bluuebunny/crossref_metadata_2025 huggingface dataset:
Applicable Law to Transnational Personal Data: Trends and Dynamics
Authors: Huang Jie (Jeanne)
Published: September 2020

The recent COVID-19 outbreak has pushed the tension of protecting personal data in a transnational context to an apex. Using a real case where the personal data of an international traveler was illegally released by Chinese media, this Article identifies three trends that have emerged at each stage of conflict-of-laws analysis for lex causae: (1) The EU, the US, and China characterize the right to personal data differently; (2) the spread-out unilateral applicable law approach comes from the fact that all three jurisdictions either consider the law for personal data protection as a mandatory law or adopt connecting factors leading to the law of the forum; and (3) the EU and China strongly advocate deAmericanization of substantive data protection laws. The trends and their dynamics provide valuable implications for developing the choice of laws for transnational personal data. First, this finding informs parties that jurisdiction is a predominant issue in data breach cases because courts and regulators would apply the law of the forum. Second, currently, there is no international treaty or model law on choice-of-law issues for transnational personal data. International harmonization efforts will be a long and difficult journey considering how the trends demonstrate not only the states’ irreconcilable interests but also how states may consider these interests as their fundamental values that they do not want to trade off. Therefore, for states and international organizations, a feasible priority is to achieve regional coordination or interoperation among states with similar values on personal data protection.
LOCATING THE WALLACHIAN REVOLUTION OF 1848
Authors: MORRIS JAMES
Published: September 2020

This article offers a new interpretation of the Wallachian revolution of 1848. It places the revolution in its imperial and European contexts and suggests that the course of the revolution cannot be understood without reference to these spheres. The predominantly agrarian principality faced different but commensurate problems to other European states that experienced revolution in 1848. Revolutionary leaders attempted to create a popular political culture in which all citizens, both urban and rural, could participate. This revolutionary community formed the basis of the government's attempts to enter into relations with its Ottoman suzerain and its Russian protector. Far from attempting to subvert the geopolitical order, this article argues that the Wallachians positioned themselves as loyal subjects of the sultan and saw their revolution as a meeting point between the Ottoman Empire and European civilization. The revolution was not a staging post on the road to Romanian unification, but a brief moment when it seemed possible to realize internal regeneration on a European model within an Ottoman imperial framework. But the Europe of 1848 was too unstable for the revolutionaries to succeed. The passing of this moment would lead some to lose faith in both the Ottoman Empire and Europe.
Effect ofINSIG1on the milk fat synthesis of buffalo mammary epithelial cells
Authors: Fan Xinyang , Qiu Lihua , Teng Xiaohong , Zhang Yongyun , Miao Yongwang
Published: September 2020

We hypothesized that insulin-induced gene 1 (INSIG1) affects milk fat synthesis in buffalo. For this reason, the protein abundance of INSIG1 in the mammary tissue of buffalo during the peak period of lactation and dry-off period was evaluated. The results showed that the expression of INSIG1 at the peak of lactation was lower than that in the dry-off period. To explore the role of INSIG1 in milk fat synthesis, the buffalo mammary epithelial cells (BMECs) were isolated and purified from buffalo mammary tissue, andINSIG1gene were overexpressed and knocked down by constructing the recombinant lentivirus vector ofINSIG1gene and transfecting into BMECs. Results revealed thatINSIG1overexpression decreased the expression ofINSIG2,SREBP,PPARG,SCD,GPAM,DGAT2andAGPAT6, which led to reduction of triglycerides (TAG) content in the cell. In contrast, knockdown ofINSIG1had a positive effect on mRNA expression of the above genes. Overall, the data provide strong support for a key role of INSIG1 in the regulation of milk fat synthesis in BMECs.
Associations between monthly rainfall and mortality in cattle due to East Coast fever, anaplasmosis and babesiosis
Authors: Chepkwony Richard , Castagna Carolina , Heitkönig Ignas , van Bommel Severine , van Langevelde Frank
Published: September 2020

Weather conditions can impact infectious disease transmission, causing mortalities in humans, wild and domestic animals. Although rainfall in dry tropical regions is highly variable over the year, rainfall is thought to play an important role in the transmission of tick-borne diseases. Whether variation in rainfall affects disease-induced mortalities, is, however, poorly understood. Here, we use long-term data on monthly rainfall and Boran cattle mortality (1998–2017) to investigate associations between within-year variation in rainfall and cattle mortalities due to East Coast fever (ECF), anaplasmosis and babesiosis in Laikipia, Kenya, using ARIMAX modelling. Results show a negative correlation between monthly rainfall and cattle mortality for ECF and anaplasmosis, with a lag effect of 2 and 6 months, respectively. There was no association between babesiosis-induced mortalities and monthly rainfall. The results of this study suggest that control of the tick-borne diseases ECF and anaplasmosis to reduce mortalities should be intensified during rainy periods after the respective estimated time lags following dry periods.
Comparison among FLOTAC, Kato-Katz and formalin ether concentration techniques for diagnosis of intestinal parasitic infections in school children in an Egyptian rural setting
Authors: Allam Amal Farahat , Farag Hoda Fahmy , Lotfy Wael , Fawzy Hayam Hussien , Elhadad Heba , Shehab Amel Youssef
Published: September 2020

