Phenotypic Variation Research Articles

Relatedness of Luther Burbank’s Plum (Prunus sp.) Introductions Based on Genotyping by Sequencing

The renowned horticultural artist and plant breeder Luther Burbank worked with many species of plants. During his 50-year career, he introduced more than 800 cultivars, including more than 150 accessions of plums (Prunus spp.) in the late 1800s and early 1900s. Burbank preferred using wide, interspecific crosses to create a vast range of phenotypic variation and then artificially select from the extremes. Although a great artist, Burbank was a substandard scientist because he was derelict in pedigree note-taking. Although many of his introductions are extinct, hobbyists, enthusiasts, and international collections retain nearly a third of the economically viable cultivars he bred. For a century, many of his hybridizations remained inscrutable mysteries until modern genomic and computational tools developed their resolution and statistical power. Today, genotyping by sequencing (GBS) is a useful tool for pedigree reconstruction in the absence of reliable records. GBS can inform principal component analyses, identity by descent (IBD) kinship, and phylogenetic admixture, revealing complex relationships among taxa. In this study, whole genome sequencing was performed on 53 Prunus taxa used by Burbank in his breeding experiments in the most comprehensive genetic survey of his work to date. Exact parent–offspring relationships between this population may be impossible to discern due to years of back crossing, sibling mating, and open pollination. However, the proportion of genomic similarity among these taxa provides information on the relatedness of the genotypes in Burbank’s Prunus experiments, defining four primary lineages within his breeding population. These lineages comprised primarily P. salicina and P. simonii but also have influences from P. americana, P. cerasifera, P. domestica, and P. rivularis. The prevalence of P. simonii in Burbank’s Prunus introductions appears to have been vastly underreported, indicating that some of the seedstock founders of his breeding population could have been P. salicina × P. simonii hybrids at the inception of his career. This research has implications for pedigree reconstruction and prioritizing conservation in collections curation for future studies.

Clonal Transgenerational Effects of Parental Grazing Environment on Offspring Shade Avoidance

Grassland plants that endure livestock grazing exhibit a dwarf phenotype, which can be transmitted to clonal offspring. Yet to date, it remains poorly understood whether such transgenerational dwarf effects alter the plants’ response to shade. Here, we conducted a common garden experiment under sunlight and shade conditions with clonal Leymus chinensis offspring, the parents of which had endured livestock overgrazing (OG) and non-grazing (NG) in the field, respectively. Plant morphological, physiological, and transcriptomic analyses were carried out. The results indicated that NG offspring showed greater shade avoidance than OG offspring. That is, NG offspring exhibited greater plasticity of vegetative height and leaf width, which may be contributed to their greater photosynthetic capacity and gibberellin (GA3) content compared with OG offspring when treated with shade. In addition, RNA-Seq profiling showed that differentially expressed genes in NG offspring were mainly enriched in RNA modification and metabolic processes, which facilitated rapid response to shade. Phytochrome interacting factors (PIFs) promoted downstream shade marker genes in NG offspring by significantly downregulating the expression of PHYC, SPY, and DELLA. Our findings suggest that light conditions should be taken into account to better understand transgenerational dwarf effects induced by livestock grazing on grassland ecosystems. These results provide new insights into the inducible factors of phenotypic variations in grassland plants that experience grazing.

Individual and ecological heterogeneity promote complex communication in social vertebrate group decisions.

