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1.
BMC Genomics ; 25(1): 871, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39289604

RESUMEN

BACKGROUND: The family Batrachoididae are a group of ecologically important teleost fishes with unique life histories, behavior, and physiology that has made them popular model organisms. Batrachoididae remain understudied in the realm of genomics, with only four reference genome assemblies available for the family, with three being highly fragmented and not up to current assembly standards. Among these is the Gulf toadfish, Opsanus beta, a model organism for serotonin physiology which has recently been bred in captivity. RESULTS: Here we present a new, de novo genome and transcriptome assemblies for the Gulf toadfish using PacBio long read technology. The genome size of the final assembly is 2.1 gigabases, which is among the largest teleost genomes. This new assembly improves significantly upon the currently available reference for Opsanus beta with a final scaffold count of 62, of which 23 are chromosome scale, an N50 of 98,402,768, and a BUSCO completeness score of 97.3%. Annotation with ab initio and transcriptome-based methods generated 41,076 gene models. The genome is highly repetitive, with ~ 70% of the genome composed of simple repeats and transposable elements. Satellite DNA analysis identified potential telomeric and centromeric regions. CONCLUSIONS: This improved assembly represents a valuable resource for future research using this important model organism and to teleost genomics more broadly.


Asunto(s)
Batrachoidiformes , Genoma , Genómica , Animales , Batrachoidiformes/genética , Genómica/métodos , Anotación de Secuencia Molecular , Transcriptoma
2.
Cureus ; 16(8): e67158, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39295708

RESUMEN

Introduction Hospital-acquired infections, also called nosocomial infections, are infectious diseases acquired in healthcare facilities at least 48 hours after admission and can't be present at the time of admission. Nosocomial bloodstream infection is a serious medical complication from hospitalization, and it can be potentially preventable by taking certain precautions. Aim The aim of this study is to determine the prevalence of central line-related bloodstream infections (CLABSI) with different organisms between January 2022 and February 2024 at the intensive care unit (ICU) at Prince Mohammed bin Abdulaziz Hospital, Riyadh, Saudi Arabia. Patients and methods This retrospective cross-sectional study was conducted among ICU adult patients. The data were collected from medical and infection control records. All data for intensive care patients with positive blood cultures, except for the pediatric age group, were collected. Data were tabulated and cleaned in MS Excel, and subsequent data analyses were performed in IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States). Results Data from 21 patients were collected and analyzed. The mean age of the participants was 62.9 (SD 15.1) years. Female participants (61.9% (13)) were higher than males (38.1% (8)). All patients were inserted with a non-tunneled central venous catheter (CVC). The mortality rate was 76.2% (16). Vancomycin-resistant enterococci (VRE) was the most commonly detected organism in seven cultures (33.3%), followed by Candida species in six cultures (28.6%). Candida species were prevalent in younger patients (p=0.021) and those sensitive to medication (p=0.015). Survival analyses between age, gender, and organisms yielded insignificant results (p>0.05). Conclusion The major sources of bloodstream infection among adult ICU patients were VRE and Candida species. Mortality was common in this population, particularly among patients who were resistant to medication. Hence, strategies to reduce hospital-acquired bloodstream infections are warranted.

3.
Heliyon ; 10(17): e37202, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296023

RESUMEN

With the yearly increasing market penetration of new-energy vehicles in China, the retirement of power batteries has gradually become a scale, and most of the waste batteries have entered informal recycling channels, which has induced a series of environmental problems. Considering this issue, we introduced the system dynamics (SD), stimulus organism response (SOR), and the theory of planned behavior (TPB) in behavioral economics to establish the environmental economic benefit evaluation model of power battery recycling strategies, and we performed a dynamic simulation analysis on the effect of government subsidy policy, policy advocacy, and other recycling strategies. The results show that: (1) the recovery subsidy policy can improve the formal recycling quantity and economic benefits of recovery, but the effect on the degree of environmental pollution is limited. (2) The combination of environmental awareness promotion strategy and subsidy policy can overcome the shortcomings of subsidy policy and has significant environmental and economic performance. (3) Compared with the benchmark scenario, the formal recycling quantity, the CO2 emission reduction, and the economic benefits of recovery in scenario 4 (high subsidy-high policy propaganda strategy) increased by approximately 112 %, 208 %, and 223 %, respectively, and the degree of environmental pollution decreased by approximately 65 %.

