Gut Microbes. 2023 Jan-Dec;15(1):2177488. doi: 10.1080/19490976.2023.2177488.

ABSTRACT

The human gut virome has been increasingly explored in recent years. However, nearly all virome-sequencing efforts rely solely on fecal samples and few studies leverage multiomic approaches to investigate phage-host relationships. Here, we combine metagenomics, metaviromics, and metatranscriptomics to study virome-bacteriome interactions at the colonic mucosal-luminal interface in a cohort of three individuals with inflammatory bowel disease; non-IBD controls were not included in this study. We show that the mucosal viral population is distinct from the stool virome and houses abundant crAss-like phages that are undetectable by fecal sampling. Through viral protein prediction and metatranscriptomic analysis, we explore viral gene transcription, prophage activation, and the relationship between the presence of integrase and temperate phages in IBD subjects. We also show the impact of deep sequencing on virus recovery and offer guidelines for selecting optimal sequencing depths in future metaviromic studies. Systems biology approaches such as those presented in this report will enhance our understanding of the human virome and its interactions with our microbiome and our health.

PMID:36823020 | DOI:10.1080/19490976.2023.2177488

Antiviral Res. 2023 Feb 21:105560. doi: 10.1016/j.antiviral.2023.105560. Online ahead of print.

ABSTRACT

Venezuelan equine encephalitis virus (VEEV) is an alphavirus transmitted by mosquitos that can cause a febrile illness and induce severe neurological complications in humans and equine populations. Currently there are no FDA approved vaccines or antiviral treatments to combat VEEV. Proteomic techniques were utilized to create an interactome of the E1 fusion glycoprotein of VEEV. VEEV E1 interacted with a number of cellular chaperone proteins including protein disulfide isomerase family A member 6 (PDIa6). PDI inhibition through LOC14 and/or nitazoxanide treatment effectively decreased production of VEEV and other alphaviruses in vitro, including eastern equine encephalitis virus, Sindbis virus, and chikungunya virus. Decreased oxidoreductive capabilities of PDIs through LOC14 or nitazoxanide treatment impacted both early and late events in viral replication, including the production of non-infectious virions and decreased VEEV E1 disulfide bond formation. Results from this study identified PDIs as critical regulators of alphavirus replication and potential therapeutic targets.

PMID:36822370 | DOI:10.1016/j.antiviral.2023.105560

Drug Discov Today. 2023 Feb 21:103540. doi: 10.1016/j.drudis.2023.103540. Online ahead of print.

ABSTRACT

Serial analysis of circulating tumor DNA (ctDNA) over the disease course is emerging as a prognostic, predictive and patient-monitoring biomarker. In the metastatic setting, several multigene ctDNA assays have been approved or recommended by regulatory organizations for personalized targeted therapy, especially for lung cancer. By contrast, in nonmetastatic disease, detection of ctDNA resulting from minimal residual disease (MRD) following multimodal treatment with curative intent presents major technical challenges. Several studies using tumor genotyping-informed serial ctDNA profiling have provided promising findings on the sensitivity and specificity of ctDNA in predicting the risk of recurrence. We discuss progress, limitations and future perspectives relating to the use of ctDNA as a biomarker to guide targeted therapy in metastatic disease, as well as the use of ctDNA MRD detection to guide adjuvant treatment in the nonmetastatic setting. Teaser: Noninvasive analysis of circulating tumor DNA (ctDNA) in patients with metastatic or early-stage disease is transforming the clinical care of cancer patients by guiding meaningful multimodal treatment.

PMID:36822363 | DOI:10.1016/j.drudis.2023.103540

Am J Pathol. 2023 Feb 21:S0002-9440(23)00051-2. doi: 10.1016/j.ajpath.2023.02.003. Online ahead of print.