To receive the benefits of social living, individuals must make effective group decisions that enable them to achieve behavioural coordination and maintain cohesion. However, heterogeneity in the physical and social environments surrounding group decision-making contexts can increase the level of difficulty social organisms face in making decisions. Groups that live in variable physical environments (high ecological heterogeneity) can experience barriers to information transfer and increased levels of ecological uncertainty. In addition, in groups with large phenotypic variation (high individual heterogeneity), individuals can have substantial conflicts of interest regarding the timing and nature of activities, making it difficult for them to coordinate their behaviours or reach a consensus. In such cases, active communication can increase individuals' abilities to achieve coordination, such as by facilitating the transfer and aggregation of information about the environment or individual behavioural preferences. Here, we review the role of communication in vertebrate group decision-making and its relationship to heterogeneity in the ecological and social environment surrounding group decision-making contexts. We propose that complex communication has evolved to facilitate decision-making in specific socio-ecological contexts, and we provide a framework for studying this topic and testing related hypotheses as part of future research in this area. This article is part of the theme issue 'The power of sound: unravelling how acoustic communication shapes group dynamics'.

Robust hydraulic traits correlation in woody species despite large trait variation along natural and experimental environmental gradients

Abstract Hydraulic traits are major determinants of plant fitness, thus exerting control over vegetation structure, function and distribution. Yet it remains unclear whether and how hydraulic traits respond to environmental stimuli (i.e. phenotypic variation of hydraulic traits; PVHT) and if the coordination between different hydraulic traits and the trait–climate relationship are affected by PVHT. Here, we synthesized data of PVHT (maximum hydraulic conductivity and water potential inducing 50% loss of hydraulic conductivity) and potentially related morphological and anatomical traits (e.g. sapwood density, branch Huber value, mean and hydraulic weighted conduit diameter). We analysed the magnitude, direction and source of variation of the plastic response, as well as the influence of environmental factors on trait coordination. Additionally, we compared the intra‐ and inter‐specific variation between key hydraulic traits and climate metrics (mean annual precipitation and mean annual temperature) at the site of growth, as well as across the population range. PVHT was highly variable in both magnitude and direction, which was contingent on the environmental factor. The variation in PVHT mainly occurred at high taxonomic levels (i.e. family and genus), whereas phenology explained little variation for PVHT. Despite the high variability, trait correlation remained robust in the presence of environmental stimuli. Moreover, trait–climate relationships differed at inter‐specific and intra‐specific levels. The intra‐specific variation of hydraulic traits in most species showed no correlation with climate metrics compared with the high correlation of hydraulic traits with climate metrics across species. Our findings suggest that the high variability of PVHT does not affect the trait correlation which may be valuable in predicting vegetation dynamics under varying environments. The distinct trait–climate relationships highlight the need to unravel the driving force of PVHT, as well as the adaptive strategy across populations. Read the free Plain Language Summary for this article on the Journal blog.

Habitat-specific allocations of elements in Atriplex lentiformis seeds hint at adaptation to metal toxicity.

Self-sustaining vegetation in metal-contaminated areas is essential for rebuilding the ecological resilience and community stability in degraded lands. Metal-tolerant plants originating from contaminated post-mining areas may hold the key to successful plant establishment and growth. Yet, little is known about the impact of metal toxicity on reproductive strategies, metal accumulation and allocation patterns at the seed stage. Our research focused on metal tolerant Atriplex lentiformis, examining the effects of toxic metal(loid) concentration in soils on variability in its reproductive strategies, including germination patterns, elemental uptake, and allocation within the seeds. We employed advanced imaging techniques like synchrotron X-ray Fluorescence Microscopy (XFM; 2D scans and 3D tomograms) combined with ICP-MS to reveal significant differences in metal(loid) concentration and distribution within the seed structures of A. lentiformis from contrasting habitats. Exclusive Zn hotspots of high concentrations were found in the seeds of the metallicolous accession, primarily in the sensitive tissues of shoot apical meristems and root zones of the seed embryos. The findings of this study offer novel insights into phenotypic variability, metal tolerance and accumulation in plants from extreme environments. This knowledge can be applied to enhance plant survival and performance in land restoration efforts.

The Reduced Uterine Perfusion Pressure as a model for preeclampsia and fetal growth restriction in murine: a systematic review and meta-analysis.

