bluuebunny/crossref_metadata_2025 huggingface dataset:
Detecting SARS-CoV-2 Orf3a and E ion channel activity in COVID-19 blood samples
Authors: Yu Han-Gang , Sizemore Gina , Smoot Katy , Perrotta Peter
Published: September 2021

Background:

SARS-CoV-2 has been found in the heart of COVID-19 patients. It is unclear how the virus passes from the upper respiratory tract to the myocardium. We hypothesized that SARS-CoV-2 is present in the blood of COVID-19 infected patients, spreading to other organs such as heart.

Methods:

We targeted two viroporins, Orf3a and E, in SARS-CoV-2. Orf3a and E form non-voltage-gated ion channels. A combined fluorescence potassium ion assay with three channel modulators (4-aminopyridine, emodin-Orf3a channel blocker, and gliclazide-E channel blocker) was developed to detect SARS-CoV-2 Orf3a/E channel activity. In blood samples, we subtracted the fluorescence signals in the absence and presence of emodin/gliclazide to detect Orf3a and E channel activity.

Results:

In lentivirus-spiked samples, we detected significant channel activity of Orf3a/E based on increase in fluorescence induced by 4-aminopyridine, and this increase in fluorescence was inhibited by emodin and gliclazide. In 18 antigen/PCR-positive samples, our test results found 15 are positive, demonstrating 83.3% concordance. In 24 antigen/PCR-negative samples, our test results found 21 are negative, showing 87.5% concordance.

Conclusions:

We developed a cell-free test that can detect Orf3a/E channel activity of SARS-CoV-2 in blood samples from COVID-19-infected individuals, confirming a hypothesis that the virus spreads to the heart via blood circulation.
Convection in a mushy layer along a vertical heated wall
Authors: Boury S. , Meyer C.R. , Vasil G.M. , Wells A.J.
Published: September 2021

Motivated by the mushy zones of sea ice, volcanoes and icy moons of the outer solar system, we perform a theoretical and numerical study of boundary-layer convection along a vertical heated wall in a bounded ideal mushy region. The mush is comprised of a porous and reactive binary alloy with a mixture of saline liquid in a solid matrix, and is studied in the near-eutectic approximation. Here, we demonstrate the existence of four regions and study their behaviour asymptotically. Starting from the bottom of the wall, the four regions are (i) an isotropic corner region; (ii) a buoyancy dominated vertical boundary layer; (iii) an isotropic connection region; and (iv) a horizontal boundary layer at the top boundary with strong gradients of pressure and buoyancy. Scalings from numerical simulations are consistent with the theoretical predictions. Close to the heated wall, the convection in the mushy layer is similar to a rising buoyant plume abruptly stopped at the top, leading to increased pressure and temperature in the upper region, whose impact is discussed as an efficient melting mechanism.
Saturnus Cryptensis sur une nouvelle inscription des environs de Maxula (Tunisie)
Authors: Ben Romdhane Hamden , Aounallah Samir
Published: September 2021

A new votive inscription to Saturn cryptensis using vulgar and poor Latin, but with a very original content, enriches the corpus of Saturnian names with a new topical epithet and sheds light on a mystical aspect of the cult of the most revered god in Africa.
Qualitative properties of singular solutions to fractional elliptic equations
Authors: Huang Shuibo , Zhang Zhitao , Liu Zhisu
Published: September 2021

In this paper, by the moving spheres method, Caffarelli-Silvestre extension formula and blow-up analysis, we study the local behaviour of nonnegative solutions to fractional elliptic equations
\begin{align*} (-\Delta)^{\alpha} u =f(u),~~ x\in \Omega\backslash \Gamma, \end{align*}
where $0<\alpha <1$, $\Omega = \mathbb {R}^{N}$ or $\Omega$ is a smooth bounded domain, $\Gamma$ is a singular subset of $\Omega$ with fractional capacity zero, $f(t)$ is locally bounded and positive for $t\in [0,\,\infty )$, and $f(t)/t^{({N+2\alpha })/({N-2\alpha })}$ is nonincreasing in $t$ for large $t$, rather than for every $t>0$. Our main result is that the solutions satisfy the estimate
\begin{align*} f(u(x))/ u(x)\leq C d(x,\Gamma)^{{-}2\alpha}. \end{align*}
This estimate is new even for $\Gamma =\{0\}$. As applications, we derive the spherical Harnack inequality, asymptotic symmetry, cylindrical symmetry of the solutions.
5 YEARS OF ION-LASER INTERACTION MASS SPECTROMETRY—STATUS AND PROSPECTS OF ISOBAR SUPPRESSION IN AMS BY LASERS
Authors: Martschini Martin , Lachner Johannes , Hain Karin , Kern Michael , Marchhart Oscar , Pitters Johanna , Priller Alfred , Steier Peter , Wiederin Andreas , Wieser Alexander , Golser Robin
Published: September 2021

