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41 pages, 4704 KB  
Review
Integrative Genomics and Precision Breeding for Stress-Resilient Cotton: Recent Advances and Prospects
by Zahra Ghorbanzadeh, Bahman Panahi, Leila Purhang, Zhila Hossein Panahi, Mehrshad Zeinalabedini, Mohsen Mardi, Rasmieh Hamid and Mohammad Reza Ghaffari
Agronomy 2025, 15(10), 2393; https://doi.org/10.3390/agronomy15102393 - 15 Oct 2025
Viewed by 2028
Abstract
Developing climate-resilient and high-quality cotton cultivars remains an urgent challenge, as the key target traits yield, fibre properties, and stress tolerance are highly polygenic and strongly influenced by genotype–environment interactions. Recent advances in chromosome-scale genome assemblies, pan-genomics, and haplotype-resolved resequencing have greatly enhanced [...] Read more.
Developing climate-resilient and high-quality cotton cultivars remains an urgent challenge, as the key target traits yield, fibre properties, and stress tolerance are highly polygenic and strongly influenced by genotype–environment interactions. Recent advances in chromosome-scale genome assemblies, pan-genomics, and haplotype-resolved resequencing have greatly enhanced the capacity to identify causal variants and recover non-reference alleles linked to fibre development and environmental adaptation. Parallel progress in functional genomics and precision genome editing, particularly CRISPR/Cas, base editing, and prime editing, now enables rapid, heritable modification of candidate loci across the complex tetraploid cotton genome. When integrated with high-throughput phenotyping, genomic selection, and machine learning, these approaches support predictive ideotype design rather than empirical, trial-and-error breeding. Emerging digital agriculture tools, such as digital twins that combine genomic, phenomic, and environmental data layers, allow simulation of ideotype performance and optimisation of trait combinations in silico before field validation. Speed breeding and phenomic selection further shorten generation time and increase selection intensity, bridging the gap between laboratory discovery and field deployment. However, the large-scale implementation of these technologies faces several practical constraints, including high infrastructural costs, limited accessibility for resource-constrained breeding programmes in developing regions, and uneven regulatory acceptance of genome-edited crops. However, reliance on highly targeted genome editing may inadvertently narrow allelic diversity, underscoring the need to integrate these tools with broad germplasm resources and pangenomic insights to sustain long-term adaptability. To realise these opportunities at scale, standardised data frameworks, interoperable phenotyping systems, robust multi-omic integration, and globally harmonised, science-based regulatory pathways are essential. This review synthesises recent progress, highlights case studies in fibre, oil, and stress-resilience engineering, and outlines a roadmap for translating integrative genomics into climate-smart, high-yield cotton breeding programmes. Full article
(This article belongs to the Special Issue Crop Genomics and Omics for Future Food Security)
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58 pages, 548 KB  
Article
Recent Results on Large Gaps Between Primes
by Michael Th. Rassias
Axioms 2025, 14(3), 198; https://doi.org/10.3390/axioms14030198 - 6 Mar 2025
Viewed by 1633
Abstract
One of the themes of this paper is recent results on large gaps between primes. The first of these results was achieved in the paper by Ford, Green, Konyagin and Tao. It was later improved in the joint paper of these four authors [...] Read more.
One of the themes of this paper is recent results on large gaps between primes. The first of these results was achieved in the paper by Ford, Green, Konyagin and Tao. It was later improved in the joint paper of these four authors with Maynard. One of the main ingredients of these results is old methods from Erdős and Rankin. Other ingredients are important breakthrough results from Goldston, Pintz and Yildirim, and their extension by Maynard on small gaps between primes. All these previous results are discussed in brief. The results on the appearance of k-th powers of primes contained in those large gaps obtained by the author in joint work with Maier are based on a combination of the results just described with the matrix method of Maier. Full article
(This article belongs to the Section Algebra and Number Theory)
31 pages, 35674 KB  
Article
Discussion Points of the Remote Sensing Study and Integrated Analysis of the Archaeological Landscape of Rujm el-Hiri
by Olga Khabarova, Michal Birkenfeld and Lev V. Eppelbaum
Remote Sens. 2024, 16(22), 4239; https://doi.org/10.3390/rs16224239 - 14 Nov 2024
Cited by 1 | Viewed by 9654
Abstract
Remote sensing techniques provide crucial insights into ancient settlement patterns in various regions by uncovering previously unknown archaeological sites and clarifying the topological features of known ones. Meanwhile, in the northern part of the Southern Levant, megalithic structures remain largely underexplored with these [...] Read more.