The Reduced Uterine Perfusion Pressure (RUPP) model is frequently used to study preeclampsia and fetal growth restriction. An improved understanding of influential factors might improve reproducibility and reduce animal use considering the variability in RUPP phenotype. We performed a systematic review and meta-analysis by searching Medline and Embase (until 03-28-2023) for RUPP studies in murine. Primary outcomes included: maternal blood pressure (BP) or proteinuria, fetal weight or crown-rump-length, fetal reabsorptions, or anti-angiogenic factors. We aimed to identify influential factors by meta-regression analysis. We included 155 studies. Our meta-analysis showed that the RUPP procedure results in significantly higher BP (MD 24.1 mmHg; [22.6;25.7]; n=148), proteinuria (SMD 2.3; [0.9; 3.8]; n=28), fetal reabsorptions (MD 50.4%; [45.5; 55.2]; n=42), circulating soluble FMS-like tyrosine kinase-1 (sFlt-1) (SMD 2.6; [1.7; 3.4]; n=34), and lower fetal weight (MD -0.4 g; [-0.47; -0.34]; n=113. The heterogeneity (variability between studies) in primary outcomes appeared ≥90%. Our meta-regression identified influential factors in the method and time point of BP measurement, randomization in fetal weight, and type of control group in sFlt-1. The RUPP is a robust model considering the evident differences in maternal and fetal outcomes. The high heterogeneity reflects the observed variability in phenotype. Due to underreporting, we observed reporting bias and a high risk of bias. We recommend standardizing study design by optimal time point and method chosen for readout measures to limit the variability. This contributes to improved reproducibility and thereby eventually improves the translational value of the RUPP model.

Elucidating Diversity of Linseed (Linum usitatissimum) Germplasms by Applying DUS Guideline to Examine Morphological Features

Flax, or Linum usitatissimum, is a multipurpose crop that may be produced in a variety of climates for use in industry, feed, fibre, and food. It is crucial to characterize and assess an array of genotypes to comprehend the potential of linseed in agriculture. The present investigation focused on agro-morphological characteristics to identify the best germplasm that may be utilized as future donors for linseed breeding. The goal of this study was to find the best germplasm to be used as future donors for linseed breeding by focusing on agro-morphological traits. In the current study, an expanded design was used to test 92 genotypes in total, both alien and native, throughout the course of two seasons, Rabi 2022-23 and Rabi 2023-24. The ninety-two genotypes were found to be organized into seven primary clusters by cluster analysis. Cluster I consist of twenty-four genotypes. Whereas cluster II and cluster III each encompass one genotype i.e., IC394118 and IC0599415 respectively. While cluster IV consists of seventeen genotypes, cluster V contain thirty-one genotypes. Cluster VI consist of seven genotypes. Whereas cluster VII which is the last cluster included eleven genotypes. A broad variation of genetic diversity was found using cluster analysis. The findings of this study open the door for focused breeding initiatives and environmentally friendly farming methods by offering insightful information about the genetic diversity and phenotypic variability of linseed.

Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy

Drug-recalcitrant infections are a leading global-health concern. Bacterial cells benefit from phenotypic variation, which can suggest effective antimicrobial strategies. However, probing phenotypic variation entails spatiotemporal analysis of individual cells that is technically challenging, and hard to integrate into drug discovery. In this work, we develop a multi-condition microfluidic platform suitable for imaging two-dimensional growth of bacterial cells during transitions between separate environmental conditions. With this platform, we implement a dynamic single-cell screening for pheno-tuning compounds, which induce a phenotypic change and decrease cell-to-cell variation, aiming to undermine the entire bacterial population and make it more vulnerable to other drugs. We apply this strategy to mycobacteria, as tuberculosis poses a major public-health threat. Our lead compound impairs Mycobacterium tuberculosis via a peculiar mode of action and enhances other anti-tubercular drugs. This work proves that harnessing phenotypic variation represents a successful approach to tackle pathogens that are increasingly difficult to treat.

