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PubMed2026

Advances in the Application of Adenine Base Editor (ABE) in Biology and Medicine: Prospects and Challenges.

Adenine base editors (ABEs), which achieve A·T to G·C conversions in the genome precisely, symbolize a groundbreaking development in genetic engineering across animal, plant, and microbial systems. This review systematically summed up the research progress and current challenges of ABE in medical and biological applications: it outlined the historical context and pivotal milestones of its technological development; it emphasized major therapeutic advances for genetic diseases including spinal muscular atrophy, mitochondrial genetic disorders, and hyperlipidemia; it provided a comprehensive overview of its prospective uses for enhancing genetic traits in agricultural crops, including grains and fruits; this review conducted a multidimensional assessment of ABE performance through systematic comparison with other base editing technologies, comprehensively evaluating both editing efficiency and inherent limitations. It specifically addresses biosecurity risks such as off-target effects and genomic instability. Finally, safety concerns were proposed as the central challenge hindering its clinical translation, although ABE holds immense promise for precision medicine and agricultural breeding. Unlike previous reviews that mainly summarized early ABE development and general applications, this review particularly emphasizes recently engineered ABE systems, translational bottlenecks, delivery strategies, comparative clinical feasibility, and unresolved biosafety challenges that currently limit broader therapeutic and agricultural applications.

Adenine base editors↗
PubMed1998

[Use of transgenic animals in the European Union]

Transgenic animals present unique possibilities for medical, agricultural and fundamental research, and as a means of producing valuable pharmaceutical and nutrient products. Their use has increased dramatically in recent years and is set to increase further in the near future. It has been claimed that transgenic animals might allow reduction and refinement in animal use, via more-precise gene targeting in breeding programmes. However, these objectives are threatened by transgenic procedures which may promote greater animal use, more-varied applications, and the greater likelihood of animal suffering. Current legislation on animal experimentation, for example, Directive 86/609/EU, was passed and implemented before the full implications of transgenesis were recognised. For this reason, ECVAM organised a workshop which was held in Southwell, Nottinghamshire, UK, on 7-11 April 1997. The aim of this workshop was to reach a consensus on a set of guidelines designed to assist regulatory authorities in their decision-making process. The conclusions of the workshop are subdivided into general considerations, proposals to use transgenic animals, production and use of transgenic animals, specific considerations relating to animals used as basic research/disease models, animals used in testing for toxicity and carcinogenicity, and transgenic farm animals. 14 recommendations have been derived from these conclusions and should make an important contribution to ensuring that the interests and welfare of animals are given due respect. They demonstrate a willingness by scientists to respond to public concerns and they should facilitate a consistent, harmonised and equitable regulatory approach within the EU.

Journal Article↗
PubMed1999

Genetic engineering of crops as potential source of genetic hazard in the human diet.

The benefits of genetic engineering of crop plants to improve the reliability and quality of the world food supply have been contrasted with public concerns raised about the food safety of the resulting products. Debates have concentrated on the possible unforeseen risks associated with the accumulation of new metabolites in crop plants that may contribute to toxins, allergens and genetic hazards in the human diet. This review examines the various molecular and biochemical mechanisms by which new hazards may appear in foods as a direct consequence of genetic engineering in crop plants. Such hazards may arise from the expression products of the inserted genes, secondary or pleiotropic effects of transgene expression, and random insertional mutagenic effects resulting from transgene integration into plant genomes. However, when traditional plant breeding is evaluated in the same context, these mechanisms are no different from those that have been widely accepted from the past use of new cultivars in agriculture. The risks associated with the introduction of new genes via genetic engineering must be considered alongside the common breeding practice of introgressing large fragments of chromatin from related wild species into crop cultivars. The large proportion of such introgressed DNA involves genes of unknown function linked to the trait of interest such as pest or disease resistance. In this context, the potential risks of introducing new food hazards from the applications of genetic engineering are no different from the risks that might be anticipated from genetic manipulation of crops via traditional breeding. In many respects, the precise manner in which genetic engineering can control the nature and expression of the transferred DNA offers greater confidence for producing the desired outcome compared with traditional breeding.

