bluuebunny/crossref_metadata_2025 huggingface dataset:
Chiridota heheva—the cosmopolitan holothurian
Authors: Thomas Elin A. , Liu Ruoyu , Amon Diva , Copley Jon T. , Glover Adrian G. , Helyar Sarah J. , Olu Karine , Wiklund Helena , Zhang Haibin , Sigwart Julia D.
Published: November 2020

Chemosynthetic ecosystems have long been acknowledged as key areas of enrichment for deep-sea life, supporting hundreds of endemic species. Echinoderms are among the most common taxa inhabiting the periphery of chemosynthetic environments, and of these, chiridotid holothurians are often the most frequently observed. Yet, published records of chiridotids in these habitats are often noted only as supplemental information to larger ecological studies and several remain taxonomically unverified. This study therefore aimed to collate and review all known records attributed to Chiridota Eschscholtz, 1829, and to conduct the first phylogenetic analysis into the relationship of these chiridotid holothurians across global chemosynthetic habitats. We show that Chiridota heheva Pawson & Vance, 2004 is a globally widespread, cosmopolitan holothurian that occupies all three types of deep-sea chemosynthetic ecosystem—hydrothermal vents, cold seeps and organic falls—as an organic-enrichment opportunist. Furthermore, we hypothesise that C. heheva may be synonymous with another vent-endemic chiridotid, Chiridota hydrothermica Smirnov et al., 2000, owing to the strong morphological, ecological and biogeographical parallels between the two species, and predict that any chiridotid holothurians subsequently discovered at global reducing environments will belong to this novel species complex. This study highlights the importance of understudied, peripheral taxa, such as holothurians, to provide insights to biogeography, connectivity and speciation at insular deep-sea habitats.
Familial Ties, Location of Occupation, and Congregational Exit in Geographically-Based Congregations: A Case Study of the Amish
Authors: Corcoran Katie E. , Stein Rachel E. , Colyer Corey J. , Kowalski Brittany M.
Published: November 2020

Background

While many studies have examined the relationship between social ties and joining social movements and religious groups, few studies have investigated the relationship between social ties and the likelihood of exiting such groups. Additionally, research has not considered how geography affects the membership dynamics of geographically-based congregations, specifically whether factors associated with residential mobility may also affect congregational exit in geographically-based congregations.

Purpose

The purpose of this study is to examine how familial ties and place of employment affect congregational exit in geographically-based congregations. Drawing on social network and residential mobility research, this study hypothesizes that having parents and/or adult children in the same congregation and having minor children decreases the likelihood of congregational exit and working farther away from the congregation increases it.

Methods

This study draws on longitudinal archival data from one Amish congregation in the Holmes County Ohio Settlement. It tests the hypotheses using logistic regression models.

Results

The results show that having one's parents/adult children in the congregation and working close to the congregation are associated with a reduced likelihood of congregational exit. Having minor children in one's household is not associated with congregational exit.

Conclusions and Implications

This is one of the first studies to consider how geographical requirements for congregational membership has implications for congregational exit. Given the results, congregations may be able to increase member retention by creating multigenerational ministries that support extended families and by advertising in local places of employment. As occupations increasingly shift to being primarily outside the home, Amish congregations in particular may experience more member turnover and membership instability.
Sesamol Alleviates the Cytotoxic Effect of Cyclophosphamide on Normal Human Lung WI-38 Cells via Suppressing RAGE/NF-κB/Autophagy Signaling
Authors: El-Emam Soad Z.
Published: November 2020

Cyclophosphamide (CYL) is a chemotherapeutic medication commonly used in managing various malignancies like breast cancer or leukemia. Though, CYL has been documented to induce lung toxicity. Mechanism of CYL toxicity is through oxidative stress and the release of damage-associated molecular patterns (DAMPs). Sesamol (SES) is a natural antioxidant isolated from Sesamum indicum and its effect against CYL-induced lung toxicity is not studied yet. This study aims to investigate whether SES could prevent any deleterious effects induced by CYL on lung using normal human lung cells, WI-38 cell line, without suppressing its efficacy. Cells were pretreated with SES and/or CYL for 24 h, then cell viability was estimated by MTS and trypan blue assays. The mode of cell death was determined by AO/EB staining. Additionally, caspase-3 level, oxidative stress, and inflammatory markers were evaluated by colorimetric and ELISA techniques. qRT-PCR was performed to evaluate RAGE, NF-κB, and Beclin-1 mRNA-expression. CYL-treated WI-38 cells developed a significantly increased cell death with enhanced oxidative and RAGE/NF-κb/Autophagy signaling, which were all attenuated after pretreatment with SES. Thus, we concluded that SES offered a protective role against CYL-induced lung injury via suppressing oxidative stress and RAGE/NF-κB/Autophagy signaling, which is a natural safe therapeutic option against CYL toxicities.

