Front Bioeng Biotechnol. 2023 Feb 6;11:1146729. doi: 10.3389/fbioe.2023.1146729. eCollection 2023.

NO ABSTRACT

PMID:36814716 | PMC:PMC9939894 | DOI:10.3389/fbioe.2023.1146729

Front Endocrinol (Lausanne). 2023 Feb 6;14:1020368. doi: 10.3389/fendo.2023.1020368. eCollection 2023.

ABSTRACT

Teneurin C-terminal associated peptide (TCAP) is an ancient bioactive peptide that is highly conserved in metazoans. TCAP administration reduces cellular and behavioural stress in vertebrate and urochordate models, yet despite numerous studies in higher animals, there is limited knowledge of its role in invertebrates. In particular, there are no studies on TCAP's effects on the heart of any metazoan, which is a critical organ in the stress response. We used the Sydney rock oyster (SRO) as an invertebrate model to investigate a potential role for sroTCAP in regulating cardiac activity, including during stress. sroTCAP is localized to the neural innervation network of the SRO heart, and suggested binding with various heart proteins related to metabolism and stress, including SOD, GAPDH and metabotropic glutamate receptor. Intramuscular injection of sroTCAP (10 pmol) significantly altered the expression of heart genes that are known to regulate remodelling processes under different conditions, and modulated several gene families responsible for stress mitigation. sroTCAP (1 and 10 pmol) was shown to cause transient bradycardia (heart rate was reduced by up to 63% and for up to 40 min post-administration), indicative of an unstressed state. In summary, this study has established a role for a TCAP in the regulation of cardiac activity through modulation of physiological and molecular components associated with energy conservation, stress and adaptation. This represents a novel function for TCAP and may have implications for higher-order metazoans.

PMID:36814576 | PMC:PMC9939839 | DOI:10.3389/fendo.2023.1020368

Behav Res Methods. 2023 Feb 22. doi: 10.3758/s13428-023-02076-7. Online ahead of print.

ABSTRACT

The zebrafish is a laboratory species that gained increasing popularity the last decade in a variety of subfields of biology, including toxicology, ecology, medicine, and the neurosciences. An important phenotype often measured in these fields is behaviour. Consequently, numerous new behavioural apparati and paradigms have been developed for the zebrafish, including methods for the analysis of learning and memory in adult zebrafish. Perhaps the biggest obstacle in these methods is that zebrafish is particularly sensitive to human handling. To overcome this confound, automated learning paradigms have been developed with varying success. In this manuscript, we present a semi-automated home tank-based learning/memory test paradigm utilizing visual cues, and show that it is capable of quantifying classical associative learning performance in zebrafish. We demonstrate that in this task, zebrafish successfully acquire the association between coloured-light and food reward. The hardware and software components of the task are easy and cheap to obtain and simple to assemble and set up. The procedures of the paradigm allow the test fish to remain completely undisturbed by the experimenter for several days in their home (test) tank, eliminating human handling or human interference induced stress. We demonstrate that the development of cheap and simple automated home-tank-based learning paradigms for the zebrafish is feasible. We argue that such tasks will allow us to better characterize numerous cognitive and mnemonic features of the zebrafish, including elemental as well as configural learning and memory, which will, in turn, also enhance our ability to study neurobiological mechanisms underlying learning and memory using this model organism.

PMID:36814006 | DOI:10.3758/s13428-023-02076-7

Nat Metab. 2023 Feb 22. doi: 10.1038/s42255-023-00748-4. Online ahead of print.

NO ABSTRACT

PMID:36814000 | DOI:10.1038/s42255-023-00748-4

Sci Rep. 2023 Feb 22;13(1):3111. doi: 10.1038/s41598-023-30033-z.

NO ABSTRACT

PMID:36813794 | DOI:10.1038/s41598-023-30033-z

Nat Commun. 2023 Feb 22;14(1):986. doi: 10.1038/s41467-023-36517-w.

