Identification and Analysis of the Heparan Sulfate-Binding Domain and Cellular Factors Involved in the Entry of Human Endogenous Retrovirus K HERV-K (HML-2)

The human endogenous retroviruses (HERVs) are remnant elements of ancient retroviruses that infected the human ancestors' germline and integrated into their genome, and thereby passed down to their descendants in a mendelian fashion. The HERV-K (HML-2) family includes the most intact and complete sequences of human-specific elements with conserved ORF for most of their proteins and the ability to produce viral particles. The viral envelope protein (Env) promoted the initial endogenization activities and was shown to have a broad tropism. It mediates the viral entry through interaction with the cell surface heparan sulfates (HS). In this study, we demonstrated first that the specified receptor binding site (RBS) of HML-2 Env is not involved in binding HS. Further, to identify the involved domain in binding HS, we aligned the protein sequence of HML-2 Env to that of the mouse mammary tumor virus (MMTV). This way, we identified an HS-binding domain (HBD) at the N-terminus of the HML-2 Env between residues 216 and 236, corresponding to MMTV HBD. Generated mutations in all positively charged residues of this domain impaired binding to heparin-coated beads and blocked viral entry. Moreover, mutations in the residues R216, K219, and K223, were influential in HS binding and the viral entry. In the second and third parts of the study, we aimed to identify the cellular factors or requirements for HML-2 Env in its early entry pathway utilizing two approaches. In the first approach, we successfully generated a trimer fusion protein for HML-2 consisting of the SU subunit fused with fibritin, a trimerization domain derived from the bacteriophage T4. The trimer fusion protein bound HS similarly to the native Env. However, it did not block HML-2 Env viral entry. Using this trimer fusion protein, we specifically co-purified the Golgi membrane protein 73 (GP73) as a potential attachment factor for HML-2 Env. The second approach included using HML-2 Env pseudotyped viral particles in conducting a functional screening of a cDNA library for transmembrane proteins in a non-permissive cell line. Screening results identified six transmembrane proteins (TMEM9, C12ORF59, IL1RAP, PSCA, LETMD1, and MPEG1) involved in the entry pathway of HML-2 that confer the susceptibility to it. We also found that only IL1RAP and MPEG1 proteins confer susceptibility in a different non-permissive cell line. Our results affirmed the role of HS in the HML-2 Env attachments and identified the specific HBD involved. They also affirmed the contribution of another molecule(s) that serves as the receptor(s). In those lines seven transmembrane proteins involved in the entry pathway of HML-2 Env were identified.Die Humanen Endogenen Retroviren (HERVs) sind Restbestandteile alter Retroviren, die die Keimbahn der menschlichen Vorfahren infizierten und in ihr Genom integriert wurden. Sie werden seither nach den Mendelschen Regeln an ihre Nachkommen weitergegeben. Die HERV-K (HML-2)-Familie umfasst die intaktesten und vollständigsten Sequenzen mit konservierten Leserahmen für die meisten ihrer Proteine und die Fähigkeit, virale Partikel zu produzieren. Das virale Hüllprotein (Env) förderte die anfängliche Endogenisierung und zeigt einen breiten Tropismus. Es vermittelt die Infektion durch erste Wechselwirkung mit Heparansulfaten (HS) auf der Zelloberfläche. In dieser Studie zeigten wir, dass die Rezeptorbindungsstelle (RBS) von HML-2 Env nicht an der Bindung von HS beteiligt ist. Um die daran beteiligte Domäne zu identifizieren, haben wir die Proteinsequenz von HML-2 Env mit der des Maus-Mammatumorvirus (MMTV) verglichen. Am N-Terminus des HML-2 Env wurde so eine potentielle homologe HS-bindende Domäne (HBD) zwischen den Positionen 216 und 236 identifiziert. Mutationen in allen positiv geladenen Resten dieser Domäne beeinträchtigten die Bindung an Heparin-beschichtete Beads und blockierten die Infektion. Darüber hinaus waren Mutationen an den Positionen R216, K219 und K223 für die HS-Bindung und den viralen Zelleintritt maßgeblich. Im zweiten und dritten Teil der Studie wollten wir die zellulären Faktoren für den HML-2 Env vermittelten Zelleintritt mit zwei Ansätzen identifizieren. Im ersten Ansatz ist es gelungen, ein Trimer-Fusionsprotein für HML-2 zu erzeugen, das aus der SU-Untereinheit besteht, die mit der Trimerisierungs-domäne fusioniert ist. Sie ist vom Fibritin des Bakteriophagen T4 abgeleitet. Das Trimer-Fusionsprotein bindet HS ähnlich wie das native Env. Es blockierte jedoch nicht den Eintritt von HML-2 in die Zellen. Mit diesem Fusionsprotein wurde das Golgi-Membranprotein 37 (GP73) als potenzieller Bindungsfaktor für HML-2 Env gefunden. Der zweite Ansatz umfasste die Verwendung von HML-2 Env-Pseudoviren bei der Durchführung eines funktionellen Screenings einer cDNA-Bibliothek mit einer nicht-permissiven Zelllinie. Damit wurden 6 Transmembranproteine (TMEM9, C12ORF59, IL1RAP, PSCA, LETMD1 und MPEG1) identifiziert, die am Infektionsprozess von HML-2 beteiligt sind. Nur IL1RAP und MPEG1 konnten allerding den Eintritt in eine andere nicht-permissiven Zelllinie vermitteln. Die Arbeiten bestätigen die Rolle von HS bei der Zelladhärenz von HML-2 Env und identifizierten die spezifische HBD. Sie bestätigten auch die Beteiligung eines oder mehrerer anderer Moleküle, die als Rezeptor(en) dienen. In diesem Zusammenhang wurden 7 Transmembranproteine identifiziert, die am Eintrittsweg von HML-2 beteiligt sind

