Effect Of Genotype Research Articles

PNPLA3 risk allele is associated with risk of hepatocellular carcinoma but not decompensation in compensated cirrhosis.

The PNPLA3-rs738409-G, TM6SF2-rs58542926-T, and HSD17B13-rs6834314-A polymorphisms have been associated with cirrhosis, hepatic decompensation, and HCC. However, whether they remain associated with HCC and decompensation in people who already have cirrhosis remains unclear, which limits the clinical utility of genetics in risk stratification as HCC is uncommon in the absence of cirrhosis. We aimed to characterize the effects of PNPLA3, TM6SF2, and HSD17B13 genotype on hepatic decompensation, HCC, and liver-related mortality or liver transplant in patients with baseline compensated cirrhosis. We conducted a single-center retrospective study of patients in the Michigan Genomics Initiative who underwent genotyping. The primary predictors were PNPLA3, TM6SF2, and HSD17B13 genotypes. Primary outcomes were either hepatic decompensation, HCC, or liver-related mortality/transplant. We conducted competing risk Fine-Gray analyses on our cohort. We identified 732 patients with baseline compensated cirrhosis. During follow-up, 50% of patients developed decompensation, 13% developed HCC, 24% underwent liver transplant, and 27% died. PNPLA3-rs738409-G genotype was associated with risk of incident HCC: adjusted subhazard hazard ratio 2.42 (1.40-4.17), p=0.0015 for PNPLA3-rs738409-GG vs. PNPLA3-rs738409-CC genotype. The 5-year cumulative incidence of HCC was higher in PNPLA3-rs738409-GG carriers than PNPLA3-rs738409-CC/-CG carriers: 15.6% (9.0%-24.0%) vs. 7.4% (5.2%-10.0%), p<0.001. PNPLA3 genotype was not associated with decompensation or the combined outcome of liver-related mortality or liver transplant. TM6SF2 and HSD17B13 genotypes were not associated with decompensation or HCC. The PNPLA3-rs738409-G allele is associated with an increased risk of HCC among patients with baseline compensated cirrhosis. People with cirrhosis and PNPLA3-rs738409-GG genotype may warrant more intensive HCC surveillance.

Multi-Locational Evaluation of Forage-Suited Selected Sudan Pearl Millet [Pennisetum glaucum (L.) R. Br.] Accessions Identified High-Yielding and Stable Genotypes in Irrigated, Arid Environments

Pearl millet [Pennisetum glaucum (L.) R. Br.] is a subtropical grain and forage crop. It is privileged with several desirable forage attributes. Nevertheless, research on pearl millet is limited, especially as a forage crop, in developing countries. Therefore, the objectives of this study were to investigate the field performance and stability of pearl millet genotypes for forage yield across seven environments. The study was conducted in seven environments (combination of locations and seasons) during the 2016/2017–2018/2019 seasons. Twenty-five pearl millet genotypes, selected based on forage yield from a core collection of 200 accessions, were arranged in an alpha lattice design with three replications. The parameters measured were fresh forage yield, days to flowering, plant height, number of culms m−2, leaf-to-stem ratio, and stem girth. The combined analysis revealed that environments, genotypes, and their interaction had significant effects on all traits studied except the genotypic effect on stem girth. Across the seven environments, four genotypes (G14, G01, G12, and G22) outyielded the check genotype in fresh matter yield by 20.7, 16.5, 11.0 and 9.8%, respectively. The additive main effects and multiplicative interaction (AMMI) analysis showed that the genotype, environment, and their interaction were highly significant (p ≤ 0.001) for fresh matter yield. The results of AMMI stability values (ASVs) and the genotype selection index (GSI) combined with the AMMI estimate-based selection showed that genotypes G14, G22 and G01 were the most stable and adapted genotypes and were superior to the check genotype. These results indicate that forage pearl millet varieties could be developed directly through evaluating the wealth of available collections or indirectly through hybridization in crop breeding programs.