The study aimed to compare the diagnostic performance of the Kato-Katz, formalin ether concentration method (FECM) and FLOTAC using Sheather's sugar solution (FS1), saturated sodium chloride (FS2) and zinc sulfate (FS7) for the diagnosis of intestinal parasites among school children, focusing onSchistosoma mansoni. Ninety fecal samples were examined using the above mentioned techniques. The overall infection rate was 87.7%. Concerning protozoa, FLOTAC (FS1 and FS2) and FECM detected nearly equal infection rates (43.3% and 44.4%, respectively) with very good agreement. Kato-Katz diagnosed the highest helminthic infection rate (57.8%) followed by FLOTAC FS7 (44.4%) and FECM showed the lowest helminthic infection rate (27.7%). As forS. mansoni, Kato-Katz showed an infection rate of 38.8%vsFLOTAC (22.2%) and FECM (11.1%). The three techniques detected the same infection rate (11.1%) with egg counts more than 72 eggs/gram of feces. The FLOTAC sensitivity and accuracy for the diagnosis of protozoa were 97% and 99%, respectively. Regarding helminths diagnosis, FLOTAC technique showed higher sensitivity (77%) and accuracy (87%) compared to FECM (48% sensitivity and 70% accuracy). Therefore, FLOTAC can be used synchronously or in replacement to other diagnostic techniques. This can strategically impact future control programmes of intestinal parasitic infections in limited resources settings.
Path Planning Methodology for Multi-Layer Welding of Intersecting Pipes Considering Collision Avoidance
Authors: Shahabi M. , Ghariblu H. , Beschi M. , Pedrocchi N.
Published: September 2020

The V-groove joint of thick wall intersecting pipes must be filled by multi-layer weld. The welding path of intersecting pipes is complicated, and hence multi-layer welds increase the complexity of the problem. This paper proposes a methodology for path planning of multi-layer weld of thick wall intersecting pipes. The methodology is based on measuring the electrode pose located in both side and front views of intersecting pipes. In order to compensate for the path deviation around the pipe circumference, the measured values are used to interpolate the path of each pass between two views. The methodology has been applied in a case study. Simulation results approve that multi-layer weld appropriately fills the V-groove joint space around the pipe circumference. In addition, collision avoidance between welding torch and pipes is considered by introducing a safety ring. While the robot wrist moves inside the safety ring, no collision occurs. Simulation results show the robustness of the proposed path planning method, introduced for collision avoidance.
Watery Relations and Creations: Ancient Maya Engagement with the Cara Blanca Pools
Authors: Larmon Jean T.
Published: September 2020

Many archaeologists have sought to interpret the archaeological record with an understanding that non-humans are active constituents within myriad human ontologies. I suggest that to truly understand the spaces with which we exist, we need not invite non-humans into our ontologies, but rather reincorporate ourselves into theirs. This approach decenters humans and puts forth an ontology of matter, within which diverse human ontologies can unfold but to which we are all subject. A closer look at water, specifically at the ancient Maya pilgrimage site of Cara Blanca, Belize, offers an example of how humans exist as only one part of many that participate in the formation of landscapes and shows how water's affect preempts cultural relationships with water. The inherent qualities of water are affective, and it is this affect that integrates Cara Blanca. I introduce my adoption of the concept of kinesis, a territorializing force that allows for the possibility of non-humans to cause history. Thus, I follow water through the archaeological data, elucidating how water's kinesis created possibility at Cara Blanca.
Still Burning: An Exploration of the Impacts of the 2018/2019 Tasmanian Summer Bushfires on Community Pharmacy Operations in Affected Communities
Authors: Singleton Judith A. , Khng Sherley , McCourt Elizabeth M. , Watson Kaitlyn E. , Lau Esther T.L.
Published: September 2020

Introduction:

Human-induced climate change is increasing the likelihood and severity of wildfires across the globe. This has negative consequences for the health of affected communities through the loss of health systems’ infrastructure and disrupted health services. Community pharmacies are a central hub between patients and the health care system and can provide continuity of care during wildfires. However, there is little in peer-reviewed literature about the impacts of wildfires on community pharmacy operations.

Study Objective:

The aim of this study was therefore to explore the impacts of the 2018/2019 summer bushfires in Tasmania, Australia on community pharmacy operations in affected areas.

Methods:

Semi-structured telephone interviews were conducted with four community pharmacists who were working in the affected region during the bushfires. Interviews were audio recorded and transcribed verbatim. Qualitative data were analyzed using two methods– manual coding utilizing NVivo software and Leximancer analysis. Inter-rater reliability was ensured by two researchers analyzing the data independently. Differences in coding were discussed and agreement reached through negotiation amongst the research team.

Results:

From the manual coding analysis, five key themes emerged – communication and collaboration; support; patient health challenges; pharmacist experiences in delivering health care; and future planning. These aligned with the five themes that emerged from the Leximancer analysis – community; local; town; patients; and work. Participants described working during the wildfires as difficult, with multiple challenges reported including communication difficulties, operational barriers such as power cuts, legislative barriers, logistical issues with obtaining and storing medication supplies, and lack of preparation, support, and funding. They highlighted a lack of operational and financial support from the government and received most assistance from local council bodies and local branches of professional pharmacy organizations.

