bluuebunny/crossref_metadata_2025 huggingface dataset:
HİCRÎ II. VE III. ASIRLARDA YAŞAYAN HANEFÎ FAKİHLERİN RESMÎ GÖREV ALMA TUTUMLARI AÇISINDAN SİYASÎ OTORİTE İLE İLİŞKİLERİ
Authors: DUMAN Soner , HOYLADI Adnan
Published: March 2021

Hanefîler, teşekkül döneminde siyasî otoriteyle çeşitli sebeplerle ilişki kurmuşlardır. Mezhebin kendisine izafe edildiği Ebû Hanîfe, Emevîler ve Abbâsîler döneminde siyasî otoriteye mesafeli durmuş onların resmî görev tekliflerini geri çevirmiştir. Ebû Hanîfe’nin kendisine yapılan görev tekliflerini kabul etmemesinin nedenleri olarak Emevî ve Abbâsî idarelerinin Ehl-i beyte karşı takınmış olduğu katı tutum, Emevî ve Abbâsî iktidarlarının Müslümanların istişaresi ve hür iradeleriyle vermiş oldukları biatle seçilmesi gerektiği ilkesine muhalif olarak istişare olmaksızın ve baskı ile biat almaları, Ebû Hanîfe’nin mevcut şartlarda siyasî otoriteye tabi olarak görev alması dışarıdan meşruiyetinde sıkıntı olan bir iktidara tam meşruiyet verdiği şeklinde okunacağı endişesi gibi ihtimaller sayılabilir. Ebû Hanîfe’nin öğrencileri arasında ve sonraki nesillerde onun bu tutumunu benimseyenler olmasına karşın Züfer, Ebû Yûsuf, Muhammed b. Hasan gibi önde gelen öğrencileri yanında sonraki nesil Hanefîlerden de siyasî idarenin resmî görev tekliflerini kabul edenler olmuştur. Resmî görev alan Hanefî fakihlerin bu kararlarında mezhebin yayılmasına katkıda bulunma, şeriatın gerekleri doğrultusunda kadılık görevinin yerine getirilmesi, halifenin talebi gibi sebepler etkili olmuştur. Resmî görev almayanların kararlarında ise Ebû Hanîfe’den farklı olarak, ilimle meşgul olma istekleri, sağlık durumlarının el vermemesi gibi kişisel nedenler etkili olmuştur. Bunun yanında bazı dönemlerde, devletin siyasal politikaları çerçevesinde Hanefî fakihlerin kadı atamalarında öncelikli tercih edildikleri bazı dönemlerde de arka planda kaldıkları görülmektedir.
Tingkat Kepuasan Mahasiswa IAIN Langsa terhadap pembelajaran Daring dengan End User Computing Satisfaction (EUCS)
Authors: Pratiwi Siti Habsari , Wahyuni Wahyuni
Published: March 2021

Penelitian bertujuan untuk menilai kepuasan mahasiswa terhadap pembelajaran daring dengan menggunakan End User Computing Satisfaction (EUCS) yang dikembangkan oleh Doll. Ada lima indikator EUCS yang akan menentukan tingkat kepuasan yaitu isi, akurasi, bentuk, kemudahan penggunaan, dan ketepatan waktu. . Instrument EUCS yang dimodifikasi dengan sebelumnya telah melalui tahapan validitas dan uji coba, ada 12 item pertanyaan. Sampel dalam penelitian ini berjumlah 108 responden. Pengambilan data dilakukan dengan menggunakan kuisioner google form. Hasil penelitian menunjukkan bahwa mahasiswa IAIN Langsa memiliki tingkat kepuasan cukup untuk isi, akurasi, dan bentuk pembelajaran daring. Sedangkan pada item kemudahan penggunaan dan ketepatan waktu pembelajaran daring kepuasan mahasiswa bernilai baik.
EFFECTIVENESS OF TEACHING MATERIALS BASED MULTICULTURAL INDONESIAN TO IMPROVE CRITICAL THINKING SKILLS
Authors: Wibowo Sony Ari , Murtono Murtono , Utaminingsih Sri
Published: March 2021

This study aimed to describe the effectiveness of teaching materials based multicultural Indonesian to improve critical thinking skills of the fourth grade students from elementary schools in the district of Jepara. This type of research used in this research is the Research and Development (R & D). The research was conducted in the fourth grade 1 Tritis and fourth grade 1 Karangnongko as an experimental group and fourth grade 1 Daren and fourth grade 3 Nalumsari as the control group in the district of Jepara regency Nalumsari. Data collection techniques in this research was conducted through observation, interviews, and documentation. Indonesian teaching materials are developed based on the material-based multicultural Indonesian on the theme of 4 different jobs in the fourth grade of elementary school. Results showed that the Indonesian teaching materials based multicultural effectively used to enhance the critical thinking skills of the fourth grade students from elementary schools in the district of Jepara. The results of the t-test on the experimental and control groups, namely 8.994. The t-test results showed that t> t table is 8.994> 1.699, then as the basis for decision making can be concluded that Ho is rejected and Ha accepted. Thus, it can be concluded that the application of teaching materials based multicultural Indonesian effective and fit for use in improving critical thinking skills of the fourth grade students from elementary schools in the district of Jepara.
ARAH POLITIK PENDIDIKAN ISLAM INDONESIA ABAD KE 21
Authors: Rahmatullah M. Asep , Munawati Siti , Suryagalih Sugih
Published: March 2021