Crops, Agricultural↗
PubMed2005

Possibilities with today's reproductive technologies.

Reproductive efficiency is critical to economic viability for cow/calf producers; however, very few producers take advantage of available reproductive technologies that can increase profitability. Today, more opportunities are available for producers who want to capture value from known genetics. Through the use of artificial insemination (AI), the average producer has access to a wide range of high-accuracy sires that can be selected to match production goals. Systems to synchronize estrus and ovulation can now produce pregnancy rates to a single fixed-timed AI that are 10-15% greater than those of the previous generation. Increased age and weight of calves at weaning is sufficient in some situations to pay for the cost of synchronization and AI. As a result of synchronization, more cows calve early the next year and in subsequent years of synchronization. The breeding season can be shortened without reducing end-of-season pregnancy rates, since synchronized cows have one more chance to conceive than unsynchronized cows in a 22-25 day interval. Cow nutrition can be more economically and precisely managed with a shorter breeding period. Producers that establish AI programs now will be prepared to take advantage of newly identified superior genetics or other technologies, e.g. sexed semen, when they become available. Trends towards more value-based marketing and improvements in pregnancy rates from synchronization systems, make this a key time to be aware of the possibilities using reproductive technologies.

Animals↗
PubMed2001

Health evaluation of penguins (Sphenisciformes) following mortality in the Falklands (South Atlantic).

In the Falklands, heavy mortality of rock-hopper penguins Eudyptes chrysocome occurred during the 1985-86 breeding season. Starvation was diagnosed as the primary cause of death, possibly caused by a shortage of euphausiid crustaceans (krill) due to unusual meterological conditions. 'Puffinosis' may possibly have been a contributory factor; otherwise no conclusive evidence of infectious disease or toxicosis was found and also no evidence of radioactive contamination. In the 1986-87 breeding season no unusual mortality occurred, but 99 apparently healthy penguins were examined, i.e., rockhoppers Eudyptes chrysocome syn E. crestatus, gentoos Pygoscelis papua and Magellanics Spheniscus magellanicus. Full necropsies were carried out on 54. Tissue examinations were made for cadmium, copper, iron, manganese, mercury, lead and zinc. High tissue cadmium concentrations found in healthy birds in 1987 were similar to those in penguins which died in 1986, and therefore not considered to be of pathological significance. Although there has been no repetition of the unusually hot 1985-86 breeding season in the Falklands, penguins and other seabirds have had fluctuating breeding successes since then. The precise cause, including the roles of meteorological conditions and overexploitation of some forms of prey species, is unclear.

Animals↗
PubMed1987

Orientation behaviour of toads (Bufo bufo) displaced from the breeding site.

The sensory basis and spatial range of orientation to the breeding site were studied in the toad Bufo bufo, during two breeding seasons. Toads were displaced passively from their breeding pond and fitted with a tracking device to record the path of migration in individuals. The directional choice and the straightness of trails after release were used to quantify the effect of experimental treatments. In both years, control (untreated) toads headed to the breeding site with the same precision at all release sites. The initial orientation of toads blinded by opaque tape over their eyes did not differ from controls, but the return paths were not as direct. The directional choice of anosmic toads was apparently random, however, individuals followed a straight path in a chosen direction. Anosmic toads also blinded were completely disoriented, moving in cycloid trails. Bar magnets glued to the head caused an increase in dispersion of toads. However, in some individual releases a directional bias without increased dispersion was observed. Sky conditions (clear or overcast) did not influence the initial orientation or the dispersion of toads. Nevertheless, the breeding site component was significantly correlated with wind direction in relation to the breeding site. Wind blowing from the breeding site improved the initial orientation, whereas wind from the opposite direction reduced the breeding site component. The spatial range for the ability to relocate the breeding pond after displacement exceeded 3 km, but the time taken to select the correct direction increased with the displacement distance. The results indicate that after displacement the initial orientation of B. bufo is based mainly on olfactory and magnetic cues, with visual control of straightness.