Conclusion:

During disasters, community pharmacies help reduce the burden on public hospitals by maintaining medication supplies and treating patients with minor ailments. However, increased support and inclusion in disaster management planning is needed to continue this role.
Crisis Standards of Care Implementation at the State Level in the United States
Authors: Margus Colton , Sarin Ritu R. , Molloy Michael , Ciottone Gregory R.
Published: September 2020

Introduction:

In 2009, the Institute of Medicine published guidelines for implementation of Crisis Standards of Care (CSC) at the state level in the United States (US). Based in part on the then concern for H1N1 pandemic, there was a recognized need for additional planning at the state level to maintain health system preparedness and conventional care standards when available resources become scarce. Despite the availability of this framework, in the years since and despite repeated large-scale domestic events, implementation remains mixed.

Problem:

Coronavirus disease 2019 (COVID-19) rejuvenates concern for how health systems can maintain quality care when faced with unrelenting burden. This study seeks to outline which states in the US have developed CSC and which areas of care have thus far been addressed.

Methods:

An online search was conducted for all 50 states in 2015 and again in 2020. For states without CSC plans online, state officials were contacted by email and phone. Public protocols were reviewed to assess for operational implementation capabilities, specifically highlighting guidance on ventilator use, burn management, sequential organ failure assessment (SOFA) score, pediatric standards, and reliance on influenza planning.

Results:

Thirty-six states in the US were actively developing (17) or had already developed (19) official CSC guidance. Fourteen states had no publicly acknowledged effort. Eleven of the 17 public plans had updated within five years, with a majority addressing ventilator usage (16/17), influenza planning (14/17), and pediatric care (15/17), but substantially fewer addressing care for burn patients (9/17).

Conclusion:

Many states lacked publicly available guidance on maintaining standards of care during disasters, and many states with specific care guidelines had not sufficiently addressed the full spectrum of hazard to which their health care systems remain vulnerable.
Mental Health and Fieldwork
Authors: Hummel Calla , El Kurd Dana
Published: September 2020

Researchers discuss the logistics of successful fieldwork but not the mental health considerations that fieldwork and the research process introduce. Successful fieldwork and fruitful academic careers hinge on acknowledging and managing our mental health. We discuss peer-support networks, secondary trauma, coping skills, therapy, and researchers’ mental health options before, during, and after fieldwork.
Physical function after dietary weight loss in overweight and obese adults with osteoarthritis: a systematic review and meta-analysis
Authors: Webb Emily J , Osmotherly Peter G , Baines Surinder K
Published: September 2020

Objective:

Osteoarthritis (OA) is associated with functional limitations that can impair mobility and reduce quality of life in affected individuals. Excess body weight in OA can exacerbate impaired physical function, highlighting the importance of weight management in this population. The aim of this systematic review was to compare the effects of different dietary interventions for weight loss on physical function in overweight and obese individuals with OA.

Design:

A comprehensive search of five databases was conducted to identify relevant articles for inclusion. Studies were included that examined the effect of dietary weight loss interventions, with or without exercise, on physical function in adults with OA who were overweight or obese. Quality and risk of bias were assessed using the Quality Criteria Checklist for primary research. Primary and secondary outcomes were extracted, including change in weight and physical function which included performance-based and self-report measures.

Results:

Nineteen relevant studies were included, which incorporated lifestyle interventions (n8), diet in combination with meal replacements (DMR;n5) and very low-energy diets (VLED;n6) using meal replacements only. Pooled data for eight RCT indicated a mean difference in Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function of 12·4 and 12·5 % following DMR or VLED interventions, respectively; however, no statistically significant change was detected for lifestyle interventions.

Conclusions:

Our findings suggest that partial use of meal replacements is as effective as their sole use in the more restrictive VLED. Both dietary interventions are more effective than lifestyle programmes to induce significant weight loss and improvements in physical function.
Eating behaviour of Indonesian adolescents: a systematic review of the literature
Authors: Rachmi Cut Novianti , Jusril Hafizah , Ariawan Iwan , Beal Ty , Sutrisna Aang
Published: September 2020

Objectives:

Global evidence has shown that behaviour acquired during adolescence often lasts into adulthood. Diet quality of and malnutrition in Indonesian adolescents is a neglected area of research. The current study reviews all studies related to eating behaviour in Indonesian adolescents to support evidence-based policy to improve diets.

Design:

We searched electronic databases (six international and one local), from January 2000 to April 2018. The search terms used were (1) prevalence (prevalence OR number* OR case*, incidence OR survey), (2) adolescents (adolescen* OR school-age OR young adult), (3) Indonesia (Indonesia*) and (4) eating pattern (eat* OR fruit OR vegetable OR food recall OR food OR frequenc* OR consumption OR dietary intake). Articles were assessed against a critical appraisal tool.

Setting:

Indonesia.

Participants:

10–19 years.

Results:

We discovered 15 studies related to eating behaviour, 5 of which were secondary analyses of nationally representative surveys and one was a nationwide survey. Of the nine studies, one study was conducted in multiple cities, and the rest were conducted in a single city or smaller area. There were seven main topics from the included studies: nutrient adequacy, fruit and vegetable consumption, water and beverage intake, Na intake, breakfast habit, snacking frequency and western fast food consumption.