Abstarct The Political Direction of Islamic Education In the 21st century, history has noted that Islamic education in Indonesia has taken root since the entry of Islam into the archipelago, that Islamic education is perfectly upright and perfect is inseparable from the role of the sultans, scholars, and Muslims continues to try to carry out the study of science majors , discussion, writing in the context of jihad fi sabillilah tafaqohu fiddien for the glory of Islam. It is also supported by Islamic political policies that are very beneficial for the interests of the world of Islamic education. Since the destruction of the Caliphate of the Ottoman Turkish Islamic government and the destruction of the Islamic kingdoms in Indonesia and the world. Then the condition of Islamic education experienced ups and downs and the lack of support from the Indonesian government. Therefore, after Indonesia's independence and the increasingly open world of globalization and modernization, it is necessary to look for ideas and ideal forms that are integrally holistic for the world of Islamic education. As well as being able to influence the policies of the Indonesian government and master the political policies of 21st century Islamic education for the future of Indonesian Muslims.Abstark Arah Politik Pendidikan Islam Abad ke 21, sejarah telah mencatat bahwa pendidikan Islam di Indonesia telah mengakar dari sejak masuknya Islam ke nusantara, pendidikan Islam tegak secara sempurna dan paripurna tidak lepas dari peranan para sultan, ulama, dan kaum muslimin yang terus berupaya melakukan kajian majlis ilmu, diskusi, menulis serta aktif dalam gerakan dakwah dan jihad fi sabillilah untuk kejayaan islam. Setelah menancapkan kekuasaan Islam, maka sistem pendidikan islam di topang oleh kebijakan politik Islam yang sangat menguntungkan bagi kepentingan dunia pendidikan Islam. Sejak kehancuran kekhalifahan pemerintahan Islam turki utsmani dan kehancuran kerajan-kerajaan Islam di Indonesia dan dunia. Maka kondisi pendidikan Islam mengalami pasang surut kemunduran dan kurangnya dukungan pemerintah Indonesia. Oleh karena itu, setelah Indonesia merdeka dan semakin terbukanya dunia globalisasi dan modernisasi, maka perlu mencari ide, dan format yang ideal secara integralistik holistik untuk dunia pendidikan Islam. Serta dapat mempengaruhi kebijakan pemerintah Indonesia dan menguasai kebijakan politik pendidikan Islam abad ke 21 untuk masa depan umat Islam bangsa Indonesia.
POLIGAMI/POLIGINI PERSPEKTIF HUKUM ISLAM
Authors: Mas'ud Muhamad , Abdurrahman Asep , Al-Fahmi Faiz Fikri
Published: March 2021

AbstractMarriage is formed to create a harmonious, happy, and prosperous family (sakinah, mawaddah, and rahmah). Polygyny or better known as polygamy has always been a subject of fiqh which has always been excellent among fiqh experts and researchers of Islamic law. This form of polygamy is well known among medes, babylonia, abyssinia, and Persians. The Prophet Muhammad allowed polygamy among his people because it was also practiced by the Greeks, among whom even a wife could not only be exchanged but could also be traded commonly among them. Australia and Mormons in America. Even Hinduism in India does not prohibit polygamy. The jahiliyyah Arabs married a number of women and regarded them as possessions, even in large part, especially as they were not part of a marriage because the women could be brought, owned and sold as they pleased. Polygamy becomes an emergency exit for a husband who has been established in household mahligai as a protection against adultery.  AbstrakPerkawinan dibentuk untuk menciptakan keluarga yang bernuansa harmonis, bahagia, dan sejahtera, (sakinah, mawaddah, dan rahmah). Poligini atau lebih dikenal dengan istilah poligami senantiasa menjadi bahasan fiqih yang selalu menjadi primadona dikalangan para ahli fiqih dan para peneliti hukum Islam. Bentuk poligami telah dikenal diantara orang-orang medes, babilonia, abesinia, dan Persia. Nabi Muhammad SAW membolehkan poligami diantara masyarakatnya karena telah dipraktekkan juga oleh orang-orang yunani yang diantaranya bahkan seorang istri bukan hanya dapat dipertukarkan tetapi juga dapat diperjual belikan secara lazim diantara mereka. Australia serta mormon di Amerika. Bahkan ajaran hindu di India tidak melarang poligami. Orang-orang arab jahiliyyah menikahi sejumlah wanita dan menganggap mereka sebagai barang kepunyaan bahkan dalam sebagian besar khususnya ia bukanlah bagian perkawinan karena para wanita itu dapat dibawa, dimiliki, dan dijual sekehendaknya. Poligami menjadi sebuah emergency exit bagi seorang suami yang telah mapan dalam mahligai rumah tangga sebagai proteksi terhadap perbuatan perzinaan.
KAIDAH PENAFSIRAN MENURUT MUHAMMAD JAMAL AL-DIN AL-QASIMI
Authors: Haromaini Ahmad
Published: March 2021

Tafsir merupakan produk teks dari sumber teks al-Qur’an. Kehadiran tafsir sangat dibutuhkan dalam menjelaskan petunjuk-petunjuk al-Qur’an. Namun apakah penafsiran yang dilakukan sudah sesuai dengan ketentuan kaidah penafsiran? Lalu apakah setiap ulama tafsir menuliskan kaidah penafsiran sebelum menafsirkan al-Qur’an di kitab tafsirnya? Ulama kontemporer seperti Muhammad Jamal al-Din al-Qasimi sebelum memulai penafsiran al-Qur’an, terlebih dulu menjelaskan beberapa kaidah penafsiran  yang harus dipenuhi bagi mereka yang ingin menafsirkan al-Qur’an. Penelitian ini menggunakan metode penelitian kualitatif dengan mengolah data dari kitab Tafsir Mahasin al-Ta’wil karya Muhammad Jamal al-Din al-Qasimi sebagai data primer dan kitab-kitab tafsir lain sebagai data sekunder. Dari hasil penelitian ditemukan bahwa kaidah penafsiran oleh Muhammad Jamal al-Din al-Qasimi dibagi menjadi qawa’id fi makhaidz tafsir dan kaidah memilih tafsir yang shahih dan yang paling shahih. Kaidah yang pertama Al-Qasimi didasari dari kaidah-kaidah penafsiran yang ditulis Jalal al-Din al-Suyuti dalam kitab al-Itqan fi ‘Ulum al-Qur’an
EVALUASI PENERAPAN E-SPT TAHUNAN TERHADAP TINGKAT KEPATUHAN WAJIB PAJAK ORANG PRIBADI (Studi Kasus Pada KPP Pratama Tangerang Barat)
Authors: Nurhasanah Nissa , Kurniawan Irvan Arif
Published: March 2021

