bluuebunny/crossref_metadata_2025 huggingface dataset:
PRINCIPAL LEADERSHIP IN DEVELOPING AL-QUR'AN LEARNING MANAGEMENT
Authors: Salim Salim , Hasanah Enung
Published: April 2021

This study aims to determine the implementation of the Principal's leadership in developing Al-Qur'an learning management that has been implemented in SMP Negeri 8 Yogyakarta City. The output of learning the Qur'an which makes the majority of students of SMP Negeri 8 Yogyakarta City able to read the Qur'an well, even some students are able to memorize the Qur'an up to 2 juz is something that is interesting to study. This research uses a qualitative approach. Participants in this study were the Principal, Islamic religious teachers and teachers of the Qur'an. The techniques used in data collection were done by using interviews, observation and documentation. Data analysis was carried out in two stages; (1) research in the field, the analysis results in this first stage are in the form of temporary conclusions obtained from the results of observations and document studies using the inductive analysis model. The conclusion data obtained in the first stage of analysis is then developed in the second stage of analysis, namely analysis after data collection. At this stage, all data were analyzed inductively by using descriptive qualitative research. The conclusion of this study shows that the Principal can develop the management of learning the Qur'an well.
DETERMINATION OF IMAGE INTENSIFIER VIEW FIELD PURITY LEVEL
Authors:   Siberian State University of Geosystems and Technologies, Nikulin Dmitry M. , Raychert Valery A. ,   Siberian State University of Geosystems and Technologies
Published: April 2021

The article offers a method for determining image intensifier working view field purity. In order to solve this problem, it is suggested to automate control under view field purity by using application program package. The automatic control is supposed to get an image of working view field and carry out its further processing by computer means. It allows to determine a permissible zonal amount of points and spots, as well as sizes and locations of light and dark defects. The article presents an algo-rithm for image intensifier view field purity level control developed by the authors simplifies control by means of measuring instruments and auxiliaries provided by GOST. It shows the results of field-emission bright point defect control and the view field purity level within the working field of a pho-tocathode using a source of light.
Валентина Крапівіна та виставка «Скарби Південної України» у Миколаєві
Authors: Vitryk Iryna
Published: April 2021

У публікації висвітлюються етапи підготовки й особливості проведення масштабного виставкового проекту «Скарби Південної України» (1997 р.) у Миколаївському обласному художньому музеї, який було створено на основі колекцій Наукових фондів та Археологічного музею Інституту археології НАН України й Історико-археологічного заповідника «Ольвія». Проект відбувся завдяки спільним зусиллям Валентини Володимирівни Крапівіної та Валерія Анатолійовича Карнауха.
De Titulis Olbiae Ponticae Et Viciniis. I
Authors: Shelov-Kovedyaev Fedor
Published: April 2021

Стаття присвячена розгляду низки епіграфічних документів, опублікованих різними авторами в останні десятиліття. Не атрибутовані А.І. Іванчиком в IOSPE I3 40 два фрагменти фронтону з написом являють собою початок декрету, який вотований розташованим на півострові Халкідіка полісом Сана на честь громадянина Ніконію. Видані В.П. Алексєєвим і С.Ю. Саприкіним, як ніконійські, три мармурових уламки належать: перший – декрету Ольвії, другий – надгробку боспорянки, третій – херсонеському декрету. Опубліковане тими ж авторами графітто на чорнолаковому черепку є листом Геракліда, який відноситься до часу перебування у Херсонесі трупи акторів. Непрофесійно введена в обіг О.В. Бєлоусовим свинцева пластина, у виправленому вигляді, – ольвійське закляття, відмічене яскравими ознаками навмисного спотворення імен недругів того, хто писав листа.
Аттична чорнолакова кераміка з експозиції Миколаївського обласного краєзнавчого музею «Старофлотські казарми»
Authors: Chechulina Iryna
Published: April 2021

Аттична чорнолакова кераміка завжди привертала увагу дослідників своїми витонченими формами, вишуканим орнаментуванням та якістю покриття. Хоча ця категорія матеріалу належить до парадного столового посуду, знахідки його доволі чисельні. Цей посуд ввозився з Аттики e регіон Північного Причорномор’я протягом століть, і за цей час він став однією з найважливіших категорії імпорту до регіону. Колекція чорнолакового посуду, що експонується у Миколаївському обласному краєзнавчому музеї є репрезентативною, має як популярні, так і унікальні форми. Саме тому аналіз колекції представляє неабиякий інтерес і практичне значення для подальшої роботи з цією категорією посуду.
Salt Removal by Combining a Permanent Skip Furrow Irrigation and Salt Removal Sheet
Authors: Onishi Junya , Paluashova Gaukhar K. , Shirokova Yulia I. , Fujimaki Haruyuki
Published: April 2021

Skip furrow irrigation (SFI) can save water by irrigating every alternate furrow. Usually, irrigated furrows are alternated at each irrigation event under SFI. If irrigated furrows are fixed (permanent SFI, PSFI), more water may be saved by reducing the wetting area, and salts may accumulate on the dry side of the ridge. Salt removal sheet, a method of collecting salts on the sheet laid on the soil surface utilizing high evaporation demand in drylands, may be an efficient measure for removal of accumulated salt under PSFI. We evaluated salinity movement and water saving under PSFI through a field experiment in Uzbekistan. In addition, a salt removal sheet was applied to the shoulder of the ridge on the drier side under PSFI to evaluate its potential in removing salt from the soil with the practice. The results showed that salts tend to accumulate on the dry side of the ridge, and the amount of irrigation water was halved without a large crop yield reduction. The PSFI + Sheet was able to catch 6.4% of salts in the top 10 cm soil layer.
Short-Term Inhalation of Ultrafine Zinc Particles Could Alleviate Cardiac Dysfunctions in Rats of Myocardial Infarction
Authors: Li Li , Niu Pei , Wang Xuan , Bing Fangbo , Tan Wenchang , Huo Yunlong
Published: April 2021