ABSTRACT

Retinopathy of prematurity (ROP), a blinding condition affecting preterm infants, is an interruption of retinal vascular maturation which is incomplete when born preterm birth. Although ROP demonstrates delayed onset following preterm birth, representing a window for therapeutic intervention, we cannot cure or prevent this disease. The in-utero environment, including placental function, is increasingly recognized for contributions to preterm infant disease risk. Herein, we identify a protective association between acute placental inflammation and preterm infant ROP development using logistic regression, with the most significant association found for infants without gestational exposure to maternal preeclampsia and those with earlier preterm birth. Expression analysis of proteins with described ROP risk associations demonstrates significantly decreased placental HTRA1 and FABP4 protein expression for infants with acute placental inflammation compared to those without. Within the post-natal peripheral circulation, HTRA1 and VEGFA demonstrate inverse longitudinal trends for infants born in the presence compared to absence of acute placental inflammation. An agnostic approach, including whole transcriptome and differential methylation placental analysis, further identifies novel mediators and pathways that may underly protection. Taken together, these data build on emerging literature showing a protective association between acute placental inflammation and ROP development and identifies novel mechanisms that may inform postnatal risk associations in preterm infants.

PMID:36822266 | DOI:10.1016/j.ajpath.2023.02.003

ACS Chem Neurosci. 2023 Feb 23. doi: 10.1021/acschemneuro.2c00783. Online ahead of print.

ABSTRACT

The α7 nicotinic acetylcholine receptor (α7nAChR) mediates signaling in the central nervous system and cholinergic anti-inflammatory pathways. Ivermectin is a positive allosteric modulator of a full-length α7nAChR and an agonist of the α7nAChR construct containing transmembrane (TMD) and intracellular (ICD) domains, but structural insights of the binding have not previously been determined. Here, combining nuclear magnetic resonance as a primary experimental tool with Rosetta comparative modeling and molecular dynamics simulations, we have revealed details of ivermectin binding to the α7nAChR TMD + ICD and corresponding structural changes in an ivermectin-induced desensitized state. Ivermectin binding was stabilized predominantly by hydrophobic interactions from interfacial residues between adjacent subunits near the extracellular end of the TMD, where the inter-subunit gap was substantially expanded in comparison to the apo structure. The ion-permeation pathway showed a profile distinctly different from the resting-state profile but similar to profiles of desensitized α7nAChR. The ICD also exhibited structural changes, including reorientation of the MX and h3 helices relative to the channel axis. The resulting structures of the α7nAChR TMD + ICD in complex with ivermectin provide opportunities for discovering new modulators of therapeutic potential and exploring the structural basis of cytoplasmic signaling under different α7nAChR functional states.

PMID:36821490 | DOI:10.1021/acschemneuro.2c00783

ACS Nano. 2023 Feb 23. doi: 10.1021/acsnano.2c12503. Online ahead of print.

ABSTRACT

The ability to engineer synthetic polymers with the same structural precision as biomacromolecules is crucial to enable the de novo design of robust nanomaterials with biomimetic function. Peptoids, poly(N-substituted) glycines, are a highly controllable bio-inspired polymer family that can assemble into a variety of functional, crystalline nanostructures over a wide range of sequences. Extensive investigation on the molecular packing in these lattices has been reported; however, many key atomic-level details of the molecular structure remain underexplored. Here, we use cryo-TEM 3D reconstruction to directly visualize the conformation of an individual polymer chain within a peptoid nanofiber lattice in real space at 3.6 Å resolution. The backbone in the N-decylglycine hydrophobic core is shown to clearly adopt an extended, all-cis-sigma strand conformation, as previously suggested in many peptoid lattice models. We also show that packing interactions (covalent and noncovalent) at the solvent-exposed N-termini have a dominant impact on the local chain ordering and hence the ability of the chains to pack into well-ordered lattices. Peptoids in pure water form fibers with limited growth in the a direction (<14 molecules in width), whereas in the presence of formamide, they grow to over microns in length in the a direction. This dependence points to the significant role of the chain terminus in determining the long-range order in the packing of peptoid lattices and provides an opportunity to modulate lattice stability and nanoscale morphology by the addition of exogenous small molecules. These findings help resolve a major challenge in the de novo structure-based design of sequence-defined biomimetic nanostructures based on crystalline domains and should accelerate the design of functional nanostructures.

