bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac differentiation of bone marrow resident c-kit+ stem cells by L-carnitine increases through secretion of VEGF, IL6, IGF-1 and TGF-β
Authors: Farahzadi Raheleh , Fathi Ezzatollah , Vietor Ilja , Javanmardi Sara 
Published: April 2020

Abstract
Background: The idea of regenerating lost myocardium via cell therapies remains highly considerable. Also, C-kit+ stem/progenitor cells are represented to be suitable candidates for cardiac regeneration compared to other stem cells. A multitude of cytokines from these cells are known to give such multifunctional properties; however, associated mechanisms of these factors must still be absolutely understood. On the other hand, loss of cell survival and functionality, is one of the main problems in regenerative medicine. The aim of the present study was to investigate the in vitro effect of L-carnitine (LC) on cardiac differentiation of c-kit+ cells via cytokines secretion assay. Methods: For this purpose, bone marrow resident-c-kit+ cells were enriched by MACS method, and were differentiated to cardiac cells in the absence (-LC) and presence of LC (+LC). Also, Characterization of enriched c-kit+ cells was performed using flow cytometry and immunocytochemistry. At the end of the treatment period, the cells were subjected to real-time PCR along with western blotting assay for gene and protein assessment, respectively. Then, culture medium was collected from both control (-LC) and experimental groups (+LC) for cytokine array. Results: It was found that 0.2 mM LC induces cardiac differentiation of c-kit+ cells via increasing the cardiac markers expression of Ang-1, Ang-2, C-TnI, VEGF, vWF, and SMA. Also, the significant presence of IL-6, IGF-1, TGF-β, and VEGF were obvious in the cultured media. Conclusion: It can be concluded that in vitro effects of LC on cardiac differentiation of c-kit+ cells could be due to the secreted cytokines IL-6, IGF-1, TGF-β, and VEGF.
Spatial patterns of microbial nitrogen genes along precipitation gradient in different temperate grasslands of Inner Mongolia, China
Authors: Zhou Shutong , Xue Kai , Zhang Biao , Tang Li , Pang Zhe , Wang Fang , Che Rongxiao , Ran Qinwei , Xia Anquan , Wang Kui , Li Linfeng , Dong Junfu , Du Jianqing , Hu Ronghai , Hao Yanbin , Cui Xiaoyong , Wang Yanfen 
Published: April 2020

Abstract
Background: Despite the importance of microorganisms in soil nitrogen (N) cycling, studies on spatial patterns of microbial N genes in the temperate grassland are still lacking, whose productivity is limited by N. Here, we investigated microbial N genes from 60 temperate grassland sites across 1 161 km in Inner Mongolia, China. Results: All N gene abundances tended to decrease from northeast to southwest, consistent with precipitation change but contrary to temperature trend. Most N gene abundances increased with rising precipitation when < 321 or 403 mm, but remained stable after breaking points, indicating non-linear saturation curves dominated response patterns. Moreover, decay relationships were discovered for N gene community over geographic distance, whose effect was direct in temperate desert steppe but indirect via environmental heterogeneity in temperate meadow and typical steppe. Representativeness of geographic distance on historical-contingency was dominant only in temperate meadow (81.2%). N gene community similarity decay was mainly attributed to plant community (76.98%), with wider range, in typical steppe; while contemporary-disturbance was the attributor more important in temperate meadow (29.41%). Conclusions: Overall, we discovered non-linear patterns of N genes along precipitation gradient, and quantified attributions of geographic distance, plant community, historical-contingency and contemporary-disturbance to N gene community similarity decay, clearly ecosystem-dependent.
Triggering outer membrane leakiness of a novel E. coli strain for recombinant protein production
Authors: Kastenhofer Jens , Rettenbacher Lukas , Feuchtenhofer Lukas , Mairhofer Jürgen , Spadiut Oliver 
Published: April 2020

