Insects. 2023 Feb 3;14(2):157. doi: 10.3390/insects14020157.

ABSTRACT

The oil palm-pollinating weevil (Elaeidobius kamerunicus Faust) was introduced from Cameroon, West Africa, to Malaysia in 1981, and subsequently, to other oil palm-growing countries as well. This study aims to develop a set of robust E. kamerunicus-specific nuclear DNA markers to directly assess the genetic diversity of the weevil populations. A total of 19,148 SNP and 223,200 SSR were discovered from 48 weevils representing three origins (Peninsular Malaysia, Sabah, and Riau) using RAD tag sequencing. Subsequent filtering steps further reduced these to 1000 SNP and 120 SSR. The selected 220 SNP exhibited a polymorphism information content (PIC) of 0.2387 (±0.1280), and 8 SSR had the PIC of 0.5084 (±0.1928). These markers were found to show sufficient polymorphism, making it possible to assign 180 weevils into three major clusters from Ghana, Cameroon, and Southeast Asia (mainly in Malaysia and Indonesia). These DNA markers successfully confirmed the Cameroon origin of the Southeast Asian cluster. However, the presence of null alleles in the SSR markers, due to limited flexibility of the probe design on the short RAD tags, led to an underestimation of heterozygosity within the populations. Hence, the developed SNP markers turned out to be more efficient than the SSR markers in the genetic diversity assessment of the E. kamerunicus populations. The genetic information provides useful insight into developing guidelines for the genetic monitoring and conservation planning of E. kamerunicus.

PMID:36835726 | DOI:10.3390/insects14020157

Insects. 2023 Feb 3;14(2):156. doi: 10.3390/insects14020156.

ABSTRACT

Differences in the semi-natural vegetation of field margins will affect the biological control services derived from the presence of these semi-natural habitats adjacent to fields. Of the plant functional traits that are most relevant for insects, plant life forms reflect different aspects of plant structure and functioning that can help predict the value of marginal vegetation for arthropods in agricultural systems. The aim of this study was to determine the effect of the vegetation structure of field margins on cereal aphids and on some of their natural enemies (parasitoids, hoverflies and ladybugs) in terms of plant life forms. We characterized margin vegetation using the relative cover of each life form and sampled insects in crops along transects parallel to field margins. Our results show that in the studied areas, the abundance of natural enemies was greater near margins dominated by annual plants than in margins dominated by perennial plants. On the other hand, the abundances of aphids and parasitism rates were higher near margins dominated by perennial woody plants than near margins dominated by perennial herbaceous plants. By promoting specific life forms in existing margins, farmers can enhance the conservation biological control and relieve aphid pressure on their crops.

PMID:36835725 | DOI:10.3390/insects14020156

Int J Mol Sci. 2023 Feb 20;24(4):4246. doi: 10.3390/ijms24044246.

ABSTRACT

The non-histone chromatin binding protein High Mobility Group AT-hook protein 2 (HMGA2) has important functions in chromatin remodeling, and genome maintenance and protection. Expression of HMGA2 is highest in embryonic stem cells, declines during cell differentiation and cell aging, but it is re-expressed in some cancers, where high HMGA2 expression frequently coincides with a poor prognosis. The nuclear functions of HMGA2 cannot be explained by binding to chromatin alone but involve complex interactions with other proteins that are incompletely understood. The present study used biotin proximity labeling, followed by proteomic analysis, to identify the nuclear interaction partners of HMGA2. We tested two different biotin ligase HMGA2 constructs (BioID2 and miniTurbo) with similar results, and identified known and new HMGA2 interaction partners, with functionalities mainly in chromatin biology. These HMGA2 biotin ligase fusion constructs offer exciting new possibilities for interactome discovery research, enabling the monitoring of nuclear HMGA2 interactomes during drug treatments.

PMID:36835656 | DOI:10.3390/ijms24044246

Int J Mol Sci. 2023 Feb 20;24(4):4177. doi: 10.3390/ijms24044177.

