J Physiol. 2023 Aug 28. doi: 10.1113/JP284422. Online ahead of print.

ABSTRACT

Living organisms are multiscale complex systems that have evolved high degrees of multifunctionality and redundancy in the structure-function relationship. A number of factors, only in part determined genetically, affect the jobs of proteins. The overall structural organization confers unique molecular properties that provide the potential to perform a pattern of activities, some of which are co-opted by specific environments. The variety of multifunctional proteins is expanding, but most cases are handled individually and according to the still dominant 'one structure-one function' approach, which relies on the attribution of canonical names typically referring to the first task identified for a given protein. The present topical review focuses on the multifunctionality of ion channels as a paradigmatic example. Mounting evidence reports the ability of many ion channels (including members of voltage-dependent, ligand-gated and transient receptor potential families) to exert biological effects independently of their ion conductivity. 'Functionally based' nomenclature (the practice of naming a protein or family of proteins based on a single purpose) is a conceptual bias for three main reasons: (i) it increases the amount of ambiguity, deceiving our understanding of the multiple contributions of biomolecules that is the heart of the complexity; (ii) it is in stark contrast to protein evolution dynamics, largely based on multidomain arrangement; and (iii) it overlooks the crucial role played by the microenvironment in adjusting the actions of cell structures and in tuning protein isoform diversity to accomplish adaptational requirements. Biological information in protein physiology is distributed among different entwined layers working as the primary 'locus' of natural selection and of evolutionary constraints.

PMID:37635695 | DOI:10.1113/JP284422

Neuroimage. 2023 Aug 25:120346. doi: 10.1016/j.neuroimage.2023.120346. Online ahead of print.

ABSTRACT

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. However, the AD mechanism has not yet been fully elucidated to date, hindering the development of effective therapies. In our work, we perform a brain imaging genomics study to link genetics, single-cell gene expression data, tissue-specific gene expression data, brain imaging-derived volumetric endophenotypes, and AD diagnosis to discover potential underlying neurobiological pathways for AD. To do so, we perform brain-wide genome-wide colocalization analyses to integrate multidimensional imaging genomic biobank data. Specifically, we use (1) the individual-level imputed genotyping data and magnetic resonance imaging (MRI) data from the UK Biobank, (2) the summary statistics of the genome-wide association study (GWAS) from multiple European ancestry cohorts, and (3) the tissue-specific cis-expression quantitative trait loci (cis-eQTL) summary statistics from the GTEx project. We apply a Bayes factor colocalization framework and mediation analysis to these multi-modal imaging genomic data. As a result, we derive the brain regional level GWAS summary statistics for 145 brain regions with 482,831 single nucleotide polymorphisms (SNPs) followed by posthoc functional annotations. Our analysis yields the discovery of a potential AD causal pathway from a systems biology perspective: the SNP chr10:124165615:G>A (rs6585827) mutation upregulates the expression of BTBD16 gene in oligodendrocytes, a specialized glial cells, in the brain cortex, leading to a reduced risk of volumetric loss in the entorhinal cortex, resulting in the protective effect on AD. We substantiate our findings with multiple evidence from existing imaging, genetic and genomic studies in AD literature. Our study connects genetics, molecular and cellular signatures, regional brain morphologic endophenotypes, and AD diagnosis, providing new insights into the mechanistic understanding of the disease. Our findings can provide valuable guidance for subsequent therapeutic target identification and drug discovery in AD.

PMID:37634885 | DOI:10.1016/j.neuroimage.2023.120346

Protein J. 2023 Aug 27. doi: 10.1007/s10930-023-10149-x. Online ahead of print.

ABSTRACT

INTRODUCTION: L-asparaginase (also known as L-ASNase) is a crucial therapeutic enzyme that is widely used in treatment of ALL (acute lymphoblastic leukemia) as a chemotherapeutic drug. Besides, this enzyme is used in the food industry as a food processing reagent to reduce the content of acrylamide in addition to the clinical industry. The improvement of activity and kinetic parameters of the L-ASNase enzyme may lead to higher efficiency resulting in practical achievement. In order to achieve this goal, we chosen glycine residue in position 88 as a potential mutation with advantageous outcomes.

METHOD: In this study, firstly to find the appropriate mutation on glycine 88, various in silico analyses, such as MD simulation and molecular docking, were carried out. Then, the rational design was adopted as the best strategy for molecular modifications of the enzyme to improve its enzymatic properties.