A setup for ion-laser interaction was coupled to the state-of-the-art AMS facility VERA five years ago and its potential and applicability as a new means of isobar suppression in accelerator mass spectrometry (AMS) has since been explored. Laser photodetachment and molecular dissociation processes of anions provide unprecedented isobar suppression factors of >1010 for several established AMS isotopes like 36Cl or 26Al and give access to new AMS isotopes like 90Sr, 135Cs or 182Hf at a 3-MV-tandem facility. Furthermore, Ion-Laser InterAction Mass Spectrometry has been proven to meet AMS requirements regarding reliability and robustness with a typical reproducibility of results of 3%. The benefits of the technique are in principle available to any AMS machine, irrespective of attainable ion beam energy. Since isobar suppression via this technique is so efficient, there often is no need for any additional element separation in the detection setup and selected nuclides may even become accessible without accelerator at all.
HAZOR EB III CITY ABANDONMENT AND IBA PEOPLE RETURN: RADIOCARBON CHRONOLOGY AND ITS IMPLICATIONS
Authors: Lev Ron , Bechar Shlomit , Boaretto Elisabetta
Published: September 2021

Tel Hazor is one of only a few sites in Israel where remains of the Intermediate Bronze Age (IBA) in the second half of the 3rd millennium BC were found on top of Early Bronze III (EB III) city remains. A probe excavation was held at Hazor in 2017 to explore the chronological relation between the EB III and the IBA occupation. The radiocarbon (14C) absolute dates generated from this probe excavation show that following the EB III city demise, the site was abandoned for up to a few hundred years before it was resettled in the IBA.14C dates obtained from the last level of the EB III city are well before 2500 BCE, fully aligned with the recent “High Chronology” for the EBA in the southern Levant. The excavation also produced dates associated with IBA “Black Wheel-Made Ware” vessels, which were found in large numbers at Hazor.
Does State Repression Spark Protests? Evidence from Secret Police Surveillance in Communist Poland
Authors: HAGER ANSELM , KRAKOWSKI KRZYSZTOF
Published: September 2021

Does physical surveillance hinder or foster antiregime resistance? A common view holds that surveillance prevents resistance by providing regimes with high-quality intelligence on dissident networks and by instilling fear in citizens. We contrast this view using formerly classified data from Communist Poland. We find that communities exposed to secret police officers were more likely to organize protests but also engaged in less sabotage. To ensure that the relationship is causal, we use an instrumental variable strategy, which exploits the exogenous assignment of Catholic “spy priests” to local communities. To trace the underlying mechanisms, we draw on qualitative interviews and archival sources. We document that Poland’s comprehensive use of surveillance created widespread anger as well as an incentive for citizens to reveal their true loyalties, thus facilitating antiregime collective action. Once on the streets, protesters refrained from sabotage to signal their political motivation to bystanders and authorities alike.
‘DAY WATCH’ OR BAYWATCH? A NOTE ON ΗΜΕΡΟΣΚΟΠΟΣ (AR.LYS. 849)
Authors: Janse Mark
Published: September 2021

This article argues thatἡμεροσκόποςatLys. 849 constitutes a pun based on iotacism, a well-known feature of female speech in fifth-century Athens aptly illustrated by Socrates in Plato'sCratylus. By describing herself asἡμεροσκόπος‘day watch’ pronounced asἱμεροσκόπος‘lust watch’, Lysistrata perverts the military term associated with the occupation-plot to a sexually charged word associated with the strike-plot. Its use would be very appropriate in a scene in which theφαλληφόριαof the men (not just Cinesias’ but later on also the Spartan herald's and the Spartan and Athenian delegates’) become the subject of aφαλλοσκοπίαby the women (not just Lysistrata but later on also the chorus of women) and perforce also by the onlooking audience. Additional contemporary evidence from orthographic mistakes made by schoolboys suggests that Athenian elite women of the late fifth century were the avant-garde of socially prestigious innovations such as iotacism, which would definitively catch on with the male population in the fourth century and change the face of Greek phonology forever.
From Legislation to Everyday Practices in Guatemala's Violence against Women Courts
Authors: Beck Erin , Stephen Lynn
Published: September 2021

We explore how formal mandates associated with Guatemala's 2008 ‘Law against Femicide and Other Forms of Violence against Women’ and with specialised violence against women (VAW) courts have encountered significant challenges due to state-imposed constraints. Drawing on courtroom observations, analyses of case files, and interviews, we find that while formal mandates incorporated feminist understandings of violence against women, which were often internalised among court officials, in daily practice specialised courts reproduced tendencies to depict violence as interpersonal, fragment people's experiences and enact narrow forms of justice that do not incorporate the full intent of the 2008 VAW Law and institutions intended to support it. This case study thus illuminates how and why legal solutions alone are not sufficient to reduce gender-based violence and feminicide, particularly in the face of uneven and openly hostile challenges posed by governments.
Aberrant adapting of beliefs under stress: a mechanism relevant to the formation of paranoia?
Authors: Krkovic Katarina , Nowak Ulrike , Kammerer Mathias K. , Bott Antonia , Lincoln Tania M.
Published: September 2021

Background

Difficulties in the ability to adapt beliefs in the face of new information are associated with psychosis and its central symptom – paranoia. As cognitive processes and psychotic symptoms are both known to be sensitive to stress, the present study investigated the exact associations between stress, adapting of beliefs [reversal learning (RL), bias against disconfirmatory evidence (BADE), and jumping to conclusions (JTC)] and paranoia. We hypothesized that paranoia would increase under stress and that difficulties in adapting of beliefs would mediate or moderate the link between stress and paranoia. Furthermore, we hypothesized that the investigated effects would be strongest in the group of individuals diagnosed with a psychotic disorder.