Conclusions:

Adolescents consume inadequate amounts of protein, fruits and vegetables, and excessive amounts of Na and western fast food. Measures are needed to improve and motivate adolescents to adopt healthier eating patterns. Furthermore, there is a need to have one standard definition and measurement of eating behaviour in Indonesia.
Qualitative evaluation of a social media campaign to improve healthy food habits among urban adolescent females in Indonesia
Authors: Januraga Pande Putu , Izwardi Doddy , Crosita Yessi , Indrayathi Putu Ayu , Kurniasari Eny , Sutrisna Aang , Tumilowicz Alison
Published: September 2020

Objective:

The current study focuses on how adolescent girls in urban Indonesia accept technology in a social media (SM) campaign to promote healthy eating habits.

Design:

The study was a qualitative evaluation of the online campaign. In-depth interviews using semi-structured interview guidelines and focus group discussions were used to collect data. Data were analysed using a general inductive approach to provide simple and straightforward answers to our study questions.

Settings:

The study was conducted in two urban areas in Indonesia: Jakarta and Jogjakarta.

Participants:

Adolescent girls aged 16–19 years.

Results:

The SM campaign was perceived as beneficial for increasing participants’ knowledge. The campaign helped increase participants’ awareness of healthy diets and the health risks of unhealthy diets as well as increase their motivation to change their behaviour and avoid foods containing salt, sugar and excess fat. The participants perceived information from the online campaign as complete and trustworthy. Instagram was cited as the easiest platform to use, while the website was cited as having the most complete information. YouTube provided the best viewing experience but was considered a data-heavy platform. The barriers to change were perceptions of taste, limited choices for healthy but affordable ingredients and family-related factors.

Conclusions:

The online nutrition campaign was well accepted by Indonesian urban adolescent females and motivated them to act to protect their health. Future nutrition-related SM campaigns aimed at this demographic should focus on platforms with the greatest benefit and ease of use.
Identitätsbildung in der Pflegepraxis – Einpassung in die Verwertung oder Bildungsmuster?
Authors: Kühme Benjamin
Published: September 2020

Zusammenfassung. Auszubildende starten Ihre Pflegeausbildung motiviert, legen aber oft in der ernüchternden Praxisrealität ihre Ideale ab. Hier stoßen die Lernenden auf das an Verwertung ausgerichtete System Krankenhaus – und nicht auf einen Lernort, in dem pädagogisch geleitete Ausbildung stattfindet. Die Erfahrungen von Lernenden zeigen, dass die Geschehnisse eine Einpassung als Arbeitskraft abfordern. Entscheidend ist nun, wie die Auszubildenden damit umgehen.
Of men in mice: the development and application of a humanized gnotobiotic mouse model for microbiome therapeutics
Authors: Park John Chulhoon , Im Sin-Hyeog
Published: September 2020

Considerable evidence points to the critical role of the gut microbiota in physiology and disease. The administration of live microbes as a therapeutic modality is increasingly being considered. However, key questions such as how to identify candidate microorganisms and which preclinical models are relevant to recapitulate human microbiota remain largely unanswered. The establishment of a humanized gnotobiotic mouse model through the fecal microbiota transplantation of human feces into germ-free mice provides an innovative and powerful tool to mimic the human microbial system. However, numerous considerations are required in designing such a model, as various elements, ranging from the factors pertaining to human donors to the mouse genetic background, affect how microbes colonize the gut. Thus, it is critical to match the murine context to that of human donors to provide a continuous and faithful progression of human flora in mice. This is of even greater importance when the need for accuracy and reproducibility across global research groups are taken into account. Here, we review the key factors that affect the formulation of a humanized mouse model representative of the human gut flora and propose several approaches as to how researchers can effectively design such models for clinical relevance.
Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) with OT-82 induces DNA damage, cell death, and suppression of tumor growth in preclinical models of Ewing sarcoma
Authors: Gibson Anna E. , Yeung Choh , Issaq Sameer H. , Collins Victor J. , Gouzoulis Michael , Zhang Yiping , Ji Jiuping , Mendoza Arnulfo , Heske Christine M.
Published: September 2020

NAMPT mediates the rate-limiting step of the NAD salvage pathway, which maintains cellular bioenergetics and provides a necessary substrate for functions essential to rapidly proliferating cancer cells. In this study, we evaluated the efficacy and mechanisms of action of OT-82, a novel, high-potency NAMPT inhibitor with a favorable toxicity profile, in preclinical models of Ewing sarcoma (EWS), an aggressive pediatric malignancy with previously reported selective sensitivity to NAMPT inhibition. We show that OT-82 decreased NAD concentration and impaired proliferation of EWS cells in a dose-dependent manner, with IC50values in the single-digit nanomolar range. Notably, genetic depletion of NAMPT phenocopied pharmacological inhibition. On-target activity of OT-82 was confirmed with the addition of NMN, the product of NAMPT, which rescued NAD concentration and EWS cellular viability. Mechanistically, OT-82 treatment resulted in impaired DNA damage repair through loss of PARP activity, G2 cell-cycle arrest, and apoptosis in EWS cells. Additional consequences of OT-82 treatment included reduction of glycolytic and mitochondrial activity. In vivo, OT-82 impaired tumor growth and prolonged survival in mice bearing EWS xenografts. Importantly, antitumor effect correlated with pharmacodynamic markers of target engagement. Furthermore, combining low-dose OT-82 with low doses of agents augmenting DNA damage demonstrated enhanced antitumor activity in vitro and in vivo. Thus, OT-82 treatment represents a potential novel targeted approach for the clinical treatment of EWS.
Polygenic risk for schizophrenia and subcortical brain anatomy in the UK Biobank cohort
Authors: Grama Steluta , Willcocks Isabella , Hubert John J. , Pardiñas Antonio F. , Legge Sophie E. , Bracher-Smith Matthew , Menzies Georgina E. , Hall Lynsey S. , Pocklington Andrew J. , Anney Richard J. L. , Bray Nicholas J. , Escott-Price Valentina , Caseras Xavier
Published: September 2020

