Systems Biology
iColon, a patient-focused mobile application for perioperative care in colorectal surgery: Results from 444 patients
J Telemed Telecare. 2023 Oct 11:1357633X231203064. doi: 10.1177/1357633X231203064. Online ahead of print.
ABSTRACT
AIM: The aim of this study is to assess if a patient-focused mobile application can increase compliance with active Enhanced Recovery After Surgery (ERAS) items and thereby improve surgery-related outcomes and patient satisfaction.
METHOD: This is a prospective observational study of patients admitted for elective colorectal surgery, under the ERAS protocol, and having access to the mobile application iColon during all perioperative phases.
RESULTS: The 444 participants were included in the study. The overall adherence to the use of iColon was 62.4%. The overall adherence to active ERAS items was 74.1%. Adherence to the use of iColon significantly impacted adherence to active ERAS items. The use of the application was negatively related with factors such as age, type of disease, and postoperative complications. In the postdischarge phase, low adherence to active ERAS items typically indicates an increased likelihood of readmission; however, the use of iColon correlated significantly with a reduction in the 30-day readmission rate. A survey regarding patient satisfaction and confidence in using iColon resulted in positive feedback in more than 94% of cases, while 92.7% reported better quality of care.
CONCLUSION: Our findings suggest that digital health tools are beneficial and effective in the follow up of patients after early discharge. Our mobile application, iColon, represents user-friendly technology that is well-accepted. It has real-world implications in increasing adherence to active ERAS items, which results in an improvement in perceived quality of care by its users.
PMID:37820368 | DOI:10.1177/1357633X231203064
AGAMOUS mediates timing of guard cell formation during gynoecium development
PLoS Genet. 2023 Oct 11;19(10):e1011000. doi: 10.1371/journal.pgen.1011000. Online ahead of print.
ABSTRACT
In Arabidopsis thaliana, stomata are composed of two guard cells that control the aperture of a central pore to facilitate gas exchange between the plant and its environment, which is particularly important during photosynthesis. Although leaves are the primary photosynthetic organs of flowering plants, floral organs are also photosynthetically active. In the Brassicaceae, evidence suggests that silique photosynthesis is important for optimal seed oil content. A group of transcription factors containing MADS DNA binding domains is necessary and sufficient to confer floral organ identity. Elegant models, such as the ABCE model of flower development and the floral quartet model, have been instrumental in describing the molecular mechanisms by which these floral organ identity proteins govern flower development. However, we lack a complete understanding of how the floral organ identity genes interact with the underlying leaf development program. Here, we show that the MADS domain transcription factor AGAMOUS (AG) represses stomatal development on the gynoecial valves, so that maturation of stomatal complexes coincides with fertilization. We present evidence that this regulation by AG is mediated by direct transcriptional repression of a master regulator of the stomatal lineage, MUTE, and show data that suggests this interaction is conserved among several members of the Brassicaceae. This work extends our understanding of the mechanisms underlying floral organ formation and provides a framework to decipher the mechanisms that control floral organ photosynthesis.
PMID:37819989 | DOI:10.1371/journal.pgen.1011000
Disruption of the rice <em>4-DEOXYOROBANCHOL HYDROXYLASE</em> unravels specific functions of canonical strigolactones
Proc Natl Acad Sci U S A. 2023 Oct 17;120(42):e2306263120. doi: 10.1073/pnas.2306263120. Epub 2023 Oct 11.