It is not clear for inhalation of ultrafine metal particles in air pollution to impair human health. In the study, we aimed to investigate whether short-term (4 weeks) inhalation of ultrafine zinc particles could deteriorate the cardiac and hemodynamic functions in rats of myocardial infarction (MI). MI was induced in Wistar rats through coronary artery ligation surgery and given an inhalation of ultrafine zinc particles for 4 weeks (post-MI 4 weeks, 4 days per week, and 4 h per day). Cardiac strain and strain rate were quantified by the speckle tracking echocardiography. The pressure and flow wave were recorded in the carotid artery and analyzed by using the Womersley model. Myocardial infarction resulted in the LV wall thinning, LV cavity dilation, remarkable decrease of ejection fraction, dp/dt Max, −dp/dt Min, myocardial strain and strain rates, and increased LV end-diastolic pressure, as well as impaired hemodynamic environment. The short-term inhalation of ultrafine zinc particles significantly alleviated cardiac and hemodynamic dysfunctions, which could protect from the MI-induced myocardial and hemodynamic impairments albeit it is unknown for the long-term inhalation.
Nitrite and Nitrate Levels in Follicular Fluid From Human Oocyte Donors Are Related to Ovarian Response and Embryo Quality
Authors: Staicu Florentin-Daniel , Canha-Gouveia Analuce , Soriano-Úbeda Cristina , Martínez-Soto Juan Carlos , Adoamnei Evdochia , Chavarro Jorge E. , Matás Carmen
Published: April 2021

Nitric oxide, a key regulatory molecule in the follicular fluid, has been suggested as a possible biomarker to predict ovarian response in stimulated cycles and the potential of the retrieved oocytes for developing high-quality embryos. Nevertheless, a consensus on whether or not nitric oxide can help in this context has not been reached. We simultaneously measured the oxidation products of nitric oxide, nitrite, and nitrate, via high-performance liquid chromatography (HPLC)-UV in follicular fluid samples from 72 oocyte donors. We found no associations of follicular fluid nitrite, nitrate, total nitric oxide, or nitrate/nitrite ratio with total or metaphase II (MII) oocyte yield. However, nitrite and nitrate levels were related to the yield of MII oocytes when this outcome was expressed as a proportion of all oocytes retrieved. The adjusted MII proportion in the lowest and highest nitrite levels were 68% (58–77%) and 79% (70–85%), respectively (p, linear trend = 0.02), whereas the adjusted MII proportion in extreme tertiles of nitrate levels were 79% (70–85%) and 68% (57–77%) (p, linear trend = 0.03). In addition, nitrate levels showed a suggestive inverse correlation with embryos with maximum or high potential of implantation (p = 0.07). These results suggest that the follicular fluid concentrations of nitrite and nitrate may be a useful tool in predicting how healthy oocyte donors respond to superovulation and the implantation potential of the embryos produced from their oocytes.
Phospho-Site Mutations in Transcription Factor Suppressor of Hairless Impact Notch Signaling Activity During Hematopoiesis in Drosophila
Authors: Frankenreiter Lisa , Gahr Bernd M. , Schmid Hannes , Zimmermann Mirjam , Deichsel Sebastian , Hoffmeister Philipp , Turkiewicz Aleksandra , Borggrefe Tilman , Oswald Franz , Nagel Anja C.
Published: April 2021

The highly conserved Notch signaling pathway controls a multitude of developmental processes including hematopoiesis. Here, we provide evidence for a novel mechanism of tissue-specific Notch regulation involving phosphorylation of CSL transcription factors within the DNA-binding domain. Earlier we found that a phospho-mimetic mutation of theDrosophilaCSL ortholog Suppressor of Hairless [Su(H)] at Ser269impedes DNA-binding. By genome-engineering, we now introduced phospho-specificSu(H)mutants at the endogenousSu(H)locus, encoding either a phospho-deficient [Su(H)S269A] or a phospho-mimetic [Su(H)S269D] isoform.Su(H)S269Dmutants were defective of Notch activity in all analyzed tissues, consistent with impaired DNA-binding. In contrast, the phospho-deficientSu(H)S269Amutant did not generally augment Notch activity, but rather specifically in several aspects of blood cell development. Unexpectedly, this process was independent of the corepressorHairlessacting otherwise as a general Notch antagonist inDrosophila. This finding is in agreement with a novel mode of Notch regulation by posttranslational modification of Su(H) in the context of hematopoiesis. Importantly, our studies of the mammalian CSL ortholog (RBPJ/CBF1) emphasize a potential conservation of this regulatory mechanism: phospho-mimetic RBPJS221Dwas dysfunctional in both the fly as well as two human cell culture models, whereas phospho-deficient RBPJS221Arather gained activity during fly hematopoiesis. Thus, dynamic phosphorylation of CSL-proteins within the DNA-binding domain provides a novel means to fine-tune Notch signal transduction in a context-dependent manner.
Cucurbituril Ameliorates Liver Damage Induced by Microcystis aeruginosa in a Mouse Model
Authors: Saleh Na'il , Al-Jassabi Saad , Eid Ali H. , Nau Werner M.
Published: April 2021