Abstract
BackgroundRecombinant proteins in Escherichia coli are expressed inside the cell. With the growing interest in continuous cultivation, secretion of product to the medium is not only a benefit, but a necessity in future bioprocessing. In this study, we present a novel E. coli production host for growth decoupled recombinant protein production that can leak up to 90% of recombinant protein to the extracellular space. We investigated the effects of the process parameters temperature and specific glucose uptake rate on physiology, productivity, lysis and leakiness. Two model proteins were used, Protein A and a VHH single-domain antibody, and performance was compared to the industrial standard strain BL21(DE3).ResultsWe show that inducible growth repression in the novel E. coli strain enGenes-X-press, the effect of the metabolic burden on host physiology can be greatly reduced compared to BL21(DE3). Furthermore, in both strains, increasing temperature and specific substrate enhanced productivity and leakiness. Using the enGenes-X-press strain, extracellular Protein A and VHH titer reached up to 349 mg/g and 19.6 mg/g, respectively, comprising between 80 and 90% of total soluble product, while keeping cell lysis to a minimum. BL21(DE3) leaked 198 mg/g and 3.9 mg/g of Protein A and VHH to the medium, accounting for only 56% and 34% of total soluble product, respectively.ConclusionsWe confined the parameter space in which outer membrane leakiness can be controlled, while maintaining cell viability. Moreover, our findings demonstrate that the enGenes-X-press strain constitutes a superior host for extracellular production of recombinant protein.
Evaluation of the Effect of Cumulative Cisplatin Dose in Locoregionally Advanced Nasopharyngeal Carcinoma Patients Receiving Intensity-Modulated Radiotherapy
Authors: Lin Sheng-Chiao , Lin Yu-Hsuan , Lin Yaoh-Shiang , Kang Bor-Hwang , Chang Kuo-Ping , Chang Ting-Shou 
Published: April 2020

Abstract
Background: In nasopharyngeal carcinoma (NPC), the cut-off value of cumulative cisplatin dose (CCD) associated with survival benefits remains controversial. This study aimed to determine a CCD cut-off value for favorable survival outcomes and to identify specific patient groups benefitting from higher CCDs. Methods: We retrospectively reviewed the records of 161 patients (male-to-female ratio of 2.6:1.0) with NPC receiving concurrent chemoradiotherapy ± adjuvant chemotherapy (AC) from February 2006 through September 2015 at our referral center. The CCD was calculated for each patient, and 3-year locoregional-free survival (LRFS), distant-metastasis free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were analyzed using a multivariable Cox regression model. Results: Stage N3 patients and stage IV patients had lower DMFS, DSS, and OS. A CCD ≥ 200 mg/m 2 or AC was not associated with survival benefits. After adjusting for other factors, N3 status remained robustly correlated with DMFS ( p < 0.001) and DSS ( p = 0.001). In subgroup analyses, stage N3 patients treated with CCD ≥ 200 mg/m 2 exhibited evident trends toward higher OS ( p = 0.119), DSS ( p = 0.119), DMFS ( p = 0.201), and LRFS ( p = 0.125) than patients treated with CCD < 200 mg/m 2 . Conclusions: A CCD ≥ 200 mg/m 2 might result in better survival outcomes in stage N3 patients. Larger CCDs may be exclusively used in cases of regionally advanced disease to avoid rigorous toxicity.
A unique radioprotective effect of resolvin E1 reduces irradiation-induced damage to the inner ear by inhibiting the inflammatory response
Authors: Zhang Jie , Xu Anting , Niu Tingting , Liu Chengcheng , Zhang Yongju , Li Tao , Wang Jihua , Wang Yongjing , Sun Dianshui 
Published: April 2020

Abstract
Background In addition to the direct effects of irradiation, the induced inflammatory response may play an important role in the damage to the inner ear caused by radiotherapy for the treatment of head and neck cancers. Resolvin E1 has anti-inflammatory activity, acting by reducing neutrophil infiltration and proinflammatory cytokine expression. Therefore, in this study we sought to confirm whether the inflammation induced by irradiation was involved in damage to the inner ear after radiotherapy and to investigate the protective effect and underlying mechanism of resolvin E1 using mouse models. Methods A dose of resolvin E1 was delivered by intraperitoneal injection to mice before irradiation. Changes in the auditory brainstem response, relative balance ability, inner ear morphology and the expression levels of proinflammatory cytokines in the inner ear were analyzed on days 7 and 14 after irradiation and compared among three experimental groups. Results Morphological analysis of the inner ear showed severe damage to the cochlea and vestibule after irradiation. In contrast, damage to the cochlea and vestibule was significantly reduced in the resolvin E1-pretreated group, which nonetheless remained damaged compared to the wild-type group. Proinflammatory cytokines also showed expression patterns matching the morphological observations. Conclusions We believe that the inflammation induced by irradiation is involved in the damage to the inner ear caused by radiotherapy, and that resolvin E1 reduces the damage caused by irradiation to the inner ear by regulating the induced inflammatory response.
Optimized method for extraction of exosomes from human primary muscle cells
Authors: Gall Laura Le , Ouandaogo Zamalou Gisele , Anakor Ekene , Connolly Owen , Browne Gillian Butler , Laine Jeanne , Duddy William John , Duguez Stephanie 
Published: April 2020

