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BackgroundLamins A/C (encoded by the LMNA gene) can lead to dilated cardiomyopathy (DCM). LMNA DCM to be ranked clinically as one of the most dreaded forms of DCM because of its high propensity for sudden cardiac death and advanced heart failure. However, lamin heart disease (LHD) remains to be poorly understood. Thus, this study sought to undertake proteomic analysis of myocardial tissue to explore the postgenomic phenotype of end-stage lamin heart disease.MethodsThis prospective clinical trial (NCT03860454) enrolled consecutive patients with end-stage LHD (LMNA-group, n=7) and ischaemic DCM (ICM-group, n=7) who were undergoing heart transplantation. For comparison, samples from healthy unused control donor hearts (CTRL, n=6) collected from the University of Sydney Heart Bank were also included. Samples were obtained from left atrium (LA), left ventricle (LV), right atrium (RA), right ventricle (RV) and interventricular septum (IVS). Liquid chromatography combined with mass-spectrometry (MS) was used to quantify protein concentrations. We compared protein concentrations in cardiac samples between LMNA and ICM groups. Proteins were considered differentially abundant if two simultaneous criteria were met: (1) there was a 1.5-fold increase/decrease, and (2) the p-value passed the correction for multiple testing at a false discovery rate of 0.01 (i.e., q-value<0.05). Given the slight differences in MS methodologies, only qualitative comparisons were made with the CTRL group. Gene ontology (GO) enrichment analysis explored the related biological processes. Biological processes, cellular components and molecular function GO categories with >2 members were considered.ResultsParticipant characteristics are presented in Table 1. 4,247 proteins were identified in LMNA and ICM samples, of which 633 were differentially abundant in LA, 39 in LV, 181 in RA, 52 in RV, and 85 in IVS (Table 2). The top 25 differentially abundant proteins ranked by q-value are presented using volcano plots in Figure 1. Abundance of lamin A/C was reduced but lamin B (LMNB) increased in LMNA LA/RA tissue compared to ICM, but not in LV/RV, with lamin B being absent in CTRL septal samples. Across all tissue samples, ECM proteins levels were differently abundant with pro-fibrotic fibrillar proteins being found at higher levels. Transthyretin was more abundant in the LV/RV of LMNA compared to ICM while sarcomeric proteins such as titin and cardiac myosin heavy chain were generally reduced in RA/LA of LMNA. In RV/LV, glycolysis enzymes and sarcoendoplasmic reticulum calcium-binding proteins appeared to be decreased. Protein expression profiling and GO enrichment analysis revealed sarcopenia, extracellular matrix (ECM) remodeling, deficient myocardial energetics, redox imbalances, and abnormal calcium handling in LMNA samples. For LV, box plots comparing the intensities of the top 25 differentially abundant proteins between LMNA and ICM based on q-value, and the top 20 enriched biological processes are presented in Figure 2.ConclusionLHD is a biventricular and biatrial disease, characterized by sarcopenia, aberrant metabolism, and ECM remodeling. LMNB and transthyretin were unexpectedly abundant in the atria and ventricles respectively of patients with end-stage lamin heart disease potentially hinting to the possibility of compensatory responses.Abstract 125 Table 1Participant characteristics LMNA (n=7) ICM (n=7) p-value* Demographics Age, years42 (39.0, 43.4)52 (48.0, 60.5)0.306Sex, Males4 (57.1%)6 (85.7%)0.554Body Mass Index (kg/m2)28.5 (26.0, 29.3)26.1 (24.5, 28.7)0.699Ethnicity, White5 (71.4%)4 (57.1%)0.503 Co-morbidities High cholesterol, yes1 (14.3%)3 (42.9%)0.306Diabetes, yes1 (14.3%)2 (28.6%)1.00Atrial Fibrillation, yes5 (71.4%)1 (14.3%)0.105 Echocardiography LVIDd, mm60 (57.0, 62.0)58.0 (51.0, 62.0)0.807IVSd thickness, mm8.4 (7.9, 8.5)8.1 (8.0, 8.3)0.807Ejection Fraction (%)24.3 (14.5, 32.3)24.0 (20.3, 25.6)0.876LV mass (grams)173.2 (161.1, 205.2)209.0 (143.9, 209.9)1.00Medial E/e’15.8 (11.6, 24.5)15.0 (12.0, 18.1)0.659TAPSE, cm1.7 (1.2, 1.8)1.5 (1.4, 1.7)0.679*Reported p values were derived using Mann Whitney U-test, χ2 or Fisher’s exact test as appropriate.d, diastolic; IVS, interventricular septum; LV, left ventricle; LVID, LV internal diameter; TAPSE, tricuspid annular plane systolic excursion. Abstract 125 Table 2Contingency table showing number of differentially abundant proteins between heart regions (RA, RV, LA, LV, IVS) and between groups (LMNA, ICM) LA_ICM LA_LMNA LV_ICM LV_LMNA RA_ICM RA_LMNA RV_ICM RV_LMNA IVS_ICM IVS_LMNA LA_ICM N/A 633 156185307443194224318242 LA_LMNA N/A721723177838489481053952 LV_ICM N/A 39 530779396413277 LV_LMNA N/A484769592816633 RA_ICM N/A 181 639715838685 RA_LMNA N/A9099481077944 RV_ICM N/A 52 6747 RV_LMNA N/A11610 IVS_ICM N/A 85 IVS_LMNA N/AAbstract 125 Figure 1Volcano plots of differentially expressed proteins.Proteins in the (A) right atrium, (B) left atrium, (C) right ventricle, (D) left ventricle and (E) interventricular septum differentially abundant between LMNA and ICM samples. Only the top 25 differentially expressed proteins ranked by q-value are annotated in red in these volcano plots.ICM, ischaemic dilated cardiomyopathy; IVS, interventricular septum; LA, left atrium; LMNA, lamin; log, logarithm; LV, left ventricle; RA, right atrium; RV, right ventricle.Abstract 125 Figure 2Left ventricular myocardial proteins and their gene ontology.A. Box plots comparing intensities of the top 25 LV proteins between LMNA and ICM based on q-value. Genes coding for the proteins rather than the proteins themselves are named.B. The top 20 enriched biological processes across the 39 proteins differentially abundant in the LV myocardium of LMNA and ICM, are presented in the rightmost panel. The raw (red), Benjamini-Hochberg corrected (green) and Bonferroni corrected enrichment p-values are displayed in the leftmost panel. Fold enrichment is shown in the middle panel.Abbreviations as in Figure 2.Conflict of InterestNone

