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1.
G3 (Bethesda) ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271181

RESUMEN

The MiniMUGA genotyping array is a popular tool for genetic quality control of laboratory mice and genotyping samples from most experimental crosses involving laboratory strains, particularly for reduced complexity crosses. The content of the production version of the MiniMUGA array is fixed; however, there is the opportunity to improve the array's performance and the associated report's usefulness by leveraging thousands of samples genotyped since the initial description of MiniMUGA. Here, we report our efforts to update and improve marker annotation, increase the number and the reliability of the consensus genotypes for classical inbred strains and substrains, and increase the number of constructs reliably detected with MiniMUGA. In addition, we have implemented key changes in the informatics pipeline to identify and quantify the contribution of specific genetic backgrounds to the makeup of a given sample, remove arbitrary thresholds, include the Y Chromosome and mitochondrial genome in the ideogram, and improve robust detection of the presence of commercially available substrains based on diagnostic alleles. Finally, we have updated the layout of the report to simplify the interpretation and completeness of the analysis and added a section summarizing the ideogram in table format. These changes will be of general interest to the mouse research community and will be instrumental in our goal of improving the rigor and reproducibility of mouse-based biomedical research.

2.
Front Plant Sci ; 15: 1434388, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224844

RESUMEN

Quinoa is emerging as a key seed crop for global food security due to its ability to grow in marginal environments and its excellent nutritional properties. Because quinoa is partially allogamous, we have developed quinoa inbred lines necessary for molecular genetic analysis. Our comprehensive genomic analysis showed that the quinoa inbred lines fall into three genetic subpopulations: northern highland, southern highland, and lowland. Lowland and highland quinoa are the same species, but have very different genotypes and phenotypes. Lowland quinoa has relatively small grains and a darker grain color, and is widely tested and grown around the world. In contrast, the white, large-grained highland quinoa is grown in the Andean highlands, including the region where quinoa originated, and is exported worldwide as high-quality quinoa. Recently, we have shown that viral vectors can be used to regulate endogenous genes in quinoa, paving the way for functional genomics to reveal the diversity of quinoa. However, although a high-quality assembly has recently been reported for a lowland quinoa line, genomic resources of the quality required for functional genomics are not available for highland quinoa lines. Here we present high-quality chromosome-level genome assemblies for two highland inbred quinoa lines, J075 representing the northern highland line and J100 representing the southern highland line, using PacBio HiFi sequencing and dpMIG-seq. In addition, we demonstrate the importance of verifying and correcting reference-based scaffold assembly with other approaches such as linkage maps. The assembled genome sizes of J075 and J100 are 1.29 and 1.32 Gb, with contigs N50 of 66.3 and 12.6 Mb, and scaffold N50 of 71.2 and 70.6 Mb, respectively, comprising 18 pseudochromosomes. The repetitive sequences of J075 and J100 represent 72.6% and 71.5% of the genome, the majority of which are long terminal repeats, representing 44.0% and 42.7% of the genome, respectively. The de novo assembled genomes of J075 and J100 were predicted to contain 65,303 and 64,945 protein-coding genes, respectively. The high quality genomes of these highland quinoa lines will facilitate quinoa functional genomics research on quinoa and contribute to the identification of key genes involved in environmental adaptation and quinoa domestication.