Diverse gene regulatory mechanisms alter rattlesnake venom gene expression at fine evolutionary scales.

Understanding and predicting the relationships between genotype and phenotype is often challenging, largely due to the complex nature of eukaryotic gene regulation. A step towards this goal is to map how phenotypic diversity evolves through genomic changes that modify gene regulatory interactions. Using the Prairie Rattlesnake (Crotalus viridis) and related species, we integrate mRNA-seq, proteomic, ATAC-seq and whole genome resequencing data to understand how specific evolutionary modifications to gene regulatory network components produce differences in venom gene expression. Through comparisons within and between species, we find a remarkably high degree of gene expression and regulatory network variation across even a shallow level of evolutionary divergence. We use these data to test hypotheses about the roles of specific trans-factors and cis-regulatory elements, how these roles may vary across venom genes and gene families, and how variation in regulatory systems drive diversity in venom phenotypes. Our results illustrate that differences in chromatin and genotype at regulatory elements play major roles in modulating expression. However, we also find that enhancer deletions, differences in transcription-factor expression, and variation in activity of the insulator protein CTCF also likely impact venom phenotypes. Our findings provide insight into the diversity and gene-specificity of gene regulatory features and highlight the value of comparative studies to link gene regulatory network variation to phenotypic variation.

LMNA–RELATED DILATED CARDIOMYOPATHY PRESENTING WITH REGIONAL WALL AKINESIS AND TRANSMURAL LATE GADOLINIUM ENHANCEMENT

Abstract A 26–year–old girl was admitted at hospital in December 2022 for a syncopal episode. She referred fatigue and dyspnea in the last 2 months. EKG was markedly abnormal showing peripheral low voltages, poor R wave progression in prechordial leads, negative T waves V4–V6, DII, DIII and aVF, fragmented QRS (Fig.1). Echo showed moderately dilated left ventricle (LV) with apical akinesia and apical aneurysm (no thrombi) and hypo–akinesia and hyperechoic appearance of the middle segments of the infero–posterior and lateral wall (Fig.2a). EF was 38%. There was no family history for sudden cardiac death and cardiomyopathy. Creatine kinase and neurological examination were normal. The diagnostic work–up included: myocardial scintigraphy which showed fixed tracer uptake deficit at apical and posterolateral levels (Fig.2b); cardiac magnetic resonance (CMR): apical aneurysm with extended late gadolinium enhancement (LGE) due to fibrosis, focally transmural, on the left ventricle’s midapical and infero–lateral thinned–hypokinetic myocardial walls (Fig.3a, 3b); Coronary angiography showed no stenosis. Due to myocardial aneurysm in absence of CAD, Chagas disease was excluded. We performed LV endomyocardial biopsy which showed cardiomyopathic changes and replacement fibrosis. Due to fibrosis extension, complex ventricular extrasystoles detected on monitoring and syncope, ICD was implanted. Finally genetic testing showed c.1621C>Tp.Arg541Cys LMNA pathogenetic mutation leading to the diagnosis of LMNA–related LV cardiomyopathy, with extensive fibrosis in multiple areas of left ventricle including the apical segments at a very young age. Patients with LMNA mutation-related heart disease are characterized by conduction abnormalities, ventricular tachyarrhythmias (VA) and high risk of sudden cardiac death with mildly impaired systolic function, often without chamber dilation. About 88% LMNA– cardiomyopathy have typical myocardial fibrosis, predominantly in the mid-myocardium of the basal septum. However, our patient and previous reported cases with the same p.R541 LMNA mutation presents with a specific phenotype including regional LV akinesis, segmental transmural LGE, significant LV dilatation and systolic dysfunction and VA without conduction abnormality. Of note, EKG shows normal A–V conduction but low voltage and negative T waves in precordial and inferior leads. These features are not typical for LMNA–disease and underline the phenotypic variability of cardiomyopathies.