Integrating genetic and socioeconomic data to predict the progression of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally, with an estimated prevalence exceeding 25%. Variants in the PNPLA3 and HSD17B13 genes have been a focus of investigations surrounding the etiology and progression of NAFLD and are believed to contribute to a greater burden of disease experienced by Hispanic Americans. However, little is known about socioeconomic factors influencing NAFLD progression or its increased prevalence among Hispanics. We cross-sectionally analyzed 264 patients to assess the role of genetic and socioeconomic variables in the development of advanced liver fibrosis in individuals at risk for NAFLD. Adjusting for age, sex, body mass index, and PNPLA3 genotype, lacking a college degree was associated with 3.3 times higher odds of advanced fibrosis (95% confidence interval [CI]: 1.21-8.76, p = 0.019), an effect comparable to that of possessing the major PNPLA3 risk variant. Notably, the effect of PNPLA3 genotype on advanced fibrosis was attenuated to nonsignificance following adjustment for education and other socioeconomic markers. The effect of the protective HSD17B13 variant, moreover, diminished after adjustment for education (odds ratio [OR]: 0.39 [95% CI: 0.13-1.16, p = 0.092]), while lower education continued to predict advanced fibrosis following multivariable adjustment with an OR of 8.0 (95% CI: 1.91-33.86, p = 0.005). Adjusting for education attenuated the effects of genotype and Hispanic ethnicity on liver fibrosis, suggesting that social factors-rather than genes or ethnicity-may be driving disease severity within some populations. Findings reveal the importance of including socioenvironmental controls when considering the role of genetics or ethnicity in complex disease.

Evaluation of sugar beet (Beta vulgaris L.) cultivars for some biochemical and agronomic traits under drought stress

This experiment aimed to evaluate quantitative and qualitative characteristics, tolerance to water deficit, and stability of white sugar in sugar beet cultivars. The experimental design was a split plot based on a randomized complete block design with three replications, where the irrigation levels (normal and water shortage) were assigned to the main plots and 18 sugar beet cultivars were assigned to the subplots. The result revealed that Palma achieved the maximum root and white sugar yield under normal and water deficit; furthermore, the highest indices of YP, YS, MP, STI, HM, YI, DI, REI and MRP belonged to the Palma cultivar. The results of the AMMI analysis based on white sugar yield showed that the additive effects of genotype and environment and the multiplicative effect of G×E accounted for 75.52, 17.05 and 6.76 % of the total data variance. Based on AMMI stability value, the Delta, Pars, Paya and Novodoro cultivars were recognized as stable varieties. Also, the first 2 significant components of the interaction effect (G×E) accounted for 99.12 % of interaction effects variation. Based on the biplot results of the first 2 significant components against white sugar yield, Azare and Merak were the appropriate cultivars. Finally, Based on the multi-trait stability index, Azara, Novodoro and Merak cultivars were selected as stable genotypes. In 2 years and 2 conditions, the Palma cultivar was identified as a cultivar with high yield and drought tolerance and low stability and the Merak cultivar was identified as a cultivar with white sugar yield and acceptable stability.

Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia.

Cognitive reserve (CR) and the catechol-O-methyltransferase (COMT) Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia. However, the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined. To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism. In a cross-sectional study, 54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype, CR, and negative symptoms. CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale. COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes. In the total sample, significant negative correlations were found between negative symptoms and information, similarities. Associations between information, similarities and negative symptoms were observed in Val homozygotes only, with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms (information, β = -0.282, 95%CI: -0.552 to -0.011, P = 0.042; similarities, β = -0.250, 95%CI: -0.495 to -0.004, P = 0.046). This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.

Effects of fast and slow-wilting soybean genotypes on fall armyworm (Spodoptera frugiperda) growth and development

ABSTRACT Soybean (Glycine max) is the most important plant protein source, and Fall Armyworm (FAW, Spodoptera frugiperda) is considered a major pest. This study aimed to examine the impact of FAW feeding on soybean accessions that vary in their water use efficiency (WUE) traits, by examining FAW growth and life history parameters along with plant growth response to pest damage. Soybean accessions were grown in a greenhouse and exposed to FAW larval feeding for 48 h at three different soybean growth stages: V3, R3, and R6. The growth and development of the FAW and soybeans were monitored. Results showed that faster wilting soybean accessions grow taller and have more leaves than slower wilting accessions, but yield was higher in slower wilting soybean accessions. FAW experienced the highest mortality on mid-stage (R3) soybean plants, but they gained the least mass on early stage (V3) soybean plants. These results can assist in better understanding plant insect-interactions at different life stages in both soybean and FAW with implications for management.