3.
BMC Genomics ; 25(1): 822, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223519

RESUMEN

BACKGROUND: Traditional recombinant inbred lines (RILs) are generated from repeated self-fertilization or brother-sister mating from the F1 hybrid of two inbred parents. Compared with the F2 population, RILs cumulate more crossovers between loci and thus increase the number of recombinants, resulting in an increased resolution of genetic mapping. Since they are inbred to the isogenic stage, another consequence of the heterozygosity reduction is the increased genetic variance and thus the increased power of QTL detection. Self-fertilization is the primary form of developing RILs in plants. Brother-sister mating is another way to develop RILs but in small laboratory animals. To ensure that the RILs have at least 98% of homozygosity, we need about seven generations of self-fertilization or 20 generations of brother-sister mating. Prior to homozygosity, these lines are called pre-recombinant inbred lines (PRERIL). Phenotypic values of traits in PRERILs are often collected but not used in QTL mapping. To perform QTL mapping in PRERILs, we need the recombination fraction between two markers at generation t for t < 7 (selfing) or t < 20 (brother-sister mating) so that the genotypes of QTL flanked by the markers can be inferred. RESULTS: In this study, we developed formulas to calculate the recombination fractions of PRERILs at generation t in self-fertilization, brother-sister mating, and random mating. In contrast to existing works in this topic, we used computer code to construct the transition matrix to form the Markov chain of genotype array between consecutive generations, the so-called recurrent equations. CONCLUSIONS: We provide R functions to calculate the recombination fraction using the newly developed recurrent equations of ordered genotype array. With the recurrent equations and the R code, users can perform QTL mapping in PRERILs. Substantial time and effort can be saved compared with QTL mapping in RILs.


Asunto(s)
Endogamia , Sitios de Carácter Cuantitativo , Recombinación Genética , Mapeo Cromosómico , Homocigoto , Modelos Genéticos , Genotipo , Fenotipo
4.
Bull Exp Biol Med ; 177(2): 256-260, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39093472

RESUMEN

The study revealed no effects of pregnancy and childbirth on the course of tuberculosis in female BALB/c mice after aerosol infection with Mycobacterium tuberculosis. However, we demonstrated a negative effect of tuberculosis infection on the fertility of infected females, which manifested in a longer period from mating to pregnancy and in a smaller litter size. Impaired reproductive function in response to the effect of the systemic infectious process was accompanied by the development of immunosuppression confirmed by an immunological test (delayed-type hypersensitivity to tuberculin) and the formation of genital tract dysbiosis during pregnancy and postpartum period.


Asunto(s)
Fertilidad , Ratones Endogámicos BALB C , Mycobacterium tuberculosis , Tuberculosis , Animales , Femenino , Ratones , Fertilidad/fisiología , Embarazo , Mycobacterium tuberculosis/patogenicidad , Mycobacterium tuberculosis/inmunología , Tuberculosis/inmunología , Tuberculosis/microbiología , Disbiosis/microbiología , Disbiosis/inmunología , Hipersensibilidad Tardía/inmunología , Tamaño de la Camada
5.
Front Plant Sci ; 15: 1406550, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39109052

RESUMEN

Biofortification of provitamin A in maize is an attractive and sustainable remedy to the problem of vitamin A deficiency in developing countries. The utilization of molecular markers represents a promising avenue to facilitate the development of provitamin A (PVA)-enriched maize varieties. We screened 752 diverse tropical yellow/orange maize lines using kompetitive allele-specific PCR (KASP) makers to validate the use of KASP markers in PVA maize breeding. To this end, a total of 161 yellow/orange inbred lines, selected from among the 752 lines, were evaluated for their endosperm PVA and other carotenoid compounds levels in two separate trials composed of 63 and 98 inbred lines in 2020 and 2021, respectively. Significant differences (p < 0.001) were observed among the yellow maize inbred lines studied for all carotenoid profiles. An inbred line TZMI1017, introduced by the International Institute of Tropical Agriculture (IITA) showed the highest level of PVA (12.99 µg/g) and ß-carotene (12.08 µg/g). The molecular screening showed 43 yellow maize inbred lines carrying at least three of the favorable alleles of the KASP markers. TZMI1017 inbred line also carried the favorable alleles of almost all markers. In addition, nine locally developed inbred lines had medium to high PVA concentrations varying from 5.11 µg/g to 10.76 µg/g and harbored the favorable alleles of all the KASP PVA markers. Association analysis between molecular markers and PVA content variation in the yellow/orange maize inbred lines did not reveal a significant, predictable correlation. Further investigation is warranted to elucidate the underlying genetic architecture of the PVA content in this germplasm. However, we recommend strategic utilization of the maize-inbred lines with higher PVA content to enhance the PVA profile of the breeding program's germplasm.