Tujuan dari penelitian ini adalah untuk mengetahui evaluasi penerapan e-SPT terhadap kepatuhan wajib pajak orang pribadi studi kasus pada Kantor Pelayanan Pajak (KPP) Pratama Tangerang Barat. Metode penelitian yang digunakan adalah metode deskripsi kuantitatif. Adapun data yang digunakan dalam penelitian ini menggunakan jumlah Wajib Pajak Terdaftar, Wajib Pajak Orang Pribadi yang wajib menyampaikan, OP Non karyawan dan OP karyawan, Wajib Pajak yang menyampaikan SPT manual, Wajib Pajak yang wajib menyampaikan SPT elektronik dan presentase yang diharapkan tentang kepatuhan wajib pajak. Hasil penelitian ini menunjukkan bahwa kepatuhan Wajib Pajak untuk Orang Pribadi dari tahun ke tahun mengalami peningkatan dari jumlah Wajib Pajak dalam penerapan e-SPT. Pada tahun 2017 terlihat persentase kepatuhan sebesar 46,47%, tahun 2018 sebesar 48,46 %, dan tahun 2019 persentase kepatuhan sebesar 49,28%. Sedangkan penerapan e-SPT untuk Wajib Pajak Orang Pribadi yang melaporkan dengan SPT Tahunan kurang efektif karena kurangnya pengetahuan, pemahaman dan sosialisasi tentang penerapan e-SPT.
ANALISIS YURIDIS PEMBERIAN DISPENSASI TERHADAP PERKAWINAN YANG DILAKUKAN ANAK DI BAWAH UMUR MENURUT UNDANG-UNDANG NOMOR 1 TAHUN 1974
Authors: Myranika Annie , Khairunnisa Putri
Published: March 2021

Pembatasan usia nikah dalam Undang-Undang Nomor 1 Tahun 1974 Tentang Perkawinan merupakan suatu kesepakatan nasional, karena dalam hukum Islam tidak diatur masalah batas usia menikah. Permasalahan dalam penelitian ini yaitu bagaimana pertimbangan hakim dalam mengabulkan dispensasi perkawinan di bawah umur menurut Undang-Undang Nomor 1 Tahun 1974 dalam Kasus Putusan Nomor: 0111/Pdt.P/2018/PA.Tng dan apa saja faktor-faktor yang melatarbelakangi diajukannya dispensasi perkawinan yang dilakukan anak di bawah umur. Teorinya mengacu pada UU Nomor 1 Tahun 1974 Tentang Perkawinan Pasal 7. Dari hasil penelitian menunjukkan hakim mempertimbangkan keputusannya dengan melihat kemaslahatan umat atau kepentingan umum dari para pihak dan menghindari kemudaratan. Sedangkan mengenai faktor-faktor yang melatarbelakangi diajukannya dispensasi perkawinan adalah faktor kekhawatiran orang tua, faktor ekonomi, faktor hamil di luar nikah, dan faktor menghindari zina khususnya bagi anak yang belum cukup umur.
Sistem Pendukung Keputusan Kinerja Dosen Menggunakan Metode Weighted Product (Studi Kasus : Fakultas Teknik Univesitas Islam Syekh-Yusuf Tangerang)
Authors: Syam Syahriani
Published: March 2021

Penelitian ini dilatar belakangi oleh beberapa persoalan yang berkaitan dengan belumoptimalnya pelaksanaan penilaian kinerja dosen pada kegiatan belajar mengajar berdasarkanpendekatan logika Metode Weigh Product (WP) di Fakultas Teknik. Hal ini menjadi satu keprihatinanyang perlu disikapi dalam kompetensi pembelajaran, karena dapat berdampak terhadap rendahnyadisiplin dan proses pembelajaran pada mahasiswa serta penilaian kenaikan pangkat dosen. Kegiatanpenilaian kinerja dilakukan setiap tahun sebagai bagian dari proses pengembangan karir danpromosi dosen untuk kenaikan pangkat dan jabatan fungsionalnya. Proses penilaian yang dilakukanmeliputi penilaian dosen oleh mahasiswa, kedisiplinan dosen terhadap memberi kuliah, alokasi waktudalam mengajar, pendidikan terakhir, jabatan akademik serta karya ilmiah yang dihasilkan perpriode oleh setiap dosen. Menggunakan Metode Weighted Product (WP) dapat membantu dalampengambilan keputusan untuk menentukan penilaian kinerja dosen pada perguruan tinggi, sertaproses penilaian kinerja dosen lebih efisien sehinga ketua jurusan lebih cepat mendapatkan informasitentang kinerja dosen. Sistem pendukung keputusan yang memiliki database, dan penilaian kinerjadosenKata kunci: sistem pendukung keputusan, weight product, kinerja dosen, UNIS
Sistem Pendukung Keputusan Potensi Siswa Dengan Metode Fuzzy Multiple-Attribute Decision Making (FMADM) (Studi Kasus : Pada SDN Maccini 1 Makassar)
Authors: Syam Syahriani
Published: March 2021

Setiap siswa SDN Maccini 1 Makassar memiliki watak, pola pikir, emosi, kepribadian yangberbeda-beda, sangat sulit untuk mencari solusi pembelajaran yang baik untuk setiap siswa, dan caraberfikir siswa sekolah dasar yang masih belum fokus dalam suatu hal dapat mempersulit guru dalammemberikan keputusan solusi yang baik untuk setiap siswa. Dampaknya setiap siswa dalampengembangan potensinya kurang efektif, karena metode pembelajaran yang tidak sesuai untuk siswasatu dengan siswa yang lain, perlunya peningkatan potensi setiap siswa untuk memaksimalkan potensisetiap siswa yang ada. Aplikasi Sistem Pendukung Keputusan sangat membantu dalam meningkatkanpotensi setiap siswa, mempermudah guru dalam mengoptimalkan potensi siswa. Guru dapat lebihefisiensi waktu dalam menentukan potensi siswa di masa depan, Karena setiap siswa perlu meningkatkankualitas diri, maka aplikasi ini sangat berguna untuk guru dalam meningkatkan potensi siswanyaKata kunci: potensi, siswa, fuzzy
Rancang Bangun Sistem Informasi Administrasi Pembayaran Spp dan Administrasi Sekolah Pada Smk Pgri 11 Ciledug menggunakan Metodologi Berorientasi Obyek
Authors: Maryam Siti
Published: March 2021