RESULT: Our in silico findings show that the four mutations G88Q, G88L, G88K, and G88A may be able to increase L-ASNase's asparaginase activity. The catalytic efficiency of each enzyme (kcat/Km) is the most important feature for comparing the catalytic activity of the mutants with the wild type form. The laboratory experiments showed that the kcat/Km for the G88Q mutant is 36.32% higher than the Escherichia coli K12 ASNase II (wild type), which suggests that L-ASNase activity is improved at lower concentration of L-ASN. Kinetic characterization of the mutants L-ASNase activity confirmed the high turnover rate (kcat) with ASN as substrate relative to the wild type enzyme.

CONCLUSION: In silico analyses and laboratory experiments demonstrated that the G88Q mutation rather than other mutation (G88L, G88K, and G88A) could improve the kinetics of L-ASNase.

PMID:37634213 | DOI:10.1007/s10930-023-10149-x

BMC Med. 2023 Aug 26;21(1):326. doi: 10.1186/s12916-023-03023-1.

ABSTRACT

BACKGROUND: Moderate and late preterm (MLPT) birth accounts for the vast majority of preterm births, which is a global public health problem. The association between MLPT and neurobehavioral developmental delays in children and the underlying biological mechanisms need to be further revealed. The "placenta-brain axis" (PBA) provides a new perspective for gene regulation and risk prediction of neurodevelopmental delays in MLPT children.

METHODS: The authors performed multivariate logistic regression models between MLPT and children's neurodevelopmental outcomes, using data from 129 MLPT infants and 3136 full-term controls from the Ma'anshan Birth Cohort (MABC). Furthermore, the authors identified the abnormally regulated PBA-related genes in MLPT placenta by bioinformatics analysis of RNA-seq data and RT-qPCR verification on independent samples. Finally, the authors established the prediction model of neurodevelopmental delay in children with MLPT using multiple machine learning models.

RESULTS: The authors found an increased risk of neurodevelopmental delay in children with MLPT at 6 months, 18 months, and 48 months, especially in boys. Further verification showed that APOE and CST3 genes were significantly correlated with the developmental levels of gross-motor domain, fine-motor domain, and personal social domain in 6-month-old male MLPT children.

CONCLUSIONS: These findings suggested that there was a sex-specific association between MLPT and neurodevelopmental delays. Moreover, APOE and CST3 were identified as placental biomarkers. The results provided guidance for the etiology investigation, risk prediction, and early intervention of neurodevelopmental delays in children with MLPT.

PMID:37633927 | DOI:10.1186/s12916-023-03023-1

Plant Sci. 2023 Aug 24:111842. doi: 10.1016/j.plantsci.2023.111842. Online ahead of print.

ABSTRACT

Nitrogen is the most abundant element in the atmosphere and serves as the foundation block of life, including plants on earth. Unlike carbon fixation through photosynthesis, plants rely heavily on external supports to acquire nitrogen. To this end, plants have adapted various strategies such as forming mutualistic relationships with nitrogen-fixing bacteria and evolving a large regulatory network that includes multiple transporters, sensors, and transcription factors for fine-tuning nitrate sensing and signaling. Nodule Inception (NIN) and NIN-like protein (NLP) are central in this network by executing multiple functions such as initiating and regulating the nodule symbiosis for nitrogen fixation, acting as the intracellular sensor to monitor the nitrate fluctuations in the environment, and activating the transcription of nitrate-responsive genes for optimal nitrogen uptake, assimilation, and usage. The involvement of NLPs in intracellular nitrate binding and early nitrate responses highlight their pivotal role in the primary nitrate response (PNR). Genome-wide reprogramming in response to nitrate by NLP is highly transient and rapid, requiring regulation in a precise and dynamic manner. This review aims to summarize recent progress in the study of NIN/NLP for a better understanding of the molecular basis of their roles and regulations in nitrate sensing and signaling, with the hope of shedding light on increasing biological nitrogen fixation and improving nitrogen use efficiency (NUE) to minimize fertilizer input in agriculture.

PMID:37633494 | DOI:10.1016/j.plantsci.2023.111842

Curr Biol. 2023 Aug 16:S0960-9822(23)01046-1. doi: 10.1016/j.cub.2023.08.003. Online ahead of print.