VARIABILITY OF SIGNS OF MILK PRODUCTIVITY OF COWS DEPENDING ON THEIR LINEAL AFFILIATION

Data on the signs of milk productivity of cows of the Ukrainian Black-and-White dairy breed depending on their lineal affiliation are given. The research was conducted in SE DG "Oleksandrivske" Vinnytsia region (Forest-Steppe zone, n=714), the LLC JV "Imeni Volovikova" Rivne region (Polissya zone, n=1,840) and the SE "Experimental farm "Askaniyske" (Steppe zone, n=926 ) on firstborn and full-grown (III lactation) animals. It was found that cows of the Chif line 1427381 (6384 kg) were the most productive in the first lactation in the Forest Steppe zone, in the third - Eleveishn line 1491007 (7325), in the Polissya zone – Starbak line 352790 for both lactations (6126 and 6521 kg, respectively), and in the Steppe zone – Annas Adema 30587 lines (6570 kg and 7482 kg). The highest content of fat in the milk of the SE DG "Oleksandrivske" was found in the first-borns of the Valiant line 1650414 (3.65%) and in full-aged cows of the Starbak line 352790 (3.59%), in the LLC JV "Imeni Volovikova" – Eleveyshn 1491007 (3.67 %) and Valiant 1650414 (3.68%), in SE "Experimental farm "Askaniyske" – Chif 1427381 (4.19%) and Bell 1667366 (4.19%). It is worth noting that the lowest milk yield for the first lactation in the above-mentioned farms was observed, respectively, in cows of lines Haneve 1629391 (5465 kg), Valiant 1650414 (4545 kg) and Bell 1667366 (6055 kg), for the third lactation - in individuals of lines Valiant 1650414 (6633 kg), Eleveishn 1491007 (6058 kg) and Bella 1667366 (6464 kg). In the Forest Steppe zone, the first-borns of the Eleveyshn 1491007 and Starbak 352790 lines were the least fat-milk – 3.59%, and full-aged cows of the Chif 1427381 and Valiant 1650414 lines – 3.56%, in the Polissya zone – the Chif 1427381 and Starbak 352 lines – 3.62% 790 – 3, 62%, and in the Steppe zone – the Annas Adem 30587 line for both lactations – 3.95 and 3.89%, respectively. Variance analysis confirmed the conditionality of the phenotypic variability of the quantitative traits of milk production depending on the lineal belonging of cows established by the comparison of group averages. At the same time, the line had a more significant effect on hope than on fat. Depending on the farm and lactation, the strength of the influence on the milk fat content was in the range of 4.1–21.1%, and in the range of .4–12.4%. Therefore, the linear belonging of cows to some extent can serve as a criterion for predicting their milk productivity.

Genomic loci associated with grain yield under well-watered and water-stressed conditions in multiple bi-parental maize populations

Smallholder maize farming systems in sub-Saharan Africa (SSA) are vulnerable to drought-induced yield losses, which significantly impact food security and livelihoods within these communities. Mapping and characterizing genomic regions associated with water stress tolerance in tropical maize is essential for future breeding initiatives targeting this region. In this study, three biparental F3 populations composed of 753 families were evaluated in Kenya and Zimbabwe and genotyped with high-density single nucleotide polymorphism (SNP) markers. Quantitative trait loci maping was performed on these genotypes to dissect the genetic architecture for grain yield (GY), plant height (PH), ear height (EH) and anthesis-silking interval (ASI) under well-watered (WW) and water-stressed (WS) conditions. Across the studied maize populations, mean GY exhibited a range of 4.55–8.55 t/ha under WW and 1.29–5.59 t/ha under WS, reflecting a 31–59% reduction range under WS conditions. Genotypic and genotype-by-environment (G × E) variances were significant for all traits except ASI. Overall broad sense heritabilities for GY were low to high (0.25–0.60). For GY, these genetic parameters were decreased under WS conditions. Linkage mapping revealed a significant difference in the number of QTLs detected, with 93 identified under WW conditions and 41 under WS conditions. These QTLs were distributed across all maize chromosomes. For GY, eight and two major effect QTLs (>10% phenotypic variation explained) were detected under WW and WS conditions, respectively. Under WS conditions, Joint Linkage Association Mapping (JLAM) identified several QTLs with minor effects for GY and revealed genomic region overlaps in the studied populations. Across the studied water regimes, five-fold cross-validation showed moderate to high prediction accuracies (−0.15–0.90) for GY and other agronomic traits. Our findings demonstrate the polygenic nature of WS tolerance and highlights the immense potential of using genomic selection in improving genetic gain in maize breeding.

