bluuebunny/crossref_metadata_2025 huggingface dataset:
PERUBAHAN BENTUK BADAN HUKUM USAHA MILIK DAERAH BERDASARKAN PERATURAN PEMERINTAH NO. 54 TAHUN 2017 DALAM UPAYA PENINGKATAN PENDAPATAN ASLI DAERAH
Authors: Widodo Ibnu Sam
Published: July 2021

ABSTRACTThe business entity regulated in Law No. 23 of 2014 which is then technically regulated in Government Regulation No. 54 of 2017 concerning Regional Owned Enterprises in which requires two forms of BUMD, namely regional companies or in short with Perseroda and the second form is Regional Public Company. In many areas there are many forms of business entities that are still in the form of Regional Companies, as a consequence of the enactment of Law No. 32 of 2004 on Local Government and Government Regulation No. 54 of 2017 on Regional Owned Enterprises, each form of Regional Company must be changed to a Regional Company or Regional Public Company. In this journal, the author will explore the procedures for the change from a Regional Company to a Regional Public Company based on Normative Juridical research methods using a statutory approach and literature studies with various literature books, journals, and articles related to the theme that the author adopted. The purpose of the authors to convey from the results of this study is how the influence of changes in the form of regional-owned enterprises in increasing the original income of the region so that the region.Keywords:  BUMD, regional public companies, regional revenues.  ABSTRAKBadan usaha yang diatur di dalam Undang Undang Nomor 23 Tahun 2014 yang kemudian secara teknis di atur di dalam Peraturan Pemerintah Nomor 54 Tahun 2017 tentang Badan Usaha Milik Daerah yang di dalam nya mesyaratkan dua bentuk BUMD yaitu berbentuk Perseroan Daerah atau yang di singkat dengan Perseroda dan bentuk kedua adalah Perusahaan Umum Daerah. Di banyak daerah bentuk badan usaha yang ada banyak yang masih berupa Perusahaan Daerah, sebagai konsekuensi dari berlaku nya Undang Undang Nomor 32 Tahun 2004 tentang Pemerintahan Daerah dan Peraturan Pemerintah Nomor 54 Tahun 2017 tentang Badan Usaha Milik Daerah maka setiap bentuk Perusahaan Daerah harus berubah menjadi Perseroan Daerah atau Perusahaan Umum Daerah. Dalam jurnal ini penulis akan mengupas tentang tata cara perubahan dari Perusahaan Daerah menjadi Perusahaan Umum Daerah berdasarkan metode penelitian Normatif Yuridis dengan menggunakan pendekatan perundang undangan dan studi kepustakaan dengan berbagai literatur buku, jurnal dan artikel yang terkait dengan tema yang penulis angkat. Tujuan yang ingin penulis sampaikan dari hasil penelitian ini adalah bagaimana pengaruh perubahan bentuk badan usaha milik daerah dalam peningkatan pendapatan asli daerah sehingga daerah. Kata kunci : BUMD, perusahaan umum daerah, pendapatan daerah
UPAYA HUKUM ATAS PENENTUAN NILAI LIMIT LELANG OLEH BANK DI BAWAH HARGA PASAR
Authors: Tektona Rahmadi Indra , Mutiarachmah Ulhfah
Published: July 2021

Nilai Limit merupakan salah satu bagian terpenting dalam pelaksanaan lelang. Bank sebagai penjual menentukan nilai limit lelang berdasarkan penilaian dari penilai dan penaksiran dari penaksir yang diatur dalam Pasal 44 ayat (1) dan (2) dan Pasal 45 Peraturan Menteri Keuangan No.27/PMK.06/2016 tentang Petunjuk Pelaksanaan Lelang. Permasalahannya adalah apakah pembatalan lelang dapat dilakukan dengan dasar penentuan nilai limit di bawah harga pasar? kedua, apa upaya hukum yang dapat dilakukan debitur jika penentuan nilai limit lelang oleh bank di bawah harga pasar? Penelitian ini merupakan penelitian yuridis normatif. Berdasarkan hasil penelitian, peneliti berkesimpulan bahwa penentuan nilai limit lelang di bawah harga pasar tidak dapat menjadi dasar pembatalan lelang pada tahapan pra lelang dan tahapan pelaksanaan lelang karena pembatalan lelang hanya dapat dibatalkan atas permintaan penjual atau berdasarkan penetapan/ putusan pengadilan. Debitur yang merasa dirugikan atas penentuan nilai limit lelang dapat melakukan upaya hukum dengan mengajukan gugatan.Kata kunci : Nilai Limit, Lelang, Bank
A Etnomatemática na formação inicial dos futuros professores de Matemática: revelando olhares e marcas
Authors: Soares Gisele Americo , Fantinato Maria Cecilia
Published: July 2021

Este artigo é baseado em uma pesquisa de doutorado que  teve como objetivo analisar como a disciplina do currículo de formação na Licenciatura em Matemática, que traz no título a palavra Etnomatemática, pode contribuir para a construção dos saberes dos futuros professores de Matemática.  Identificamos por meio de consulta à plataforma e-MEC os cursos que apresentam uma disciplina intitulada de Etnomatemática, elegemos como sujeitos da pesquisa o professor atual da disciplina e alunos que já cursaram essa disciplina. Temos ao todo 37 sujeitos para pesquisa: 5 professores que lecionam a disciplina Etnomatemática e 32 alunos que já cursaram a mesma. A metodologia envolveu uma entrevista com cada um desses professores e um questionário eletrônico com cada um desses alunos. Em seguida buscamos estabelecer articulações, aproximações e distanciamento entre os discursos. Este artigo traz alguns resultados  da pesquisa, e aborda algumas contribuições da Etnomatemática, no que tange a quebrando paradigmas em relação a universalidade da Matemática e as suas implicações na perspectiva de ensino aprendizagem dos futuros professores. Os graduandos que participaram da pesquisa apontaram como marcas: a necessidade da valorização do contexto social, econômico e cultural dos futuros estudantes, o reconhecimento da Matemática como uma construção humana e uma  das etnomatemáticas existentes, a abertura para o diálogo e a humanização do processo de ensino aprendizagem.
Carbon and fossil resource depletion footprints of milk production from Canterbury dairy farms
Authors: Mazzetto Andre , Falconer Shelley , Ledgard Stewart
Published: July 2021