Abstract
Skeletal muscle is increasingly considered as an endocrine organ secreting myokines and extracellular vesicles (exosomes and microvesicles), which can effect physiological changes with impact in different pathological conditions, including regenerative processes, aging and myopathies. Primary human myoblasts are an essential tool to study the muscle vesicle secretome . Since their differentiation in conditioned media does not induce any signs of cell death or cell stress, artefactual effects from those processes are unlikely. However, adult human primary myoblasts senesce in long-term tissue culture, so a major technical challenge is posed by the need to avoid artefactual effects resulting from pre-senescent changes. Since these cells should be studied within a strictly controlled pre-senescent division count (< 21 divisions), and yields of myoblasts per muscle biopsy are low, it is difficult or impossible to amplify sufficiently large cell numbers (some 250 x 10 6 myoblasts) to obtain sufficient conditioned medium for the standard ultracentrifugation approach to exosome isolation.
Thus an optimized strategy to extract and study secretory muscle vesicles is needed. In this study, conditions are optimized for the in vitro cultivation of human myoblasts, and the quality and yield of exosomes extracted using an ultracentrifugation protocol are compared with a modified polymer-based precipitation strategy combined with extra washing steps. Both vesicle extraction methods successfully enriched exosomes, as vesicles were positive for CD63, CD82, CD81, floated at identical density ( 1.15-1.27 g.ml -1 ), and exhibited similar size and cup-shape using electron microscopy and NanoSight tracking. However, the modified polymer-based precipitation was a more efficient strategy to extract exosomes, allowing their extraction in sufficient quantities to explore their content or to isolate a specific subpopulation, while requiring >30 times fewer differentiated myoblasts than what is required for the ultracentrifugation method. In addition, exosomes could still be integrated into recipient cells such as human myotubes or iPSC -derived motor neurons.
Modified polymer-based precipitation combined with extra washing steps optimizes exosome yield from a lower number of differentiated myoblasts and less conditioned medium, avoiding senescence and allowing the execution of multiple experiments without exhausting the proliferative capacity of the myoblasts.
High-throughput screening reveals novel mutations in spinal muscular atrophy patients
Authors: Zhang Ruiping , Gu Chunyu , Pu Linjie , Meng Yingtao , Shu Jianbo , Cai Chunquan 
Published: April 2020

Abstract
Background Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease associated with severe muscle atrophy and weakness in the limbs and trunk. The discovery of genes mutated by SMA is helpful in diagnosis and treatment. Methods 83 whole blood samples were collected from 28 core families of clinically suspected SMA, and multiplex ligation probe amplification (MLPA) was firstly performed. Afterwards, the complete gene sequence of SMN1 gene was detected. Furthermore, 20 SMA patients were selected from the 28 probands, and 5 non SMA children as controls. The Life Technologies SOLiD™ technology with mate-pair chemistry was utilized to conduct the whole exome high-throughput sequencing. Results 22 probands were SMA patients, 3 probands carriers, and 3 probands normal individuals. Moreover, 2 parents from 2 SMA families were with 3 SMN1 exon7 copies. 6 SMN1 single nucleotide variants (SNVs) were identified in the 83 samples, and c.[84C>T], c.[271C>T], c.[-39A>G] and g.[70240639G>C] were novel. Compared with control group, 9102 mutation were selected out in SMA patients. SPTA1 mutation c.[-41_-40insCTCT], FUT5 SNV c.[1001A>G], and MCCC2 SNV c.[-117A>G] were the 3 most frequent mutations in SMA group (95%, 85% and 75%, respectively). Conclusions We identified some mutations in both SMN1 and other genes, and c.[271C>T], c.[-41_-40insCTCT], c.[1001A>G] and c.[-117A>G] might be associated with the onset of SMA.
Post Occupancy Evaluation of Adaptively Reused Buildings: Case Study of an Office Building in Saudi Arabia
Authors: HAMIDA Mohammad B. , HASSANAIN Mohammad A. 
Published: April 2020