Effect of HLA Genotype on Anti-PD-1 Antibody Treatment for Advanced Renal Cell Carcinoma in the SNiP-RCC Study.

Immune checkpoint blockade therapies are widely used for cancer treatment, including advanced renal cell carcinoma (RCC). This study aimed to investigate the impact of zygosity in HLA genes and individual HLA genotypes on the efficacy of an anti-PD-1 Ab, nivolumab, in treating advanced RCC. Patient enrollment was conducted across 23 institutions in Japan from August 19, 2019, to September 30, 2020, with follow-up concluding on March 31, 2021. HLA genotype imputation of HLA-A, B, and C, DQB1, and DRB1 loci was performed. Among 222 patients, the presence of at least one homozygosity of the HLA-II allele significantly improved the best objective response (hazard ratio, 0.34; 95% confidence interval, 0.21-0.96; p = 0.042). The HLA evolutionary divergence (HED) of the HLA-A and HLA-B loci was higher than the HLA-C (p < 0.0001 and p < 0.0001, respectively), with high HED of the HLA-B locus correlating to clinical benefits in nivolumab treatment (hazard ratio, 0.44; 95% confidence interval, 0.21-0.90; p = 0.024) and improving cancer-specific survival compared with the low group (p = 0.0202). Additionally, high HED of the HLA-B locus was correlated with the number of infiltrated CD8+ cells in the tumor microenvironment (correlation coefficient, 0.4042). These findings indicate that the diversity of the HLA-B locus plays a significant role in the anti-tumor effect of nivolumab treatment in advanced RCC, potentially offering insights for improved risk stratification in nivolumab treatment and leading to better medical management of advanced RCC.

Interaction of age and CYP2C19 genotypes on voriconazole steady-state trough concentration in Chinese patients.

Both age and CYP2C19 genotypes affect voriconazole plasma concentration; the interaction of age and CYP2C19 genotypes on voriconazole plasma concentration remains unknown. This study aims to investigate the combined effects of age and CYP2C19 genotypes on voriconazole plasma concentration in Chinese patients. A total of 480 patients who received voriconazole treatment were recruited. CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) polymorphisms were genotyped. Patients were divided into the young and the elderly groups by age of 60 years old. Influence of CYP2C19 genotype on steady-state trough concentration (Css-min) in overall patients and in age subgroups was analyzed. Voriconazole Css-min correlated positively with age, and mean voriconazole Css-min was significantly higher in the elderly group (P < 0.001). CYP2C19 poor metabolizers showed significantly increased mean voriconazole Css-min in the young but not the elderly group. The percentage of patients with subtherapeutic voriconazole Css-min (<1.0 mg/l) was higher in the young group and that of supratherapeutic voriconazole Css-min (>5.5 mg/l) was higher in the elderly patients. When the average Css-min in the CYP2C19 normal metabolizer genotype was regarded as a reference, CYP2C19 genotypes showed greater impact on voriconazole Css-min in the young group, while the influence of age on voriconazole Css-min exceeded CYP2C19 genotypes in the elderly. CYP2C19 genotypes affects voriconazole exposure is age dependent. Influence of CYP2C19 poor metabolizer genotype on increased voriconazoleexposure is prominent in the young, while age is a more important determinant factor for increased voriconazole exposure in the elderly patients.

Genotype by year interaction for selected traits in sweet maize (Zea maize L.) hybrids using AMMI model

This study investigated genotype × environment interactions for the stability of expression of four productivity traits (cobs yield, cobs I class trade share, lend of cobs and fulfilment of cobs) of sweet maize hybrids (Zea mays L.). The additive main effects and multiplicative interaction (AMMI) model was employed to assess genotype × environment interaction. AMMI stability value was used to evaluate both stability and genotype. The genotype selection index was calculated for each hybrid, incorporating both the average trait value and the stability index. Ten sweet maize hybrids were evaluated: Golda, GSS 1453, GSS 3071, GSS 5829, GSS 8529, Overland, Noa, Shinerock, Sindon, and Tessa. Trials were ran conducted over four vegetative seasons at a single location in the Wielkopolska region using replicated field experiments. The AMMI model revealed significant genotypic and environmental effects for all analyzed traits. Based on their superior stability and favorable average trait values, both the Golda cultivar and the GSS 3071 hybrid are recommended for further breeding program inclusion.