Puerperal Metritis in Crossbreed (Tarentaise X Baladi) Cows: Metabolism-Related Biochemical and Haematological changes

Breeding of crossbreed cow is of great significance in tropical and subtropical countries in order to maintain both high productivity and high ability to accommodate. To understand the haematological and biochemical changes related with puerperal metritis in crossbred cows as well as the effect of puerperal metritis on the fertility, the current study evaluated the relations of some metabolic, and biochemical changes to the puerperal metritis. After thorough clinical and gynaecological examination, blood and urine samples were collected from both the control cows (n=20) and metritis cows (n=19). Haemoglobin (Hb) concentrations and leukocytes count was determined. The concentrations of glucose, triglycerides, cholesterol, non-esterified fatty acids (NEFA), calcium, phosphorus, sodium, potassium, albumin, total protein, urea and progesterone hormone (P4) in blood, and ketone bodies were detected in urine at the following time-points (prepartum, partum, 1-week postpartum, and 2-weeks postpartum). Cows in the metritis group showed low Hb and high leukocytes count in the postpartum period. The metritis cows showed low glucose, low cholesterol, high NEFA, and low calcium levels. Blood NEFA, glucose, triglycerides, and calcium levels change significantly in puerperal metritis in crossbreed cows

Urban Health Related Air Quality Indicators over the Middle East and North Africa Countries Using Multiple Satellites and AERONET Data

Air pollution is reported as one of the most severe environmental problems in the Middle East and North Africa (MENA) region. Remotely sensed data from newly available TROPOMI - TROPOspheric Monitoring Instrument on board Sentinel-5 Precursor, shows an annual mean of high-resolution maps of selected air quality indicators (NO2, CO, O3, and UVAI) of the MENA countries for the first time. The correlation analysis among the aforementioned indicators show the coherency of the air pollutants in urban areas. Multi-year data from the Aerosol Robotic Network (AERONET) stations from nine MENA countries are utilized here to study the aerosol optical depth (AOD) and Ångström exponent (AE) with other available observations. Additionally, a total of 65 different machine learning models of four categories, namely: linear regression, ensemble, decision tree, and deep neural network (DNN), were built from multiple data sources (MODIS, MISR, OMI, and MERRA-2) to predict the best usable AOD product as compared to AERONET data. DNN validates well against AERONET data and proves to be the best model to generate optimized aerosol products when the ground observations are insufficient. This approach can improve the knowledge of air pollutant variability and intensity in the MENA region for decision makers to operate proper mitigation strategies

Typology of e-commerce shoppers: the case of COVID-19

Purpose: The spread of coronavirus disease (COVID-19) has drastically changed the entire market structure and shopping behaviors across the world. While shoppers rushed toward e-commerce platforms during the pandemic, the key debate that rose was on how this behavior will evolve post COVID-19. The purpose of this study was to explore the different categories of e-commerce platforms’ users and propose a distinctive customer typology in the era of the COVID-19 pandemic. Design/methodology/approach: An exploratory qualitative research design was adopted because of the novelty of the subject. In total, 43 participants were interviewed, including 27 consumers and 16 experts in the field of e-commerce. Findings: Based on the findings, this study distinguishes between two stages of e-commerce usage during the pandemic. Furthermore, this study identifies four key typologies of e-commerce shoppers that are expected to form at the end of the coronavirus: duty-bound, e-watcher, makeshift and onli-vorous shoppers. The characteristics and businesses strategies pertaining to each of the identified groups are discussed. Originality/value: To the best of the authors’ knowledge, this research is among the first to identify the different stages, while proposing an innovative typology of e-commerce platform post COVID-19. This study also offers useful recommendations to deal with similar future crises