Methods

We exposed 155 participants (38 diagnosed with a psychotic disorder, 40 individuals with attenuated psychotic symptoms, 39 clinical controls diagnosed with an obsessive-compulsive disorder, and 38 healthy controls) to a control condition and a stress condition, in which we assessed their levels of paranoia and their ability to adapt beliefs. We applied multilevel models to analyze the data.

Results

Paranoia was higher in the stress condition than in the control condition, b = 1.142, s.e. = 0.338, t(150) = 3.381, p < 0.001. RL, BADE, and JTC did not differ between conditions and did not mediate or moderate the association between stress and paranoia (all ps > 0.05).

Conclusions

The results support the assumption that stress triggers paranoia. However, the link between stress and paranoia does not seem to be affected by the ability to adapt beliefs.
Through the Mirror of CCP History: Four Perspectives
Authors: Thornton Patricia M.
Published: September 2021

Perhaps the most oft-quoted part of Xi Jinping's defiant 1st July speech marking the Party's centenary was his warning than any external forces attempting to “bully, oppress or subjugate” China will “dash their heads against the Great Wall of steel built with the flesh and blood of more than 1.4 billion Chinese people.” Foreign news organizations covering the ceremony also noted the “visual trick” of Xi's donning of a grey Mao suit identical to the one worn by the Great Helmsman in the portrait that hangs on Tiananmen, just feet below the rostrum from which Xi delivered his address; others doubted the functional significance of the five identical microphones, ascribing to them a very different significance. Xi's repeated references to the importance of Party history, however, drew far less attention in the Western press, although Xi gravely warned a cheering and flag-waving audience of more than 70,000 that while the CCP's original mission “is easy to define, ensuring that we stay true to this mission is a more difficult task.”

By learning from history, we can understand why powers rise and fall. Through the mirror of history, we can find where we currently stand and gain foresight into the future. Looking back on the Party's 100-year history, we can see why we were successful in the past and how we can continue to succeed in the future.

Indeed, in the months leading up to the centennial celebration, the Party launched a comprehensive campaign requiring CCP members to study the Party's past closely; A Short History of the Chinese Communist Party was revised and updated, eliminating a previous discussion of the consequences of the Great Leap Forward, which had concluded with the open acknowledgement that “This bitter historical lesson shouldn't be forgotten.” Also expunged was a frank evaluation of the excesses of the Cultural Revolution, which was replaced with an account that restricted its focus to highlighting various industrial, technological and diplomatic advances made over the course of that period, without acknowledging the social and political turmoil that accompanied those developments.
The Italian Constitutional Court in its Context: A Narrative
Authors: Tega Diletta
Published: September 2021

Italian Constitutional Court, development of re-centralised case law against the displacement of national constitutional courts – Italian Constitutional Court challenges the Simmenthal doctrine – Double preliminary questions – The Italian Constitutional Court’s continuous need for legitimation – The Italian Constitutional Court’s adaptation of its case law and doctrines to the legal and political context
Polygamy, the Commodification of Women, and Underdevelopment
Authors: Seligson Daniel , McCants Anne E. C.
Published: September 2021

Family systems shape social institutions, yet they are rarely considered in histories of economic development. In this article, we show that a suite of social conventions—such as age gaps at marriage, bride price, sequestration, and discrimination and violence against women—are overrepresented in polygamous societies as compared to monogamous societies. This dichotomy can be explained on the grounds that polygamy produces a chronic scarcity of marriageable females. We argue that this suite, which we call gamos and which we quantify by two different methods, has demonstrably significant consequences for social, institutional, and economic development.
Comprehensive Geophysical Study at Wabar Crater, Rub Al‐Khali Desert, Saudi Arabia
Authors: Hanafy Sherif M. , Soupios Pantelis , Stampolidis Alexandros , Koch Christian Bender , Al‐Ramadan Khalid , Al‐Shuhail Abdullatif , Solling Theis , Argadestya Ignatius
Published: September 2021

Interest in impact craters on the earth's surface has increased worldwide and is being investigated by using remote sensing, geological, boreholes, geophysical, and laboratory measurements. These measurements are used to build dynamic models to study crater formation. In this work, the near‐crater sediments at the young Wabar crater field in Saudi Arabia have been investigated using magnetic, transient electromagnetic (TEM), seismic, and ground‐penetrating radar (GPR) methods. The main objectives of this research were to (a) explore the possibility of any remnant major pieces of the meteorite, (b) investigate the meteoroid direction, and (c) map the deformational structures associated with the meteorite impact. Our results show five different magnetic anomaly types and three layers in the subsurface. The maximum depth of deformation due to the impact of the meteorite is about 25 m as shown by the seismic travel time tomogram, the quasi‐2D TEM, and the 3D GPR model. TEM survey confirmed the geometrical characteristics of the major crater and located another small crater (known as Philby‐A). The magnetic survey shows no evidence of any remnant major pieces of the meteorite; however, it was used to trace ejecta material containing highly dilute magnetic material. The magnetic carrier is most likely spheres of metal incorporated in the black/green glasses. During the expedition, many small pieces of the meteoroid were found and collected for further geochemical analysis. Based on the geophysical findings, the meteorite direction was found to be from north to south.
High‐Resolution Land Surface Modeling of the Effect of Long‐Term Urbanization on Hydrothermal Changes Over Beijing Metropolitan Area
Authors: Ji Peng , Yuan Xing , Liang Xin‐Zhong , Jiao Yang , Zhou Yuyu , Liu Zan
Published: September 2021