Sistem pembinaan terpadu yang didukung oleh guru dan staff berpendidikan pada Sekolah Menengah Kejuruan (SMK) PGRI 11 CILEDUG, berupaya agar peserta didik yang diamanahkan dapat berkembang secara maksimal sehingga mereka akan menjadi insan-insan sukses yang dapat membangun peradaban bangsa dan masyarakat yang bertujuan menjadi sekolah yang dapat melahirkan generasi cerdas, kreatif, dan memiliki budi pekerti yang baik. Penyampaian laporan pembayaran yang tidak tepat waktu yang saat ini menjadi permasalahan yang dihadapi pada SMK PGRI 11 CILEDUG, disebabkan prosedur yang belum jelas, sehingga siswa dapat mengabaikan prosedur yang ada. Penulis mengambil judul “Rancangan Bangun Sistem Informasi Administrasi Pembayaran Spp Dan Administrasi Sekolah Dengan Metodologi Berorientasi Obyek”. Harapan dengan adanya rancangan bangun sistem informasi, dapat membantu staff administrasi SPP dapat menangani proses pembayaran dan dapat memperkecil kesalahan pencatatan data
ANALISIS BEBAN KERJA FISIOLOGIS MAHASISWA SAAT PRAKTIKUM ANALISA PERANCANGAN KERJA DENGAN MENGGUNAKAN METODE 10 DENYUT
Authors: Rahayu Monita
Published: March 2021

Penelitian ini bertujuan untuk mengetahui beban kerja fisiologis pada mahasiswa saat melakukan praktikum  Analisa Perancangan Kerja Program Studi Teknik Industri Fakultas Teknik Universitas Islam Syekh-Yusuf. Pengukuran denyut nadi merupakan salah satu cara untuk mengetahui beban kerja seseorang. Metode yang digunakan adalah metode 10 denyut. Dalam penelitian ini terdapat sampel sebanyak 6 orang mahasiswa yang akan diukur denyut nadi saat beraktivitas dan saat istirahat saat melakukan praktikum. Selain itu juga dihitung HR reverse, %CVL, konsumsi energi serta waktu istirahat. Dari hasil penelitian berdasarkan %CVL berada pada kategori tidak terjadi kelelahan sedangkan dari jumlah konsumsi energi rata-rata mahasiswa berada pada kategori ringan.Kata Kunci : beban kerja, denyut nadi, %CVL
Evaluasi Kinerja Kualitas Pemasok Bahan Baku di PT. X Menggunakan Peta Kendali dan Analisis Kemampuan Proses
Authors: Khamaludin Khamaludin
Published: March 2021

Kualitas suatu produk dapat dipengaruhi oleh kualitas bahan baku dari pemasok. Untuk menjaga agar apa yang diinginkan oleh sebuah perusahan terhadap pemasok dengan kinerja kualitas bahan baku yang baik, maka perusahan harus menetapkan standar dari kinerja kualitas pemasok dan mengevaluasinya. Penelitian ini dilakukan di PT. X dengan menggunakan data sekunder hasil pengukuran diameter, panjang, dan berat dari sampel insert weight roller selama periode Januari-Maret 2020. Dengan menggunakan peta kendali Individual Moving Range (I-MR) untuk data panjang dan berat insert weight roller dan peta kendali Xbar-R untuk data diameter insert weight roller diharapkan mampu mengetahui seberapa banyak data dalam batas kendali atau tidak. Analisis kemampuan proses dilakukan apakah proses mampu memenuhi spesifikasi desain atau tidak. Hasil analisis kemampuan proses yang perlu diperbaiki adalah proses panjang insert weight roller karena indeks kapabilitas prosesnya kurang dari 1, sedangkan kemampuan proses untuk diameter dan berat insert weight roller bisa dipertahankan dengan tetap memperkecil variasi produknya.
Analisis Beton Ringan Dengan Penambahan Batu Apung Dan Zat Additive Untuk Pengujian Kuat Tekan Beton
Authors: Basid Abdul
Published: March 2021

Beton ringan merupakan material penting dan diminati sehingga saat ini telah diaplikasikan pada struktur bangunan dan jembatan.  Beton ringan mempunyai keuntungan ekonomi jika dibandingkan beton agregat normal, meskipun biaya per volume beton lebih tinggi tetapi karena beratnya yang lebih ringan menyebabkan pengurangan dimensi struktur sehingga secara keseluruhan akan memberikan biaya yang rendah.  Penambahan batu apung yang dijadikan agregat ringan dalam pembuatan beton ringan dengan penambahan zat additive penta 003 dan juga agent foam dapat mempengaruhi terhadap berat jenis beton tersebut sesuai SNI 03-2847-2002 (Beton ringan adalah beton yang mempunyai berat satuan tidak lebih dari 1900 kg/m3). Didapati berat jenis 1m3 sebesar 1772,6 kg/m3 . Dari hasil penelitan beton normal yang dibandingkan dengan beton ringan memiliki perbandingan berat jenis 1m3 sebesar 458,4 kg/m3 , hal ini menjelaskan bahwa batu apung yang dijadikan agregat halus dapat dijadikan bahan dasar untuk pembuatan beton ringan. Pada pengujian kuat tekan beton ringan didapati peningkatan dalam kuat tekan beton pada umur 7 hari ke 14 hari sebesar 26,77% , lalu umur 14 ke 28 hari sebesar 20,21% dan yang terakhir perbandingan pada umur 7 hari ke 28 hari memiliki kuat tekan 41,72%.Kata kunci: Beton ringan, breksi batu apung, kuat tekan, zat additive
Origins of the African Offshore Oil and Gas Cooperation Milestone: The Nigeria – São Tomé & Principe Regime
Authors: Ferrara Pablo
Published: March 2021

This paper aims at identifying and explaining the design principles of the joint development regime between Nigeria and São Tomé & Principe, analysing the subsequent dynamics – the nature of cooperation – generated by the regime's design.