Exploring cannabidiol variations, investigation of genetic diversity, population structure and unveiling male-specific genetic marker in industrial hemp (Cannabis sativa L.)

AbstractCannabis sativa played a pivotal role across different industries. Recently, industrial hemp, particularly in the case of Cannabidiol (CBD), gained attention for its therapeutic potential. This study evaluated cannabinoid variability and genetic diversity within 43 industrial hemp individuals, primarily Turkish, across various plant parts and growth stages, and inflorescences of females showed significant CBD content. The highest contents were observed in Turkish landraces (0.55–8.05% with an average of 3.26%), making them valuable genetic resources for high CBD. Genetic structure revealed distinct populations based on gender and influenced by geographical origin. Analysis of Molecular Variance showed 92% of genetic variation observed within populations and indicated a promising source of novel allelic diversity in the Turkish gene pool. Turkish females showed significant genetic diversity [No. of Different Alleles (Na) 1.507, No. of Effective Alleles (Ne) 1.226, Shannon’s Information Index (I) 0.258, and Percentage of Polymorphic Loc (%P) 74.91], exhibiting richer genetic variation than their international peers. Principal Coordinate Analysis unveiled gender-specific genetic differences, and admixture clusters shed light on genetic interactions and historical connections among diverse populations. Unweighted Pair-Group Method with Arithmetic Averaging highlighted unique genetic profiles and distinct genetic lineages. Genome-wide association study revealed a highly significant male-specific genetic marker explained 50% of the phenotypic variation. These findings inform future breeding strategies and conservation efforts and contribute to varietal identification methods, Marker-Assisted Selection, and efficient cultivar development in upcoming programs.

Pharmacotherapies for the Treatment of Progressive Supranuclear Palsy: A Narrative Review.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder resulting from the deposition of misfolded and neurotoxic forms of tau protein in specific areas of the midbrain, basal ganglia, and cortex. It is one of the most representative forms of tauopathy. PSP presents in several different phenotypic variations and is often accompanied by the development of concurrent neurodegenerative disorders. PSP is universally fatal, and effective disease-modifying therapies for PSP have not yet been identified. Several tau-targeting treatment modalities, including vaccines, monoclonal antibodies, and microtubule-stabilizing agents, have been investigated and have had no efficacy. The need to treat PSP and other tauopathies is critical, and many clinical trials investigating tau-targeted treatments are underway. In this review, the PubMed database was queried to collect information about preclinical and clinical research on PSP treatment. Additionally, the US National Library of Medicine's ClinicalTrials.gov website was queried to identify past and ongoing clinical trials relevant to PSP treatment. This narrative review summarizes our findings regarding these reports, which include potential disease-modifying drug trials, modifiable risk factor management, and symptom treatments.

