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[Evaluation of the incidence of nephrotoxicity associated with the use of aminoglycosides in patients with extrahepatic biliary obstruction].

In the present publication we discuss nephrotoxicity (NT) incidence by reviewing all the clinical histories of one year (May 1989-May 1990) with diagnosis of obstructive jaundice or cholangitis. Of a total of 90 patients. 53 were treated with aminoglycosides and 37 received other antibiotics. Nephrotoxicity developed in nine patients of the group that received aminoglycosides (17%), versus only three patients (8%) in the other group. Both groups were comparable regarding sex, age and liver and renal basal functions. Analysis of the variables that could be associated with a higher incidence in the nephrotoxicity group that received aminoglycosides showed that there were no differences regarding age, sex, dosage, duration of treatment, plasmatic levels of aminoglycosides and liver and renal basal functions. Only simultaneous administration o furosemide was significantly associated with the development of nephrotoxicity. Results of this study underline the need of a prospective follow-up of patients with biliary obstruction during treatment with aminoglycosides. Meanwhile the evidence available allows us to recommend the monitoring of renal function in this type of patients.

Aged

Selective saccular plasticity under microgravity links peripheral transcriptomic remodeling to postflight vestibular dysfunction.

Long-duration exposure to microgravity disrupts human balance and spatial orientation, yet the molecular mechanisms underlying vestibular adaptation to spaceflight remain poorly understood. Here, we tested the hypothesis that the saccule, the primary gravity-sensing otolith organ, undergoes selective remodeling during spaceflight and contributes to transient postflight postural instability. Using a cross-species approach, we combined transcriptomic analysis of mouse otolith organs with physiological assessments in astronauts. Laser microdissection-based RNA sequencing of mouse otolith sensory epithelia after a 35-d spaceflight revealed pronounced, organ-specific transcriptomic remodeling in the saccule, whereas the utricle remained stable. Principal component and clustering analyses demonstrated that the saccular transcriptome shifted toward an utricle-like profile under microgravity, accompanied by changes in genes related to synaptic and neuronal function. Promoter motif analysis identified NFAT-associated transcriptional networks, suggesting Ca2+-dependent regulation of synaptic plasticity as a potential molecular substrate of gravity-dependent adaptation. In parallel, vestibular testing in astronauts following long-duration missions (157 to 328 d) revealed selective attenuation of saccule-mediated cervical vestibular-evoked myogenic potentials and increased postural sway immediately after return to Earth, while utricle-mediated responses and semicircular canal function were preserved. Both saccular function and postural stability recovered within approximately 10 d. Notably, early postflight postural instability was partially mitigated by noisy galvanic vestibular stimulation, consistent with stochastic resonance-mediated sensory enhancement. Together, these findings identify the saccule as a plastic gravity sensor and establish a mechanistic link between peripheral molecular remodeling and functional balance deficits after spaceflight, providing a framework for developing countermeasures to facilitate vestibular readaptation during human space exploration.

Animals

Smoking, pulmonary function, and mortality.

The association of pulmonary function (as percent of predicted forced expiratory volume in 1 second [FEV1]) with total and cause-specific mortality over 15 to 18 years was investigated in a large cohort (5924) of prospectively followed Japanese-American men. Among those who never smoked, pulmonary function was found not to be significantly predictive of total mortality in a multivariate model in which adjustment for variables that might confound the results was made. Among past and current smokers, highly significant associations were found (P < 0.0001). The positive relationship of pulmonary function to mortality in smokers was so strong that it overshadowed these differences in nonsmokers in a model including all smoking groups combined, even after adjusting for smoking. A smoking-pulmonary function interaction term added to this model was statistically significant (P < 0.003). This illustrates the need for attention to the potential for complex interactions between biologic variables when carrying out multivariate statistical analysis. Findings for cardiovascular and noncardiovascular mortality were similar. This analysis indicates that while pulmonary function is associated with subsequent mortality, the relationship is significantly associated with smoking history.

Asian

The quantitative analysis of uronic acid polymers by infrared spectroscopy.

I.r. absorption bands associated with the functional groups of carboxylic acid derivatives are useful for the analysis of alginates and pectins. The ester, amide, and uronate contents of pectins and the uronate content of alginates were determined, respectively, from the ester-carbonyl stretching band (1740 cm- minus 1), the amide I band (1650 cm- minus 1), and the carboxylate antisymmetric stretching band (1607 cm- minus 1) obtained from the spectra of solutions in D2O-phosphate buffer. The results are accurate to within plus or minus 2-4%, are self consistent, and agree well with the few reliable results that are available. The method should be applicable for the determination of carboxylic acid derivatives in other polysaccharides.

