Systems Biology

Identifying antimicrobials and their metabolites in wastewater and surface water with effect-directed analysis

Thu, 2023-02-09 06:00

Chemosphere. 2023 Feb 7:138093. doi: 10.1016/j.chemosphere.2023.138093. Online ahead of print.

ABSTRACT

This study aimed to identify antimicrobial contaminants in the aquatic environment with effect-directed analysis. Wastewater influent, effluent, and surface water (up- and downstream of the discharge location) were sampled at two study sites. The samples were enriched, subjected to high-resolution fractionation, and the resulting 80 fractions were tested in an antibiotics bioassay. The resulting bioactive fractions guided the suspect and nontargeted identification strategy in the high-resolution mass spectrometry data that was recorded in parallel. Chemical features were annotated with reference databases, assessed on annotation quality, and assigned identification confidence levels. To identify antibiotic metabolites, Phase I metabolites were predicted in silico for over 500 antibiotics and included as a suspect list. Predicted retention times and fragmentation patterns reduced the number of annotations to consider for confirmation testing. Overall, the bioactivity of three fractions could be explained by the identified antibiotics (clarithromycin and azithromycin) and an antibiotic metabolite (14-OH(R) clarithromycin), explaining 78% of the bioactivity measured at one study site. The applied identification strategy successfully identified antibiotic metabolites in the aquatic environment, emphasizing the need to include the toxic effects of bioactive metabolites in environmental risk assessments.

PMID:36758810 | DOI:10.1016/j.chemosphere.2023.138093

Categories: Literature Watch

<sup>13</sup>C-Metabolic flux analysis of 3T3-L1 adipocytes illuminates its core metabolism under hypoxia

Thu, 2023-02-09 06:00

Metab Eng. 2023 Feb 7:S1096-7176(23)00022-8. doi: 10.1016/j.ymben.2023.02.002. Online ahead of print.

ABSTRACT

Hypoxia has been identified as a major factor in the pathogenesis of adipose tissue inflammation, which is a hallmark of obesity and obesity-linked type 2 diabetes mellitus. In this study, we have investigated the impact of hypoxia (1% oxygen) on the physiology and metabolism of 3T3-L1 adipocytes, a widely used cell culture model of adipose. Specifically, we applied parallel labeling experiments, isotopomer spectral analysis, and 13C-metabolic flux analysis to quantify the impact of hypoxia on adipogenesis, de novo lipogenesis and metabolic flux reprogramming in adipocytes. We found that 3T3-L1 cells can successfully differentiate into lipid-accumulating adipocytes under hypoxia, although the production of lipids was reduced by about 40%. Quantitative flux analysis demonstrated that short-term (1 day) and long-term (7 days) exposure to hypoxia resulted in similar reprogramming of cellular metabolism. Overall, we found that hypoxia: 1) reduced redox and energy generation by more than 2-fold and altered the patterns of metabolic pathway contributions to production and consumption of energy and redox cofactors; 2) redirected glucose metabolism from pentose phosphate pathway and citric acid cycle to lactate production; 3) rewired glutamine metabolism, from net glutamine production to net glutamine catabolism; 4) suppressed branched chain amino acid consumption; and 5) reduced biosynthesis of odd-chain fatty acids and mono-unsaturated fatty acids, while synthesis of saturated even-chain fatty acids was not affected. Together, these results highlight the profound impact of extracellular microenvironment on adipocyte metabolic activity and function.

PMID:36758664 | DOI:10.1016/j.ymben.2023.02.002

Categories: Literature Watch

Improving recombinant protein production in CHO cells using the CRISPR-Cas system

Thu, 2023-02-09 06:00

Biotechnol Adv. 2023 Feb 7:108115. doi: 10.1016/j.biotechadv.2023.108115. Online ahead of print.