ABSTRACT
Strigolactones (SLs) regulate many developmental processes, including shoot-branching/tillering, and mediate rhizospheric interactions. SLs originate from carlactone (CL) and are structurally diverse, divided into a canonical and a noncanonical subfamily. Rice contains two canonical SLs, 4-deoxyorobanchol (4DO) and orobanchol (Oro), which are common in different plant species. The cytochrome P450 OsMAX1-900 forms 4DO from CL through repeated oxygenation and ring closure, while the homologous enzyme OsMAX1-1400 hydroxylates 4DO into Oro. To better understand the biological function of 4DO and Oro, we generated CRISPR/Cas9 mutants disrupted in OsMAX1-1400 or in both OsMAX1-900 and OsMAX1-1400. The loss of OsMAX1-1400 activity led to a complete lack of Oro and an accumulation of its precursor 4DO. Moreover, Os1400 mutants showed shorter plant height, panicle and panicle base length, but no tillering phenotype. Hormone quantification and transcriptome analysis of Os1400 mutants revealed elevated auxin levels and changes in the expression of auxin-related, as well as of SL biosynthetic genes. Interestingly, the Os900/1400 double mutant lacking both Oro and 4DO did not show the observed Os1400 architectural phenotypes, indicating their being a result of 4DO accumulation. Treatment of wild-type plants with 4DO confirmed this assumption. A comparison of the Striga seed germinating activity and the mycorrhization of Os900, Os900/1400, and Os1400 loss-of-function mutants demonstrated that the germination activity positively correlates with 4DO content while disrupting OsMAX1-1400 has a negative impact on mycorrhizal symbiosis. Taken together, our paper deciphers the biological function of canonical SLs in rice and reveals their particular contributions to establishing architecture and rhizospheric communications.
PMID:37819983 | DOI:10.1073/pnas.2306263120
Use of 3-Dimensional Stereophotogrammetry to Detect Disease Progression in Craniofacial Morphea
JAMA Dermatol. 2023 Oct 11. doi: 10.1001/jamadermatol.2023.3649. Online ahead of print.
ABSTRACT
IMPORTANCE: Objectively determining disease progression in craniofacial morphea (CM) is challenging, as clinical findings of disease activity are often lacking.
OBJECTIVE: To evaluate the utility of 3-dimensional (3D) stereophotogrammetry in detecting disease progression in CM over time.
DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study included 27 pediatric and adult patients with CM from 2 hospitals in Boston (Boston Children's Hospital and Brigham & Women's Hospital) consecutively enrolled from April 1, 2019, to March 1, 2023. Review of 3D stereophotogrammetry images and data analysis occurred from March 1 to April 1, 2023.
MAIN OUTCOMES AND MEASURES: Clinical and 3D stereophotogrammetry assessments were performed at 2- to 12-month intervals, depending on the clinical context. The 3D stereophotogrammetry images were then qualitatively rated as demonstrating no progression or definitive progression by an expert (board-certified plastic craniofacial surgeon) and nonexpert (board-certified dermatologist) in 3D stereophotogrammetry. In addition, κ coefficients were calculated for interrater reliability.
RESULTS: Of 27 patients with CM (19 female; median age, 14 [range, 5-40] years) and 3D stereophotogrammetry images obtained from a minimum of 2 time points (median, 4 [range, 2-10] images) spaced a median of 3 (range, 2-12) months apart, 10 experienced progression of their disease based on clinical assessments performed during the study period. In all cases in which clinical progression was favored, blinded qualitative assessment of 3D stereophotogrammetry images also favored progression with substantial interrater reliability (κ = 0.80 [95% CI, 0.61-0.99]). Furthermore, review of 3D stereophotogrammetry detected occult progression of asymmetry not noted on clinical examination in 3 additional patients.
CONCLUSIONS AND RELEVANCE: In this prospective cohort study, blinded assessment of sequential 3D stereophotogrammetry images in patients with CM not only corroborated clinical assessment of disease progression but also detected occult progression of facial asymmetry not appreciable on clinical examination alone. Therefore, 3D stereophotogrammetry may serve as a useful adjunct to clinical examination of patients with CM over time. Future investigations are warranted to validate 3D stereophotogrammetry as an outcome measure in CM.
PMID:37819665 | DOI:10.1001/jamadermatol.2023.3649
Engineering Green-light-responsive Heterologous Gene Expression in Pseudomonas
Methods Mol Biol. 2024;2721:35-44. doi: 10.1007/978-1-0716-3473-8_3.