De-aluminated metakaolin-cement composite modified with commercial titania as a new green building material for gamma-ray shielding applications

Sustainable disposal of dealuminated metakaolin (DAK) is a crucial environmental issue for the alum production industry. In previous studies, DAK was utilized as eco-friendly cementitious materials, but only 10 wt% was used instead of cement as DAK's high percentage has a detri-mental effect on the mechanical properties, so the environmental problem of DAK has not yet been solved. In this study, commercial titanium oxide (TiO2) was incorporated in a cement matrix containing DAK that reached 50 wt% to benefit from TiO2's properties in enhancing the me-chanical performance of binding materials and producing cementitious blends used as blocking materials against harmful gamma radiation. Five pastes were prepared to reach the main target; ordinary Portland cement (OPC), OPC-10%DAK (D10), OPC-30%DAK (D30), OPC-50%DAK (D50) and OPC-45%DAK-5%TiO2 (D45-T5). By means of a mini-slump test, all fresh blends have very close flowability using the appreciated additions of polycarboxylate superplasticizer. The hardened composites were cured in tap water for up to 28-days. Compressive strength results at 28 days for OPC, D10, D30 and D50 were 80, 94.6, 60.8 and 57.6 MPa, respectively. An obvious turning point in strength value from 57.6 to 88 MPa after replacement of DAK by 5 wt% TiO2 (D45-T5). A gamma-ray shielding test was performed using two radioactive isotopes (Co-60 and Cs-137). The inclusion of 5% TiO2 has a great impact on the development of shielding power of D45-T5 compared with OPC; the linear attenuation coefficient (mu) values were enhanced from 0.127 +/- 0.003 cm(-1) to 0.199 +/- 0.007 cm(-1) at 661.6 Kev and from 0.118 +/- 0.003 cm(-1) to 0.144 +/- 0.005 cm(-1) at 1332.5 Kev. The unique properties of specimens containing the anatase phase may be attributed to the fact that the TiO2 may act as a nano-filler and active seeds for the formation of further hydration products such as CSHs, CAHs and CASHs as detected by X-ray diffraction (XRD), thermal analyses techniques (TGA/DSC) and scanning electron microscope (SEM/EDX). TiO2 caused rearrangement of the textural structure of D45-T5 composite to meso pores, as proved by N-2-adsorption/desorption technique. Moreover, the TiO2's tetragonal struc-ture makes it has dosimetric characteristics of high adsorbent for gamma rays