ABSTRACT

The placenta is a vital organ of pregnancy, regulating adaptation to pregnancy, gestational parent/fetal exchange, and ultimately, fetal development and growth. Not surprisingly, in cases of placental dysfunction-where aspects of placental development or function become compromised-adverse pregnancy outcomes can result. One common placenta-mediated disorder of pregnancy is preeclampsia (PE), a hypertensive disorder of pregnancy with a highly heterogeneous clinical presentation. The wide array of clinical characteristics observed in pregnant individuals and neonates of a PE pregnancy are likely the result of distinct forms of placental pathology underlying the PE diagnosis, explaining why no one common intervention has proven effective in the prevention or treatment of PE. The historical paradigm of placental pathology in PE highlights an important role for utero-placental malperfusion, placental hypoxia and oxidative stress, and a critical role for placental mitochondrial dysfunction in the pathogenesis and progression of the disease. In the current review, the evidence of placental mitochondrial dysfunction in the context of PE will be summarized, highlighting how altered mitochondrial function may be a common feature across distinct PE subtypes. Further, advances in this field of study and therapeutic targeting of mitochondria as a promising intervention for PE will be discussed.

PMID:36835587 | DOI:10.3390/ijms24044177

Int J Mol Sci. 2023 Feb 17;24(4):4100. doi: 10.3390/ijms24044100.

ABSTRACT

Pharmaceutical compounds are among several classes of contaminants of emerging concern, such as pesticides, heavy metals and personal care products, all of which are a major concern for aquatic ecosystems. The hazards posed by the presence of pharmaceutical is one which affects both freshwater organisms and human health-via non-target effects and by the contamination of drinking water sources. The molecular and phenotypic alterations of five pharmaceuticals which are commonly present in the aquatic environment were explored in daphnids under chronic exposures. Markers of physiology such as enzyme activities were combined with metabolic perturbations to assess the impact of metformin, diclofenac, gabapentin, carbamazepine and gemfibrozil on daphnids. Enzyme activity of markers of physiology included phosphatases, lipase, peptidase, β-galactosidase, lactate dehydrogenase, glutathione-S-transferase and glutathione reductase activities. Furthermore, targeted LC-MS/MS analysis focusing on glycolysis, the pentose phosphate pathway and the TCA cycle intermediates was performed to assess metabolic alterations. Exposure to pharmaceuticals resulted in the changes in activity for several enzymes of metabolism and the detoxification enzyme glutathione-S-transferase. Metabolic perturbations on key pathways revealed distinct groups and metabolic fingerprints for the different exposures and their mixtures. Chronic exposure to pharmaceuticals at low concentrations revealed significant alterations of metabolic and physiological endpoints.

PMID:36835510 | DOI:10.3390/ijms24044100

Int J Mol Sci. 2023 Feb 15;24(4):3917. doi: 10.3390/ijms24043917.

ABSTRACT

ATP-dependent SWI/SNF chromatin remodelling complexes are conserved multi-subunit assemblies that control genome activity. Functions of SWI/SNF complexes in plant development and growth have been well established, but the architecture of particular assemblies is unclear. In this study, we elucidate the organization of Arabidopsis SWI/SNF complexes formed around a BRM catalytic subunit, and define the requirement of bromodomain-containing proteins BRD1/2/13 for the formation and stability of the entire complex. Using affinity purification followed by mass spectrometry, we identify a set of BRM-associated subunits and demonstrate that the BRM complexes strongly resemble mammalian non-canonical BAF complexes. Furthermore, we identify BDH1 and 2 proteins as components of the BRM complex and, using mutant analyses, show that BDH1/2 are important for vegetative and generative development, as well as hormonal responses. We further show that BRD1/2/13 represent unique subunits of the BRM complexes, and their depletion severely affects the integrity of the complex, resulting in the formation of residual assemblies. Finally, analyses of BRM complexes after proteasome inhibition revealed the existence of a module consisting of the ATPase, ARP, and BDH proteins, assembled with other subunits in a BRD-dependent manner. Together, our results suggest modular organization of plant SWI/SNF complexes and provide a biochemical explanation for mutant phenotypes.

PMID:36835328 | DOI:10.3390/ijms24043917

Int J Mol Sci. 2023 Feb 13;24(4):3747. doi: 10.3390/ijms24043747.