Adaptive potential of winter common wheat varieties in the Penza region

The current paper has presented the results of long-term study (2014–2023) of productivity, adaptability parameters and correlation between a genotype and environment of winter common wheat varieties in the forest-steppe conditions of the Penza region. The purpose of the study was to determine the response of winter common wheat varieties in changing agroclimatic conditions according to productivity. The vegetation conditions during the years of study varied in temperature and amount of precipitation, which served as a good background for conducting research on the issue in question. The objects for the study were 9 zoned varieties approved for cultivation in the Middle Volga region and 5 winter common wheat varieties developed by the FSBRI CBFC. The zoned winter common wheat variety ‘Fotiniya’ was used as a standard. The years of the varieties’ study were divided into favorable, typical (mean) and unfavorable (dry, excessively wet). Winter common wheat productivity in favorable years averaged 5.68 t/ha, in typical years it was 4.32 t/ha and 2.19 t/ in unfavorable years. As a result of determining the response of winter common wheat varieties in changing agroclimatic conditions according to productivity, there was proven a strong effect of environmental conditions and genotype. There have been proposed for breeding use such valuable and stable genotypes of winter common wheat as ‘Biryuza’, ‘Skipetr’, ‘Don-eko’, ‘Alyonushka’, ‘Pamyati Krivobocheka’, ‘Surskaya Nika’, ‘Dargo’, which should be placed on a high and medium agricultural background. The varieties ‘Fotiniya’ and ‘Klavdiya 2’ are highly adaptable to unfavorable cultivation conditions and will have an advantage over other varieties in medium and low agricultural backgrounds.

Association between executive functions and COMT Val108/158Met polymorphism among healthy younger and older adults: A preliminary study.

Genetic variability in the dopaminergic system could contribute to age-related impairments in executive control. In this study, we examined whether genetic polymorphism for catechol-O-methyltransferase (COMT Val158Met) is related to performance on updating, shifting and inhibition tasks. We administered a battery of executive tasks assessing updating, shifting and inhibition functions to 45 older and 55 younger healthy participants, and created composite z-scores associated to each function. Six groups were created based on genetic alleles (Val/Val, Val/Met, Met/Met) derived from the COMT gene and age (younger, older). Age and genotype effects were assessed with t-test and ANOVA (p<0.05). A lower performance was observed in the older group for the three executive processes, and more particularly for inhibition. Moreover, older participants homozygous for the Val allele have a lower performance on the inhibition composite in comparison to younger Val/Val. These results confirm presence of executive performance decrease in healthy aging. With regard to genetic effect, older participants seem particularly disadvantaged when they have a lower baseline dopamine level (i.e., Val/Val homozygous) that is magnified by aging, and when the executive measure emphasize the need of stable representations (as in inhibition task requiring to maintain active the instruction to not perform an automated process).

Impact of the leptin receptor gene on pig performance and quality traits

The recessive T allele of the missense polymorphism rs709596309 C > T of the leptin receptor gene is associated with intramuscular fat. However, its overall impact on pork production is still partial. In this work, we investigated the all-round effects of the TT genotype on lean growth efficiency and carcass, meat and fat quality using data from an experiment that compared the performance of 48 TT and 48 C– (24 CT and 24 CC) Duroc barrows. The TT pigs were less efficient for lean growth than the C– pigs. Although heavier, their carcasses had less lean content, were shorter and had lighter loins. Apart from increasing marbling and saturated fatty acid content, changes caused by the TT genotype in meat and fat quality are likely not enough to be perceived by consumers. The effect on visual marbling score exceeded that on intramuscular fat content, which suggests a direct influence of the T allele on the pattern of fat distribution in muscle. With current low-protein diets, the T allele is expected to be cost-effective only in niche markets where a very high level of marbling is critical.