Alginates

The relationship between airway responsiveness to histamine and pulmonary function level in a random population sample.

The association of nonspecific bronchial responsiveness (BR) with pulmonary function level has been studied in a random population sample of 2,156 male and female subjects 15 to 64 yr of age participating in the Vlagtwedde-Vlaardingen field survey on chronic obstructive pulmonary disease (COPD) being conducted in the Netherlands. About 25% of the subjects responded with a decrease in baseline FEV1 of 10% or more after challenge with histamine in a concentration of 16 mg/ml or less inhaled over 30 s (PC10). In a stratified analysis, pulmonary function level appeared to be associated with BR in a dose-response relationship. The mean %FEV1 was consistently lower in the more responsive subjects. This relationship was confirmed in linear regression analyses, adjusting for age, sex, area of residence, and smoking habits. Exclusion of subjects with %FEV1 less than 80% diminished but did not change the association between FEV1 and BR. The magnitude of the effect of responsiveness on level of pulmonary function was considerable and statistically significant. In the subjects older than 21 yr of age, male responders (PC10 at less than or equal to 16 mg/ml) on average had an adjusted FEV1 of 32.5 centiliters less than nonresponders, and female responders had an adjusted FEV1 of 30.5 centiliters less (p less than 0.001). BR appeared to be an independent predictor of pulmonary function level after adjustment for age, sex, area of residence, respiratory symptom prevalence, and cigarette smoking. The effect of cigarette smoking on pulmonary function level in this population sample was significant only in men older than 21 yr of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Integrated proteomic network analysis reveals PTPRC as a central hub protein orchestrating co-expression modules and metabolic dysregulation in renal carcinoma: PTPRC protein molecular action.

The occurrence of renal carcinoma is closely related to a variety of molecular mechanisms and metabolic disorders. PTPRC (protein tyrosine phosphatase receptor C), as an important regulatory protein, was studied to reveal the role of PTPRC in renal carcinoma through comprehensive proteomic network analysis, especially its core position in the coordination of co-expression modules and metabolic disorders. This study was the first to download and process multiple publicly available renal cancer transcriptome data to conduct differential gene expression analysis across datasets. Functional enrichment and disease ontology analysis were performed on the transcriptome of renal cancer, and weighted gene co-expression network (WGCNA) was constructed. The results showed that comprehensive principal component analysis revealed significant differences in the transcriptome of renal cancer, and functional annotation revealed specific pathways associated with renal cancer. WGCNA analysis identified tumor-associated co-expression modules, while multi-omics analysis further identified core regulatory networks including PTPRC. As a central hub protein, PTPRC plays an important coordinating role in the co-expression module and metabolic dysregulation of renal carcinoma. This discovery provides a new perspective for understanding the molecular mechanism of kidney cancer.

Humans

T11/CD2 activation of cloned human natural killer cells results in increased conjugate formation and exocytosis of cytolytic granules.

The T11 (CD2) antigen has been found to be an alternate pathway for antigen-independent activation of resting T cells. T11 triggering also results in activation of NK cells and enhancement of their cytolytic function. The present studies were carried out to further define the mechanisms whereby cytotoxicity is enhanced after T11 activation. A series of clonal human NK cell lines were analyzed after incubation with monoclonal anti-T112 and anti-T113 antibodies specific for different epitopes of the CD2 protein. Anti-T112/3 triggering resulted in increased cytotoxicity against a variety of target cells. Similar results were obtained with F(ab')2 fragments of anti-T112/3, indicating that this effect was not mediated through binding of FcR. The induction of cytotoxicity was found to be associated with increased formation of effector cell-target cell conjugates and with release of secretory granule-localized 35S-labeled proteoglycans. Both enhanced conjugate formation and cytotoxicity could be blocked by anti-lymphocyte function-associated antigen (LFA-1) mAb. Ultrastructural analysis of NK cells after T11 activation demonstrated increased adherence of effector cells to targets and other NK cells as well as a directional reorientation of cytoplasm and intracellular granules toward the area of contact between cells. Discharge of granules occurred into pockets bounded by closely apposed plasma membranes. In the presence of anti-LFA-1 and anti-T112/3, the close apposition and formation of pockets between effector cells and target cells did not occur but the cells exocytosed their intracellular granules. T11 activation of NK cloned cells also resulted in the formation of the homotypic conjugates and autocytotoxicity. As seen with resistant allogeneic targets, autocytotoxicity was mediated by F(ab')2 fragments of T112/3 antibodies and could be blocked by anti-LFA-1 antibody. Ultrastructural analysis of NK cloned cells after T11 activation confirmed the presence of homotypic conjugates with reorientation of effector cells toward one another and discharge of cytolytic granules into pockets formed between NK cloned cells. Taken together, these results indicate that T11-induced cytolytic function of NK cells is, in part, mediated through increased binding of effector cells and targets and that enhanced conjugate formation is at least in part mediated by the LFA-1 antigen. In addition, T11 activation results in the triggering of the cytolytic mechanism of NK cells and the exocytosis of cytolytic granules and their constituents.