ABSTRACT

Adjuvant endocrine therapy (AET) is the treatment of choice for early-stage estrogen receptor alpha (ERα)-positive breast cancer (BC). However, almost 40% of tamoxifen-treated cases display no response or a partial response to AET, thus increasing the need for new treatment options and strong predictors of the therapeutic response of patients at high risk of relapse. In addition to ERα, BC research has focused on ERβ1 and ERβ2 (isoforms of ERβ), the second ER isotype. At present, the impact of ERβ isoforms on ERα-positive BC prognosis and treatment remains elusive. In the present study, we established clones of MCF7 cells constitutively expressing human ERβ1 or ERβ2 and investigated their role in the response of MCF7 cells to antiestrogens [4-hydroxytamoxifen (OHΤ) and fulvestrant (ICI182,780)] and retinoids [all-trans retinoic acid (ATRA)]. We show that, compared to MCF7 cells, MCF7-ERβ1 and MCF7-ERβ2 cells were sensitized and desensitized, respectively, to the antiproliferative effect of the antiestrogens, ATRA and their combination and to the cytocidal effect of the combination of OHT and ATRA. Analysis of the global transcriptional changes upon OHT-ATRA combinatorial treatment revealed uniquely regulated genes associated with anticancer effects in MCF7-ERβ1 cells and cancer-promoting effects in MCF7-ERβ2 cells. Our data are favorable to ERβ1 being a marker of responsiveness and ERβ2 being a marker of resistance of MCF7 cells to antiestrogens alone and in combination with ATRA.

PMID:36835157 | DOI:10.3390/ijms24043747

Int J Mol Sci. 2023 Feb 6;24(4):3231. doi: 10.3390/ijms24043231.

ABSTRACT

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that is used against cognitive impairment in mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the neurobiological mechanisms underlying the rTMS therapeutic effects are still only partially investigated. Maladaptive plasticity, glial activation, and neuroinflammation, including metalloproteases (MMPs) activation, might represent new potential targets of the neurodegenerative process and progression from MCI to AD. In this study, we aimed to evaluate the effects of bilateral rTMS over the dorsolateral prefrontal cortex (DLPFC) on plasmatic levels of MMP1, -2, -9, and -10; MMPs-related tissue inhibitors TIMP1 and TIMP2; and cognitive performances in MCI patients. Patients received high-frequency (10 Hz) rTMS (MCI-TMS, n = 9) or sham stimulation (MCI-C, n = 9) daily for four weeks, and they were monitored for six months after TMS. The plasmatic levels of MMPs and TIMPs and the cognitive and behavioral scores, based on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Beck Depression Inventory II, Beck Anxiety Inventory, and Apathy Evaluation Scale, were assessed at baseline (T0) and after 1 month (T1) and 6 months (T2) since rTMS. In the MCI-TMS group, at T2, plasmatic levels of MMP1, -9, and -10 were reduced and paralleled by increased plasmatic levels of TIMP1 and TIMP2 and improvement of visuospatial performances. In conclusion, our findings suggest that targeting DLPFC by rTMS might result in the long-term modulation of the MMPs/TIMPs system in MCI patients and the neurobiological mechanisms associated with MCI progression to dementia.

PMID:36834642 | DOI:10.3390/ijms24043231

Int J Mol Sci. 2023 Feb 6;24(4):3197. doi: 10.3390/ijms24043197.

ABSTRACT

The DEAD-box proteins, one family of RNA-binding proteins (RBPs), participate in post-transcriptional regulation of gene expression with multiple aspects. Among them, DDX6 is an essential component of the cytoplasmic RNA processing body (P-body) and is involved in translational repression, miRNA-meditated gene silencing, and RNA decay. In addition to the cytoplasmic function, DDX6 is also present in the nucleus, but the nuclear function remains unknown. To decipher the potential role of DDX6 in the nucleus, we performed mass spectrometry analysis of immunoprecipitated DDX6 from a HeLa nuclear extract. We found that adenosine deaminases that act on RNA 1 (ADAR1) interact with DDX6 in the nucleus. Utilizing our newly developed dual-fluorescence reporter assay, we elucidated the DDX6 function as negative regulators in cellular ADAR1p110 and ADAR2. In addition, depletion of DDX6 and ADARs results in the opposite effect on facilitation of RA-induced differentiation of neuronal lineage cells. Our data suggest the impact of DDX6 in regulation of the cellular RNA editing level, thus contributing to differentiation in the neuronal cell model.