ABSTRACT

Chinese hamster ovary (CHO) cells are among the most widely used mammalian cell lines in the biopharmaceutical industry. Therefore, it is not surprising that significant efforts have been made around the engineering of CHO cells using genetic engineering methods such as the CRISPR-Cas system. In this review, we summarize key recent studies that have used different CRISPR-Cas systems such as Cas9, Cas13 or dCas9 fused with effector domains to improve recombinant protein (r-protein) production in CHO cells. Here, every relevant stage of production was considered, underscoring the advantages and limitations of these systems, as well as discussing their bottlenecks and probable solutions. A special emphasis was given on how these systems could disrupt and/or regulate genes related to glycan composition, which has relevant effects over r-protein properties and in vivo activity. Furthermore, the related promising future applications of CRISPR to achieve a tunable, reversible, or highly stable editing of CHO cells are discussed. Overall, the studies covered in this review show that despite the complexity of mammalian cells, the synthetic biology community has developed many mature strategies to improve r-protein production using CHO cells. In this regard, CRISPR-Cas technology clearly provides efficient and flexible genetic manipulation and allows for the generation of more productive CHO cell lines, leading to more cost-efficient production of biopharmaceuticals, however, there is still a need for many emerging techniques in CRISPR to be reported in CHO cells; therefore, more research in these cells is needed to realize the full potential of this technology.

PMID:36758652 | DOI:10.1016/j.biotechadv.2023.108115

Categories: Literature Watch

Coughs, colds and "freshers' flu" survey in the University of Cambridge, 2007-2008

Thu, 2023-02-09 06:00

Epidemics. 2022 Dec 23;42:100659. doi: 10.1016/j.epidem.2022.100659. Online ahead of print.

ABSTRACT

Universities provide many opportunities for the spread of infectious respiratory illnesses. Students are brought together into close proximity from all across the world and interact with one another in their accommodation, through lectures and small group teaching and in social settings. The COVID-19 global pandemic has highlighted the need for sufficient data to help determine which of these factors are important for infectious disease transmission in universities and hence control university morbidity as well as community spillover. We describe the data from a previously unpublished self-reported university survey of coughs, colds and influenza-like symptoms collected in Cambridge, UK, during winter 2007-2008. The online survey collected information on symptoms and socio-demographic, academic and lifestyle factors. There were 1076 responses, 97% from University of Cambridge students (5.7% of the total university student population), 3% from staff and <1% from other participants, reporting onset of symptoms between September 2007 and March 2008. Undergraduates are seen to report symptoms earlier in the term than postgraduates; differences in reported date of symptoms are also seen between subjects and accommodation types, although these descriptive results could be confounded by survey biases. Despite the historical and exploratory nature of the study, this is one of few recent detailed datasets of influenza-like infection in a university context and is especially valuable to share now to improve understanding of potential transmission dynamics in universities during the current COVID-19 pandemic.

PMID:36758342 | DOI:10.1016/j.epidem.2022.100659

Categories: Literature Watch

Multi-omics Analyses Reveal Sex Differences in Mouse Renal Proximal Subsegments

Thu, 2023-02-09 06:00

J Am Soc Nephrol. 2023 Feb 9. doi: 10.1681/ASN.0000000000000089. Online ahead of print.

ABSTRACT

BACKGROUND: Sex differences have been increasingly recognized as important in kidney physiology and pathophysiology, but limited resources are available for comprehensive interrogation of sex differences.

METHODS: RNA-seq and ATAC-seq of microdissected mouse proximal tubules and protein mass spectrometry of homogenized perfused mouse kidneys reveal differences in proximal tubule cells of males and females.

RESULTS: The transcriptomic data indicated that the major differences in the proximal tubules between the sexes were in the S2/S3 segments and the majority of the sex-biased transcripts mapped to autosomes rather than to the sex chromosomes. Many of the transcripts exhibiting sex-biased expression are involved in monocarboxylic acid metabolic processes, organic anion transport, and organic acid transport. The ATAC-seq method on microdissected tubules captured chromatin accessibility. Many of the more than 7,000 differentially accessible DNA regions identified were in distal regions. Motif analyses revealed a lack of direct involvement of estrogen receptors or the androgen receptor (absence of canonical hormone response elements), suggesting an indirect regulatory role of sex hormones. Instead, analyses identified several transcription factors (Tead1, Nfia/b, and Pou3f3) whose interplay with proximal tubule-specific transcription factors (e.g. Hnf1b, Hnf4a) may contribute to sex differences. Finally, the whole-kidney proteome was correlated with the transcriptome and many sex-biased proteins (e.g. Cyp2e1, Acsm2/3) were identified.

CONCLUSION: Sex-dependent cis-regulatory elements interact with transcription factors in ways that lead to sex-biased gene expression in proximal tubule cells. These data are provided as a user-friendly web page at https://esbl.nhlbi.nih.gov/MRECA/PT/.