In order to fulfil its objectives, it shall start by explaining the applicable socio-legal research methodology, then continue with the analysis of the case study, finishing with the relevant conclusions. Characterized by large oil reserves, low development capacity, international oil companies appetite, and corrupt governments, this work depicts Nigeria and São Tomé e Príncipe as large oil reservists with potential but low development capacity, resulting in a dyad of international oil companies keen on offshore development and corrupt governments looking to exploit it. On the other hand, recognition of the offshore development potential in their overlapping claim zone and international oil companies’ pressured the States to improve their political governance, developing on both countries the decision to achieve an international development regime (JDZ) proven profitable for both countries in many ways – not only economic.
Call for paper
Authors: Cuadra Carin , Hansson Kristofer , Michailakis Dimitris , Neergaard Anders
Published: March 2021

Välkomna att skicka in bidrag till nästa specialnummer I PANDEMINS SPÅR – Socialvetenskapliga perspektiv på Covid-19
Recent Advances in Producing Sugar Alcohols and Functional Sugars by Engineering Yarrowia lipolytica
Authors: Abbasi Abdul Rahman , Liu Jinle , Wang Zhi , Zhao Anqi , Ying Hanjie , Qu Lingbo , Alam Md. Asraful , Xiong Wenlong , Xu Jingliang , Lv Yongkun
Published: March 2021

The sugar alcohols and functional sugars have wide applications in food, pharmaceutical, and chemical industries. However, the smaller quantities of natural occurring sugar alcohols and functional sugars restricted their applications. The enzymatic and whole-cell catalyst production is emerging as the predominant alternatives. The properties of Yarrowia lipolytica make it a promising sugar alcohol and functional sugar producer. However, there are still some issues to be resolved. As there exist reviews about the chemical structures, physicochemical properties, biological functions, applications, and biosynthesis of sugar alcohols and/or functional sugars in Y. lipolytica, this mini review will not only update the recent advances in enzymatic and microbial production of sugar alcohols (erythritol, D-threitol, and xylitol) and functional sugars (isomaltulose, trehalose, fructo-oligosaccharides, and galacto-oligosaccharides) by using recombinant Y. lipolytica but also focus on the studies of gene discovery, pathway engineering, expanding substrate scope, bioprocess engineering, and novel breeding methods to resolve the aforementioned issues.
Is Malaysia Ready for Human Gene Editing: A Regulatory, Biosafety and Biosecurity Perspective
Authors: Kalidasan V. , Theva Das Kumitaa
Published: March 2021

Gene editing platforms have revolutionized the field of genetics with a direct impact on the public health system. Although there are apparent benefits, it is often accompanied by public debates over its uncertainties and risks. In the Malaysian context, modern biotechnology has raised questions about how to best govern gene editing in regulations, biosafety, and biosecurity. Even though standards and guidelines on stem cell and cell-based therapies have been developed, there are no appropriate legal frameworks available for gene editing yet. Nevertheless, biosafety regulations were established to balance promoting biotechnology and protecting against their potential environmental and human health risks. There is also a need to address the potential of genetically modified organisms (GMOs) as bioweapons. Numerous frameworks from several international organizations may provide valuable input in formulating documents on gene editing. By establishing comprehensive guidelines, legal policies, and standards to tackle the challenges and risks associated with gene editing, Malaysia can successfully apply this modern technology in this country.
OPCML Methylation and the Risk of Ovarian Cancer: A Meta and Bioinformatics Analysis
Authors: Shao Yang , Kong Jing , Xu Hanzi , Wu Xiaoli , Cao YuePeng , Li Weijian , Han Jing , Li Dake , Xie Kaipeng , Wu Jiangping
Published: March 2021

Background: The association of opioid binding protein cell adhesion molecule-like (OPCML) gene methylation with ovarian cancer risk remains unclear.

Methods: We identified eligible studies by searching the PubMed, Web of Science, ScienceDirect, and Wanfang databases. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to determine the association of OPCML methylation with ovarian cancer risk. Meta-regression and subgroup analysis were used to assess the sources of heterogeneity. Additionally, we analyzed the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets to validate our findings.

Results: Our study included 476 ovarian cancer patients and 385 controls from eight eligible studies. The pooled OR was 33.47 (95% CI = 12.43–90.16) in the cancer group vs. the control group under the random-effects model. The association was still significant in subgroups according to sample type, control type, methods, and sample sizes (all P < 0.05). Sensitivity analysis showed that the finding was robust. No publication bias was observed in Begg's (P = 0.458) and Egger's tests (P = 0.261). We further found that OPCML methylation was related to III/IV (OR = 4.20, 95% CI = 1.59–11.14) and poorly differentiated grade (OR = 4.37; 95% CI = 1.14–16.78). Based on GSE146552 and GSE155760, we validated that three CpG sites (cg16639665, cg23236270, cg15964611) in OPCML promoter region were significantly higher in cancer tissues compared to normal tissues. However, we did not observe the associations of OPCML methylation with clinicopathological parameters and overall survival based on TCGA ovarian cancer data.

Conclusion: Our findings support that OPCML methylation is associated with an increased risk of ovarian cancer.
Microarchitecture of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva: An HR-pQCT Case Series
Authors: Botman Esmée , Bevers Melissa S. A. M. , Wyers Caroline E. , van Rietbergen Bert , Teunissen Bernd P. , Raijmakers Pieter G. , Netelenbos Jan Coen , van den Bergh Joop P. , Eekhoff Elisabeth M. W.
Published: March 2021