4.
Pestic Biochem Physiol ; 204: 106036, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39277363

RESUMEN

Herbicide exposure can pose a considerable threat to non-target aquatic animals. We aimed to study changes in the liver proteome of a model cyprinid fish species, zebrafish Danio rerio, to provide a molecular basis for the adverse effects of environmentally relevant concentrations of glyphosate (100 µg/L), its breakdown product aminomethylphosphonic acid (AMPA; 100 µg/L), and a mixture of both (50 + 50 µg/L) in the presence of humic acid (20 mg/L), which simulated a component of natural organic matter in the aquatic environment. Proteomic analysis was performed by means of high-performance liquid chromatography-tandem mass spectrometry employing a label-free quantification approach. The results present molecular evidence of the stress responses and disturbance of primary metabolic processes such as immune response, dysregulation in DNA repair, necroptosis and apoptosis signaling pathways, oxidative phosphorylation, cholesterol, lipoprotein, and carbohydrate metabolism. We registered the synergistic effect of the glyphosate and AMPA co-exposure, which was expressed in a substantial increase in the number of dysregulated proteins compared to the solo treatments. Humic acid alleviated the effects of glyphosate and its mixture with AMPA and aggravated the impact of AMPA exposure. RuvB-like 2, a protein taking part in DNA repair, and EIF2S1, involved in the regulation of stress-induced gene expression, were downregulated in the liver of zebrafish from all treatments.


Asunto(s)
Glicina , Glifosato , Herbicidas , Sustancias Húmicas , Hígado , Proteoma , Pez Cebra , Animales , Pez Cebra/metabolismo , Glicina/análogos & derivados , Glicina/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Proteoma/metabolismo , Proteoma/efectos de los fármacos , Herbicidas/toxicidad , Organofosfonatos/toxicidad , Contaminantes Químicos del Agua/toxicidad
5.
Cureus ; 16(8): e66912, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39280445

RESUMEN

Emphysematous osteomyelitis (EO) is a rare and severe bone infection characterized by the presence of gas within the bone and surrounding soft tissues, commonly caused by gas-forming bacteria. We present a case of an elderly patient with extensive EO due to Escherichia coli infection. The patient exhibited systemic signs of infection and severe localized pain. Radiological assessments, including computed tomography and magnetic resonance imaging, demonstrated significant gas accumulation within the bone and adjacent tissues, confirming the diagnosis. Despite intensive antibiotic treatment and surgical intervention, the patient's condition initially worsened, highlighting the high morbidity and mortality associated with this infection. However, through prompt action and targeted intervention, a positive outcome was ultimately achieved. This case emphasizes the critical need for early diagnosis and aggressive management of EO to improve patient outcomes.

6.
iScience ; 27(9): 110606, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39246443

RESUMEN

The biological mechanisms underlying the development of myopia have not yet been completely elucidated. The retina is critical for visual signal processing, which primarily utilizes aerobic glycolysis to produce lactate as a metabolic end product. Lactate facilitates lysine lactylation (Kla), a posttranslational modification essential for transcriptional regulation. This study found increased glycolytic flux and lactate accumulation in the retinas of form-deprived myopic guinea pigs. Subsequently, a comprehensive analysis of Kla levels in retinal proteins revealed that Kla was upregulated at 124 sites in 92 proteins and downregulated at three sites in three proteins. Functional enrichment and protein interaction analyses showed significant enrichment in pathways related to energy metabolism, including glutathione metabolism, glycolysis, and the hypoxia-inducible factor-1 signaling pathway. Parallel-reaction monitoring confirmed data reliability. These findings suggest a connection between myopia and retinal energy metabolism imbalance, providing new insights into the pathogenesis of myopia.