ABSTRACT
Engineering bacterial properties requires precision and fine-tuning for optimal control of the desired application. In consequence, it is essential to accurately turn the function of interest from OFF to ON state and vice versa, avoiding any type of residual activation. For this type of purpose, light switches have revealed a clean and powerful tool in which control does not depend on the addition of chemical compounds that may remain in the media. To reach this degree of directed regulation through light, the switch based on the cyanobacterial two-component system CcaSR system was previously adapted to manipulate Pseudomonas putida for transcription of a gene of interest. In this chapter, we describe how to induce biofilm formation by placing the expression of the c-di-GMP-producing diguanylate cyclase PleD from Caulobacter sp. under the control of the CcaSR system. The regulation through optogenetics accomplished with this protocol promotes higher exploitation of biofilm beneficial features in a cheaper and cleaner way compared to chemical induction.
PMID:37819513 | DOI:10.1007/978-1-0716-3473-8_3
Investigating Pseudomonas aeruginosa Gene Function During Pathogenesis Using Mobile-CRISPRi
Methods Mol Biol. 2024;2721:13-32. doi: 10.1007/978-1-0716-3473-8_2.
ABSTRACT
CRISPR interference (CRISPRi) is a robust gene silencing technique that is ideal for targeting essential and conditionally essential (CE) genes. CRISPRi is especially valuable for investigating gene function in pathogens such as P. aeruginosa where essential and CE genes underlie clinically important phenotypes such as antibiotic susceptibility and virulence. To facilitate the use of CRISPRi in diverse bacteria-including P. aeruginosa-we developed a suite of modular, mobilizable, and integrating vectors we call, "Mobile-CRISPRi." We further optimized Mobile-CRISPRi for use in P. aeruginosa mouse models of acute lung infection by expressing the CRISPRi machinery at low levels constitutively, enabling partial knockdown of essential and CE genes without the need for an exogenous inducer. Here, we describe protocols for creating Mobile-CRISPRi knockdown strains and testing their phenotypes in a mouse pneumonia model of P. aeruginosa infection. In addition, we provide comprehensive guide RNA designs to target genes in common laboratory strains of P. aeruginosa and other Pseudomonas species.
PMID:37819512 | DOI:10.1007/978-1-0716-3473-8_2
MAPKKK5 is required for the enhanced-resistance to powdery mildew phenotype of edr1 mutants
Plant Physiol. 2023 Oct 11:kiad541. doi: 10.1093/plphys/kiad541. Online ahead of print.
NO ABSTRACT
PMID:37819049 | DOI:10.1093/plphys/kiad541
MAMI: a comprehensive database of mother-infant microbiome and probiotic resources
Nucleic Acids Res. 2023 Oct 11:gkad813. doi: 10.1093/nar/gkad813. Online ahead of print.
ABSTRACT
Extensive evidence has demonstrated that the human microbiome and probiotics confer great impacts on human health, particularly during critical developmental stages such as pregnancy and infancy when microbial communities undergo remarkable changes and maturation. However, a major challenge in understanding the microbial community structure and interactions between mothers and infants lies in the current lack of comprehensive microbiome databases specifically focused on maternal and infant health. To address this gap, we have developed an extensive database called MAMI (Microbiome Atlas of Mothers and Infants) that archives data on the maternal and neonatal microbiome, as well as abundant resources on edible probiotic strains. By leveraging this resource, we can gain profound insights into the dynamics of microbial communities, contributing to lifelong wellness for both mothers and infants through precise modulation of the developing microbiota. The functionalities incorporated into MAMI provide a unique perspective on the study of the mother-infant microbiome, which not only advance microbiome-based scientific research but also enhance clinical practice. MAMI is publicly available at https://bioinfo.biols.ac.cn/mami/.
PMID:37819042 | DOI:10.1093/nar/gkad813
Where the minor things are: a pan-eukaryotic survey suggests neutral processes may explain much of minor intron evolution
Nucleic Acids Res. 2023 Oct 11:gkad797. doi: 10.1093/nar/gkad797. Online ahead of print.