The impacts of urbanization on terrestrial thermal and hydrological changes should be considered for sustainable development of urban environment and economy. However, previous studies mainly focused on the impacts at short time scales, which is insufficient to provide the needed information. This study augmented the high‐resolution Conjunctive Surface‐Subsurface Process version 2 (CSSPv2) land model with an urban canopy model that incorporates domestic wastewater recharge (DWWR) and dynamical impervious surface area (ISA) to develop a new CSSPv2_Urban model and conducted 38‐year simulations over the Beijing metropolitan area at 1 km resolution to quantify the urbanization impacts. Compared with CSSPv2, CSSPv2_Urban decreases the root‐mean‐square errors in surface latent/sensible heat fluxes, near‐surface air temperature and land surface temperature by 15%–66%, increases Kling‐Gupta efficiency for streamflow by 27%–34%, and reproduces the observed long‐term trends of land surface temperature and streamflow. It also reduces the corresponding errors in the modern reanalysis products by up to 70%. The model sensitivity analyses showed that the urbanization over Beijing area contributed to 31% of the surface warming during 1979–2017 and kept the warming trend over the new development zone during 2000–2013 when global warming slowed down. Although the large fraction of ISA in the city center increased streamflow by generating more surface runoff, 39%–62% of the increasing trend of streamflow was caused by the increased DWWR. Our study highlights the importance of the urban heat island effect from a climatological perspective and suggests that the influences of urbanization on streamflow may be underestimated if ignoring DWWR.
Evolution and dispersal of snakes across the Cretaceous-Paleogene mass extinction
Authors: Klein Catherine G. , Pisani Davide , Field Daniel J. , Lakin Rebecca , Wills Matthew A. , Longrich Nicholas R.
Published: September 2021

Mass extinctions have repeatedly shaped global biodiversity. The Cretaceous-Paleogene (K-Pg) mass extinction caused the demise of numerous vertebrate groups, and its aftermath saw the rapid diversification of surviving mammals, birds, frogs, and teleost fishes. However, the effects of the K-Pg extinction on the evolution of snakes—a major clade of predators comprising over 3,700 living species—remains poorly understood. Here, we combine an extensive molecular dataset with phylogenetically and stratigraphically constrained fossil calibrations to infer an evolutionary timescale for Serpentes. We reveal a potential diversification among crown snakes associated with the K-Pg mass extinction, led by the successful colonisation of Asia by the major extant clade Afrophidia. Vertebral morphometrics suggest increasing morphological specialisation among marine snakes through the Paleogene. The dispersal patterns of snakes following the K-Pg underscore the importance of this mass extinction event in shaping Earth’s extant vertebrate faunas.
Near 100% ethene selectivity achieved by tailoring dual active sites to isolate dehydrogenation and oxidation
Authors: Wang Chaojie , Yang Bing , Gu Qingqing , Han Yujia , Tian Ming , Su Yang , Pan Xiaoli , Kang Yu , Huang Chuande , Liu Hua , Liu Xiaoyan , Li Lin , Wang Xiaodong
Published: September 2021

Prohibiting deep oxidation remains a challenging task in oxidative dehydrogenation of light alkane since the targeted alkene is more reactive than parent substrate. Here we tailor dual active sites to isolate dehydrogenation and oxidation instead of homogeneously active sites responsible for these two steps leading to consecutive oxidation of alkene. The introduction of HY zeolite with acid sites, three-dimensional pore structure and supercages gives rise to Ni2+ Lewis acid sites (LAS) and NiO nanoclusters confined in framework wherein catalytic dehydrogenation of ethane occurs on Ni2+ LAS resulting in the formation of ethene and hydrogen while NiO nanoclusters with decreased oxygen reactivity are responsible for selective oxidation of hydrogen rather than over-oxidizing ethene. Such tailored strategy achieves near 100% ethene selectivity and constitutes a promising basis for highly selective oxidation catalysis beyond oxidative dehydrogenation of light alkane.
Multi-region exome sequencing reveals the intratumoral heterogeneity of surgically resected small cell lung cancer
Authors: Zhou Huaqiang , Hu Yi , Luo Rongzhen , Zhao Yuanyuan , Pan Hui , Ji Liyan , Zhou Ting , Zhang Lanjun , Long Hao , Fu Jianhua , Wen Zhesheng , Wang Siyu , Wang Xin , Lin Peng , Yang Haoxian , Wang Junye , Song Mengmeng , Yi Xin , Yang Ling , Xia Xuefang , Guan Yanfang , Fang Wenfeng , Yang Yunpeng , Hong Shaodong , Huang Yan , Li Pansong , Zhang Yaxiong , Zhou Ningning
Published: September 2021