Normalized Clinical Severity Scores Reveal a Correlation between X Chromosome Inactivation and Disease Severity in Rett Syndrome.

Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing the MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI), resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age-dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT severity by modeling longitudinal data collected in the US Rett Syndrome Natural History Study. This model accurately reflected individual increase in severity with age and preserved group-level genotype specific differences in severity, allowing for the creation of a normalized clinical severity score. Applying this normalized score to a RTT XCI dataset revealed that XCI influence on disease severity depends on MECP2 genotype with a correlation between XCI and severity observed only in individuals with MECP2 variants associated with increased clinical severity. This normalized measure of RTT severity provides the opportunity for future discovery of additional factors contributing to disease severity that may be masked by age and genotype effects.

Hydroponic Screening at Early Seedling Stage Identified Sources of Salinity Tolerance in Wheat (Triticum aestivum L.) Crop

Wheat is a vital crop globally, essential for agriculture, economics, and food security. However, in arid and semi-arid conditions, wheat production faces significant challenges due to low water availability, uneven rainfall distribution, and high soil salinity. The germination and early seedling stages are particularly vulnerable to these stresses. Therefore, this study assessed 15 wheat genotypes for their tolerance to salinity stress during early growth stages, using a hydroponic system with four salt stress levels (0, 50, 100, and 150 mM NaCl). Significant differences were observed for genotype and salinity main effects and their interaction on all investigated traits, indicating considerable variability in the response to salt stress among the investigated wheat cultivars. High NaCl concentrations led to substantial reductions in measured parameters across genotypes, with some showing resilience while others exhibited heightened sensitivity. Stress tolerance indices, such as mean productivity (MP), geometric mean productivity (GMP), harmonic mean (HM), stress tolerance index (STI) and yield index (YI), were identified as reliable indicators for selecting salt-tolerant wheat cultivars. Consequently, Sidi Okba (G11), Ziad (G12), Tamezghida (G13) and Zidane (G14) emerged as the most promising, displaying acceptable performance under both non-stress and salt-stress conditions. These genotypes could serve as valuable genetic resources for breeding programs aimed at enhancing wheat’s salinity tolerance, particularly in arid and semi-arid regions.

Discovering new genes for alfalfa (Medicago sativa) growth and biomass resilience in combined salinity and Phoma medicaginis infection through GWAS.

Salinity and Phoma medicaginis infection represent significant challenges for alfalfa cultivation in South Africa, Europe, Australia, and, particularly, Tunisia. These constraints have a severe impact on both yield and quality. The primary aim of this study was to establish the genetic basis of traits associated with biomass and growth of 129 Medicago sativa genotypes through genome-wide association studies (GWAS) under combined salt and P. medicaginis infection stresses. The results of the analysis of variance (ANOVA) indicated that the variation in these traits could be primarily attributed to genotype effects. Among the test genotypes, the length of the main stem, the number of ramifications, the number of chlorotic leaves, and the aerial fresh weight exhibited the most significant variation. The broad-sense heritability (H²) was relatively high for most of the assessed traits, primarily due to genetic factors. Cluster analysis, applied to morpho-physiological traits under the combined stresses, revealed three major groups of accessions. Subsequently, a GWAS analysis was conducted to validate significant associations between 54,866 SNP-filtered single-nucleotide polymorphisms (SNPs) and seven traits. The study identified 27 SNPs that were significantly associated with the following traits: number of healthy leaves (two SNPs), number of chlorotic leaves (five SNPs), number of infected necrotic leaves (three SNPs), aerial fresh weight (six SNPs), aerial dry weight (nine SNPs), number of ramifications (one SNP), and length of the main stem (one SNP). Some of these markers are related to the ionic transporters, cell membrane rigidity (related to salinity tolerance), and the NBS_LRR gene family (associated with disease resistance). These findings underscore the potential for selecting alfalfa genotypes with tolerance to the combined constraints of salinity and P. medicaginis infection.