7.
Cureus ; 16(8): e66416, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39246977

RESUMEN

Churg-Strauss syndrome is a rare multisystem disorder characterized by asthma, eosinophilia, and vasculitis. The patient presented with prolonged fever, cough with blood-stained sputum, weight loss, pain in the abdomen, and a subsequent onset of hoarseness of voice. A history of asthma, left-side vocal cord paralysis, eosinophilia, nodular opacities on radiography, and eosinophilic duodenitis on biopsy led to a diagnosis of Churg-Strauss syndrome. The patient's condition improved on treatment with steroids. This is an interesting case and presents an opportunity to learn about Churg-Strauss syndrome.

8.
Infect Drug Resist ; 17: 3793-3804, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247753

RESUMEN

Objective: To assess the efficacy and safety of colistin sulfate in treating infections caused by carbapenem-resistant organisms (CRO) and to analyze potential factors impacting its effectiveness. Methods: In this retrospective study, medical records of CRO-infected patients from June 2020 to June 2023 were analyzed, divided into effective and ineffective treatment groups, and compared for clinical outcomes and adverse reactions. Multifactorial logistic regression and ROC curve analysis were used to identify influencing factors. Results: The study included 226 patients, with 124 in the effective treatment group and 102 in the ineffective group. A total of 293 CRO strains were cultured. The clinical efficacy rate of colistin sulfate was 54.87%, the microbiological efficacy rate 46.46%, and the hospital mortality rate 20.80%, with nephrotoxicity observed in 11.50% of patients. Multifactorial analysis identified APACHE II scores and vasoactive drug use as independent predictors of ineffective treatment, while treatment duration and albumin levels predicted effective treatment. ROC analysis indicated that albumin levels >34 g/L, APACHE II scores <13, and treatment duration >10 days correlated with better clinical efficacy. Conclusion: Colistin sulfate is both safe and effective in clinical settings. Factors such as treatment duration, albumin levels, APACHE II scores, and vasoactive drug use independently affect its clinical efficacy, providing valuable guidance for its informed clinical application.

9.
Chemphyschem ; : e202400545, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39221606

RESUMEN

Proteins from Crenarchaeal organisms exhibit remarkable thermal stability. The aromatic amino acids in Cren7, a Crenarchaeal protein, regulate protein stability and further modulate DNA binding and its compaction. Specific aromatic amino acids were mutated, and using spectroscopic and theoretical approaches, we have examined the structure, DNA binding affinity, and DNA bending ability of mutants. and compared with wild-type (WT) Cren7. The reverse titration profiles were analysed by a noncooperativeMcGhee-von Hippel model to estimate affinity constant (Ka) and site size (n) associated with binding to the DNA. Biolayer interferometry (BLI) measurements showed that the binding affinity decreased at higher salt concentrations. For theoretical analysis of extent of DNA bending, radius of gyration and bending angle were compared for WT and mutants. Time evolution of order parameters based on translational and rotational motion of tryptophan residue (W26) was used for qualitative detection of stacking interactions between W26 of Cren7 and DNA nucleobases. It was observed that orientation of W26 in F41A favored formation of a new lone pair-lone pair interaction between DNA and Cren7. Consequently, in thermostable proteins, the aromatic residues at the terminus maintain structural stability, whereas the residues at the core optimize the degree of DNA bending and compaction.