ABSTRACT

In flowering plants, two fertilization products develop within the limited space of the seed: the embryo and the surrounding nutritive endosperm. The final size of the endosperm is modulated by the degree of embryo growth. In Arabidopsis thaliana, the endosperm expands rapidly after fertilization, but later gets invaded by the embryo that occupies most of the seed volume at maturity, surrounded by a single remaining aleurone-like endosperm layer.1,2,3,4 Embryo invasion is facilitated by the endosperm-expressed bHLH-type transcription factor ZHOUPI, which promotes weakening of endosperm cell walls.5,6 Endosperm elimination in zou mutants is delayed, and embryo growth is severely affected; the endosperm finally collapses around the dwarf embryo, causing the shriveled appearance of mature zou seeds.5,6,7 However, whether ZHOUPI facilitates mechanical endosperm destruction by the invading embryo or whether an active programmed cell death (PCD) process causes endosperm elimination has been subject to debate.2,8 Here we show that developmental PCD controlled by multiple NAC transcription factors in the embryo-adjacent endosperm promotes gradual endosperm elimination. Misexpressing the NAC transcription factor KIRA1 in the entire endosperm caused total endosperm elimination, generating aleurone-less mature seeds. Conversely, dominant and recessive higher-order NAC mutants led to delayed endosperm elimination and impaired cell corpse clearance. Promoting PCD in the zhoupi mutant partially rescued its embryo growth defects, while the endosperm in a zhoupi nac higher-order mutant persisted until seed desiccation. These data suggest that a combination of cell wall weakening and PCD jointly facilitates embryo invasion by an active auto-elimination of endosperm cells.

PMID:37633282 | DOI:10.1016/j.cub.2023.08.003

Mol Cell. 2023 Aug 17:S1097-2765(23)00607-X. doi: 10.1016/j.molcel.2023.08.001. Online ahead of print.

ABSTRACT

Histone H2B monoubiquitylation plays essential roles in chromatin-based transcriptional processes. A RING-type E3 ligase (yeast Bre1 or human RNF20/RNF40) and an E2 ubiquitin-conjugating enzyme (yeast Rad6 or human hRAD6A), together, precisely deposit ubiquitin on H2B K123 in yeast or K120 in humans. Here, we developed a chemical trapping strategy and successfully captured the transient structures of Bre1- or RNF20/RNF40-mediated ubiquitin transfer from Rad6 or hRAD6A to nucleosomal H2B. Our structures show that Bre1 and RNF40 directly bind nucleosomal DNA, exhibiting a conserved E3/E2/nucleosome interaction pattern from yeast to humans for H2B monoubiquitylation. We also find an uncanonical non-hydrophobic contact in the Bre1 RING-Rad6 interface, which positions Rad6 directly above the target H2B lysine residue. Our study provides mechanistic insights into the site-specific monoubiquitylation of H2B, reveals a critical role of nucleosomal DNA in mediating E3 ligase recognition, and provides a framework for understanding the cancer-driving mutations of RNF20/RNF40.

PMID:37633270 | DOI:10.1016/j.molcel.2023.08.001

J Reprod Immunol. 2023 Aug 16;159:104135. doi: 10.1016/j.jri.2023.104135. Online ahead of print.

ABSTRACT

Preeclampsia remains enigmatic and responsible for vast maternal and fetal morbidity and mortality worldwide. Our objective was to assess the strength of the effect of the 14 bp deletion/insertion polymorphism in exon 8 of the 3'UTR region of the human leukocyte antigen-G (HLA-G) gene on preeclampsia risk across different populations. A systematic review by a meta-analysis was performed to summarize the scattered epidemiologic evidence, which remains inconclusive and controversial. A systematic literature search according to the PRISMA guidelines was conducted to screen relevant publications. Odds ratio and corresponding 95% confidence interval were estimated to measure the magnitude of the association between this polymorphism and preeclampsia onset. Thirty studies comprising 9402 subjects were eligible. Pooled estimates suggested that both fetal and paternal insertion variants were significantly associated with increased odds of this disease. Nevertheless, the presence of the 14 bp insertion sequence in mothers does not seem to increase the risk of preeclampsia. Moreover, the results of subgroup analysis suggested that the fetal, maternal, and paternal polymorphism has a significant deleterious impact on the preeclampsia risk in the Asian population. In addition, the significant association between the paternal polymorphism and preeclampsia in primigravida was observed in the pooled estimation with a small sample size. By summarizing the amount of significant evidence, our study nominated this polymorphism as a potential biomarker for early risk stratification for Asians. Further large-scale validation is needed to establish fully solid and conclusive evidence for the impact of the insertion polymorphism on preeclampsia risk.