Genotypic effects on accelerated propagation of oil palm breeding materials selected (Elaeis guineensis Jacq.) using somatic embryogenesis

Vegetable oil production from oil palm (Elaeis guineensis Jacq.) is an important industry due to the rising demand every year. The somatic embryogenesis culture can propagate oil palm duplicate as the parent, which can be selected as breeding material to produce new planting germplasm with high production or disease resistance. This study aims to evaluate the genotypic effect of somatic embryogenesis, while immature leaflets were employed as explants. The culture used medium embryo induction based on Murashige and Skoog (MS) modifications that contained 5 mg/l Naphthalene Acetic acid (NAA) and 0.5 mg/l Benzyl Amino Purine (BAP). The genotypic effect was statistically significant in the percentage of callus induction, producing somatic embryos, and germination embryos. In this study, we successfully cloned thirteen oil palm genotypes (GE-02, GE-03, GE-06, GE-07, GE-09, GE-23, GE-24, GE-27, GE-28, GE-32, GE-33, GE-34, and GE-35), with the highest number of somatic embryos formed on GE-27 with a percentage of 70.1%. The cloning was successful in accelerating the propagation of oil palm for materials breeding programs to create new varieties with high production and disease resistance. It is necessary to observation the performance of the clones in the field in terms of mantle flower appearance.

Sex-Dependent Regulation of Mucin Gene Transcription and Goblet Cell Secretion Machinery Following Intra-Airway IL-13 in Mice with Conditional Loss of Club Cell Creb1

IL-13 is an important effector molecule in allergic asthma, converting secretoglobin-positive club cells into mucin-secreting goblet cells and promoting mucin hypersecretion. IL-13-mediated conversion of club cells to goblet cells requires decreased gene expression of forkhead box A2 ( FOXA2) and increased gene expression of SAM pointed domain containing ETS transcription factor ( SPDEF). In addition, IL-13-mediated mucin hypersecretion may include modulation of purinergic and muscarinic receptors that control basal and stimulated mucus secretion, respectively. We recently found that the cAMP response element-binding protein (CREB), a ubiquitous transcription factor, directly binds to FOXA2 and modulates mucus secretion mechanisms in mice. Here we tested the hypothesis that conditional loss of club cell Creb1 in murine airways modulates the pro-mucin effects of IL-13. Loss of club cell Creb1 augmented IL-13-mediated increases in gene expression of the major gel-forming secreted mucins Muc5ac and Muc5b in male murine airways, with no effect on IL-13-mediated increases in Muc5ac and Muc5b in female murine airways. Examination of mucin secretion mechanisms revealed that IL-13 decreased muscarinic 3 receptor ( M3R) mRNA expression in male murine airways, whereas loss of club cell Creb1 prevented this, resulting in a significant treatment by genotype interaction. Interestingly, in female airways, a main effect of genotype was observed, with loss of club cell Creb1 reducing M3R mRNA expression in the airway. Examination of the purinergic receptor P2Y ( P2ry2) mRNA revealed a main treatment effect for IL-13 to increase P2ry2 expression in male murine airways with no impact of loss of club cell Creb1. In the females, IL-13 increased P2ry2 mRNA in both genotypes, with loss of club cell Creb1 significantly blunting the effect of IL-13 on P2ry2 mRNA. Lastly, we examined goblet cell density and mucin secretion mechanisms using Alcian Blue-PAS staining post in vivo stimulation with a muscarinic agent. We found no major effect of treatment or genotype in the density of goblet cells containing acidic mucins in either male or female airways. In contrast, both males and females showed IL-13-mediated increases in the density of goblet cells containing neutral mucins that was not impacted by genotype. Our preliminary findings suggest that loss of club cell Creb1 decreases molecular mucin secretion mechanisms in male and female airways, and increases Muc5ac and Muc5b mRNA in male airways, though a corresponding genotype-dependent increase in goblet cell density post cholinergic stimulation was not observed. Thus, we conclude that loss of club cell Creb1 causes changes to molecules important for IL-13-mediated mucin hypersecretion, without apparent functional benefit or detriment to the murine airway. This work was supported by the National Institutes of Health (OD026582, HL152101), the Cystic Fibrosis Foundation (REZNIKO20I0, REZNIKO19I0), the Katie Rose Foundation (AWD08203), and the University of Florida McKnight Career Accelerator Award. Angelina Bonilla was funded by the National institutes of Health (R25GM115298). Pedro Trevizan Bau receives the University of Florida McKnight Brain Institute Gator NeuroScholar Fellowship. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of astaxanthin in type-2 diabetes -induced APPxhQC transgenic and NTG mice