Microcystis aeruginosa is a cyanobacterium that produces a variety of cyclic heptapeptide toxins in freshwater. The protective effects of the macromolecular container cucurbit[7]uril (CB7) were evaluated using mouse models of cyanotoxin-induced liver damage. Biochemical analysis of liver function was performed to gauge the extent of liver damage after exposure to cyanobacterial crude extract [CCE; LD50 = 35 mg/kg body weight; intraperitoneal (i.p.)] in the absence or presence of CB7 (35 mg/kg body weight, i.p.). CCE injection resulted in liver enlargement, potentiated the activities of alanine aminotransferase (ALT) and glutathione S-transferase (GST), increased lipid peroxidation (LPO), and reduced protein phosphatase 1 (PP1) activity. CCE-induced liver enlargement, ALT and GST activities, and LPO were significantly reduced when CB7 was coadministered. Moreover, the CCE-induced decline of PP1 activity was also ameliorated in the presence of CB7. Treatment with CB7 alone did not affect liver function, which exhibited a dose tolerance of 100 mg/kg body wt. Overall, our results illustrated that the addition of CB7 significantly reduced CCE-induced hepatotoxicity (P < 0.05).
iTIME.219: An Immortalized KSHV Infected Endothelial Cell Line Inducible by a KSHV-Specific Stimulus to Transition From Latency to Lytic Replication and Infectious Virus Release
Authors: Dollery Stephen J. , Maldonado Tania D. , Brenner Eric A. , Berger Edward A.
Published: April 2021

Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) is the causative agent of Kaposi’s sarcoma and two B cell lymphoproliferative disorders: primary effusion lymphoma and KSHV-associated multicentric Castleman’s disease. These distinct pathologies involve different infected cell types. In Kaposi’s sarcoma, the virus is harbored in spindle-like tumor cells of endothelial origin, in contrast with the two pathologies of B cells. These distinctions highlight the importance of elucidating potential differences in the mechanisms of infection for these alternate target cell types and in the properties of virus generated from each. To date there is no available chronically KSHV-infected cell line of endothelial phenotype that can be activated by the viral lytic switch protein to transition from latency to lytic replication and production of infectious virus. To advance these efforts, we engineered a novel KSHV chronically infected derivative of TIME (telomerase immortalized endothelial) cells harboring a previously reported recombinant virus (rKSHV.219) and the viral replication and transcription activator (RTA) gene under the control of a doxycycline-inducible system. The resulting cells (designated iTIME.219) maintained latent virus as indicated by expression of constitutively expressed (eGFP) but not a lytic phase (RFP) reporter gene and can be sustained under long term selection. When exposed to either sodium butyrate or doxycycline, the cells were activated to lytic replication as evidenced by the expression of RFP and KSHV lytic genes and release of large quantities of infectious virus. The identity of the iTIME.219 cells was confirmed both phenotypically (specific antigen expression) and genetically (short tandem repeat analysis), and cell stability was maintained following repeated serial passage. These results suggest the potential utility of the iTime.219 cells in future studies of the KSHV replication in endothelial cells, properties of virus generated from this biologically relevant cell type and mechanisms underlying KSHV tropism and pathogenesis.
Plasmodium yoelii Erythrocyte Binding Like Protein Interacts With Basigin, an Erythrocyte Surface Protein
Authors: Yuguchi Takaaki , Kanoi Bernard N. , Nagaoka Hikaru , Miura Toyokazu , Ito Daisuke , Takeda Hiroyuki , Tsuboi Takafumi , Takashima Eizo , Otsuki Hitoshi
Published: April 2021

Erythrocyte recognition and invasion is critical for the intra-erythrocytic development of Plasmodium spp. parasites. The multistep invasion process involves specific interactions between parasite ligands and erythrocyte receptors. Erythrocyte-binding-like (EBL) proteins, type I integral transmembrane proteins released from the merozoite micronemes, are known to play an important role in the initiation and formation of tight junctions between the apical end of the merozoite and the erythrocyte surface. In Plasmodium yoelii EBL (PyEBL), a single amino acid substitution in the putative Duffy binding domain dramatically changes parasite growth rate and virulence. This suggests that PyEBL is important for modulating the virulence of P. yoelii parasites. Based on these observations, we sought to elucidate the receptor of PyEBL that mediates its role as an invasion ligand. Using the eukaryotic wheat germ cell-free system, we systematically developed and screened a library of mouse erythrocyte proteins against native PyEBL using AlphaScreen technology. We report that PyEBL specifically interacts with basigin, an erythrocyte surface protein. We further confirmed that the N-terminal cysteine-rich Duffy binding-like region (EBL region 2), is responsible for the interaction, and that the binding is not affected by the C351Y mutation, which was previously shown to modulate virulence of P. yoelii. The identification of basigin as the putative PyEBL receptor offers new insights into the role of this molecule and provides an important base for in-depth studies towards developing novel interventions against malaria.
Are Women a Missing Audience for Science on YouTube? An Exploratory Study
Authors: Landrum Asheley R.
Published: April 2021

Educational science programming on digital video platforms such as YouTube wrestle with sometimes significant gender disparities in viewership. When men engage with science and technology content on digital platforms more than women, gender gaps in the understanding of, engagement with, and interest in STEM may intensify. Therefore, there is a critical need for research aiming to aid in our understanding of these gender differences. This study provides evidence that the gender gaps may exist not in the use of YouTube itself, but in the engagement with science and technology content on the platform. Furthermore, there are gender differences in the reasons for engaging with such content, with women, perhaps, more motivated by instrumental purposes than to satisfy their science curiosity.
The Long-Term Impact of Bariatric Surgery on Development of Atrial Fibrillation and Cardiovascular Events in Obese Patients: An Historical Cohort Study
Authors: Yuan Hongtao , Medina-Inojosa Jose R. , Lopez-Jimenez Francisco , Miranda William R. , Collazo-Clavell Maria L. , Sarr Michael G. , Chamberlain Alanna M. , Hodge David O. , Bailey Kent R. , Wang Yutang , Chen Yundai , Cha Yong-Mei
Published: April 2021

Objective: To determine whether early Roux-en-Y gastric bypass surgery (RYGB) reduces the risk of Major adverse cardiovascular events (MACE) in patients with obesity.

