Cell Rep. 2024 Apr 11;43(4):114091. doi: 10.1016/j.celrep.2024.114091. Online ahead of print.

ABSTRACT

Nitric oxide (NO) is a gasotransmitter required in a broad range of mechanisms controlling plant development and stress conditions. However, little is known about the specific role of this signaling molecule during lipid storage in the seeds. Here, we show that NO is accumulated in developing embryos and regulates the fatty acid profile through the stabilization of the basic/leucine zipper transcription factor bZIP67. NO and nitro-linolenic acid target and accumulate bZIP67 to induce the downstream expression of FAD3 desaturase, which is misregulated in a non-nitrosylable version of the protein. Moreover, the post-translational modification of bZIP67 is reversible by the trans-denitrosylation activity of peroxiredoxin IIE and defines a feedback mechanism for bZIP67 redox regulation. These findings provide a molecular framework to control the seed fatty acid profile caused by NO, and evidence of the in vivo functionality of nitro-fatty acids during plant developmental signaling.

PMID:38607914 | DOI:10.1016/j.celrep.2024.114091

Planta. 2024 Apr 12;259(5):120. doi: 10.1007/s00425-024-04390-6.

ABSTRACT

This study reveals miRNA indirect regulation of C4 genes in sugarcane through transcription factors, highlighting potential key regulators like SsHAM3a. C4 photosynthesis is crucial for the high productivity and biomass of sugarcane, however, the miRNA regulation of C4 genes in sugarcane remains elusive. We have identified 384 miRNAs along the leaf gradients, including 293 known miRNAs and 91 novel miRNAs. Among these, 86 unique miRNAs exhibited differential expression patterns, and we identified 3511 potential expressed targets of these differentially expressed miRNAs (DEmiRNAs). Analyses using Pearson correlation coefficient (PCC) and Gene Ontology (GO) enrichment revealed that targets of miRNAs with positive correlations are integral to chlorophyll-related photosynthetic processes. In contrast, negatively correlated pairs are primarily associated with metabolic functions. It is worth noting that no C4 genes were predicted as targets of DEmiRNAs. Our application of weighted gene co-expression network analysis (WGCNA) led to a gene regulatory network (GRN) suggesting miRNAs might indirectly regulate C4 genes via transcription factors (TFs). The GRAS TF SsHAM3a emerged as a potential regulator of C4 genes, targeted by miR171y and miR171am, and exhibiting a negative correlation with miRNA expression along the leaf gradient. This study sheds light on the complex involvement of miRNAs in regulating C4 genes, offering a foundation for future research into enhancing sugarcane's photosynthetic efficiency.

PMID:38607398 | DOI:10.1007/s00425-024-04390-6

Cells. 2024 Apr 2;13(7):616. doi: 10.3390/cells13070616.

ABSTRACT

The management of chronic myelogenous leukemia (CML) has seen significant progress with the introduction of tyrosine kinase inhibitors (TKIs), particularly Imatinib. However, a notable proportion of CML patients develop resistance to Imatinib, often due to the persistence of leukemia stem cells and resistance mechanisms independent of BCR::ABL1 This study investigates the roles of IL6R, IL7R, and MYC in Imatinib resistance by employing CRISPR/Cas9 for gene editing and the Non-Invasive Apoptosis Detection Sensor version 2 (NIADS v2) for apoptosis assessment. The results indicate that Imatinib-resistant K562 cells (K562-IR) predominantly express IL6R, IL7R, and MYC, with IL6R and MYC playing crucial roles in cell survival and sensitivity to Imatinib. Conversely, IL7R does not significantly impact cytotoxicity, either alone or in combination with Imatinib. Further genetic editing experiments confirm the protective functions of IL6R and MYC in K562-IR cells, suggesting their potential as therapeutic targets for overcoming Imatinib resistance in CML. This study contributes to understanding the mechanisms of Imatinib resistance in CML, proposing IL6R and MYC as pivotal targets for therapeutic strategies. Moreover, the utilization of NIADS v2 enhances our capability to analyze apoptosis and drug responses, contributing to a deeper understanding of CML pathogenesis and treatment options.

PMID:38607055 | DOI:10.3390/cells13070616

J Bacteriol. 2024 Apr 12:e0000324. doi: 10.1128/jb.00003-24. Online ahead of print.