Antibodies, Monoclonal

Prognostic value of the Island sign for hematoma expansion and functional outcome after intracerebral hemorrhage: a systematic review and meta-analysis.

PURPOSE: The Island Sign (IS) is a radiological finding observed in patients with intracerebral hemorrhage (ICH). This meta-analysis aimed to evaluate the association between IS and both hematoma expansion (HE) and functional outcomes by comparing ICH patients with and without IS. METHODS: We searched PubMed, Embase and Cochrane Library for studies of intracerebral hemorrhage reporting the IS. The primary outcomes were functional status and hematoma expansion, secondary outcome was mortality. Statistical analysis was performed using RStudio, effect sizes were calculated as odds ratios (ORs) with 95% confidence interval (95% CIs), and heterogeneity was assessed with I2 statistics. In addition, meta-regression and sensitivity analyses were performed, and publication bias was assessed through funnel plots and Egger's regression test. RESULTS: We included 21 observational studies with a total of 9,459 patients with spontaneous ICH, 1,769 of them had IS, while 7,690 did not. The mean age was 63.5&#xa0;&#xb1;&#xa0;13.2 and 5,835 (61.7%) were male. Poor functional outcomes (OR 2.77, 95% CI: 2.14-3.58, p&#xa0;<&#xa0;0.0001, I2&#xa0;=&#xa0;4.9%) and hematoma expansion (OR 2.75, 95% CI: 1.87-4.03, p&#xa0;<&#xa0;0.0001, I2&#xa0;=&#xa0;77.4%) were substantially higher in patients with IS, as well as the overall mortality rate (OR 2.54, 95% CI: 1.55-4.17, p&#xa0;=&#xa0;0.0002, I2&#xa0;=&#xa0;0%). Meta-regression analysis showed no statistically significant association between imaging-related timing variables and hematoma expansion. Furthermore, the leave-one-out sensitivity analyses showed that no single study exerted a disproportionate influence on the overall effect for the examined outcomes, and Egger's linear regression tests were not statistically significant for both outcomes. CONCLUSION: Patients with the Island Sign are associated with higher rates of poor functional outcomes and hematoma expansion. Thus, IS is a relevant radiological finding with potential to support early risk stratification and optimize patient management and treatment selection.

Humans

Disease and psychosocial factors related to physical functioning in rheumatoid arthritis.

One hundred and fifty-five patients with rheumatoid arthritis (RA) were randomly selected from a tertiary care outpatient rheumatology clinic. Disease, treatment, psychosocial and demographic data were collected to test a biopsychosocial model of Physical Functioning as determined by the Arthritis Impact Measurement Scales (AIMS). Cross-sectional and longitudinal hierarchical and stepwise regression analysis were performed to identify variables associated with Physical Functioning. The results of the hierarchical regression revealed that only the disease and psychosocial sets of variables were significant. Stepwise regression revealed that Disease Severity (disease set) and Arthritis Helplessness (psychosocial set) accounted for 37% (longitudinal) to 60% (cross-sectional 12 months---greater than 12 months) of Physical Functioning variance. Our results suggest a role for the inclusion of psychosocial factors in studies of the development of physical disability in patients with RA.

Adult

Isolation, biochemical characterization and ultrastructural analysis of the limbic system-associated membrane protein (LAMP), a protein expressed by neurons comprising functional neural circuits.