ObjectivesAggregation and misfolding of amyloid beta (Aβ) and tau proteins, suggested to arise from post-translational modification processes, are thought to be the main cause of Alzheimer’s disease (AD). Additionally, a plethora of evidence exists that links metabolic dysfunctions such as obesity, type 2 diabetes (T2D), and dyslipidemia to the pathogenesis of AD. We thus investigated the combinatory effect of T2D and human glutaminyl cyclase activity (pyroglutamylation), on the pathology of AD and whether astaxanthin (ASX) treatment ameliorates accompanying pathophysiological manifestations. MethodsMale transgenic AD mice, APPxhQC, expressing human APP751 with the Swedish and the London mutation and human glutaminyl cyclase (hQC) enzyme and their non-transgenic (NTG) littermates were used. Both APPxhQC and NTG mice were allocated to 3 groups, control, T2D-control, and T2D-ASX. Mice were fed control or high fat diet ± ASX for 13 weeks starting at an age of 11-12 months. High fat diet fed mice were further treated with streptozocin for T2D induction. Effects of genotype, T2D induction, and ASX treatment were evaluated by analysing glycemic readouts, lipid concentration, Aβ deposition, hippocampus-dependent cognitive function and nutrient sensing using immunosorbent assay, ELISA-based assays, western blotting, immunofluorescence staining, and behavioral testing via Morris water maze (MWM), respectively. ResultsAPPxhQC mice presented a higher glucose sensitivity compared to NTG mice. T2D-induced brain dysfunction was more severe in NTG compared to the APPxhQC mice. T2D induction impaired memory functions while increasing hepatic LC3B, ABCA1, and p65 levels in NTG mice. T2D induction resulted in a progressive shift of Aβ from the soluble to insoluble form in APPxhQC mice. ASX treatment reversed T2D- induced memory dysfunction in NTG mice and in parallel increased hepatic pAKT while decreasing p65 and increasing cerebral p-S6rp and p65 levels. ASX treatment reduced soluble Aβ38 and Aβ40 and insoluble Aβ40 levels in T2D-induced APPxhQC mice. ConclusionsWe demonstrate that T2D induction in APPxhQC mice poses additional risk for AD pathology as seen by increased Aβ deposition. Although ASX treatment reduced Aβ expression in T2D-induced APPxhQC mice and rescued T2D-induced memory impairment in NTG mice, ASX treatment alone may not be effective in cases of T2D comorbidity and AD.

Unraveling genotype-by-environment interaction in maize using cutting edge statistical tools: Innovative empirical selection for increased yield stability

