ResearchPad - research-highlight https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[COVID-19: more evidence emerges]]> https://www.researchpad.co/article/elastic_article_9391 <![CDATA[Liquid phase condensation directs nucleosome epigenetic modifications]]> https://www.researchpad.co/article/elastic_article_9072 <![CDATA[Designing of improved drugs for COVID-19: Crystal structure of SARS-CoV-2 main protease M<sup>pro</sup>]]> https://www.researchpad.co/article/Nebaf329f-f1e7-4aa6-87d3-6bf61917352b <![CDATA[Symposium summary: Epigenetic inheritance—impact for biology and society 26–28 August 2019, Zurich, Switzerland]]> https://www.researchpad.co/article/N3bf47f0c-f584-4ccd-ba86-641813dafc7e The concept of epigenetic inheritance proposes a new and unconventional way to think about heredity in health and disease, at the interface between genetics and the environment. Epigenetic inheritance is a form of biological inheritance not encoded in the DNA sequence itself but mediated by epigenetic factors. Because epigenetic factors can be modulated by the environment, they can relay this information to the genome and modify its activity consequentially. If epigenetic changes induced by environmental exposure are present in the germline and persist in germ cells during development until conception, they have the potential to transfer the traces of ancestral exposure to the progeny.

This form of heredity relates to the extremely important question of nature versus nurture and how much of our own make-up is genetically or epigenetically determined, a question that remains largely unresolved. Because it questions the dominant dogma of genetics and brings a paradigm shift in sciences, it has to creating strong bridges between disciplines and provide solid causal evidence to be firmly established.

The second edition of a conference fully dedicated to epigenetic inheritance was held in August 2019 in Zurich, Switzerland. This symposium titled ‘Epigenetic inheritance: impact for biology and society’ (http://www.epigenetic-inheritance-zurich.ethz.ch), gathered experts in the field of epigenetic inheritance to discuss the concept and pertinent findings, exchange views and expertise about models and methods, and address challenges raised by this new discipline. The symposium offered a mix of invited lectures and short talks selected from abstracts, poster sessions and a workshop ‘Meet the experts: Q&A’. A tour of a local omics facility the Functional Genomics Center Zurich was also offered to interested participants. Additional comments and impressions were shared by attendees on Twitter #eisz19 during and after the symposium. This summary provides an overview of the different sessions and talks and describes the main findings presented.

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<![CDATA[Novel coronavirus takes flight from bats?]]> https://www.researchpad.co/article/N97559d8e-2b05-48f8-bcee-f2dca258642d

Two recent studies provide initial insights into a novel coronavirus that is associated with an outbreak of human respiratory disease.

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<![CDATA[Studying human lung infection in mice]]> https://www.researchpad.co/article/N2a884248-d4bd-467f-a302-3b4dc9e36266

Mice implanted with human lung tissue model pathogen infection and immune responses.

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<![CDATA[Lack of maternal–fetal SARS-CoV-2 transmission]]> https://www.researchpad.co/article/Ncbb55111-63b6-40b5-a170-97ae473a7508 ]]> <![CDATA[Igniting autophagy through the regulation of phase separation]]> https://www.researchpad.co/article/N503faa80-17ef-47e8-815d-699c820773a1 ]]> <![CDATA[CCR5-Δ32 biology, gene editing, and warnings for the future of CRISPR-Cas9 as a human and humane gene editing tool]]> https://www.researchpad.co/article/N499c554e-7ef5-4545-b1e8-b22ea86ca8ce

Background

Biomedical technologies have not just improved human health but also assisted in the creation of human life. Since the first birth of a healthy baby by in vitro fertilization (IVF) 40 years ago, IVF has been the mainstay treatment for couples struggling with infertility. This technology, in addition to increasingly accessible genetic testing, has made it possible for countless couples to have children. Since CRISPR-Cas9 gene editing was described in 2015, its potential for targeting genetic diseases has been much anticipated. However, the potential of using CRISPR-Cas9 for human germline modification has led to many fears of “designer babies” and widespread concerns for the impact of this technology on human evolution and its implications in Social Darwinism. In addition to these ethical/moral concerns, there remain many unknowns about CRISPR-Cas9 technology and endless unanticipated consequence to gene editing.

Methods

In this paper, we analyze the current progresses of CRISPR-Cas9 technology and discuss the theoretical advantages of certain allelic variances in the C-C chemokine receptor 5 gene (CCR5) in the setting of recent ethical/moral concerns regarding gene editing using the CRISPR-Cas9 system.

Results

These uncertainties have been highlighted recently by the birth of Chinese twins whose C-C chemokine receptor 5 (CCR5) gene had been inactivated via CRISPR-Cas9 to be theoretically protective against HIV infection. CCR5 signaling is critical for the successful infection of human immunodeficiency virus (HIV) and people with homozygous inactivating CCR5-Δ32 mutations have been shown to be protected against HIV infection. Those with the CCR5-Δ32/Δ32 mutation also have greater neuroplasticity, allowing for improved recovery from neurological trauma, and decreased Chagas cardiomyopathy. However, the CCR5-Δ32/Δ32 mutation has also been associated with earlier clinical manifestations for West Nile infection, ambiguous effects on osteoclast function, and a four-fold increased mortality from influenza infection. These detrimental health impacts, in addition to the confounding factor that these CRISPR babies do not carry this exact CCR5-Δ32/Δ32 mutation, lead to many questions regarding the children’s future health and the moral conundrum of their birth. The creation and birth of these babies was not completed with any scientific, ethical, or governmental oversight, which has spurned the acceleration of talks regarding global regulations for human genetic editing.