PMID:36758122 | DOI:10.1681/ASN.0000000000000089

Categories: Literature Watch

Young immunologists of Europe in full swing - the first yEFIS symposium

Thu, 2023-02-09 06:00

Eur J Immunol. 2023 Feb 9:e2350417. doi: 10.1002/eji.202350417. Online ahead of print.

NO ABSTRACT

PMID:36758120 | DOI:10.1002/eji.202350417

Categories: Literature Watch

Epigenetics as a mediator of plasticity in cancer

Thu, 2023-02-09 06:00

Science. 2023 Feb 10;379(6632):eaaw3835. doi: 10.1126/science.aaw3835. Epub 2023 Feb 10.

ABSTRACT

The concept of an epigenetic landscape describing potential cellular fates arising from pluripotent cells, first advanced by Conrad Waddington, has evolved in light of experiments showing nondeterministic outcomes of regulatory processes and mathematical methods for quantifying stochasticity. In this Review, we discuss modern approaches to epigenetic and gene regulation landscapes and the associated ideas of entropy and attractor states, illustrating how their definitions are both more precise and relevant to understanding cancer etiology and the plasticity of cancerous states. We address the interplay between different types of regulatory landscapes and how their changes underlie cancer progression. We also consider the roles of cellular aging and intrinsic and extrinsic stimuli in modulating cellular states and how landscape alterations can be quantitatively mapped onto phenotypic outcomes and thereby used in therapy development.

PMID:36758093 | DOI:10.1126/science.aaw3835

Categories: Literature Watch

Genome-Wide Profiling of Exosomal Long Noncoding RNAs Following Air Pollution Exposure: A Randomized, Crossover Trial

Thu, 2023-02-09 06:00

Environ Sci Technol. 2023 Feb 9. doi: 10.1021/acs.est.2c05956. Online ahead of print.

ABSTRACT

Changes in human genome-wide long noncoding RNAs (lncRNAs) associated with air pollution are unknown. This study aimed to investigate the effect of air pollution on human exosomal lncRNAs. A randomized, crossover trial was conducted among 35 healthy adults. Participants were allocated to 4 h exposure in road (high air pollution) and park (low air pollution) sessions in random order with a 2 week washout period. RNA sequencing was performed to measure lncRNAs. Differential lncRNAs were identified using a linear mixed-effect model. Mean concentrations of air pollutants such as ultrafine particles (UFP), black carbon (BC), carbon monoxide (CO), and nitrogen dioxide (NO2) were 2-3 times higher in the road than those in the park. Fifty-five lncRNAs [false discovery rate (FDR) < 0.05] including lncRNA NORAD, MALAT1, and H19 were changed in response to air pollution exposure. We found that 54 lncRNAs were associated with CO, 49 lncRNAs with UFP, 49 lncRNAs with BC, 48 lncRNAs with NO2, and 4 lncRNAs with PM2.5 (FDR < 0.05). These differential lncRNAs participated in dozens of pathways including cardiovascular signaling, epithelial cell proliferation, inflammation, and transforming growth factor. This trial for the first time profiled changes of human exosomal lncRNAs following air pollution. Our findings revealed multiple biological processes moderated by lncRNAs and provided epigenetic insights into cardiovascular effects of air pollution.

PMID:36757895 | DOI:10.1021/acs.est.2c05956

Categories: Literature Watch

Comparative assessment of coronary physiology using transthoracic pulsed-wave Doppler and myocardial contrast echocardiography in rats

Thu, 2023-02-09 06:00

Eur Radiol Exp. 2023 Feb 9;7(1):6. doi: 10.1186/s41747-022-00319-4.

ABSTRACT

BACKGROUND: Coronary physiology assessment in rodents by ultrasound is an excellent noninvasive and easy to perform technique, including pulsed-wave Doppler (PWD) and myocardial contrast echocardiography (MCE). Both techniques and the corresponding calculated parameters were investigated in this study at rest as well as their response to pharmacologically induced stress.

METHODS: Left ventricular myocardial function was assessed in eight anaesthetised rats using transthoracic echocardiography. Coronary physiology was assessed by both PWD of the left coronary artery and MCE using a bolus method. Measurements were performed at rest and under stimulation with adenosine and dobutamine. Effects of stimulation on the calculated parameters were evaluated and rated by effect size (η2).