PMID:37633154 | DOI:10.1016/j.jri.2023.104135

Pathol Res Pract. 2023 Aug 22;249:154780. doi: 10.1016/j.prp.2023.154780. Online ahead of print.

ABSTRACT

Breast cancer has been among the most prominent cancers with high mortality. Currently most of the offered therapeutics are toxic; hence, less toxic therapeutic intervention is required. Here, we studied the molecular mechanisms of the effect of a phytoestrogen Emodin on estrogen receptor positive MCF-7 and negative MDA-MB-231 cells by carrying out a comprehensive network assessment. Differentially expressed microRNAs along with their previously identified differentially expressed mRNAs were analyzed through microarrays by using integrative systems biology approach. For each cell line miRNA-target gene networks were built, gene ontology and pathway enrichment analyses were performed, enrichment maps were constructed and the potential key genes, miRNAs and miRNA-gene interactions were studied.

PMID:37633004 | DOI:10.1016/j.prp.2023.154780

J Mol Neurosci. 2023 Aug 26. doi: 10.1007/s12031-023-02148-5. Online ahead of print.

ABSTRACT

Most neurodegenerative diseases are exacerbated by aging, with symptoms often worsening over time. Programmed cell death (PCD) is a controlled cell suicide mechanism that is essential for the stability, growth, and homeostasis of organisms. Understanding the effects of aging at the level of systems biology could lead to new therapeutic approaches for a broad spectrum of neurodegenerative diseases. In the absence of comprehensive functional studies on the relationship between PCD and aging of the prefrontal cortex, this study provides prefrontal brain biomarkers of aging associated with PCD that could open the way for improved therapeutic techniques for age-related neurodegenerative diseases. To this end, publicly available transcriptome data were subjected to bioinformatic analyses such as differential gene expression, functional enrichment, and the weighted gene coexpression network analysis (WGCNA). The diagnostic utility of the biomarkers was tested using a logistic regression-based prediction model. Three genes, namely BMP4, SGSH, and SLC11A2, were found to be aging biomarkers associated with PCD. Finally, a multifactorial regulatory network with interacting proteins, transcription factors (TFs), competing endogenous RNAs (ceRNAs), and microRNAs (miRNAs) was constructed around these biomarkers. The elements of this multifactorial regulatory network were mainly enriched in BMP signaling. Further exploration of these three biomarkers and their regulatory elements would enable the development of 3PM (predictive, preventive, and personalized) medicine for the treatment of age-related neurodegenerative diseases.

PMID:37632651 | DOI:10.1007/s12031-023-02148-5

Planta. 2023 Aug 26;258(4):71. doi: 10.1007/s00425-023-04227-8.

ABSTRACT

WHIRLY1 deficient barley plants surviving growth at high irradiance displayed increased non-radiative energy dissipation, enhanced contents of zeaxanthin and the flavonoid lutonarin, but no changes in α-tocopherol nor glutathione. Plants are able to acclimate to environmental conditions to optimize their functions. With the exception of obligate shade plants, they can adjust their photosynthetic apparatus and the morphology and anatomy of their leaves to irradiance. Barley (Hordeum vulgare L., cv. Golden Promise) plants with reduced abundance of the protein WHIRLY1 were recently shown to be unable to acclimatise important components of the photosynthetic apparatus to high light. Nevertheless, these plants did not show symptoms of photoinhibition. High-light (HL) grown WHIRLY1 knockdown plants showed clear signs of exposure to excessive irradiance such as a low epoxidation state of the violaxanthin cycle pigments and an early light saturation of electron transport. These responses were underlined by a very large xanthophyll cycle pool size and by an increased number of plastoglobules. Whereas zeaxanthin increased with HL stress, α-tocopherol, which is another lipophilic antioxidant, showed no response to excessive light. Also the content of the hydrophilic antioxidant glutathione showed no increase in W1 plants as compared to the wild type, whereas the flavone lutonarin was induced in W1 plants. HPLC analysis of removed epidermal tissue indicated that the largest part of lutonarin was presumably located in the mesophyll. Since lutonarin is a better antioxidant than saponarin, the major flavone present in barley leaves, it is concluded that lutonarin accumulated as a response to oxidative stress. It is also concluded that zeaxanthin and lutonarin may have served as antioxidants in the WHIRLY1 knockdown plants, contributing to their survival in HL despite their restricted HL acclimation.