The limbic system-associated membrane protein (LAMP) is a cell surface glycoprotein expressed by cortical and subcortical regions of the mammalian CNS that comprise or receive direct projections from limbic system structures. The early and restricted expression of LAMP has led to its postulated role in neural development. Purification and biochemical characterization of LAMP was performed in order to ascertain its relationship to other, well-defined cell surface proteins in the nervous system. Subcellular fractionation, immunoaffinity chromatography, and Western blots of rodent and bovine hippocampus revealed that LAMP is an integral membrane protein with a molecular mass of 64-68 kDa and a pI of 5.2-5.5. Deglycosylation of LAMP indicates that it contains N-linked high mannose or hybrid sugars and a minor amount of sialic acid. The LAMP protein exhibits an identical molecular mass in developing hippocampus and in several different brain regions in the adult. No cross-reactivity was obtained using the monoclonal antibody that recognizes the HNK-1 carbohydrate epitope, a complex sulfated moiety expressed on members of a large family of glycoproteins. Immunocytochemical analysis at the ultrastructural level reveals that LAMP immunoreactivity is exhibited by neurons in a stereotyped pattern throughout limbic system areas. Glial cells are not immunoreactive. In the adult, LAMP-immunoreactive membrane patches are present exclusively postsynaptically on neuronal somata and dendrites. Myelinated and unmyelinated axons are not stained in any brain region examined. Analysis of LAMP expression in the developing CNS during synaptogenesis demonstrates that LAMP is located on growing axons and both pre- and postsynaptically at forming terminal complexes. Double-labeling studies of the hippocampal neurons grown in vitro reveal that the LAMP epitope is extracellular and is expressed on neurofilament- and microtubule-associated protein 2-positive neurites. Cells expressing glial fibrillary acidic protein are not LAMP-immunoreactive. These results demonstrate that in the adult brain, LAMP is expressed almost exclusively by the postsynaptic (target) elements in limbic circuits, but that during development, all components of the surface of the growing neuron contain LAMP. The stereotyped anatomical pattern of expression of LAMP in the developing and mature brain and its biochemical characteristics suggest that LAMP is a unique, system-associated membrane glycoprotein that is distinct from previously identified, developmentally important cell surface proteins.

Animals

Glaucoma and brain functional networks: a bidirectional Mendelian randomisation study.

OBJECTIVE: Glaucoma is a complex neurodegenerative ocular disorder accompanied by brain functional abnormalities that extend beyond the visual system. However, the causal association between the two remains unclear at present. This study aimed to investigate the potential causal relationships between glaucoma and brain functional networks in order to provide novel insights into the neuropathic mechanism of glaucoma. METHODS AND ANALYSIS: Based on the genome-wide association studies data of glaucoma and resting-state functional MRI (Rs-fMRI), a bidirectional Mendelian randomisation (MR) analysis was conducted between glaucoma and brain functional networks. Inverse variance weighting was applied as the primary method to estimate causality with false discovery rate correction. Additional sensitivity analyses were conducted to evaluate the robustness of the results. RESULTS: Forward MR analysis suggested that glaucoma was causally associated with two brain networks between the subcortical cerebellum and the attention or visual network (p=0.022), as well as the default mode and central executive network (p=0.008), but without significance after false discovery rate correction (q>0.1). Reverse MR analysis revealed 19 Rs-fMRI traits related to glaucoma risk, including the salience or central executive network in the frontal region (p=0.0005, q=0.08) and the motor network (p=0.0009, q=0.08) with significant causality. CONCLUSIONS: This MR study revealed potentially causal relationships between glaucoma and brain functional networks. Especially, the functional connectivity of the motor network between the postcentral or precentral areas may potentially lead to increased risk of glaucoma.

Humans

HLA matching for cadaver renal transplantation in SEOPF: the impact of cyclosporine. Southeastern Organ Procurement Foundation.

Since the introduction of CsA in 1983, several changes in SEOPF activity have been observed: 1. Organ recovery has increased at a rate slower than candidate registration, whereas the utilization rate has increased substantially. 2. Overall organ sharing has decreased for both CsA and non-CsA-treated patients. 3. The percentage of poor HLA-A,B matched recipients has increased for both CsA- and non-CsA-treated patients. 4. The use of cold storage preservation has increased for both CsA- and non-CsA-treated patients. 5. The use of ALS has decreased, predominantly in CsA-treated patients. 6. A majority of diabetics are being treated with CsA. 7. There is substantial individual variation in SEOPF center preferences for CsA use, HLA matching, and use of shared kidneys. In terms of graft outcome, the following associations have been observed: 1. The incidence of delayed graft function has increased with shared kidneys only, suggesting sharing of poorer quality as well as fewer kidneys. 2. First transplant recipients receiving CsA tend to have lower delayed graft function rates, possibly as a result of treatment selection. However, the risk of graft failure associated with delayed function is greater in patients receiving CsA. 3. By univariate analysis, there is an additive benefit of HLA-A,B matching and CsA use in patients receiving local kidneys with immediate function. 4. By multivariate analysis, there is a significant relative risk of graft rejection associated with poor HLA-A,B matching in patients receiving CsA. 5. By multivariate analysis, there is an apparent risk of graft loss associated with shared organs, but only in patients receiving CsA. One possible explanation is that poorer quality kidneys are being accepted for patients treated with CsA. 6. By multivariate subset analysis, there is a significant benefit of CsA use in patients whose HLA is poorly matched, but no observed benefit in well-matched patients. 7. Definitive evaluation of the relative effects of CsA and HLA matching on cadaver renal allograft survival must await long-term follow-up data on survival and function, and the ability to control for center bias in sharing, HLA matching, and CsA use.