Animals↗
PubMed1995

The mh gene causing double-muscling in cattle maps to bovine Chromosome 2.

While the hereditary nature of the "double-muscling" phenotype (a generalized muscular hypertrophy documented in several cattle breeds) is well established, its precise segregation mode has remained controversial. Both monogenic models (autosomal dominant or recessive) and oligogenic models have been proposed. Using a panel of 213 bovine microsatellite markers, and an experimental pedigree obtained by backing "double-muscled (Belgian Blue) x conventional (Friesian)"1 dams to double-muscle sire, we have mapped a locus on bovine Chromosome (CHr) 2 that accounts for all the phenotypic variance in the backcross generation. This locus, referred to as mh (muscular hypertrophy), has been positioned with respects to a map composed of seven Chr 2-specific microsatellites, at 2 cM from the closet marker. This result confirms the validity in the Belgian Blue population of the monogenic model involving an autosomal mh locus, characterized by a wild-type "+" and a recessive "mh" allele, causing the double-muscling phenotype in the homozygous condition. The linkage relationship between the mh locus and the Chr 2 markers was confirmed in three informative pedigrees collected from the general Belgian Blue Cattle population, reinforcing the notice of genetic homogeneity of the double-muscling trait in this breed. This work paves the way towards marker-assisted selection for or against the double muscling trait, and towards positional cloning of the corresponding gene.

Animals↗
PubMed2026

Plant nitrogen nutrition: enhancing plant resilience to abiotic stresses.

Nitrogen (N) is not only an essential macronutrient for plant growth and development but also functions as a pivotal signaling molecule that orchestrates adaptive responses to various abiotic stresses, including acidic stress, aluminum toxicity, salinity, drought, and extreme temperatures. This review synthesizes recent advances in our understanding of the molecular mechanisms by which N signaling, mediated by different N forms (e.g., NH4+ and NO3-), integrates with core stress-response pathways. We specifically discuss the genetic crosstalk between N sensing and key signaling cascades, including abscisic acid (ABA) signaling, the salt overly sensitive (SOS) pathway, and reactive oxygen species (ROS) homeostasis. The review details how this integration modulates physiological and transcriptional reprogramming through central regulators such as NIN-like proteins (NLPs), calcineurin B-like protein (CBL)-interacting protein kinase (CIPK), and the target of rapamycin (TOR) kinase, ultimately optimizing the trade-off between growth and tolerance. By establishing a unified genetic and molecular framework, this review aims to provide a theoretical basis for developing novel strategies in precision N management and molecular breeding to synergistically enhance N use efficiency (NUE) and abiotic stress tolerance in crops.

Nitrogen↗
PubMed2004

Natal homing in juvenile loggerhead turtles (Caretta caretta).

Juvenile loggerhead turtles (Caretta caretta) from West Atlantic nesting beaches occupy oceanic (pelagic) habitats in the eastern Atlantic and Mediterranean, whereas larger juvenile turtles occupy shallow (neritic) habitats along the continental coastline of North America. Hence the switch from oceanic to neritic stage can involve a trans-oceanic migration. Several researchers have suggested that at the end of the oceanic phase, juveniles are homing to feeding habitats in the vicinity of their natal rookery. To test the hypothesis of juvenile homing behaviour, we surveyed 10 juvenile feeding zones across the eastern USA with mitochondrial DNA control region sequences (N = 1437) and compared these samples to potential source (nesting) populations in the Atlantic Ocean and Mediterranean Sea (N = 465). The results indicated a shallow, but significant, population structure of neritic juveniles (PhiST = 0.0088, P = 0.016), and haplotype frequency differences were significantly correlated between coastal feeding populations and adjacent nesting populations (Mantel test R2 = 0.52, P = 0.001). Mixed stock analyses (using a Bayesian algorithm) indicated that juveniles occurred at elevated frequency in the vicinity of their natal rookery. Hence, all lines of evidence supported the hypothesis of juvenile homing in loggerhead turtles. While not as precise as the homing of breeding adults, this behaviour nonetheless places juvenile turtles in the vicinity of their natal nesting colonies. Some of the coastal hazards that affect declining nesting populations may also affect the next generation of turtles feeding in nearby habitats.