ABSTRACT

In most actinomycetes, GlnR governs both nitrogen and non-nitrogen metabolisms (e.g., carbon, phosphate, and secondary metabolisms). Although GlnR has been recognized as a global regulator, its regulatory role in central carbon metabolism [e.g., glycolysis, gluconeogenesis, and the tricarboxylic acid (TCA) cycle] is largely unknown. In this study, we characterized GlnR as a direct transcriptional repressor of the pckA gene that encodes phosphoenolpyruvate carboxykinase, catalyzing the conversion of the TCA cycle intermediate oxaloacetate to phosphoenolpyruvate, a key step in gluconeogenesis. Through the transcriptomic and quantitative real-time PCR analyses, we first showed that the pckA transcription was upregulated in the glnR null mutant of Amycolatopsis mediterranei. Next, we proved that the pckA gene was essential for A. mediterranei gluconeogenesis when the TCA cycle intermediate was used as a sole carbon source. Furthermore, with the employment of the electrophoretic mobility shift assay and DNase I footprinting assay, we revealed that GlnR was able to specifically bind to the pckA promoter region from both A. mediterranei and two other representative actinomycetes (Streptomyces coelicolor and Mycobacterium smegmatis). Therefore, our data suggest that GlnR may repress pckA transcription in actinomycetes, which highlights the global regulatory role of GlnR in both nitrogen and central carbon metabolisms in response to environmental nutrient stresses.

IMPORTANCE: The GlnR regulator of actinomycetes controls nitrogen metabolism genes and many other genes involved in carbon, phosphate, and secondary metabolisms. Currently, the known GlnR-regulated genes in carbon metabolism are involved in the transport of carbon sources, the assimilation of short-chain fatty acid, and the 2-methylcitrate cycle, although little is known about the relationship between GlnR and the TCA cycle and gluconeogenesis. Here, based on the biochemical and genetic results, we identified GlnR as a direct transcriptional repressor of pckA, the gene that encodes phosphoenolpyruvate carboxykinase, a key enzyme for gluconeogenesis, thus highlighting that GlnR plays a central and complex role for dynamic orchestration of cellular carbon, nitrogen, and phosphate fluxes and bioactive secondary metabolites in actinomycetes to adapt to changing surroundings.

PMID:38606980 | DOI:10.1128/jb.00003-24

J Int Soc Sports Nutr. 2024 Dec;21(1):2340574. doi: 10.1080/15502783.2024.2340574. Epub 2024 Apr 12.

ABSTRACT

BACKGROUND: Growing evidence supports the ergogenic effects of creatine supplementation on muscle power/strength, but its effects on endurance performance remain unclear. We assessed the effects of high-dose short-term creatine supplementation in professional cyclists during a training camp.

METHODS: The study followed a double-blind, randomized parallel design. Twenty-three professional U23 cyclists (19 ± 1 years, maximum oxygen uptake: 73.0 ± 4.6 mL/kg/min) participated in a 6-day training camp. Participants were randomized to consume daily either a recovery drink (containing carbohydrates and protein) with a 20-g creatine supplement (creatine group, n = 11) or just the recovery drink (placebo group, n = 12). Training loads and dietary intake were monitored, and indicators of fatigue/recovery (Hooper index, countermovement jump height), body composition, and performance (10-second sprint, 3-, 6-, and 12-minute time trials, respectively, as well as critical power and W') were assessed as study outcomes.

RESULTS: The training camp resulted in a significant (p < 0.001) increase of training loads (+50% for total training time and + 61% for training stress score, compared with the preceding month) that in turn induced an increase in fatigue indicators (significant time effect [p < 0.001] for delayed-onset muscle soreness, fatigue, and total Hooper index) and a decrease in performance (significant time effect [p = 0.020] for critical power, which decreased by -3.8%). However, no significant group-by-time interaction effect was found for any of the study outcomes (all p > 0.05).

CONCLUSIONS: High-dose short-term creatine supplementation seems to exert no consistent beneficial effects on recovery, body composition or performance indicators during a strenuous training period in professional cyclists.

PMID:38606895 | DOI:10.1080/15502783.2024.2340574

Bioinform Adv. 2024 Apr 4;4(1):vbae042. doi: 10.1093/bioadv/vbae042. eCollection 2024.

