Biochemical Society transactions · 2022
Takahiro Ishizaki、Sophia Hernandez、Martina S Paoletta 等
The ∼30 Mb genomes of the Plasmodium parasites that cause malaria each encode ∼5000 genes, but the functions of the majority remain unknown. This is due to a paucity of functional annotation from sequence homology, which is compounded by low genetic tractability compared with many model organisms. In recent years technical breakthroughs have made forward and reverse genome-scale screens in Plasmodium possible. Furthermore, the adaptation of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-Associated protein 9 (CRISPR/Cas9) technology has dramatically improved gene editing efficiency at the single gene level. Here, we review the arrival of genetic screens in malaria parasites to analyse parasite gene function at a genome-scale and their impact on understanding parasite biology. CRISPR/Cas9 screens, which have revolutionised human and model organism research, have not yet been implemented in malaria parasites due to the need for more complex CRISPR/Cas9 gene targeting vector libraries. We therefore introduce the reader to CRISPR-based screens in the related apicomplexan Toxoplasma gondii and discuss how these approaches could be adapted to develop CRISPR/Cas9 based genome-scale genetic screens in malaria parasites. Moreover, since more than half of Plasmodium genes are required for normal asexual blood-stage reproduction, and cannot be targeted using knockout methods, we discuss how CRISPR/Cas9 could be used to scale up conditional gene knockdown approaches to systematically assign function to essential genes.
Current biology : CB · 2023
Volker M Lueth、Ralf Reski
Often overlooked, these small but otherwise brilliant plants began covering Earth's land masses more than 450 million years ago. They saw the dinosaurs come and go, and they saw us humans coming. Mosses, liverworts and hornworts comprise the bryophytes, the second largest monophyletic clade of land plants (embryophytes), after the vascular plants (tracheophytes). Like all embryophytes, mosses exhibit a haplodiplontic life cycle. This alternation of generations (originally termed Generationswechsel in German) between the haploid gametophyte and the diploid sporophyte implies that every plant genome encodes two distinct ontogenies, in contrast to animal genomes. Contrary to tracheophytes, the haploid gametophyte is the dominant generation in mosses. Haploidy of the major tissues facilitates gene-function annotation via reverse genetics. Nevertheless, the diploid sporophyte of mosses, the spore capsule, is a visible structure unlike the gametophyte of flowering plants, which is largely reduced and embedded in the sporophyte. Visibility of both generations on one plant facilitates the analysis of the alternation of generations, and in a broader sense evo-devo studies. Whereas the conservation of moss morphology over hundreds of millions of years suggests stasis, molecular data reveal fast evolving moss genomes, leaving an enigma for evolutionary biologists. Finally, the extraordinary resilience of mosses may provide lessons for current man-made climate change. In this Primer, we will highlight some of the peculiarities of mosses from historical observations to current genomic data, with an emphasis on their development, reproduction, evolution, biotic interactions, and potential for biotechnology. Mosses from three genera - the living fossil Takakia, the ecosystems engineer Sphagnum, and the model moss Physcomitrella - exemplify the scientific insights and the applications mosses have to offer.
Nature · 2015
Eric D Green、James D Watson、Francis S Collins
The Human Genome Project, which launched a quarter of a century ago this week, still holds lessons for the consortium-based science it ushered in, say Eric D. Green, James D. Watson and Francis S. Collins.
International Journal of Integrated Care · 2025
R. Smeets、D. Hertroijs、D. Ruwaard 等
Context and stakeholders: Integrated care is considered a promising alternative care model to deal with the rising demands for care and – related to that – high work pressure. The TARGET program is an initiative to provide primary care professionals with the required knowledge, skills and confidence to implement integrated care in practice. TARGET was developed by combing scientific insights with practice-based experiences, preferences and needs. Different steering groups including care professionals, patient representatives, policy makers and health insurers co-created and improved the program. In this pilot study, frontrunner general practices were invited to implement the program in practice for the first time. Aims were to assess feasibility and acceptability of TARGET for professionals and patients. Secondly, this study helped to derive lessons for both professionals and supporting networks of professionals about how to make integrated care successful in practice.
Methods and results: Between August 2020 and February 2021, the TARGET program was pilot-tested in seven general practices. The program consists of three main components, of which the first two were studied: a population segmentation tool to identify patients with complex care needs, a person-centred needs assessment to get a holistic view of patients’ needs, and network support to enhance cooperation and referral. The components were accompanied by tools, trainings and meetings with peers. In this study, we reviewed the program through non-participant observations and interviews with professionals and patients. Results shows that the program is considered feasible and acceptable by most professionals and patients. For instance, the trainings, tools and peer meetings helped professionals to – amongst others – acquire new conversational skills. The program was considered acceptable as well: TARGET enabled meaningful patient-doctor interactions and a comprehensive, positive focus on health, which aligned well with the values of both professionals and patients. Practices were generally positive about continuation of TARGET. However, not all practices implemented the program with full team commitment and adequate network relations were sometimes lacking.
Lessons learned and next steps: Tools, trainings and peer meetings are crucial to make a transformation to integrated primary care. Furthermore, developing and improving this ‘equipment’ in co-creation with professionals, policy makers and health insurers is key to ensure feasibility and acceptability in practice. Starting small with the implementation of integrated care is above all helpful to take big steps in the end: it enables improvement of tools and the implementation strategy. For instance, to enhance team commitment to the program, practices should be supported to tailor the program to their needs. By using a ‘practice development plan’, practices are currently encouraged to develop a practice-wide vision on their practice, as a foundation for tailoring the program. In addition, practices should be offered inspiring ‘best practices’ about network enhancement, to enable adequate referral and lower work pressure in primary care. The implementation of TARGET has steadily increased: since October 2023, more than 100 practices use the program. This enables evaluation of ‘how, why and under what circumstances’ the TARGET program leads to changes in the Quadruple Aim.
