qi Ruijuan , Hou Rui , Cai Runlan , Peng Cheng , Qi Yun
Published: August 2020

Immediate hypersensitivity reaction (IHR) can be divided into allergic- and non-allergic-mediated, while “anaphylaxis” is reserved for severe IHR. Clinically, true penicillin allergy is rare and most reported penicillin allergy is “spurious”. Penicillin-initiated anaphylaxis is possible to occur in skin test- and specific IgE-negative patients. The contact system is a plasma protease cascade initiated by activation of factor XII (FXII). Many agents with negative ion surface can activate FXII to drive contact system. Our data showed that penicillin significantly induced hypothermia in propranolol- or pertussis toxin-pretreated mice. It also caused a rapid and reversible drop in rat blood pressure, which did not overlap with IgE-mediated hypotension. These effects could be countered by a bradykinin-B2 receptor antagonist icatibant, and consistently, penicillin indeed increased rat plasma bradykinin. Moreover, penicillin not only directly activated contact system FXII-dependently, but also promoted bradykinin release in plasma incubated-human umbilical vein endothelial cells. In fact, besides penicillin, other beta-lactams also activated the contact system in vitro. Since the autoactivation of FXII can be affected by multiple-factors, plasma from different healthy individuals showed vastly different amidolytic activity in response to penicillin, suggesting the necessity of determining the potency of penicillin to induce individual plasma FXII activation. These results clarify that penicillin-initiated non-allergic anaphylaxis is attributed to contact system activation, which might bring more effective diagnosis options for predicting penicillin-induced fatal risk and avoiding costly and inappropriate treatment clinically.