ABSTRACT

Abiotic stresses negatively impact ecosystems and the yield of crops, and climate change will increase their frequency and intensity. Despite progress in understanding how plants respond to individual stresses, our knowledge of plant acclimatization to combined stresses typically occurring in nature is still lacking. Here, we used a plant with minimal regulatory network redundancy, Marchantia polymorpha, to study how seven abiotic stresses, alone and in 19 pairwise combinations, affect the phenotype, gene expression, and activity of cellular pathways. While the transcriptomic responses show a conserved differential gene expression between Arabidopsis and Marchantia, we also observe a strong functional and transcriptional divergence between the two species. The reconstructed high-confidence gene regulatory network demonstrates that the response to specific stresses dominates those of others by relying on a large ensemble of transcription factors. We also show that a regression model could accurately predict the gene expression under combined stresses, indicating that Marchantia performs arithmetic multiplication to respond to multiple stresses. Lastly, two online resources ( https://conekt.plant.tools and http://bar.utoronto.ca/efp_marchantia/cgi-bin/efpWeb.cgi ) are provided to facilitate the study of gene expression in Marchantia exposed to abiotic stresses.

PMID:36813788 | DOI:10.1038/s41467-023-36517-w

Prog Mol Biol Transl Sci. 2023;196:59-97. doi: 10.1016/bs.pmbts.2022.09.007. Epub 2022 Nov 2.

ABSTRACT

AMPA receptors are glutamate-gated ion channels, present in a wide range of neuron types and in glial cells. Their main role is to mediate fast excitatory synaptic transmission, and therefore, they are critical for normal brain function. In neurons, AMPA receptors undergo constitutive and activity-dependent trafficking between the synaptic, extrasynaptic and intracellular pools. The kinetics of AMPA receptor trafficking is crucial for the precise functioning of both individual neurons and neural networks involved in information processing and learning. Many of the neurological diseases evoked by neurodevelopmental and neurodegenerative malfunctions or traumatic injuries are caused by impaired synaptic function in the central nervous system. For example, attention-deficit/hyperactivity disorder (ADHD), Alzheimer's disease (AD), tumors, seizures, ischemic strokes, and traumatic brain injury are all characterized by impaired glutamate homeostasis and associated neuronal death, typically caused by excitotoxicity. Given the important role of AMPA receptors in neuronal function, it is not surprising that perturbations in AMPA receptor trafficking are associated with these neurological disorders. In this book chapter, we will first introduce the structure, physiology and synthesis of AMPA receptors, followed by an in-depth description of the molecular mechanisms that control AMPA receptor endocytosis and surface levels under basal conditions or synaptic plasticity. Finally, we will discuss how impairments in AMPA receptor trafficking, particularly endocytosis, contribute to the pathophysiology of various neurological disorders and what efforts are being made to therapeutically target this process.

PMID:36813366 | DOI:10.1016/bs.pmbts.2022.09.007

Carbohydr Polym. 2023 May 15;308:120649. doi: 10.1016/j.carbpol.2023.120649. Epub 2023 Feb 3.

ABSTRACT

Heparin, a major anticoagulant drug, comprises a complex mixture of motifs. Heparin is isolated from natural sources while being subjected to a variety of conditions but the detailed effects of these on heparin structure have not been studied in depth. Therefore, the result of exposing heparin to a range of buffered environments, ranging pH values from 7 to 12, and temperatures of 40, 60 and 80 °C were examined. There was no evidence of significant N-desulfation or 6-O-desulfation in glucosamine residues, nor of chain scission, however, stereochemical re-arrangement of α-L-iduronate 2-O-sulfate to α-L-galacturonate residues occurred in 0.1 M phosphate buffer at pH 12/80 °C. The results confirm the relative stability of heparin in environments like those during extraction and purification processes; on the other hand, the sensitivity of heparin to pH 12 in buffered solution at high temperature is highlighted, providing an important insight for heparin manufacturers.