By prioritizing high yields in ideal conditions, traditional breeding might miss out that genotypes with superior yield and stability. Thus,this study seeks to identify stable genotypes that offer more predictable and reliable yields; under both stress and resourceful environments, leading to not only greater food security but financial stability as well. Incorporating both fixed (AMMI&GGI) and random effects models (BLUP & MTSI), not only leveraged theoretical but also empirical comparisons-weakness of each model is covered by all 4 models-to select elites hybrids Maize. Furthermore, a multi-environment trial assessed 41 hybrids across 4 research stations in 2 winter seasons using RCB design. Likewise, compiled cutting-edge statistical methods for GEI analyses from the “metan” package (R-Software), selected hybrids with consistent performance with meticulous analysis. AMMI(Additive Main effects and Multiplicative Interaction)analysis revealed that of significant (p ≤ 0.05) effects of genotype, environment, & genotype-environment interaction (GEI), explaining yield variance with interaction effects were captured by 3 interaction principal components (IPCs). Moreover,GEI graphics of AMMI biplots elucidates four hybrids(MRM-4062, Super-22, PAC-744, and Gen-4118) with high yield stability and above-average performance. Additionally, eight hybrids (4118, 4558, 5454, NMH1258, PAC 746, PAC 745 Gold, and SUPER 9090) exhibited superior yield, regardless of their stability. Nepalgunj exhibited the lowest GEI value. Conversely, Rampur displayed an above-average GEI, indicating a strong ability to modulate varieties performance. Besides this, GGE biplot revealed two potential mega-environments based on yield similarities. Nine high-yielding hybrids (SUPPER 6768, SUPPER 9396, PAC750, MBS5622, PAC745 Gold, MRM4065, NMH8392, Gen-4118, and Gen-4558) were identified as vertex hybrids, signifying their superior performance across wide environments. Even supposing, mixed effects model, both the best linear unbiased prediction (BLUP) weighted with average absolute score standardized by yields (WAASBY) models, Gen-4118 ranked highest in terms of average yield, followed by NMH-8392, TMH2858, and others, and Multi-Trait Stability Index (MTSI) identified SUPPER-9090 as the most stable and high-yielding genotype, followed by NMH4040, Super-22, Gen-4118, MBS-1144, and NMH1255. In a nutshell, Gen-4118, Super-9090, MRM-4062, NMH1258, NMH-8392, TMH2858, PAC 746, PAC 745 Gold emerge as the highest-yielding and most consistently high-performinghybrids, offering promise for commercial farming across diverse environments. Clearly,this study has potential to mitigate risks for farmers (economic burden, crop failure) and bolster food security/climate resilience. What's more, it paves the way for future research on cold tolerance genes for even greater crop improvement.

Adrenal circadian clock protein BMAL1 regulates aldosterone and renal excretory function in a sex- and time-dependent manner

BMAL1 is a core circadian clock protein that is important for circadian rhythms of physiological function, as well as maintaining physiological homeostasis, including aspects of kidney function. Global Bmal1 knockout (KO) male mice exhibit loss of diurnal rhythm of renal sodium (Na) excretion in response to a normal or high salt diet. However, renal Na excretion rhythm remained intact in kidney-specific Bmal1 KO male mice. The adrenal gland synthesizes hormones, such as aldosterone, which influence renal electrolyte handling. The role of adrenal BMAL1 in the regulation of renal function remains unknown. The study objective was to test the hypothesis that adrenal BMAL1 is required for normal rhythms of aldosterone and renal Na handling. Male and female adrenal-specific aldosterone synthase Cre positive (AS) Bmal1 KO and littermate Cre negative, floxed control mice ( n=5-9/genotype) were acclimated to metabolic cages for 3 days then samples were collected for three days with mice on a normal salt diet followed by 7 days on a low salt diet to challenge the mice to stimulate aldosterone production. Twelve-hour food intake was measured, and urine samples were collected to measure night/day patterns in renal Na balance. Urinary aldosterone excretion was measured by ELISA. Both day and night urinary aldosterone excretion were increased following a low salt diet in control and KO male mice (ANOVA main effect of diet, p&lt;0.05). Male AS Bmal1 KO mice displayed a significant increase in day urinary aldosterone excretion following a normal and low salt diet (ANOVA main effect of genotype, p=0.0230), with a trend for an increase in night urinary aldosterone excretion ( p=0.0571). Interestingly, these genotype effects were not seen in female AS Bmal1 KO mice. Urinary aldosterone was increased following a low salt diet in female mice, but only during the nighttime in control and KO mice ( p=0.0205). Sex differences were also observed in renal Na balance, where Na balance was more positive during the day in male, but not female, AS Bmal1 KO vs. control mice (ANOVA main effect of genotype, p=0.0282). Together, these data suggest adrenal BMAL1 is required for normal rhythms of aldosterone and renal Na balance in a sex-dependent manner. Future work will investigate whether the changes in aldosterone contribute to changes in renal Na balance. This work was supported by the American Heart Association (Postdoctoral FellowshipP0240441 to H.C.; Established Investigator Award 19EIA34660135 to M.G), theRobert and Mary Cade Professorship in Physiology (to M.G.) and the NIH(F32DK121424 to G.R.C.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.