PMID:36821346 | DOI:10.1021/acsnano.2c12503

Geroscience. 2023 Feb 23. doi: 10.1007/s11357-023-00750-4. Online ahead of print.

ABSTRACT

Sex differences in muscle aging are poorly understood, but could be crucial for the optimization of sarcopenia-related interventions. To gain insight into potential sex differences in muscle aging, we recruited young (23 ± 2 years, 13 males and 13 females) and old (80 ± 3.5 years, 28 males and 26 females) participants. Males and females in both groups were highly matched, and vastus lateralis muscle parameters of old versus young participants were compared for each sex separately, focusing on gene expression. The overall gene expression profiles separated the sexes, but similar gene expression patterns separated old from young participants in males and females. Genes were indeed regulated in the same direction in both sexes during aging; however, the magnitude of differential expression was sex specific. In males, oxidative phosphorylation was the top-ranked differentially expressed process, and in females, this was cell growth mediated by AKT signaling. Findings from RNA-seq data were studied in greater detail using alternative approaches. In addition, we confirmed our data using publicly available data from three independent human studies. In conclusion, top-ranked pathways differ between males and females, but were present and altered in the same direction in both sexes. We conclude that the same processes are associated with skeletal muscle aging in males and females, but the differential expression of those processes in old vs. young participants is sex specific.

PMID:36820956 | DOI:10.1007/s11357-023-00750-4

Elife. 2023 Feb 23;12:e86893. doi: 10.7554/eLife.86893.

ABSTRACT

PMID:36820823 | DOI:10.7554/eLife.86893

Microlife. 2023 Feb 6;4:uqad006. doi: 10.1093/femsml/uqad006. eCollection 2023.

ABSTRACT

Tuberculosis, a deadly infectious lung disease caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of bacterial disease-related deaths worldwide. Mtb reprograms and disables key antibacterial response pathways, many of which are regulated by epigenetic mechanisms that control the accessibility of chromatin to the transcriptional machinery. Recent reports suggest that host phosphatases, such as PPM1A, contribute to regulating chromatin accessibility during bacterial infections. However, changes in genome-wide chromatin accessibility during Mtb infection and whether PPM1A plays a role in this process remains unknown. Herein, we use combinatorial chromatin accessibility (ATAC-seq) and transcriptomic (RNA-seq) profiling of wild-type, PPM1A knockout and PPM1A overexpressing macrophages to demonstrate that Mtb infection induces global chromatin remodelling consistent with changes in gene expression. The strongest concordant changes to chromatin accessibility and gene expression triggered by Mtb infection were enriched for genes involved in type I interferon (IFN) signalling pathways. A panel of 15 genes with the strongest concordant changes in chromatin accessibility and gene expression were validated to be significantly upregulated in Mtb-infected human monocyte-derived macrophages. PPM1A expression affects chromatin accessibility profiles during Mtb infection that are reflected in the total number, chromosome location, and directionality of change. Transcription factor binding motif analysis revealed enrichment for transcription factors involved in the type I IFN pathway during Mtb infection, including members of the IRF, MEF2, and AP-1 families. Our study shows that altered type I IFN responses in Mtb-infected macrophages occur due to genome-wide changes in chromatin accessibility, and that PPM1A could influence a subset of these signatures.

PMID:36820061 | PMC:PMC9936219 | DOI:10.1093/femsml/uqad006

PeerJ. 2023 Feb 15;11:e14729. doi: 10.7717/peerj.14729. eCollection 2023.

ABSTRACT

Mirror exposure elicits a wide range of behavioral responses, some of which have been considered as part of possible evidence of mirror self-recognition (MSR). These responses can range from social behaviors, indicating that an animal considers its own reflection as a conspecific, to mirror-guided and self-directed actions. Evidence of MSR has been found categorically in only a few species, such as in magpies, chimpanzees, horses, and elephants. Evidence in corvids is currently debated due to inconsistent findings. In this study, we investigated the reaction of Eurasian jays when presenting them with three mirror-stimulation tasks. Based on the overall behavioral patterns across these three tasks, conclusions about birds' understanding of a reflective surface, and their perception of the reflection as either themselves or as a conspecific, appear premature. We highlight how the high neophobia of corvids and other methodological constraints might have hindered the likelihood to approach and explore a mirror, preventing the emergence of behaviors typically associated with MSR. Furthermore, we discuss how motivational factors, methodological constraints and species differences should be considered when interpreting behavioral responses to mirrors.