PMID:36813341 | DOI:10.1016/j.carbpol.2023.120649

Biotechnol Adv. 2023 Feb 20:108117. doi: 10.1016/j.biotechadv.2023.108117. Online ahead of print.

ABSTRACT

Living organisms produce a wide range of metabolites. Because of their potential antibacterial, antifungal, antiviral, or cytostatic properties, such natural molecules are of high interest to the pharmaceutical industry. In nature, these metabolites are often synthesized via secondary metabolic biosynthetic gene clusters that are silent under the typical culturing conditions. Among different techniques used to activate these silent gene clusters, co-culturing of "producer" species with specific "inducer" microbes is a particularly appealing approach due to its simplicity. Although several "inducer-producer" microbial consortia have been reported in the literature and hundreds of different secondary metabolites with attractive biopharmaceutical properties have been described as a result of co-cultivating inducer-producer consortia, less attention has been devoted to the understanding of the mechanisms and possible means of induction for production of secondary metabolites in co-cultures. This lack of understanding of fundamental biological functions and inter-species interactions significantly limits the diversity and yield of valuable compounds using biological engineering tools. In this review, we summarize and categorize the known physiological mechanisms of production of secondary metabolites in inducer-producer consortia, and then discuss approaches that could be exploited to optimize the discovery and production of secondary metabolites.

PMID:36813010 | DOI:10.1016/j.biotechadv.2023.108117

PLOS Digit Health. 2023 Jan 5;2(1):e0000162. doi: 10.1371/journal.pdig.0000162. eCollection 2023 Jan.

ABSTRACT

The accuracy and flexibility of artificial intelligence (AI) systems often comes at the cost of a decreased ability to offer an intuitive explanation of their predictions. This hinders trust and discourage adoption of AI in healthcare, exacerbated by concerns over liabilities and risks to patients' health in case of misdiagnosis. Providing an explanation for a model's prediction is possible due to recent advances in the field of interpretable machine learning. We considered a data set of hospital admissions linked to records of antibiotic prescriptions and susceptibilities of bacterial isolates. An appropriately trained gradient boosted decision tree algorithm, supplemented by a Shapley explanation model, predicts the likely antimicrobial drug resistance, with the odds of resistance informed by characteristics of the patient, admission data, and historical drug treatments and culture test results. Applying this AI-based system, we found that it substantially reduces the risk of mismatched treatment compared with the observed prescriptions. The Shapley values provide an intuitive association between observations/data and outcomes; the associations identified are broadly consistent with expectations based on prior knowledge from health specialists. The results, and the ability to attribute confidence and explanations, support the wider adoption of AI in healthcare.

PMID:36812617 | DOI:10.1371/journal.pdig.0000162

PLOS Digit Health. 2022 Sep 6;1(9):e0000101. doi: 10.1371/journal.pdig.0000101. eCollection 2022 Sep.

ABSTRACT

Clinical time-to-event studies are dependent on large sample sizes, often not available at a single institution. However, this is countered by the fact that, particularly in the medical field, individual institutions are often legally unable to share their data, as medical data is subject to strong privacy protection due to its particular sensitivity. But the collection, and especially aggregation into centralized datasets, is also fraught with substantial legal risks and often outright unlawful. Existing solutions using federated learning have already demonstrated considerable potential as an alternative for central data collection. Unfortunately, current approaches are incomplete or not easily applicable in clinical studies owing to the complexity of federated infrastructures. This work presents privacy-aware and federated implementations of the most used time-to-event algorithms (survival curve, cumulative hazard rate, log-rank test, and Cox proportional hazards model) in clinical trials, based on a hybrid approach of federated learning, additive secret sharing, and differential privacy. On several benchmark datasets, we show that all algorithms produce highly similar, or in some cases, even identical results compared to traditional centralized time-to-event algorithms. Furthermore, we were able to reproduce the results of a previous clinical time-to-event study in various federated scenarios. All algorithms are accessible through the intuitive web-app Partea (https://partea.zbh.uni-hamburg.de), offering a graphical user interface for clinicians and non-computational researchers without programming knowledge. Partea removes the high infrastructural hurdles derived from existing federated learning approaches and removes the complexity of execution. Therefore, it is an easy-to-use alternative to central data collection, reducing bureaucratic efforts but also the legal risks associated with the processing of personal data to a minimum.