It is challenging to study heterotopic ossification (HO) in patients with fibrodysplasia ossificans progressiva (FOP) due to the contraindication of invasive techniques (i.e., bone biopsies), which can trigger flare-ups. The aim of this case study was to assess mature HO at the microarchitectural level non-invasively with high-resolution peripheral quantitative computed tomography (HR-pQCT). Depending on the patient’s mobility, HR-pQCT scans were acquired of peripherally located HO and standard distal radius and tibia regions in two FOP patients, a 33-year-old woman and a 23-year-old man, with the classical mutation (p.R206H). HO was located around the halluces, the ankles, and in the Achilles tendon. Standard HR-pQCT analyses were performed of the distal radius, tibia, and HO to quantify bone mineral density (BMD) and bone microarchitecture. Micro-finite element analysis was used to estimate failure load (FL). The outcomes were compared between HO and neighboring skeletal bone and with an age- and gender-matched normative dataset from literature. The bone parameters of the radius were within the interquartile range (IQR) of normative data. In contrast, in the tibiae of both patients, total and trabecular BMD were below the IQR, as were trabecular bone volume fraction, number, and thickness, cortical thickness, and FL. Trabecular separation and heterogeneity were above the IQR. Isolated HO in the Achilles tendon had a lower total, trabecular, and cortical BMD, trabecular bone volume fraction, and cortical thickness than the normative tibia data. Trabecular microarchitecture was within the IQR, and FL was approximately 10% higher than that of the neighboring tibia after accounting for areal differences. Other scanned HO could only be qualitatively assessed, which revealed coalescence with the neighboring skeletal bone, development of a neo-cortex, and partial replacement of the original skeletal cortex with trabeculae. To conclude, isolated HO seemed microarchitecturally more comparable to reference tibia data than the peripheral skeleton of the FOP patients. HO and skeleton also appear to be able to become one entity when contiguous.
Targeting the Mitochondria-Proteostasis Axis to Delay Aging
Authors: Zimmermann Andreas , Madreiter-Sokolowski Corina , Stryeck Sarah , Abdellatif Mahmoud
Published: March 2021

Human life expectancy continues to grow globally, and so does the prevalence of age-related chronic diseases, causing a huge medical and economic burden on society. Effective therapeutic options for these disorders are scarce, and even if available, are typically limited to a single comorbidity in a multifaceted dysfunction that inevitably affects all organ systems. Thus, novel therapies that target fundamental processes of aging itself are desperately needed. In this article, we summarize current strategies that successfully delay aging and related diseases by targeting mitochondria and protein homeostasis. In particular, we focus on autophagy, as a fundamental proteostatic process that is intimately linked to mitochondrial quality control. We present genetic and pharmacological interventions that effectively extend health- and life-span by acting on specific mitochondrial and pro-autophagic molecular targets. In the end, we delve into the crosstalk between autophagy and mitochondria, in what we refer to as the mitochondria-proteostasis axis, and explore the prospect of targeting this crosstalk to harness maximal therapeutic potential of anti-aging interventions.
The Association of TLR2, TLR3, and TLR9 Gene Polymorphisms With Susceptibility to Talaromycosis Among Han Chinese AIDS Patients in Guangdong
Authors: Wang Min , Li Linghua , Xiao Saiyin , Chen Wanshan , Hu Fengyu , Li Feng , Guo Pengle , Chen Xiejie , Cai Weiping , Tang Xiaoping
Published: March 2021

Background

Talaromycosis (TM) caused by Talaromyces marneffei (T. marneffei) is a growing public health concern. Although Toll-like receptor (TLR) genes play a critical role in the host defense against fungal infection, the influence of polymorphisms in these genes on the susceptibility of acquired immune deficiency syndrome (AIDS) patients to TM remains unknown. This study aims to uncover the associations of single nucleotide polymorphisms (SNPs) in TLR genes with TM susceptibility among patients with AIDS.

Methods

Altogether 200 AIDS patients complicated with TM, 200 matched AIDS patients without TM, and 76 healthy controls (HCs) were enrolled in this case-control study. In total, 23 SNPs in the TLR2, TLR4, and TLR9 genes, which may influence the susceptibility of AIDS patients to TM, were checked by the time of flight mass spectrometry (TOF/MS) method among these Han Chinese subjects.

Results

No significant differences in genotype or allele frequencies of selected SNPs were found among the TM group, Non-TM group, and HC group. Haplotype analysis also demonstrated no correlation of these SNPs with TM. However, subgroup analysis showed that the genotype TT and the T allele in TLR2 SNP rs1339 were more frequent in typical TM cases than controls (50.0 vs. 35.8%, 70.5 vs. 59.7%); the frequency of the GT genotype in TLR2 SNP rs7656411 was markedly higher in severe TM cases compared to controls (57.8 vs. 34.4%).

Conclusion

Our results demonstrate a genetic connection of TLR2 SNPs rs1339 and rs7656411 with an increased susceptibility and severity of TM among Han Chinese populations.
Alpha-Tubulin Acetylation in Trypanosoma cruzi: A Dynamic Instability of Microtubules Is Required for Replication and Cell Cycle Progression
Authors: Alonso Victoria Lucia , Carloni Mara Emilia , Gonçalves Camila Silva , Martinez Peralta Gonzalo , Chesta Maria Eugenia , Pezza Alejandro , Tavernelli Luis Emilio , Motta Maria Cristina M. , Serra Esteban
Published: March 2021