Klebsiella oxytoca is a causative agent of various community-acquired and nosocomial infections, including urinary tract infections, nosocomial pneumonia, antibiotic-associated diarrhea, etc. However, the virulence factors of the species are still incompletely understood. The adhesive potential of the urological isolate K. oxytoca NK-1 was characterized using several substrates. The strain was found to efficiently adhere to epithelial cell lines, glycosylated and nonglycosylated proteins, and polystyrene and to induce yeast cell agglutination, indicating the presence of type 1 and type 3 fimbriae, which are organelles that facilitate adhesion of enterobacteria to a wide range of substrates. Both type 1 and type 3 fimbrial operons were identified in the strain genome, the latter occurring in two copies. Mutants with inactivated fimbrial genes were constructed. Inactivation of type 1 fimbrial genes did not affect bacterial adhesion. Inactivation of type 3 fimbrial genes increased adhesion of K. oxytoca NK-1 to lung epithelial cells (line H1299), and mannose was shown to serve as an additional inducer of higher adhesion. Adhesion of the mutant to other substrates was not affected. The findings suggested a multifactorial nature for the K. oxytoca adhesive apparatus and the possibility of compensatory expression or overexpression of genes for alternative adhesins in the absence of type 1 and/or 3 fimbriae.

In the eye, an increase in galectin-1 is associated with various chorioretinal diseases, in which retinal pigment epithelium (RPE) cells play a crucial role in disease development and progression. Since little is known about the function of endogenous galectin-1 in these cells, we developed a galectin-1-deficient immortalized RPE cell line (ARPE-19-LGALS1−/−) using a sgRNA/Cas9 all-in-one expression vector and investigated its cell biological properties. Galectin-1 deficiency was confirmed by Western blot analysis and immunocytochemistry. Cell viability and proliferation were significantly decreased in ARPE-19-LGALS1−/− cells when compared to wild-type controls. Further on, an increased attachment of galectin-1-deficient RPE cells was observed by cell adhesion assay when compared to control cells. The diminished viability and proliferation, as well as the enhanced adhesion of galectin-1-deficient ARPE-19 cells, could be blocked, at least in part, by the additional treatment with human recombinant galectin-1. In addition, a significantly reduced migration was detected in ARPE-19-LGALS1−/− cells. In comparison to control cells, galectin-1-deficient RPE cells had enhanced expression of sm-α-actin and N-cadherin, whereas expression of E-cadherin showed no significant alteration. Finally, a compensatory expression of galectin-8 mRNA was observed in ARPE-19-LGALS1−/− cells. In conclusion, in RPE cells, endogenous galectin-1 has crucial functions for various cell biological processes, including viability, proliferation, migration, adherence, and retaining the epithelial phenotype.