6.
Physiol Mol Biol Plants ; 30(8): 1277-1295, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39184555

RESUMEN

Water deficit stress reduces crop yield in field crops, including sunflowers, at any growth stage. In response, most plants activate hormonal and gene expression patterns to mitigate damage. In this study, we evaluated changes in the physiological and gene transcription levels of two sunflower (Helianthus annuus L.) inbred lines -one sensitive (B59 line) and one water stress-tolerant (B71)-in response to water stress, by using mannitol to simulate water deficit conditions, which provides moderate stress in both sunflower lines. The analyses of the accumulation of various phytohormones under this stress revealed that Jasmonic acid (JA) significantly increased in the shoots of both lines. Similarly, Salicylic acid (SA) increased in the shoots of both lines, although it also accumulated in B71 roots. In addition, Abscisic acid (ABA) and Indole-3-acetic acid (IAA) showed a considerable increase in the B59 shoots. Regarding the JA and SA pathways, the WRKY70 transcription levels were higher in the shoots of both lines and the roots of B71. The B59 line showed overtranscription of a gene related to the ABA pathway (XERICO) and genes associated with IAA (ARF9 and ARF16 genes). The B71 line, on the other hand, simultaneously triggered the JA, SA and ABA hormonal pathways in response to this stress condition. The ABA and JA hormonal pathways activated different TFs, such as RD20, RD22, RD26, ANAC19 and ANAC29, through MYC2. Both the JA and SA hormonal pathways activated the WRKY70 transcription factor. Altogether, each line triggered the hormonal and transcriptional pathways in response to water stress, although at varying intensities. The results suggest that the hormonal pathways of JA, SA, IAA and ABA, along with their primary associated genes, are activated in response to water deficit at the early growth stage in sunflower seedlings, which mitigates damage. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01497-8.

7.
Physiol Mol Biol Plants ; 30(8): 1313-1328, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39184561

RESUMEN

Fagopyrum tataricum, an important medicinal and edible crop, possesses significant agricultural and economic value. However, the development of buckwheat varieties and yields has been hindered by the delayed breeding progress despite the abundant material resources in China. Current research indicates that quantitative trait loci (QTLs) play a crucial role in controlling plant seed type and yield. To address these limitations, this study constructed recombinant inbred lines (RILs) utilizing both cultivated species and wild buckwheat as raw materials. In total, 84,521 Single Nucleotide Polymorphism (SNP) markers were identified through Genotyping-by-Sequencing (GBS) technology, and high-resolution and high-density SNP genetic maps were developed, which had significant value for QTL mapping, gene cloning and comparative mapping of buckwheat. In this study, we successfully identified 5 QTLs related to thousand grain weight (TGW), 9 for grain length (GL), and 1 for grain width (GW) by combining seed type and TGW data from 202 RIL populations in four different environments, within which one co-located QTL for TGW were discovered on the first chromosome. Transcriptome analysis during different grain development stages revealed 59 significant expression differences between the two materials, which can serve as candidate genes for further investigation into the regulation of grain weight and yield enhancement. The mapped major loci controlling TGW, GL and GW will be valuable for gene cloning and reveal the mechanism underlying grain development and marker-assisted selection in Tartary buckwheat.

8.
Bull Exp Biol Med ; 177(3): 313-317, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39126543

RESUMEN

Inbred mouse strains KK.Cg-a/a and KK.Cg-Ay/a known as genetic models of type 2 diabetes mellitus significantly surpassed the control strain C57BL/6J in the body weight, relative weight of extractable fat, and basal blood glucose levels. Real-timePCR of fecal samples from KK.Cg-a/a and KK.Cg-Ay/a mice revealed dysbiosis typical of type 2 diabetes mellitus in humans and animals. Long-term intragastric administration of a suspension of Hafnia alvei bacteria had no effect on the above morphometric and biochemical parameters. At the same time, recovery of the Bacteroides spp. population in KK.Cg-Ay/a mice and a decrease in the number of Bifidobacterium spp. in KK.Cg-a/a mice were observed. The possibility of therapeutic use of the probiotic based on H. alvei is discussed.