Cyclosporins

Integrative analysis of gene expression and histone modifications for DES, DSP, GJA1 and SMOC2&#xa0;in adipose tissue reveals potential relationship to cardiometabolic health.

BACKGROUND: Adipose tissue influences cardiometabolic health through its endocrine activity and its role in regulating inflammation, lipid metabolism, and cardiovascular function. The expression of cardiac-associated genes within adipose tissue may reflect or contribute to cardiometabolic risk, yet this relationship remains poorly understood. This study investigates the expression profiles of the cardiac function associated genes GJA1, DES, DSP and SMOC2 in human adipose tissue, and analyses their associations with cardiometabolic traits. Additionally, we explore epigenomic mechanisms that may underlie their differential gene expression. METHODS: Expression profiling and functional enrichment analyses were conducted to identify depot-specific cardiac gene expression patterns. Quantitative PCR validated gene expression in paired subcutaneous (SAT) and omental visceral adipose tissue (OVAT) samples from 78 individuals with obesity. Gene expression was further validated in three independent cohorts (N&#x2009;=&#x2009;1,548 total). Associations with clinical traits were assessed using Spearman correlations and multivariate linear regression, adjusted for age, sex, and BMI. Integration with transcriptomic and proteomic datasets publicly available from the Adipose Tissue Knowledge Portal was performed to strengthen clinical relevance. Epigenomic profiling using genome-wide ChIP-seq for histone marks (H3K4me3, H3K4me1, H3K27ac, H3K27me3) was conducted in paired SAT and OVAT samples from five individuals. RESULTS: DES, DSP, GJA1, and SMOC2 were significantly upregulated in OVAT compared to SAT. DES, DSP, and SMOC2 showed consistent expression patterns across all cohorts, while GJA1 exhibited context-dependent regulation. Gene expression in SAT was negatively correlated with cardiometabolic traits, including blood pressure, insulin resistance, and liver function markers. These associations were confirmed by regression analysis and supported by publicly available multi-omics data. Epigenetic analyses revealed OVAT-specific enrichment of active histone marks and reduced repressive marks, supporting higher differential transcriptional activity in OVAT. CONCLUSIONS: Depot-specific gene expression of DES, DSP, and SMOC2 in adipose tissue is robustly linked to cardiometabolic traits and supported by distinct epigenetic landscapes in OVAT vs SAT, highlighting their potential as novel biomarkers for cardiometabolic health.

Humans

Long-term (>7-year) parental consumption of genetically modified maize (Cry1Ab/Cry2Aj and EPSPS) induces no adverse sperm DNA methylation alterations across two generations of cynomolgus monkeys.

This study assessed the long-term safety of genetically modified (GM) maize from a male reproductive perspective, using a non-human primate model. We analyzed the sperm DNA methylation profiles in cynomolgus monkeys fed GM maize, non-GM parental maize, or a conventional diet over two generations (F0/F1). Whole-genome bisulfite sequencing (WGBS) revealed no significant differences in global methylation levels among groups. The identified differentially methylated regions (DMRs) were short, enriched in non-regulatory genomic areas, and did not cluster after treatment. Functional enrichment analysis showed that DMR-associated genes were consistently involved in the same core biological pathways (e.g., mTOR and Wnt signaling) across all dietary comparisons. These findings indicate that GM maize consumption did not induce specific adverse epigenetic alterations in sperm, with the observed changes reflecting common physiological adaptations to dietary variations rather than GM-related effects.

Animals

Genomic and cDNA actin sequences from a virulent strain of Entamoeba histolytica.