Environmental stress is a major driver of ecological community dynamics and agricultural productivity. This is especially true for soil water availability, because drought is the greatest abiotic inhibitor of worldwide crop yields. Here, we test the genetic basis of drought responses in the genetic model for C 4 perennial grasses, Panicum hallii , through population genomics, field-scale gene-expression (eQTL) analysis, and comparison of two complete genomes. While gene expression networks are dominated by local cis-regulatory elements, we observe three genomic hotspots of unlinked trans-regulatory loci. These regulatory hubs are four times more drought responsive than the genome-wide average. Additionally, cis- and trans-regulatory networks are more likely to have opposing effects than expected under neutral evolution, supporting a strong influence of compensatory evolution and stabilizing selection. These results implicate trans-regulatory evolution as a driver of drought responses and demonstrate the potential for crop improvement in drought-prone regions through modification of gene regulatory networks. Drought is a major factor limiting crop productivity. Here, via eQTL analysis and comparative genomics, the authors show compensatory evolution between trans-regulatory loci and transcription factor binding sites that shape the drought response networks in the model C4 grass Panicum hallii .

Compensatory growth (CG) in fish is heavily influenced by nutrient metabolism. However, there are limited studies examining how nutrient metabolism is regulated during this process. For silver pomfret, an important commercial marine fish, it's crucial to establish effective starvation and re-feeding strategies to ensure good water quality and fast growth. To identify the complete compensatory growth model of silver pomfret, we conducted an experiment with a control group (normal feeding) and three starvation/re-feeding groups. We observed that the recovery of weight and condition factor in the 14-day starvation and 14-day re-feeding groups was significantly faster than other groups, indicating full compensatory growth. Thus, we selected this group for the next experiment. We performed untargeted metabolomics and transcriptome analysis of muscle tissue on Day 14, 21 and 28 (CG process), and examined the key regulatory genes of nutrient metabolism on Day 0, 7, 14, 21 and 28 (starvation and re-feeding process). Our data revealed that during starvation, silver pomfret first utilized carbohydrates and short-chain lipids, followed by proteins and long-chain lipids. After re-feeding, lipids accumulated first, resulting in rapid growth, followed by the recovery of protein content in muscle. During starvation, the expression of anabolic-related genes such as TER and CALR decreased, and catabolic-related genes such as TSC2 and MLYCD increased, promoting the AMPK pathway. During re-feeding, anabolic-related gene expression increased without AMPK inhibition. Our findings provide insights into the energy utilization strategies of fish and molecular regulation during compensatory growth in fish.

Compensatory growth (CG) is a physiological response that accelerates growth following a period of nutrient limitation, with the potential to improve growth efficiency and meat quality in cattle. However, the underlying molecular mechanisms remain poorly understood. In this study, 60 Huaxi cattle were divided into one ad libitum feeding (ALF) group and two restricted feeding groups (75% restricted, RF75; 50% restricted, RF50) undergoing a short-term restriction period followed by evaluation of CG. Detailed comparisons of growth performance during the experimental period, as well as carcass and meat quality traits, were conducted, complemented by a comprehensive transcriptome analysis of the longissimus dorsi muscle using differential expression analysis, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and weighted correlation network analysis (WGCNA). The results showed that irrespective of the restriction degree, the restricted animals exhibited CG, achieving final body weights comparable to the ALF group. Compensating animals showed differences in meat quality traits, such as pH, cooking loss, and fat content, compared to the ALF group. Transcriptomic analysis revealed 57 genes and 31 pathways differentially regulated during CG, covering immune response, acid-lipid metabolism, and protein synthesis. Notably, complement–coagulation–fibrinolytic system synergy was identified as potentially responsible for meat quality optimization in RF75. This study provides novel and valuable genetic insights into the regulatory mechanisms of CG in beef cattle.

