Non-Random Pattern of Integration for Epstein-Barr Virus with Preference for Gene-Poor Genomic Chromosomal Regions into the Genome of Burkitt Lymphoma Cell Lines

Background: Epstein-Barr virus (EBV) is an oncogenic virus found in about 95% of endemic Burkitt lymphoma (BL) cases. In latently infected cells, EBV DNA is mostly maintained in episomal form, but it can also be integrated into the host genome, or both forms can coexist in the infected cells. Methods: In this study, we mapped the chromosomal integration sites of EBV (EBV-IS) into the genome of 21 EBV+ BL cell lines (BL-CL) using metaphase fluorescence in situ hybridization (FISH). The data were used to investigate the EBV-IS distribution pattern in BL-CL, its relation to the genome instability, and to assess its association to common fragile sites and episomes. Results: We detected a total of 459 EBV-IS integrated into multiple genome localizations with a preference for gene-poor chromosomes. We did not observe any preferential affinity of EBV to integrate into common and rare fragile sites or enrichment of EBV-IS at the chromosomal breakpoints of the BL-CL analyzed here, as other DNA viruses do. Conclusions: We identified a non-random integration pattern into 13 cytobands, of which eight overlap with the EBV-IS in EBV-transformed lymphoblastoid cell lines and with a preference for gene- and CpGs-poor G-positive cytobands. Moreover, it has been demonstrated that the episomal form of EBV interacts in a non-random manner with gene-poor and AT-rich regions in EBV+ cell lines, which may explain the observed affinity for G-positive cytobands in the EBV integration process. Our results provide new insights into the patterns of EBV integration in BL-CL at the chromosomal level, revealing an unexpected connection between the episomal and integrated forms of EBV.

Genome-Wide Profiling Reveals HPV Integration Pattern and Activated Carcinogenic Pathways in Penile Squamous Cell Carcinoma

Human papillomavirus (HPV) is a significant etiologic driver of penile squamous cell carcinoma (PSCC). The integration pattern of HPV and its carcinogenic mechanism in PSCC remain largely unclear. We retrospectively reviewed 108 PSCC cases who received surgery between 2008 and 2017. Using high-throughput viral integration detection, we identified 35 HPV-integrated PSCCs. Unlike cervical cancer, the HPV E2 oncogene was not prone to involvement in integration. Eleven of the 35 (31.4%) HPV-integrated PSCCs harbored intact HPV E2; these tumors had lower HPV E6 and E7 expression and higher expression of p53 and pRb proteins than those with disrupted E2 did (p < 0.001 and p = 0.024). Integration breakpoints are preferentially distributed in or near host genes, including previously reported hotspots (KLF5, etc.) and newly identified hotspots (CADM2, etc.), which are mainly involved in oncogenic signaling pathways (MAPK, JAK/STAT, etc.). Regarding the phosphorylation levels of JNK, p38 was higher in HPV-positive tumors with MAPK-associated integration than those in HPV-positive tumors with other integration and those in HPV-negative tumors. In vitro, KLF5 knockdown inhibited proliferation and invasion of PSCC cells, while silencing CADM2 promoted migration and invasion. In conclusion, this study enhances our understanding of HPV-induced carcinogenesis in PSCC, which may not only rely on the E6/E7 oncogenes, but mat also affect the expression of critical genes and thus activate oncogenic pathways.

Spillage-Adaptive Fixed-Geometry Bump Inlet of Wide Speed Range

In this work, a new spillage-adaptive bump inlet concept is proposed to widen the speed range for hypersonic air-breathing flight vehicles. Various approaches to improve the inlet start-ability are summarized and compared, among which the bump-inlet pattern holds the merits of high lift-to-drag ratio, boundary layer diversion, and flexible integration ability. The proposed spillage-adaptive concept ensures the inlet starting performance by spilling extra mass flow away at low speed number conditions. The inlet presetting position is determined by synthetically evaluating the flow uniformity and the low-kinetic-energy fluid proportion. The numerical results show that the flow spillage of the inlet increases with the inflow speed decrease, which makes the inlet easier to start at low speed conditions (M 2.5–6.0). The effects of the boundary layer on spillage are also studied in this work. The new integration pattern releases the flow spillage potentials of three-dimensional inward-turning inlets by reasonably arranging the inlet compression on the bump surface. Future work will focus on the spillage-controllable design method.