Invasiveness of Entamoeba histolytica strains that cause acute amoebiasis is characterized by aggressive behavior associated with cell motility and actin function. Analysis of actin genes from E. histolytica was initiated by devising methods for the isolation of biologically active nucleic acids, which allowed the preparation of cDNA and genomic DNA libraries. E. histolytica actin-encoding cDNAs and genomic clones have been isolated from libraries prepared from the virulent HM1:IMSS strain using a heterologous actin probe. Nucleotide sequence analysis of three independent cDNA clones and one genomic clone reveals a highly unusual codon bias and the absence of intervening sequences in E. histolytica actin. The coding sequence of the genomic clone is identical to that of two of the three cDNA clones. These represent at least two distinct mRNAs differing only by five silent changes in the protein coding sequence. Multiple genomic copies of the actin gene can be detected by Southern hybridization. E. histolytica actin exhibits a higher degree of homology to cytoplasmic than to muscle actin. Although the protein has been shown not to bind DNase I, the inferred amino acid sequence indicates conservation of all residues implied to participate in this binding.

Actins

Discovery of a MET -driven monogenic cause of steatotic liver disease.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease affects about a third of adults worldwide and is projected soon to be the leading cause of liver cirrhosis. It occurs when fat accumulates in hepatocytes and can progress to metabolic dysfunction-associated steatohepatitis, liver cirrhosis, and HCC. Metabolic dysfunction-associated steatotic liver disease pathogenesis is believed to involve a combination of genetic and environmental risk factors. Single nucleotide polymorphisms have been implicated, but non-syndromic monogenic causes are lacking. APPROACH AND RESULTS: We identified a novel genetic variant in a familial case of metabolic dysfunction-associated steatohepatitis and performed deep variant functional analysis, including protein modeling, dynamics, and cell-based assays to assess molecular mechanisms of dysfunction and altered cellular signaling. We analyzed exome sequencing data of 3904 individuals with steatotic liver disease (SLD) to identify additional cases and establish the link between specific gene variants and SLD diagnosis. We discovered and functionally validated the NM_000245.4:c.3505A>T; p.(Ile1169Phe) variant in the MET (mesenchymal-epithelial transition) kinase domain as a monogenic cause of SLD. Subsequently, we detected additional ultra-rare, previously uninterpreted, and likely deleterious variants in MET from screening sequencing data. Among individuals with confirmed SLD based on electronic record review, 1.1% (45/3904) had rare predicted deleterious MET variants. Eight of 45 (17.7%) individuals had predicted deleterious variants in the MET kinase domain confirmed to be functionally like the familial case variant. CONCLUSIONS: We report the first germline nonmalignant rare MET -driven disease, a monogenic form of SLD.

Adult

Genes associated with translation and oxidative phosphorylation as components of the translational response in nodulated and water-restricted soybean.

BACKGROUND: Soybean primarily acquires nitrogen through symbiosis with nitrogen-fixing bacteria. Water deficit (WD) is a major stress limiting crop yield. Nodulation may enhance drought tolerance in legumes by modulating nitrogen and hormone metabolism, osmotic adjustment, and antioxidant defenses; however, the molecular basis underlying the differential WD responses between N-fix and N-fed plants remain unclear. Translational control of gene expression is a key regulatory mechanism during stress. RESULTS: We compared the transcriptome and translatome of soybean roots from N-fix and N-fed plants exposed to WD across four combined treatments. N-fix plants under WD exhibited more complex responses in terms of total differentially expressed genes (DEGs) compared to N-fed plants. This increased complexity was also evident among translationally regulated DEGs and differentially expressed transcription factors, whose involvement in WD responses of N-fix plants is novel. Co-expression network analysis identified modules associated with core biological processes encompassing nodulation, WD, and notably, their interplay was particularly prominent in Module 1, which was enriched in genes related to ribosomal protein synthesis and oxidative phosphorylation (OXPHOS). Guilt-by-Association analysis enabled the prediction of novel functions for differentially expressed, uncharacterized hub genes related to stress and/or nodulation responses. CONCLUSIONS: Translational regulation of genes involved in OXPHOS and translation initiation emerged as a central response in N-fix plants under WD. These findings reveal distinct molecular adaptations in N-fix soybean roots facing WD and highlight translational control as a key regulatory layer. We also identified promising candidate genes-including transcription factors and uncharacterized hub genes under translational regulation-that represent potential targets for improving drought tolerance in legumes once validated functionally.

Glycine max