Graphic Abstract
Die öffentliche Förderung des Breitbandausbaus, eine kritische Würdigung
Authors: Klein Gordon J.
Published: November 2020

Die Digitalisierung als ein Querschnittsthema betrifft verschiedenste Ebenen des wirtschaftlichen und gesellschaftlichen Lebens. Es ist somit wenig überraschend, dass Politik diesen Prozess gestalten möchte. Dabei werden verschiedene Akzente durch Förderprogramme gesetzt, von denen einige beispielhaft dargestellt werden. Im besonderen Fokus dieser Arbeit steht das Bundesbreitbandförderprogramm. Hier wird zunächst die Lage bezüglich des Ausbaus aufgezeigt, eine Übersicht über heterogene Fördermaßnahmen dargelegt und dann ein normativer Eingriffsbedarf ermittelt. Es folgt eine kritische Würdigung der aktuellen Förderung, bei der dargestellt wird, dass diese sehr weitgehend ist und dabei wahrscheinlich auch dort fördert, wo es auch ohne Förderung zu einem Ausbau gekommen wäre.
Kostenloser ÖPNV: Akzeptanz in der Bevölkerung und mögliche Auswirkungen auf das Mobilitätsverhalten
Authors: Andor Mark A. , Fink Lukas , Frondel Manuel , Gerster Andreas , Horvath Marco
Published: November 2020

Der PKW-Verkehr dominiert auch heute noch das Verkehrsaufkommen in Deutschland. Ein häufig diskutierter Vorschlag, um dies zu ändern, lautet, den Öffentlichen Personennahverkehr (ÖPNV) kostenlos anzubieten. Auf Basis einer Erhebung aus dem Jahr 2018, bei der knapp 7000 Haushaltsvorstände des forsa-Haushalts-Panels Antworten zu ihrem Mobilitätsverhalten sowie zu ihrer Einstellung gegenüber vieldiskutierten Verkehrsmaßnahmen liefern, untersucht der vorliegende Beitrag die allgemeine Zustimmung zur kostenlosen Nutzung des ÖPNV sowie die möglichen Auswirkungen dieser Maßnahme auf das Mobilitätsverhalten. Die Ergebnisse zeigen eine starke Befürwortung der Maßnahme: Rund 72 % der Antwortenden stimmten für die Einführung eines kostenlosen ÖPNVs. Eine mehrheitliche Zustimmung findet sich in jeder gesellschaftlichen Gruppe, gleich ob männlich oder weiblich, jung oder alt, arm oder reich, sowie in allen politischen Lagern. Nach Einführung eines kostenlosen ÖPNV in Deutschland würden die Befragten die Anzahl ihrer Fahrten mit dem ÖPNV nach eigenen Angaben durchschnittlich um ca. 230 % steigern. Wenngleich es sich um rein hypothetische Antworten handelt und die Ergebnisse daher mit einer gewissen Vorsicht betrachtet werden sollten, deuten diese auf einen relativ starken potenziellen Anstieg der ÖPNV-Nutzung hin. Abschließend diskutieren wir, warum es trotzdem nicht sinnvoll erscheint, den ÖPNV kostenlos anzubieten und welche alternativen Politiken erfolgsversprechender erscheinen.
Behavioural biometrics in action
Authors: Bhattacharya Nandini
Published: November 2020

The importance of identifying and authenticating individuals has increased significantly with the rising levels of terrorism and cyber-crime. At the same time, the growth in the Internet of Things (IoT) will ensure an increase in the number of connections, meaning that billions of connected devices will need to be secured in the years ahead.
Poussin's Women
Authors: Thomas Troy
Published: November 2020

Poussin's Women: Sex and Gender in the Artist's Works examines the paintings and drawings of the well-known seventeenth-century French painter Nicolas Poussin (1594-1665) from a gender studies perspective, focusing on a critical analysis of his representations of women. The book's thematic chapters investigate Poussin's women in their roles as predators, as lustful or the objects of lust, as lovers, killers, victims, heroines, or models of virtue. Poussin's paintings reflect issues of gender within his social situation as he consciously or unconsciously articulated its conflicts and assumptions. A gender studies approach brings to light new critical insights that illuminate how the artist represented women, both positively and negatively, within the framework in his seventeenth-century culture. This book covers the artist's works from Classical mythology, Roman history, Tasso, and the Bible. It serves as a good overview of Poussin as an artist, discussing the latest research and including new interpretations of his major works.
The impact of coronavirus disease 2019 (COVID-19) on provider use of electronic hand hygiene monitoring technology
Authors: Hess Olivia C. R. , Armstrong-Novak Jo Dee , Doll Michelle , Cooper Kaila , Bailey Pamela , Godbout Emily , Stevens Michael P. , Bearman Gonzalo
Published: November 2020

The use of an electronic hand hygiene monitoring system (EHHMS) decreased due to the coronavirus disease 2019 (COVID-19) pandemic. We analyzed dispenser use, hand hygiene (HH) badge use, and HH compliance to determine the effect of COVID-19 on EHHMS use and HH compliance. HH product shortages and other pandemic-induced challenges influenced EHHMS use.
A HARMONIC SUM OVER NONTRIVIAL ZEROS OF THE RIEMANN ZETA-FUNCTION
Authors: BRENT RICHARD P. , PLATT DAVID J. , TRUDGIAN TIMOTHY S.
Published: November 2020

We consider the sum

$\sum 1/\gamma $
, where

$\gamma $
ranges over the ordinates of nontrivial zeros of the Riemann zeta-function in an interval