Trypanosomatids have a cytoskeleton arrangement that is simpler than what is found in most eukaryotic cells. However, it is precisely organized and constituted by stable microtubules. Such microtubules compose the mitotic spindle during mitosis, the basal body, the flagellar axoneme and the subpellicular microtubules, which are connected to each other and also to the plasma membrane forming a helical arrangement along the central axis of the parasite cell body. Subpellicular, mitotic and axonemal microtubules are extensively acetylated inTrypanosoma cruzi. Acetylation on lysine (K) 40 of α-tubulin is conserved from lower eukaryotes to mammals and is associated with microtubule stability. It is also known that K40 acetylation occurs significantly on flagella, centrioles, cilia, basal body and the mitotic spindle in eukaryotes. Several tubulin posttranslational modifications, including acetylation of K40, have been cataloged in trypanosomatids, but the functional importance of these modifications for microtubule dynamics and parasite biology remains largely undefined. The primary tubulin acetyltransferase was recently identified in several eukaryotes as Mec-17/ATAT, a Gcn5-related N-acetyltransferase. Here, we report thatT. cruziATAT acetylates α-tubulinin vivoand is capable of auto-acetylation.TcATAT is located in the cytoskeleton and flagella of epimastigotes and colocalizes with acetylated α-tubulin in these structures. We have expressedTcATAT with an HA tag using the inducible vector pTcINDEX-GW inT. cruzi. Over-expression ofTcATAT causes increased levels of the alpha tubulin acetylated species, induces morphological and ultrastructural defects, especially in the mitochondrion, and causes a halt in the cell cycle progression of epimastigotes, which is related to an impairment of the kinetoplast division. Finally, as a result ofTcATAT over-expression we observed that parasites became more resistant to microtubule depolymerizing drugs. These results support the idea that α-tubulin acetylation levels are finely regulated for the normal progression ofT. cruzicell cycle.
Seipin Deficiency Accelerates Heart Failure Due to Calcium Handling Abnormalities and Endoplasmic Reticulum Stress in Mice
Authors: Wu Xiaoyue , Liu Xuejing , Wang Huan , Zhou Zihao , Yang Chengzhi , Li Zijian , Zhang Youyi , Shi XiaoLu , Zhang Ling , Wang Yuhui , Xian Xunde , Liu George , Huang Wei
Published: March 2021

Seipin deficiency can induce hypertrophic cardiomyopathy and heart failure, which often leads to death in humans. To explore the effects and the possible mechanisms of Seipin deficiency in myocardial remodeling, Seipin knockout (SKO) mice underwent transverse aortic constriction (TAC) for 12 weeks. We found a more severe left ventricular hypertrophy and diastolic heart failure and increases in inflammatory cell infiltration, collagen deposition, and apoptotic bodies in the SKO group compared to those in the wild type (WT) group after TAC. Electron microscopy also showed a more extensive sarcoplasmic reticulum expansion, deformation of microtubules, and formation of mitochondrial lesions in the cardiomyocytes of SKO mice than in those of WT mice after TAC. Compared with the WT group, the SKO group showed increases in endoplasmic reticulum (ER) stress-, inflammation-, and fibrosis-related gene expression, while calcium ion-related factors, such as Serca2a and Ryr, were decreased in the SKO group after TAC. Increased levels of the ER stress-related protein GRP78 and decreased SERCA2a and P-RYR protein levels were detected in the SKO group compared with the WT group after TAC. Slowing of transient Ca2+ current decay and an increased SR Ca2+ content in myocytes were detected in the cardiomyocytes of SKO mice. Adipose tissue transplantation could not rescue the cardiac hypertrophy after TAC in SKO mice. In conclusion, we found that Seipin deficiency could promote cardiac hypertrophy and diastolic heart failure after TAC in mice. These changes may be related to the impairment of myocardial calcium handling, ER stress, inflammation, and apoptosis.
A Laboratory Forced-Oscillation Apparatus for Measurements of Elastic and Anelastic Properties of Rocks at Seismic Frequencies
Authors: Mikhaltsevitch Vassily , Lebedev Maxim , Chavez Rafael , Vargas Euripedes A. , Vasquez Guilherme F.
Published: March 2021

In presented paper, we describe the technical and physical aspects of the application of a low-frequency (LF) apparatus based on a longitudinal type of forced oscillations. In particular, we investigate the influence of the strain gauge position on a tested sample on measurement results, we also examine the creep effect associated with the mineralogy of rocks, as well as the dispersion and attenuation in a liquid-saturated rock sample caused by the presence of the volume of pore fluid exterior to the sample (dead volume). The effect of the position of the strain gauges is investigated using a cylindrical acrylic sample and two pairs of strain gauges fixed in the middle and at one of the sample ends under a uniaxial pressure of 15 MPa. The obtained results demonstrate that elastic and anelastic parameters of the tested sample are independent from the location of the strain gauges. The impact of the creep phenomenon on elastic moduli was studied using three room-dry samples of Savonnieres limestone, Berea sandstone and Eagle Ford shale. The measurements were conducted for 120 h at a frequency of 2 Hz under a uniaxial pressure of 10 MPa and demonstrated that the LF moduli of all rocks were noticeably reduced with time. The effect of dead volume was investigated at seismic frequencies using limestone saturated with n-decane. It was found that the Young’s and bulk moduli exhibit strong dispersion at frequencies above 10 Hz if the dead volume is close to or greater than the pore volume of the sample. We also found that the characteristic frequency of dispersion corresponding to the attenuation peak is independent of the size of the dead volume and determined only by the physical parameters of the sample and pore fluid. We present also the results of the Young’s modulus and attenuation measurements conducted at seismic frequencies on vertical and horizontal shale samples saturated with water. It was shown that the relationship between the extensional attenuation and the Young’s modulus dispersion observed in the samples saturated at a relative humidity of 97.5% is consistent with the Kramers–Kronig relation.
Low Doses of Glyphosate/Roundup Alter Blood–Testis Barrier Integrity in Juvenile Rats
Authors: Gorga Agostina , Rindone Gustavo Marcelo , Centola Cecilia Lucía , Sobarzo Cristian M. , Pellizzari Eliana Herminia , Camberos María del Carmen , Marín-Briggiler Clara Isabel , Cohen Debora J. , Riera Maria Fernanda , Galardo Maria Noel , Meroni Silvina Beatriz
Published: March 2021