RESULTS: Changes could be demonstrated by selected parameters of PWD and MCE. The clearest effect in PWD was found for diastolic peak velocity (η2 = 0.58). It increased from 528 ± 110 mm/s (mean ± standard deviation) at rest to 839 ± 342 mm/s (p = 0.001) with adenosine and 1093 ± 302 mm/s with dobutamine (p = 0.001). The most distinct effect from MCE was found for the normalised wash-in rate (η2 = 0.58). It increased from 1.95 ± 0.35% at rest to 3.87 ± 0.85% with adenosine (p = 0.001) and 3.72 ± 1.03% with dobutamine (p = 0.001).

CONCLUSION: Induced changes in coronary physiology by adenosine and dobutamine could successfully be monitored using MCE and PWD in anaesthetised rats. Due to the low invasiveness of the measurements, this protocol could be used for longitudinal animal studies.

PMID:36757486 | DOI:10.1186/s41747-022-00319-4

Categories: Literature Watch

Chromosome-level genome assembly of Euphorbia peplus, a model system for plant latex, reveals that relative lack of Ty3 transposons contributed to its small genome size

Thu, 2023-02-09 06:00

Genome Biol Evol. 2023 Feb 9:evad018. doi: 10.1093/gbe/evad018. Online ahead of print.

ABSTRACT

Euphorbia peplus (petty spurge) is a small, fast-growing plant that is native to Eurasia and has become a naturalized weed in North America and Australia. E. peplus is not only medicinally valuable, serving as a source for the skin cancer drug ingenol mebutate, but also has great potential as a model for latex production owing to its small size, ease of manipulation in the laboratory, and rapid reproductive cycle. To help establish E. peplus as a new model, we generated a 267.2 Mb Hi-C-anchored PacBio HiFi nuclear genome assembly with an BUSCO score of 98.5%, a genome annotation based on RNA-seq data from six organs, and publicly accessible tools including a genome browser and an interactive organ-specific expression atlas. Chromosome number is highly variable across Euphorbia species. Using a comparative analysis of our newly sequenced E. peplus genome with other Euphorbiaceae genomes, we show that variation in Euphorbia chromosome number between E. peplus and E. lathyris is likely due to fragmentation and rearrangement rather than chromosomal duplication followed by diploidization of the duplicated sequence. Moreover, we found that the E. peplus genome is relatively compact compared to related members of the genus in part due to restricted expansion of the Ty3 transposon family. Finally, we identify a large gene cluster that contains many previously identified enzymes in the putative ingenol mebutate biosynthesis pathway, along with additional gene candidates for this biosynthetic pathway. The genomic resources we have created for E. peplus will help advance research on latex production and ingenol mebutate biosynthesis in the commercially important Euphorbiaceae family.

PMID:36757383 | DOI:10.1093/gbe/evad018

Categories: Literature Watch

Community diversity is associated with intra-species genetic diversity and gene loss in the human gut microbiome

Thu, 2023-02-09 06:00

Elife. 2023 Feb 9;12:e78530. doi: 10.7554/eLife.78530. Online ahead of print.

ABSTRACT

The human gut microbiome contains a diversity of microbial species that varies in composition over time and across individuals. These species (and strains within species) can migrate across hosts and evolve by mutation and recombination within hosts. How the ecological process of community assembly interacts with intra-species diversity and evolutionary change is a longstanding question. Two contrasting hypotheses have been proposed based on ecological observations and theory: Diversity Begets Diversity (DBD), in which taxa tend to become more diverse in already diverse communities, and Ecological Controls (EC), in which higher community diversity impedes diversification within taxa. Previously, using 16S rRNA gene amplicon data across a range of environments, we showed a generally positive relationship between taxa diversity and community diversity at higher taxonomic levels, consistent with the predictions of DBD (Madi et al., 2020). However, this positive 'diversity slope' reaches a plateau at high levels of community diversity. Here we show that this general pattern holds at much finer genetic resolution, by analyzing intra-species strain and nucleotide variation in static and temporally sampled shotgun-sequenced fecal metagenomes from cohorts of healthy human hosts. We find that both intra-species polymorphism and strain number are positively correlated with community Shannon diversity. This trend is consistent with DBD, although we cannot exclude abiotic drivers of diversity. Shannon diversity is also predictive of increases in polymorphism over time scales up to ~4-6 months, after which the diversity slope flattens and then becomes negative-consistent with DBD eventually giving way to EC. Also supporting a complex mixture of DBD and EC, the number of strains per focal species is positively associated with Shannon diversity but negatively associated with richness. Finally, we show that higher community diversity predicts gene loss in a focal species at a future time point. This observation is broadly consistent with the Black Queen Hypothesis, which posits that genes with functions provided by the community are less likely to be retained in a focal species' genome. Together, our results show that a mixture of DBD, EC, and Black Queen may operate simultaneously in the human gut microbiome, adding to a growing body of evidence that these eco-evolutionary processes are key drivers of biodiversity and ecosystem function.