Among the different sustainability metrics, the carbon footprint is the most commonly reported, but the depletion of non-renewable resources such as fossil fuels, is also important. This study aimed to calculate the “cradle to farm-gate” carbon and fossil resource depletion footprint of milk production in Canterbury, New Zealand, comparing two different farm systems: one pasture-based with a relatively small amount of brought-in feed (Lincoln University Dairy Farm, LUDF) and an average Canterbury farm. The estimate of the carbon footprint of milk production was 0.68 and 0.80 kg CO2-eq/kg of fat and protein-corrected milk (FPCM) for the LUDF and Canterbury average, respectively. The main contributor to the carbon footprint for both farms was enteric fermentation, but differences were found mainly in the emissions from the supplementary feed. Conversely, the Canterbury average farm showed lower fossil resource depletion footprint (1.05 MJ/kg FPCM) when compared with the LUDF farm (1.13 MJ/kg FPCM). The differences were mainly related to fertiliser use. However, this difference is small if compared with farms overseas. The study shows that it is important to look at more than one environmental metric when proposing mitigation practices.
LAW REASONING OF CHILD CUSTODIAL RIGHT FOR NON-MUSLIM MOTHER
Authors: Mashudi Ahmad Ali
Published: July 2021

This article is result of library research. This research is included in the category of normative legal research. This research discussion aims to explain the legal status of non-Muslim mothers in the context of post-divorce child care. The findings of this study are that according to the ulama' of the four schools of thought, the haānah rights of an apostate mother should not be granted. The argument that is built is that haānah does not only take care of physically but also includes children's religious education. The non-Muslim mother is feared to have a direct or indirect influence on the child. The legal status of an apostate also affects legal action. The apostasy reduces the ability to raise children, so the majority of scholars' abort the haānah rights for apostate mothers. KHI explains child custody/haānah in general as regulated in article 105. Parenting rights of non-Muslim mothers are not regulated by KHI.

Keywords: Parenting rights, non-Muslim mothers, legal reasoning

 

Abstrak

Artikel ini adalah hasil dari penelitian pustaka (library research). Penelitian ini masuk dalam kategori penelitian hukum normatif. Diskusi penelitian ini bertujuan menjelaskan status hukum ibu nonmuslim dalam konteks pengasuhan anak pascaperceraian. Temuan penelitian ini adalah bahwa menurut ulama’ empat mazhab, hak haḍānah ibu murtad, tidak boleh diberikan. Argumen yang dibangun adalah haḍānah  tidak  hanya merawat secara jasmani saja akan tetapi haḍānah juga meliputi pendidikan agama anak. Ibu nonmuslim itu dikhawatirkan memberi pengaruh baik langsung maupun tidak langsung kepada anak. Status hukum seorang yang murtad juga mempengaruhi tindakan hukum. Kemurtadan itu mengurangi kecakapan dalam mengasuh anak, sehingga mayoritas ulama’ menggugurkan hak haḍānah bagi ibu murtad. KHI menjelaskan hak asuh anak/haḍānah secara umum saja sebagaimana diatur dalam pasal 105. Hak Pengasuhan ibu non muslim tidak diatur oleh KHI.

Kata kunci: Hak pengasuhan, ibu nonomuslim, nalar hukum
MEDIATOR'S PERSUASIVE APPROACH IN MEDIATION PRACTICE: CASE STUDY OF DIVORCE AT GRESIK RELIGIOUS COURT
Authors: Hasanah Faridatul
Published: July 2021

This research was field qualitative. Purpose is (1) To determine the strategy of judges mediators in settling divorce cases through mediation in the religious Gresik (2) To know the views of people about the existence of mediation as a way to prevent divorce (3) To find out how the effectiveness of the mediation process in handling divorce cases in the religious Gresik. The variables of this research is the role of the judge Mediator Mediation Divorce Case. The study population was numbered 7 people, samples of this study is 4 mediators as informants for only two the informant can be reached. For people who are litigants, 4 as the samples which are in neighborhood religious Courts Gresik. Data collection techniques used were interview and documentation. The results of this study indicate that. (1) strategy judge mediator in case of divorce mediation is to maximize the mediation process by providing advice and consideration if later married couples end up with divorce where previously done caucus or to each party alternately on mediation it self. (2) The view of the public about the existence of the mediation is a good thing because it provides education in the form of advice and teach harmony and the community is also considered that mediation in the religious should stay there. (3) the effectiveness of mediation in the religious Gresik which is not very effective because the number that failed in mediation more than a successful mediation.