Asunto(s)
Diabetes Mellitus Tipo 2 , Heces , Microbioma Gastrointestinal , Hafnia alvei , Ratones Endogámicos C57BL , Probióticos , Animales , Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Microbioma Gastrointestinal/genética , Ratones , Probióticos/administración & dosificación , Hafnia alvei/genética , Heces/microbiología , Masculino , Bacteroides/genética , Bifidobacterium/genética , Glucemia/metabolismo , Peso Corporal , Disbiosis/microbiología , Modelos Animales de Enfermedad
9.
Artículo en Inglés | MEDLINE | ID: mdl-39150393

RESUMEN

Excess sodium consumption contributes to arterial dysfunction in humans. The C57BL/6 strain of mice have been used to identify mechanisms by which arterial dysfunction occurs after excess sodium consumption. However, there are concerns that C57BL/6 mice have strain-specific resistance to high-sodium (HS) diet-induced hypertension. To address this concern, we performed a meta-analysis to determine if excess sodium consumption in C57BL/6 mice induces arterial dysfunction. Databases were searched for HS vs. standard diet studies that measured arterial function (i.e., systolic blood pressure [BP], endothelium-dependent dilation [EDD], and central arterial stiffness) in C57BL/6 mice. A total of 39 studies were included, demonstrating that HS condition resulted in higher systolic BP than control mice with a mean difference of 9.8 mmHg (95% CI [5.6, 14], P<0.001). Subgroup analysis indicated that the systolic BP was higher in HS compared to the control condition when measured during night compared to daytime with telemetry (P<0.001). We also identified that the difference in systolic BP between HS and control was ~2.5-fold higher when administered through drinking water than through food (P<0.001). A total of 12 studies were included, demonstrating that HS condition resulted in lower EDD than control with a weighted mean difference of -12.0% (95% CI [-20.0, -4.1], P=0.003). It should be noted that there was considerable variability across studies with more than half of the studies showing no effect of HS condition on systolic BP and EDD. In summary, excess sodium consumption elevates systolic BP and impairs EDD in C57BL/6 mice.

10.
Front Plant Sci ; 15: 1394676, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39011302

RESUMEN

For soybean, novel single dominant Resistance to Phytophthora sojae (Rps) genes are sought to manage Phytophthora root and stem rot. In this study, resistance to P. sojae was mapped individually in four recombinant inbred line (RIL) populations derived from crosses of the susceptible cultivar Williams with PI 407985, PI 408029, PI 408097, and PI424477 previously identified as putative novel sources of disease resistance. Each population was screened for resistance with five to seven isolates of P. sojae separately over multiple F7-F10 generations. Additionally, three of the populations were screened with inoculum from the combination of three P. sojae isolates (PPR), which comprised virulence to 14 Rps genes. Over 2,300 single-nucleotide polymorphism markers were used to construct genetic maps in each population to identify chromosomal regions associated with resistance to P. sojae. Resistance segregated as one or two genes to the individual isolates and one gene toward PPR in each population and mapped to chromosomes 3, 13, or 18 in one or more of the four RIL populations. Resistance to five isolates mapped to the same chromosome 3 region are as follows: OH7 (PI 424477 and PI408029), OH12168, OH7/8, PPR (PI 407985), and 1.S.1.1 (PI408029). The resistance regions on chromosome 13 also overlapped for OH1, OH25, OH-MIA (PI424477), PPR (PI 424477, PI 407985, and PI 408097), PPR and OH0217 (PI 408097), and OH4 (PI 408029), but were distinct for each population suggesting multiple genes confer resistance. Two regions were identified on chromosome 18 but all appear to map to known loci; notably, resistance to the combined inoculum (PPR) did not map at this locus. However, there are putative new alleles in three of four populations, three on chromosome 3 and two on chromosome 13 based on mapping location but also known virulence in the isolate used. This characterization of all the Rps genes segregating in these populations to these isolates will be informative for breeding, but the combined inoculum was able to map a novel loci. Furthermore, within each of these P. sojae isolates, there was virulence to more than the described Rps genes, and the effectiveness of the novel genes requires testing in larger populations.

