Emerging Topics in Life Sciences最新文献

Approximately half of the human genome includes repetitive sequences, and these DNA sequences (as well as their transcribed repetitive RNA and translated amino-acid repeat sequences) are known as the repeatome. Within this repeatome there are a couple of million tandem repeats, dispersed throughout the genome. These tandem repeats have been estimated to constitute ∼8% of the entire human genome. These tandem repeats can be located throughout exons, introns and intergenic regions, thus potentially affecting the structure and function of tandemly repetitive DNA, RNA and protein sequences. Over more than three decades, more than 60 monogenic human disorders have been found to be caused by tandem-repeat mutations. These monogenic tandem-repeat disorders include Huntington's disease, a variety of ataxias, amyotrophic lateral sclerosis and frontotemporal dementia, as well as many other neurodegenerative diseases. Furthermore, tandem-repeat disorders can include fragile X syndrome, related fragile X disorders, as well as other neurological and psychiatric disorders. However, these monogenic tandem-repeat disorders, which were discovered via their dominant or recessive modes of inheritance, may represent the 'tip of the iceberg' with respect to tandem-repeat contributions to human disorders. A previous proposal that tandem repeats may contribute to the 'missing heritability' of various common polygenic human disorders has recently been supported by a variety of new evidence. This includes genome-wide studies that associate tandem-repeat mutations with autism, schizophrenia, Parkinson's disease and various types of cancers. In this article, I will discuss how tandem-repeat mutations and polymorphisms could contribute to a wide range of common disorders, along with some of the many major challenges of tandem-repeat biology and medicine. Finally, I will discuss the potential of tandem repeats to be therapeutically targeted, so as to prevent and treat an expanding range of human disorders.

The genetic improvement of crops faces the significant challenge of feeding an ever-increasing population amidst a changing climate, and when governments are adopting a 'more with less' approach to reduce input use. Plant breeding has the potential to contribute to the United Nations Agenda 2030 by addressing various sustainable development goals (SDGs), with its most profound impact expected on SDG2 Zero Hunger. To expedite the time-consuming crossbreeding process, a genomic-led approach for predicting breeding values, targeted mutagenesis through gene editing, high-throughput phenomics for trait evaluation, enviromics for including characterization of the testing environments, machine learning for effective management of large datasets, and speed breeding techniques promoting early flowering and seed production are being incorporated into the plant breeding toolbox. These advancements are poised to enhance genetic gains through selection in the cultigen pools of various crops. Consequently, these knowledge-based breeding methods are pursued for trait introgression, population improvement, and cultivar development. This article uses the potato crop as an example to showcase the progress being made in both genomic-led approaches and gene editing for accelerating the delivery of genetic gains through the utilization of genetically enhanced elite germplasm. It also further underscores that access to technological advances in plant breeding may be influenced by regulations and intellectual property rights.

Biocultural diversity is the ever-evolving and irreplaceable sum total of all living organisms inhabiting the Earth. It plays a significant role in sustainable productivity and ecosystem services that benefit humanity and is closely allied with human cultural diversity. Despite its essentiality, biodiversity is seriously threatened by the insatiable and inequitable human exploitation of the Earth's resources. One of the benefits of biodiversity is its utilization in crop improvement, including cropping improvement (agronomic cultivation practices) and genetic improvement (plant breeding). Crop improvement has tended to decrease agricultural biodiversity since the origins of agriculture, but awareness of this situation can reverse this negative trend. Cropping improvement can strive to use more diverse cultivars and a broader complement of crops on farms and in landscapes. It can also focus on underutilized crops, including legumes. Genetic improvement can access a broader range of biodiversity sources and, with the assistance of modern breeding tools like genomics, can facilitate the introduction of additional characteristics that improve yield, mitigate environmental stresses, and restore, at least partially, lost crop biodiversity. The current legal framework covering biodiversity includes national intellectual property and international treaty instruments, which have tended to limit access and innovation to biodiversity. A global system of access and benefit sharing, encompassing digital sequence information, would benefit humanity but remains an elusive goal. The Kunming-Montréal Global Biodiversity Framework sets forth an ambitious set of targets and goals to be accomplished by 2030 and 2050, respectively, to protect and restore biocultural diversity, including agrobiodiversity.

Crop biofortification has significantly progressed in the last few decades. The first biofortification success was quality protein maize, leading to double the amount of the essential amino acids lysine and tryptophan. This was followed by biofortification of staple crops such as maize, wheat, rice, legumes and cassava for nutrients such as Fe and Zn and provitamin A. These crops have reached millions of households, especially in the developing regions of the world. The development and release of these biofortified crops through conventional breeding generally took 8-10 years. To speed up the process, molecular markers, genome-wide association studies and genomic selection have been incorporated into breeding efforts. Genetic engineering has the potential to increase the efficiency of crop biofortification through multi-nutrient biofortification in a short timespan and to combine biofortification with climate resilience. Regulatory issues still prevent the dissemination of genetically modified crops in many countries. This could be overcome by CRISPR-Cas-mediated genome editing, as it seems that many countries will regulate products of genome editing less strictly than transgenic crops. Effective policies on national or regional level are needed for the sustainable production of biofortified crops. The availability of affordable quality biofortified seed and other inputs should be ensured through local seed systems, which will increase the production and adoption of biofortified crops. There is scope to expand the crops and the range of nutrients for biofortification. Genetic engineering should be combined with conventional breeding as a approach for future improvement of multi-nutrient crops.