ABSTRACT

MOTIVATION: Mechanistic modeling based on ordinary differential equations has led to numerous findings in systems biology by integrating prior knowledge and experimental data. However, the manual curation of knowledge necessary when constructing models poses a bottleneck. As the speed of knowledge accumulation continues to grow, there is a demand for a scalable means of constructing executable models.

RESULTS: We previously introduced BioMASS-an open-source, Python-based framework-to construct, simulate, and analyze mechanistic models of signaling networks. With one of its features, Text2Model, BioMASS allows users to define models in a natural language-like format, thereby facilitating the construction of large-scale models. We demonstrate that Text2Model can serve as a tool for integrating external knowledge for mathematical modeling by generating Text2Model files from a pathway database or through the use of a large language model, and simulating its dynamics through BioMASS. Our findings reveal the tool's capabilities to encourage exploration from prior knowledge and pave the way for a fully data-driven approach to constructing mathematical models.

AVAILABILITY AND IMPLEMENTATION: The code and documentation for BioMASS are available at https://github.com/biomass-dev/biomass and https://biomass-core.readthedocs.io, respectively. The code used in this article are available at https://github.com/okadalabipr/text2model-from-knowledge.

PMID:38606187 | PMC:PMC11007111 | DOI:10.1093/bioadv/vbae042

Bioinform Adv. 2024 Mar 26;4(1):vbae047. doi: 10.1093/bioadv/vbae047. eCollection 2024.

ABSTRACT

MOTIVATION: Predicting anticancer treatment response from baseline genomic data is a critical obstacle in personalized medicine. Machine learning methods are commonly used for predicting drug response from gene expression data. In the process of constructing these machine learning models, one of the most significant challenges is identifying appropriate features among a massive number of genes.

RESULTS: In this study, we utilize features (genes) extracted using the text-mining of scientific literatures. Using two independent cancer pharmacogenomic datasets, we demonstrate that text-mining-based features outperform traditional feature selection techniques in machine learning tasks. In addition, our analysis reveals that text-mining feature-based machine learning models trained on in vitro data also perform well when predicting the response of in vivo cancer models. Our results demonstrate that text-mining-based feature selection is an easy to implement approach that is suitable for building machine learning models for anticancer drug response prediction.

AVAILABILITY AND IMPLEMENTATION: https://github.com/merlab/text_features.

PMID:38606185 | PMC:PMC11009020 | DOI:10.1093/bioadv/vbae047

Front Oncol. 2024 Mar 28;14:1383043. doi: 10.3389/fonc.2024.1383043. eCollection 2024.

NO ABSTRACT

PMID:38606097 | PMC:PMC11007194 | DOI:10.3389/fonc.2024.1383043

Phenomics. 2023 Sep 21;4(1):51-55. doi: 10.1007/s43657-023-00120-2. eCollection 2024 Feb.

ABSTRACT

Cardiovascular health metrics are now widely recognized as modifiable risk factors for cognitive decline and dementia. Metabolic perturbations might play roles in the linkage of cardiovascular diseases and dementia. Circulating metabolites profiling by metabolomics may improve understanding of the potential mechanism by which cardiovascular risk factors contribute to cognitive decline. In a prospective community-based cohort in China (n = 725), 312 serum metabolic phenotypes were quantified, and cardiovascular health score was calculated including smoking, exercise, sleep, diet, body mass index, blood pressure, and blood glucose. Cognitive function assessments were conducted in baseline and follow-up visits to identify longitudinal cognitive decline. A better cardiovascular health was significantly associated with lower risk of concentration decline and orientation decline (hazard ratio (HR): 0.84-0.90; p < 0.05). Apolipoprotein-A1, high-density lipoprotein (HDL) cholesterol, cholesterol ester, and phospholipid concentrations were significantly associated with a lower risk of longitudinal memory and orientation decline (p < 0.05 and adjusted-p < 0.20). Mediation analysis suggested that the negative association between health status and the risk of orientation decline was partly mediated by cholesterol ester and total lipids in HDL-2 and -3 (proportion of mediation: 7.68-8.21%, both p < 0.05). Cardiovascular risk factors were associated with greater risks of cognitive decline, which were found to be mediated by circulating lipoproteins, particularly the medium-size HDL components. These findings underscore the potential of utilizing lipoproteins as targets for early stage dementia screening and intervention.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-023-00120-2.