Remote sensing techniques provide crucial insights into ancient settlement patterns in various regions by uncovering previously unknown archaeological sites and clarifying the topological features of known ones. Meanwhile, in the northern part of the Southern Levant, megalithic structures remain largely underexplored with these methods. This study addresses this gap by analyzing the landscape around Rujm el-Hiri, one of the most prominent Southern Levantine megaliths dated to the Chalcolithic/Early Bronze Age, for the first time. We discuss the type and extent of the archaeological remains identified in satellite images within a broader context, focusing on the relationships between landscapes and these objects and the implications of their possible function. Our analysis of multi-year satellite imagery covering the 30 km region surrounding the Sea of Galilee reveals several distinct patterns: 40–90-m-wide circles and thick walls primarily constructed along streams, possibly as old as Rujm el-Hiri itself; later-period linear thin walls forming vast rectangular fields and flower-like clusters of ~ 20 m diameter round-shaped fences found in wet areas; tumuli, topologically linked to the linear walls and flower-like fences. Although tumuli share similar forms and likely construction techniques, their spatial distribution, connections to other archaeological features, and the statistical distribution in their sizes suggest that they might serve diverse functions. The objects and patterns identified may be used for further training neural networks to analyze their spatial properties and interrelationships. Most archaeological structures in the region were reused long after their original construction. This involved adding new features, building walls over older ones, and reshaping the landscape with new objects. Rujm el-Hiri is a prime example of such a complex sequence. Geomagnetic analysis shows that since the entire region has rotated over time, the Rujm el-Hiri’s location shifted from its original position for tens of meters for the thousands of years of the object’s existence, challenging theories of the alignment of its walls with astronomical bodies and raising questions regarding its possible identification as an observatory. Full article
(This article belongs to the Section Remote Sensing for Geospatial Science)
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17 pages, 828 KB  
Review
Exploring the Utility of Long Non-Coding RNAs for Assessing the Health Consequences of Vaping
by Ahmad Besaratinia, Hannah Blumenfeld and Stella Tommasi
Int. J. Mol. Sci. 2024, 25(15), 8554; https://doi.org/10.3390/ijms25158554 - 5 Aug 2024
Cited by 3 | Viewed by 2842
Abstract
Electronic cigarette (e-cig) use, otherwise known as “vaping”, is widespread among adolescent never-smokers and adult smokers seeking a less-harmful alternative to combustible tobacco products. To date, however, the long-term health consequences of vaping are largely unknown. Many toxicants and carcinogens present in e-cig [...] Read more.