$(0,T]$
, and examine its behaviour as

$T \to \infty $
. We show that, after subtracting a smooth approximation

$({1}/{4\pi }) \log ^2(T/2\pi ),$
the sum tends to a limit

$H \approx -0.0171594$
, which can be expressed as an integral. We calculate H to high accuracy, using a method which has error

$O((\log T)/T^2)$
. Our results improve on earlier results by Hassani [‘Explicit approximation of the sums over the imaginary part of the non-trivial zeros of the Riemann zeta function’, Appl. Math. E-Notes16 (2016), 109–116] and other authors.
Exploration of baseline and early changes in neurocognitive characteristics as predictors of treatment response to bupropion, sertraline, and placebo in the EMBARC clinical trial
Authors: Ang Yuen-Siang , Bruder Gerard E. , Keilp John G. , Rutherford Ashleigh , Alschuler Daniel M. , Pechtel Pia , Webb Christian A. , Carmody Thomas , Fava Maurizio , Cusin Cristina , McGrath Patrick J. , Weissman Myrna , Parsey Ramin , Oquendo Maria A. , McInnis Melvin G. , Cooper Crystal M. , Deldin Patricia , Trivedi Madhukar H. , Pizzagalli Diego A.
Published: November 2020

Background

Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.

Methods

In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.

Results

Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.

Conclusion

These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
Differentiating tardive dyskinesia: a video-based review of antipsychotic-induced movement disorders in clinical practice
Authors: Hauser Robert A. , Meyer Jonathan M. , Factor Stewart A. , Comella Cynthia L. , Tanner Caroline M. , Xavier Rose Mary , Caroff Stanley N. , Lundt Leslie
Published: November 2020

Accurate diagnosis and appropriate treatment of tardive dyskinesia (TD) are imperative, as its symptoms can be highly disruptive to both patients and their caregivers. Misdiagnosis can lead to incorrect interventions with suboptimal or even deleterious results. To aid in the identification and differentiation of TD in the psychiatric practice setting, we review its clinical features and movement phenomenology, as well as those of other antipsychotic-induced movement disorders, with accompanying links to illustrative videos. Exposure to dopamine receptor blocking agents (DRBAs) such as antipsychotics or antiemetics is associated with a spectrum of movement disorders including TD. The differential diagnosis of TD is based on history of DRBA exposure, recent discontinuation or dose reduction of a DRBA, and movement phenomenology. Common diagnostic challenges are the abnormal behaviors and dyskinesias associated with advanced age or chronic mental illness, and other movement disorders associated with DRBA therapy, such as akathisia, parkinsonian tremor, and tremor related to use of mood stabilizing agents (eg, lithium, divalproex). Duration of exposure may help rule out acute drug-induced syndromes such as acute dystonia or acute/subacute akathisia. Another important consideration is the potential for TD to present together with other drug-induced movement disorders (eg, parkinsonism, parkinsonian tremor, and postural tremor from mood stabilizers) in the same patient, which can complicate both diagnosis and management. After documentation of the phenomenology, severity, and distribution of TD movements, treatment options should be reviewed with the patient and caregivers.
Recruitment and participation of a survey in a public–private primary care setting: experience from the QUALICOPC Malaysia
Authors: Husin Masliyana , Ab Rahman Norazida , Wong Xin Ci , Mohamad Noh Kamaliah , Tong Seng Fah , Schäfer Willemijn , Boerma Wienke , Atun Rifat , Sivasampu Sheamini
Published: November 2020

Aim:

The purpose of this paper is to describe the recruitment strategies, the response rates and the reasons for non-response of Malaysian public and private primary care doctors in an international survey on the quality, cost and equity in primary care.

Background:

Low research participation by primary care doctors, especially those working in the private sector, is a challenge to quality benchmarking.

Methods:

Primary care doctors were sampled through multi-stage sampling. The first stage-sampling unit was the primary care clinics, which were randomly sampled from five states in Malaysia to reflect their proportions in two strata – sector (public/private) and location (urban/rural). Strategies through endorsement, personalised invitation, face-to-face interview and non-monetary incentives were used to recruit public and private doctors. Data collection was carried out by fieldworkers through structured questionnaires.

Findings:

A total of 221 public and 239 private doctors participated in the study. Among the public doctors, 99.5% response rates were obtained. Among the private doctors, a 32.8% response rate was obtained. Totally, 30% of private clinics were uncontactable by telephone, and when these were excluded, the overall response rate is 46.8%. The response rate of the private clinics across the states ranges from 31.5% to 34.0%. A total of 167 answered the non-respondent questionnaire. Among the non-respondents, 77.4 % were male and 22.6% female (P = 0.011). There were 33.6% of doctors older than 65 years (P = 0.003) and 15.9% were from the state of Sarawak (P = 0.016) when compared to non-respondents. Reason for non-participation included being too busy (51.8%), not interested (32.9%), not having enough patients (9.1%) and did not find it beneficial (7.9%). Our study demonstrated the feasibility of obtaining favourable response rate in a survey involving doctors from public and private primary care settings
National identity between democracy and autocracy: a comparative analysis of 24 countries
Authors: Erhardt Julian , Wamsler Steffen , Freitag Markus
Published: November 2020