Keywords: Role of Judges, Mediation, Divorce

 

Abstrak

Penelitian ini adalah kualitatif lapangan. Arahnya ialah (1) Untuk dapat memahami cara  mediator dalam menangani kasus perceraian melalui proses juru damai (2) Untuk mendapatkan hasil mengenai pandangan masyarakat tentang adanya mediasi yang berperan sebagai juru damai mengenai perceraian (3) Untuk dapat memahami seberapa penting efektifitas proses mediasi dalam menyelesaikan permasalahan yang terjadi. penelitian ini ialah inovasi mediator dalam menentukan keberhasilan mediasi kasus perceraian. Populasi penelitian ini adalah berjumlah 7 orang, yang diteliti ada 4 orang sebagai informan  mediator. Untuk masyarakat yang melakukan mediasi diambil dua pasang. Tehnik yang digunakan yakni tehnik wawancara dan dokumentasi. Hasil penelitian ini menjelaskan bahwa. (1) cara yang dipakai juru damai untuk menangani masalah cerai adalah mempermudah proses mediasi ,mediator berulangkali menyelipkan nasehat -nasehat yang berujung perdamaian, meskipun nantinya tidak dapat rukun kembali, alangkah baiknya berpisah dengan cara baik-baik.(2) Pandangan masyarakat mengenai adanya mediasi ini antusiasnya begitu baik, karena juru damai seperti ini yang dibutuhkan saat ini, lebih bersifat kekeluargaan. (3) efektifitas mediasi belum sempurna disebabkan meningkatnya orang yang ingin cerai dan juru damai yang mempunyai sertifikat sangat kurang.

Kata Kunci: Inovasi Mediator, Mediasi, Perceraian
Solar System Wave Function and its Achievements
Authors: Soltani Abolfazl
Published: July 2021

Pluto, Ceres and all planets of solar system except Neptune, with a high approximation, follow a rule called Titius-Bode rule or Bode rule, which can by no means be considered as a stochastic event. This rule shows that the distance of the planets from the sun in Solar system is regulated. Here, we prove that the existence of a standing and cosine wave packet in solar system, with the wavelength λ = 0.6 AU (AU represents the distance of earth from the sun) and the phase constant ∅_0=π/6, is the reason for Bode rule. Moreover, we prove that this huge wave packet belongs to the sun. In the following of the article, based on the solar system wave function, we will enter into the atomic field and arrive to a new atomic model that helps us to describe many phenomena such as the normal Zeeman effect.
Effect of Estrogen on Heteronemin-Induced Anti-proliferative Effect in Breast Cancer Cells With Different Estrogen Receptor Status
Authors: Yang Yu-Chen S. H. , Li Zi-Lin , Huang Tung-Yung , Su Kuan-Wei , Lin Chi-Yu , Huang Chi-Hung , Chen Han-Yu , Lu Mei-Chin , Huang Haw-Ming , Lee Sheng-Yang , Whang-Peng Jaqueline , Lin Hung-Yun , Davis Paul J. , Wang Kuan
Published: July 2021

Estrogen (E2) has multiple functions in breast cancers including stimulating cancer growth and interfering with chemotherapeutic efficacy. Heteronemin, a marine sesterterpenoid-type natural product, has cytotoxicity on cancer cells. Breast cancer cell lines, MCF-7 and MDA-MB-231, were used for investigating mechanisms involved in inhibitory effect of E2 on heteronemin-induced anti-proliferation in breast cancer cells with different estrogen receptor (ER) status. Cytotoxicity was detected by cell proliferation assay and flow cytometry, gene expressions were determined by qPCR, mechanisms were investigated by Western blot and Mitochondrial ROS assay. Heteronemin exhibited potent cytotoxic effects against both ER-positive and ER-negative breast cancer cells. E2 stimulated cell growth in ER-positive breast cancer cells. Heteronemin induced anti-proliferation via suppressing activation of ERK1/2 and STAT3. Heteronemin suppressed E2-induced proliferation in both breast cancer cells although some gene expressions and anti-proliferative effects were inhibited in the presence of E2 in MCF-7 and MDA-MB-231 cells with a higher concentration of heteronemin. Heteromenin decreased the Bcl-2/Bax ratio to inhibit proliferation in MDA-MB-231 but not in MCF-7 cells. Both heteronemin and E2 increased mitochondrial reactive oxygen species but combined treatment reversed superoxide dismutase (SOD)s accumulation in MCF-7 cells. Heteronemin caused G0/G1 phase arrest and reduced the percentage of cells in the S phase to suppress cancer cell growth. In conclusion, Heteronemin suppressed both ER-positive and ER-negative breast cancer cell proliferation. Interactions between E2 and heteronemin in signal transduction, gene expressions, and biological activities provide insights into the complex pathways by which anti-proliferation is induced by heteronemin in E2-replete environments.
RECQ1 Promotes Stress Resistance and DNA Replication Progression Through PARP1 Signaling Pathway in Glioblastoma
Authors: Zhang Jing , Lian Hao , Chen Kui , Pang Ying , Chen Mu , Huang Bingsong , Zhu Lei , Xu Siyi , Liu Min , Zhong Chunlong
Published: July 2021

Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor, and patients with GBM have a median survival of 20 months. Clinical therapy resistance is a challenging barrier to overcome. Tumor genome stability maintenance during DNA replication, especially the ability to respond to replication stress, is highly correlated with drug resistance. Recently, we identified a protective role for RECQ1 under replication stress conditions. RECQ1 acts at replication forks, binds PCNA, inhibits single-strand DNA formation and nascent strand degradation in GBM cells. It is associated with the function of the PARP1 protein, promoting PARP1 recruitment to replication sites. RECQ1 is essential for DNA replication fork protection and tumor cell proliferation under replication stress conditions, and as a target of RECQ1, PARP1 effectively protects and restarts stalled replication forks, providing new insights into genomic stability maintenance and replication stress resistance. These findings indicate that tumor genome stability targeting RECQ1-PARP1 signaling may be a promising therapeutic intervention to overcome therapy resistance in GBM.
Markup: A Web-Based Annotation Tool Powered by Active Learning
Authors: Dobbie Samuel , Strafford Huw , Pickrell W. Owen , Fonferko-Shadrach Beata , Jones Carys , Akbari Ashley , Thompson Simon , Lacey Arron
Published: July 2021