It has been postulated that glyphosate (G) or its commercial formulation Roundup (R) might lead to male fertility impairment. In this study, we investigated the possible effects of G or R treatment of juvenile male rats on blood-testis barrier function and on adult male sperm production. Pups were randomly assigned to the following groups: control group (C), receiving water; G2 and G50 groups, receiving 2 and 50 mg/kg/day G respectively; and R2 and R50 groups receiving 2 and 50 mg/kg/day R respectively. Treatments were performed orally from postnatal day (PND) 14 to 30, period of life that is essential to complete a functional blood-testis barrier. Evaluation was done on PND 31. No differences in body and testis weight were observed between groups. Testis histological analysis showed disorganized seminiferous epithelium, with apparent low cellular adhesion in treated animals. Blood-testis barrier permeability to a biotin tracer was examined. A significant increase in permeable tubules was observed in treated groups. To evaluate possible mechanisms that could explain the effects on blood-testis barrier permeability, intratesticular testosterone levels, androgen receptor expression, thiobarbituric acid reactive substances (TBARS) and the expression of intercellular junction proteins (claudin11, occludin, ZO-1, connexin43, 46, and 50 which are components of the blood-testis barrier) were examined. No modifications in the above-mentioned parameters were detected. To evaluate whether juvenile exposure to G and R could have consequences during adulthood, a set of animals of the R50 group was allowed to grow up until PND 90. Histological analysis showed that control and R50 groups had normal cellular associations and complete spermatogenesis. Also, blood-testis barrier function was recovered and testicular weight, daily sperm production, and epididymal sperm motility and morphology did not seem to be modified by juvenile treatment. In conclusion, the results presented herein show that continuous exposure to low doses of G or R alters blood-testis barrier permeability in juvenile rats. However, considering that adult animals treated during the juvenile stage showed no differences in daily sperm production compared with control animals, it is feasible to think that blood-testis barrier impairment is a reversible phenomenon. More studies are needed to determine possible damage in the reproductive function of human juvenile populations exposed to low doses of G or R.
Psychotropic Drugs Levels in Seminal Fluid: A New Therapeutic Drug Monitoring Analysis?
Authors: Mazzilli Rossella , Curto Martina , De Bernardini Donatella , Olana Soraya , Capi Matilde , Salerno Gerardo , Cipolla Fabiola , Zamponi Virginia , Santi Daniele , Mazzilli Fernando , Simmaco Maurizio , Lionetto Luana
Published: March 2021

The aim of this observational study was to develop a new quantitative liquid chromatography-mass spectrometry (LC-MS/MS) method for Therapeutic-Drug-Monitoring (TDM) of psychotropic drugs in seminal fluid to investigate potential gonadotoxic effects in patients with reduced fertility. After the validation of the LC-MS/MS method for psychotropics’ levels determination in seminal fluid, we included 20 male partners of infertile couples with idiopathic and/or unexplained male infertility, treated with psychotropic medications for more than 3 months and 10 untreated fertile controls. General and andrological clinical examination, semen analysis and seminal drugs, and metabolites levels determination were performed for each subject. Of the 20 patients included, 6 were treated with antidepressants; 4 with benzodiazepines and 10 with antipsychotics. Seminal drugs and metabolites levels were detectable in all samples. In particular, alprazolam, olanzapine, and levetiracetam showed seminal and serum similar concentrations, while fluoxetine, quetiapine, and aripiprazole were detectable, but seminal levels were significantly lower than the serum therapeutic range. Sperm progressive motility was significantly reduced in subjects treated with psychotropic drugs compared to the untreated controls (p = 0.03). Sperm concentration and progressive motility were significantly reduced in subjects treated with antipsychotics compared to the untreated controls and to the other classes of psychotropics (p < 0.05). In conclusion, this study reports a validated LC-MS/MS method for the detection of seminal psychotropic levels and preliminary data suggesting a potential correlation of seminal psychotropics with alterations of sperm concentration and motility. Pending larger studies, semen TDM might represent a new pivotal tool in the clinical management of reduced fertility in males treated with psychotropic medications.
Patient-Derived Organoid Models of Human Neuroendocrine Carcinoma
Authors: Dijkstra Krijn K. , van den Berg José G. , Weeber Fleur , van de Haar Joris , Velds Arno , Kaing Sovann , Peters Dennis D. G. C. , Eskens Ferry A. L. M. , de Groot Derk-Jan A. , Tesselaar Margot E. T. , Voest Emile E.
Published: March 2021

Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a poorly understood disease with limited treatment options. A better understanding of this disease would greatly benefit from the availability of representative preclinical models. Here, we present the potential of tumor organoids, three-dimensional cultures of tumor cells, to model GEP-NEC. We established three GEP-NEC organoid lines, originating from the stomach and colon, and characterized them using DNA sequencing and immunohistochemistry. Organoids largely resembled the original tumor in expression of synaptophysin, chromogranin and Ki-67. Models derived from tumors containing both neuroendocrine and non-neuroendocrine components were at risk of overgrowth by non-neuroendocrine tumor cells. Organoids were derived from patients treated with cisplatin and everolimus and for the three patients studied, organoid chemosensitivity paralleled clinical response. We demonstrate the feasibility of establishing NEC organoid lines and their potential applications. Organoid culture has the potential to greatly extend the repertoire of preclinical models for GEP-NEC, supporting drug development for this difficult-to-treat tumor type.
Lessons from Human Islet Transplantation Inform Stem Cell-Based Approaches in the Treatment of Diabetes
Authors: Triolo Taylor M. , Bellin Melena D.
Published: March 2021

Diabetes mellitus is characterized by the body’s inability to control blood glucose levels within a physiological range due to loss and/or dysfunction of insulin producing beta cells. Progressive beta cell loss leads to hyperglycemia and if untreated can lead to severe complications and/or death. Treatments at this time are limited to pharmacologic therapies, including exogenous insulin or oral/injectable agents that improve insulin sensitivity or augment endogenous insulin secretion. Cell transplantation can restore physiologic endogenous insulin production and minimize hyper- and hypoglycemic excursions. Islet isolation procedures and management of transplant recipients have advanced over the last several decades; both tight glycemic control and insulin independence are achievable. Research has been conducted in isolating islets, monitoring islet function, and mitigating the immune response. However, this procedure is still only performed in a small minority of patients. One major barrier is the scarcity of human pancreatic islet donors, variation in donor pancreas quality, and variability in islet isolation success. Advances have been made in generation of glucose responsive human stem cell derived beta cells (sBCs) and islets from human pluripotent stem cells using directed differentiation. This is an emerging promising treatment for patients with diabetes because they could potentially serve as an unlimited source of functional, glucose-responsive beta cells. Challenges exist in their generation including long term survival of grafts, safety of transplantation, and protection from the immune response. This review focuses on the progress made in islet allo- and auto transplantation and how these advances may be extrapolated to the sBC context.