Analysis of Variance↗
PubMed2004

Magnetocardiographic differences of ventricular repolarization parameters between Wistar rats and guinea pigs.

UNLABELLED: The morphology and range of duration of the action potential (AP) in normal Wistar rat's (WR) myocyte markedly differ from those of guinea pigs (GP), whose plateau (phase 2) duration is longer. Thus a clear-cut T wave can be easy defined in GP but not in WR. Aim of this study was to differentiate magnetocardiographic (MCG) ventricular repolarization (VR) parameters of healthy adult WR and GP. METHODS: 10 female animals (5 Guinea pigs and 5 Wistar rats) were studied with a 36-channel MCG system (sensitivity of 20 fT/square root of Hz1/2) and with one ECG lead, in an unshielded hospital room. To assess VR, HR-corrected, JTpeak, JTend, Tpeak-end and QTend, intervals were measured from both MCG waveforms. Timing was improved by MCG maps analysis. Magnetic field orientation (MFO), its dynamics (MFD) and stability (JTS) during the JT interval, were also automatically computed from MCG maps. RESULTS: All repolarization intervals were significantly shorter in WR than in GP, except the Tpeak-end, which was longer. MFO and MFD also differed. CONCLUSIONS: MCG estimate of VR parameters, in adult WR and GP, is precise enough to evidence breed-related differences, consistent with physiological heterogeneity of duration during phases 2 and 3 of the AP, and with an higher degree of transmural dispersion of repolarization in WR.

Animals↗
PubMed2002

The methods to generate transgenic animals and to control transgene expression.

Transgenic animals have been used for years to study gene function and to create models for the study of human diseases. This approach has become still more justified after the complete sequencing of several genomes. Transgenic animals are ready to become industrial bioreactors for the preparation of pharmaceuticals in milk and probably in the future in egg white. Improvement of animal production by transgenesis is still in infancy. Despite its intensive use, animal transgenesis is still suffering from technical limitations. The generation of transgenics has recently become easier or possible for different species thanks to the use of transposons or retrovirus, to incubation of sperm which DNA followed by fertilization by intracellular sperm injection or not and to the use of the cloning technique using somatic cells in which genes have been added or inactivated. The Cre-LoxP system is more and more used to withdraw a given sequence from the genome or to target the integration of a foreign DNA. The tetracycline system has been improved and can more and more frequently be used to obtain faithful expression of transgenes. Several tools: RNA forming a triple helix with DNA, antisense RNA including double strand RNA inducing RNA interference and ribozymes, and also expression of proteins having a negative transdominant effect, are tentatively being improved to inhibit specifically the expression of host or viral genes.All these techniques are expected to offer experimenters new and more precise models to study gene function even in large animals. Improvement of breeding by transgenesis has become more plausible including through the precise allele replacement in farm animals.

Animals↗
PubMed1992

Factors affecting the reproductive performance of the weaned sow.