PMID:37632541 | DOI:10.1007/s00425-023-04227-8

Vaccines (Basel). 2023 Jul 31;11(8):1302. doi: 10.3390/vaccines11081302.

ABSTRACT

Mycobacterium smegmatis (M.sm) is frequently used as an alternative model organism in Mycobacterium tuberculosis (M.tb) studies. While containing high sequence homology with M.tb, it is considered non-pathogenic in humans. As such it has been used to study M.tb and other infections in vivo and more recently been explored for potential therapeutic applications. A body of previous research has highlighted the potential of using genetically modified M.sm displaying rapid growth and unique immunostimulatory characteristics as an effective vaccine vector. Novel systems biology techniques can further serve to optimize these delivery constructs. In this article, we review recent advancements in vaccinomics tools that support the efficacy of a M.sm-based vaccine vector. Moreover, the integration of systems biology and molecular omics techniques in these pioneering studies heralds a potential accelerated pipeline for the development of next-generation recombinant vaccines against rapidly developing diseases.

PMID:37631870 | DOI:10.3390/vaccines11081302

Vaccines (Basel). 2023 Jul 25;11(8):1278. doi: 10.3390/vaccines11081278.

ABSTRACT

Plant virus nanoparticles (PVNPs) have garnered considerable interest as a promising nanotechnology approach to combat cancer. Owing to their biocompatibility, stability, and adjustable surface functionality, PVNPs hold tremendous potential for both therapeutic and imaging applications. The versatility of PVNPs is evident from their ability to be tailored to transport a range of therapeutic agents, including chemotherapy drugs, siRNA, and immunomodulators, thereby facilitating targeted delivery to the tumor microenvironment (TME). Furthermore, PVNPs may be customized with targeting ligands to selectively bind to cancer cell receptors, reducing off-target effects. Additionally, PVNPs possess immunogenic properties and can be engineered to exhibit tumor-associated antigens, thereby stimulating anti-tumor immune responses. In conclusion, the potential of PVNPs as a versatile platform for fighting cancer is immense, and further research is required to fully explore their potential and translate them into clinical applications.

PMID:37631846 | DOI:10.3390/vaccines11081278

Plants (Basel). 2023 Aug 21;12(16):3014. doi: 10.3390/plants12163014.

ABSTRACT

Plant organ growth results from the combined activity of cell division and cell expansion. The co-ordination of these two processes depends on the interplay between multiple hormones that determine the final organ size. Using the semidominant Hairy Sheath Frayed1 (Hsf1) maize mutant that hypersignals the perception of cytokinin (CK), we show that CK can reduce leaf size and growth rate by decreasing cell division. Linked to CK hypersignaling, the Hsf1 mutant has an increased jasmonic acid (JA) content, a hormone that can inhibit cell division. The treatment of wild-type seedlings with exogenous JA reduces maize leaf size and growth rate, while JA-deficient maize mutants have increased leaf size and growth rate. Expression analysis revealed the increased transcript accumulation of several JA pathway genes in the Hsf1 leaf growth zone. A transient treatment of growing wild-type maize shoots with exogenous CK also induced the expression of JA biosynthetic genes, although this effect was blocked by the co-treatment with cycloheximide. Together, our results suggest that CK can promote JA accumulation, possibly through the increased expression of specific JA pathway genes.

PMID:37631225 | DOI:10.3390/plants12163014

Pharmaceuticals (Basel). 2023 Aug 12;16(8):1147. doi: 10.3390/ph16081147.