Abstract
Adaptive reuse of buildings is the practice of converting the use of an originally designed built-environment to suit a new use. This conversion process has a direct bearing on the performance of the building, and the satisfaction of the users with the conditions of the converted built-environment. This paper presents the findings of a post occupancy evaluation (POE) of an adaptively reused student housing facility to an office building, as a case study. The POE was conducted to investigate the consequences of the conversion process on the technical and functional elements of performance of the adapted building. A review of literature was performed to identify the technical and functional elements of performance pertaining to the new use of the building, along with their recommended performance criteria in codes and standards. The study employed multiple data collection methods, including a walkthrough tour to develop insights about the performance of the building elements; interviews to confirm the validity of the identified technical and functional performance elements, and initiate discussion with the users based on the findings of the walkthrough tour; and a user satisfaction survey to obtain the users’ feedback on the performance of the building. The findings of the study resulted in developing a series of recommendations to improve the performance of the case study building. The paper serves to guide design professionals involved in the planning and design of adaptive reuse projects, and facilities managers in charge of the daily operations of adaptively reused buildings.
TRPC3-Based Protein Signaling Complex as a Therapeutic Target of Myocardial Atrophy
Authors: Nishiyama Kazuhiro , Tanaka Tomohiro , Nishimura Akiyuki , Nishida Motohiro 
Published: April 2020

Background:
Transient receptor potential (TRP) channels, especially canonical TRP channel subfamily
members 3 (TRPC3) and 6 (TRPC6), have attracted attention as a putative therapeutic target of heart
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failure. Moreover, TRPC3 and TRPC6 channels are physiologically important for maintaining cellular
homeostasis. How TRPC3/C6 channels alter intracellular signaling from adaptation to maladaptation has
been discussed for many years. We recently showed that formation of a protein signal complex between
TRPC3 and NADPH oxidase (Nox) 2 caused by environmental stresses (e.g., hypoxia, nutritional
deficiency, and anticancer drug treatment) promotes Nox2-dependent reactive oxygen species production
and cardiac stiffness, including myocardial atrophy and interstitial fibrosis, in rodents. In fact,
pharmacological prevention of the TRPC3-Nox2 protein complex can maintain cardiac flexibility in mice
after anti-cancer drug treatment.

Conclusion:
In this mini-review, we discuss the relationship between TRPC3/C6 channels and
cardiovascular disease, and propose a new therapeutic strategy by focusing on pathology-specific protein–
protein interactions.
Influence of Biocompatible Coating on Titanium Surface Characteristics
Authors: Petrović Željka , Katić Jozefina , Šarić Ankica , Despotović Ines , Matijaković Nives , Kralj Damir , Leskovac Mirela , Petković Marin 
Published: April 2020

Background:
Nowadays investigations in the field of dental implants engineering are focused
on bioactivity and osseointegration properties.

Objective:
In this study, the oxide-covered titanium was functionalized by vitamin D3 molecules via a
simple self-assembly method with the aim to design more corrosion-resistant and at the same time
more bioactive surface.

Methods:
Surface properties of the D3-coated titanium were examined by scanning electron microscopy,
attenuated total reflectance Fourier transform infrared spectroscopy, and contact angle measurements,
while long-term corrosion stability during immersion in an artificial saliva solution was
investigated in situ by electrochemical impedance spectroscopy.

Results:
Results of all techniques confirmed a successful formation of the vitamin D3 layer on the
oxide-covered titanium. Besides very good corrosion resistivity (~5 MΩ cm2), the D3-modified titanium
surface induced spontaneous formation of biocompatible bone-like calcium phosphates (CaP).

Conclusion:
Observed in vitro CaP-forming ability as a result of D3-modified titanium/artificial saliva
interactions could serve as a promising predictor of in vivo bioactivity of implant materials.
Kontroversi Surat Al-Fatihah Dalam Pandangan Arthur Jeffery
Authors: Dhulkifli Muhammad Luthfi 
Published: April 2020