11.
Anim Reprod ; 21(2): e20230124, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39021499

RESUMEN

In 2015-2016, the Zika virus (ZIKV) caused a major epidemic in the Americas, increasing cases of microcephaly and Guillain-Barré syndrome. During this period, the discovery of ZIKV sexual transmission intensified studies on the impact of this virus on the reproductive organs. For this study, 2-month-old male BALB/c mice were infected with 1.26 x 106 PFU/mL of ZIKV in solution via the intravenous route. After three, seven, and fourteen days post-infection (DPI), blood and testicle samples were obtained to detect ZIKV RNA. The authors observed that the infected animals had slower weight gain than the control group. Viremia occurred only at 3DPI, and the ZIKV RNA was detected in one testis sample at 7DPI. The histopathological analysis of this organ revealed intense disorganization of the seminiferous tubules' structure, inflammatory infiltrate, necrosis, hemorrhage, fluid accumulation, congestion of blood vessels, and reduced sperm count. Ultrastructural analysis showed nuclear changes in tubule cells, activation of interstitial cells, and morphological changes in spermatozoa, in addition to fragmentation and decreased electron density of the genetic material of these cells. Thus, despite causing predominantly asymptomatic infections, ZIKV can cause significant subclinical and transient damage, including to male reproductive organs.

12.
Int J Mol Sci ; 25(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38892425

RESUMEN

Spontaneous tumour formation in higher plants can occur in the absence of pathogen invasion, depending on the plant genotype. Spontaneous tumour formation on the taproots is consistently observed in certain inbred lines of radish (Raphanus sativus var. radicula Pers.). In this paper, using Oxford Nanopore and Illumina technologies, we have sequenced the genomes of two closely related radish inbred lines that differ in their ability to spontaneously form tumours. We identified a large number of single nucleotide variants (amino acid substitutions, insertions or deletions, SNVs) that are likely to be associated with the spontaneous tumour formation. Among the genes involved in the trait, we have identified those that regulate the cell cycle, meristem activity, gene expression, and metabolism and signalling of phytohormones. After identifying the SNVs, we performed Sanger sequencing of amplicons corresponding to SNV-containing regions to validate our results. We then checked for the presence of SNVs in other tumour lines of the radish genetic collection and found the ERF118 gene, which had the SNVs in the majority of tumour lines. Furthermore, we performed the identification of the CLAVATA3/ESR (CLE) and WUSCHEL (WOX) genes and, as a result, identified two unique radish CLE genes which probably encode proteins with multiple CLE domains. The results obtained provide a basis for investigating the mechanisms of plant tumour formation and also for future genetic and genomic studies of radish.


Asunto(s)
Genoma de Planta , Raphanus , Secuenciación Completa del Genoma , Raphanus/genética , Secuenciación Completa del Genoma/métodos , Tumores de Planta/genética , Polimorfismo de Nucleótido Simple , Proteínas de Plantas/genética
13.
Heliyon ; 10(10): e31507, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38831819

RESUMEN

Diploid inbred-based F1 hybrid True Potato Seed (DHTPS) breeding is a novel technique to transform potato breeding and cultivation across the globe. Significant efforts are being made to identify elite diploids, dihaploids and develop diploid inbred lines for heterosis exploitation in potatoes. Self-incompatibility is the first obstacle for developing inbred lines in diploid potatoes, which necessitates the introgression of a dominant S locus inhibitor gene (Sli) for switching self-incompatibility to self-compatibility. We evaluated a set of 357 diploid clones in different selfing generations for self-compatibility and degree of homozygosity using Kompetitive Allele Specific PCR (KASP) Single Nucleotide Polymorphism (SNP) markers. A subset of 10 KASP markers of the Sli candidate region on chromosome 12 showed an association with the phenotype for self-compatibility. The results revealed that the selected 10 KASP markers for the Sli gene genotype could be deployed for high throughput rapid screening of self-compatibility in diploid populations and to identify new sources of self-compatibility. The homozygosity assessed through 99 KASP markers distributed across all the chromosomes of the potato genome was 20-78 % in founder diploid clones, while different selfing generations, i.e., S0, S1, S2 and S3 observed 36.1-80.4, 56.9-82.8, 59.5-85.4 and 73.7-87.8 % average homozygosity, respectively. The diploid plants with ∼80 % homozygosity were also observed in the first selfing generation, which inferred that homozygosity assessment in the early generations itself could identify the best plants with high homozygosity to speed up the generation of diploid inbred lines.