Small cell lung cancer (SCLC) is a highly malignant tumor which is eventually refractory to any treatment. Intratumoral heterogeneity (ITH) may contribute to treatment failure. However, the extent of ITH in SCLC is still largely unknown. Here, we subject 120 tumor samples from 40 stage I-III SCLC patients to multi-regional whole-exome sequencing. The most common mutant genes are TP53 (88%) and RB1 (72%). We observe a medium level of mutational heterogeneity (0.30, range 0.0~0.98) and tumor mutational burden (TMB, 10.2 mutations/Mb, range 1.1~51.7). Our SCLC samples also exhibit somatic copy number variation (CNV) across all patients, with an average CNV ITH of 0.49 (range 0.02~0.99). In terms of mutation distribution, ITH, TMB, mutation clusters, and gene signatures, patients with combined SCLC behave roughly the same way as patients with pure SCLC. This condition also exists in smoking patients and patients with EGFR mutations. A higher TMB per cluster is associated with better disease-free survival while single-nucleotide variant ITH is linked to worse overall survival, and therefore these features may be used as prognostic biomarkers for SCLC. Together, these findings demonstrate the intratumoral genetic heterogeneity of surgically resected SCLC and provide insights into resistance to treatment.
A common goal to CARE: Cancer Advocates, Researchers, and Clinicians Explore current treatments and clinical trials for breast cancer brain metastases
Authors: Joe Natalie S. , Hodgdon Christine , Kraemer Lianne , Redmond Kristin J. , Stearns Vered , Gilkes Daniele M.
Published: September 2021

Breast cancer is the most commonly diagnosed cancer in women worldwide. Approximately one-tenth of all patients with advanced breast cancer develop brain metastases resulting in an overall survival rate of fewer than 2 years. The challenges lie in developing new approaches to treat, monitor, and prevent breast cancer brain metastasis (BCBM). This review will provide an overview of BCBM from the integrated perspective of clinicians, researchers, and patient advocates. We will summarize the current management of BCBM, including diagnosis, treatment, and monitoring. We will highlight ongoing translational research for BCBM, including clinical trials and improved detection methods that can become the mainstay for BCBM treatment if they demonstrate efficacy. We will discuss preclinical BCBM research that focuses on the intrinsic properties of breast cancer cells and the influence of the brain microenvironment. Finally, we will spotlight emerging studies and future research needs to improve survival outcomes and preserve the quality of life for patients with BCBM.
Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy
Authors: Apostolidis Sokratis A. , Kakara Mihir , Painter Mark M. , Goel Rishi R. , Mathew Divij , Lenzi Kerry , Rezk Ayman , Patterson Kristina R. , Espinoza Diego A. , Kadri Jessy C. , Markowitz Daniel M. , E. Markowitz Clyde , Mexhitaj Ina , Jacobs Dina , Babb Allison , Betts Michael R. , Prak Eline T. Luning , Weiskopf Daniela , Grifoni Alba , Lundgreen Kendall A. , Gouma Sigrid , Sette Alessandro , Bates Paul , Hensley Scott E. , Greenplate Allison R. , Wherry E. John , Li Rui , Bar-Or Amit
Published: September 2021

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.
Immunoregulatory mechanism studies of ginseng leaves on lung cancer based on network pharmacology and molecular docking
Authors: Li Zao-Hui , Yu Dan , Huang Nan-Nan , Wu Jun-Kai , Du Xiao-Wei , Wang Xi-Jun
Published: September 2021

Panax ginseng is one of the oldest and most generally prescribed herbs in Eastern traditional medicine to treat diseases. Several studies had documented that ginseng leaves have anti-oxidative, anti-inflammatory, and anticancer properties similar to those of ginseng root. The aim of this research was to forecast of the molecular mechanism of ginseng leaves on lung cancer by molecular docking and network pharmacology so as to decipher ginseng leaves' entire mechanism. The compounds associated with ginseng leaves were searched by TCMSP. TCMSP and Swiss Target Prediction databases were used to sort out the potential targets of the main chemical components. Targets were collected from OMIM, PharmGKB, TTD, DrugBank and GeneCards which related to immunity and lung cancer. Ginseng leaves exert its lung cancer suppressive function by regulating the several signaling proteins, such as JUN, STAT3, AKT1, TNF, MAPK1, TP53. GO and KEGG analyses indicated that the immunoreaction against lung cancer by ginseng leaves might be related to response to lipopolysaccharide, response to oxidative stress, PI3K-Akt, MAPK and TNF pathway. Molecular docking analysis demonstrated that hydrogen bonding was interaction's core forms. The results of CCK8 test and qRT-PCR showed that ginseng leaves inhibit cell proliferation and regulates AKT1 and P53 expression in A549. The present study clarifies the mechanism of Ginseng leaves against lung cancer and provides evidence to support its clinical use.
Development of an efficient gene-targeting system for elucidating infection mechanisms of the fungal pathogen Trichosporon asahii
Authors: Matsumoto Yasuhiko , Nagamachi Tae , Yoshikawa Asami , Yamazaki Hideki , Yamasaki Yusuke , Yamada Tsuyoshi , Sugita Takashi
Published: September 2021

Trichosporon asahii is a pathogenic fungus that causes severe, deep-seated fungal infections in neutropenic patients. Elucidating the infection mechanisms of T. asahii based on genetic studies requires a specific gene-targeting system. Here, we established an efficient gene-targeting system in a highly pathogenic T. asahii strain identified using the silkworm infection model. By comparing the pathogenicity of T. asahii clinical isolates in a silkworm infection model, T. asahii MPU129 was identified as a highly pathogenic strain. Using an Agrobacterium tumefaciens-mediated gene transfer system, we obtained a T. asahii MPU129 mutant lacking the ku70 gene, which encodes the Ku70 protein involved in the non-homologous end-joining repair of DNA double-strand breaks. The ku70 gene-deficient mutant showed higher gene-targeting efficiency than the wild-type strain for constructing a mutant lacking the cnb1 gene, which encodes the beta-subunit of calcineurin. The cnb1 gene-deficient mutant showed reduced pathogenicity against silkworms compared with the parental strain. These results suggest that an efficient gene-targeting system in a highly pathogenic T. asahii strain is a useful tool for elucidating the molecular mechanisms of T. asahii infection.
ECG data dependency for atrial fibrillation detection based on residual networks
Authors: Seo Hyo-Chang , Oh Seok , Kim Hyunbin , Joo Segyeong
Published: September 2021