PMID:36757364 | DOI:10.7554/eLife.78530

Categories: Literature Watch

Programmable regulation of translation by harnessing the CRISPR-Cas13 system

Thu, 2023-02-09 06:00

Chem Commun (Camb). 2023 Feb 9. doi: 10.1039/d3cc00058c. Online ahead of print.

ABSTRACT

The ability to control protein expression at both the transcriptional and post-transcriptional levels is instrumental for the cell to integrate multiple molecular signals and then reach high operational sophistication. Although challenging, fully artificial regulations at different levels are required for boosting systems and synthetic biology. Here, we report the development of a novel framework to regulate translation by repurposing the CRISPR-Cas13 immune system, which uses an RNA-guided ribonuclease. By exploiting a cell-free expression system for prototyping gene regulatory structures, our results demonstrate that CRISPR-dCas13a ribonucleoproteins (d means catalytically dead) can be programmed to repress or activate translation initiation. The performance assessment of the engineered systems also revealed guide RNA design principles. Moreover, we show that the system can work in vivo. This development complements the ability to regulate transcription with other CRISPR-Cas systems and offers potential applications.

PMID:36757178 | DOI:10.1039/d3cc00058c

Categories: Literature Watch

Functionalized Fluorescent Nanostructures Generated from Self-Assembly of a Cationic Tripeptide Direct Cell-Selective Chemotherapeutic Drug Delivery

Thu, 2023-02-09 06:00

ACS Appl Bio Mater. 2023 Feb 9. doi: 10.1021/acsabm.2c00996. Online ahead of print.

ABSTRACT

Nanodrug delivery systems (NDDs) capable of conveying chemotherapeutics directly into malignant cells without harming healthy ones are of significant interest in the field of cancer therapy. However, the development of nanostructures with the requisite biocompatibility, inherent optical properties, cellular penetration ability, encapsulation capability, and target selectivity has remained elusive. In an effort to develop cell-selective NDDs, we have synthesized a cationic tripeptide Boc-Arg-Trp-Phe-OMe (PA1), which self-assembles into well-ordered spheres in 100% aqueous medium. The inherent fluorescence properties of the peptide PA1 were shifted from the ultraviolet to the visible region by the self-assembly. These fluorescent nanostructures are proteolytically stable, photostable, and biocompatible, with characteristic blue fluorescence signals that permit us to monitor their intracellular entry in real time. We also demonstrate that these tripeptide spherical structures (TPSS) have the capacity to entrap the chemotherapeutic drug doxorubicin (Dox), shuttle the encapsulated drug within cancerous cells, and initiate the DNA damage signaling cascade, which culminates in apoptosis. Next, we functionalized the TPSS with an epithelial-cell-specific epithelial cell adhesion molecule aptamer. Aptamer-conjugated PA1 (PA1-Apt) facilitated efficient Dox delivery into the breast cancer epithelial cell line MCF7, resulting in cell death. However, cells of the human cardiomyocyte cell line AC16 were resistant to the cell killing actions of PA1-Apt. Together, these data demonstrate that not only can the self-assembly of cationic tripeptides like PA1 be exploited for efficient drug encapsulation and delivery but their unique chemistry also allows for functional modifications, which can improve the selectivity of these versatile NDDs.

PMID:36757106 | DOI:10.1021/acsabm.2c00996

Categories: Literature Watch

Distinct subsets of neutrophils crosstalk with cytokines and metabolites in patients with sepsis

Thu, 2023-02-09 06:00

iScience. 2023 Jan 7;26(2):105948. doi: 10.1016/j.isci.2023.105948. eCollection 2023 Feb 17.