Long-read sequencing reveals the structural complexity of genomic integration of HBV DNA in hepatocellular carcinoma

The integration of HBV DNA into the human genome can disrupt its structure in hepatocellular carcinoma (HCC), but the complexity of HBV genomic integration remains elusive. Here we applied long-read sequencing to precisely elucidate the HBV integration pattern in the human hepatocellular genome. The DNA library was sequenced using the long-read sequencing on GridION and PacBio Sequel II, respectively. The DNA and mRNA were sequenced using next-generation sequencing on Illumina NextSeq. BLAST (Basic Local Alignment Search Tool) and local scripts were used to analyze HBV integration patterns. We established an analytical strategy based on the long-read sequences, and analyzed the complexity of HBV DNA integration into the hepatocellular genome. A total of 88 integrated breakpoints were identified. HBV DNA integration into human genomic DNA was mainly fragmented with different orientations, rarely with a complete genome. The same HBV integration breakpoints were identified among the three platforms. Most breakpoints were observed at P, X, and S genes in the HBV genome, and observed at introns, intergenic sequences, and exons in the human genome. Tumor tissue harbored a much higher integrated number than the adjacent tissue, and the distribution of HBV integrated into human chromosomes was more concentrated. HBV integration shows different patterns between cancer cells and adjacent normal cells. We for the first time obtained the entire HBV integration pattern through long-read sequencing and demonstrated the value of long-read sequencing in detecting the genomic integration structures of viruses in host cells.

Assessment of Value Changes and Spatial Differences in Land Use Based on an Empirical Survey in the Manas River Basin

Land integration is an important means of increasing the multifunctional value of arable land. The scientific measurement of the integrative value of arable land before and after land consolidation can improve farmers’ overall understanding of the value of arable land, increase their awareness of arable land protection, and encourage them to implement arable land protection policies. Additionally, it can provide a theoretical basis for the formulation of reasonable compensation standards for arable land in various areas of the Manas River Basin and effectively promote the use of the “Shawan model”. In this paper, the sample used for the survey was made up of 380 farmers from 10 villages in three different regions of Shawan City (county-level city). The participatory farmer assessment (PRA) method was used to conduct a detailed investigation of the integration of farmers’ cultivated land, while the landscape pattern index method was used to analyze the intensity of the cultivated land integration pattern. By constructing a measurement system for the integrative value of cultivated land and adding up the economic, pro-ecological, and social values before and after the integration of the cultivated land, estimated using the income reduction method, the equivalent factor method, and the shadow engineering method, we found that the cultivated land in each region of Shawan City (county-level city) was more effectively integrated, the scale of the field expanded, the shape of the patches tended to be more regular, and the field surface more flat. However, the degree of integration varied from region to region, with the degree of integration from the largest to the smallest as follows: oasis agricultural zone > oasis/desert ecological zone > hilly zone. We found that the integration of cultivated land has a significant effect on the integrated value of cultivated land, and the value of cultivated land in different regions showed different degrees of improvement after integration. The cultivated land of villages located in the oasis/desert ecotone showed a significant overall improvement after integration, followed by cultivated land in the oasis agricultural area. The value of cultivated land increased significantly, while the value of cultivated land in the hilly area showed less improvement after integration. The value of cultivated land integration in different regions is related to the intensity of the cultivated land integration, the per capita cultivated land area, the ecosystem biomass, and the crop planting area. The purpose of this paper is to effectively diagnose and promote the “Shawan Model” (land integration), formulate reasonable compensation standards for cultivated land in different regions of the Manas River Basin, and implement cultivated land protection policies.

The Integration Pattern of Human Papillomavirus in the Host Genome as a Promising Guide for Precise Radiation Therapy in Cervical Cancer

Context: Cervical cancer (CC) is one of the most common cancers among women worldwide. Infection with high-risk human papillomavirus (HPV) is the leading risk factor for this cancer. Currently, concurrent chemotherapy and radiotherapy are the standard of care for patients with locally advanced CC. However, the response to radiotherapy varies widely among patients, underscoring the need to identify biomarkers to predict patients’ treatment outcomes. Evidence Acquisition: In order to find relevant articles, we performed a systematic search using ISI Web of Science, Scopus, PubMed, and Embase, with a combination of the keywords “human papillomaviruses”, “cervical cancer”, “radiotherapy”, “biomarkers”, “viral integration”, and “episome”. All types of studies, including observational or retrospective studies, clinical trials, congress abstracts, and case reports or case series, were examined to find relevant data. No time limitation was considered for the studies. Results: The integration of HPV DNA into the host genome is considered to be a critical step in HPV carcinogenesis. The HPV integration pattern has been investigated as a potent prognostic factor for the tailored treatment of CC. Conclusions: It is indicated that the integration state of the HPV genome in host DNA is a potential prognostic or predictive biomarker for CC response to radiotherapy.