Atrial fibrillation (AF) is an arrhythmia that can cause blood clot and may lead to stroke and heart failure. To detect AF, deep learning-based detection algorithms have recently been developed. However, deep learning models were often trained with limited datasets and were evaluated within the same datasets, which makes their performance generally drops on the external datasets, known as data dependency. For this study, three different databases from PhysioNet were used to investigate the data dependency of deep learning-based AF detection algorithm using the residual neural network (Resnet). Resnet 18, 34, 50 and 152 model were trained with raw electrocardiogram (ECG) signal extracted from independent database. The highest accuracy was about 98–99% which is evaluation results of test dataset from the own database. On the other hand, the lowest accuracy was about 53–92% which was evaluation results of the external dataset extracted from different source. There are data dependency according to the train dataset and the test dataset. However, the data dependency decreased as a large amount of train data.
Confining Trypanosoma brucei in emulsion droplets reveals population variabilities in division rates and improves in vitro cultivation
Authors: Oldenburg Simone H. , Buisson Lionel , Beneyton Thomas , Pekin Deniz , Thonnus Magali , Bringaud Frédéric , Rivière Loïc , Baret Jean-Christophe
Published: September 2021

Trypanosome parasites are infecting mammals in Sub-Saharan Africa and are transmitted between hosts through bites of the tsetse fly. The transmission from the insect vector to the mammal host causes a number of metabolic and physiological changes. A fraction of the population continuously adapt to the immune system of the host, indicating heterogeneity at the population level. Yet, the cell to cell variability in populations is mostly unknown. We develop here an analytical method for quantitative measurements at the single cell level based on encapsulation and cultivation of single-cell Trypanosoma brucei in emulsion droplets. We first show that mammalian stage trypanosomes survive for several hours to days in droplets, with an influence of droplet size on both survival and growth. We unravel various growth patterns within a population and find that droplet cultivation of trypanosomes results in 10-fold higher cell densities of the highest dividing cell variants compared to standard cultivation techniques. Some variants reach final cell titers in droplets closer to what is observed in nature than standard culture, of practical interest for cell production. Droplet microfluidics is therefore a promising tool for trypanosome cultivation and analysis with further potential for high-throughput single cell trypanosome analysis.
Meta-analysis of gene expression disease signatures in colonic biopsy tissue from patients with ulcerative colitis
Authors: Linggi Bryan , Jairath Vipul , Zou Guangyong , Shackelton Lisa M. , McGovern Dermot P. B. , Salas Azucena , Verstockt Bram , Silverberg Mark S. , Nayeri Shadi , Feagan Brian G. , Vande Casteele Niels
Published: September 2021

Publicly available ulcerative colitis (UC) gene expression datasets from observational studies and clinical trials include inherently heterogeneous disease characteristics and methodology. We used meta-analysis to identify a robust UC gene signature from inflamed biopsies. Eight gene expression datasets derived from biopsy tissue samples from noninflammatory bowel disease (IBD) controls and areas of active inflammation from patients with UC were publicly available. Expression- and meta-data were downloaded with GEOquery. Differentially expressed genes (DEG) in individual datasets were defined as those with fold change > 1.5 and a Benjamini–Hochberg adjusted P value < .05. Meta-analysis of all DEG used a random effects model. Reactome pathway enrichment analysis was conducted. Meta-analysis identified 946 up- and 543 down-regulated genes in patients with UC compared to non-IBD controls (1.2 and 1.7 times fewer up- and down-regulated genes than the median of the individual datasets). Top-ranked up- and down-regulated DEG were LCN2 and AQP8. Multiple immune-related pathways (e.g., ‘Chemokine receptors bind chemokine’ and ‘Interleukin-10 signaling’) were significantly up-regulated in UC, while ‘Biological oxidations’ and ‘Fatty acid metabolism’ were downregulated. A web-based data-mining tool with the meta-analysis results was made available (https://premedibd.com/genes.html). A UC inflamed biopsy disease gene signature was derived. This signature may be an unbiased reference for comparison and improve the efficiency of UC biomarker studies by increasing confidence for identification of disease-related genes and pathways.
First report of Borrelia burgdorferi sensu stricto detection in a commune genospecies in Apodemus agrarius in Gwangju, South Korea
Authors: Kim Choon Mee , Park So Young , Kim Dong-Min , Park Jung Wook , Chung Jae Keun
Published: September 2021