Research has shown differences in subcortical brain volumes between participants with schizophrenia and healthy controls. However, none of these differences have been found to associate with schizophrenia polygenic risk. Here, in a large sample (n = 14,701) of unaffected participants from the UK Biobank, we test whether schizophrenia polygenic risk scores (PRS) limited to specific gene-sets predict subcortical brain volumes. We compare associations with schizophrenia PRS at the whole genome level (‘genomic’, including all SNPs associated with the disorder at ap-value threshold < 0.05) with ‘genic’ PRS (based on SNPs in the vicinity of known genes), ‘intergenic’ PRS (based on the remaining SNPs), and genic PRS limited to SNPs within 7 gene-sets previously found to be enriched for genetic association with schizophrenia (‘abnormal behaviour,’ ‘abnormal long-term potentiation,’ ‘abnormal nervous system electrophysiology,’ ‘FMRP targets,’ ‘5HT2C channels,’ ‘CaV2 channels’ and ‘loss-of-function intolerant genes’). We observe a negative association between the ‘abnormal behaviour’ gene-set PRS and volume of the right thalamus that survived correction for multiple testing (ß = −0.031, pFDR = 0.005) and was robust to different schizophrenia PRSp-value thresholds. In contrast, the only association with genomic PRS surviving correction for multiple testing was for right pallidum, which was observed using a schizophrenia PRSp-value threshold < 0.01 (ß = −0.032,p = 0.0003, pFDR = 0.02), but not when using other PRSP-value thresholds. We conclude that schizophrenia PRS limited to functional gene sets may provide a better means of capturing differences in subcortical brain volume than whole genome PRS approaches.
UBE2O targets Mxi1 for ubiquitination and degradation to promote lung cancer progression and radioresistance
Authors: Huang Yumei , Yang Xijie , Lu Yanwei , Zhao Ye , Meng Rui , Zhang Sheng , Dong Xiaorong , Xu Shuangbing , Wu Gang
Published: September 2020

UBE2O, an E2/E3 hybrid ubiquitin-protein ligase, has been implicated in the regulation of adipogenesis, erythroid differentiation, and tumor proliferation. However, its role in cancer radioresistance remains completely unknown. Here, we uncover that UBE2O interacts and targets Mxi1 for ubiquitination and degradation at the K46 residue. Furthermore, we show that genetical or pharmacological blockade of UBE2O impairs tumor progression and radioresistance in lung cancer in vitro and in vivo, and these effects can be restored by Mxi1 inhibition. Moreover, we demonstrate that UBE2O is overexpressed and negatively correlated with Mxi1 protein levels in lung cancer tissues. Collectively, our work reveals that UBE2O facilitates tumorigenesis and radioresistance by promoting Mxi1 ubiquitination and degradation, suggesting that UBE2O is an attractive radiosensitization target for the treatment of lung cancer.
M2 macrophage-induced lncRNA PCAT6 facilitates tumorigenesis and angiogenesis of triple-negative breast cancer through modulation of VEGFR2
Authors: Dong Fang , Ruan Shengnan , Wang Jinlong , Xia Yun , Le Kehao , Xiao Xiaoyun , Hu Ting , Wang Qiong
Published: September 2020

As a common female malignancy, triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancers (BC). This study further studied the role of long noncoding RNA (lncRNA) prostate cancer-associated transcript 6 (PCAT6) in TNBC. Functional assays, including EdU, wound healing, transwell, and immunofluorescence staining, revealed the effect of PCAT6 on cell proliferation, migration, and EMT process. The tube-formation assay disclosed the function of PCAT6 on angiogenesis. In vivo assays were also established to explore the impact of PCAT6 on tumor growth and microangiogenesis. The results revealed that PCAT6 boosted TNBC cell proliferation, migration, and angiogenesis both in vitro and in vivo. Then, this study unveiled that M2 macrophage secreted VEGF to stimulate the upregulation of PCAT6, thus promoting angiogenesis in TNBC. Next, through bioinformatics analysis and mechanism assays, we identified that PCAT6 positively regulated VEGFR2 expression via ceRNA pattern and then participated in VEGFR/AKT/mTOR signaling pathway to accelerate angiogenesis. Moreover, PCAT6 bound USP14, a deubiquitinase, to induce the deubiquitination of VEGFR2. On the whole, M2 macrophage-induced upregulation of PCAT6 facilitates TNBC tumorigenesis through modulation of VEGFR2 expression via ceRNA and deubiquitination patterns.
KAP1-associated transcriptional inhibitory complex regulates C2C12 myoblasts differentiation and mitochondrial biogenesis via miR-133a repression
Authors: Zhang Jialing , Hua Chaoju , Zhang Yu , Wei Peng , Tu Yaping , Wei Taotao
Published: September 2020