PMID:36819998 | PMC:PMC9938653 | DOI:10.7717/peerj.14729

Front Microbiol. 2023 Feb 1;14:1077106. doi: 10.3389/fmicb.2023.1077106. eCollection 2023.

ABSTRACT

The rise and extensive spread of antimicrobial resistance (AMR) has become a growing concern, and a threat to the environment and human health globally. The majority of current AMR identification methods used in clinical setting are based on traditional microbiology culture-dependent techniques which are time-consuming or expensive to be implemented, thus appropriate antibiotic stewardship is provided retrospectively which means the first line of treatment is to hope that a broad-spectrum antibiotic works. Hence, culture-independent and single-cell technologies are needed to allow for rapid detection and identification of antimicrobial-resistant bacteria and to support a more targeted and effective antibiotic therapy preventing further development and spread of AMR. In this study, for the first time, a non-destructive phenotyping method of optical photothermal infrared (O-PTIR) spectroscopy, coupled with deuterium isotope probing (DIP) and multivariate statistical analysis was employed as a metabolic fingerprinting approach to detect AMR in Uropathogenic Escherichia coli (UPEC) at both single-cell and population levels. Principal component-discriminant function analysis (PC-DFA) of FT-IR and O-PTIR spectral data showed clear clustering patterns as a result of distinctive spectral shifts (C-D signature peaks) originating from deuterium incorporation into bacterial cells, allowing for rapid detection and classification of sensitive and resistant isolates at the single-cell level. Furthermore, the single-frequency images obtained using the C-D signature peak at 2,163 cm-1 clearly displayed the reduced ability of the trimethoprim-sensitive strain for incorporating deuterium when exposed to this antibiotic, compared to the untreated condition. Hence, the results of this study indicated that O-PTIR can be employed as an efficient tool for the rapid detection of AMR at the single-cell level.

PMID:36819022 | PMC:PMC9929359 | DOI:10.3389/fmicb.2023.1077106

Evid Based Complement Alternat Med. 2023 Feb 9;2023:1430839. doi: 10.1155/2023/1430839. eCollection 2023.

ABSTRACT

BACKGROUND: Drug resistance is currently possible anywhere in the world. Due to the discovery of antimicrobials, medicine, and health have made tremendous advances over the past several decades.

AIM: This research evaluated the antimicrobial and cytotoxicity effects of green synthesis of copper oxide nanoparticles (CuO NPs) on Lactobacillus acidophilus and human embryonic kidney 293 cells (HEK). Method and Materials. Propolis was sampled and extracted. Green synthesis of CuO NPs was synthesized and characterized using SEM, TEM, DLS, BET, and zeta potential methods. L. acidophilus (ATCC 4356) was used, and the antimicrobial tests were carried out at different concentrations (10≥ mg/ml). Moreover, the cytotoxicity was evaluated using an MTT assay on human embryonic kidney 293 cells (HEK).

RESULTS: Synthesized CuO NPs using propolis extracts from Khalkhal (sample 1) and Gillan (sample 2) showed -13.2 and -14.4 mV, respectively. The hydrodynamic sizes of well-dispersed samples 1 and 2 were 3124.9 nm and 1726.7 nm, respectively. According to BET analysis, samples 1 and 2 had 5.37 and 8.45 m2/g surface area, respectively. The surface area was decreased due to the addition of propolis extract, and the pore size was increased. CuO NPs of samples 1 and 2 were visible on SEM images with diameters ranging from 75 to 145 nm and 120 to 155 nm, respectively. Based on TEM analysis, the size of CuO particles was increased in samples 1 and 2. CuO NPs particles had narrow size distributions with evenly dispersed NPs on all sides. The cell viability of the CuO NPs of samples 1 and 2 after 24, 48, and 72 hours was greater than 50%. As a result of the MIC and MBC tests, it was determined that samples 1 and 2 had the same effect against L. acidophilus (0.0024 mg/ml). Biofilm formation and degradation of sample 1 were more efficient against L. acidophilus.