Across various domains, such as health and social care, law, news, and social media, there are increasing quantities of unstructured texts being produced. These potential data sources often contain rich information that could be used for domain-specific and research purposes. However, the unstructured nature of free-text data poses a significant challenge for its utilisation due to the necessity of substantial manual intervention from domain-experts to label embedded information. Annotation tools can assist with this process by providing functionality that enables the accurate capture and transformation of unstructured texts into structured annotations, which can be used individually, or as part of larger Natural Language Processing (NLP) pipelines. We present Markup (https://www.getmarkup.com/) an open-source, web-based annotation tool that is undergoing continued development for use across all domains. Markup incorporates NLP and Active Learning (AL) technologies to enable rapid and accurate annotation using custom user configurations, predictive annotation suggestions, and automated mapping suggestions to both domain-specific ontologies, such as the Unified Medical Language System (UMLS), and custom, user-defined ontologies. We demonstrate a real-world use case of how Markup has been used in a healthcare setting to annotate structured information from unstructured clinic letters, where captured annotations were used to build and test NLP applications.
Evaluation of Automated Hypnogram Analysis on Multi-Scored Polysomnographies
Authors: Van der Plas Dries , Verbraecken Johan , Willemen Marc , Meert Wannes , Davis Jesse
Published: July 2021

A new method for automated sleep stage scoring of polysomnographies is proposed that uses a random forest approach to model feature interactions and temporal effects. The model mostly relies on features based on the rules from the American Academy of Sleep Medicine, which allows medical experts to gain insights into the model. A common way to evaluate automated approaches to constructing hypnograms is to compare the one produced by the algorithm to an expert's hypnogram. However, given the same data, two expert annotators will construct (slightly) different hypnograms due to differing interpretations of the data or individual mistakes. A thorough evaluation of our method is performed on a multi-labeled dataset in which both the inter-rater variability as well as the prediction uncertainties are taken into account, leading to a new standard for the evaluation of automated sleep stage scoring algorithms. On all epochs, our model achieves an accuracy of 82.7%, which is only slightly lower than the inter-rater disagreement. When only considering the 63.3% of the epochs where both the experts and algorithm are certain, the model achieves an accuracy of 97.8%. Transition periods between sleep stages are identified and studied for the first time. Scoring guidelines for medical experts are provided to complement the certain predictions by scoring only a few epochs manually. This makes the proposed method highly time-efficient while guaranteeing a highly accurate final hypnogram.
Intensified Moisture Sources of Heavy Precipitation Events Contributed to Interannual Trend in Precipitation Over the Three-Rivers-Headwater Region in China
Authors: Zhao Ruiyu , Chen Bin , Xu Xiangde
Published: July 2021

Evidence has indicated an overall wetting trend over the Three-Rivers Headwater Region (TRHR) in the recent decades, whereas the possible mechanisms for this change remain unclear. Detecting the main moisture source regions of the water vapor and its increasing trend over this region could help understand the long-term precipitation change. Based on the gauge-based precipitation observation analysis, we find that the heavy precipitation events act as the main contributor to the interannual increasing trend of summer precipitation over the TRHR. A Lagrangian moisture tracking methodology is then utilized to identify the main moisture source of water vapor over the target region for the boreal summer period of 1980–2017, with focus particularly on exploring its change associated with the interannual trend of precipitation. On an average, the moisture sources for the target regions cover vast regions, including the west and northwest of the Tibetan Plateau by the westerlies, the southwest by the Indian summer monsoon, and the adjacent regions associated with the local recycling. However, the increased interannual precipitation trend over the TRHR could be largely attributed to the enhanced moisture sources from the neighboring northeastern areas of the targeted region, particularly associated with the heavy precipitation events. The increased water vapor transport from the neighboring areas of the TRHR potentially related to the enhanced local hydrological recycling over these regions plays a first leading role in the recent precipitation increase over the TRHR.
Are Students of Secondary Schools of Seven Districts Different on Their Self-Estimates of Multiple Intelligences? A Case Study of Southern Districts of Khyber Pakhtunkhwa
Authors: Shahzada Gulap , Khan Habib Nawaz , Muhammad Khan Ayaz , Ullah Hakim
Published: July 2021

Self-assessment of intelligence is a personal belief of ability, which is counted for an important portion of success in life. With 905 students of secondary schools of seven districts of Khyber Pakhtunkhwa, a survey study was conducted in order to find out students’ self-estimates and the differences of self-estimates on multiple intelligences. Data were collected from the subjects through a valid and reliable inventory. For a selection of the sample, a stratified, random, and proportion allocation technique was used; tests of between-subject effects, analysis of variance, and post hoc were applied as an inferential statistical test. The result of the study revealed that students of Lakki Marwat estimated their logical/mathematical, intrapersonal, verbal/linguistic, and visual/spatial intelligence to be higher than those of the students in the other districts. Students of Bannu rated their musical intelligences higher than that of the students of other districts. Students of Hango estimated their bodily/kinesthetic intelligence higher than that of the students of other districts. Students of Kohat estimated their existential intelligence higher than that of the students of other districts. Researchers suggested that schools should give such an environment of learning to the students where all the intelligences can be focused and promoted.
Nonalcoholic Fatty Liver Disease, Liver Fibrosis and Cardiovascular Disease in the Adult US Population
Authors: Ciardullo Stefano , Cannistraci Rosa , Mazzetti Simone , Mortara Andrea , Perseghin Gianluca
Published: July 2021

Background

Cardiovascular disease (CVD) risk is higher in patients with nonalcoholic fatty liver disease (NAFLD).