Patients and Methods: We conducted a study of patients with class II and III obesity [body mass index (BMI) > 35 kg/m2] from Olmsted County, Minnesota, who underwent obesity clinic consultation between the years 1993–2012, and had either RYGB surgery within 1 year (RYGB-1Y group), or medically managed (No-RYGB group). The composite endpoint of MACE (all-cause mortality, stroke, heart failure admission and acute myocardial infarction) was the primary endpoint, with new-onset AF as the secondary endpoint.

Results: Of the 1,009 study patients, 308 had RYGB-1Y and 701 were medically managed (No-RYGB). Overall, the age was 44.0 ± 12.4 (mean ± SD) years; BMI was 45.0 ± 6.8 kg/m2. The RYGB-1Y group had a lower rate of MACE (adjusted hazard ratio (HR), 0.62; 95% CI, 0.44–0.88; P = 0.008) and lower mortality (adjusted HR, 0.51; 95% CI, 0.26–0.96; P = 0.04) than the No-RYGB group. The RYGB-1Y surgery was not associated with lower AF occurrence (HR, 0.66; 95% CI, 0.40–1.10; P = 0.11).

Conclusion: An early RYGB approach for BMI reduction was associated with lower rates of MACE.
Downregulation of Cullin 3 Ligase Signaling Pathways Contributes to Hypertension in Preeclampsia
Authors: Zhang Ya , Jiang Gengru , Zhang Chong
Published: April 2021

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality; however, its etiology and pathophysiology remain obscure. PE is initiated by inadequate spiral artery remodeling and subsequent placental ischemia/hypoxia, which stimulates release of bioactive factors into maternal circulation, leading to hypertension and renal damage.

Methods and Results: Abundance of key components of cullin 3-ring ubiquitin ligase (CRL3), including cullin 3 (CUL3) and its neddylated modification, and adaptors including Kelch-like 2 (KLHL2) and Rho-related BTB domain containing protein 1 was all decreased in spiral arteries and placentas of PE patients. Similar changes were found in aortic tissues and renal distal tubules of pregnant mice treated with Nω-nitro-l-arginine methyl ester hydrochloride. The downregulation of CRL3 function led to accumulation of with-no-lysine kinases, phosphodiesterase 5, and RhoA in vessels and renal distal tubules, which promoted vasoconstriction and Na–Cl cotransporter activation in the distal convoluted tubule (DCT), as well as vascular and DCT structure remodeling. Proton pump inhibitor esomeprazole partially restored CRL3 function. In vitro studies have shown that increased abundance of JAB1, a component of the COP9 signalosome, inhibited CUL3 neddylation and promoted the expression of hypoxia-inducible factor 1α, which downregulated peroxisome proliferator–activated receptor γ and further promoted CUL3 inactivation. KLHL3/2 was degraded by increased autophagy.

Conclusion: These findings support that the downregulation of CRL3 function disrupts the balance of vasoconstriction and vasodilation and aggravates excess reabsorption of sodium in PE.
Effects of Grain Size Distribution on Landslide Dam Breaching—Insights From Recent Cases in China
Authors: Mei Shengyao , Chen Shengshui , Zhong Qiming , Shan Yibo
Published: April 2021

Landslide dams are common geological features in mountainous areas, which may have serious consequences due to sudden breaching of the dam. An effective emergency response requires rapid and accurate forecasts regarding the landslide dam breach process. However, most existing models use physical, mechanical, and erosion properties of the mean or characteristic grain sizes to represent the landslide deposits. The grain size distribution and variations in soil erodibility with the depth in the landslide dam are not considered, resulting in an incorrect estimation of the breach flow hydrograph. In this paper, a simplified landslide dam classification is presented based on the formation mechanism and grain size distribution of landslide dams. Additionally, the influences of grain size distribution on the residual dam height and breach process of landslide dams are analyzed. This paper proposes a numerical method to rapidly obtain the breach hydrographs and breach morphology evolution of landslide dams. The new method can quickly classify landslide dams according to geological survey data and predict the landslide dam breach process. Three types of representative landslide dams in China are simulated to validate the proposed method. The breach flow discharge is significantly affected by spillway excavation. This contribution can provide rapid prediction of the landslide dam breach process and can be used for the emergency response planning before dam breaching.
The Use of Virtual Reality in Pharmacy Education in Hong Kong: Lessons Learnt
Authors: Li Joyce T. S. , Ng Enoch E. N. , Lee Vivian W. Y.
Published: April 2021