تحليل العوامل للتكاليف الإنتاجية والتنبؤ بإنتاجية أهم المحاصيل الحقلية في مصر

The research problem is to answer the question: What are the main components of the production costs items for the most important field crops (wheat, rice, summer maize) in Egyptian agriculture? Are there changes in the area of these crops? In achieving its goals, the research relied on a descriptive and quantitative analysis method, relying on tabular and graphical presentation, percentages, engineering and mathematical averages, and growth rates, in addition to Runs Test, Factor Analysis using the major or fundamental component analysis method (PCA) for the most important Items of costs (workers’ wages, seeds, fertilizers, mechanization, other) of the field crops under study question. The research reached a number of results, including: •Wheat crop: From the test runs of the wheat crop area in the four geographical regions during the study period, it is noted that the number of courses during the study period reached two courses for the sea side, 4 courses in Middle Egypt, 6 courses for the tribal face and the total of the republic, and it is expected that the value of acre productivity in In 2024 to 20.9 million erdeb for Lower Egypt and Middle Egypt, 16.7 million erdeb for Upper Egypt, 20.7 million erdeb for the total Egypt. •Rice crop: Results of the test runs for the rice crop area in the four geographical regions during the study period. It is noted that the number of courses during the study period reached 8 courses for the sea side and the total of the republic, 11 courses in Middle Egypt, 7 courses for the tribal face, and it is expected that the value of acre productivity In the year 2024 to 3.4 million tons for Lower Egypt and the total Egypt, 3.5 million tons for Middle Egypt, 4.3 million tons for Upper Egypt. •Maize crop: Runs test for the rice crop area in the four geographical regions during the study period, from which it is noted that the number of courses during the study period reached 14 courses for Lower Egypt, 6 courses in Middle Egypt, 4 courses for Upper Egypt and the total of the Republic, and it is expected that the value of productivity will reach to 25.8 million erdeb in 2024 for Lower Egypt, 22.3 million erdeb for Middle Egypt, 17.8 million erdeb for Upper Egypt, 23.6 million erdeb for the total Egypt. تتمثل مشكلة البحث في الإجابة على التساؤلات التالية: ما هي المكونات الأساسية لبنود التكاليف الإنتاجية لأهم المحاصيل الحقلية (القمح، الأرز، الذرة الشامية الصيفية) في الزراعة المصرية؟ وهل هناك تغيرات فى المساحة لهذه المحاصيل؟ واعتمد البحث في تحقيق أهدافه على أسلوب التحليل الوصفي والكمي، معتمداً على العرض الجدولي والبياني، والنسب المئوية، والمتوسطات الحسابية والهندسية، ومعدلات النمو، بالإضافة إلى اختبار الأشواطRuns Test، تحليل العوامل Factor Analysis باستخدام طريقة تحليل المكون الرئيسي أو الأساسي Principle Component Analysis “PCA” لأهم بنود التكاليف (أجور العمال، التقاوي، الأسمدة، الميكنة، أخرى) للمحاصيل موضع البحث، وتوصل البحث إلى عدد من النتائج منها: • محصول القمح: من اختبار الأشواط لمساحة محصول القمح بالمناطق الجغرافية الثلاثة بالإضافة إلى إجمالي الجمهورية خلال فترة الدراسة، يُلاحظ أن عدد الدورات خلال فترة الدراسة بلغ دورتين للوجه البحري، 4 دورات في مصر الوسطى، 6 دورات للوجه القبلي وإجمالي الجمهورية، ومن المتوقع أن تصل قيمة الإنتاجية الفدانية في عام 2024 إلى 20.9 مليون أردب للوجه البحري ومصر الوسطى، 16.7 مليون أردب للوجه القبلي، 20.7 مليون أردب لإجمالي الجمهورية. • محصول الأرز: نتائج اختبار الأشواط لمساحة محصول الأرز بالمناطق الجغرافية الأربعة خلال فترة الدراسة، يُلاحظ أن عدد الدورات خلال فترة الدراسة بلغ 8دورات للوجه البحري وإجمالي الجمهورية، 11 دورات في مصر الوسطى، 7 دورات للوجه القبلي، ومن المتوقع أن تصل قيمة الإنتاجية الفدانية في عام 2024 إلى 3.4 مليون طن للوجه البحريوإجمالي الجمهورية، 3.5 مليون طن لمصر الوسطى، 4.3 مليون طن للوجه القبلي. • محصول الذرة الشامية: اختبار الأشواط لمساحة محصول الأرز بالمناطق الجغرافية الأربعة خلال فترة الدراسة، ومنها يُلاحظ أن عدد الدورات خلال فترة الدراسة بلغ 14 دورة للوجه البحري، 6 دورات في مصر الوسطى، 4 دورات للوجه القبلي وإجمالي الجمهورية، ومن المتوقع أن تصل قيمة الإنتاجية الفدانية في عام 2024 إلى 25.8 مليون أردب للوجه البحري، 22.3 مليون أردب لمصر الوسطى، 17.8 مليون أردب للوجه القبلي، 23.6 مليون أردب لإجمالي الجمهورية. الكلمات الدليلية: تحليل العوامل Factor Analysis، اختبار الأشواط Runs Test، التنبؤ، الإنتاجية

A Review of the Effects of Omega-3 and Omega-6 on Alcoholic and Non-Alcoholic Fatty Liver