CONCLUSION: There was no evidence of cytotoxicity in the samples. In addition, results showed that the green synthesized CuO NPs from Khalkhal propolis were effective against L. acidophilus. Thus, the green synthesized CuO NPs from Khalkhal propolis were the best candidates for clinical application.

PMID:36818232 | PMC:PMC9935807 | DOI:10.1155/2023/1430839

Front Mol Biosci. 2023 Feb 2;10:1122201. doi: 10.3389/fmolb.2023.1122201. eCollection 2023.

ABSTRACT

To identify novel solutions to improve rice yield under rising temperatures, molecular components of thermotolerance must be better understood. Alternative splicing (AS) is a major post-transcriptional mechanism impacting plant tolerance against stresses, including heat stress (HS). AS is largely regulated by splicing factors (SFs) and recent studies have shown their involvement in temperature response. However, little is known about the splicing networks between SFs and AS transcripts in the HS response. To expand this knowledge, we constructed a co-expression network based on a publicly available RNA-seq dataset that explored rice basal thermotolerance over a time-course. Our analyses suggest that the HS-dependent control of the abundance of specific transcripts coding for SFs might explain the widespread, coordinated, complex, and delicate AS regulation of critical genes during a plant's inherent response to extreme temperatures. AS changes in these critical genes might affect many aspects of plant biology, from organellar functions to cell death, providing relevant regulatory candidates for future functional studies of basal thermotolerance.

PMID:36818043 | PMC:PMC9932781 | DOI:10.3389/fmolb.2023.1122201

Comput Struct Biotechnol J. 2023 Jan 31;21:1372-1382. doi: 10.1016/j.csbj.2023.01.043. eCollection 2023.

ABSTRACT

Cancer progression is linked to gene-environment interactions that alter cellular homeostasis. The use of biomarkers as early indicators of disease manifestation and progression can substantially improve diagnosis and treatment. Large omics datasets generated by high-throughput profiling technologies, such as microarrays, RNA sequencing, whole-genome shotgun sequencing, nuclear magnetic resonance, and mass spectrometry, have enabled data-driven biomarker discoveries. The identification of differentially expressed traits as molecular markers has traditionally relied on statistical techniques that are often limited to linear parametric modeling. The heterogeneity, epigenetic changes, and high degree of polymorphism observed in oncogenes demand biomarker-assisted personalized medication schemes. Deep learning (DL), a major subunit of machine learning (ML), has been increasingly utilized in recent years to investigate various diseases. The combination of ML/DL approaches for performance optimization across multi-omics datasets produces robust ensemble-learning prediction models, which are becoming useful in precision medicine. This review focuses on the recent development of ML/DL methods to provide integrative solutions in discovering cancer-related biomarkers, and their utilization in precision medicine.

PMID:36817954 | PMC:PMC9929204 | DOI:10.1016/j.csbj.2023.01.043

Health Data Sci. 2022;2022:0002. doi: 10.34133/hds.0002. Epub 2022 Dec 27.

ABSTRACT

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARB), the most commonly prescribed antihypertensive medications, counter renin-angiotensin-aldosterone system (RAAS) activation via induction of angiotensin-converting enzyme 2 (ACE2) expression. Considering that ACE2 is the functional receptor for SARS-CoV-2 entry into host cells, the association of ACEi and ARB with COVID-19 outcomes needs thorough evaluation.

METHODS: We conducted retrospective analyses using both unmatched and propensity score (PS)-matched cohorts on electronic health records (EHRs) to assess the impact of RAAS inhibitors on the risk of receiving invasive mechanical ventilation (IMV) and 30-day mortality among hospitalized COVID-19 patients. Additionally, we investigated the immune cell gene expression profiles of hospitalized COVID-19 patients with prior use of antihypertensive treatments from an observational prospective cohort.