Aim

To evaluate whether this can be attributed to the link between NAFLD and known CVD risk factors or to an independent contribution of liver steatosis and fibrosis.

Methods

This is an analysis of data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey. We included participants older than 40 years with available data on vibration-controlled transient elastography (VCTE) and without viral hepatitis and significant alcohol consumption. Steatosis and fibrosis were diagnosed by the median value of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. History of CVD was self-reported and defined as a composite of coronary artery disease and stroke/transient ischemic attacks.

Results

Among the 2734 included participants, prevalence of NAFLD was 48.6% (95% CI 45.1-51.4), 316 participants (9.7%, 95% CI 8.1-11.6) had evidence of significant liver fibrosis and 371 (11.5%, 95% CI 9.5-13.9) had a history of CVD. In univariate analysis, patients with CVD had a higher prevalence of steatosis (59.6% vs 47.1%, p=0.013), but not fibrosis (12.9% vs 9.3%, p=0.123). After adjustment for potential confounders in a multivariable logistic regression model, neither steatosis nor significant fibrosis were independently associated with CVD and heart failure.

Conclusions

In this population-based study, we did not identify an independent association between steatosis and fibrosis and CVD. Large prospective cohort studies are needed to provide a more definitive evidence on this topic.
Mitigating the Impacts of Development Corridors on Biodiversity: A Global Review
Authors: Juffe-Bignoli Diego , Burgess Neil D. , Hobbs Jonathan , Smith Robert J. , Tam Christine , Thorn Jessica P. R. , Bull Joseph W.
Published: July 2021

Development corridors are extensive, often transnational and linear, geographical areas targeted for investment to help achieve sustainable development. They often comprise the creation of hard infrastructure (i.e., physical structures) and soft infrastructure (i.e., policies, plans, and programmes) involving a variety of actors. They are globally widespread, and likely to be a significant driver of habitat loss. Here, we describe the development corridors phenomenon from a biodiversity perspective and identify the elements of best practice in biodiversity impact mitigation. We use these to carry out a review of the peer reviewed literature on corridors to respond to three questions: (i) how impacts on biodiversity and ecosystem services are assessed; (ii) what mitigation measures are discussed to manage these impacts; and (iii) to what extent do these measures approximate to best practice. We found that of 271 publications on development corridors across all continents (except for Antarctica) mentioning biodiversity or ecosystem services, only 100 (37%) assessed impacts on biodiversity and 7 (3%) on ecosystem services. Importantly, only half of these (52, 19% of the total 271 articles) discussed mitigation measures to manage these impacts. These measures focused on avoidance and minimisation and there was scant mention of restoration or ecological compensation illustrating a deficient application of the mitigation hierarchy. We conclude that the academic literature on corridors does not give sufficient consideration to comprehensive mitigation of biodiversity impacts. To change this, impact assessment research needs to acknowledge the complexity of such multi-project and multi-stakeholder initiatives, quantify biodiversity losses due to the full suite of their potential direct, indirect and cumulative impacts, and follow all the steps of the mitigation hierarchy impact framework. We suggest a series of research avenues and policy recommendations to improve impact assessments of corridors towards achieving better biodiversity outcomes.
Comprehensive Analysis of the Expression Characteristics of the Enhancer of the Zeste Homolog 2 Gene in Pan-Cancer
Authors: Kang Yuanyuan , Zhang Ying , Sun Yan
Published: July 2021

Although more and more studies have shown that EZH2 was closely related to human cancer, no pan-cancer analysis is available. Therefore, we summarized and analyzed the potential carcinogenic effect of EZH2 for the first time based on TCGA (cancer genome map) datasets. EZH2 is expressed highly in most tumors and there is a significant correlation between the EZH2 expression and the prognosis of patients. We observed the increased phosphorylation levels of T487 in breast cancer, colon cancer, UCEC, and LUAD. The expression of EZH2 was associated with the CD8+, tregs, macrophage, and cancer-associated fibroblast infiltration in some tumors. In addition, the cell cycle and cellular biology were involved in the functional mechanisms of EZH2. Our study summarized and analyzed the carcinogenic effect of EZH2 in different tumors comprehensively and provided a theoretical basis for targeting EZH2 therapy.
Immune-Intrinsic Myd88 Directs the Production of Antibodies With Specificity for Extracellular Matrix Components in Primary Sjögren’s Syndrome
Authors: Kiripolsky Jeremy , Kasperek Eileen M. , Zhu Chengsong , Li Quan-Zhen , Wang Jia , Yu Guan , Kramer Jill M.
Published: July 2021