Virtual reality (VR) refers to an artificial environment which is experienced through sensory stimuli (such as sights and sounds) provided by a computer and in which one's actions partially determine what happens in the environment (Merriam-Webster.com Dictionary, Merriam-Webster, 2020). In recent years, VR is increasingly used in different fields, and its role in medical practice is expanding quickly (Darekar et al., 2015; Chirico et al., 2016). One important feature of VR technology is its reproducibility (Ramnanan and Pound, 2017; Cao and Cerfolio, 2019). Practitioners can rehearse a procedure on a virtual patient or simulated tissue as many times as they wish before performing it on real patients. In medical education, VR allows students to see through body tissues and visualize the underneath areas (Cao and Cerfolio, 2019; Yu et al., 2019; Siyar et al., 2020). Practice experience is an essential element in pharmacy education (Teramachi et al., 2018). It is effective in boosting students' communication skills and problem-solving skills, which are both crucial for the provision of patient-centered care in a team-based approach (Lang et al., 2019). Unfortunately, actual practice experience can be limited by various factors, such as the policies at attachment sites, patients' preference, and availability of teaching staff (Wartman, 2019; Shrestha et al., 2020). Therefore, institutions are looking for alternative channels for students to practice their skills. One strategy is to adopt simulated patient cases (Kurup et al., 2017; Willemsen-Dunlap et al., 2018; Silva et al., 2019). In this paper, we share our experience of using VR learning tools in pharmacy education in a Hong Kong university. We will discuss the opportunities, challenges, and suggestions for future development of VR in pharmacy education.
Preterm Birth and Birth Weight and the Risk of Type 1 Diabetes in Chinese Children
Authors: Huang Ke , Si Shuting , Chen Ruimin , Wang Chunlin , Chen Shaoke , Liang Yan , Yao Hui , Zheng Rongxiu , Liu Fang , Cao Binyan , Su Zhe , Mireguli Maimaiti , Luo Feihong , Li Pin , Du Hongwei , Zhu Min , Yang Yu , Cui Lanwei , Yu Yunxian , Fu Junfen
Published: April 2021

Aims

Findings from previous studies about the association of preterm birth as well as birth weight with the risk of T1DM were still inconsistent. We aimed to further clarify these associations based on Chinese children and explore the role of gender therein.

Methods

A nationwide multicenter and population-based large cross-sectional study was conducted in China from 2017 to 2019. Children aged between 3 and 18 years old with complete information were included in this analysis. Multiple Poisson regression models were used for evaluating the associations of birth weight as well as preterm birth with T1DM in children.

Results

Out of 181,786 children, 82 childhood T1DM cases were identified from questionnaire survey. Children with preterm birth (<37 weeks) had higher risk of type 1 diabetes (OR: 3.17, 95%CI: 1.76-5.71). Children born with high birth weight (≥4,000g) had no statistically significant risk of T1DM (OR:1.71, 95%CI: 0.90-3.22). However, children’s gender might modify the effect of high birth weight on T1DM (girls: OR: 3.15, 95%CI: 1.33-7.47; boys: OR: 0.99, 95%CI: 0.38-2.55, p for interaction=0.065). In addition, children with low birth weight were not associated with T1DM (OR: 0.70, 95%CI: 0.24-2.08). The findings from matched data had the similar trend.

Conclusions

In China mainland, preterm birth increased the risk of childhood T1DM, but high birth weight only affected girls. Therefore, early prevention of T1DM may start with prenatal care to avoid adverse birth outcomes and more attention should be paid to children with preterm birth and girls with high birth weight after birth.
In-Silico Study of Immune System Associated Genes in Case of Type-2 Diabetes With Insulin Action and Resistance, and/or Obesity
Authors: Eldakhakhny Basmah Medhat , Al Sadoun Hadeel , Choudhry Hani , Mobashir Mohammad
Published: April 2021

Type-2 diabetes and obesity are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches and are among the most frequent and highly complex and heterogeneous in nature. Based on epidemiological evidence, it is known that the patients suffering from obesity are considered to be at a significantly higher risk of type-2 diabetes. There are several pieces of evidence that support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of type-2 diabetes. Multi-level unwanted alterations such as (epi-) genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major sources that promote several complex diseases, and such a heterogeneous level of complexity is considered as a major barrier in the development of therapeutics. With so many known challenges, it is critical to understand the relationships and the shared causes between type-2 diabetes and obesity, and these are difficult to unravel and understand. For this purpose, we have selected publicly available datasets of gene expression for obesity and type-2 diabetes, have unraveled the genes and the pathways associated with the immune system, and have also focused on the T-cell signaling pathway and its components. We have applied a simplified computational approach to understanding differential gene expression and patterns and the enriched pathways for obesity and type-2 diabetes. Furthermore, we have also analyzed genes by using network-level understanding. In the analysis, we observe that there are fewer genes that are commonly differentially expressed while a comparatively higher number of pathways are shared between them. There are only 4 pathways that are associated with the immune system in case of obesity and 10 immune-associated pathways in case of type-2 diabetes, and, among them, only 2 pathways are commonly altered. Furthermore, we have presented SPNS1, PTPN6, CD247, FOS, and PIK3R5 as the overexpressed genes, which are the direct components of TCR signaling.
Triple-Mode Grid-Balancing Plants via Biomass Gasification and Reversible Solid-Oxide Cell Stack: Economic Feasibility Evaluation via Plant Capital-Cost Target
Authors: Zhang Yumeng , Wang Ningling , Li Chengzhou , Pérez-Fortes Mar , Duan Liqiang , Van herle Jan , Maréchal François , Lin Tzu-En , Wang Ligang , Yang Yongping
Published: April 2021