ABSTRACT

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated, comprehensive studies linking different data layers are lacking. Using an integrated systems immunology approach, we evaluated neutrophil phenotypes and concomitant changes in cytokines and metabolites in patients with sepsis. Our findings identify differentially expressed mature and immature neutrophil subsets in patients with sepsis. These subsets correlate with various proteins, metabolites, and lipids, including pentraxin-3, angiopoietin-2, and lysophosphatidylcholines, in patients with sepsis. These results enabled the construction of a statistical model based on weighted multi-omics linear regression analysis for sepsis biomarker identification. These findings could help inform early patient stratification and treatment options, and facilitate further mechanistic studies targeting the trifecta of surface marker expression, cytokines, and metabolites.

PMID:36756375 | PMC:PMC9900520 | DOI:10.1016/j.isci.2023.105948

Categories: Literature Watch

Heat-induced proteomic changes in anthers of contrasting rice genotypes under variable stress regimes

Thu, 2023-02-09 06:00

Front Plant Sci. 2023 Jan 13;13:1083971. doi: 10.3389/fpls.2022.1083971. eCollection 2022.

ABSTRACT

Heat stress drastically affects anther tissues resulting in poor plant fertility, necessitating an urgent need to determine the key proteome regulation associated with mature anther in response to heat stress. We identified several genotype - specific protein alterations in rice anthers of Moroberekan (Japonica, heat sensitive), IR64 (Indica, moderately heat tolerant), and Nagina22 (Aus, heat tolerant) in the short-term (ST_HS; one cycle of 42°C, 4 hours before anthesis) and long-term (LT_HS; 6 cycles of 38°C, 6 hours before anthesis) heat stress. The proteins upregulated in long-term heat stress in Nagina22 were enriched in biological processes related to unfolded protein binding and carboxylic acid metabolism, including amino acid metabolism. In short-term heat stress, Nagina22 anthers were enriched in proteins associated with vitamin E biosynthesis and GTPase activator activity. In contrast, downregulated proteins were related to ribosomal proteins. The expression of different Hsp20 and DnaJ was genotype specific. Overall, the heat response in Nagina22 was associated with its capacity for adequate metabolic control and cellular homeostasis, which may be critical for its higher reproductive thermotolerance. This study improves our understanding of thermotolerance mechanisms in rice anthers during anthesis and lays a foundation for breeding thermotolerant varieties via molecular breeding.

PMID:36756226 | PMC:PMC9901367 | DOI:10.3389/fpls.2022.1083971

Categories: Literature Watch

The microbiota as a modulator of mucosal inflammation and HIV/HPV pathogenesis: From association to causation

Thu, 2023-02-09 06:00

Front Immunol. 2023 Jan 23;14:1072655. doi: 10.3389/fimmu.2023.1072655. eCollection 2023.

ABSTRACT

Although the microbiota has largely been associated with the pathogenesis of viral infections, most studies using omics techniques are correlational and hypothesis-generating. The mechanisms affecting the immune responses to viral infections are still being fully understood. Here we focus on the two most important sexually transmitted persistent viruses, HPV and HIV. Sophisticated omics techniques are boosting our ability to understand microbiota-pathogen-host interactions from a functional perspective by surveying the host and bacterial protein and metabolite production using systems biology approaches. However, while these strategies have allowed describing interaction networks to identify potential novel microbiota-associated biomarkers or therapeutic targets to prevent or treat infectious diseases, the analyses are typically based on highly dimensional datasets -thousands of features in small cohorts of patients-. As a result, we are far from getting to their clinical use. Here we provide a broad overview of how the microbiota influences the immune responses to HIV and HPV disease. Furthermore, we highlight experimental approaches to understand better the microbiota-host-virus interactions that might increase our potential to identify biomarkers and therapeutic agents with clinical applications.

PMID:36756132 | PMC:PMC9900135 | DOI:10.3389/fimmu.2023.1072655

Categories: Literature Watch

Layer-specific correlates of detected and undetected auditory targets during attention

Thu, 2023-02-09 06:00

Curr Res Neurobiol. 2023 Jan 25;4:100075. doi: 10.1016/j.crneur.2023.100075. eCollection 2023.