Primary Sjögren’s syndrome is an autoimmune disease that is predominantly seen in women. The disease is characterized by exocrine gland dysfunction in combination with serious systemic manifestations. At present, the causes of pSS are poorly understood. Pulmonary and renal inflammation are observed in pSS mice, reminiscent of a subset of pSS patients. A growing body of evidence indicates that inflammation mediated by Damage-Associated Molecular Patterns (DAMPs) contributes to autoimmunity, although this is not well-studied in pSS. Degraded extracellular matrix (ECM) constituents can serve as DAMPs by binding pattern-recognition receptors and activating Myd88-dependent signaling cascades, thereby exacerbating and perpetuating inflammatory cascades. The ECM components biglycan (Bgn) and decorin (Dcn) mediate sterile inflammation and both are implicated in autoimmunity. The objective of this study was to determine whether these ECM components and anti-ECM antibodies are altered in a pSS mouse model, and whether this is dependent on Myd88 activation in immune cells. Circulating levels of Bgn and Dcn were similar among pSS mice and controls and tissue expression studies revealed pSS mice had robust expression of both Bgn and Dcn in the salivary tissue, saliva, lung and kidney. Sera from pSS mice displayed increased levels of autoantibodies directed against ECM components when compared to healthy controls. Further studies using sera derived from conditional knockout pSS mice demonstrated that generation of these autoantibodies relies, at least in part, on Myd88 expression in the hematopoietic compartment. Thus, this study demonstrates that ECM degradation may represent a novel source of chronic B cell activation in the context of pSS.
Long-Term Protection of CHBP Against Combinational Renal Injury Induced by Both Ischemia–Reperfusion and Cyclosporine A in Mice
Authors: Zhang Yufang , Wu Yuanyuan , Wang Wei , Liu Feng , Zhang Yiwen , Yang Cheng , Liu Aifen , Wu Jing , Zhu Tongyu , Nicholson Michael L. , Fan Yaping , Yang Bin
Published: July 2021

Renal ischemia–reperfusion (IR) injury and cyclosporine A (CsA) nephrotoxicity affect allograft function and survival. The prolonged effects and underlying mechanisms of erythropoietin derived cyclic helix B peptide (CHBP) and/or caspase-3 small interfering RNA (CASP-3siRNA) were investigated in mouse kidneys, as well as kidney epithelial cells (TCMK-1), subjected to transplant-related injuries. Bilateral renal pedicles were clamped for 30 min followed by reperfusion for 2 and 8 weeks, with/without 35 mg/kg CsA gavage daily and/or 24 nmol/kg CHBP intraperitoneal injection every 3 days. The ratio of urinary albumin to creatinine was raised by IR injury, further increased by CsA and lowered by CHBP at 2, 4, 6 and 8 weeks, whereas the level of SCr was not significantly affected. Similar change trends were revealed in tubulointerstitial damage and fibrosis, HMGB1 and active CASP-3 protein. Increased apoptotic cells in IR kidneys were decreased by CsA and CHBP at 2 and/or 8 weeks. p70 S6 kinase and mTOR were reduced by CsA with/without CHBP at 2 weeks, so were S6 ribosomal protein and GSK-3β at 8 weeks, with reduced CASP-3 at both time points. CASP-3 was further decreased by CHBP in IR or IR + CsA kidneys at 2 or 8 weeks. Furthermore, in TCMK-1 cells CsA induced apoptosis was decreased by CHBP and/or CASP-3siRNA treatment. Taken together, CHBP predominantly protects kidneys against IR injury at 2 weeks and/or CsA nephrotoxicity at 8 weeks, with different underlying mechanisms. Urinary albumin/creatinine is a good biomarker in monitoring the progression of transplant-related injuries. CsA divergently affects apoptosis in kidneys and cultured kidney epithelial cells, in which CHBP and/or CASP-3siRNA reduces inflammation and apoptosis.
Borrelia Infection in Bank Voles Myodes glareolus Is Associated With Specific DQB Haplotypes Which Affect Allelic Divergence Within Individuals
Authors: Scherman Kristin , Råberg Lars , Westerdahl Helena
Published: July 2021

The high polymorphism of Major Histocompatibility Complex (MHC) genes is generally considered to be a result of pathogen-mediated balancing selection. Such selection may operate in the form of heterozygote advantage, and/or through specific MHC allele–pathogen interactions. Specific MHC allele–pathogen interactions may promote polymorphism via negative frequency-dependent selection (NFDS), or selection that varies in time and/or space because of variability in the composition of the pathogen community (fluctuating selection; FS). In addition, divergent allele advantage (DAA) may act on top of these forms of balancing selection, explaining the high sequence divergence between MHC alleles. DAA has primarily been thought of as an extension of heterozygote advantage. However, DAA could also work in concert with NFDS though this is yet to be tested explicitly. To evaluate the importance of DAA in pathogen-mediated balancing selection, we surveyed allelic polymorphism of MHC class II DQB genes in wild bank voles (Myodes glareolus) and tested for associations between DQB haplotypes and infection by Borrelia afzelii, a tick-transmitted bacterium causing Lyme disease in humans. We found two significant associations between DQB haplotypes and infection status: one haplotype was associated with lower risk of infection (resistance), while another was associated with higher risk of infection (susceptibility). Interestingly, allelic divergence within individuals was higher for voles with the resistance haplotype compared to other voles. In contrast, allelic divergence was lower for voles with the susceptibility haplotype than other voles. The pattern of higher allelic divergence in individuals with the resistance haplotype is consistent with NFDS favouring divergent alleles in a natural population, hence selection where DAA works in concert with NFDS.
Combination Therapy of Mithramycin A and Immune Checkpoint Inhibitor for the Treatment of Colorectal Cancer in an Orthotopic Murine Model
Authors: Dutta Rinku , Khalil Roukiah , Mayilsamy Karthick , Green Ryan , Howell Mark , Bharadwaj Srinivas , Mohapatra Shyam S. , Mohapatra Subhra
Published: July 2021