10.
Eur Spine J ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223430

RESUMEN

PURPOSE: This study aimed to evaluate the difference in treatment duration and unplanned additional surgeries between patients with unidentified causative organisms on empiric antibiotics and those with identified organisms on selective antibiotics in treating thoracolumbar pyogenic spondylitis with minimally invasive posterior fixation. METHODS: This multicenter retrospective cohort study included patients with thoracolumbar pyogenic spondylitis refractory to conservative treatment who underwent minimally invasive posterior fixation. Patients were divided into the identified (known causative organism) and unidentified groups (unknown causative organism). We analyzed data on demographics, antibiotic use, surgical outcomes, and infection control indicators. RESULTS: We included 74 patients, with 52 (70%) and 22 (30%) in the identified and unidentified groups, respectively. On admission, the identified group had higher C-reactive protein (CRP) levels and more iliopsoas abscesses. The duration to postoperative CRP negative was similar in the identified and unidentified groups (7.13 vs. 6.48 weeks, p = 0.74). Only the identified group had unplanned additional surgeries due to poor infection control, affecting 6 of 52 patients (12%). Advanced age and causative organism identification increased the additional surgery odds (odds ratio [OR], 8.25; p = 0.033 and OR, 6.83; p = 0.034, respectively). CONCLUSION: The use of empiric antibiotics in minimally invasive posterior fixation was effective without identifying the causative organism and did not prolong treatment duration. In patients with identified organisms, 12% required unplanned additional surgery, indicating a more challenging infection control. Causative organism identification was associated with the need for additional surgery, suggesting a more cautious treatment strategy for these patients.

11.
J Hazard Mater ; 479: 135782, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39259986

RESUMEN

Spiders are important in ecosystem and serve as predators in the biological control of pest insects in agroecosystem, where they encounter various harsh challenges including pesticides and low temperature in winter. Glyphosate-based herbicides (GBH) are widely and frequently applied to diminish weeds, exposing spiders a disturbed habitat, especially to overwintering spiders. We conducted a study combining field surveys and lab assays, to assess the effects of a GBH on the overwintering of the agrobiont wolf spider, Pardosa pseudoannulata. The GBH significantly reduced the overall overwintering spider population by about 69 %, and reduced the number of vulnerable juveniles by about 80 %. The survivors exhibited substantial fitness costs such as reproductive dysfunctions and enhanced oxidative stress responses. We then mimicked the overwinter process in lab. We housed spiders on soil patches with and without weeds to examine whether weeds contributed to the GBH's sublethal effects. Spiders overwintered independent of weeds when GBH was not applied. When GBH was applied before or during overwintering, juvenile spiders overwintered in weedy habitats exhibited reduced survival and fecundity, and increased oxidative stress compared to their counterparts in weed-free habitats. Therefore, GBH-containing weeds contributed to the persistent adverse effects of GBH on overwintering spiders. The findings revealed the cross-talk among weeds, herbicides, low temperature, and non-target organisms. The study provides novel information on the environmental risk assessment of pesticides and rational scheduling of pesticide application.

12.
iScience ; 27(9): 110618, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39262771

RESUMEN

Given the resurgence of syphilis, research endeavors to improve current assays for serological diagnosis and management of this disease are a priority. A proteome-scale platform for high-throughput profiling of the humoral response to Treponema pallidum (T. pallidum) proteins during infection could identify antigens suitable to ameliorate the performance and capabilities of treponemal tests for syphilis. Additionally, because infection-induced immunity is partially protective, profiling the response to T. pallidum outer membrane proteins (OMPs) could help select vaccine candidates. Therefore, we developed a pan-proteome array (PPA) based on the Nichols and SS14 strain complete proteomes and used it to define the immunoglobulin M (IgM) and IgG humoral response to T. pallidum proteins in sera collected longitudinally from long-term infected rabbits and from rabbits that were infected, treated, and re-infected. We identified antigens that could facilitate early diagnosis and immunity to a core set of OMP that could explain protection upon reinfection.