The differentiation of myoblasts plays a key role in the growth of biological individuals and the reconstruction of muscle tissue. Several microRNAs are significantly upregulated during the differentiation of myoblasts and their target genes have been explored. However, the molecular mechanisms underlying the transcriptional regulation of microRNAs remain elusive. In the present study, we found that the expression of miR-133a is increased during the differentiation of C2C12 myoblasts. miR-133a mimic is sufficient to induce the biogenesis of mitochondria and differentiation of C2C12 myoblasts whereas miR-133a inhibitor abolishes cell differentiation. Using CRISPR affinity purification in situ of regulatory elements (CAPTURE) technique, we further dissected the regulatory mechanisms of miR-133a expression and found that KAP1-associated transcription complex accounts for the suppression of miR-133a in C2C12 myoblasts. Knockdown of KAP1 increased the expression of miR-133a, which contributed to the biogenesis of mitochondria and differentiation of C2C12 myoblasts. To our knowledge, this is the first study using the CAPTURE technology to identify the regulatory factors of miR-133a during cell differentiation, which may provide new ideas for understanding the precision regulatory machinery of microRNAs during different biological processes.
Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model
Authors: Pradhan Priyadarshika , Majhi Olivia , Biswas Abhijit , Joshi Vinod Kumar , Sinha Devanjan
Published: September 2020

Parkinson’s disease (PD) is a neuromotor disorder, primarily manifested by motor anomalies due to progressive loss of dopaminergic neurons. Although alterations in genetic factors have been linked with its etiology, exponential accumulation of environmental entities such as reactive oxygen species (ROS) initiate a cyclic chain reaction resulting in accumulation of cellular inclusions, dysfunctional mitochondria, and overwhelming of antioxidant machinery, thus accelerating disease pathogenesis. Involvement of oxidative stress in PD is further substantiated through ROS induced Parkinsonian models and elevated oxidative markers in clinical PD samples; thereby, making modulation of neuronal oxidative load as one of the major approaches in management of PD. Here we have found a potent antioxidant moiety Scopoletin (Sp), a common derivative in most of the nootropic herbs, with robust neuroprotective ability. Sp increased cellular resistance to ROS through efficient recycling of GSH to prevent oxidative damage. The Sp treated cells showed higher loads of reduced glutathione making them resistant to perturbation of antioxidant machinery or neurotoxin MPP+. Sp could restore the redox balance, mitochondrial function, and prevented oxidative damage, leading to recovery of dopaminergic neural networks and motion abilities in Drosophila genetic model of PD. Our data also suggest that Sp, in combination increases the therapeutic potency of L-DOPA by mitigating its chronic toxicity. Together, we highlight the possible ability of Sp in preventing oxidative stress mediated loss of dopaminergic neurons and at the same time enhance the efficacy of dopamine recharging regimens.
A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer
Authors: Du Ye , Wei Na , Ma Ruolin , Jiang Shuheng , Song Dong
Published: September 2020

Reprogrammed energy metabolism, especially the Warburg effect (aerobic glycolysis), is an emerging hallmark of cancer. Different from other breast cancer subtypes, triple-negative breast cancer (TNBC) exhibits high metabolic remodeling, increased aggressiveness and lack of targeted therapies. MicroRNAs (miRNA) are essential to TNBC malignant phenotypes. However, little is known about the contribution of miRNA to aerobic glycolysis in TNBC. Through an integrated analysis and functional verification, we reported that several miRNAs significantly correlates to the Warburg effect in TNBC, including miR-210-3p, miR-105-5p, and miR-767-5p. Ectopic expression of miR-210-3p enhanced glucose uptake, lactate production, extracellular acidification rate, colony formation ability, and reduced serum starvation-induced cell apoptosis. Moreover, GPD1L and CYGB were identified as two functional mediators of miR-210-3p in TNBC. Mechanistically, miR-210-3p targeted GPD1L to maintain HIF-1α stabilization and suppressed p53 activity via CYGB. Ultimately, miR-210-3p facilitated aerobic glycolysis through modulating the downstream glycolytic genes of HIF-1α and p53. Taken together, our results decipher miRNAs that regulate aerobic glycolysis and uncover that miR-210-3p specifically contributes to the Warburg effect in TNBC.
Correction: Melatonin suppresses chronic restraint stress-mediated metastasis of epithelial ovarian cancer via NE/AKT/β-catenin/SLUG axis
Authors: Bu Shixia , Wang Qian , Sun Junyan , Li Xiao , Gu Tingting , Lai Dongmei
Published: September 2020

Author Xiao Li was incorrectly associated with Department of Obstetrics and Gynaecology, Shanghai Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai 200233, China. The correct affiliation is Shanghai Municipal Key Clinical Speciality, Shanghai 20030, China.
miR-378-3p maintains the size of mouse primordial follicle pool by regulating cell autophagy and apoptosis
Authors: Sun Xiaowen , Klinger Francesca Gioia , Liu Jing , De Felici Massimo , Shen Wei , Sun Xiaofeng
Published: September 2020