ABSTRACT
Spliceosomal introns are gene segments removed from RNA transcripts by ribonucleoprotein machineries called spliceosomes. In some eukaryotes a second 'minor' spliceosome is responsible for processing a tiny minority of introns. Despite its seemingly modest role, minor splicing has persisted for roughly 1.5 billion years of eukaryotic evolution. Identifying minor introns in over 3000 eukaryotic genomes, we report diverse evolutionary histories including surprisingly high numbers in some fungi and green algae, repeated loss, as well as general biases in their positional and genic distributions. We estimate that ancestral minor intron densities were comparable to those of vertebrates, suggesting a trend of long-term stasis. Finally, three findings suggest a major role for neutral processes in minor intron evolution. First, highly similar patterns of minor and major intron evolution contrast with both functionalist and deleterious model predictions. Second, observed functional biases among minor intron-containing genes are largely explained by these genes' greater ages. Third, no association of intron splicing with cell proliferation in a minor intron-rich fungus suggests that regulatory roles are lineage-specific and thus cannot offer a general explanation for minor splicing's persistence. These data constitute the most comprehensive view of minor introns and their evolutionary history to date, and provide a foundation for future studies of these remarkable genetic elements.
PMID:37819006 | DOI:10.1093/nar/gkad797
PLANTdataHUB: a collaborative platform for continuous FAIR data sharing in plant research
Plant J. 2023 Oct 11. doi: 10.1111/tpj.16474. Online ahead of print.
ABSTRACT
In modern reproducible, hypothesis-driven plant research, scientists are increasingly relying on research data management (RDM) services and infrastructures to streamline the processes of collecting, processing, sharing, and archiving research data. FAIR (i.e., findable, accessible, interoperable, and reusable) research data play a pivotal role in enabling the integration of interdisciplinary knowledge and facilitating the comparison and synthesis of a wide range of analytical findings. The PLANTdataHUB offers a solution that realizes RDM of scientific (meta)data as evolving collections of files in a directory - yielding FAIR digital objects called ARCs - with tools that enable scientists to plan, communicate, collaborate, publish, and reuse data on the same platform while gaining continuous quality control insights. The centralized platform is scalable from personal use to global communities and provides advanced federation capabilities for institutions that prefer to host their own satellite instances. This approach borrows many concepts from software development and adapts them to fit the challenges of the field of modern plant science undergoing digital transformation. The PLANTdataHUB supports researchers in each stage of a scientific project with adaptable continuous quality control insights, from the early planning phase to data publication. The central live instance of PLANTdataHUB is accessible at (https://git.nfdi4plants.org), and it will continue to evolve as a community-driven and dynamic resource that serves the needs of contemporary plant science.
PMID:37818860 | DOI:10.1111/tpj.16474
Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release
EMBO Rep. 2023 Oct 11:e57224. doi: 10.15252/embr.202357224. Online ahead of print.
ABSTRACT
The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon-induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS-CoV-2 infection causes tetherin downregulation and that tetherin depletion from cells enhances SARS-CoV-2 viral titres. We investigate the potential viral proteins involved in abrogating tetherin function and find that SARS-CoV-2 ORF3a reduces tetherin localisation within biosynthetic organelles where Coronaviruses bud, and increases tetherin localisation to late endocytic organelles via reduced retrograde recycling. We also find that expression of Spike protein causes a reduction in cellular tetherin levels. Our results confirm that tetherin acts as a host restriction factor for SARS-CoV-2 and highlight the multiple distinct mechanisms by which SARS-CoV-2 subverts tetherin function.
PMID:37818801 | DOI:10.15252/embr.202357224
Editorial: The immunological role of platelet activation in the pathophysiology of COVID-19
Front Immunol. 2023 Sep 25;14:1285355. doi: 10.3389/fimmu.2023.1285355. eCollection 2023.
NO ABSTRACT
PMID:37818358 | PMC:PMC10562013 | DOI:10.3389/fimmu.2023.1285355
Editorial: Developing high-yielding plant cell bio-factories for high-value low-volume phytochemicals
Front Plant Sci. 2023 Sep 25;14:1281385. doi: 10.3389/fpls.2023.1281385. eCollection 2023.
NO ABSTRACT
PMID:37818317 | PMC:PMC10561325 | DOI:10.3389/fpls.2023.1281385
Editorial: Insights in human and medical genomics: 2022
Front Genet. 2023 Sep 25;14:1287894. doi: 10.3389/fgene.2023.1287894. eCollection 2023.