Electricity production and consumption must be balanced for the electrical grid. However, the rapidly growing intermittent power sources are now challenging the supply-demand balance, leading to large flexibility needs for grid management. The plant integrating biomass gasification and reversible solid-oxide cell stacks can be potential means of flexibility, which could flexibly switch among power generation, power storage, and power neutral modes. This paper investigates the economic feasibility of such grid-balancing plants, i.e., plant capital expenditure (CAPEX) target, via a systematic overall decomposition-based methodology for real geographical zones and flexibility-need scenarios. The plant CAPEX target (€/ref-stack) is defined as the maximum affordable investment cost for each reference stack (active cell area 5,120 cm2). The results show that, for a 5-year payback time, 5-year stack lifetime, and 40 €/MWh grid balancing price, the plant concept with 10–100 MWth gasifier has high economic potential with target reaching 17,000 €/ref-stack; however, the plant concept with 100–1,000 MWth gasifier has a limited commercialization potential with the target reaching below 1,000 €/ref-stack due to high biomass supply costs. Considering the sale of chemical product, plant CAPEX target can reach up to 22,000 and 3,000–12,000 €/ref-stack for the plants with 10–100 and 100–1,000 MWth, respectively. The plant CAPEX target is decreased by increasing the total capacities of all plants deployed since more and more capacities will be put into power neutral mode (isolated from the electrical grid) via the coordination of multiple plants. The plant CAPEX target can be further increased by higher grid up/down-regulating price and longer payback years.
Changes in Urban Gas-Phase Persistent Organic Pollutants During the COVID-19 Lockdown in Barcelona
Authors: Prats Raimon M. , van Drooge Barend L. , Fernández Pilar , Marco Esther , Grimalt Joan O.
Published: April 2021

The composition of polycyclic aromatic hydrocarbons (PAHs), polychlorobiphenyls (PCBs), hexachlorobenzene (HCB), pentachlorobenzene (PeCB), and organophosphate flame retardants (OPFRs) present in the gas-phase fraction of the atmosphere of Barcelona was analyzed during the SARS-CoV-2 coronavirus disease (COVID-19) lockdown and prior to this period. The changes in daily concentrations of CO, NO, NO2, O3 and particulate matter smaller than 10 μm (PM10) were considered for comparison. Bayesian analysis considering serial dependencies and seasonality showed statistically significant decreases of CO, NO, NO2, and PM10 (between −28 and −76%) and O3 increases (+45%) during lockdown. However, the lockdown concentration decreases of PeCB (−90.5%, from 8.5 to 0.8 pg m–3), HCB (−79%, 25.5–5.4 pg m–3) and some PAHs, such as benz[a]anthracene (−87%, 120–17 pg m–3) and pyrene (−81%, 3,500–680 pg m–3), were even stronger. The PAH depletion ranged between −68 and −87% that could be primarily associated with the strong reduction of traffic mobility during this period (−80%). Besides traffic reduction, the observed air quality improvements could be related to lower generation of solid urban residues (−25%) and the subsequent decrease of urban waste incineration (between −25 and −28%). Tributyl phosphate also showed a reduction in concentration during lockdown but the other OPFRs were seemingly not affected by this restriction, possibly as a result of the uniform release from the emission sources, e.g., construction material, industrial applications, and household products.
Geographical Information System Applied to a Biological System: Pelvic Girdle Ontogeny as a Morphoscape
Authors: Abdala Virginia , Cristobal Luciana , Solíz Mónica C. , Dos Santos Daniel A.
Published: April 2021

Geographic Information System (GIS) is a system that captures, stores, manipulates, analyzes, manages, and presents spatial or geographical data. As this technological environment has been created to deal with space problems, it is perfectly adaptable to solve these type of issues in the context of vertebrate comparative morphology. The pectoral and pelvic girdles are key structures that relate the axial skeleton with the limbs in tetrapods. Owed to their importance in locomotion, the morphology, development, and morphogenesis of these structures have been widely studied. The complexity of the structures and tissues implied in the development of the girdles make quantitative approaches extremely difficult. The use of GIS technology provides a visual interpretation of the histological data, a general quantitative assessment of the processes taking place during the ontogeny of any structure, and would allow collecting information about the changes in the surface occupied by the different tissues across the ontogenetic processes of any vertebrate taxa. GIS technology applied to map morphological structures would be a main contribution to the construction of the vertebrate ontologies, as it would facilitate the identification and location of the structures. GIS technology would allow also us to construct a shared database of histological quantitative changes across the ontogeny in any vertebrate. The main objective of this study is to use GIS technology for spatial analysis of histological samples such as these of the pelvic girdle using histological cuts of anurans and chicken, allowing thus to construct a morphoscape, analogous to a landscape. This is the first attempt to apply GIS tools to ontogenetic series to infer biological properties of the spatial analysis in the context of comparative biology. More frequent use of this technology would contribute to obtaining more profitable and biologically informative results.
Only Females Oviposit: Chemical Discrimination of Adult Stink Bug Sex by the Egg Parasitoid Trissolcus japonicus
Authors: Arif Mokhtar Abdulsattar , Alınç Tuğcan , Guarino Salvatore , Colazza Stefano , Cusumano Antonino , Peri Ezio
Published: April 2021