14.
J Fungi (Basel) ; 10(6)2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38921412

RESUMEN

Animal models are frequently used as surrogates to understand human disease. In the fungal pathogen Cryptococcus species complex, several variations of a mouse model of disease were developed that recapitulate different aspects of human disease. These mouse models have been implemented using various inbred and outbred mouse backgrounds, many of which have genetic differences that can influence host response and disease outcome. In this review, we will discuss the most commonly used inbred mouse backgrounds in C. neoformans infection models.

15.
Stroke ; 55(7): 1914-1922, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38860370

RESUMEN

BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.


Asunto(s)
Bloqueadores de los Canales de Calcio , Enfermedades de los Pequeños Vasos Cerebrales , Cognición , Modelos Animales de Enfermedad , Nimodipina , Ratas Endogámicas SHR , Animales , Nimodipina/farmacología , Nimodipina/uso terapéutico , Masculino , Enfermedades de los Pequeños Vasos Cerebrales/tratamiento farmacológico , Ratas , Cognición/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/uso terapéutico , Circulación Cerebrovascular/efectos de los fármacos , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/prevención & control
16.
Eur Radiol Exp ; 8(1): 74, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38872042

RESUMEN

BACKGROUND: New immunotherapies activate tumor-associated macrophages (TAMs) in the osteosarcoma microenvironment. Iron oxide nanoparticles (IONPs) are phagocytosed by TAMs and, therefore, enable TAM detection on T2*- and T2-weighted magnetic resonance images. We assessed the repeatability and reproducibility of T2*- and T2-mapping of osteosarcomas in a mouse model. METHODS: Fifteen BALB/c mice bearing-murine osteosarcomas underwent magnetic resonance imaging (MRI) on 3-T and 7-T scanners before and after intravenous IONP infusion, using T2*-weighted multi-gradient-echo, T2-weighted fast spin-echo, and T2-weighted multi-echo sequences. Each sequence was repeated twice. Tumor T2 and T2* relaxation times were measured twice by two independent investigators. Repeatability and reproducibility of measurements were assessed. RESULTS: We found excellent agreement between duplicate acquisitions for both T2* and T2 measurements at either magnetic field strength, by the same individual (repeatability), and between individuals (reproducibility). The repeatability concordance correlation coefficient (CCC) for T2* values were 0.99 (coefficients of variation (CoV) 4.43%) for reader 1 and 0.98 (CoV 5.82%) for reader 2. The reproducibility of T2* values between the two readers was 0.99 (CoV 3.32%) for the first acquisitions and 0.99 (CoV 6.30%) for the second acquisitions. Regarding T2 values, the repeatability of CCC was similar for both readers, 0.98 (CoV 3.64% for reader 1 and 4.45% for reader 2). The CCC of the reproducibility of T2 was 0.99 (CoV 3.1%) for the first acquisition and 0.98 (CoV 4.38%) for the second acquisition. CONCLUSIONS: Our results demonstrated high repeatability and reproducibility of quantitative T2* and T2 mapping for monitoring the presence of TAMs in osteosarcomas. RELEVANCE STATEMENT: T2* and T2 measurements of osteosarcomas on IONP-enhanced MRI could allow identifying patients who may benefit from TAM-modulating immunotherapies and for monitoring treatment response. The technique described here could be also applied across a wide range of other solid tumors. KEY POINTS: • Optimal integration of TAM-modulating immunotherapies with conventional chemotherapy remains poorly elucidated. • We found high repeatability of T2* and T2 measurements of osteosarcomas in a mouse model, both with and without IONPs contrast, at 3-T and 7-T MRI field strengths. • T2 and T2* mapping may be used to determine response to macrophage-modulating cancer immunotherapies.