Recognizing democratic backsliding and increasing support for authoritarianism, research on public preferences for democracy and its authoritarian alternatives has gained traction. Moving beyond the extant focus on economic determinants, our analysis examines the effect of national identity, demonstrating that it is a double-edged sword for regime preferences. Using recent European Values Survey data on 24 European countries from 2017 to 2018, we show that civic national identity is associated with a higher support for democracy and lower support for authoritarian regimes, whereas the reverse holds for ethnic identities. Further, economic hardship moderates these relationships: it strengthens both the negative effect of ethnic national identities and, to some extent, the positive effect of civic national identities on democracy supportvis-à-visauthoritarian alternatives. This has important implications for the survival of democracy in times of crises and the study of a cultural backlash, since social identity matters substantively for individuals’ responses to economic hardship.
THE CITY SPEAKS: CITIES, CITIZENS, AND CIVIC DISCOURSE IN LATE ANTIQUITY AND THE EARLY MIDDLE AGES
Authors: WELTON MEGAN
Published: November 2020

This article investigates how civic discourse connects the virtue of citizens and the fortunes of cities in a variety of late antique and early medieval sources in the post-Roman west. It reveals how cities assume human qualities through the rhetorical technique of personification and, crucially, the ways in which individuals and communities likewise are described with civic terminology. It also analyzes the ways in which the city and the civic community are made to speak to one another at times of crisis and celebration. By examining a diverse range of sources including epideictic poetry, chronicles, hagiographies, and epigraphic inscriptions, this article addresses multiple modes of late antique and early medieval thought that utilize civic discourse. It first explores how late antique and early medieval authors employed civic discourse in non-urban contexts, including how they conceptualized the interior construction of an individual's mind and soul as a fortified citadel, how they praised ecclesiastical and secular leaders as city structures, and how they extended civic terminology to the preeminently non-urban space of the monastery. The article then examines how personified cities spoke to their citizens and how citizens could join their cities in song through urban procession. Civic encomia and invective further illustrate how medieval authors sought to unify the virtuous conduct of citizens with the ultimate fate of the city's security. The article concludes with a historical and epigraphic case study of two programs of mural construction in ninth-century Rome. Ultimately, this article argues that the repeated and emphatic exhortations to civic virtue provide access to how late antique and early medieval authors sought to intertwine the fate of the city with the conduct of her citizens, in order to persuade their audiences to act in accordance with the precepts of virtue.
Netflix & Kill
Authors: M. Braun Linda , Nienaber André , Wabnitz Pascal
Published: November 2020

Zusammenfassung. Suizidalität ist ein weltweites Phänomen. Global gesehen suizidiert sich alle 40 Sekunden ein Mensch. Demgegenüber steht der illustriert und detailliert gezeigte Suizid der adoleszenten Protagonistin in der populären Serie „13 Reasons Why“ des US-amerikanischen Streamingdienst Netflix. Diese mediale Darstellung ist für die gesamte Öffentlichkeit zugänglich. Allerdings wurden Zuschauer vor möglichen negativen Folgen kaum gewarnt. In diesem Zusammenhang stellen sich die Fragen, welche Risiken die Suiziddarstellung innerhalb der Medien birgt und ob sie sogar Chancen für einen bewussten Umgang mit dem tabuisierten Thema bereithält.
Naa20, the catalytic subunit of NatB complex, contributes to hepatocellular carcinoma by regulating the LKB1–AMPK–mTOR axis
Authors: Jung Taek-Yeol , Ryu Jae-Eun , Jang Mi-Mi , Lee Soh-Yeon , Jin Gyu-Rin , Kim Chan-Woo , Lee Chae-Young , Kim Hyelee , Kim EungHan , Park Sera , Lee Seonjeong , Lee Cheolju , Kim Wankyu , Kim TaeSoo , Lee Soo-Young , Ju Bong-Gun , Kim Hyun-Seok
Published: November 2020

N-α-acetyltransferase 20 (Naa20), which is a catalytic subunit of the N-terminal acetyltransferase B (NatB) complex, has recently been reported to be implicated in hepatocellular carcinoma (HCC) progression and autophagy, but the underlying mechanism remains unclear. Here, we report that based on bioinformatic analysis of Gene Expression Omnibus and The Cancer Genome Atlas data sets, Naa20 expression is much higher in HCC tumors than in normal tissues, promoting oncogenic properties in HCC cells. Mechanistically, Naa20 inhibits the activity of AMP-activated protein kinase (AMPK) to promote the mammalian target of rapamycin signaling pathway, which contributes to cell proliferation, as well as autophagy, through its N-terminal acetyltransferase (NAT) activity. We further show that liver kinase B1 (LKB1), a major regulator of AMPK activity, can be N-terminally acetylated by NatB in vitro, but also probably by NatB and/or other members of the NAT family in vivo, which may have a negative effect on AMPK activity through downregulation of LKB1 phosphorylation at S428. Indeed, p-LKB1 (S428) and p-AMPK levels are enhanced in Naa20-deficient cells, as well as in cells expressing the nonacetylated LKB1-MPE mutant; moreover, importantly, LKB1 deficiency reverses the molecular and cellular events driven by Naa20 knockdown. Taken together, our findings suggest that N-terminal acetylation of LKB1 by Naa20 may inhibit the LKB1–AMPK signaling pathway, which contributes to tumorigenesis and autophagy in HCC.
Orthodontic patients’ oral hygiene compliance by utilizing a smartphone application (Brush DJ): a randomized clinical trial
Authors: Farhadifard Homa , Soheilifar Sepideh , Farhadian Maryam , Kokabi Hadi , Bakhshaei Anahita
Published: November 2020