Electronic cigarette (e-cig) use, otherwise known as “vaping”, is widespread among adolescent never-smokers and adult smokers seeking a less-harmful alternative to combustible tobacco products. To date, however, the long-term health consequences of vaping are largely unknown. Many toxicants and carcinogens present in e-cig vapor and tobacco smoke exert their biological effects through epigenetic changes that can cause dysregulation of disease-related genes. Long non-coding RNAs (lncRNAs) have emerged as prime regulators of gene expression in health and disease states. A large body of research has shown that lncRNAs regulate genes involved in the pathogenesis of smoking-associated diseases; however, the utility of lncRNAs for assessing the disease-causing potential of vaping remains to be fully determined. A limited but growing number of studies has shown that lncRNAs mediate dysregulation of disease-related genes in cells and tissues of vapers as well as cells treated in vitro with e-cig aerosol extract. This review article provides an overview of the evolution of e-cig technology, trends in use, and controversies on the safety, efficacy, and health risks or potential benefits of vaping relative to smoking. While highlighting the importance of lncRNAs in cell biology and disease, it summarizes the current and ongoing research on the modulatory effects of lncRNAs on gene regulation and disease pathogenesis in e-cig users and in vitro experimental settings. The gaps in knowledge are identified, priorities for future research are highlighted, and the importance of empirical data for tobacco products regulation and public health is underscored. Full article
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15 pages, 1887 KB  
Article
Economic Implications of Government Flood Control Policy: A Case of Rice in Japan
by Shinichi Kurihara, Yuki Yano and Atsushi Maruyama
Agriculture 2024, 14(6), 814; https://doi.org/10.3390/agriculture14060814 - 23 May 2024
Cited by 1 | Viewed by 2018
Abstract
Japan’s susceptibility to and severity of floods have necessitated flood control policies by the government. “Overflowing flood control”, in which the floods due to torrential rains are systematically diverted to agricultural lands in the upper to middle reaches, is one of them. More [...] Read more.
Japan’s susceptibility to and severity of floods have necessitated flood control policies by the government. “Overflowing flood control”, in which the floods due to torrential rains are systematically diverted to agricultural lands in the upper to middle reaches, is one of them. More information is needed on the public assessment of the overflowing flood control policy, and this research seeks to bridge this gap. Data evaluating rice affected by the policy were collected from a random nth-price auction using a developed online system. The sample consisted of 47 consumers living in the downstream areas of the Edogawa River, one of Japan’s first-class, or prime, rivers. Data on their attitudes toward the policy were collected with a questionnaire. Multiple ordered probit models are used for regression analysis. The results show that the sample respondents were willing to pay an average of JPY 1578 for 5 kg of rice, slightly higher than the national average rice production cost, and that 36% of the sample agreed with the flood control policy, which is positively associated with large families or owning many assets. Full article
(This article belongs to the Special Issue Agricultural Economics of Climate-Smart Practices)
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24 pages, 2962 KB  
Review
Functional Allele Validation by Gene Editing to Leverage the Wealth of Genetic Resources for Crop Improvement
by Michael J. Thomson, Sudip Biswas, Nikolaos Tsakirpaloglou and Endang M. Septiningsih
Int. J. Mol. Sci. 2022, 23(12), 6565; https://doi.org/10.3390/ijms23126565 - 12 Jun 2022
Cited by 20 | Viewed by 5385
Abstract
Advances in molecular technologies over the past few decades, such as high-throughput DNA marker genotyping, have provided more powerful plant breeding approaches, including marker-assisted selection and genomic selection. At the same time, massive investments in plant genetics and genomics, led by whole genome [...] Read more.
Advances in molecular technologies over the past few decades, such as high-throughput DNA marker genotyping, have provided more powerful plant breeding approaches, including marker-assisted selection and genomic selection. At the same time, massive investments in plant genetics and genomics, led by whole genome sequencing, have led to greater knowledge of genes and genetic pathways across plant genomes. However, there remains a gap between approaches focused on forward genetics, which start with a phenotype to map a mutant locus or QTL with the goal of cloning the causal gene, and approaches using reverse genetics, which start with large-scale sequence data and work back to the gene function. The recent establishment of efficient CRISPR-Cas-based gene editing promises to bridge this gap and provide a rapid method to functionally validate genes and alleles identified through studies of natural variation. CRISPR-Cas techniques can be used to knock out single or multiple genes, precisely modify genes through base and prime editing, and replace alleles. Moreover, technologies such as protoplast isolation, in planta transformation, and the use of developmental regulatory genes promise to enable high-throughput gene editing to accelerate crop improvement. Full article
(This article belongs to the Collection Feature Papers in Molecular Plant Sciences)
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50 pages, 578 KB  
Article
Combinatorial Models of the Distribution of Prime Numbers
by Vito Barbarani
Mathematics 2021, 9(11), 1224; https://doi.org/10.3390/math9111224 - 27 May 2021
Cited by 4 | Viewed by 7110
Abstract
This work is divided into two parts. In the first one, the combinatorics of a new class of randomly generated objects, exhibiting the same properties as the distribution of prime numbers, is solved and the probability distribution of the combinatorial counterpart of the [...] Read more.
