The number of children born since the origin of Assisted Reproductive Technologies (ART) exceeds 5 million. The majority seem healthy, but a higher frequency of defects has been reported among ...ART-conceived infants, suggesting an epigenetic cost. We report the first whole-genome DNA methylation datasets from single pig blastocysts showing differences between in vivo and in vitro produced embryos. Blastocysts were produced in vitro either without (C-IVF) or in the presence of natural reproductive fluids (Natur-IVF). Natur-IVF embryos were of higher quality than C-IVF in terms of cell number and hatching ability. RNA-Seq and DNA methylation analyses showed that Natur-IVF embryos have expression and methylation patterns closer to in vivo blastocysts. Genes involved in reprogramming, imprinting and development were affected by culture, with fewer aberrations in Natur-IVF embryos. Methylation analysis detected methylated changes in C-IVF, but not in Natur-IVF, at genes whose methylation could be critical, such as IGF2R and NNAT.
Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation ...establishment remain poorly understood, but a number of post-translational modifications of histones are implicated in antagonizing or recruiting the de novo DNA methylation complex. In mouse oogenesis, DNA methylation establishment occurs on a largely unmethylated genome and in nondividing cells, making it a highly informative model for examining how histone modifications can shape the DNA methylome. Using a chromatin immunoprecipitation (ChIP) and genome-wide sequencing (ChIP-seq) protocol optimized for low cell numbers and novel techniques for isolating primary and growing oocytes, profiles were generated for histone modifications implicated in promoting or inhibiting DNA methylation. CGIs destined for DNA methylation show reduced protective H3K4 dimethylation (H3K4me2) and trimethylation (H3K4me3) in both primary and growing oocytes, while permissive H3K36me3 increases specifically at these CGIs in growing oocytes. Methylome profiling of oocytes deficient in H3K4 demethylase KDM1A or KDM1B indicated that removal of H3K4 methylation is necessary for proper methylation establishment at CGIs. This work represents the first systematic study performing ChIP-seq in oocytes and shows that histone remodeling in the mammalian oocyte helps direct de novo DNA methylation events.
Flower classification is a challenging task due to the wide range of flower species, which have a similar shape, appearance or surrounding objects such as leaves and grass. In this study, the authors ...propose a novel two-step deep learning classifier to distinguish flowers of a wide range of species. First, the flower region is automatically segmented to allow localisation of the minimum bounding box around it. The proposed flower segmentation approach is modelled as a binary classifier in a fully convolutional network framework. Second, they build a robust convolutional neural network classifier to distinguish the different flower types. They propose novel steps during the training stage to ensure robust, accurate and real-time classification. They evaluate their method on three well known flower datasets. Their classification results exceed 97% on all datasets, which are better than the state-of-the-art in this domain.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Previously, a role was demonstrated for transcription in the acquisition of DNA methylation at imprinted control regions in oocytes. Definition of the oocyte DNA methylome by whole genome approaches ...revealed that the majority of methylated CpG islands are intragenic and gene bodies are hypermethylated. Yet, the mechanisms by which transcription regulates DNA methylation in oocytes remain unclear. Here, we systematically test the link between transcription and the methylome.
We perform deep RNA-Seq and de novo transcriptome assembly at different stages of mouse oogenesis. This reveals thousands of novel non-annotated genes, as well as alternative promoters, for approximately 10 % of reference genes expressed in oocytes. In addition, a large fraction of novel promoters coincide with MaLR and ERVK transposable elements. Integration with our transcriptome assembly reveals that transcription correlates accurately with DNA methylation and accounts for approximately 85-90 % of the methylome. We generate a mouse model in which transcription across the Zac1/Plagl1 locus is abrogated in oocytes, resulting in failure of DNA methylation establishment at all CpGs of this locus. ChIP analysis in oocytes reveals H3K4me2 enrichment at the Zac1 imprinted control region when transcription is ablated, establishing a connection between transcription and chromatin remodeling at CpG islands by histone demethylases.
By precisely defining the mouse oocyte transcriptome, this work not only highlights transcription as a cornerstone of DNA methylation establishment in female germ cells, but also provides an important resource for developmental biology research.
The maternal and paternal copies of the genome are both required for mammalian development, and this is primarily due to imprinted genes, those that are monoallelically expressed based on ...parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilization. There are a large number of germline DMRs that have not yet been associated with imprinting, and their function in development is unknown. In this study, we developed a genome-wide approach to identify novel imprinted DMRs in the human placenta and investigated the dynamics of these imprinted DMRs during development in somatic and extraembryonic tissues. DNA methylation was evaluated using the Illumina HumanMethylation450 array in 134 human tissue samples, publicly available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas. Forty-three known and 101 novel imprinted DMRs were identified in the human placenta by comparing methylation between diandric and digynic triploid conceptions in addition to female and male gametes. Seventy-two novel DMRs showed a pattern consistent with placental-specific imprinting, and this monoallelic methylation was entirely maternal in origin. Strikingly, these DMRs exhibited polymorphic imprinted methylation between placental samples. These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation.
This study was designed to assess the effect of COVID-19 home quarantine and its lifestyle challenges on the sleep quality and mental health of a large sample of undergraduate University students in ...Jordan. It is the first study applied to the Jordanian population. The aim was to investigate how quarantine for several weeks changed the students' habits and affected their mental health.
A cross-sectional study was conducted using a random representative sample of 6,157 undergraduate students (mean age 19.79 ± 1.67 years, males 28.7%) from the University of Jordan through voluntarily filling an online questionnaire. The Pittsburgh Sleep Quality Index (PSQI) and the Center for Epidemiologic Studies-Depression Scale (CES-D) were used to assess sleep quality and depressive symptoms, respectively.
