Transduplication resulted in the incorporation of two protein-coding sequences into the Turmoil-1 transposable element of C. elegans

Transposable elements may acquire unrelated gene fragments into their sequences in a process called transduplication. Transduplication of protein-coding genes is common in plants, but is unknown of in animals. Here, we report that the Turmoil-1 transposable element in C. elegans has incorporated two protein-coding sequences into its inverted terminal repeat (ITR) sequences. The ITRs of Turmoil-1 contain a conserved RNA recognition motif (RRM) that originated from the rsp- 2 gene and a fragment from the protein-coding region of the cpg-3 gene. We further report that an open reading frame specific to C. elegans may have been created as a result of a Turmoil-1 insertion. Mutations at the 5' splice site of this open reading frame may have reactivated the transduplicated RRM moti

SERpredict: Detection of tissue- or tumor-specific isoforms generated through exonization of transposable elements

Background: Transposed elements (TEs) are known to affect transcriptomes, because either new exons are generated from intronic transposed elements (this is called exonization), or the element inserts into the exon, leading to a new transcript. Several examples in the literature show that isoforms generated by an exonization are specific to a certain tissue (for example the heart muscle) or inflict a disease. Thus, exonizations can have negative effects for the transcriptome of an organism. Results: As we aimed at detecting other tissue- or tumor-specific isoforms in human and mouse genomes which were generated through exonization of a transposed element, we designed the automated analysis pipeline SERpredict (SER = Specific Exonized Retroelement) making use of Bayesian Statistics. With this pipeline, we found several genes in which a transposed element formed a tissue- or tumor-specific isoform. Conclusion: Our results show that SERpredict produces relevant results, demonstrating the importance of transposed elements in shaping both the human and the mouse transcriptomes. The effect of transposed elements on the human transcriptome is several times higher than the effect on the mouse transcriptome, due to the contribution of the primate-specific Alu element

The role of transposable elements in the evolution of non-mammalian vertebrates and invertebrates

Background: Transposable elements (TEs) have played an important role in the diversification and enrichment of mammalian transcriptomes through various mechanisms such as exonization and intronization (the birth of new exons/introns from previously intronic/exonic sequences, respectively), and insertion into first and last exons. However, no extensive analysis has compared the effects of TEs on the transcriptomes of mammals, non-mammalian vertebrates and invertebrates. Results: We analyzed the influence of TEs on the transcriptomes of five species, three invertebrates and two non-mammalian vertebrates. Compared to previously analyzed mammals, there were lower levels of TE introduction into introns, significantly lower numbers of exonizations originating from TEs and a lower percentage of TE insertion within the first and last exons. Although the transcriptomes of vertebrates exhibit significant levels of exonization of TEs, only anecdotal cases were found in invertebrates. In vertebrates, as in mammals, the exonized TEs are mostly alternatively spliced, indicating that selective pressure maintains the original mRNA product generated from such genes. Conclusions: Exonization of TEs is widespread in mammals, less so in non-mammalian vertebrates, and very low in invertebrates. We assume that the exonization process depends on the length of introns. Vertebrates, unlike invertebrates, are characterized by long introns and short internal exons. Our results suggest that there is a direct link between the length of introns and exonization of TEs and that this process became more prevalent following the appearance of mammals

Reflections on Palliative Care from the Jewish and Islamic Tradition

Spiritual care is a vital part of holistic patient care. Awareness of common patient beliefs will facilitate discussions about spirituality. Such conversations are inherently good for the patient, deepen the caring staff-patient-family relationship, and enhance understanding of how beliefs influence care decisions. All healthcare providers are likely to encounter Muslim patients, yet many lack basic knowledge of the Muslim faith and of the applications of Islamic teachings to palliative care. Similarly, some of the concepts underlying positive Jewish approaches to palliative care are not well known. We outline Jewish and Islamic attitudes toward suffering, treatment, and the end of life. We discuss our religions' approaches to treatments deemed unnecessary by medical staff, and consider some of the cultural reasons that patients and family members might object to palliative care, concluding with specific suggestions for the medical team

Comparative analysis of transposed element insertion within human and mouse genomes reveals Alu's unique role in shaping the human transcriptome