The axis of Programmed cell death-1 receptor (PD-1) with its ligand (PD-L1) plays a critical role in colorectal cancer (CRC) in escaping immune surveillance, and blocking this axis has been found to be effective in a subset of patients. Although blocking PD-L1 has been shown to be effective in 5–10% of patients, the majority of the cohorts show resistance to this checkpoint blockade (CB) therapy. Multiple factors assist in the growth of resistance to CB, among which T cell exhaustion and immunosuppressive effects of immune cells in the tumor microenvironment (TME) play a critical role along with other tumor intrinsic factors. We have previously shown the polyketide antibiotic, Mithramycin-A (Mit-A), an effective agent in killing cancer stem cells (CSCs) in vitro and in vivo in a subcutaneous murine model. Since TME plays a pivotal role in CB therapy, we tested the immunomodulatory efficacy of Mit-A with anti-PD-L1 mAb (αPD-L1) combination therapy in an immunocompetent MC38 syngeneic orthotopic CRC mouse model. Tumors and spleens were analyzed by flow cytometry for the distinct immune cell populations affected by the treatment, in addition to RT-PCR for tumor samples. We demonstrated the combination treatment decreases tumor growth, thus increasing the effectiveness of the CB. Mit-A in the presence of αPD-L1 significantly increased CD8+ T cell infiltration and decreased immunosuppressive granulocytic myeloid-derived suppressor cells and anti-inflammatory macrophages in the TME. Our results revealed Mit-A in combination with αPD-L1 has the potential for augmented CB therapy by turning an immunologically “cold” into “hot” TME in CRC.
ILC1s and ILC3s Exhibit Inflammatory Phenotype in Periodontal Ligament of Periodontitis Patients
Authors: Li Changyi , Liu Jianyue , Pan Jie , Wang Yuhui , Shen Lei , Xu Yan
Published: July 2021

Innate lymphoid cells (ILCs) are emerging as important players in inflammatory diseases. The oral mucosal barrier harbors all ILC subsets, but how these cells regulate the immune responses in periodontal ligament tissue during periodontitis remains undefined. Here, we show that total ILCs are markedly increased in periodontal ligament of periodontitis patients compared with healthy controls. Among them, ILC1s and ILC3s, particularly NKp44+ILC3 subset, are the predominant subsets accumulated in the periodontal ligament. Remarkably, ILC1s and ILC3s from periodontitis patients produce more IL-17A and IFN-γ than that from healthy controls. Collectively, our results highlight the role of ILCs in regulating oral immunity and periodontal ligament inflammation and provide insights into targeting ILCs for the treatment of periodontitis.
Dichotomic Potency of IFNγ Licensed Allogeneic Mesenchymal Stromal Cells in Animal Models of Acute Radiation Syndrome and Graft Versus Host Disease
Authors: Chinnadurai Raghavan , Bates Paul D. , Kunugi Keith A. , Nickel Kwangok P. , DeWerd Larry A. , Capitini Christian M. , Galipeau Jacques , Kimple Randall J.
Published: July 2021

Mesenchymal stromal cells (MSCs) are being tested as a cell therapy in clinical trials for dozens of inflammatory disorders, with varying levels of efficacy reported. Suitable and robust preclinical animal models for testing the safety and efficacy of different types of MSC products before use in clinical trials are rare. We here introduce two highly robust animal models of immune pathology: 1) acute radiation syndrome (ARS) and 2) graft versus host disease (GvHD), in conjunction with studying the immunomodulatory effect of well-characterized Interferon gamma (IFNγ) primed bone marrow derived MSCs. The animal model of ARS is based on clinical grade dosimetry precision and bioluminescence imaging. We found that allogeneic MSCs exhibit lower persistence in naïve compared to irradiated animals, and that intraperitoneal infusion of IFNγ prelicensed allogeneic MSCs protected animals from radiation induced lethality by day 30. In direct comparison, we also investigated the effect of IFNγ prelicensed allogeneic MSCs in modulating acute GvHD in an animal model of MHC major mismatched bone marrow transplantation. Infusion of IFNγ prelicensed allogeneic MSCs failed to mitigate acute GvHD. Altogether our results demonstrate that infused IFNγ prelicensed allogeneic MSCs protect against lethality from ARS, but not GvHD, thus providing important insights on the dichotomy of IFNγ prelicensed allogenic MSCs in well characterized and robust animal models of acute tissue injury.
Uncovering the Composition and Diversity of Pelagic Copepods in the Oligotrophic Blue Water of the South Pacific Subtropical Gyre
Authors: Medellín-Mora Johanna , Escribano Rubén , Corredor-Acosta Andrea , Hidalgo Pamela , Schneider Wolfgang
Published: July 2021