Asunto(s)
Neoplasias Óseas , Modelos Animales de Enfermedad , Imagen por Resonancia Magnética , Ratones Endogámicos BALB C , Osteosarcoma , Animales , Osteosarcoma/diagnóstico por imagen , Ratones , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Neoplasias Óseas/diagnóstico por imagen , Femenino
17.
Cell Genom ; 4(5): 100545, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38697120

RESUMEN

Knowing the genes involved in quantitative traits provides an entry point to understanding the biological bases of behavior, but there are very few examples where the pathway from genetic locus to behavioral change is known. To explore the role of specific genes in fear behavior, we mapped three fear-related traits, tested fourteen genes at six quantitative trait loci (QTLs) by quantitative complementation, and identified six genes. Four genes, Lamp, Ptprd, Nptx2, and Sh3gl, have known roles in synapse function; the fifth, Psip1, was not previously implicated in behavior; and the sixth is a long non-coding RNA, 4933413L06Rik, of unknown function. Variation in transcriptome and epigenetic modalities occurred preferentially in excitatory neurons, suggesting that genetic variation is more permissible in excitatory than inhibitory neuronal circuits. Our results relieve a bottleneck in using genetic mapping of QTLs to uncover biology underlying behavior and prompt a reconsideration of expected relationships between genetic and functional variation.


Asunto(s)
Miedo , Sitios de Carácter Cuantitativo , Animales , Femenino , Masculino , Ratones , Conducta Animal/fisiología , Mapeo Cromosómico , Miedo/fisiología , Ratones Endogámicos C57BL , Prueba de Complementación Genética
18.
Mol Biol Rep ; 51(1): 626, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38717621

RESUMEN

BACKGROUND: Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the most devastating diseases of rice leading to huge yield losses in Southeast Asia. The recessive resistance gene xa-45(t) from Oryza glaberrima IRGC102600B, mapped on rice chromosome 8, spans 80 Kb with 9 candidate genes on Nipponbare reference genome IRGSP-1.0. The xa-45(t) gene provides durable resistance against all the ten Xanthomonas pathotypes of Northern India, thus aiding in the expansion of recessive bacterial blight resistance gene pool. Punjab Rice PR127, carrying xa-45(t), was released for wider use in breeding programs. This study aims to precisely locate the target gene among the 9 candidates conferring resistance to bacterial blight disease. METHODS AND RESULTS: Sanger sequencing of all nine candidate genes revealed seven SNPs and an Indel between the susceptible parent Pusa 44 and the resistant introgression line IL274. The genotyping with polymorphic markers identified three recombinant breakpoints for LOC_Os08g42370, and LOC_Os08g42400, 15 recombinants for LOC_Os08g423420 and 26 for LOC_Os08g42440 out of 190 individuals. Relative expression analysis across six time intervals (0, 8, 24, 48, 72, and 96 h) after bacterial blight infection showed over expression of LOC_Os08g42410-specific transcripts in IL274 compared to Pusa 44, with a significant 4.46-fold increase observed at 72 h post-inoculation. CONCLUSIONS: The Indel marker at the locus LOC_Os08g42410 was found co-segregating with the phenotype, suggesting its candidacy towards xa-45(t). The transcript abundance assay provides strong evidence for the involvement of LOC_Os08g42410 in the resistance conferred by the bacterial blight gene xa-45(t).


Asunto(s)
Mapeo Cromosómico , Resistencia a la Enfermedad , Oryza , Enfermedades de las Plantas , Mapeo Cromosómico/métodos , Cromosomas de las Plantas/genética , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas/genética , Genes de Plantas/genética , Genes Recesivos , Genotipo , Oryza/genética , Oryza/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Polimorfismo de Nucleótido Simple/genética , Xanthomonas/patogenicidad
19.
Plant Mol Biol ; 114(3): 62, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771394