NO ABSTRACT
PMID:37818104 | PMC:PMC10561311 | DOI:10.3389/fgene.2023.1287894
A physiologically based model of bile acid metabolism in mice
iScience. 2023 Sep 17;26(10):107922. doi: 10.1016/j.isci.2023.107922. eCollection 2023 Oct 20.
ABSTRACT
Bile acid (BA) metabolism is a complex system that includes a wide variety of primary and secondary, as well as conjugated and unconjugated BAs that undergo continuous enterohepatic circulation (EHC). Alterations in both composition and dynamics of BAs have been associated with various diseases. However, a mechanistic understanding of the relationship between altered BA metabolism and related diseases is lacking. Computational modeling may support functional analyses of the physiological processes involved in the EHC of BAs along the gut-liver axis. In this study, we developed a physiologically based model of murine BA metabolism describing synthesis, hepatic and microbial transformations, systemic distribution, excretion, and EHC of BAs at the whole-body level. For model development, BA metabolism of specific pathogen-free (SPF) mice was characterized in vivo by measuring BA levels and composition in various organs, expression of transporters along the gut, and cecal microbiota composition. We found significantly different BA levels between male and female mice that could only be explained by adjusted expression of the hepatic enzymes and transporters in the model. Of note, this finding was in agreement with experimental observations. The model for SPF mice could also describe equivalent experimental data in germ-free mice by specifically switching off microbial activity in the intestine. The here presented model can therefore facilitate and guide functional analyses of BA metabolism in mice, e.g., the effect of pathophysiological alterations on BA metabolism and translation of results from mouse studies to a clinically relevant context through cross-species extrapolation.
PMID:37817939 | PMC:PMC10561051 | DOI:10.1016/j.isci.2023.107922
A computational model of the DNA damage-induced IKK/ NF-κB pathway reveals a critical dependence on irradiation dose and PARP-1
iScience. 2023 Sep 14;26(10):107917. doi: 10.1016/j.isci.2023.107917. eCollection 2023 Oct 20.
ABSTRACT
The activation of IKK/NF-κB by genotoxic stress is a crucial process in the DNA damage response. Due to the anti-apoptotic impact of NF-κB, it can affect cell-fate decisions upon DNA damage and therefore interfere with tumor therapy-induced cell death. Here, we developed a dynamical model describing IKK/NF-κB signaling that faithfully reproduces quantitative time course data and enables a detailed analysis of pathway regulation. The approach elucidates a pathway topology with two hubs, where the first integrates signals from two DNA damage sensors and the second forms a coherent feedforward loop. The analyses reveal a critical role of the sensor protein PARP-1 in the pathway regulation. Introducing a method for calculating the impact of changes in individual components on pathway activity in a time-resolved manner, we show how irradiation dose influences pathway activation. Our results give a mechanistic understanding relevant for the interpretation of experimental and clinical studies.
PMID:37817938 | PMC:PMC10561052 | DOI:10.1016/j.isci.2023.107917
Sex-specific adipose tissue's dynamic role in metabolic and inflammatory response following peripheral nerve injury
iScience. 2023 Sep 15;26(10):107914. doi: 10.1016/j.isci.2023.107914. eCollection 2023 Oct 20.
ABSTRACT
Epidemiological data and research highlight increased neuropathy and chronic pain prevalence among females, spanning metabolic and normometabolic contexts, including murine models. Prior findings demonstrated diverse immune and neuroimmune responses between genders in neuropathic pain (NeP), alongside distinct protein expression in sciatic nerves. This study unveils adipose tissue's (AT) role in sex-specific NeP responses after peripheral nerve injury. Metabolic assessments, metabolomics, energy expenditure evaluations, AT proteomic analyses, and adipokine mobilization depict distinct AT reactions to nerve damage. Females exhibit altered lipolysis, fatty acid oxidation, heightened energy expenditure, and augmented steroids secretion affecting glucose and insulin metabolism. Conversely, male neuropathy prompts glycolysis, reduced energy expenditure, and lowered unsaturated fatty acid levels. Males' AT promotes regenerative molecules, oxidative stress defense, and stimulates peroxisome proliferator-activated receptors (PPAR-γ) and adiponectin. This study underscores AT's pivotal role in regulating gender-specific inflammatory and metabolic responses to nerve injuries, shedding light on female NeP susceptibility determinants.