PMID:38605906 | PMC:PMC11003945 | DOI:10.1007/s43657-023-00120-2

Front Public Health. 2024 Mar 28;12:1301095. doi: 10.3389/fpubh.2024.1301095. eCollection 2024.

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) is a prevalent public health concern globally, significantly impacting quality of life. In Thailand, the prevalence of AR is rising, with grass and weed pollen identified as primary outdoor triggers.

OBJECTIVES: This study aimed to (1) assess patterns of pollen sensitization in Thai AR patients and (2) investigate correlations between demographics/clinical data and SPT results.

METHODS: A total of 121 individuals aged ≥18 years with clinically diagnosed AR were recruited. Skin prick testing (SPT) was performed using a panel of commonly encountered tropical grass and weed pollen extracts. SPT wheal sizes and clinical symptom scores were recorded. Correlations between SPT outcomes and symptom scores were analyzed.

RESULTS: Among the participants, 104 (85.95%) exhibited positive SPT reactions to at least one pollen type. Nutsedge (76/121), para grass (57/121), and Bermuda grass (48/121) were the most frequently identified allergens. Hurricane grass elicited the strongest reaction, evidenced by the highest average wheal size (6.2 mm). Poly-sensitization was observed in 77 (63.6%) of the SPT-positive individuals, with most cases involving two different pollen extracts (35/77). Notably, AR severity positively correlated with both average wheal size and the number of positive SPT tests.

CONCLUSION: This study highlights nutsedge, para grass, and Bermuda grass as major allergenic pollen sources for Thai AR patients. Including nutsedge, hurricane grass, and careless weed in clinical SPT panels is recommended for improved diagnostic accuracy. Additionally, the positive correlation between AR severity and pollen reaction strength emphasizes the importance of implementing patient education and avoidance strategies.

PMID:38605873 | PMC:PMC11007029 | DOI:10.3389/fpubh.2024.1301095

Mol Ther. 2024 Apr 10:S1525-0016(24)00236-3. doi: 10.1016/j.ymthe.2024.04.019. Online ahead of print.

ABSTRACT

The role of CD8+ T-cells in SARS-CoV-2 pathogenesis or mRNA-LNP vaccine-induced protection from lethal COVID-19 is unclear. Using mouse-adapted SARS-CoV-2 virus (MA30) in C57BL/6 mice, we show that CD8+ T-cells are unnecessary for the intrinsic resistance of female or the susceptibility of male mice to lethal SARS-CoV-2 infection. Also, mice immunized with a di-proline prefusion-stabilized full-length SARS-CoV-2 Spike (S-2P) mRNA-LNP vaccine, which induces Spike-specific antibodies and CD8+ T-cells specific for the Spike-derived VNFNFNGL peptide, are protected from SARS-CoV-2 infection-induced lethality and weight loss, while mice vaccinated with mRNA-LNPs encoding only VNFNFNGL are protected from lethality but not weight loss. CD8+ T-cell depletion ablates protection in VNFNFNGL but not in S-2P mRNA-LNP-vaccinated mice. Therefore, mRNA-LNP vaccine-induced CD8+ T-cells are dispensable when protective antibodies are present but essential for survival in their absence. Hence, vaccine-induced CD8+ T-cells may be critical to protect against SARS-CoV-2 variants that mutate epitopes targeted by protective antibodies.

PMID:38605519 | DOI:10.1016/j.ymthe.2024.04.019

J Immunol Methods. 2024 Apr 9:113670. doi: 10.1016/j.jim.2024.113670. Online ahead of print.

ABSTRACT

Cytotoxicity studies determining hemolytic properties of antimicrobial peptides or other drugs are an important step in the development of novel therapeutics for clinical use. Hemolysis is an affordable, accessible, and rapid method for initial assessment of cellular toxicity for all drugs under development. However, variability in species of red blood cells and protocols used may result in significant differences in results. AMPs generally possess higher selectivity for bacterial cells but can have toxicity against host cells at high concentrations. Knowing the hemolytic activity of the peptides we are developing contributes to our understanding of their potential toxicity. Computational approaches for predicting hemolytic activity of AMPs exist and were tested head-to-head with our experimental results.