Lyme disease is a tick-borne infectious disease caused by theBorrelia burgdorferisensu lato complex. However, the distribution ofBorreliagenospecies and the tissue detection rate ofBorreliain wild rodents have rarely been investigated. Here, we studied 27 wild rodents (Apodemus agrarius) captured in October and November 2016 in Gwangju, South Korea, and performed nested polymerase chain reaction targetingpyrGandospAto confirmBorreliainfection. Eight rodents (29.6%) tested positive forBorreliainfection. The heart showed the highest infection rate (7/27; 25.9%), followed by the spleen (4/27; 14.8%), kidney (2/27; 7.4%), and lungs (1/27; 3.7%). TheB. afzeliiinfection rate was 25.9%, with the highest rate observed in the heart (7/27; 25.9%), followed by that in the kidney and spleen (both 2/27; 7.4%).B. gariniiandB. burgdorferisensu stricto were detected only in the spleen (1/27; 3.7%). This is the first report ofB. burgdorferisensu stricto infection in wild rodents in South Korea. The rodent hearts showed a highB. afzeliiinfection rate, whereas the rodent spleens showed highB. gariniiandB. burgdorferisensu stricto infection rates. BesidesB. gariniiandB. afzelii,B. burgdorferisensu stricto may cause Lyme disease in South Korea.
Molecular underpinnings of division of labour among workers in a socially complex termite
Authors: Elsner Daniel , Hartfelder Klaus , Korb Judith
Published: September 2021

Division of labour characterizes all major evolutionary transitions, such as the evolution of eukaryotic cells or multicellular organisms. Social insects are characterized by reproductive division of labour, with one or a few reproducing individuals (queens) and many non-reproducing nestmates (workers) forming a colony. Among the workers, further division of labour can occur with different individuals performing different tasks such as foraging, brood care or building. While mechanisms underlying task division are intensively studied in social Hymenoptera, less is known for termites, which independently evolved eusociality. We investigated molecular mechanisms underlying task division in termite workers to test for communality with social Hymenoptera. We compared similar-aged foraging workers with builders of the fungus-growing termiteMacrotermes bellicosususing transcriptomes, endocrine measures and estimators of physiological condition. Based on results for social Hymenoptera and theory, we tested the hypotheses that (i) foragers are in worse physiological conditions than builders, (ii) builders are more similar in their gene expression profile to queens than foragers are, and (iii) builders invest more in anti-ageing mechanism than foragers. Our results support all three hypotheses. We found storage proteins to underlie task division of these similar-aged termite workers and these genes also characterize reproductive division of labour between queens and workers. This implies a co-option of nutrient-based pathways to regulate division of labour across lineages of termites and social Hymenoptera, which are separated by more than 133 million years.
Comparing the results of manual and automated quantitative corneal neuroanalysing modules for beginners
Authors: Wu Po-Ying , Wu Jo-Hsuan , Hsieh Yi-Ting , Chen Lin Chih-Chieh , Cheng Ting , Wu Po-Yi , Hsieh Bing-Jun , Huang Wei-Lun , Huang Sheng-Lung , Chen Wei-Li
Published: September 2021

This study aimed to evaluate the reliability of in vivo confocal microscopic neuroanalysis by beginners using manual and automated modules. Images of sub-basal corneal nerve plexus (SCNP) from 108 images of 18 healthy participants were analyzed by 7 beginner observers using manual (CCMetrics, [CCM]) and automated (ACCMetrics, [ACCM]) module. SCNP parameters analyzed included corneal nerve fiber density (NFD), corneal nerve branch density (NBD), corneal nerve fiber length (NFL), and tortuosity coefficient (TC). The intra-observer repeatability, inter-observer reliability, inter-module agreement, and left–right eye symmetry level of SCNP parameters were examined. All observers showed good intra-observer repeatability using CCM (intraclass correlation coefficient [ICC] > 0.60 for all), except when measuring TC. Two observers demonstrated especially excellent repeatability in analyzing NFD, NBD, and NFL using manual mode, indicating the quality of interpretation may still be observer-dependent. Among all SCNP parameters, NFL had the best inter-observer reliability (Spearman’s rank-sum correlation coefficient [SpCC] and ICC > 0.85 for the 3 original observers) and left–right symmetry level (SpCC and ICC > 0.60). In the additional analysis of inter-observer reliability using results by all 7 observers, only NFL showed good inter-observer reliability (ICC = 0.79). Compared with CCM measurements, values of ACCM measurements were significantly lower, implying a poor inter-module agreement. Our result suggested that performance of quantitative corneal neuroanalysis by beginners maybe acceptable, with NFL being the most reliable parameter, and automated method cannot fully replace manual work.
Factors associating with disability of non-specific low back pain in different subgroups: A hierarchical linear regression analysis
Authors: Miki Takahiro , Higuchi Daisuke , Takebayashi Tsuneo , Samukawa Mina
Published: September 2021

This study aimed to explore factors associating with disability, which means physical impairment affecting a person’s mobility, capacity, stamina, or agility, of non-specific low back pain (NSLBP) of the acute and non-acute groups. Two hundred thirty-five patients with NSLBP of less than 8 weeks’ duration as acute groups (n = 124) and more than 8 weeks’ duration as non-acute group (n = 111) were recruited. It was collected data on pain intensity, disability and psychosocial factors, including pain catastrophising, fear of movement and pain self-efficacy. Disability was measured Roland Morris Disability Questionnaire. A hierarchical multiple regression analysis was performed to analyse factors associating with disability of the acute and non-acute groups. The Result was that explanatory power increased with each additional variable of the order of demographic characteristics, pain intensity and psychosocial factors for both groups. Pain intensity, pain catastrophising and pain self-efficacy had significant explanatory power, with pain self-efficacy having the most significant association on the acute group. Only pain self-efficacy having the most significant association on disability of the non-acute group. In conclusion, the factors associating with disability differed depending on the duration of the disease, and pain self-efficacy might be one of the factors associating with disability of patients with NSLBP.
Verification and dissection of one quantitative trait locus for grain size and weight on chromosome 1 in rice
Authors: Cheng Yi-chen , Li Guan , Yin Man , Adegoke Tosin Victor , Wang Yi-feng , Tong Xiao-hong , Zhang Jian , Ying Jie-zheng
Published: September 2021