RESULTS: The retrospective analysis revealed that there was no increased risk associated with either ACEi or ARB use. In fact, the use of ACEi showed decreased risk for mortality. Survival analyses using PS-matched cohorts suggested no significant relationship between RAAS inhibitors with a hospital stay and in-hospital mortality compared to non-RAAS medications and patients not on antihypertensive medications. From the analysis of gene expression profiles, we observed a noticeable up-regulation in the expression of 1L1R2 (an anti-inflammatory receptor) and RETN (an immunosuppressive marker) genes in monocytes among prior users of ACE inhibitors.

CONCLUSION: Overall, the findings do not support the discontinuation of ACEi or ARB treatment and suggest that ACEi may moderate the COVID-19 hyperinflammatory response.

PMID:36817759 | PMC:PMC9934012 | DOI:10.34133/hds.0002

Nat Phys. 2023;19(2):177-183. doi: 10.1038/s41567-022-01822-6. Epub 2022 Nov 21.

ABSTRACT

Animal organs exhibit complex topologies involving cavities and tubular networks, which underlie their form and function1-3. However, how topology emerges during the development of organ shape, or morphogenesis, remains elusive. Here we combine tissue reconstitution and quantitative microscopy to show that tissue topology and shape is governed by two distinct modes of topological transitions4,5. One mode involves the fusion of two separate epithelia and the other involves the fusion of two ends of the same epithelium. The morphological space is captured by a single control parameter that can be traced back to the relative rates of the two epithelial fusion modes. Finally, we identify a pharmacologically accessible pathway that regulates the frequency of two modes of epithelial fusion, and demonstrate the control of organoid topology and shape. The physical principles uncovered here provide fundamental insights into the self-organization of complex tissues6.

PMID:36815964 | PMC:PMC9928582 | DOI:10.1038/s41567-022-01822-6

Front Bioeng Biotechnol. 2023 Feb 3;11:1006066. doi: 10.3389/fbioe.2023.1006066. eCollection 2023.

ABSTRACT

Osteoarthritis (OA) is a debilitating joint disease characterized by articular cartilage degradation, inflammation and pain. An extensive range of in vivo and in vitro studies evidences that mechanical loads induce changes in chondrocyte gene expression, through a process known as mechanotransduction. It involves cascades of complex molecular interactions that convert physical signals into cellular response(s) that favor either chondroprotection or cartilage destruction. Systematic representations of those interactions can positively inform early strategies for OA management, and dynamic modelling allows semi-quantitative representations of the steady states of complex biological system according to imposed initial conditions. Yet, mechanotransduction is rarely integrated. Hence, a novel mechano-sensitive network-based model is proposed, in the form of a continuous dynamical system: an interactome of a set of 118 nodes, i.e., mechano-sensitive cellular receptors, second messengers, transcription factors and proteins, related among each other through a specific topology of 358 directed edges is developed. Results show that under physio-osmotic initial conditions, an anabolic state is reached, whereas initial perturbations caused by pro-inflammatory and injurious mechanical loads leads to a catabolic profile of node expression. More specifically, healthy chondrocyte markers (Sox9 and CITED2) are fully expressed under physio-osmotic conditions, and reduced under inflammation, or injurious loadings. In contrast, NF-κB and Runx2, characteristic of an osteoarthritic chondrocyte, become activated under inflammation or excessive loading regimes. A literature-based evaluation shows that the model can replicate 94% of the experiments tested. Sensitivity analysis based on a factorial design of a treatment shows that inflammation has the strongest influence on chondrocyte metabolism, along with a significant deleterious effect of static compressive loads. At the same time, anti-inflammatory therapies appear as the most promising ones, though the restoration of structural protein production seems to remain a major challenge even in beneficial mechanical environments. The newly developed mechano-sensitive network model for chondrocyte activity reveals a unique potential to reflect load-induced chondroprotection or articular cartilage degradation in different mechano-chemical-environments.