Anabasis aphylla ( A. aphylla ), a species of the Amaranthaceae family, is widely distributed in northwestern China and has high pharmacological value and ecological functions. However, the growth characteristics are poorly understood, impeding its industrial development for biopesticide development. Here, we explored the regenerative capacity of A. aphylla . To this end, different lengths of the secondary branches of perennial branches were mowed at the end of March before sprouting. The four treatments were no mowing (M0) and mowing 1/3, 2/3, and the entire length of the secondary branches of perennial branches (M1–M3, respectively). Next, to evaluate the compensatory growth after mowing, new assimilate branches’ related traits were recorded every 30 days, and the final biomass was recorded. The mowed plants showed a greater growth rate of assimilation branches than un-mowed plants. Additionally, with the increasing mowing degree, the growth rate and the final biomass of assimilation branches showed a decreasing trend, with the greatest growth rate and final biomass in response to M1. To evaluate the mechanism of the compensatory growth after mowing, a combination of dynamic (0, 1, 5, and 8 days after mowing) plant hormone-targeted metabolomics and transcriptomics was performed for the M0 and M1 treatment. Overall, 26 plant hormone metabolites were detected, 6 of which significantly increased after mowing compared with control: Indole-3-acetyl-L-valine methyl ester, Indole-3-carboxylic acid, Indole-3-carboxaldehyde, Gibberellin A24, Gibberellin A4, and cis (+)-12-oxo-phytodienoic acid. Additionally, 2,402 differentially expressed genes were detected between the mowed plants and controls. By combining clustering analysis based on expression trends after mowing and gene ontology analysis of each cluster, 18 genes related to auxin metabolism were identified, 6 of which were significantly related to auxin synthesis. Our findings suggest that appropriate mowing can promote A. aphylla growth, regulated by the auxin metabolic pathway, and lays the foundation for the development of the industrial value of A. aphylla .

Background Spinibarbus hollandi is an economically important fish species in southern China. This fish is known to have nutritional and medicinal properties; however, its farming is limited by its slow growth rate. In the present study, we observed that a compensatory growth phenomenon could be induced by adequate refeeding following 7 days of fasting in S. hollandi . To understand the starvation response and compensatory growth mechanisms in this fish, the muscle transcriptomes of S. hollandi under control, fasting, and refeeding conditions were profiled using next-generation sequencing (NGS) techniques. Results More than 4.45 × 10 8 quality-filtered 150-base-pair Illumina reads were obtained from all nine muscle samples. De novo assemblies yielded a total of 156,735 unigenes, among which 142,918 (91.18%) could be annotated in at least one available database. After 7 days of fasting, 2422 differentially expressed genes were detected, including 1510 up-regulated genes and 912 down-regulated genes. Genes involved in fat, protein, and carbohydrate metabolism were significantly up-regulated, and genes associated with the cell cycle, DNA replication, and immune and cellular structures were inhibited during fasting. After refeeding, 84 up-regulated genes and 16 down-regulated genes were identified. Many genes encoding the components of myofibers were significantly up-regulated. Histological analysis of muscle verified the important role of muscle hypertrophy in compensatory growth. Conclusion In the present work, we reported the transcriptome profiles of S. hollandi muscle under different conditions. During fasting, the genes involved in the mobilization of stored energy were up-regulated, while the genes associated with growth were down-regulated. After refeeding, muscle hypertrophy contributed to the recovery of growth. The results of this study may help to elucidate the mechanisms underlying the starvation response and compensatory growth.

Plasmids promote adaptation of bacteria by facilitating horizontal transfer of diverse genes, notably those conferring antibiotic resistance. Some plasmids, like those of the incompatibility group IncP-1, are known to replicate and persist in a broad range of bacteria. We investigated a poorly understood exception, the IncP-1β plasmid pBP136 from a clinical Bordetella pertussis isolate, which quickly became extinct in laboratory Escherichia coli populations. Through experimental evolution, we found that the inactivation of a previously uncharacterized plasmid gene, upf31, drastically improved plasmid persistence in E. coli. The gene inactivation caused alterations in the plasmid regulatory system, including decreased transcription of the global plasmid regulators (korA, korB, and korC) and numerous genes in their regulons. This is consistent with our findings that Upf31 represses its own transcription. It also caused secondary transcriptional changes in many chromosomal genes. In silico analyses predicted that Upf31 interacts with the plasmid regulator KorB at its C-terminal dimerization domain (CTD). We showed experimentally that adding the CTD of upf31/pBP136 to the naturally truncated upf31 allele of the stable IncP-1β archetype R751 results in plasmid destabilization in E. coli. Moreover, mutagenesis showed that upf31 alleles encoded on nearly half of the sequenced IncP-1β plasmids also possess this destabilization phenotype. While Upf31 might be beneficial in many hosts, we show that in E. coli some alleles have harmful effects that can be rapidly alleviated with a single mutation. Thus, broad-host-range plasmid adaptation to new hosts can involve fine-tuning their transcriptional circuitry through evolutionary changes in a single gene.