Background: Transposed elements (TEs) have a substantial impact on mammalian evolution and are involved in numerous genetic diseases. We compared the impact of TEs on the human transcriptome and the mouse transcriptome. Results: We compiled a dataset of all TEs in the human and mouse genomes, identifying 3,932,058 and 3,122,416 TEs, respectively. We than extracted TEs located within human and mouse genes and, surprisingly, we found that 60% of TEs in both human and mouse are located in intronic sequences, even though introns comprise only 24% of the human genome. All TE families in both human and mouse can exonize. TE families that are shared between human and mouse exhibit the same percentage of TE exonization in the two species, but the exonization level of Alu, a primatespecific retroelement, is significantly greater than that of other TEs within the human genome, leading to a higher level of TE exonization in human than in mouse (1,824 exons compared with 506 exons, respectively). We detected a primate-specific mechanism for intron gain, in which Alu insertion into an exon creates a new intron located in the 3' untranslated region (termed 'intronization'). Finally, the insertion of TEs into the first and last exons of a gene is more frequent in human than in mouse, leading to longer exons in human. Conclusion: Our findings reveal many effects of TEs on these two transcriptomes. These effects are substantially greater in human than in mouse, which is due to the presence of Alu elements in human

The Alternative Choice of Constitutive Exons throughout Evolution

Alternative cassette exons are known to originate from two processes exonization of intronic sequences and exon shuffling. Herein, we suggest an additional mechanism by which constitutively spliced exons become alternative cassette exons during evolution. We compiled a dataset of orthologous exons from human and mouse that are constitutively spliced in one species but alternatively spliced in the other. Examination of these exons suggests that the common ancestors were constitutively spliced. We show that relaxation of the 59 splice site during evolution is one of the molecular mechanisms by which exons shift from constitutive to alternative splicing. This shift is associated with the fixation of exonic splicing regulatory sequences (ESRs) that are essential for exon definition and control the inclusion level only after the transition to alternative splicing. The effect of each ESR on splicing and the combinatorial effects between two ESRs are conserved from fish to human. Our results uncover an evolutionary pathway that increases transcriptome diversity by shifting exons from constitutive to alternative splicin

The Medical Necessity for Medicinal Cannabis: Prospective, Observational Study Evaluating the Treatment in Cancer Patients on Supportive or Palliative Care

Background. Cancer patients using cannabis report better influence from the plant extract than from synthetic products. However, almost all the research conducted to date has been performed with synthetic products. We followed patients with a medicinal cannabis license to evaluate the advantages and side effects of using cannabis by cancer patients. Methods. The study included two interviews based on questionnaires regarding symptoms and side effects, the first held on the day the license was issued and the second 6–8 weeks later. Cancer symptoms and cannabis side effects were documented on scales from 0 to 4 following the CTCAE. The distress thermometer was used also. Results. Of the 211 patients who had a first interview, only 131 had the second interview, 25 of whom stopped treatment after less than a week. All cancer or anticancer treatment-related symptoms showed significant improvement (P<0.001). No significant side effects except for memory lessening in patients with prolonged cannabis use (P=0.002) were noted. Conclusion. The positive effects of cannabis on various cancer-related symptoms are tempered by reliance on self-reporting for many of the variables. Although studies with a control group are missing, the improvement in symptoms should push the use of cannabis in palliative treatment of oncology patients

Transforming Pain into Beauty: On Art, Healing, and Care for the Spirit

From drawing to sculpture, poetry to journaling, and dance to music and song, the arts can have a major impact on patients’ spiritual well-being and health. The arts empower patients to fulfill the basic human drive to create and give patients a sense of possibility. Through creative expression, patients regain a feeling of wholeness, individually and as part of the larger world. Although spiritual caregivers have made occasional use of the arts, it would be better for the arts to be seen as a pillar of spiritual care provision. This paper provides a model for arts-based spiritual care (chaplaincy) in oncology/hematology and elsewhere. We discuss how to match the art form intervention to the individual patient and give examples of many kinds of uniquely spiritual arts-based interventions. In life, there are occasional “caseuras,” or ruptures. Using a theoretical foundation drawn from theologian Michael Fishbane, our model of arts-based spiritual care bridges the experience of the caesura to a renewed sense of meaning, or spiritual reorientation, that can be discovered within the reality of illness. Additionally, the ambiguity and playfulness inherent to creative expression strengthen the patient’s flexibility and resilience