Considering the widespread use of smartphones and their applications (apps), as well as the undeniable role of reminders and apps in behavioral interventions, this study aimed to assess the efficacy of a smartphone app (Brush DJ) for oral hygiene compliance of patients with fixed orthodontic appliances. In this randomized clinical trial, 120 patients between 15 to 25 years who had just started fixed orthodontic treatment were randomly divided into two groups (n = 60). Control patients received conventional oral hygiene instruction, while patients in the intervention group were asked to use the Brush DJ smartphone app, after receiving conventional oral hygiene instruction. The plaque index (PI) and gingival index (GI) were measured at baseline (T0), and at 4 weeks (T1), 8 weeks (T2) and 12 weeks (T3) after the onset of study. A questionnaire was given to all patients to assess the frequency and duration of tooth brushing per day, and the frequency of app usage and reminder noticing in the intervention group. Improvements in PI and GI were noted in the intervention group; while these parameters increased in the control group. Significant differences were noted in PI and GI changes between the two groups (p < 0.001). Brushing frequency and duration were positively correlated with app usage during the follow-up period. Ultimately, we believe that smartphone apps, as motivators and reminders, can greatly help in improving the orthodontic patients’ oral hygiene compliance, especially in adolescents
Deletion of the deISGylating enzyme USP18 enhances tumour cell antigenicity and radiosensitivity
Authors: Pinto-Fernandez Adan , Salio Mariolina , Partridge Tom , Chen Jianzhou , Vere George , Greenwood Helene , Olie Cyriel Sebastiaan , Damianou Andreas , Scott Hannah Claire , Pegg Henry Jack , Chiarenza Alessandra , Díaz-Saez Laura , Smith Paul , Gonzalez-Lopez Claudia , Patel Bhavisha , Anderton Emma , Jones Neil , Hammonds Tim R. , Huber Kilian , Muschel Ruth , Borrow Persephone , Cerundolo Vincenzo , Kessler Benedikt M.
Published: November 2020

Background

Interferon (IFN) signalling pathways, a key element of the innate immune response, contribute to resistance to conventional chemotherapy, radiotherapy, and immunotherapy, and are often deregulated in cancer. The deubiquitylating enzyme USP18 is a major negative regulator of the IFN signalling cascade and is the predominant human protease that cleaves ISG15, a ubiquitin-like protein tightly regulated in the context of innate immunity, from its modified substrate proteins in vivo.

Methods

In this study, using advanced proteomic techniques, we have significantly expanded the USP18-dependent ISGylome and proteome in a chronic myeloid leukaemia (CML)-derived cell line. USP18-dependent effects were explored further in CML and colorectal carcinoma cellular models.

Results

Novel ISGylation targets were characterised that modulate the sensing of innate ligands, antigen presentation and secretion of cytokines. Consequently, CML USP18-deficient cells are more antigenic, driving increased activation of cytotoxic T lymphocytes (CTLs) and are more susceptible to irradiation.

Conclusions

Our results provide strong evidence for USP18 in regulating antigenicity and radiosensitivity, highlighting its potential as a cancer target.
Long noncoding RNA ASB16-AS1 inhibits adrenocortical carcinoma cell growth by promoting ubiquitination of RNA-binding protein HuR
Authors: Long Bo , Yang Xufei , Xu Xixia , Li Xiaoxin , Xu Xinjie , Zhang Xuebin , Zhang Shuyang
Published: November 2020

Adrenocortical carcinoma is one of the aggressive malignancies and it originates from the cortex of adrenal gland. Dysregulation of long non-coding RNA plays important roles in the development of adrenocortical carcinoma. Here, we found that lncRNA ASB16-AS1 was down-regulated in adrenocortical carcinoma and ASB16-AS1 functions as tumor suppressor in vitro and in vivo. We then found that IGF1R and CDK6 are regulated by ASB16-AS1 in adrenocortical carcinoma cells by transcriptome RNA sequencing. ASB16-AS1 associates with RNA-binding protein HuR (ELAVL1) as revealed by RNA pull-down following mass spectrometry. Also, ASB16-AS1 inhibits HuR expression post-translationally by promoting its ubiquitination. ASB16-AS1 regulates IGF1R and CDK6 mRNA expression through RNA-binding protein HuR. We then found that inhibition of ASB16-AS1 attenuates the binding of ubiquitin E3 ligase BTRC to HuR and subsequently inhibits HuR protein unbiquitination and degradation. BTRC knock-down could reverse the effect of AB16-AS1 on HuR, CDK6, and IGF1R levels. Collectively, these results demonstrate that ASB16-AS1 regulates adrenocortical carcinoma cell proliferation and tackling the level of ASB16-AS1 may be developed to treat adrenocortical carcinoma.
Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes
Authors: Zhou Jing-dong , Zhang Ting-juan , Xu Zi-jun , Deng Zhao-qun , Gu Yu , Ma Ji-chun , Wen Xiang-mei , Leng Jia-yan , Lin Jiang , Chen Su-ning , Qian Jun
Published: November 2020

The potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.
Ultrasound-guided platelet-rich plasma injection and multimodality ultrasound examination of peripheral nerve crush injury
Authors: Zhu Yaqiong , Jin Zhuang , Wang Jing , Chen Siming , Hu Yongqiang , Ren Ling , Wang Yu , Song Qing , Tian Xiaoqi , Xie Fang , Peng Jiang , Peng Nan , Luo Yukun , Wang Yuexiang
Published: November 2020

Ultrasound-guided platelet-rich plasma (PRP) injection is able to make up for the limitations of applying a single growth factor. The goal of this study was to investigate the effects of serial ultrasound-guided PRP injections of the appropriate concentration on the treatment of sciatic nerve crush injury, and explore the value of multimodality ultrasound techniques in evaluating the prognosis of crushed peripheral nerve. In vitro, optimal concentration of PRP (from 150%, 250%, 450%, and 650%) was screened due for its maximal effect on proliferation and neurotrophic function of Schwann cells (SCs). In vivo, ninety rabbits were equally and randomly divided into normal control, model, PRP-2.5×, PRP-4.5×, and PRP-6.5× groups. The neurological function and electrophysiological recovery evaluation, and the comparison of the multimodality ultrasound evaluation with the histological results of sciatic nerve crush injury were performed to investigate the regenerative effects of PRP at different concentrations on the sciatic nerve crush injury. Our results showed that the PRP with a 4.5-fold concentration of whole blood platelets could significantly stimulate the proliferation and secretion of SCs and nerve repair. The changes in stiffness and blood perfusion were positively correlated with the collagen area percentage and VEGF expression in the injured nerve, respectively. Thus, serial ultrasound-guided PRP injections at an appropriate concentration accelerates the recovery of axonal function. Multimodality ultrasound techniques provide a clinical reference for prognosis by allowing the stiffness and microcirculation perfusion of crush-injured peripheral nerves to be quantitatively evaluated.
Dynamics of picosecond laser ablation for surgical treatment of colorectal cancer
Authors: Beck R. J. , Bitharas I. , Hand D. P. , Maisey T. , Moore A. J. , Shires M. , Thomson R. R. , West N. P. , Jayne D. G. , Shephard J. D.
Published: November 2020

Endoluminal surgery for the treatment of colorectal neoplasia is typically carried out using electrocautery tools which imply limited precision and the risk of harm through collateral thermal damage to the adjacent healthy tissue. As a potential alternative, we present the successful colonic epithelial laser ablation by means of picosecond laser pulses. Laser ablation studies performed in ex-vivo colon tissue result in cavities with comparable thickness to early stage colorectal cancers. The corresponding histology sections exhibit only minimal collateral damage to the surrounding tissue and the depth of the ablation can be controlled precisely by means of the pulse energy. High-speed imaging has been used for the first time to visualize picosecond laser ablation of cancerous tissue in a clinically relevant model. This information was correlated with histopathology and optical surface profilometry revealing the dynamic nature of the laser tissue interaction and the need for temporal or spatial separation of pulses for optimum efficacy with regards to tissue removal. Overall, the application of picosecond laser pulses to ablate endoluminal bowel lesions demonstrates significantly improved precision and reduced thermal damage to the adjacent tissue in comparison to conventional procedures and hence will enable more precise surgical treatment of cancers.
Quantitative comparison of the biomass-degrading enzyme repertoires of five filamentous fungi
Authors: Arntzen Magnus Ø. , Bengtsson Oskar , Várnai Anikó , Delogu Francesco , Mathiesen Geir , Eijsink Vincent G. H.
Published: November 2020

The efficiency of microorganisms to degrade lignified plants is of great importance in the Earth’s carbon cycle, but also in industrial biorefinery processes, such as for biofuel production. Here, we present a large-scale proteomics approach to investigate and compare the enzymatic response of five filamentous fungi when grown on five very different substrates: grass (sugarcane bagasse), hardwood (birch), softwood (spruce), cellulose and glucose. The five fungi included the ascomycetes Aspergillus terreus, Trichoderma reesei, Myceliophthora thermophila, Neurospora crassa and the white-rot basidiomycete Phanerochaete chrysosporium, all expressing a diverse repertoire of enzymes. In this study, we present comparable quantitative protein abundance values across five species and five diverse substrates. The results allow for direct comparison of fungal adaptation to the different substrates, give indications as to the substrate specificity of individual carbohydrate-active enzymes (CAZymes), and reveal proteins of unknown function that are co-expressed with CAZymes. Based on the results, we present a quantitative comparison of 34 lytic polysaccharide monooxygenases (LPMOs), which are crucial enzymes in biomass deconstruction.
Exceptional sulfur and iron isotope enrichment in millimetre-sized, early Palaeozoic animal burrows
Authors: Harazim Dario , Virtasalo Joonas J. , Denommee Kathryn C. , Thiemeyer Nicolas , Lahaye Yann , Whitehouse Martin J.
Published: November 2020