Non-alcoholic fatty liver disease is a type of fatty fat that causes an increase in alcohol consumption. Excessive alcohol consumption causes inflammation, and liver damage. The certain fatty acids (FAs) may be involved in this liver damage. Anti-inflammatory and blood lipid lowering effects are the effects of omega-3 unsaturated fatty acids (n-3 PUFAs). NAFLD is the hepatic manifestation of metabolic syndrome because obesity and insulin resistance are the main pathogenic factors of both diseases. NAFLD is a disease associated with metabolic syndrome. Most patients with NAFLD are obese, although the disease can also affect non-obese people. Metabolic and genetic factors play an important role in the occurrence of this disease. Oxidative stress, lipotoxicity and inflammation play a key role in the development of NAFLD. There is a lot of evidence for the therapeutic potential of omega-3 PUFAs fatty acids (n-3 PUFA), mainly docosahexaenoic acid and eicosatetraenoic acid in the treatment of metabolic diseases due to their antioxidant and anti-inflammatory properties. Therefore, in this review article, we examined the effects of omega-3 and omega-6 on alcoholic and non-alcoholic fatty liver disease

Endoscopic retrograde cholangiopancreatography versus conservative treatment for patients with symptomatic small common bile duct stones: A randomized controlled trial

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the recommended treatment for common bile duct stones (CBDS). However, CBDS, tiny ones, can spontaneously pass through the ampulla of Vater, reducing unnecessary ERCP and its related significant complications. Objectives: This study compared endoscopic stone extraction versus conservative treatment for managing symptomatic small CBDS. Patients and methods: This randomized controlled trial included 168 patients with symptomatic CBDS (≤ 7 mm) and gallbladder stones. Of these, 85 patients underwent endoscopic stone extraction, and 83 patients underwent conservative treatment for the CBDS, followed by laparoscopic cholecystectomy and intraoperative cholangiography between June 2019 and March 2023. The primary outcome was the overall success rate, while useless procedures, morbidity, mortality, length of hospital stay, total cost, and recurrent biliary symptoms were considered secondary outcomes. Results: Our study showed that the ERCP group had a significantly higher overall success rate (96.5% vs. 22.9%, P < 0.001), fewer useless procedures (14.1% vs. 77.1%, P < 0.001), a shorter median hospital stay (5 vs. 8 days, P < 0.001), and reduced total costs (1810 vs. 2250 US$, P < 0.001). Both groups had no significant difference in morbidity or recurrent biliary symptoms (2.4% vs. 7.2%, P = 0.14). There was no mortality rate in both groups. Conclusion: Symptomatic small CBDS should be managed surgically as early as possible. Endoscopic stone extraction has a significantly high success rate, a shorter hospital stay, and a lower total cost. The conservative treatment for symptomatic small CBDS is useless and should not be practiced

Imaging of choroidal neovascular membrane by optical coherence tomography Angiography

Background: Optical coherence tomography angiography (OCTA) is a new safe imaging technique that uses motion contrast imaging to high-resolution volumetric blood stream information to produce angiographic pictures in a matter of seconds. Objectives: We aimed to identify different patterns and types of CNV by OCTA and the relationship between these patterns and activity of CNV. Patients and Methods: Fifty eyes of 50 patients presented with CNV had a regular diagnostic evaluation that included FA and/or OCT. Suspected cases with CNV underwent scanning by OCTA in this study. Patients with media opacity or bad image quality had been excluded. Results: In 80% of patients, there is a statistically significant correlation between the patterns of CNV and its activity (P-value =0.0001). Conclusion: OCTA is a critical technique for better characterizing the various forms and patterns of CNV, as well as the link between these patterns and CNV activity

Synthesis of quinone-based heterocycles of broad-spectrum anticancer activity

A synthesis of benzo[e][1,2,4]triazines and 1,2,4-triazolospiro[4,5]deca-2,6,9-trien-8-ones has been developed from reactions of amidrazones with 2-chloro-1,4-benzoquinone in EtOAc containing 0.5 mL of piperidine. This highly regioselective and one-pot process provided rapid access to 1,2,4-triazolospiro[4,5]deca-2,6,9-trien-8-ones (60%-70%) and benzo[e][1,2,4]triazines (11%-18%). On reacting amidrazones with 5-hydroxy-1,4-naphthoquinone in an EtOAc/piperidine mixture, the reaction proceeded to give 5-hydroxy-2-(piperidin-1-yl)naphthalene-1,4-dione. The structures of the isolated products were proved by infrared, NMR (2D-NMR), mass spectra, and elemental analyses in addition to X-ray structure analysis. The reaction mechanisms are discussed. The anticancer screening of selected compounds showed broad-spectrum anticancer activity against most melanoma cancer cell lines, ovarian cancer OVCAR-3, central nervous system cancer SF-295 and U251, non-small cell lung cancer NCI-H23, renal cancer SN12C, and colon cancer HCT-15 and HCT-116. The selected compounds exhibited moderate to weak anticancer activity to other cell lines.Peer reviewe