This work is divided into two parts. In the first one, the combinatorics of a new class of randomly generated objects, exhibiting the same properties as the distribution of prime numbers, is solved and the probability distribution of the combinatorial counterpart of the n-th prime number is derived together with an estimate of the prime-counting function π(x). A proposition equivalent to the Prime Number Theorem (PNT) is proved to hold, while the equivalent of the Riemann Hypothesis (RH) is proved to be false with probability 1 (w.p. 1) for this model. Many identities involving Stirling numbers of the second kind and harmonic numbers are found, some of which appear to be new. The second part is dedicated to generalizing the model to investigate the conditions enabling both PNT and RH. A model representing a general class of random integer sequences is found, for which RH holds w.p. 1. The prediction of the number of consecutive prime pairs as a function of the gap d, is derived from this class of models and the results are in agreement with empirical data for large gaps. A heuristic version of the model, directly related to the sequence of primes, is discussed, and new integral lower and upper bounds of π(x) are found. Full article
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12 pages, 3264 KB  
Review
Use of Ground Penetrating Radar in the Evaluation of Wood Structures: A Review
by Brunela Pollastrelli Rodrigues, Christopher Adam Senalik, Xi Wu and James Wacker
Forests 2021, 12(4), 492; https://doi.org/10.3390/f12040492 - 16 Apr 2021
Cited by 22 | Viewed by 6418
Abstract
This paper is a review of published studies involving the use of ground penetrating radar (GPR) on wood structures. It also contains background information to help the reader understand how GPR functions. The use of GPR on wood structures began to grow in [...] Read more.
This paper is a review of published studies involving the use of ground penetrating radar (GPR) on wood structures. It also contains background information to help the reader understand how GPR functions. The use of GPR on wood structures began to grow in popularity at the turn of the millennium. GPR has many characteristics that make it attractive as an inspection tool for wood: it is faster than many acoustic and stress wave techniques; it does not require the use of a couplant; while it can also detect the presence of moisture. Moisture detection is of prime concern, and several researchers have labored to measure internal moisture using GPR. While there have been several laboratory studies involving the use of GPR on wood, its use as an inspection tool on large wood structures has been limited. This review identified knowledge gaps that need to be addressed to improve the efficacy of GPR as a reliable inspection tool of wood structure. Chief among these gaps, is the ability to distinguish the type of internal feature from the GPR output and the ability to identify internal decay. Full article
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29 pages, 8266 KB  
Review
Whole-Brain Models to Explore Altered States of Consciousness from the Bottom Up
by Rodrigo Cofré, Rubén Herzog, Pedro A.M. Mediano, Juan Piccinini, Fernando E. Rosas, Yonatan Sanz Perl and Enzo Tagliazucchi
Brain Sci. 2020, 10(9), 626; https://doi.org/10.3390/brainsci10090626 - 10 Sep 2020
Cited by 44 | Viewed by 17643
Abstract
The scope of human consciousness includes states departing from what most of us experience as ordinary wakefulness. These altered states of consciousness constitute a prime opportunity to study how global changes in brain activity relate to different varieties of subjective experience. We consider [...] Read more.