The PSQI mean score for the study participants was 8.1 ± 3.6. The sleep quality of three-quarters of the participants was negatively affected by the extended quarantine. Nearly half of the participants reported poor sleep quality. The prevalence of poor sleep quality among participants was 76% (males: 71.5% and females: 77.8%). Similarly, the prevalence of the depressive symptoms was 71% (34% for moderate and 37% for high depressive symptoms), with females showing higher prevalence than males. The overall mean CES-D score for the group with low depressive symptoms is 9.3, for the moderate group is 19.8, while it is 34.3 for the high depressive symptoms group. More than half of the students (62.5%) reported that the quarantine had a negative effect on their mental health. Finally, females, smokers, and students with decreased income levels during the extended quarantine were the common exposures that are significantly associated with a higher risk of developing sleep disturbances and depressive symptoms.
Mass and extended quarantine succeeded in controlling the spread of the COVID-19 virus; however, it comes with a high cost of potential psychological impacts. Most of the students reported that they suffer from sleeping disorders and had a degree of depressive symptoms. Officials should provide psychological support and clear guidance to help the general public to reduce these potential effects and overcome the quarantine period with minimum negative impacts.
Online social networks have established virtual platforms enabling people to express their opinions, interests and thoughts in a variety of contexts and domains, allowing legitimate users as well as ...spammers and other untrustworthy users to publish and spread their content. Hence, it is vital to have an accurate understanding of the contextual content of social users, thus establishing grounds for measuring their social influence accordingly. In particular, there is the need for a better understanding of domain-based social trust to improve and expand the analysis process and determining the credibility of Social Big Data. The aim of this paper is to determine domain-based social influencers by means of a framework that incorporates semantic analysis and machine learning modules to measure and predict users’ credibility in numerous domains at different time periods. The evaluation of the experiment conducted herein validates the applicability of semantic analysis and machine learning techniques in detecting highly trustworthy domain-based influencers.
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CEKLJ, NUK, ODKLJ, UL, UM, UPUK
COVID-19 is a global pandemic that affected the everyday life activities of billions around the world. It is an unprecedented crisis that the modern world had never experienced before. It mainly ...affected the economic state and the health care system. The rapid and increasing number of infected patients overwhelmed the healthcare infrastructure, which causes high demand and, thus, shortage in the required staff members and medical resources. This shortage necessitates practical and ethical suggestions to guide clinicians and medical centers when allocating and reallocating scarce resources for and between COVID-19 patients. Many studies proposed a set of ethical principles that should be applied and implemented to address this problem. In this study, five different ethical principles based on the most commonly recommended principles and aligned with WHO guidelines and state-of-the-art practices proposed in the literature were identified, and recommendations for their applications were discussed. Furthermore, a recent study highlighted physicians' propensity to apply a combination of more than one ethical principle while prioritizing the medical resource allocation. Based on that, an ethical framework that is based on Fuzzy inference systems was proposed. The proposed framework's input is the identified ethical principles, and the output is a weighted value (per patient). This value can be used as a rank or a priority factor given to the patients based on their condition and other relevant information, like the severity of their disease status. The main idea of implementing fuzzy logic in the framework is to combine more than one principle when calculating the weighted value, hence mimicking what some physicians apply in practice. Moreover, the framework's rules are aligned with the identified ethical principles. This framework can help clinicians and guide them while making critical decisions to allocate/reallocate the limited medical resources during the current COVID-19 crisis and future similar pandemics.
Identifying loci with parental differences in DNA methylation is key to unraveling parent-of-origin phenotypes. By conducting a MeDIP-Seq screen in maternal-methylation free postimplantation mouse ...embryos (Dnmt3L-/+), we demonstrate that maternal-specific methylation exists very scarcely at midgestation. We reveal two forms of oocyte-specific methylation inheritance: limited to preimplantation, or with longer duration, i.e. maternally imprinted loci. Transient and imprinted maternal germline DMRs (gDMRs) are indistinguishable in gametes and preimplantation embryos, however, de novo methylation of paternal alleles at implantation delineates their fates and acts as a major leveling factor of parent-inherited differences. We characterize two new imprinted gDMRs, at the Cdh15 and AK008011 loci, with tissue-specific imprinting loss, again by paternal methylation gain. Protection against demethylation after fertilization has been emphasized as instrumental in maintaining parent-of-origin methylation inherited from the gametes. Here we provide evidence that protection against de novo methylation acts as an equal major pivot, at implantation and throughout life.
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► Lifelong maintenance of parent-specific methylation marks is rare in mammals ► De novo methylation acts as a major leveling factor of parent-inherited differences ► Imprinted methylation marks can exist in a tissue-specific manner ► It is very likely that very few new imprinted loci remain to be discovered
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
The incorporation of data analytics in the healthcare industry has made significant progress, driven by the demand for efficient and effective big data analytics solutions. Knowledge graphs (KGs) ...have proven utility in this arena and are rooted in a number of healthcare applications to furnish better data representation and knowledge inference. However, in conjunction with a lack of a representative KG construction taxonomy, several existing approaches in this designated domain are inadequate and inferior. This paper is the first to provide a comprehensive taxonomy and a bird’s eye view of healthcare KG construction. Additionally, a thorough examination of the current state-of-the-art techniques drawn from academic works relevant to various healthcare contexts is carried out. These techniques are critically evaluated in terms of methods used for knowledge extraction, types of the knowledge base and sources, and the incorporated evaluation protocols. Finally, several research findings and existing issues in the literature are reported and discussed, opening horizons for future research in this vibrant area.
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