Toward Tumor Fight and Tumor Microenvironment Remodeling: PBA Induces Cell Cycle Arrest and Reduces Tumor Hybrid Cells’ Pluripotency in Bladder Cancer

Bladder cancer (BC) is the second most frequent cancer of the genitourinary system. The most successful therapy since the 1970s has consisted of intravesical instillations of Bacillus Calmette–Guérin (BCG) in which the tumor microenvironment (TME), including macrophages, plays an important role. However, some patients cannot be treated with this therapy due to comorbidities and severe inflammatory side effects. The overexpression of histone deacetylases (HDACs) in BC has been correlated with macrophage polarization together with higher tumor grades and poor prognosis. Herein we demonstrated that phenylbutyrate acid (PBA), a HDAC inhibitor, acts as an antitumoral compound and immunomodulator. In BC cell lines, PBA induced significant cell cycle arrest in G1, reduced stemness markers and increased PD-L1 expression with a corresponding reduction in histone 3 and 4 acetylation patterns. Concerning its role as an immunomodulator, we found that PBA reduced macrophage IL-6 and IL-10 production as well as CD14 downregulation and the upregulation of both PD-L1 and IL-1β. Along this line, PBA showed a reduction in IL-4-induced M2 polarization in human macrophages. In co-cultures of BC cell lines with human macrophages, a double-positive myeloid–tumoral hybrid population (CD11b+EPCAM+) was detected after 48 h, which indicates BC cell–macrophage fusions known as tumor hybrid cells (THC). These THC were characterized by high PD-L1 and stemness markers (SOX2, NANOG, miR-302) as compared with non-fused (CD11b−EPCAM+) cancer cells. Eventually, PBA reduced stemness markers along with BMP4 and IL-10. Our data indicate that PBA could have beneficial properties for BC management, affecting not only tumor cells but also the TME.

Designing the best breeding strategy for Coffea canephora: Genetic evaluation of pure and hybrid individuals aiming to select for productivity and disease resistance traits

Breeding programs of the species Coffea canephora rely heavily on the significant genetic variability between and within its two varietal groups (conilon and robusta). The use of hybrid families and individuals has been less common. The objectives of this study were to evaluate parents and families from the populations of conilon, robusta, and its hybrids and to define the best breeding and selection strategies for productivity and disease resistance traits. As such, 71 conilon clones, 56 robusta clones, and 20 hybrid families were evaluated over several years for the following traits: vegetative vigor, incidence of rust and cercosporiosis, fruit ripening time, fruit size, plant height, canopy diameter, and yield per plant. Components of variance and genetic parameters were estimated via residual maximum likelihood (REML) and genotypic values were predicted via best linear unbiased prediction (BLUP). Genetic variability among parents (clones) and hybrid families was detected for most of the evaluated traits. The Mulamba-Rank index suggests potential gains up to 17% for the genotypic aggregate of traits in the hybrid population. An intrapopulation recurrent selection within the hybrid population would be the best breeding strategy because the genetic variability, narrow and broad senses heritabilities and selective accuracies for important traits were maximized in the crossed population. Besides, such strategy is simple, low cost and quicker than the concurrent reciprocal recurrent selection in the two parental populations, and this maximizes the genetic gain for unit of time.

A cultivar of brown mustard Alisa

Brown mustard is one of the valuable oil crops which allows increasing the production of edible vegetable oil. In the conditions of insufficient moisture in the Rostov region, new cultivars of brown mustard are being developed, which combine yield, early maturity with high product quality and are resistant to stress factors. A new cultivar of brown mustard Alisa was bred by the method of individual selection from the hybrid population G-2384 (G-2319 × 50041). According to the results of competitive trials for 2017–2019, the cultivar Alisa exceeded the standard cultivar Lux by seed yield by 0.31 t per ha, seed oil content – by 0.8%. The brown mustard cultivar Alisa is characterized by a lower plant height, increased tolerance to major pathogens, and greater resistance to lodging. Plants are well uniformed in height, blooming and maturity. The cultivar was registered in 2020 in the State Register of breeding achievements approved for production. It is recommended for cultivation for grain in all regions of the Russian Federation.