Conclusions

Although we can try to regulate for ethical, health-related only use of this technology, moral and governmental oversights need to be supplemented by technical regulations. For instance, whole genome sequencing needs to be used to eliminate off-target mutations that could affect the health and safety of infants born to this process. Like Pandora’s Box, we cannot pretend to forget CRISPR-Cas9 technology, all we can do is ensure a safe, moral, and equitable used of this technology.

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<![CDATA[“On the bat’s back I do fly”]]> https://www.researchpad.co/article/N056b5510-fdb1-41c1-ba79-0faaddd6f730

Two recent studies provide new insights into bat virus spillover.

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<![CDATA[SARS-CoV-2 and COVID-19: The most important research questions]]> https://www.researchpad.co/article/N1a9ec320-8d5a-4cd4-a8b1-ecddee5933ee

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis.

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<![CDATA[Switching off DNA repair—how colorectal cancer evades targeted therapies through adaptive mutability]]> https://www.researchpad.co/article/N5a2e80c3-6f73-4d96-8395-ca333557df0a ]]> <![CDATA[Capturing the complexity of sex differences requires multidimensional behavioral models]]> https://www.researchpad.co/article/Na420cda6-d8ff-4189-a30b-055feb326cf0 ]]> <![CDATA[The Genome of Opium Poppy Reveals Evolutionary History of Morphinan Pathway]]> https://www.researchpad.co/article/5ca25da5d5eed0c4846d5772 ]]> <![CDATA[Sin1–mTORC2 signaling drives glycolysis of developing thymocytes]]> https://www.researchpad.co/article/5c929cd8d5eed0c4843875dc ]]> <![CDATA[Meeting Announcement: 2nd Symposium ‘Epigenetic Inheritance: Impact for Biology and Society’ 26–28 August 2019, ETH Zurich, Switzerland]]> https://www.researchpad.co/article/5c80115ad5eed0c484a99075 ]]> <![CDATA[Current and emerging trends in prostate cancer immunotherapy]]> https://www.researchpad.co/article/5c7560f7d5eed0c484cb3bf3

There have been a number of recent developments in the treatment of castration-resistant prostate cancer which seek to exploit the hormonal axis. Still, the castration-resistant prostate cancer remains a major challenge since this is the lethal and incurable phenotype which results in tens of thousands of deaths every year. There has been emerging interest in utilizing anticancer immunotherapy in prostate cancer, especially since the development of sipuleucel-T. Several other prostate cancer therapeutic vaccines including autologous and allogeneic vaccines, as well as viral vector-based vaccines, have demonstrated promising results in early trials. The checkpoint inhibitors which have shown some dramatic results in other cancers are now being studied in advanced prostate cancer setting. Studies are examining the therapeutic effects for both CTLA-4 inhibitors and PD-1/PD-L1 inhibitors. It appears that definitions and measurements of response used in cytotoxic therapies may not be valid in determining response to immunotherapy. Early reports suggest that combination therapies, either concurrent or sequential, may be needed to achieve the desired response against advanced prostate cancer.

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<![CDATA[PSA screening - for whom and when?]]> https://www.researchpad.co/article/5c7560f0d5eed0c484cb3b6c

Reasons for and against screening of prostate cancer have been discussed widely over the last decade. In 2014, the European Randomized Trial for Screening of Prostate Cancer (ERSPC) has reported a relative reduction of the cancer-specific survival of 27% in participants who definitely followed the screening protocol. This relative advantage has proven to be stable from year 7 to year 13 after the beginning of screening. Still, the disadvantages of overdiagnosis and overtreatment are the downsides of a population-based screening approach. But given the overall advantage of screening, a risk-adapted prostate-specific antigen (PSA) screening using a baseline PSA value at ages 45-50 may significantly reduce the number needed to diagnose maintaining the benefits of screening. PROBASE is a randomized risk-adapted screening trial currently ongoing in Germany to answer this important question.

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<![CDATA[No luck replicating the immune response in twins]]> https://www.researchpad.co/article/5989daabab0ee8fa60ba95f5

Recent twin studies highlight the astonishing impact of non-heritable contributions to our immune health and wellbeing. Immunologists, long familiar with heterogeneity generated from within cells, must now grapple with heterogeneity between and within individuals which is present to an extraordinary degree. The capacity to interpret and find patterns in the face of such immune system diversity may be limited when sampling is restricted to blood, necessitating the development of new approaches.

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<![CDATA[Insights into cancer mechanisms from genomic research on urological cancers]]> https://www.researchpad.co/article/5989daf9ab0ee8fa60bc4271

Molecular mechanisms driving cancer development and progression are rarely unique to one cancer type. Rather, recent genomic studies of urological cancers suggest that common mechanisms recur with variations. Examples include alterations in hypoxia response regulation, epigenetic regulator proteins, and signal transduction pathways in renal, prostatic and urothelial carcinomas. Consideration of these variations alongside the common basic cancer mechanisms might be important for the successful development of targeted therapies.

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