The majority of sows return to estrus within 2 weeks after weaning. Swine practitioners attempt to optimize production by reducing the WEI. Some sows fail to resume estrous cyclicity after weaning; however, the endocrinologic pathogenesis of these anestrous sows is speculative. The average WEI is influenced by numerous factors, including season, environmental temperature, photoperiod, nutrition, stress, facility design, lactation length, and management practices. It is evident that the majority of these factors have a more profound influence on primiparous sows than on multiparous sows. Optimum protein and energy consumption by sows during lactation and after weaning and effective utilization of breeding facilities reduce the WEI. The precise roles of photoperiodic changes, elevated environmental temperatures, and stress in seasonal infertility remain poorly understood. Fortunately, current management techniques have reduced the WEI on most farms without instituting therapeutic measures.

Anestrus↗
PubMed2006

Approaches to increasing the salt tolerance of wheat and other cereals.

This review describes physiological mechanisms and selectable indicators of gene action, with the aim of promoting new screening methods to identify genetic variation for increasing the salt tolerance of cereal crops. Physiological mechanisms that underlie traits for salt tolerance could be used to identify new genetic sources of salt tolerance. Important mechanisms of tolerance involve Na+ exclusion from the transpiration stream, sequestration of Na+ and Cl- in the vacuoles of root and leaf cells, and other processes that promote fast growth despite the osmotic stress of the salt outside the roots. Screening methods for these traits are discussed in relation to their use in breeding, particularly with respect to wheat. Precise phenotyping is the key to finding and introducing new genes for salt tolerance into crop plants.

Edible Grain↗
PubMed1997

Spontaneous rate of sister chromatid exchanges (SCEs) in mitotic chromosomes of sheep (Ovis aries L.) and comparison with cattle (Bos taurus L.), goat (Capra hircus L.) and river buffalo (Bubalus bubalis L.).

The spontaneous level of sister chromatid exchanges (SCEs) in the sheep, estimated by exposing peripheral blood lymphocytes in 0.1 microgram/ml of 5'-bromodeoxyuridine (BrdU), was 4.08 +/- 2.47 SCE/cell, 2.04 SCE/cell cycle, 0.038 SCE/chromosome. The dose-response relationships, observed by exposing the cells to 0.1, 0.25, 0.5, 1.0, 2.5, and 5.0 micrograms/ml of BrdU, rose rapidly from 0.1 to 0.25 microgram/ml, and less rapidly at higher concentrations, thus reaching a saturation level. The analysis of variance, performed on the square root transformed data at 0.1 and 5 micrograms/ml of BrdU, indicated significant differences (P < 0.001) among the four donors tested. The distribution of the SCE/cell frequencies in the cell population of the four donors followed the Poisson 'mixture' probability function, thus confirming previous findings. The spontaneous rate of SCE/cell of sheep is compared with those previously reported for cattle, goat and river buffalo. The theoretical and practical implications of the spontaneous sister chromatid exchanges are discussed in relation to their possible use in animal production for (a) better genetic evaluation of the breeding animals under selection, (b) more precise monitoring of the genotoxic effects of environmental pollutants.

Animals↗
PubMed1993

Haematological parameters of the Polish Primitive Horses.

Average values of chosen haematological parameters have been described in a population of 90 clinically normal Polish Primitive Horses. The comparison of the results with values given in literature for horses as a whole and for other breeds enabled us to state that Polish Primitive Horses' blood is characterized by relatively low values of RBC, PCV, segmented neutrophils and monocytes, and high percentage of lymphocytes. It was demonstrated that values of some blood parameters of examined animals are similar to typical results obtained for primitive and cold-blooded horses. Moreover, it was proved that age, sex, and season have influence upon many blood parameters' values of the Polish Primitive Horses. More precise evaluation of results received with that breed will be possible when that influence is taken into consideration.

Aging↗
PubMed2026

CRISPR-Cas technologies for precision genome editing in plants: advances, applications, and future perspectives.