The scope of human consciousness includes states departing from what most of us experience as ordinary wakefulness. These altered states of consciousness constitute a prime opportunity to study how global changes in brain activity relate to different varieties of subjective experience. We consider the problem of explaining how global signatures of altered consciousness arise from the interplay between large-scale connectivity and local dynamical rules that can be traced to known properties of neural tissue. For this purpose, we advocate a research program aimed at bridging the gap between bottom-up generative models of whole-brain activity and the top-down signatures proposed by theories of consciousness. Throughout this paper, we define altered states of consciousness, discuss relevant signatures of consciousness observed in brain activity, and introduce whole-brain models to explore the biophysics of altered consciousness from the bottom-up. We discuss the potential of our proposal in view of the current state of the art, give specific examples of how this research agenda might play out, and emphasize how a systematic investigation of altered states of consciousness via bottom-up modeling may help us better understand the biophysical, informational, and dynamical underpinnings of consciousness. Full article
(This article belongs to the Special Issue Recent Advances in the Study of Altered State of Consciousness)
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18 pages, 9227 KB  
Article
Feasibility Study on Energy Audit and Data Driven Analysis Procedure for Building Energy Efficiency: Bench-Marking in Korean Hospital Buildings
by Dong Kon Hwang, Jinkyun Cho and Junghwan Moon
Energies 2019, 12(15), 3006; https://doi.org/10.3390/en12153006 - 3 Aug 2019
Cited by 18 | Viewed by 6701
Abstract
Growths in population, increasing demand for health care services and comfort levels, together with patients on the rise in time spent inside hospitals, assure the upward trend that energy demand will continue in the future. Since the hospital buildings operate 24 hours, 365 [...] Read more.
Growths in population, increasing demand for health care services and comfort levels, together with patients on the rise in time spent inside hospitals, assure the upward trend that energy demand will continue in the future. Since the hospital buildings operate 24 hours, 365 days a year for the treatment and restoration of patients, they are approximately 2–3 times more energy-intensive than normal buildings. For this reason, energy efficiency in hospitals is one of the prime objectives for energy policy at regional, national and international levels. This study aims to find how meaningful energy performance, reflecting good energy management and energy conservation measures (ECMs), can be operated for hospital buildings, a category encompassing complex buildings with different systems and large gaps between them. Energy audit allows us to obtain knowledge from the healthcare facility, in order to define and tune data driven analysis rules. The use of benchmarking in the energy audit of healthcare facilities enables immediate comparison between hospitals. Data driven energy analysis also allows ascertaining their expected energy consumption and estimating the possible savings margin by using the building energy flow chart. In the 2015–2017 periods, bench-marking of four public hospitals in Seoul were audited for the energy consumption related to weather conditions, total area, bed numbers, employee numbers, and analyzed for building energy flow by zones, energy sources, systems and equipment. This is a practice-based learning in a hospital project. The results reveal that the average annual energy consumption of a hospital under normal conditions, and energy efficiency factors are divided into energy baselines, energy consumption goals for energy saving and energy usage trends for setting ECMs, respectively. The indicator dependent on the area of inpatients (number of beds) proved to be the most suitable as a reference to quantify the energy consumption of a hospital. Full article
(This article belongs to the Section G: Energy and Buildings)
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14 pages, 1894 KB  
Review
Synaptic Vesicles Having Large Contact Areas with the Presynaptic Membrane are Preferentially Hemifused at Active Zones of Frog Neuromuscular Junctions Fixed during Synaptic Activity
by Jae Hoon Jung
Int. J. Mol. Sci. 2019, 20(11), 2692; https://doi.org/10.3390/ijms20112692 - 31 May 2019
Cited by 6 | Viewed by 5218
Abstract
Synaptic vesicles dock on the presynaptic plasma membrane of axon terminals and become ready to fuse with the presynaptic membrane or primed. Fusion of the vesicle membrane and presynaptic membrane results in the formation of a pore between the membranes, through which the [...] Read more.