Diversity of short interspersed nuclear elements (SINEs) in lepidopteran insects and evidence of horizontal SINE transfer between baculovirus and lepidopteran hosts

Background Short interspersed nuclear elements (SINEs) belong to non-long terminal repeat (non-LTR) retrotransposons, which can mobilize dependent on the help of counterpart long interspersed nuclear elements (LINEs). Although 234 SINEs have been identified so far, only 23 are from insect species (SINEbase: http://sines.eimb.ru/). Results Here, five SINEs were identified from the genome of Plutella xylostella, among which PxSE1, PxSE2 and PxSE3 were tRNA-derived SINEs, PxSE4 and PxSE5 were 5S RNA-derived SINEs. A total of 18 related SINEs were further identified in 13 lepidopteran insects and a baculovirus. The 3′-tail of PxSE5 shares highly identity with that of LINE retrotransposon, PxLINE1. The analysis of relative age distribution profiles revealed that PxSE1 is a relatively young retrotransposon in the genome of P. xylostella and was generated by recent explosive amplification. Integration pattern analysis showed that SINEs in P. xylostella prefer to insert into or accumulate in introns and regions 5 kb downstream of genes. In particular, the PxSE1-like element, SlNPVSE1, in Spodoptera litura nucleopolyhedrovirus II genome is highly identical to SfSE1 in Spodoptera frugiperda, SlittSE1 in Spodoptera littoralis, and SlituSE1 in Spodoptera litura, suggesting the occurrence of horizontal transfer. Conclusions Lepidopteran insect genomes harbor a diversity of SINEs. The retrotransposition activity and copy number of these SINEs varies considerably between host lineages and SINE lineages. Host-parasite interactions facilitate the horizontal transfer of SINE between baculovirus and its lepidopteran hosts.

Integrating Science and Religion at Malaysian and Indonesian Higher Education

This article analyzes the integration model between science and religion in Malaysian and Indonesian Higher Education. So far, the dichotomy of science and religion is considered to be one of the causes for the exit of the Islamic world from the Western world. In this century, educational institutions in the Islamic world began to re-select the integration pattern of science. This study uses qualitative methods, by collecting data through observation, visiting two higher education institutions studied, and conducting in-depth interviews with relevant parties, namely the International Islamic University Malaysia (IIUM) in Malaysia and Universitas Muhammadiyah Malang (UMM) in Indonesia. Data collection is also done by searching documents and referral sources in various data sources available online. From the research conducted, it was found that, integration carried out by Islamic universities in Malaysia and Indonesia was to open faculties and study programs without any religious or public claims. Everything is the same, and there are no restrictions on the rules for students based on religion to enter into it. So, education is inclusive, it can be for anyone. This model succeeded in advancing Islamic educational institutions.

A Pragmatic Analytics of Covid Data Patterns for Predictive Mining of Patients

The year 2020 has emerged as a menace and threat for the human being whereby the social as well as professional livings getting affected. In the global perspectives, the human lives are affecting and huge demise occurring. In this research work, the effectual implementation towards the usage of Artificial Intelligence is done with the machine learning so that the overall outcomes and predictive mining can be done with higher degree of performance. The work is having the integration pattern of COVID datasets of patients with benchmark characteristics and thereby to have the predictions for the upcoming tests and by this way overall prediction can be done.

Otoritas dan Gerakan Keagamaan Daengguru: Studi Sejarah Islamisasi di Sulawesi Selatan

This paper is about the Islamization movement of the kingdoms in South Sulawesi, sointegrated sara 'is into a social institution called pangadereng (Bugis) angadakkang (Makassar). To ensure the upholding of Islamic law, which has been integrated into the social system, a religious bureaucracy (Islam) known aswas formed sara '. The royal bureaucratic officials who handle this institution, from the central level to the village or village level are called parewa sara ', which in this study uses the term daengguru. This integration pattern was developed in almost all Islamic kingdoms in South Sulawesi. Adat has its own field and sharia controls its own field. One another should not disturb each other. When the King of Bone La Maddarremmeng was about to confront Islam and customs, he was opposed by all parties. When Arung Matowa Wajo declared a strong Islamization, he was also evicted from his position.