Pyrite-δ34S and -δ56Fe isotopes represent highly sensitive diagnostic paleoenvironmental proxies that express high variability at the bed (< 10 mm) scale that has so far defied explanation by a single formative process. This study reveals for the first time the paleoenvironmental context of exceptionally enriched pyrite-δ34S and -δ56Fe in bioturbated, storm-reworked mudstones of an early Ordovician storm-dominated delta (Tremadocian Beach Formation, Bell Island Group, Newfoundland). Very few studies provide insight into the low-temperature sulfur and iron cycling from bioturbated muddy settings for time periods prior to the evolution of deep soil horizons on land. Secondary ion mass spectroscopy (SIMS) analyses performed on Beach Formation muddy storm event beds reveal spatially distinct δ34S and δ56Fe values in: (a) tubular biogenic structures and trails (δ34S ~ +40‰; δ56Fe ~ −0.5‰), (b) silt-filled Planolites burrows (δ34S ~ +40‰; δ56Fe ~ +0.5 to + 2.1‰), and (c) non-bioturbated mudstone (δ34S ~ +35‰; δ56Fe ~ +0.5‰). δ34S values of well above + 40.0‰ indicate at least some pyrite precipitation in the presence of a 34S-depleted pore water sulfide reservoir, via closed system (Raleigh-type) fractionation. The preferential enrichment of 56Fe in Planolites burrows is best explained via microbially-driven liberation of Fe(II) from solid iron parent phases and precipitation from a depleted 54Fe dissolved Fe(II) reservoir. Rigorous sedimentological analysis represents a gateway to critically test the paleoenvironmental models describing the formation of a wide range of mudstones and elucidates the origins of variability in the global stable S and Fe isotope record.
Morphology, ultrastructure, genomics, and phylogeny of Euplotes vanleeuwenhoeki sp. nov. and its ultra-reduced endosymbiont “Candidatus Pinguicoccus supinus” sp. nov.
Authors: Serra Valentina , Gammuto Leandro , Nitla Venkatamahesh , Castelli Michele , Lanzoni Olivia , Sassera Davide , Bandi Claudio , Sandeep Bhagavatula Venkata , Verni Franco , Modeo Letizia , Petroni Giulio
Published: November 2020

Taxonomy is the science of defining and naming groups of biological organisms based on shared characteristics and, more recently, on evolutionary relationships. With the birth of novel genomics/bioinformatics techniques and the increasing interest in microbiome studies, a further advance of taxonomic discipline appears not only possible but highly desirable. The present work proposes a new approach to modern taxonomy, consisting in the inclusion of novel descriptors in the organism characterization: (1) the presence of associated microorganisms (e.g.: symbionts, microbiome), (2) the mitochondrial genome of the host, (3) the symbiont genome. This approach aims to provide a deeper comprehension of the evolutionary/ecological dimensions of organisms since their very first description. Particularly interesting, are those complexes formed by the host plus associated microorganisms, that in the present study we refer to as “holobionts”. We illustrate this approach through the description of the ciliateEuplotes vanleeuwenhoekisp. nov. and its bacterial endosymbiont “CandidatusPinguicoccus supinus” gen. nov., sp. nov. The endosymbiont possesses an extremely reduced genome (~ 163 kbp); intriguingly, this suggests a high integration between host and symbiont.
Characteristics of temperature evolution from 1960 to 2015 in the Three Rivers’ Headstream Region, Qinghai, China
Authors: Liu Xiaoqiong , Zhang Yuyang , Liu Yansui , Zhao Xinzheng , Zhang Jian , Rui Yang
Published: November 2020

The cumulative anomaly analysis, the ensemble empirical mode decomposition (EEMD), the Bernaola Galvan heuristic segmentation algorithm (BGSA), the Le Page test, the moving t test at different sub-series scales, and the quasi-periodic oscillations (QPOs) were used to demonstrate the statistical characteristics of the temperature changes in the study area from 1960 to 2015. The results were as follows: the temperatures varied obviously among subregions and seasons and they generally increased; the climate tendency rates of autumn mean temperatures were higher than those of summer and spring; additionally, the temperatures in the three subregions of the Three Rivers’ Headstream Region (THRHR) were relatively low in the 1960s, especially in the early 1960s, followed by those in the 1970s, and the annual mean temperature has been increasing since the mid-late 1980s, especially in the middle 1990s. The results of EEMD showed that the QPOs of the annual mean temperature series in the study area were mainly quasi-3 years, quasi-5–8 years, quasi-12–15 years, and quasi-35–38 years. The results of the annual mean temperature series mutational sites showed that a significant warming mutation began in approximately 1997; and the mutational sites of seasonal mean temperature series in the three subregions of the THRHR all began in the middle and late 1990s. The prediction result of the temperature series trend based on multiple methods showed that the warming persistence of annual and seasonal mean temperature series would be stronger, and their seasonal and regional differences were obvious.
Fabrication of selective and sensitive chemical sensor probe based on ternary nano-formulated CuO/MnO2/Gd2O3 spikes by hydrothermal approach
Authors: Rahman Mohammed M. , Alam M. M. , Asiri Abdullah M. , Opo Firoz A. D. M.
Published: November 2020