RESUMEN

Fusarium head blight (FHB) stands out as one of the most devastating wheat diseases and leads to significantly grain yield losses and quality reductions in epidemic years. Exploring quantitative trait loci (QTL) for FHB resistance is a critical step for developing new FHB-resistant varieties. We previously constructed a genetic map of unigenes (UG-Map) according to the physical positions using a set of recombinant-inbred lines (RILs) derived from the cross of 'TN18 × LM6' (TL-RILs). Here, the number of diseased spikelets (NDS) and relative disease index (RDI) for FHB resistance were investigated under four environments using TL-RILs, which were distributed across 13 chromosomes. A number of 36 candidate genes for NDS and RDI from of 19 stable QTLs were identified. The average number of candidate genes per QTL was 1.89, with 14 (73.7%), two (10.5%), and three (15.8%) QTLs including one, two, and 3-10 candidate genes, respectively. Among the 24 candidate genes annotated in the reference genome RefSeq v1.1, the homologous genes of seven candidate genes, including TraesCS4B02G227300 for QNds/Rdi-4BL-4553, TraesCS5B02G303200, TraesCS5B02G303300, TraesCS5B02G303700, TraesCS5B02G303800 and TraesCS5B02G304000 for QNds/Rdi-5BL-9509, and TraesCS7A02G568400 for QNds/Rdi-7AL-14499, were previously reported to be related to FHB resistance in wheat, barely or Brachypodium distachyon. These genes should be closely associated with FHB resistance in wheat. In addition, the homologous genes of five genes, including TraesCS1A02G037600LC for QNds-1AS-2225, TraesCS1D02G017800 and TraesCS1D02G017900 for QNds-1DS-527, TraesCS1D02G018000 for QRdi-1DS-575, and TraesCS4B02G227400 for QNds/Rdi-4BL-4553, were involved in plant defense responses against pathogens. These genes should be likely associated with FHB resistance in wheat.


Asunto(s)
Mapeo Cromosómico , Resistencia a la Enfermedad , Fusarium , Enfermedades de las Plantas , Sitios de Carácter Cuantitativo , Triticum , Triticum/genética , Triticum/microbiología , Sitios de Carácter Cuantitativo/genética , Fusarium/fisiología , Fusarium/patogenicidad , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , Genes de Plantas , Cromosomas de las Plantas/genética
20.
BMC Genomics ; 25(1): 541, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38822259

RESUMEN

BACKGROUND: Flight can drastically enhance dispersal capacity and is a key trait defining the potential of exotic insect species to spread and invade new habitats. The phytophagous European spongy moths (ESM, Lymantria dispar dispar) and Asian spongy moths (ASM; a multi-species group represented here by L. d. asiatica and L. d. japonica), are globally invasive species that vary in adult female flight capability-female ASM are typically flight capable, whereas female ESM are typically flightless. Genetic markers of flight capability would supply a powerful tool for flight profiling of these species at any intercepted life stage. To assess the functional complexity of spongy moth flight and to identify potential markers of flight capability, we used multiple genetic approaches aimed at capturing complementary signals of putative flight-relevant genetic divergence between ESM and ASM: reduced representation genome-wide association studies, whole genome sequence comparisons, and developmental transcriptomics. We then judged the candidacy of flight-associated genes through functional analyses aimed at addressing the proximate demands of flight and salient features of the ecological context of spongy moth flight evolution. RESULTS: Candidate gene sets were typically non-overlapping across different genetic approaches, with only nine gene annotations shared between any pair of approaches. We detected an array of flight-relevant functional themes across gene sets that collectively suggest divergence in flight capability between European and Asian spongy moth lineages has coincided with evolutionary differentiation in multiple aspects of flight development, execution, and surrounding life history. Overall, our results indicate that spongy moth flight evolution has shaped or been influenced by a large and functionally broad network of traits. CONCLUSIONS: Our study identified a suite of flight-associated genes in spongy moths suited to exploration of the genetic architecture and evolution of flight, or validation for flight profiling purposes. This work illustrates how complementary genetic approaches combined with phenotypically targeted functional analyses can help to characterize genetically complex traits.


Asunto(s)
Vuelo Animal , Especies Introducidas , Mariposas Nocturnas , Animales , Mariposas Nocturnas/genética , Mariposas Nocturnas/fisiología , Femenino , Estudio de Asociación del Genoma Completo , Fenotipo , Transcriptoma , Complejo de Polillas Esponjosas Voladoras
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