ABSTRACT

In everyday life, the processing of acoustic information allows us to react to subtle changes in the auditory scene. Yet even when closely attending to sounds in the context of a task, we occasionally miss task-relevant features. The neural computations that underlie our ability to detect behavioral relevant sound changes are thought to be grounded in both feedforward and feedback processes within the auditory hierarchy. Here, we assessed the role of feedforward and feedback contributions in primary and non-primary auditory areas during behavioral detection of target sounds using submillimeter spatial resolution functional magnetic resonance imaging (fMRI) at high-fields (7 T) in humans. We demonstrate that the successful detection of subtle temporal shifts in target sounds leads to a selective increase of activation in superficial layers of primary auditory cortex (PAC). These results indicate that feedback signals reaching as far back as PAC may be relevant to the detection of targets in the auditory scene.

PMID:36755988 | PMC:PMC9900365 | DOI:10.1016/j.crneur.2023.100075

Categories: Literature Watch

Crosslinked and Multi-Responsive Polymeric Vesicles as A Platform to Study Enzyme-mediated Undocking Behavior: Towards Future Artificial Organelle Communication

Thu, 2023-02-09 06:00

Macromol Rapid Commun. 2023 Feb 8:e2200885. doi: 10.1002/marc.202200885. Online ahead of print.

ABSTRACT

Various cellular functions are successfully mimicked, opening the door to the next generation of therapeutic approaches and systems biology. Here, the first steps are taken towards the construction of artificial organelles for mimicking cell communication by docking and undocking of cargo in the membrane of swollen artificial organelles. Stimuli-responsive and crosslinked polymeric vesicles are used to allow docking processes at acidic pH at which ferrocene units in the swollen membrane state can undergo desired specific host-guest interaction using β-cyclodextrin as model cargo. The release of the cargo mediated by two different enzymes, glucose oxidase and α-amylase, is investigated, triggered by distinct enzymatic undocking mechanisms. Different release times for a useful transport are shown that can be adapted to different communication pathways. In addition, FRET experiments further support the hypotheses of host-guest inclusion complexation formation and their time-dependent breakdown. This work paves a way to a platform based on polymeric vesicles for synthetic biology, cell functions mimicking and the construction of multifunctional cargo delivery system. This article is protected by copyright. All rights reserved.

PMID:36755359 | DOI:10.1002/marc.202200885

Categories: Literature Watch

Structural Analysis and Intrinsic Enzyme Mimicking Activities of Ligand-Free PtAg Nanoalloys

Thu, 2023-02-09 06:00

Small. 2023 Feb 8:e2206772. doi: 10.1002/smll.202206772. Online ahead of print.

ABSTRACT

Nanozymes are nanomaterials with biocatalytic properties under physiological conditions and are one class of artificial enzymes to overcome the high cost and low stability of natural enzymes. However, surface ligands on nanomaterials will decrease the catalytic activity of the nanozymes by blocking the active sites. To address this limitation, ligand-free PtAg nanoclusters (NCs) are synthesized and applied as nanozymes for various enzyme-mimicking reactions. By taking advantage of the mutual interaction of zeolitic imidazolate frameworks (ZIF-8) and Pt precursors, a good dispersion of PtAg bimetal NCs with a diameter of 1.78 ± 0.1 nm is achieved with ZIF-8 as a template. The incorporation of PtAgNCs in the voids of ZIF-8 is confirmed with structural analysis using the atomic pair-distribution function and powder X-ray diffraction. Importantly, the PtAgNCs present good catalytic activity for various enzyme-mimicking reactions, including peroxidase-/catalase- and oxidase-like reactions. Further, this work compares the catalytic activity between PtAg NCs and PtAg nanoparticles with different compositions and finds that these two nanozymes present a converse dependency of Ag-loading on their activity. This study contributes to the field of nanozymes and presents a potential option to prepare ligand-free bimetal biocatalysts with sizes in the nanocluster regime.

PMID:36755199 | DOI:10.1002/smll.202206772

Categories: Literature Watch

An oracle predicts regulators of cell identity

Thu, 2023-02-09 06:00

Nature. 2023 Feb 8. doi: 10.1038/d41586-023-00251-6. Online ahead of print.

NO ABSTRACT

PMID:36755144 | DOI:10.1038/d41586-023-00251-6

Categories: Literature Watch

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