13.
iScience ; 27(9): 110631, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39262804

RESUMEN

Imbalanced dietary intake, such as a high-fat diet (HFD) during pregnancy, has been associated with adverse offspring outcomes. Metabolic stress from imbalanced food intake alters the function of epigenetic regulators, resulting in abnormal transcriptional outputs in embryos to cause congenital disorders. We report herein that maternal HFD exposure causes metabolic changes in pregnant mice and non-compaction cardiomyopathy (NCC) in E15.5 embryos, accompanied by decreased 5-hydroxymethylcytosine (5hmC) levels and altered chromatin accessibility in embryonic heart tissues. Remarkably, maternal vitamin C supplementation mitigates these detrimental effects, likely by restoring iron, a cofactor for Tet enzymes, in a reduced state. Using a genetic approach, we further demonstrated that the cardioprotective benefits of vitamin C under HFD conditions are attributable to enhanced Tet activity. Our results highlight an interaction between maternal diet, specifically HFD or vitamin C, and epigenetic modifications during early heart development, emphasizing the importance of balanced maternal nutrition for healthy embryonic development.

14.
J Mol Biol ; 436(17): 168705, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39237194

RESUMEN

We introduce XGR-model (or XGRm), a web server made accessible at http://www.xgrm.pro, with the aim of meeting the increasing demand for effectively interpreting summary-level genomic data in model organisms. Currently, it hosts two enrichment analysers and two subnetwork analysers to support enrichment and subnetwork analyses for user-input mouse genomic data, whether gene-centric or genomic region-centric. The enrichment analysers identify ontology term enrichments for input genes (GElyser) or for genes linked from input genomic regions (RElyser). The subnetwork analysers rely on our previously established network algorithm to identify gene subnetworks from input gene-centric summary data (GSlyser) or from input region-centric summary data (RSlyser), leveraging network information about either functional interactions or pathway-derived interactions. Collectively, XGRm offers an all-in-one solution for gaining systems biology insights into summary-level genomic data in mice, underpinned by our commitment to regular updates as well as natural extensions to other model organisms.


Asunto(s)
Genómica , Internet , Programas Informáticos , Animales , Ratones , Genómica/métodos , Redes Reguladoras de Genes , Biología Computacional/métodos , Algoritmos , Genoma
15.
Wiad Lek ; 77(7): 1415-1419, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39241141

RESUMEN

OBJECTIVE: Aim: To study the spectrum, frequency of isolation and level of colonization of dental biofilm with microorganisms in generalized periodontitis against the background of different body reactivity. PATIENTS AND METHODS: Materials and Methods: 216 people with the diagnosis of generalized periodontitis. Depending on the state of reactivity of the organism, the patients were divided into 3 groups: with normo-, hyper- and with hyporeaction. The patients underwent patch surgery. After the surgery, dental biofilm was taken. Microbiological studies included the isolation and species identification of dental biofilm microorganisms, the results of quantitative studies of microflora: the level of colonization was expressed in colony-forming units per 1 ml (CFU/ml); the frequency of microorganisms isolation was expressed in absolute numbers. Statistical processing of the obtained digital data was performed using the computer program Statistica 8.0. RESULTS: Results: The studies have shown that in different states of the body's reactivityi n patients with generalized periodontitis after flap surgery, different quantitative and qualitative composition of the microflora of the dental biofilm is determined. In case of normal body reactivity, there are predominantly aerobic-anaerobic associations with a wide range and quantitative predominance of aerobic microflora; in case of impaired (hyper- and hypo-) reactivity, there are predominantly aerobic-anaerobic associations with an expansion of the spectrum, frequency of isolation and level of colonization of facultative and obligate anaerobes. CONCLUSION: Conclusions: The identified differences in the quantitative and qualitative composition of the microflora of the dental biofilm indicate the key role of the body's reactivity in the studied processes.