RESULTS: Starting with an observation of high hemolytic activity of LL-37 peptide against human red blood cells that were collected in EDTA, we explored alternative approaches to develop a more robust, accurate and simple hemolysis assay using defibrinated human blood. We found significant differences between the sensitivity of defibrinated red blood cells and EDTA treated red blood cells.

SIGNIFICANCE: Accurately determining the hemolytic activity using human red blood cells will allow for a more robust calculation of the therapeutic index of our potential antimicrobial compounds, a critical measure in their pre-clinical development.

CONCLUSION: We introduce a standardized, more accurate protocol for assessing hemolytic activity using defibrinated human red blood cells. This approach, facilitated by the increased commercial availability of de-identified human blood and defibrination methods, offers a robust tool for evaluating toxicity of emerging drug compounds, especially AMPs.

PMID:38604530 | DOI:10.1016/j.jim.2024.113670

Prog Biophys Mol Biol. 2024 Apr 9:S0079-6107(24)00036-1. doi: 10.1016/j.pbiomolbio.2024.04.002. Online ahead of print.

ABSTRACT

Gene regulatory network (GRN) comprises complicated yet intertwined gene-regulator relationships. Understanding the GRN dynamics will unravel the complexity behind the observed gene expressions. Insect gene regulation is often complicated due to their complex life cycles and diverse ecological adaptations. The main interest of this review is to have an update on the current mathematical modelling methods of GRNs to explain insect science. Several popular GRN architecture models are discussed, together with examples of applications in insect science. In the last part of this review, each model is compared from different aspects, including network scalability, computation complexity, robustness to noise and biological relevancy.

PMID:38604435 | DOI:10.1016/j.pbiomolbio.2024.04.002

EMBO J. 2024 Apr 11. doi: 10.1038/s44318-024-00082-9. Online ahead of print.

ABSTRACT

Prenatal lethality associated with mouse knockout of Mettl16, a recently identified RNA N6-methyladenosine (m6A) methyltransferase, has hampered characterization of the essential role of METTL16-mediated RNA m6A modification in early embryonic development. Here, using cross-species single-cell RNA sequencing analysis, we found that during early embryonic development, METTL16 is more highly expressed in vertebrate hematopoietic stem and progenitor cells (HSPCs) than other methyltransferases. In Mettl16-deficient zebrafish, proliferation capacity of embryonic HSPCs is compromised due to G1/S cell cycle arrest, an effect whose rescue requires Mettl16 with intact methyltransferase activity. We further identify the cell-cycle transcription factor mybl2b as a directly regulated by Mettl16-mediated m6A modification. Mettl16 deficiency resulted in the destabilization of mybl2b mRNA, likely due to lost binding by the m6A reader Igf2bp1 in vivo. Moreover, we found that the METTL16-m6A-MYBL2-IGF2BP1 axis controlling G1/S progression is conserved in humans. Collectively, our findings elucidate the critical function of METTL16-mediated m6A modification in HSPC cell cycle progression during early embryonic development.

PMID:38605226 | DOI:10.1038/s44318-024-00082-9

Nat Cell Biol. 2024 Apr 11. doi: 10.1038/s41556-024-01402-1. Online ahead of print.

ABSTRACT

Blocking the import of nutrients essential for cancer cell proliferation represents a therapeutic opportunity, but it is unclear which transporters to target. Here we report a CRISPR interference/activation screening platform to systematically interrogate the contribution of nutrient transporters to support cancer cell proliferation in environments ranging from standard culture media to tumours. We applied this platform to identify the transporters of amino acids in leukaemia cells and found that amino acid transport involves high bidirectional flux dependent on the microenvironment composition. While investigating the role of transporters in cystine starved cells, we uncovered a role for serotonin uptake in preventing ferroptosis. Finally, we identified transporters essential for cell proliferation in subcutaneous tumours and found that levels of glucose and amino acids can restrain proliferation in that environment. This study establishes a framework for systematically identifying critical cellular nutrient transporters, characterizing their function and exploring how the tumour microenvironment impacts cancer metabolism.

PMID:38605144 | DOI:10.1038/s41556-024-01402-1

Nat Food. 2024 Apr 11. doi: 10.1038/s43016-024-00958-3. Online ahead of print.