Genetic analysis of the hybrid rice population ‘Mavr × Kontakt’

Rice can form not only white-color kernels, but also of red, brown and black colors. In black-color rice kernels, the pericarp contains anthocyanin, which has antioxidant activity and therefore has a positive effect on human health. The purpose of the current study was to develop rice samples with black pericarp. The paper has presented the study results of the hybrid population ‘Mavr × Kontakt’ of the second generation. The variety ‘Mavr’ has a black pericarp, the variety ‘Kontakt’ has a white one. In the process of hybridological analysis there have been identified the patterns of inheritance of the main quantitative traits affecting productivity; there have been identified the best samples, in which formed compact erect panicles and black kernels; there has been selected the initial material for breeding work. The study was carried out in 2020 on the plots of the ES “Proletarskoye” in the Rostov region. There was established that the color of pericarp was inherited according to the type of complementary interaction of two genes. There was found an overdominance and interaction of two pairs of genes of different strengths according to ‘plant height’. There was also seen partial positive dominance, transgressions, and digenic differences of the initial varieties according to ‘panicle length’. According to the traits ‘number of spikelets per panicle’, there was identified overdominance of large values and positive transgression. There were found the forms with well-kerneled panicles. The trait ‘1000 kernel weight’ was characterized by negative dominance and dihybrid cleavage of 9:6:1. There have been selected the best morphotype F2 forms with black pericarp, which possessed optimal plant height, long panicles, larger kernel size, and an average 1000 kernel weight.

A Novel Pear Scab (Venturia nashicola) Resistance Gene, Rvn3, from Interspecific Hybrid Pear (Pyrus pyrifolia × P. communis)

Asian pear scab is a fungal disease caused by Venturia nashicola. The identification of genes conferring scab resistance could facilitate the breeding of disease-resistant cultivars. Therefore, the present study aimed to identify a scab-resistance gene using an interspecific hybrid population ((Pyrus pyrifolia × P. communis) × P. pyrifolia). Artificial inoculation of V. nashicola was carried out for two years. The segregation ratio (1:1) of resistant to susceptible individuals indicated that resistance to V. nashicola was inherited from P. communis and controlled by a single dominant gene. Based on two years phenotypic data with the Kruskal–Wallis test and interval mapping, 12 common markers were significantly associated with scab resistance. A novel scab resistance gene, Rvn3, was mapped in linkage group 6 of the interspecific hybrid pear, and co-linearity between Rvn3 and one of the apple scab resistance genes, Rvi14, was confirmed. Notably, an insertion in pseudo-chromosome 6 of the interspecific hybrid cultivar showed homology with apple scab resistance genes. Hence, the newly discovered Rvn3 was considered an ortholog of the apple scab resistance gene. Since the mapping population used in the present study is a pseudo-BC1 population, pyramiding of multiple resistance genes to pseudo-BC1 could facilitate the breeding of pear cultivars with durable resistance.

Heterosis Related to Fitness and Phenotypic Variance in the Evolution of Diploid Gene Regulatory Network

Heterosis describes the phenomenon whereby a hybrid population has higher fitness than an inbred population, and has previously been explained by either Mendelian dominance or overdominance, where it is generally assumed that one gene controls one trait. However, recent studies have demonstrated that genes interact through a complex gene regulatory network (GRN). Furthermore, phenotypic variance due to noise is reportedly lower for heterozygotes, whereas the origin of such variance-related heterosis remains elusive. Therefore, a theoretical analysis linking heterosis to GRN evolution and stochastic gene expression dynamics is required. Here, we investigate heterosis related to fitness and phenotypic variance in a system with interacting genes, by numerically evolving diploid GRNs. According to the results, the heterozygote population exhibited higher fitness than the homozygote population, that is, fitness-related heterosis resulting from evolution. In addition, the heterozygote population expressed lower noise-related phenotypic variance in expression levels than the homozygous population, implying that the heterozygote population is more robust to noise. Furthermore, the distribution of the ratio of heterozygote phenotypic variance to homozygote phenotypic variance exhibited quantitative agreement with previous experimental results. By applying dominance and overdominance to the gene expression pattern rather than only a single gene expression, we confirmed the correlation between heterosis and overdominance. We explain our results by proposing that the convex high-fitness region is evolutionarily shaped in the genetic space to gain noise robustness under genetic mixing through sexual reproduction.