Developing climate-smart crops with enhanced crop productivity, nutritional quality, resistance to biological and environmental stressors is vital for global food security. While hybrid breeding forms the cornerstone of modern crop improvement, conventional breeding approaches are limited by genetic barriers and prolonged breeding cycles. CRISPR-Cas based genome editing has revolutionized plant biology by allowing precise, efficient, and multiplex genetic modifications. This review provides a comprehensive synthesis of a recent advances in CRISPR-Cas technologies and their strategic applications in crop genetics and hybrid breeding. We summarize major genome-editing strategies, including gene knock-out, base editing (BE), knock-in, gene replacement, epigenome editing, and transcriptional regulation. Furthermore, we contrast stable, transient, and DNA-free delivery systems, highlighting ribonucleoprotein (RNP)-mediated delivery for minimizing off-target effects and avoiding transgene integration. We showcase how these technologies accelerate hybrid breeding by engineering male sterility systems, fixing heterosis, and generating high-throughput mutant libraries for trait discovery. Finally, we synthesize major bottlenecks in tissue culture-independent transformation and delivery systems, while outlining how emerging paradigms like de novo domestication and synthetic biology will shape the future of climate-resilient agriculture.

CRISPR/Cas↗
PubMed2005

Effects of hypothyroidism on gonadal function after transition of short day photoperiod in male golden hamsters (Mesocricetus auratus).

Thyroid hormones permit the annual reproductive transition of seasonal breeders. Although, precise function of thyroid hormones in seasonal breeding is not well understood. In the present study, we examined effects of hypothyroidism on the hypothalamus-pituitary-gonadal axis in adult male golden hamsters after transition of the short-day photoperiod (SD; 8 h light: 16 h dark) condition. We confirmed that hypothyroid, which had been induced by administration of thiouracil in drinking water for 4 weeks, did not have direct effects on testes in male hamsters under the long-day photoperiod. Plasma concentrations of free T3 and T4 decreased 15 weeks after transition of SD condition. Plasma concentrations of testosterone in the hypothyroid group decreased earlier than in the control group after the transition from LD to SD. In animals treated with testosterone after castration, plasma concentrations of LH in the hypothyroid group decreased earlier than in the control group after the transition of SD. On the other hand, pituitary response to GnRH for LH release did not change in castrated hamsters as a result of hypothyroidism. These results suggest that thyroid hormones act the hypothalamus and might be required to maintain GnRH secretion in male golden hamsters.

Androgens↗
PubMed1996

Major involvement of rabbit liver cytochrome P4501A in thiabendazole 5-hydroxylation.

1. Thiabendazole is a widely used food preservative and anthelmintic drug for breeding animal species. In order to characterize precisely the cytochrome P450 isozyme(s) involved in its major route of metabolism, a rapid and sensitive spectrofluorimetric method was developed for the simultaneous determination of thiabendazole and its main hepatic metabolite 5-hydroxythiabendazole. 2. The kinetics of thiabendazole 5-hydroxylation were determined in microsomal preparations from control rabbits or animals previously treated with either beta-naphthoflavone, isosafrole, phenobarbital, rifampicin or clofibrate. These treatments led to specific induction of CYP1A1, 1A2, 2B4, 3A6 and 4A1 respectively. 3. By considering this panel of characterised microsomal preparations, only those obtained from BNF-treated rabbits exhibited an increase in thiabendazole 5-hydroxylase activity Ethoxyresorufin O-deethylation in these microsomes was solely inhibited by thiabendazole. These argue for a specific involvement of the CYP1A subfamily. 4. In the CYP1A subfamily, CYP1A2 appears to be responsible for basal 5-hydroxylation and further unidentified metabolism of thiabendazole in control livers. However, the major involvement of CYP1A1 is supported by the following characteristics of 5-hydroxylation of thiabendazole: (1) the correlation with CYP1A1 expression and (2) the inhibition by ellipticine and not by furafylline, inhibitors of CYP1A1 and CYP1A2 respectively. 5. All these data demonstrated that the rabbit cytochrome P4501A is predominantly involved in thiabendazole 5-hydroxylation which has been suspected to be critical in terms of safety of the parent drug.

Animals↗