ABSTRACT

Currently, there is no cure for human immunodeficiency virus type 1 (HIV-1) infection. However, combined antiretroviral therapy (cART) aids in viral latency and prevents the progression of HIV-1 infection into acquired immunodeficiency syndrome (AIDS). cART has extended many lives, but people living with HIV-1 (PLWH) face lifelong ailments such as HIV-associated neurocognitive disorders (HAND) that range from asymptomatic HAND to HIV-1-associated dementia. HAND has been attributed to chronic inflammation and low-level infection within the central nervous system (CNS) caused by proinflammatory cytokines and viral products. These molecules are shuttled into the CNS within extracellular vesicles (EVs), lipid bound nanoparticles, and are released from cells as a form of intercellular communication. This study investigates the impact of cannabidiol (CBD), as a promising and potential therapeutic for HAND patients, and a similar synthetic molecule, HU308, on the EVs released from HIV-1-infected myeloid cells as well as HIV-1-infected 3D neurospheres. The data shows that both CBD and HU308 decrease non-coding and coding viral RNA (TAR and env) as well as proinflammatory cytokines as IL-1β and TNF-α mRNA. This decrease in viral RNA occurs in in vitro differentiated primary macrophages, in EVs released from HIV-1-infected cells monocytes, and infected neurospheres. Furthermore, a 3D neurosphere model shows an overall decrease in proinflammatory mRNA with HU308. Finally, using a humanized mouse model of HIV-1 infection, plasma viral RNA was shown to significantly decrease with HU308 alone and was most effective in combination with cART, even when compared to the typical cART treatment. Overall, CBD or HU308 may be a viable option to decrease EV release and associated cytokines which would dampen the virus spread and may be used in effective treatment of HAND in combination with cART.

PMID:37631062 | DOI:10.3390/ph16081147

Microorganisms. 2023 Aug 9;11(8):2045. doi: 10.3390/microorganisms11082045.

ABSTRACT

Plant-microbe interactions are of rising interest in plant sustainability, biomass production, plant biology, and systems biology. These interactions have been a challenge to detect until recent advancements in mass spectrometry imaging. Plants and microbes interact in four main regions within the plant, the rhizosphere, endosphere, phyllosphere, and spermosphere. This mini review covers the challenges within investigations of plant and microbe interactions. We highlight the importance of sample preparation and comparisons among time-of-flight secondary ion mass spectroscopy (ToF-SIMS), matrix-assisted laser desorption/ionization (MALDI), laser desorption ionization (LDI/LDPI), and desorption electrospray ionization (DESI) techniques used for the analysis of these interactions. Using mass spectral imaging (MSI) to study plants and microbes offers advantages in understanding microbe and host interactions at the molecular level with single-cell and community communication information. More research utilizing MSI has emerged in the past several years. We first introduce the principles of major MSI techniques that have been employed in the research of microorganisms. An overview of proper sample preparation methods is offered as a prerequisite for successful MSI analysis. Traditionally, dried or cryogenically prepared, frozen samples have been used; however, they do not provide a true representation of the bacterial biofilms compared to living cell analysis and chemical imaging. New developments such as microfluidic devices that can be used under a vacuum are highly desirable for the application of MSI techniques, such as ToF-SIMS, because they have a subcellular spatial resolution to map and image plant and microbe interactions, including the potential to elucidate metabolic pathways and cell-to-cell interactions. Promising results due to recent MSI advancements in the past five years are selected and highlighted. The latest developments utilizing machine learning are captured as an important outlook for maximal output using MSI to study microorganisms.

PMID:37630605 | DOI:10.3390/microorganisms11082045

Microorganisms. 2023 Aug 3;11(8):2001. doi: 10.3390/microorganisms11082001.

ABSTRACT

The development of microbiome-targeted strategies is limited by individual differences in gut microbiome composition and metabolic responses to interventions. In vitro models that can replicate this variation allow us to conduct pre-clinical studies and assess efficacy. This study describes the exposure of 16 individual fecal microbiota samples to 5 different fibers using an in vitro system for the anaerobic cultivation of bacteria. The individual microbiota differed in composition and metabolite profiles (short-chain fatty acids and branched-chain fatty acids) after incubation with the fibers. Furthermore, microbiota composition after fiber incubation was significantly different between subjects with good intestinal health and subjects with Inflammatory Bowel Disease (IBD). α-diversity was differently affected by dietary fibers; for example, exposure to psyllium resulted in increased diversity in the healthy group and in decreased diversity in the IBD group. Instead, the functional metabolic profile did not differ between the two groups. Finally, the combination of all fibers, tested on the microbiota from IBD subjects, resulted in stronger overall effects on both microbiota composition and metabolite production compared to the single fibers. These results confirm that incubation with dietary fiber results in different compositional and functional effects on individual microbiota and that in vitro models represent successful tools for studying individual fiber effects.

PMID:37630561 | DOI:10.3390/microorganisms11082001

Microorganisms. 2023 Jul 30;11(8):1949. doi: 10.3390/microorganisms11081949.