SNPs in microRNA seed region and impact of miR-375 in concurrent regulation of multiple lipid accumulation-related genes

Bovine intramuscular fat (IMF), commonly referred to as marbling, is regulated by lipid metabolism, which includes adipogenesis, lipogenesis, glycerolipid synthesis, and lipolysis. In recent years, breeding researchers have identified single nucleotide polymorphisms (SNPs) as useful marker-assisted selection tools for improving marbling scores in national breeding programs. These included causal SNPs that induce phenotypic variation. MicroRNAs (miRNAs) are small highly conserved non-coding RNA molecules that bind to multiple non-coding regions. They are involved in post-transcriptional regulation. Multiple miRNAs may regulate a given target. Previously, three SNPs in the GPAM 3ʹ UTR and four miRNAs were identified through in silico assays. The aim of this study is to verify the binding ability of the four miRNAs to the SNPs within the 3ʹUTR of GPAM, and to identify the regulatory function of miR-375 in the expression of genes related to lipid metabolism in mammalian adipocytes. It was verified that the four miRNAs bind to the GPAM 3ʹUTR, and identified that the miR-375 sequence is highly conserved. Furthermore, it was founded that miR-375 upregulated the GPAM gene, C/EBPα, PPARγ and lipid metabolism-related genes and promoted lipid droplet accumulation in 3T3-L1 cells. In conclusion, these results suggest that miR-375 is a multifunctional regulator of multiple lipid metabolism-related genes and may aid in obesity research as a biomarker.

Вегетационный период сортов яровой мягкой пшеницы разных групп спелости в земледельческих зонах Красноярского края

The purpose of the study is to analyze the effect of cultivation point and meteorological factors on the duration of the growing season of spring wheat varieties of different ripeness groups. We used data from the State Variety Commission of the Krasnoyarsk Region on the yield and duration of the growing season of spring soft wheat varieties for 1999–2020. Statistical data processing was performed for varieties of four ripeness groups: early ripening, mid-early, mid-ripening and mid-late, undergoing variety testing in 6 natural zones of the Krasnoyarsk Region at 10 state variety plots: Zone III (lowland subtaiga, Kazachinsky state cultivating plot), IV (foothill subtaiga, Dzerzhinsky, Sayansky) , V (Kansk-Krasnoyarsk forest-steppe, Sukhobuzimsky, Uyarsky), VI (forest-steppe of the Chulym District, Nazarovsky, Uzhursky), VII (southern forest-steppe, Karatuzsky), VIII (foothill steppe on ordinary and southern chernozems, Krasnoturansky, Minusinsky). A significant range of variability in the studied period between variety plots was revealed for mid-ripening varieties (22 days), early-ripening (20 days), mid-early (17 days), mid-ripening varieties (12 days). A shorter growing season for all ripeness groups is shown by varieties in the Kazachinsky variety plot, a longer one – in the Sayansky and Uyarsky variety plots. A significant amplitude of variability in the duration of the growing season for all ripeness groups is observed in the Nazarovsky, Karatuzsky, and in mid-ripening and mid-late varieties – Uyarsky, Uzhursky, Minusinsky variety plots. The phenotypic varia-bility of the period under study is determined primarily by the contribution of the factor “varietal plots” (34.0–48.1 %) and the interaction “years × varietal plots” (36.0–53.2 %). The variety plots are located in different natural and climatic zones of the region and have their own characteristics according to the complex of natural conditions, which is shown by different correlations between the duration of the growing season and meteorological factors. They differ in variety areas, which represent the natural zones of the region. It has been proven that to form the duration of the growing season of mid-late varieties at the Dzerzhinsky, Sayansky, Uyarsky and Nazarovsky variety plots, average daily air temperatures are more ne¬cessary; Sayansky, Dzerzhinsky, Sukhobuzimsky – precipitation; Sayan, Dzerzhinsky, Sukhobuzimsky, Uyarsky, Nazarovsky, Uzhursky variety plots – relative air humidity than for varieties of other ripeness groups. Reliable correlations between average daily air temperature, precipitation and relative air humidity with the duration of the growing season were obtained for all ripeness groups at the Karatuz and Krasnoturan variety plots.

Unraveling Phenotypic Variability in Action Myoclonus with Renal Failure with SCARB2 Mutation in Siblings.