Synaptic vesicles dock on the presynaptic plasma membrane of axon terminals and become ready to fuse with the presynaptic membrane or primed. Fusion of the vesicle membrane and presynaptic membrane results in the formation of a pore between the membranes, through which the vesicle’s neurotransmitter is released into the synaptic cleft. A recent electron tomography study on frog neuromuscular junctions fixed at rest showed that there is no discernible gap between or merging of the membrane of docked synaptic vesicles with the presynaptic membrane, however, the extent of the contact area between the membrane of docked synaptic vesicles and the presynaptic membrane varies 10-fold with a normal distribution. The study also showed that when the neuromuscular junctions are fixed during repetitive electrical nerve stimulation, the portion of large contact areas in the distribution is reduced compared to the portion of small contact areas, suggesting that docked synaptic vesicles with the largest contact areas are greatly primed to fuse with the membrane. Furthermore, the finding of several hemifused synaptic vesicles among the docked vesicles was briefly reported. Here, the spatial relationship of 81 synaptic vesicles with the presynaptic membrane at active zones of the neuromuscular junctions fixed during stimulation is described in detail. For the most of the vesicles, the combined thickness of each of their contact sites was not different from the sum of the membrane thicknesses of the vesicle membrane and presynaptic membrane, similar to the docked vesicles at active zones of the resting neuromuscular junctions. However, the combined membrane thickness of a small portion of the vesicles was considerably less than the sum of the membrane thicknesses, indicating that the membranes at their contact sites were fixed in a state of hemifusion. Moreover, the hemifused vesicles were found to have large contact areas with the presynaptic membrane. These findings support the recently proposed hypothesis that, at frog neuromuscular junctions, docked synaptic vesicles with the largest contact areas are most primed for fusion with the presynaptic membrane, and that hemifusion is a fusion intermediate step of the vesicle membrane with the presynaptic membrane for synaptic transmission. Full article
(This article belongs to the Special Issue Neurotransmitter Secretion and Release)
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14 pages, 1857 KB  
Article
Histopathology of the Liver, Kidney, and Spleen of Mice Exposed to Gold Nanoparticles
by Khalid Elfaki Ibrahim, Mohsen Ghaleb Al-Mutary, Amel Omer Bakhiet and Haseeb Ahmad Khan
Molecules 2018, 23(8), 1848; https://doi.org/10.3390/molecules23081848 - 25 Jul 2018
Cited by 178 | Viewed by 20119
Abstract
Gold nanoparticles (GNPs) are biocompatible nanomaterials that are currently researched for biomedical applications such as imaging and targeted drug delivery. In this investigation, we studied the effects of a single dose (injected on day 1) as well as a priming dose (two injections [...] Read more.
Gold nanoparticles (GNPs) are biocompatible nanomaterials that are currently researched for biomedical applications such as imaging and targeted drug delivery. In this investigation, we studied the effects of a single dose (injected on day 1) as well as a priming dose (two injections with a gap of one week) of 5 nm, 20 nm, and 50 nm diameter GNPs on the structural and biochemical changes in the liver, kidney, and spleen of mice. The results showed that small sized GNPs (5 nm) produced significant pathological changes in the liver on day 2 that gradually reduced on day 8. The medium (20 nm) and large (50 nm) sized GNPs preferentially targeted the spleen and caused significant pathological changes to the spleen architecture on day 2 that persisted on day 8 as well. There were minimal and insignificant pathological changes to the kidneys irrespective of the GNPs size. The animals that were primed with the pre-exposure of GNPs did not show any aggravation of histological changes after the second dose of the same GNPs. None of the dose regimens of the GNPs were able to significantly affect the markers of oxidative stress including glutathione (GSH) and malondialdehyde (MDA) in all of the organs that were studied. In conclusion, the size of GNPs plays an important role in their pathological effects on different organs of mice. Moreover, the primed animals become refractory to further pathological changes after the second dose of GNPs, suggesting the importance of a priming dose in medical applications of GNPs. Full article
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21 pages, 954 KB  
Concept Paper
Maristem—Stem Cells of Marine/Aquatic Invertebrates: From Basic Research to Innovative Applications
by Loriano Ballarin, Baruch Rinkevich, Kerstin Bartscherer, Artur Burzynski, Sebastien Cambier, Matteo Cammarata, Isabelle Domart-Coulon, Damjana Drobne, Juanma Encinas, Uri Frank, Anne-Marie Geneviere, Bert Hobmayer, Helike Löhelaid, Daniel Lyons, Pedro Martinez, Paola Oliveri, Lorena Peric, Stefano Piraino, Andreja Ramšak, Sebastian Rakers, Fabian Rentzsch, Amalia Rosner, Tiago Henriques Da Silva, Ildiko Somorjai, Sherif Suleiman and Ana Varela Coelhoadd Show full author list remove Hide full author list
Sustainability 2018, 10(2), 526; https://doi.org/10.3390/su10020526 - 15 Feb 2018
Cited by 13 | Viewed by 10362
Abstract
The “stem cells” discipline represents one of the most dynamic areas in biomedicine. While adult marine/aquatic invertebrate stem cell (MISC) biology is of prime research and medical interest, studies on stem cells from organisms outside the classical vertebrate (e.g., human, mouse, and zebrafish) [...] Read more.