Primordial follicle pool provides all available oocytes throughout the whole reproductive life span. Abnormal regulation in primordial follicle assembly leads to abnormal size of primordial follicle pool, even causes infertility. Here, miR-378-3p was proved to regulate mouse primordial follicle assembly both in vivo and in vitro. The expression of miR-378-3p significantly increased in mice ovaries from 17.5 dpc (days post coitum) up to 3 dpp (day post partum) compared with the expression of 16.5 dpc ovaries, which suggested that miR-378-3p was involved in primordial follicle assembly. To uncover the underlying mechanism, newborn mice ovaries were cultured in vitro in the presence of rapamycin and 3-methyladenine, which showed that the expression of miR-378-3p changed together with the percentage of primordial follicle. Moreover, during the normal process of primordial follicle assembly between 17.6 dpc and 3 dpp, autophagy is activated, while, apoptosis is inhibited. The in vivo results showed that newborn mice starved for 1.5 days showing the increased miR-378-3p, activated autophagy and inhibited apoptosis in the ovaries, had more percentage of primordial follicles. Over-expression of miR-378-3p using miR-378-3p agomir caused increased percentage of primordial follicle, increased level of autophagy, and decreased level of apoptosis. Knockdown of miR-378-3p by miR-378-3p antiagomir had the opposite results. Using pmirGLO Dual-Luciferase miRNA Target Expression system, we confirmed both PDK1 and Caspase9 were targets of miR-378-3p, which suggested that miR-378-3p activated autophagy by targeting PDK1 and inhibited apoptosis by targeting Caspase9. MiR-378-3p could be used as a biomarker of diseases caused by abnormal size of primordial follicle pool for diagnosis, prevention, or therapy.
Forest carbon sink neutralized by pervasive growth-lifespan trade-offs
Authors: Brienen R. J. W. , Caldwell L. , Duchesne L. , Voelker S. , Barichivich J. , Baliva M. , Ceccantini G. , Di Filippo A. , Helama S. , Locosselli G. M. , Lopez L. , Piovesan G. , Schöngart J. , Villalba R. , Gloor E.
Published: September 2020

Land vegetation is currently taking up large amounts of atmospheric CO2, possibly due to tree growth stimulation. Extant models predict that this growth stimulation will continue to cause a net carbon uptake this century. However, there are indications that increased growth rates may shorten trees′ lifespan and thus recent increases in forest carbon stocks may be transient due to lagged increases in mortality. Here we show that growth-lifespan trade-offs are indeed near universal, occurring across almost all species and climates. This trade-off is directly linked to faster growth reducing tree lifespan, and not due to covariance with climate or environment. Thus, current tree growth stimulation will, inevitably, result in a lagged increase in canopy tree mortality, as is indeed widely observed, and eventually neutralise carbon gains due to growth stimulation. Results from a strongly data-based forest simulator confirm these expectations. Extant Earth system model projections of global forest carbon sink persistence are likely too optimistic, increasing the need to curb greenhouse gas emissions.
Helicase LSH/Hells regulates kinetochore function, histone H3/Thr3 phosphorylation and centromere transcription during oocyte meiosis
Authors: Baumann Claudia , Ma Wei , Wang Xiaotian , Kandasamy Muthugapatti K. , Viveiros Maria M. , De La Fuente Rabindranath
Published: September 2020

Centromeres are epigenetically determined nuclear domains strictly required for chromosome segregation and genome stability. However, the mechanisms regulating centromere and kinetochore chromatin modifications are not known. Here, we demonstrate that LSH is enriched at meiotic kinetochores and its targeted deletion induces centromere instability and abnormal chromosome segregation. Superresolution chromatin analysis resolves LSH at the inner centromere and kinetochores during oocyte meiosis. LSH knockout pachytene oocytes exhibit reduced HDAC2 and DNMT-1. Notably, mutant oocytes show a striking increase in histone H3 phosphorylation at threonine 3 (H3T3ph) and accumulation of major satellite transcripts in both prophase-I and metaphase-I chromosomes. Moreover, knockout oocytes exhibit centromere fusions, ectopic kinetochore formation and abnormal exchange of chromatin fibers between paired bivalents and asynapsed chromosomes. Our results indicate that loss of LSH affects the levels and chromosomal localization of H3T3ph and provide evidence that, by maintaining transcriptionally repressive heterochromatin, LSH may be essential to prevent deleterious meiotic recombination events at repetitive centromeric sequences.
Cropland expansion in the United States produces marginal yields at high costs to wildlife
Authors: Lark Tyler J. , Spawn Seth A. , Bougie Matthew , Gibbs Holly K.
Published: September 2020

Recent expansion of croplands in the United States has caused widespread conversion of grasslands and other ecosystems with largely unknown consequences for agricultural production and the environment. Here we assess annual land use change 2008–16 and its impacts on crop yields and wildlife habitat. We find that croplands have expanded at a rate of over one million acres per year, and that 69.5% of new cropland areas produced yields below the national average, with a mean yield deficit of 6.5%. Observed conversion infringed upon high-quality habitat that, relative to unconverted land, had provided over three times higher milkweed stem densities in the Monarch butterfly Midwest summer breeding range and 37% more nesting opportunities per acre for waterfowl in the Prairie Pothole Region of the Northern Great Plains. Our findings demonstrate a pervasive pattern of encroachment into areas that are increasingly marginal for production, but highly significant for wildlife, and suggest that such tradeoffs may be further amplified by future cropland expansion.
Amalgamated cross-species transcriptomes reveal organ-specific propensity in gene expression evolution
Authors: Fukushima Kenji , Pollock David D.
Published: September 2020