Unraveling Phenotypic Variability in Action Myoclonus with Renal Failure with SCARB2 Mutation in Siblings.

Effect of Allele-Specific Clcn7G213R siRNA Delivered Via a Novel Nanocarrier on Bone Phenotypes in ADO2 Mice on 129S Background.

Autosomal dominant osteopetrosis type 2 (ADO2) is a rare inherited bone disorder characterised by dense but brittle bones. It displays striking phenotypic variability, with the most severe symptoms, including blindness and bone marrow failure. Disease management largely relies on symptomatic treatment since there is no safe and effective treatment. Most ADO2 cases are caused by heterozygous loss-of-function mutations in the CLCN7 gene, which encodes an essential Cl-/H+ antiporter for proper bone resorption by osteoclasts. Thus, siRNA-mediated silencing of the mutant allele is a promising therapeutic approach, but targeting bone for first-in-human translation remains challenging. Here, we demonstrate the utility of silicon-stabilised hybrid lipid nanoparticles (sshLNPs) as a next-generation nucleic acid nanocarrier capable of delivering allele-specific siRNA to bone. Using a Clcn7G213R knock-in mouse model recapitulating one of the most common human ADO2 mutations and based on the 129S genetic background (which produces the most severe disease phenotype amongst current models), we show substantial knockdown of the mutant allele in femur when siRNA targeting the pathogenic variant is delivered by sshLNPs. We observed lower areal bone mineral density in femur and reduced trabecular thickness in femur and tibia, when siRNA-loaded sshLNPs were administered subcutaneously (representing the most relevant administration route for clinical adoption and patient adherence). Importantly, sshLNPs have improved stability over conventional LNPs and enable 'post hoc loading' for point-of-care formulation. The treatment was well tolerated, suggesting that sshLNP-enabled gene therapy might allow successful clinical translation of essential new treatments for ADO2 and potentially other rare genetic bone diseases.

High-density genetic map construction and QTL mapping of a zigzag-shaped stem trait in tea plant (Camellia sinensis)

The highly unique zigzag-shaped stem phenotype in tea plants boasts significant ornamental value and is exceptionally rare. To investigate the genetic mechanism behind this trait, we developed BC1 artificial hybrid populations. Our genetic analysis revealed the zigzag-shaped trait as a qualitative trait. Utilizing whole-genome resequencing, we constructed a high-density genetic map from the BC1 population, incorporating 5,250 SNP markers across 15 linkage groups, covering 3,328.51 cM with an average marker interval distance of 0.68 cM. A quantitative trait locus (QTL) for the zigzag-shaped trait was identified on chromosome 4, within a 61.2 to 97.2 Mb range, accounting for a phenotypic variation explained (PVE) value of 13.62%. Within this QTL, six candidate genes were pinpointed. To better understand their roles, we analyzed gene expression in various tissues and individuals with erect and zigzag-shaped stems. The results implicated CsXTH (CSS0035625) and CsCIPK14 (CSS0044366) as potential key contributors to the zigzag-shaped stem formation. These discoveries lay a robust foundation for future functional genetic mapping and tea plant genetic enhancement.

Brd4::Nutm1fusion gene initiates NUT carcinoma in vivo

NUT carcinoma (NC) is an aggressive cancer with no effective treatment. About 70% of NUT carcinoma is associated with chromosome translocation events that lead to the formation of aBRD4::NUTM1fusion gene. Because theBRD4::NUTM1gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model for NUT carcinoma that recapitulates the human t(15;19) chromosome translocation in mice. We demonstrated that the mouse t(2;17) syntenic chromosome translocation, forming theBrd4::Nutm1fusion gene, could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with enrichment of undifferentiated cells. Similar to the reports of human NC incidence,Brd4::Nutm1can induce NC from a broad range of tissues with a strong phenotypical variability. The consistent induction of poorly differentiated carcinoma demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC that will lead to better understanding and therapy development for NC.