2017
M. Kumari、Nalin Bharti
暂无摘要
PLoS genetics · 2016
B Jesse Shapiro、Jean-Baptiste Leducq、James Mallet
Concepts and definitions of species have been debated by generations of biologists and remain controversial. Microbes pose a particular challenge because of their genetic diversity, asexual reproduction, and often promiscuous horizontal gene transfer (HGT). However, microbes also present an opportunity to study and understand speciation because of their rapid evolution, both in nature and in the lab, and small, easily sequenced genomes. Here, we review how microbial population genomics has enabled us to catch speciation "in the act" and how the results have challenged and enriched our concepts of species, with implications for all domains of life. We describe how recombination (including HGT and introgression) has shaped the genomes of nascent microbial, animal, and plant species and argue for a prominent role of natural selection in initiating and maintaining speciation. We ask how universal is the process of speciation across the tree of life, and what lessons can be drawn from microbes? Comparative genomics showing the extent of HGT in natural populations certainly jeopardizes the relevance of vertical descent (i.e., the species tree) in speciation. Nevertheless, we conclude that species do indeed exist as clusters of genetic and ecological similarity and that speciation is driven primarily by natural selection, regardless of the balance between horizontal and vertical descent.
Biomolecules · 2019
C. M. Klinger、Elisabeth H. Richardson
Plastid genome sequences are becoming more readily available with the increase in high-throughput sequencing, and whole-organelle genetic data is available for algae and plants from across the diversity of photosynthetic eukaryotes. This has provided incredible opportunities for studying species which may not be amenable to in vivo study or genetic manipulation or may not yet have been cultured. Research into plastid genomes has pushed the limits of what can be deduced from genomic information, and in particular genomic information obtained from public databases. In this Review, we discuss how research into plastid genomes has benefitted enormously from the explosion of publicly available genome sequence. We describe two case studies in how using publicly available gene data has supported previously held hypotheses about plastid traits from lineage-restricted experiments across algal and plant diversity. We propose how this approach could be used across disciplines for inferring functional and biological characteristics from genomic approaches, including integration of new computational and bioinformatic approaches such as machine learning. We argue that the techniques developed to gain the maximum possible insight from plastid genomes can be applied across the eukaryotic tree of life.
Viruses · 2025
Rhiannon R Abrahams、Kinjal Majumder
Parvoviruses are small, single-stranded DNA viruses that have evolved sophisticated mechanisms to hijack host cell machinery for replication and persistence. One critical aspect of this interaction involves the manipulation of the host's DNA Damage Response (DDR) pathways. While the viral genome is comparatively simple, parvoviruses have developed strategies that cause significant DNA damage, activate DDR pathways, and disrupt the host cell cycle. This review will explore the impact of parvovirus infections on host genome stability, focusing on key viral species such as Adeno-Associated Virus (AAV), Minute Virus of Mice (MVM), and Human Bocavirus (HBoV), and their interactions with DDR proteins. Since parvoviruses are used as oncolytic agents and gene therapy vectors, a better understanding of cellular DDR pathways will aid in engineering potent anti-cancer agents and gene therapies for chronic diseases.
Journal of the Royal Society of New Zealand · 2025
Susan Parry、I. Bissett、J. McMenamin 等
ABSTRACT Implementation of the National Bowel Screening Programme for Aotearoa New Zealand has been a 26-year journey with many challenges and obstacles. This paper describes lessons learnt. Despite international evidence of efficacy from studies before the year 2000, country-specific decisions shaped by committed multidisciplinary teams were required. Before introducing bowel screening, many initiatives to improve related healthcare delivery were implemented, which often led to systemic improvements. A pilot study was needed to demonstrate that bowel screening was safe, affordable, and could be delivered equitably. Despite comprehensive plans based on the Pilot with ongoing adjustments, to date, the programme has fallen short of achieving equity for participation for Māori and Pacific peoples. The delays involved in developing the required population IT system were challenging resulting in a period where two different IT systems were being used simultaneously. This should be avoided. General Practice was involved from the outset, with an increasing role as the programme developed. Critics of progress were sometimes vocal, but input from global leaders in bowel screening helped keep the programme on track to national implementation. The programme has delivered in terms of safety and early diagnosis of cancer. Its lessons provide a foundation for future public health initiatives.
Viruses · 2024
Jiaojiao Fan、Zhiqiang Qin
Human Endogenous Retrovirus Sequences (HERVs) constitute up to 8% of the human genome, yet not all HERVs remain silent passengers within our genomes. Some HERVs, especially HERV type K (HERV-K), have been found to be frequently transactivated in a variety of inflammatory diseases and human cancers. Np9, a small protein translated from the HERV-K env reading frame, has been reported as an oncogenic protein and is present in a variety of tumors and transformed cells. The Np9 protein can crosstalk with many cellular factors and is involved in the pathogenicity of various diseases, including some oncogenic virus infections. In the current review, we summarize recent findings about Np9 clinical relevance/implications, its mediated cellular functions/mechanisms, and potential targeted therapies in development.
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AI 辅助短评，基于标题和摘要整理该综述聚焦RNA病毒中RNA结构介导的基因调控，整合多病毒家族机制证据并与真核转录组类比，提出RNA结构为基因表达中心调控层。优势在于跨体系视角与机制梳理，但属叙述性综述，未提供系统检索策略或证据分级，病毒与真核间保守性的推断需谨慎解读。对治疗与合成生物学潜力的论述宜视为展望而非已验证结论。