Asunto(s)
Biopelículas , Periodontitis , Humanos , Biopelículas/crecimiento & desarrollo , Periodontitis/microbiología , Femenino , Masculino , Adulto , Persona de Mediana Edad
16.
Harmful Algae ; 138: 102695, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39244231

RESUMEN

In recent years, red tides have increased worldwide in frequency, intensity, involving a higher number of causative species during the events. As the most commonly used method for control of red tides, modified clay (MC) was found to have differential ability to remove various red tide species. However, the underlying mechanisms have not yet been completely elucidated. In this study, the use of MC to remove three typical disaster-causing species, Aureococcus anophagefferens, Prorocentrum donghaiense and Heterosigma akashiwo, was investigated, and differential removal of these species was probed with insights into their biocellular properties and mechanical interactions. The results showed that removal efficiencies of the three species by MC decreased in the order P. donghaiense > A. anophagefferens > H. akashiwo, while the sedimentation rates decreased in the order H. akashiwo > P. donghaiense > A. anophagefferens. Analyses of the cell surface properties and redundancy analysis (RDA) revealed that the highest surface zeta potential of -5.32±0.39 mV made P. donghaiense the most easily removed species; the smallest cell size of 3.30±0.03 µm facilitated the removal of A. anophagefferens; and the highest hydrophobicity with a H2O surface contact angle of 98.50±4.31° made the removal of H. akashiwo difficult. X-ray photoelectron spectroscopy (XPS) data indicated that the electronegativity of P. donghaiense was caused by carboxyl groups and phosphodiester groups, and the hydrophobicity of H. akashiwo was associated with a high C-(C, H) content on the cell surface. According to the extended Derjaguin, Landau, Verwey, and Overbeek (ex-DLVO) theory calculation, differences in the interaction energies between MC and the three red tide species effectively explained their different sedimentation rates. In addition, the degree of oxidative damage caused by MC to the three red tide species differed, which also affected the removal of red tide organisms.


Asunto(s)
Arcilla , Floraciones de Algas Nocivas , Arcilla/química , Silicatos de Aluminio/química
17.
Toxicology ; 508: 153927, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39151607

RESUMEN

There is an increasing incidence and prevalence of fatty liver disease in the western world, with steatosis as the most prevalent variant. Known causes of steatosis include exposure to food-borne chemicals, and overconsumption of alcohol, carbohydrates and fat, and it is a well-known side effect of certain pharmaceuticals such as tetracycline, amiodarone and tamoxifen (drug-induced hepatic steatosis). Mechanistic knowledge on chemical-induced steatosis has greatly evolved and has been organized into adverse outcome pathways (AOPs) describing the chain of events from first molecular interaction of a substance with a biological system to the adverse outcome, intrahepatic lipid accumulation. In this study, three known steatosis-inducing pesticides (imazalil, clothianidin, and thiacloprid) were tested for their ability to induce hepatic triglyceride accumulation in the zebrafish (Danio rerio) embryo (ZFE) at 5 days post fertilization, both as single compounds and equipotent binary mixtures. The results indicate that the ZFE is very well applicable as a higher tier testing model to confirm effects in downstream key events in AOPs, that is, chemically-induced triglyceride accumulation in the whole organism and production of visible steatosis. Moreover, dose addition could be concluded for binary mixtures of substances with similar and with dissimilar modes of action.


Asunto(s)
Embrión no Mamífero , Hígado Graso , Plaguicidas , Triglicéridos , Pez Cebra , Animales , Hígado Graso/inducido químicamente , Embrión no Mamífero/efectos de los fármacos , Triglicéridos/metabolismo , Plaguicidas/toxicidad , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga
18.
mSystems ; 9(9): e0084924, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39166875