PMID:36812603 | DOI:10.1371/journal.pdig.0000101

Sci Transl Med. 2023 Feb 22;15(684):eabq8476. doi: 10.1126/scitranslmed.abq8476. Epub 2023 Feb 22.

ABSTRACT

Periodontal disease is more common in individuals with rheumatoid arthritis (RA) who have detectable anti-citrullinated protein antibodies (ACPAs), implicating oral mucosal inflammation in RA pathogenesis. Here, we performed paired analysis of human and bacterial transcriptomics in longitudinal blood samples from RA patients. We found that patients with RA and periodontal disease experienced repeated oral bacteremias associated with transcriptional signatures of ISG15+HLADRhi and CD48highS100A2pos monocytes, recently identified in inflamed RA synovia and blood of those with RA flares. The oral bacteria observed transiently in blood were broadly citrullinated in the mouth, and their in situ citrullinated epitopes were targeted by extensively somatically hypermutated ACPAs encoded by RA blood plasmablasts. Together, these results suggest that (i) periodontal disease results in repeated breaches of the oral mucosa that release citrullinated oral bacteria into circulation, which (ii) activate inflammatory monocyte subsets that are observed in inflamed RA synovia and blood of RA patients with flares and (iii) activate ACPA B cells, thereby promoting affinity maturation and epitope spreading to citrullinated human antigens.

PMID:36812347 | DOI:10.1126/scitranslmed.abq8476

Lab Chip. 2023 Feb 22. doi: 10.1039/d2lc01096h. Online ahead of print.

ABSTRACT

Single-cell proteomics (SCP) reveals phenotypic heterogeneity by profiling individual cells, their biological states and functional outcomes upon signaling activation that can hardly be probed via other omics characterizations. This has become appealing to researchers as it enables an overall more holistic view of biological details underlying cellular processes, disease onset and progression, as well as facilitates unique biomarker identification from individual cells. Microfluidic-based strategies have become methods of choice for single-cell analysis because they allow facile assay integrations, such as cell sorting, manipulation, and content analysis. Notably, they have been serving as an enabling technology to improve the sensitivity, robustness, and reproducibility of recently developed SCP methods. Critical roles of microfluidics technologies are expected to further expand rapidly in advancing the next phase of SCP analysis to reveal more biological and clinical insights. In this review, we will capture the excitement of the recent achievements of microfluidics methods for both targeted and global SCP, including efforts to enhance the proteomic coverage, minimize sample loss, and increase multiplexity and throughput. Furthermore, we will discuss the advantages, challenges, applications, and future prospects of SCP.

PMID:36811978 | DOI:10.1039/d2lc01096h

J Biol Phys. 2023 Feb 22. doi: 10.1007/s10867-022-09624-w. Online ahead of print.

ABSTRACT

Calcium ([Formula: see text]), inositol trisphosphate ([Formula: see text]), and nitric oxide (NO) signaling are essential to maintain the structural integrity and physiological activity of fibroblast cells. The accumulation of excess quantity of NO for longer periods can lead to a variety of fibrotic disorders, including heart disease, penile fibrosis in Peyronie's disease (PD), and cystic fibrosis. The dynamics of these three signaling processes and their interdependence in fibroblast cells are not clearly known to date. A systems biology model is proposed using reaction-diffusion equations for calcium, [Formula: see text], and calcium-dependent NO synthesis in fibroblast cells. The finite element method (FEM) is used to examine [Formula: see text], [Formula: see text], and NO regulation and dysregulation in cells. The results throw light on the conditions that disturb the coupled [Formula: see text] and [Formula: see text] dynamics and the influence of these factors on the levels of NO concentration in the fibroblast cell. The findings suggest that changes in source inflow, buffers, and diffusion coefficient might induce an increase or reduction in nitric oxide and [Formula: see text] synthesis, resulting in fibroblast cell diseases. Furthermore, the findings provide new information regarding the size and intensity of diseases in response to changes in several factors of their dynamics, which has been linked to the development of cystic fibrosis and cancer. This knowledge could be valuable for developing novel approaches to the diagnosis of diseases and therapies for various disorders of fibroblast cells.