The “stem cells” discipline represents one of the most dynamic areas in biomedicine. While adult marine/aquatic invertebrate stem cell (MISC) biology is of prime research and medical interest, studies on stem cells from organisms outside the classical vertebrate (e.g., human, mouse, and zebrafish) and invertebrate (e.g., Drosophila, Caenorhabditis) models have not been pursued vigorously. Marine/aquatic invertebrates constitute the largest biodiversity and the widest phylogenetic radiation on Earth, from morphologically simple organisms (e.g., sponges, cnidarians), to the more complex mollusks, crustaceans, echinoderms, and protochordates. These organisms contain a kaleidoscope of MISC-types that allow the production of a large number of novel bioactive-molecules, many of which are of significant potential interest for human health. MISCs further participate in aging and regeneration phenomena, including whole-body regeneration. For years, the European MISC-community has been highly fragmented and has established scarce ties with biomedical industries in an attempt to harness MISCs for human welfare. Thus, it is important to (i) consolidate the European community of researchers working on MISCs; (ii) promote and coordinate European research on MISC biology; (iii) stimulate young researchers to embark on research in MISC-biology; (iv) develop, validate, and share novel MISC tools and methodologies; (v) establish the MISC discipline as a forefront interest of biomedical disciplines, including nanobiomedicine; and (vi) establish collaborations with industries to exploit MISCs as sources of bioactive molecules. In order to fill the recognized gaps, the EC-COST Action 16203 “MARISTEM” has recently been launched. At its initial stage, the consortium unites 26 scientists from EC countries, Cooperating countries, and Near Neighbor Countries. Full article
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21 pages, 791 KB  
Review
Revisiting Plus-Strand DNA Synthesis in Retroviruses and Long Terminal Repeat Retrotransposons: Dynamics of Enzyme: Substrate Interactions
by Daniele Fabris, John P. Marino and Stuart F. J. Le Grice
Viruses 2009, 1(3), 657-677; https://doi.org/10.3390/v1030657 - 4 Nov 2009
Cited by 3 | Viewed by 14010
Abstract
Although polypurine tract (PPT)-primed initiation of plus-strand DNA synthesis in retroviruses and LTR-containing retrotransposons can be accurately duplicated, the molecular details underlying this concerted series of events remain largely unknown. Importantly, the PPT 3’ terminus must be accommodated by ribonuclease H (RNase H) [...] Read more.
Although polypurine tract (PPT)-primed initiation of plus-strand DNA synthesis in retroviruses and LTR-containing retrotransposons can be accurately duplicated, the molecular details underlying this concerted series of events remain largely unknown. Importantly, the PPT 3’ terminus must be accommodated by ribonuclease H (RNase H) and DNA polymerase catalytic centers situated at either terminus of the cognate reverse transcriptase (RT), and in the case of the HIV-1 enzyme, ~70Å apart. Communication between RT and the RNA/DNA hybrid therefore appears necessary to promote these events. The crystal structure of the HIV-1 RT/PPT complex, while informative, positions the RNase H active site several bases pairs from the PPT/U3 junction, and thus provides limited information on cleavage specificity. To fill the gap between biochemical and crystallographic approaches, we review a multidisciplinary approach combining chemical probing, mass spectrometry, NMR spectroscopy and single molecule spectroscopy. Our studies also indicate that nonnucleoside RT inhibitors affect enzyme orientation, suggesting initiation of plus-strand DNA synthesis as a potential therapeutic target. Full article
(This article belongs to the Special Issue Retroviral Enzymes)
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