PMID:36815875 | PMC:PMC9936426 | DOI:10.3389/fbioe.2023.1006066

Biophys J. 2022 Dec 6;121(23):4543-4559. doi: 10.1016/j.bpj.2022.10.035. Epub 2022 Oct 29.

ABSTRACT

Asymmetric distributions of peripheral membrane proteins define cell polarity across all kingdoms of life. Non-linear positive feedback on membrane binding is essential to amplify and stabilize these asymmetries, but how specific molecular sources of non-linearity shape polarization dynamics remains poorly understood. Here we show that the ability to oligomerize, which is common to many peripheral membrane proteins, can play a profound role in shaping polarization dynamics in simple feedback circuits. We show that size-dependent binding avidity and mobility of membrane-bound oligomers endow polarity circuits with several key properties. Size-dependent membrane binding avidity confers a form of positive feedback on the accumulation of oligomer subunits. Although insufficient by itself, this sharply reduces the amount of additional feedback required for spontaneous emergence and stable maintenance of polarized states. Size-dependent oligomer mobility makes symmetry breaking and stable polarity more robust with respect to variation in subunit diffusivities and cell sizes, and slows the approach to a final stable spatial distribution, allowing cells to "remember" polarity boundaries imposed by transient external cues. Together, these findings reveal how oligomerization of peripheral membrane proteins can provide powerful and highly tunable sources of non-linear feedback in biochemical circuits that govern cell surface polarity. Given its prevalence and widespread involvement in cell polarity, we speculate that self-oligomerization may have provided an accessible path to evolving simple polarity circuits.

PMID:36815706 | DOI:10.1016/j.bpj.2022.10.035

Comput Struct Biotechnol J. 2023 Feb 1;21:1262-1271. doi: 10.1016/j.csbj.2023.01.044. eCollection 2023.

ABSTRACT

Cancer cells metabolize glucose through metabolic pathways that differ from those used by healthy and differentiated cells. In particular, tumours have been shown to consume more glucose than their healthy counterparts and to use anaerobic metabolic pathways, even under aerobic conditions. Nevertheless, scientists have still not been able to explain why cancer cells evolved to present an altered metabolism and what evolutionary advantage this might provide them. Experimental and computational models have been increasingly used in recent years to understand some of these biological questions. Multicellular tumour spheroids are effective experimental models as they replicate the initial stages of avascular solid tumour growth. Furthermore, these experiments generate data which can be used to calibrate and validate computational studies that aim to simulate tumour growth. Hybrid models are of particular relevance in this field of research because they model cells as individual agents while also incorporating continuum representations of the substances present in the surrounding microenvironment that may participate in intracellular metabolic networks as concentration or density distributions. Henceforth, in this review, we explore the potential of computational modelling to reveal the role of metabolic reprogramming in tumour growth.

PMID:36814723 | PMC:PMC9939553 | DOI:10.1016/j.csbj.2023.01.044

Front Bioeng Biotechnol. 2023 Feb 6;11:1118702. doi: 10.3389/fbioe.2023.1118702. eCollection 2023.

ABSTRACT

Advances in synthetic biology and genetic engineering are bringing into the spotlight a wide range of bio-based applications that demand better sensing and control of biological behaviours. Transcription factor (TF)-based biosensors are promising tools that can be used to detect several types of chemical compounds and elicit a response according to the desired application. However, the wider use of this type of device is still hindered by several challenges, which can be addressed by increasing the current metabolite-activated transcription factor knowledge base, developing better methods to identify new transcription factors, and improving the overall workflow for the design of novel biosensor circuits. These improvements are particularly important in the bioproduction field, where researchers need better biosensor-based approaches for screening production-strains and precise dynamic regulation strategies. In this work, we summarize what is currently known about transcription factor-based biosensors, discuss recent experimental and computational approaches targeted at their modification and improvement, and suggest possible future research directions based on two applications: bioproduction screening and dynamic regulation of genetic circuits.

PMID:36814719 | PMC:PMC9939652 | DOI:10.3389/fbioe.2023.1118702