Grain size and weight are the key traits determining rice quality and yield and are mainly controlled by quantitative trait loci (QTL). In this study, one minor QTL that was previously mapped in the marker interval of JD1009-JD1019 using the Huanghuazhan/Jizi1560 (HHZ/JZ1560) recombinant inbred line (RIL) population, qTGW1-2, was validated to regulate grain size and weight across four rice-growing seasons using twenty-one near isogenic line (NIL)-F2 populations. The twenty-one populations were in two types of genetic background that were derived from the same parents HHZ and JZ1560. Twelve F9, F10 or F11 NIL-F2 populations with the sequential residual heterozygous regions covering JD1009-RM6840 were developed from one residual heterozygote (RH) in the HHZ/JZ1560 RIL population, and the remaining nine BC3F3, BC3F4 or BC3F5 NIL-F2 populations with the sequential residual heterozygous regions covering JD1009-RM6840 were constructed through consecutive backcrosses to the recurrent parent HHZ followed with marker assistant selection in each generation. Based on the QTL analysis of these genetic populations, qTGW1-2 was successfully confirmed to control grain length, width and weight and further dissected into two QTLs, qTGW1-2a and qTGW1-2b, which were respectively narrowed down to the marker intervals of JD1139-JD1127 (~ 978.2-kb) and JD1121-JD1102 (~ 54.8-kb). Furthermore, the two types of NIL-F2 populations were proved to be able to decrease the genetic background noise and increase the detection power of minor QTL. These results provided an important basis for further map-based cloning and molecular design breeding with the two QTLs in rice.
Terrestrial mesopredators did not increase after top-predator removal in a large-scale experimental test of mesopredator release theory
Authors: Castle Geoff , Smith Deane , Allen Lee R. , Allen Benjamin L.
Published: September 2021

Removal or loss of top-predators has been predicted to cause cascading negative effects for ecosystems, including mesopredator release. However, reliable evidence for these processes in terrestrial systems has been mixed and equivocal due, in large part, to the systemic and continued use of low-inference study designs to investigate this issue. Even previous large-scale manipulative experiments of strong inferential value have been limited by experimental design features (i.e. failure to prevent migration between treatments) that constrain possible inferences about the presence or absence of mesopredator release effects. Here, we build on these previous strong-inference experiments and report the outcomes of additional large-scale manipulative experiments to eradicate Australian dingoes from two fenced areas where dingo migration was restricted and where theory would predict an increase in extant European red foxes, feral cats and goannas. We demonstrate the removal and suppression of dingoes to undetectable levels over 4–5 years with no corresponding increases in mesopredator relative abundances, which remained low and stable throughout the experiment at both sites. We further demonstrate widespread absence of negative relationships between predators, indicating that the mechanism underpinning predicted mesopredator releases was not present. Our results are consistent with all previous large-scale manipulative experiments and long-term mensurative studies which collectively demonstrate that (1) dingoes do not suppress red foxes, feral cats or goannas at the population level, (2) repeated, temporary suppression of dingoes in open systems does not create mesopredator release effects, and (3) removal and sustained suppression of dingoes to undetectable levels in closed systems does not create mesopredator release effects either. Our experiments add to similar reports from North America, Asia, Europe and southern Africa which indicate that not only is there a widespread absence of reliable evidence for these processes, but there is also a large and continually growing body of experimental evidence of absence for these processes in many terrestrial systems. We conclude that although sympatric predators may interact negatively with each other on smaller spatiotemporal scales, that these negative interactions do not always scale-up to the population level, nor are they always strong enough to create mesopredator suppression or release effects.
Embryotoxic activity of 3C protease of human hepatitis A virus in developing Danio rerio embryos
Authors: Selina Polina I. , Karaseva Maria A. , Komissarov Alexey A. , Safina Dina R. , Lunina Nataliya A. , Roschina Marina P. , Sverdlov Eugene D. , Demidyuk Ilya V. , Kostrov Sergey V.
Published: September 2021

The 3C protease is a key factor in picornavirus-induced pathologies with a comprehensive action on cell targets. However, the effects induced by the enzyme have not been described at the organismic level. Here, the model of developing Danio rerio embryos was used to analyze possible toxic effects of the 3C protease of human hepatitis A virus (3Cpro) at the whole-body level. The transient 3Cpro expression had a notable lethal effect and induced a number of specific abnormalities in Danio rerio embryos within 24 h. These effects are due to the proteolytic activity of the enzyme. At the same time, the 3Cpro variant with reduced catalytic activity (3Cmut) increased the incidence of embryonic abnormalities; however, this effect was smaller compared to the native enzyme form. While the expression of 3Cmut increased the overall rate of abnormalities, no predominance of specific ones was observed. The data obtained point to a presence significant impact of picornavirus 3Cprotease at the whole-organism level and make contribution to the study of the infectious process caused by human hepatitis A virus.