ABSTRACT

How bacteria respond at the systems level to both genetic and environmental perturbations imposed at the same time is one fundamental yet open question in biology. Bioengineering or synthetic biology provides an ideal system for studying such responses, as engineered strains always have genetic changes as opposed to wildtypes and are grown in conditions which often change during growth for maximal yield of desired products. So, engineered strains were used to address the outstanding question. Two Bacillus subtilis strains (MT1 and MT2) were created previously for the overproduction of N-acetylglucosamine (GlcNAc), which were grown in an environment with a carbon shift from glucose to glucose and xylose in the same culture system. We had four groups: (1) a wildtype (WT) grown with glucose at t1; (2) a WT with glucose and xylose at t2; (3) a mutant (MT1) grown with glucose at t1; and (4) MT1 with glucose and xylose at t2. By measuring transcriptomes and metabolomes, we found that GlcNAc-producing mutants, particularly MT2, had a higher yield of N-acetylglucosamine than WT but displayed a smaller maximum growth rate than the wildtype, despite MT1 reaching higher carrying capacity. Underlying the observed growth, the engineered pathways leading to N-acetylglucosamine had both higher gene expression and associated metabolite concentrations in MT1 than WT at both t1 and t2; in bioenergetics, there was higher energy supply in terms of ATP and GTP, with the energy state metric higher in MT1 than WT at both timepoints. Additionally, most top key precursor metabolites were equally abundant in MT1 and WT at either timepoints. Besides that, one prominent feature was the high consistency between transcriptomics and metabolomics in revealing the response. First, both metabolomes and transcriptomes revealed the same PCA clusters of the four groups. Second, we found that the important functions enriched both by metabolomes and transcriptomes overlapped, such as amino acid metabolism and ABC transport. Strikingly, these functions overlapped those enriched by the genes showing a high (positive or negative) correlation with metabolites. Furthermore, these functions also overlapped the enriched KEGG pathways identified using weighted gene coexpression network analysis. All these findings suggest that the responses to simultaneous genetic and environmental perturbations are well coordinated at the metabolic and transcriptional levels: they rely heavily on bioenergetics, but core metabolism does not differ much, while amino acid metabolism and ABC transport are important. This serves as a design guide for bioengineering, synthetic biology, and systems biology.

PMID:37630509 | DOI:10.3390/microorganisms11081949

Micromachines (Basel). 2023 Aug 10;14(8):1576. doi: 10.3390/mi14081576.

ABSTRACT

Associative learning is a critical survival trait that promotes behavioral plasticity in response to changing environments. Chemosensation and mechanosensation are important sensory modalities that enable animals to gather information about their internal state and external environment. However, there is a limited amount of research on these two modalities. In this paper, a novel PDMS-agar hybrid microfluidic device is proposed for training and analyzing chemical-mechanical associative learning behavior in the nematode Caenorhabditis elegans. The microfluidic device consisted of a bottom agar gel layer and an upper PDMS layer. A chemical concentration gradient was generated on the agar gel layer, and the PDMS layer served to mimic mechanical stimuli. Based on this platform, C. elegans can perform chemical-mechanical associative learning behavior after training. Our findings indicated that the aversive component of training is the primary driver of the observed associative learning behavior. In addition, the results indicated that the neurotransmitter octopamine is involved in regulating this associative learning behavior via the SER-6 receptor. Thus, the microfluidic device provides a highly efficient platform for studying the associative learning behavior of C. elegans, and it may be applied in mutant screening and drug testing.

PMID:37630112 | DOI:10.3390/mi14081576

Life (Basel). 2023 Jul 31;13(8):1668. doi: 10.3390/life13081668.

ABSTRACT

Sequencing technologies have rapidly evolved over the past two decades, and new technologies are being continually developed and commercialized. The emerging sequencing technologies target generating more data with fewer inputs and at lower costs. This has also translated to an increase in the number and type of corresponding applications in genomics besides enhanced computational capacities (both hardware and software). Alongside the evolving DNA sequencing landscape, bioinformatics research teams have also evolved to accommodate the increasingly demanding techniques used to combine and interpret data, leading to many researchers moving from the lab to the computer. The rich history of DNA sequencing has paved the way for new insights and the development of new analysis methods. Understanding and learning from past technologies can help with the progress of future applications. This review focuses on the evolution of sequencing technologies, their significant enabling role in generating plant genome assemblies and downstream applications, and the parallel development of bioinformatics tools and skills, filling the gap in data analysis techniques.

PMID:37629524 | DOI:10.3390/life13081668