In this approach, thin spikes (NSs) of ternary nano-formulated mixed CuO/MnO2/Gd2O3were synthesized by the hydrothermal approach for efficient detection of 3-methoxyphenyl hydrazine (3-MPHyd) chemical from various environmental samples. The NSs were systematically characterized by using XPS, EDS, TEM, FTIR, UV/vis, and XRD. The fabricated NSs onto the glassy carbon electrode (GCE) was successfully applied for the selective and sensitive detection of 3-MPHyd in the phosphate buffer system (PBS), which displayed the highest sensitivity, good selectivity with ultra-trace detection limit, high stability, good reproducibility, and quick response time. The real environmental samples were tested for validation from stand point of the ternary doped nanomaterials for sensing in the practical applications using by electrochemical method.
Pivotal role of DPYSL2A in KLF4-mediated monocytic differentiation of acute myeloid leukemia cells
Authors: Noura Mina , Morita Ken , Kiyose Hiroki , Matsuo Hidemasa , Nishinaka-Arai Yoko , Kurokawa Mineo , Kamikubo Yasuhiko , Adachi Souichi
Published: November 2020

Although the biological importance of Krüppel-like factor 4 (KLF4) transcription factor in the terminal differentiation of hematopoietic cells to the monocytes has been well established, the underlying mechanisms remain elusive. To clarify the molecular basis of KLF4-mediated monocytic differentiation, we performed detailed genetic studies in acute myeloid leukemia (AML) cells. Here, we report that dihydropyrimidinase like 2 (DPYSL2), also known as CRMP2, is a novel key differentiation mediator downstream of KLF4 in AML cells. Interestingly, we discovered that KLF4-mediated monocytic differentiation is selectively dependent on one specific isoform, DPYSL2A, but not on other DPYSL family genes. Terminal differentiation to the monocytes and proliferation arrest in AML cells induced by genetic or pharmacological upregulation of KLF4 were significantly reversed by short hairpin RNA (shRNA)-mediated selective depletion of DPYSL2A. Chromatin immunoprecipitation assay revealed that KLF4 associates with the proximal gene promoter of DPYSL2A and directly transactivates its expression. Together with the unique expression patterns of KLF4 and DPYSL2 limited to the differentiated monocytes in the hematopoietic system both in human and mouse, the identified KLF4-DPYSL2 axis in leukemia cells may serve as a potential therapeutic target for the development of novel differentiation therapies for patients with AML.
Cholesteryl ester levels are elevated in the caudate and putamen of Huntington’s disease patients
Authors: Phillips Gabrielle R. , Hancock Sarah E. , Brown Simon H. J. , Jenner Andrew M. , Kreilaus Fabian , Newell Kelly A. , Mitchell Todd W.
Published: November 2020

Huntington’s disease (HD) is an autosomal dominant neurodegenerative illness caused by a mutation in the huntingtin gene (HTT) and subsequent protein (mhtt), to which the brain shows a region-specific vulnerability. Disturbances in neural cholesterol metabolism are established in HD human, murine and cell studies; however, cholesteryl esters (CE), which store and transport cholesterol in the brain, have not been investigated in human studies. This study aimed to identify region-specific alterations in the concentrations of CE in HD. The Victorian Brain Bank provided post-mortem tissue from 13 HD subjects and 13 age and sex-matched controls. Lipids were extracted from the caudate, putamen and cerebellum, and CE were quantified using targeted mass spectrometry. ACAT 1 protein expression was measured by western blot. CE concentrations were elevated in HD caudate and putamen compared to controls, with the elevation more pronounced in the caudate. No differences in the expression of ACAT1 were identified in the striatum. No remarkable differences in CE were detected in HD cerebellum. The striatal region-specific differences in CE profiles indicate functional subareas of lipid disturbance in HD. The increased CE concentration may have been induced as a compensatory mechanism to reduce cholesterol accumulation.
Field evaporation and atom probe tomography of pure water tips
Authors: Schwarz T. M. , Weikum E. M. , Meng K. , Hadjixenophontos E. , Dietrich C. A. , Kästner J. , Stender P. , Schmitz G.
Published: November 2020

Measuring biological samples by atom probe tomography (APT) in their natural environment, i.e. aqueous solution, would take this analytical method, which is currently well established for metals, semi-conductive materials and non-metals, to a new level. It would give information about the 3D chemical structure of biological systems, which could enable unprecedented insights into biological systems and processes, such as virus protein interactions. For this future aim, we present as a first essential step the APT analysis of pure water (Milli-Q) which is the main component of biological systems. After Cryo-preparation, nanometric water tips are field evaporated with assistance by short laser pulses. The obtained data sets of several tens of millions of atoms reveal a complex evaporation behavior. Understanding the field evaporation process of water is fundamental for the measurement of more complex biological systems. For the identification of the individual signals in the mass spectrum, DFT calculations were performed to prove the stability of the detected molecules.