The origins of multicellular physiology are tied to evolution of gene expression. Genes can shift expression as organisms evolve, but how ancestral expression influences altered descendant expression is not well understood. To examine this, we amalgamate 1,903 RNA-seq datasets from 182 research projects, including 6 organs in 21 vertebrate species. Quality control eliminates project-specific biases, and expression shifts are reconstructed using gene-family-wise phylogenetic Ornstein–Uhlenbeck models. Expression shifts following gene duplication result in more drastic changes in expression properties than shifts without gene duplication. The expression properties are tightly coupled with protein evolutionary rate, depending on whether and how gene duplication occurred. Fluxes in expression patterns among organs are nonrandom, forming modular connections that are reshaped by gene duplication. Thus, if expression shifts, ancestral expression in some organs induces a strong propensity for expression in particular organs in descendants. Regardless of whether the shifts are adaptive or not, this supports a major role for what might be termed preadaptive pathways of gene expression evolution.
Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis
Authors: Bolte Ashley C. , Dutta Arun B. , Hurt Mariah E. , Smirnov Igor , Kovacs Michael A. , McKee Celia A. , Ennerfelt Hannah E. , Shapiro Daniel , Nguyen Bao H. , Frost Elizabeth L. , Lammert Catherine R. , Kipnis Jonathan , Lukens John R.
Published: September 2020

Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model of TBI that mild forms of brain trauma cause severe deficits in meningeal lymphatic drainage that begin within hours and last out to at least one month post-injury. To investigate a mechanism underlying impaired lymphatic function in TBI, we examined how increased intracranial pressure (ICP) influences the meningeal lymphatics. We demonstrate that increased ICP can contribute to meningeal lymphatic dysfunction. Moreover, we show that pre-existing lymphatic dysfunction before TBI leads to increased neuroinflammation and negative cognitive outcomes. Finally, we report that rejuvenation of meningeal lymphatic drainage function in aged mice can ameliorate TBI-induced gliosis. These findings provide insights into both the causes and consequences of meningeal lymphatic dysfunction in TBI and suggest that therapeutics targeting the meningeal lymphatic system may offer strategies to treat TBI.
Single-cell transcriptome maps of myeloid blood cell lineages in Drosophila
Authors: Cho Bumsik , Yoon Sang-Ho , Lee Daewon , Koranteng Ferdinand , Tattikota Sudhir Gopal , Cha Nuri , Shin Mingyu , Do Hobin , Hu Yanhui , Oh Sue Young , Lee Daehan , Vipin Menon A. , Moon Seok Jun , Perrimon Norbert , Nam Jin-Wu , Shim Jiwon
Published: September 2020

The Drosophila lymph gland, the larval hematopoietic organ comprised of prohemocytes and mature hemocytes, has been a valuable model for understanding mechanisms underlying hematopoiesis and immunity. Three types of mature hemocytes have been characterized in the lymph gland: plasmatocytes, lamellocytes, and crystal cells, which are analogous to vertebrate myeloid cells, yet molecular underpinnings of the lymph gland hemocytes have been less investigated. Here, we use single-cell RNA sequencing to comprehensively analyze heterogeneity of developing hemocytes in the lymph gland, and discover previously undescribed hemocyte types including adipohemocytes, stem-like prohemocytes, and intermediate prohemocytes. Additionally, we identify the developmental trajectory of hemocytes during normal development as well as the emergence of the lamellocyte lineage following active cellular immunity caused by wasp infestation. Finally, we establish similarities and differences between embryonically derived- and larval lymph gland hemocytes. Altogether, our study provides detailed insights into the hemocyte development and cellular immune responses at single-cell resolution.
Long-term autophagy is sustained by activation of CCTβ3 on lipid droplets
Authors: Ogasawara Yuta , Cheng Jinglei , Tatematsu Tsuyako , Uchida Misaki , Murase Omi , Yoshikawa Shogo , Ohsaki Yuki , Fujimoto Toyoshi
Published: September 2020

Macroautophagy initiates by formation of isolation membranes, but the source of phospholipids for the membrane biogenesis remains elusive. Here, we show that autophagic membranes incorporate newly synthesized phosphatidylcholine, and that CTP:phosphocholine cytidylyltransferase β3 (CCTβ3), an isoform of the rate-limiting enzyme in the Kennedy pathway, plays an essential role. In starved mouse embryo fibroblasts, CCTβ3 is initially recruited to autophagic membranes, but upon prolonged starvation, it concentrates on lipid droplets that are generated from autophagic degradation products. Omegasomes and isolation membranes emanate from around those lipid droplets. Autophagy in prolonged starvation is suppressed by knockdown of CCTβ3 and is enhanced by its overexpression. This CCTβ3-dependent mechanism is also present in U2OS, an osteosarcoma cell line, and autophagy and cell survival in starvation are decreased by CCTβ3 depletion. The results demonstrate that phosphatidylcholine synthesis through CCTβ3 activation on lipid droplets is crucial for sustaining autophagy and long-term cell survival.