AbstractAmongst some orientalist of Qur’anic studies, Arthur Jeffery was one of the controversial figures for the idea of a critical edition of the Qur’an. For Jeffery, the Qur’an existed today is unreasonable and its arrangement is clearly haphazard. One of his critical argument is surah al-Fatihah which indicated not originally part of the Qur’an. His work “the variant readings of the Fatihah” showed some peculiar nature of al-Fatiha with the evidence of two Fatihah different versions. Jeffery’s variants study is a polemical argument as its contradicts to the Muslim scholar arguments. For Muslim scholars, al-Fatihah is an integrated part of Qur’an. Therefore, this article will analyze Jeffery’s argument on al-Fatihah through a descriptive-analytic method. Based on historical, language, and qira’ah study, Jeffery’s argument is incorrect. In addition, Jeffery failed to show the existence of his evidence of variant of al-Fatihah.Keywords: Critic; Controversy; Fatiha; Muslim; the Qur’an AbstrakDiantara sekian banyak para orientalis pengkaji al-Qur’an, Arthur Jeffery merupakan salah satu sosok yang paling kontroversial dengan gagasannya untuk membuat al-Qur’an edisi kritis. Menurut Jeffery, al-Qur’an yang ada saat ini sangat tidak jelas dan susunannya dilakukan secara sembarangan. Salah satu bagian yang Jeffery kritisi adalah surat al-Fatihah yang dianggap bukan bagian dari al-Qur’an. Dalam tulisannya yang berjudul the variant readings of the Fatihah, dia menunjukkan kejanggalan dalam surat al-Fatihah dengan menunjukkan bukti dua variasi surat al-Fatihah yang berbeda. Kajian ini mengundang polemik karena bertentangan dengan pandangan para sarjana Muslim yang menganggap al-Fatihah sebagai bagian penting dari al-Qur’an. Tulisan ini akan menganalisasi pandangan Jeffery terhadap surat al-Fatihah melalui metode deskriptif-analitis. Melalui kajian historis, kebahasaan, dan ilmu qira’at, argumen skeptis Jeffery terhadap al-Fatihah terbantahkan. Ditambah lagi, Jeffery tidak mampu membuktikan keberadaan variasi surat al-Fatihah yang dia yakini. Kata Kunci: al-Fatihah; al-Qur’an; Kontroversi; Kritik; Muslim
IMPLEMENTASI MA’NA CUM MAGHZA TERHADAP MAKNA GULUL DALAM AL-QUR’AN (Interpretasi QS. Ali Imran: 161)
Authors: Asna Hanifatul 
Published: April 2020

AbstractThe Qur’an as the first source of reference for Muslims who are always relevant in every time and place, must have an informative meaning. It can undergo meaningful transformation in line with changing times. In the time of the Prophet, the word gulūl was understood by taking war booty before it was distributed. Wherwas current context war like during the time of the Prophet is no longer happening, it is necessary to re-interpret what the meaning of gulūl along with how to contextualize the use of the word in the Qur’an especially in the QS. Ali Imrān: 161. By using the Hermeneutic approach, this specifically borrows Abdullah Saeed’s Contextual theory in understanding the meaning of gulūl in the Qur’an especially QS. Ali Imrān; 161, then an interpretation can be produced between them; first, in the initial context gulūl was a form of betrayal, like taking the spoils of war. Secondly, in the current context gulūl can be understood with broad meanings of betrayal such as being unsafe and taking things secretly even though he has the right part of the thing. This can be described as corruption both material and time. The essence of Q.S Ali Imrān: 161, it can be interpreted a leader is not possible and should not do gulūl (acts of cheating). This verse shows the existence of protection values. AbstrakAl-Qur’an sebagai sumber rujukan pertama umat muslim yang selalu relevan dalam setiap waktu dan tempat, pastilah mempunyai makna informatif dan dapat mengalami transformasi pemaknaan seiring dengan perubahan zaman. Pada zaman Nabi, kata gulūl dipahami dengan mengambil harta rampasan perang sebelum dibagikan. Sedangkan pada konteks sekarang, perang seperti pada masa Nabi sudah tidak lagi terjadi. Oleh karenanya, perlu adanya interpretasi ulang apa makna gulūl serta bagaimana kontekstualisasi penggunaan kata tersebut dalam al-Qur’an khususnya pada QS. Ali Imrān: 161. Dengan menggunakan pendekatan Hermeneutika, khususnya meminjam teori Kontekstual Abdullah Saeed dalam memahami makna gulūl dalam al-Qur’an khususnya QS. Ali Imrān ayat 161, maka dapat dihasilkan interpretasi di antaranya; pertama, dalam konteks awal gulūl merupakan bentuk pengkhianatan, seperti mengambil harta rampasan perang. Kedua, dalam konteks saat ini gulūl dapat dipahami dengan makna khianat secara luas seperti tidak amanah dan mengambil sesuatu secara sembunyi-sembunyi meskipun dia mempunyai bagian hak dari benda tersebut. Hal ini dapat digambarkan seperti korupsi secara materi maupun waktu. Adapun intisari QS. Ali Imrān: 161, dapat diartikan seorang pemimpin tidak mungkin dan tidak seharusnya melakukakan gulūl (tindak kecurangan). Ayat ini menunjukkan adanya nilai-nilai perlindungan/protectional values.Kata Kunci: Gulūl, Hermeneutika, Kontekstual, QS. Ali Imrān: 161