PMID:37817933 | PMC:PMC10561049 | DOI:10.1016/j.isci.2023.107914
Vocal tract shape variation contributes to individual vocal identity in African penguins
Proc Biol Sci. 2023 Oct 11;290(2008):20231029. doi: 10.1098/rspb.2023.1029. Epub 2023 Oct 11.
ABSTRACT
Variation in formant frequencies has been shown to affect social interactions and sexual competition in a range of avian species. Yet, the anatomical bases of this variation are poorly understood. Here, we investigated the morphological correlates of formants production in the vocal apparatus of African penguins. We modelled the geometry of the supra-syringeal vocal tract of 20 specimens to generate a population of virtual vocal tracts with varying dimensions. We then estimated the acoustic response of these virtual vocal tracts and extracted the centre frequency of the first four predicted formants. We demonstrate that: (i) variation in length and cross-sectional area of vocal tracts strongly affects the formant pattern, (ii) the tracheal region determines most of this variation, and (iii) the skeletal size of penguins does not correlate with the trachea length and consequently has relatively little effect on formants. We conclude that in African penguins, while the variation in vocal tract geometry generates variation in resonant frequencies supporting the discrimination of conspecifics, such variation does not provide information on the emitter's body size. Overall, our findings advance our understanding of the role of formant frequencies in bird vocal communication.
PMID:37817600 | DOI:10.1098/rspb.2023.1029
A supergene in seaweed flies modulates male traits and female perception
Proc Biol Sci. 2023 Oct 11;290(2008):20231494. doi: 10.1098/rspb.2023.1494. Epub 2023 Oct 11.
ABSTRACT
Supergenes, tightly linked sets of alleles, offer some of the most spectacular examples of polymorphism persisting under long-term balancing selection. However, we still do not understand their evolution and persistence, especially in the face of accumulation of deleterious elements. Here, we show that an overdominant supergene in seaweed flies, Coelopa frigida, modulates male traits, potentially facilitating disassortative mating and promoting intraspecific polymorphism. Across two continents, the Cf-Inv(1) supergene strongly affected the composition of male cuticular hydrocarbons (CHCs) but only weakly affected CHC composition in females. Using gas chromatography-electroantennographic detection, we show that females can sense male CHCs and that there may be differential perception between genotypes. Combining our phenotypic results with RNA-seq data, we show that candidate genes for CHC biosynthesis primarily show differential expression for Cf-Inv(1) in males but not females. Conversely, candidate genes for odorant detection were differentially expressed in both sexes but showed high levels of divergence between supergene haplotypes. We suggest that the reduced recombination between supergene haplotypes may have led to rapid divergence in mate preferences as well as increasing linkage between male traits, and overdominant loci. Together this probably helped to maintain the polymorphism despite deleterious effects in homozygotes.
PMID:37817592 | DOI:10.1098/rspb.2023.1494
Sheathless CESI-MS versus LC-MS: Results of qualitative and quantitative analyses of the primary and secondary metabolites of Pleioblastus amarus bamboo shoots
Electrophoresis. 2023 Oct 10. doi: 10.1002/elps.202300030. Online ahead of print.
ABSTRACT
The bamboo shoot of Pleioblastus amarus (Keng) Keng f. is a medicinal and edible resource in China. In this study, three separation techniques were applied to identify the primary and secondary metabolites component of P. amarus bamboo shoots, including sheathless capillary electrophoresis electrospray ionization-mass spectrometry (CESI-MS), reverse-phase liquid chromatography-MS (RPLC-MS), and hydrophilic interaction liquid chromatography-MS (HILIC-MS). A total of 201 metabolites were identified by the three methods. Among those metabolites, 146 were identified by RPLC-MS, 85 were identified by HILIC-MS, and 46 were identified by sheathless CESI-MS. These methods were complementary and had a linear coefficient. CESI-MS presented advantages in the identification of isomers, high sensitivity, very low sample usage, and good detection of polar and nonpolar metabolites, showing its unique applications in food analysis and prospects in metabolic research.
PMID:37817363 | DOI:10.1002/elps.202300030