PMID:36811722 | DOI:10.1007/s10867-022-09624-w

Adv Nutr. 2023 Jan;14(1):1-11. doi: 10.1016/j.advnut.2022.11.002. Epub 2022 Dec 23.

ABSTRACT

Food security has become a pressing issue in the modern world. The ever-increasing world population, ongoing COVID-19 pandemic, and political conflicts together with climate change issues make the problem very challenging. Therefore, fundamental changes to the current food system and new sources of alternative food are required. Recently, the exploration of alternative food sources has been supported by numerous governmental and research organizations, as well as by small and large commercial ventures. Microalgae are gaining momentum as an effective source of alternative laboratory-based nutritional proteins as they are easy to grow under variable environmental conditions, with the added advantage of absorbing carbon dioxide. Despite their attractiveness, the utilization of microalgae faces several practical limitations. Here, we discuss both the potential and challenges of microalgae in food sustainability and their possible long-term contribution to the circular economy of converting food waste into feed via modern methods. We also argue that systems biology and artificial intelligence can play a role in overcoming some of the challenges and limitations; through data-guided metabolic flux optimization, and by systematically increasing the growth of the microalgae strains without negative outcomes, such as toxicity. This requires microalgae databases rich in omics data and further developments on its mining and analytics methods.

PMID:36811582 | DOI:10.1016/j.advnut.2022.11.002

New Phytol. 2023 Feb 22. doi: 10.1111/nph.18828. Online ahead of print.

ABSTRACT

Phytomyxea are intracellular biotrophic parasites infecting plants and stramenopiles, including the agriculturally impactful Plasmodiophora brassicae and the brown seaweed pathogen Maullinia ectocarpii. They belong to the clade Rhizaria, where phagotrophy is the main mode of nutrition. Phagocytosis is a complex trait of eukaryotes, well documented for free-living unicellular eukaryotes and specific cellular types of animals. Data on phagocytosis in intracellular, biotrophic parasites are scant. Phagocytosis, where parts of the host cell are consumed at once, is seemingly at odds with intracellular biotrophy. Here we provide evidence that phagotrophy is part of the nutritional strategy of Phytomyxea, using morphological and genetic data (including a novel transcriptome of Maullinia ectocarpii). We document intracellular phagocytosis in P. brassicae and M. ectocarpii by transmission electron microscopy (TEM) and fluorescent in situ hybridization. Our investigations confirm molecular signatures of phagocytosis in Phytomyxea and hint at a small specialised subset of genes used for intracellular phagocytosis. Microscopic evidence confirms the existence of intracellular phagocytosis, which in Phytomyxea targets primarily host organelles. Phagocytosis seems to coexist with the manipulation of host physiology typical of biotrophic interactions. Our findings resolve long debated questions on the feeding behaviour of Phytomyxea, suggesting an unrecognised role for phagocytosis in biotrophic interactions.

PMID:36810975 | DOI:10.1111/nph.18828

Nat Commun. 2023 Feb 21;14(1):670. doi: 10.1038/s41467-023-36284-8.