ABSTRACT

Food texture, along with taste and odour, is an important factor in determining food flavour. However, the physiological properties of oral texture perception require greater examination and definition. Here we explore recent trends and perspectives related to mouthfeel and its relevance in food flavour perception, with an emphasis on the biophysical point of view and methods. We propose that atomic force microscopy, combined with other biophysical techniques and more traditional food science approaches, offers a unique opportunity to study the mechanisms of mouthfeel at cellular and molecular levels. With this knowledge, food composition could be modified to develop healthier products by limiting salt, sugar, fat and calories while maintaining sensory qualities and consumer acceptance.

PMID:38605131 | DOI:10.1038/s43016-024-00958-3

Sci Data. 2024 Apr 11;11(1):363. doi: 10.1038/s41597-024-03171-w.

ABSTRACT

Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data, but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to construct them automatically. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoint resources and abstraction algorithms), and benchmarks (e.g., prebuilt KGs). We evaluated the ecosystem by systematically comparing it to existing open-source KG construction methods and by analyzing its computational performance when used to construct 12 different large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability.

PMID:38605048 | DOI:10.1038/s41597-024-03171-w

Nat Commun. 2024 Apr 11;15(1):3149. doi: 10.1038/s41467-024-47242-3.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism.

PMID:38605037 | DOI:10.1038/s41467-024-47242-3

Nat Commun. 2024 Apr 11;15(1):3127. doi: 10.1038/s41467-024-47355-9.

ABSTRACT

Cells must sense and respond to sudden maladaptive environmental changes-stresses-to survive and thrive. Across eukaryotes, stresses such as heat shock trigger conserved responses: growth arrest, a specific transcriptional response, and biomolecular condensation of protein and mRNA into structures known as stress granules under severe stress. The composition, formation mechanism, adaptive significance, and even evolutionary conservation of these condensed structures remain enigmatic. Here we provide a remarkable view into stress-triggered condensation, its evolutionary conservation and tuning, and its integration into other well-studied aspects of the stress response. Using three morphologically near-identical budding yeast species adapted to different thermal environments and diverged by up to 100 million years, we show that proteome-scale biomolecular condensation is tuned to species-specific thermal niches, closely tracking corresponding growth and transcriptional responses. In each species, poly(A)-binding protein-a core marker of stress granules-condenses in isolation at species-specific temperatures, with conserved molecular features and conformational changes modulating condensation. From the ecological to the molecular scale, our results reveal previously unappreciated levels of evolutionary selection in the eukaryotic stress response, while establishing a rich, tractable system for further inquiry.

PMID:38605014 | DOI:10.1038/s41467-024-47355-9

J Sci Med Sport. 2024 Mar 26:S1440-2440(24)00082-3. doi: 10.1016/j.jsams.2024.03.005. Online ahead of print.

ABSTRACT

OBJECTIVES: Although the ability to attenuate power output (PO) declines after accumulated work (i.e., 'durability') is increasingly recognized as a major determinant of cycling performance, the potential role of the intensity of the previous work is unclear. We assessed the effect of work-matched levels of accumulated work at different intensities on performance in male professional cyclists.

DESIGN: Observational field-based study.

METHODS: PO data was registered in 17 cyclists during a competition season, and the critical power (CP) was repeatedly determined every 4 weeks from training sessions and competitions. Participants' maximum mean power (MMP) for different durations (5 s, 5 min, 10 min, and 20 min) and the CP were determined under 'fresh' conditions (0 kJ·kg-1) and after varying levels of accumulated work (2.5, 5.0 and 7.5 kJ·kg-1) at intensities below and above the CP.

RESULTS: A significant decline was found for all MMP values following all levels of accumulated work above the CP (-4.0 %, -1.7 %, -1.8 %, and -3.2 % for 30s, 5 min, 10 min and 20 min-MMP, respectively; all p < 0.001), versus no change after any level of accumulated work below the CP (all p > 0.05). Similar results were observed for the CP, which decreased after all levels of accumulated work above (-2.2 %, -6.1 %, and -16.2 %, after 2.5, 5.0 and 7.5 kJ·kg-1, p < 0.001) but not below this indicator (p > 0.05).

CONCLUSIONS: In male professional cyclists, accumulated work above the CP impairs performance compared with work-matched, albeit less intense efforts. This raises concerns on the use of mechanical work per se as a single fatigue/stress indicator in these athletes.

PMID:38604818 | DOI:10.1016/j.jsams.2024.03.005