Interspecific Hybridization and Complete Mitochondrial Genome Analysis of Two Ghost Moth Species

The Chinese cordyceps, a parasitic Ophiocordyceps sinensis fungus–Thitarodes/Hepialus larva complex, is a valuable biological resource endemic to the Tibetan Plateau. Protection of the Plateau environment and huge market demand make it necessary to culture this complex in an artificial system. A method for the large-scale artificial rearing of the Thitarodes/Hepialus insect host has been established. However, the deterioration of the insect rearing population and low mummification of the infected larvae by the fungus constrain effective commercial cultivation. Hybridization of Thitarodes/Hepialus populations may be needed to overcome this problem. The species T. shambalaensis (GG♂ × GG♀) and an undescribed Thitarodes species (SD♂ × SD♀) were inbred or hybridized to evaluate the biological parameters, larval sensitivity to the fungal infection and mitochondrial genomes of the resulting populations. The two parental Thitarodes species exhibited significant differences in adult fresh weights and body lengths but not in pupal emergence rates. Hybridization of T. shambalaensis and Thitarodes sp. allowed producing a new generation. The SD♂ × GG♀ population showed a higher population trend index than the SD♂ × SD♀ population, implying increased population growth compared with the male parent. The sensitivity of the inbred larval populations to four fungal isolates of O. sinensis also differed. This provides possibilities to create Thitarodes/Hepialus populations with increased growth potential for the improved artificial production of the insect hosts. The mitochondrial genomes of GG♂ × GG♀, SD♂ × SD♀ and SD♂ × GG♀ were 15,612 bp, 15,389 bp and 15,496 bp in length, with an A + T content of 80.92%, 82.35% and 80.87%, respectively. The A + T-rich region contains 787 bp with two 114 bp repetitive sequences, 554 bp without repetitive sequences and 673 bp without repetitive sequences in GG♂ × GG♀, SD♂ × SD♀ and SD♂ × GG♀, respectively. The hybrid population (SD♂ × GG♀) was located in the same clade with GG♂ × GG♀, based on the phylogenetic tree constructed by 13 PCGs, implying the maternal inheritance of mitochondrial DNA.

Adaptive divergence in shoot gravitropism creates hybrid sterility in an Australian wildflower

Natural selection is responsible for much of the diversity we see in nature. Just as it drives the evolution of new traits, it can also lead to new species. However, it is unclear whether natural selection conferring adaptation to local environments can drive speciation through the evolution of hybrid sterility between populations. Here, we show that adaptive divergence in shoot gravitropism, the ability of a plant’s shoot to bend upwards in response to the downward pull of gravity, contributes to the evolution of hybrid sterility in an Australian wildflower, Senecio lautus. We find that shoot gravitropism has evolved multiple times in association with plant height between adjacent populations inhabiting contrasting environments, suggesting that these traits have evolved by natural selection. We directly tested this prediction using a hybrid population subjected to eight rounds of recombination and three rounds of selection in the field. Our experiments revealed that shoot gravitropism responds to natural selection in the expected direction of the locally adapted population. Using the advanced hybrid population, we discovered that individuals with extreme differences in gravitropism had more sterile crosses than individuals with similar gravitropic responses, which were largely fertile, indicating that this adaptive trait is genetically correlated with hybrid sterility. Our results suggest that natural selection can drive the evolution of locally adaptive traits that also create hybrid sterility, thus revealing an evolutionary connection between local adaptation and the origin of new species.

Screening and Identification of The Key LncRNAs Associated With Fat Deposition in Ovine Tail

Background: Sheep is an important meat-producing animal, and low tail fat deposition level has become one of the main targets of meat production. LncRNAs have recently received special attention due to their critical role in many important biological processes. There are few reports on its regulatory function in ovine fat deposition. In this study, two sheep populations with different tail types in Xinjiang, Bashby sheep (fat-tailed) and the hybrid population of Bashby sheep and wild argali (small-tailed), were selected for whole transcriptome resequencing from their tail tissues. Results: First, 728 differentially expressed lncRNA (DElncRNAs) of tail fat between Bashby and F2 sheep were identified by RNA-seq. Second, the tissue expression profile and relative expression difference between Bashby and F2 sheep of 7 of 728 DE lncRNAs were analyzed by RT-PCR. We conclude that MSTRG.37980, MSTRG.38164, MSTRG.36912 and MSTRG.36913 positively regulate fat deposition, while MSTRG.8169, MSTRG.24995 and MSTRG.31389 inhibit fat deposition. Third, GO and KEGG analysis revealed that lncRNA targets were mainly participated in energy metabolism, growth and development and immunity, such as viral carcinogenesis, Chemokine signaling pathway, B cell receptor signaling pathway. And the expression pattern of target genes in each tissue was similar to that of the corresponding lncRNAs, which required us to conduct further research on target genes. Conclusions: This study was the first to systematically identify fat deposition-associated lncRNAs in ovine tail fat and construct DElncRNAs profiles. Our findings will help understand the molecular mechanism of fat deposition from transcriptomic perspectives.