ABSTRACT

In the long-lived naked mole-rat (NMR), the entire process of oogenesis occurs postnatally. Germ cell numbers increase significantly in NMRs between postnatal days 5 (P5) and P8, and germs cells positive for proliferation markers (Ki-67, pHH3) are present at least until P90. Using pluripotency markers (SOX2 and OCT4) and the primordial germ cell (PGC) marker BLIMP1, we show that PGCs persist up to P90 alongside germ cells in all stages of female differentiation and undergo mitosis both in vivo and in vitro. We identified VASA+ SOX2+ cells at 6 months and at 3-years in subordinate and reproductively activated females. Reproductive activation was associated with proliferation of VASA+ SOX2+ cells. Collectively, our results suggest that highly desynchronized germ cell development and the maintenance of a small population of PGCs that can expand upon reproductive activation are unique strategies that could help to maintain the NMR's ovarian reserve for its 30-year reproductive lifespan.

PMID:36810851 | DOI:10.1038/s41467-023-36284-8

Biotechnol Bioeng. 2023 Feb 21. doi: 10.1002/bit.28358. Online ahead of print.

ABSTRACT

COVID-19 is known to be regulated by multiple factors such as delayed immune response, impaired T cell activation, elevated levels of pro-inflammatory cytokines affecting the disease severity. Clinical management of the disease remains challenging due to interplay of various factors as drug candidates may elicit different responses depending on stage of the disease. In this context, we propose a computational framework which provides insights into the interaction between viral infection and immune response in lung epithelial cells, with an aim of predicting optimal treatment strategies based on infection severity. First, we formulate the model for visualizing the non-linear dynamics during the disease progression considering the role of T cells, macrophages and pro-inflammatory cytokines. Here, we show that the model is capable of emulating the dynamic and static data trends of viral load, T cell, macrophage levels, IL-6 and TNF-⍺ levels. Secondly, we demonstrate the ability of the framework to capture the dynamics corresponding to mild, moderate, severe, and critical condition. Our result shows that, at late phase (>15 days), severity of disease is directly proportional to pro-inflammatory cytokine IL6 and TNF-⍺ levels and inversely proportional to the number of T cells. Finally, the simulation framework was used to assess the effect of drug administration time as well as efficacy of multiple drugs on patients. The major contribution of the proposed framework is to utilize the infection progression model for clinical management and administration of drugs inhibiting virus replication, cytokine levels as well as immunosuppressant drugs based on disease staging. This article is protected by copyright. All rights reserved.

PMID:36810760 | DOI:10.1002/bit.28358

Sci Rep. 2023 Feb 21;13(1):3002. doi: 10.1038/s41598-023-30004-4.

ABSTRACT

Pumilio proteins are RNA-binding proteins that control mRNA translation and stability by binding to the 3' UTR of target mRNAs. Mammals have two canonical Pumilio proteins, PUM1 and PUM2, which are known to act in many biological processes, including embryonic development, neurogenesis, cell cycle regulation and genomic stability. Here, we characterized a new role of both PUM1 and PUM2 in regulating cell morphology, migration, and adhesion in T-REx-293 cells, in addition to previously known defects in growth rate. Gene ontology analysis of differentially expressed genes in PUM double knockout (PDKO) cells for both cellular component and biological process showed enrichment in categories related to adhesion and migration. PDKO cells had a collective cell migration rate significantly lower than that of WT cells and displayed changes in actin morphology. In addition, during growth, PDKO cells aggregated into clusters (clumps) due to an inability to escape cell-cell contacts. Addition of extracellular matrix (Matrigel) alleviated the clumping phenotype. Collagen IV (ColIV), a major component of Matrigel, was shown to be the driving force in allowing PDKO cells to monolayer appropriately, however, ColIV protein levels remained unperturbed in PDKO cells. This study characterizes a novel cellular phenotype associated with cellular morphology, migration, and adhesion which can aid in developing better models for PUM function in both developmental processes and disease.

PMID:36810759 | DOI:10.1038/s41598-023-30004-4

Plant Physiol. 2023 Feb 22:kiad109. doi: 10.1093/plphys/kiad109. Online ahead of print.

NO ABSTRACT

PMID:36810681 | DOI:10.1093/plphys/kiad109