The subtropical gyres occupy approximately 40% of the surface of the Earth and are widely recognized as oligotrophic zones. Among them, the South Pacific subtropical gyre (SPSG) shows the lowest chlorophyll-a levels (0.02–0.04 μgL–1), the deepest nutricline (>200 m) and euphotic zone (∼160 m), and the lowest rates of nitrogen fixation. The zooplankton community is poorly known in the SPSG. We report a study focused on the composition and distribution of pelagic copepods within the gyre so as to uncover the diversity and habitat conditions of this special community. Therefore, during the austral spring of 2015, an oceanographic cruise was conducted across the eastern side of the SPSG. Physical and chemical variables were measured in the upper 1000 m, while zooplankton samples were collected by means of vertically stratified hauls using a multiple net sampler for five layers (0–800 m). Satellite data were also used to assess near-surface phytoplankton biomass (Chl-a) and physical-dynamics conditions during the cruise, and 121 species of copepods were identified, which belonged to five taxonomic orders, 24 families, and 50 genera. Calanoida and Cyclopoida were the most frequent orders, containing 57% and 38% of species, respectively, whereas Harpacticoida and Mormonilloida contained 2% of species each, and Siphonostomatoida contained 1% of species. The vertical distribution of copepods revealed an ecological zonation linked to a strongly stratified water column, such that three different vertical habitats were defined: shallow (0–200 m), intermediate (200–400 m), and deep (400–800 m). Both the abundance and diversity of copepods were greater in the shallow habitat and were strongly associated with water temperature, whereas copepods in the subsurface layers subsisted with relatively low oxygen waters (2–3 mL O2 L–1) and presumably originated at the Chilean upwelling zone, being transported offshore by mesoscale eddies. Furthermore, the analysis of species composition revealed a marked dominance of small-sized copepods, which may play a key role in nutrient recycling under an oligotrophic condition, as inferred from their mostly omnivorous feeding behavior. Our findings also suggested a potentially high endemism within the gyre, although basin-scale circulation and mesoscale eddies, traveling from the coastal upwelling zone and transporting plankton, can also influence the epipelagic fauna.
Using Automatic Identification System (AIS) Data to Estimate Whale Watching Effort
Authors: Almunia Javier , Delponti Patricia , Rosa Fernando
Published: July 2021

The growing concerns about the negative effects caused by whale watching on wild cetacean populations are evincing the need to measure whale watching effort more precisely. The current alternatives do not provide sufficient information or imply time-consuming and staff-intensive tasks that limit their effectiveness to establish the maximum carrying capacity for this tourist activity. A methodology based on big data analysis, using Automatic Identification System (AIS) messages can provide valuable vessel activity information, which is necessary to estimate whale watching effort in areas with cetacean populations. We used AIS data to automatically detect whale watching operations and quantify whale watching effort with high spatial and temporal resolution in the Canary Islands off the west African coast. The results obtained in this study are very encouraging, proving that the methodology can estimate seasonal and annual trends in the whale watching effort. The methodology has also proved to be effective in providing detailed spatial information about the whale watching effort, which makes an interesting tool to manage spatial regulations and enforce exclusion zones. The widespread use of AIS devices in maritime navigation provides an enormous potential to easily extend this methodology to other regions worldwide. Any public strategy aimed at the sustainable use of marine resources should enhance the use of this kind of information technologies, collecting and archiving detailed information on the activity of all the vessels, especially in marine protected areas.
Spatial and Ontogenetic Patterns in the Trophic Ecology of Juvenile Bull Sharks (Carcharhinus leucas) From the Northwest Gulf of Mexico
Authors: TinHan Thomas C. , Wells R. J. David
Published: July 2021

A combination of stomach content and stable isotope (δ13C, δ15N, and δ34S) analyses were used to characterize and examine spatiotemporal and ontogenetic trends in the feeding ecology of juvenile bull sharks (Carcharhinus leucas) captured in estuaries throughout the northwest Gulf of Mexico (GoM) between 2013 and 2016. Shark diets were dominated by fish prey taxa [>98% index of relative importance (%IRI)], and of those identified to the family level, two families comprised greater than 50% IRI, Mugilidae (mullets: ∼32%) and Sciaenidae (drums and croakers: 27%). Clupeidae (herrings: 14%) and Ariidae (sea catfishes: 15%) also contributed substantially to the diet of juvenile sharks, though consumption of Ariidae increased as consumption of Clupeidae decreased in juvenile sharks larger than 893 mm Fork Length (FL) (∼1 year old). Values of δ15N increased significantly with shark size, indicating a shift toward larger or higher trophic level prey with increasing shark size. Latitudinal and temporal trends in δ13C and δ34S suggest isotopic variation occurred in correspondence with shifts in primary producer assemblages and environmental drivers of sampled estuaries. These results highlight the importance of teleost prey resources along the freshwater-marine continuum in the diet of juvenile bull sharks, as well as the utility of natural tracers in tracking ontogenetic trends in feeding ecology.
The Effects of Storage in vitro on Functions, Transcriptome, Proteome, and Oxidation Resistance of Giant Grouper Sperm
Authors: Yang Yang , Wang Tong , Yang Sen , Wu Xi , Huang Wenhua , Fan Bin , Xia Junhong , Meng Zining , Liu Xiaochun
Published: July 2021

Asynchrony of sexual maturity is a huge limitation in the reproduction of grouper sperm. Cold storage of sperm is an effective method to solve the problem of asynchronization. However, sperms gradually lose their activity with the prolonged storage time in vitro. In order to explore causes, the effects of cold storage on transcriptome, proteome and oxidation resistance of giant grouper sperm were analyzed. Firstly, the absolute RNA quantity and consistent transcripts existed in each spermatozoon were estimated. With the prolonged storage, the RNA quantity gradually decreased both in the cytoplasm and in the mitochondria of the spermatozoon. The decreased transcripts were mainly enriched with energy metabolism and stress response. Similar to RNAs, the absolute protein quantity was also significantly decreased during the storage of sperm. Decreased proteins were mainly enriched with the oxidative phosphorylation pathway. Proteins involved in the oxidative phosphorylation showed a faster degradation rate compared to the average total protein. In addition, the oxidation resistance and adenosine triphosphate (ATP) contents showed a significant decrease in the sperm during storage in vitro. These results implied that damages of transcriptome, proteome, and oxidation resistance have negative effects on the normal functions of sperm, especially their energy metabolism. The present study provides essential foundation for improving the storage of sperm in vitro.