Egg parasitoids foraging for suitable hosts scattered in the environment rely mainly on chemical cues. Elucidating the chemical ecology of natural enemies is important in the development of effective and successful strategies for conservation biological control. In this context, the host cuticular hydrocarbons, which are exploited by several species of egg parasitoids as contact kairomones, could be used to retain them by providing information about the presence and the sex of adults of the target species: sex is important because only females of the host species lay the eggs that can be subsequently utilized for parasitoid reproduction. However, the chemical basis of host sex discrimination in egg parasitoids is not well understood. We carried out behavioral and chemical bioassays to investigate the role played by contact chemical cues left by adults of the brown marmorated stink bug, Halyomorpha halys Stål, in host egg searching behavior and adult host sex discrimination by the egg parasitoid Trissolcus japonicus (Ashmead). A first set of bioassays showed that parasitoids spent more time exploring patches contaminated with chemicals associated with adult H. halys females compared with adult males. Similar responses were displayed by T. japonicus when hexane extracts of H. halys were tested suggesting that non-polar chemical compounds are involved in host sex discrimination. GC-MS analysis of hexane extracts revealed quantitative differences in the cuticular compounds of the two sexes, with 1-hexadecene (more abundant in males) being the most important component in determining these differences. Hexane extracts of H. halys females blended with synthetic 1-hexadecene significantly reduced the wasps’ arrestment responses compared to crude extracts.
Extracellular Vesicles Secreted by Mesenchymal Stromal Cells Exert Opposite Effects to Their Cells of Origin in Murine Sodium Dextran Sulfate-Induced Colitis
Authors: Tolomeo Anna Maria , Castagliuolo Ignazio , Piccoli Martina , Grassi Michele , Magarotto Fabio , De Lazzari Giada , Malvicini Ricardo , Caicci Federico , Franzin Chiara , Scarpa Melania , Macchi Veronica , De Caro Raffaele , Angriman Imerio , Viola Antonella , Porzionato Andrea , Pozzobon Michela , Muraca Maurizio
Published: April 2021

Several reports have described a beneficial effect of Mesenchymal Stromal Cells (MSCs) and of their secreted extracellular vesicles (EVs) in mice with experimental colitis. However, the effects of the two treatments have not been thoroughly compared in this model. Here, we compared the effects of MSCs and of MSC-EV administration in mice with colitis induced by dextran sulfate sodium (DSS). Since cytokine conditioning was reported to enhance the immune modulatory activity of MSCs, the cells were kept either under standard culture conditions (naïve, nMSCs) or primed with a cocktail of pro-inflammatory cytokines, including IL1β, IL6 and TNFα (induced, iMSCs). In our experimental conditions, nMSCs and iMSCs administration resulted in both clinical and histological worsening and was associated with pro-inflammatory polarization of intestinal macrophages. However, mice treated with iEVs showed clinico-pathological improvement, decreased intestinal fibrosis and angiogenesis and a striking increase in intestinal expression of Mucin 5ac, suggesting improved epithelial function. Moreover, treatment with iEVs resulted in the polarization of intestinal macrophages towards and anti-inflammatory phenotype and in an increased Treg/Teff ratio at the level of the intestinal lymph node. Collectively, these data confirm that MSCs can behave either as anti- or as pro-inflammatory agents depending on the host environment. In contrast, EVs showed a beneficial effect, suggesting a more predictable behavior, a safer therapeutic profile and a higher therapeutic efficacy with respect to their cells of origin.
Harnessing Tolerogenic Histone Peptide Epitopes From Nucleosomes for Selective Down-Regulation of Pathogenic Autoimmune Response in Lupus (Past, Present, and Future)
Authors: Datta Syamal K.
Published: April 2021

Autoantigen-directed tolerance can be induced by certain nucleosomal histone peptide epitope/s in nanomolar dosage leading to sustained remission of disease in mice withspontaneousSLE. By contrast, lupus isacceleratedby administration of intact (whole) histones, or whole nucleosomes in microparticles from apoptotic cells, or by post-translationally acetylated histone-peptides. Low-dose therapy with the histone-peptide epitopes simultaneously induces TGFβ and inhibits IL-6 production by DCin vivo, especially pDC, which then induce CD4+CD25+ Treg and CD8+ Treg cells that suppress pathogenic autoimmune response. Both types of induced Treg cells are FoxP3+ and act by producing TGFβ at close cell-to-cell range. No anaphylactic adverse reactions, or generalized immunosuppression have been detected in mice injected with the peptides, because the epitopes are derived from evolutionarily conserved histones in the chromatin; and the peptides are expressed in the thymus during ontogeny, and their native sequences have not been altered. The peptide-induced Treg cells can block severe lupus on adoptive transfer reducing inflammatory cell reaction and infiltration in the kidney. InHumans, similar potent Treg cells are generated by the histone peptide epitopesin vitroinlupus patients’PBMC, inhibiting anti-dsDNA autoantibody and interferon production. Furthermore, the same types of Treg cells are generated in lupus patients who are in very long-term remission (2-8 years) after undergoing autologous hematopoietic stem cell transplantation. These Treg cells are not found in lupus patients treated conventionally into clinical remission (SLEDAI of 0); and consequently they still harbor pathogenic autoimmune cells, causing subclinical damage. Although antigen-specific therapy with pinpoint accuracy is suitable for straight-forward organ-specific autoimmune diseases, Systemic Lupus is much more complex. The histone peptide epitopes have unique tolerogenic properties for inhibiting Innate immune cells (DC), T cells and B cell populations that are both antigen-specifically and cross-reactively involved in the pathogenic autoimmune response in lupus. The histone peptide tolerance is a natural and non-toxic therapy suitable for treating early lupus, and also maintaining lupus patients after toxic drug therapy. The experimental steps, challenges and possible solutions for successful therapy with these peptide epitopes are discussed in this highly focused review on Systemic Lupus.
Bispecific NKG2D-CD3 and NKG2D-CD16 Fusion Proteins as Novel Treatment Option in Advanced Soft Tissue Sarcomas
Authors: Hagelstein Ilona , Lutz Martina S. , Schmidt Moritz , Heitmann Jonas S. , Malenke Elke , Zhou Yanjun , Clar Kim L. , Kopp Hans-Georg , Jung Gundram , Salih Helmut R. , Märklin Melanie , Hinterleitner Clemens
Published: April 2021