In the current scenario of climate change, global agricultural systems are facing remarkable challenges in order to increase production, while reducing the negative environmental impact. Nano-enabled technologies have the potential to revolutionise farming practices by increasing the efficiency of inputs and minimising losses, as well as contributing to sustainable agriculture. Two promising applications of nanotechnology in agriculture are nanobiosensors and nanoformulations (NFs). Nanobiosensors can help detect biotic and abiotic stresses in plants before they affect plant production, while NFs can make agrochemicals, more efficient and less polluting. NFs are becoming new-age materials with a wide variety of nanoparticle-based formulations such as fertilisers, herbicides, insecticides, and fungicides. They facilitate the site-targeted controlled delivery of agrochemicals enhancing their efficiency and reducing dosages. Smart farming aims to monitor and detect parameters related to plant health and environmental conditions in order to help sustainable agriculture. Nanobiosensors can provide real-time analytical data, including detection of nutrient levels, metabolites, pesticides, presence of pathogens, soil moisture, and temperature, aiding in precision farming practices, and optimising resource usage. In this review, we summarise recent innovative uses of NFs and nanobiosensors in agriculture that may boost crop protection and production, as well as reducing the negative environmental impact of agricultural activities. However, successful implementation of these smart technologies would require two special considerations: (i) educating farmers about appropriate use of nanotechnology, (ii) conducting field trials to ensure effectiveness under real conditions.

Biomembranes are fundamental to our understanding of the cell, the basic building block of all life. An intriguing aspect of membranes is their ability to assume a variety of shapes, which is crucial for cell function. Here, we review various membrane shaping mechanisms with special focus on the current understanding of how local curvature and local rigidity induced by membrane proteins leads to emerging forces and consequently large-scale membrane deformations. We also argue that describing the interaction of rigid proteins with membranes purely in terms of local membrane curvature is incomplete and that changes in the membrane rigidity moduli must also be considered.

Many cellular lipid bilayers consist of leaflets that differ in their lipid composition - a non-equilibrium state actively maintained by cellular sorting processes that counter passive lipid flip-flop. While this lipidomic aspect of membrane asymmetry has been known for half a century, its elastic and thermodynamic ramifications have garnered attention only fairly recently. Notably, the torque arising when lipids of different spontaneous curvature reside in the two leaflets can be counterbalanced by a difference in lateral mechanical stress between them. Such membranes can be essentially flat in their relaxed state, despite being compositionally strongly asymmetric, but they harbor a surprisingly large but macroscopically invisible differential stress. This hidden stress can affect a wide range of other membrane properties, such as the resistance to bending, the nature of phase transitions in its leaflets, and the distribution of flippable species, most notably sterols. In this short note we offer a concise overview of our recently proposed basic framework for capturing the interplay between curvature, lateral stress, leaflet phase behavior, and cholesterol distribution in generally asymmetric membranes, and how its implied signatures might be used to learn more about the hidden but physically consequential differential stress.

Our knowledge on the asymmetric distribution of sphingomyelin (SM) in the plasma membrane is largely based on the biochemical analysis of erythrocytes using sphingomyelinase (SMase). However, recent studies showed that the product of SMase, ceramide, disturbs transmembrane lipid distribution. This led to the development of the complimentary histochemical method, which combines electron microscopy and SM-binding proteins. This review discusses the advantages and caveats of published methods of measuring transbilayer distribution of SM. Recent finding of the proteins involved in the transbilayer movement of SM will also be summarized.

Eukaryotic pathogens with an intracellular parasitic lifestyle are shielded from extracellular threats during replication and growth. In addition to many nutrients, parasites scavenge host cell lipids to establish complex membrane structures inside their host cells. To counteract the disturbance of the host cell plasma membrane they have evolved strategies to regulate phospholipid asymmetry. In this review, the function and importance of lipid asymmetry in the interactions of intracellular protozoan parasites with the target and immune cells of the host are highlighted. The malaria parasite Plasmodium infects red blood cells and extensively refurbishes these terminally differentiated cells. Cholesterol depletion and an altered intracellular calcium ion homeostasis can lead to disruption in erythrocyte membrane asymmetry and increased exposure of phosphatidylserine (PS). Binding to the PS receptor on monocytes and macrophages results in phagocytosis and destruction of infected erythrocytes. Leishmania parasites display apoptotic mimicry by actively enhancing PS exposure on their surface to trigger increased infection of macrophages. In extracellular Toxoplasma gondii a P4-type ATPase/CDC50 co-chaperone pair functions as a flippase important for exocytosis of specialised secretory organelles. Identification and functional analysis of parasite lipid-translocating proteins, i.e. flippases, floppases, and scramblases, will be central for the recognition of the molecular mechanisms of parasite/host interactions. Ultimately, a better understanding of parasitic diseases, host immunity, and immune escape by parasites require more research on the dynamics of phospholipid bilayers of parasites and the infected host cell.

The development of electron cryomicroscopy (cryo-EM) has evolved immensely in the last several decades and is now well-established in the analysis of protein structure both in isolation and in their cellular context. This review focuses on the history and application of cryo-EM to the analysis of membrane architecture. Parallels between the levels of organization of protein structure are useful in organizing the discussion of the unique parameters that influence membrane structure and function. Importantly, the timescales of lipid motion in bilayers with respect to the timescales of sample vitrification is discussed and reveals what types of membrane structure can be reliably extracted in cryo-EM images of vitrified samples. Appreciating these limitations, a review of the application of cryo-EM to examine the lateral organization of ordered and disordered domains in reconstituted and biologically derived membranes is provided. Finally, a brief outlook for further development and application of cryo-EM to the analysis of membrane architecture is provided.