RESUMEN

Engineering identical genetic circuits into different species typically results in large differences in performance due to the unique cellular environmental context of each host, a phenomenon known as the "chassis-effect" or "context-dependency". A better understanding of how genomic and physiological contexts underpin the chassis-effect will improve biodesign strategies across diverse microorganisms. Here, we combined a pangenomic-based gene expression analysis with quantitative measurements of performance from an engineered genetic inverter device to uncover how genome structure and function relate to the observed chassis-effect across six closely related Stutzerimonas hosts. Our results reveal that genome architecture underpins divergent responses between our chosen non-model bacterial hosts to the engineered device. Specifically, differential expression of the core genome, gene clusters shared between all hosts, was found to be the main source of significant concordance to the observed differential genetic device performance, whereas specialty genes from respective accessory genomes were not significant. A data-driven investigation revealed that genes involved in denitrification and components of trans-membrane transporter proteins were among the most differentially expressed gene clusters between hosts in response to the genetic device. Our results show that the chassis-effect can be traced along differences among the most conserved genome-encoded functions and that these differences create a unique biodesign space among closely related species.IMPORTANCEContemporary synthetic biology endeavors often default to a handful of model organisms to host their engineered systems. Model organisms such as Escherichia coli serve as attractive hosts due to their tractability but do not necessarily provide the ideal environment to optimize performance. As more novel microbes are domesticated for use as biotechnology platforms, synthetic biologists are urged to explore the chassis-design space to optimize their systems and deliver on the promises of synthetic biology. The consequences of the chassis-effect will therefore only become more relevant as the field of biodesign grows. In our work, we demonstrate that the performance of a genetic device is highly dependent on the host environment it operates within, promoting the notion that the chassis can be considered a design variable to tune circuit function. Importantly, our results unveil that the chassis-effect can be traced along similarities in genome architecture, specifically the shared core genome. Our study advocates for the exploration of the chassis-design space and is a step forward to empowering synthetic biologists with knowledge for more efficient exploration of the chassis-design space to enable the next generation of broad-host-range synthetic biology.


Asunto(s)
Genoma Bacteriano , Genoma Bacteriano/genética , Pseudomonas stutzeri/genética , Pseudomonas stutzeri/metabolismo , Biología Sintética/métodos , Familia de Multigenes/genética , Ingeniería Genética/métodos , Redes Reguladoras de Genes , Regulación Bacteriana de la Expresión Génica , Genómica
19.
R Soc Open Sci ; 11(6): 240042, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39092142

RESUMEN

The seafloor is inhabited by a large number of benthic invertebrates, and their importance in mediating carbon mineralization and biogeochemical cycles is recognized. However, the majority of fauna live below the sediment surface, so most means of survey rely on destructive sampling methods that are limited to documenting species presence rather than event driven activity and functionally important aspects of species behaviour. We have developed and tested a laboratory-based three-dimensional acoustic coring system that is capable of non-invasively visualizing the presence and activity of invertebrates within the sediment matrix. Here, we present reconstructed three-dimensional acoustic images of the sediment profile, with strong backscatter revealing the presence and position of individual benthic organisms. These data were used to train a three-dimensional convolutional neural network model and, using a combination of data augmentation and data correction techniques, we were able to identify individual species with an 88% accuracy. Combining three-dimensional acoustic coring with deep learning forms an effective and non-invasive means of providing detailed mechanistic information of in situ species-sediment interactions, opening new opportunities to quantify species-specific contributions to ecosystems.

20.
iScience ; 27(8): 110426, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39108737

RESUMEN

The regenerative functions associated with cytokines and growth factors have immense therapeutic potential; however, their poor pharmacokinetics, resulting from structural features, hinder their effectiveness. In this study, we aimed to enhance the pharmacokinetics of growth factors by designing receptor-binding macrocyclic peptides through in vitro mRNA display and grafting them into loops of immunoglobulin's crystallizable region (Fc). As a model, we developed peptide-grafted Fc proteins with hepatocyte growth factor (HGF) functionality that exhibited a prolonged circulation half-life and could be administered subcutaneously. The Fc-based HGF mimetic alleviated liver fibrosis in a mouse model fed a choline-deficient high-fat diet, which induces hepatic features of non-alcoholic steatohepatitis, including fibrosis, showcasing its potential as a therapeutic intervention. This study provides a basis for developing growth factor and cytokine mimetics with improved pharmacokinetics, expanding their therapeutic applications.

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