Soft tissue sarcoma (STS) constitutes a rare group of heterogeneous malignancies. Effective treatment options for most subtypes of STS are still limited. As a result, especially in metastatic disease, prognosis is still dismal. The ligands for the activating immunoreceptor NKG2D (NKG2DL) are commonly expressed in STS, but generally absent in healthy tissues. This provides the rationale for utilization of NKG2DL as targets for immunotherapeutic approaches. We here report on the preclinical characterization of bispecific fusion proteins (BFP) consisting of the extracellular domain of the NKG2D receptor fused to Fab-fragments directed against CD3 (NKG2D-CD3) or CD16 (NKG2D-CD16) for treatment of STS. After characterization of NKG2DL expression patterns on various STS cell lines, we demonstrated that both NKG2D-CD16 and NKG2D-CD3 induce profound T and NK cell reactivity as revealed by analysis of activation, degranulation and secretion of IFNγ as well as granule associated proteins, resulting in potent target cell lysis. In addition, the stimulatory capacity of the constructs to induce T and NK cell activation was analyzed in heavily pretreated STS patients and found to be comparable to healthy donors. Our results emphasize the potential of NKG2D-CD3 and NKG2D-CD16 BFP to target STS even in an advanced disease.
The Mechanism of Action of Antigen Processing Independent T Cell Epitopes Designed for Immunotherapy of Autoimmune Diseases
Authors: Shepard Ella R. , Wegner Anja , Hill Elaine V. , Burton Bronwen R. , Aerts Sarah , Schurgers Evelien , Hoedemaekers Brecht , Ng Sky T. H. , Streeter Heather B. , Jansson Lotta , Wraith David C.
Published: April 2021

Immunotherapy with antigen-processing independent T cell epitopes (apitopes) targeting autoreactive CD4+ T cells has translated to the clinic and been shown to modulate progression of both Graves’ disease and multiple sclerosis. The model apitope (Ac1-9[4Y]) renders antigen-specific T cells anergic while repeated administration induces both Tr1 and Foxp3+ regulatory cells. Here we address why CD4+ T cell epitopes should be designed as apitopes to induce tolerance and define the antigen presenting cells that they target in vivo. Furthermore, we reveal the impact of treatment with apitopes on CD4+ T cell signaling, the generation of IL-10-secreting regulatory cells and the systemic migration of these cells. Taken together these findings reveal how apitopes induce tolerance and thereby mediate antigen-specific immunotherapy of autoimmune diseases.
Independent Associations of Tumor Necrosis Factor-Alpha and Interleukin-1 Beta With Radiographic Emphysema in People Living With HIV
Authors: Thudium Rebekka F. , Ringheim Hedda , Ronit Andreas , Hoel Hedda , Benfield Thomas , Mocroft Amanda , Gerstoft Jan , Trøseid Marius , Borges Álvaro H. , Ostrowski Sisse R. , Vestbo Jørgen , Nielsen Susanne D.
Published: April 2021

Background

People living with HIV (PLWH) have increased systemic inflammation, and inflammation has been suggested to contribute to the pathogenesis of emphysema. We investigated whether elevated cytokine concentrations (interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), soluble CD14 (sCD14) and sCD163 were independently associated with radiographic emphysema in PLWH.

Methods

We included PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study without hepatitis B and C co-infection and with a plasma sample and a chest computed tomography scan available. Emphysema plus trace emphysema was defined as the percentage of low attenuation area under −950 Houndsfield Unit (%LAA-950) using a cut-off at 5%. Cytokine concentrations were measured by ELISA or Luminex immunoassays. An elevated cytokine concentration was defined as above the 75th percentile.

Results

Of 783 PLWH, 147 (18.8%) had emphysema. PLWH were predominantly male (86.0%) and 743 (94.9%) had undetectable viral replication. PLWH with emphysema had higher concentrations of TNFα (median (IQR): 8.2 (6.4-9.8) versus 7.1 (5.7-8.6) pg/ml, p<0.001), IL-1β (0.21 (0.1-0.4) versus 0.17 (0.1-0.3) pg/ml, p=0.004) and IL-6 (3.6 (2.6-4.9) versus 3.1 (2.0-4.3) pg/ml, p=0.023) than PLWH without. In a logistic regression model adjusted for age, sex, ethnicity, smoking status, BMI and CD4 nadir, elevated TNFα (adjusted odds ratio (aOR): 1.78 [95%CI: 1.14-2.76], p=0.011) and IL-1β (aOR: 1.81 [95%CI: 1.16-2.81], p=0.009) were independently associated with emphysema. The association between IL-1β and emphysema was modified by smoking (p-interaction=0.020) with a more pronounced association in never-smokers (aOR: 4.53 [95%CI: 2.05-9.98], p<0.001).

Conclusion

Two markers of systemic inflammation, TNFα and IL-1β, were independently associated with emphysema in PLWH and may contribute to the pathogenesis of emphysema. Importantly, the effect of IL-1β seems to be mediated through pathways that are independent of excessive smoking.

Clinical Trial Registration

clinicaltrials.gov, identifier NCT02382822.