PMID:36834609 | DOI:10.3390/ijms24043197

Int J Mol Sci. 2023 Feb 4;24(4):3126. doi: 10.3390/ijms24043126.

ABSTRACT

To determine the origin of oscillatory potentials (OPs), binocular electroretinogram (ERG) recordings were performed under light and dark adaptation on adult healthy C57BL/6J mice. In the experimental group, 1 μL of PBS was injected into the left eye, while the right eye was injected with 1 μL of PBS containing different agents: APB, GABA, Bicuculline, TPMPA, Glutamate, DNQX, Glycine, Strychnine, or HEPES. The OP response depends on the type of photoreceptors involved, showing their maximum response amplitude in the ERG induced by mixed rod/cone stimulation. The oscillatory components of the OPs were affected by the injected agents, with some drugs inducing the complete abolition of oscillations (APB, GABA, Glutamate, or DNQX), whereas other drugs merely reduced the oscillatory amplitudes (Bicuculline, Glycine, Strychnine, or HEPES) or did not even affect the oscillations (TPMPA). Assuming that rod bipolar cells (RBC) express metabotropic Glutamate receptors, GABAA, GABAC, and Glycine receptors and that they release glutamate mainly on Glycinergic AII amacrine cells and GABAergic A17 amacrine cells, which are differently affected by the mentioned drugs, we propose that RBC-AII/A17 reciprocal synapses are responsible for the OP generation in the ERG recordings in the mice. We conclude that the reciprocal synapses between RBC and AII/A17 are the basis of the ERG OP oscillations of the light response, and this fact must be taken into consideration in any ERG test that shows a decrease in the OPs' amplitude.

PMID:36834538 | DOI:10.3390/ijms24043126

Int J Mol Sci. 2023 Feb 4;24(4):3079. doi: 10.3390/ijms24043079.

ABSTRACT

The HD-ZIP III transcription factor REVOLUTA (REV) is involved in early leaf development, as well as in leaf senescence. REV directly binds to the promoters of senescence-associated genes, including the central regulator WRKY53. As this direct regulation appears to be restricted to senescence, we aimed to characterize protein-interaction partners of REV which could mediate this senescence-specificity. The interaction between REV and the TIFY family member TIFY8 was confirmed by yeast two-hybrid assays, as well as by bimolecular fluorescence complementation in planta. This interaction inhibited REV's function as an activator of WRKY53 expression. Mutation or overexpression of TIFY8 accelerated or delayed senescence, respectively, but did not significantly alter early leaf development. Jasmonic acid (JA) had only a limited effect on TIFY8 expression or function; however, REV appears to be under the control of JA signaling. Accordingly, REV also interacted with many other members of the TIFY family, namely the PEAPODs and several JAZ proteins in the yeast system, which could potentially mediate the JA-response. Therefore, REV appears to be under the control of the TIFY family in two different ways: a JA-independent way through TIFY8, which controls REV function in senescence, and a JA-dependent way through PEAPODs and JAZ proteins.

PMID:36834490 | DOI:10.3390/ijms24043079

Int J Environ Res Public Health. 2023 Feb 19;20(4):3702. doi: 10.3390/ijerph20043702.

ABSTRACT

Being diverse and widely distributed globally, bats are a known reservoir of a series of emerging zoonotic viruses. We studied fecal viromes of twenty-six bats captured in 2015 in the Moscow Region and found 13 of 26 (50%) samples to be coronavirus positive. Of P. nathusii (the Nathusius' pipistrelle), 3 of 6 samples were carriers of a novel MERS-related betacoronavirus. We sequenced and assembled the complete genome of this betacoronavirus and named it MOW-BatCoV strain 15-22. Whole genome phylogenetic analysis suggests that MOW-BatCoV/15-22 falls into a distinct subclade closely related to human and camel MERS-CoV. Unexpectedly, the phylogenetic analysis of the novel MOW-BatCoV/15-22 spike gene showed the closest similarity to CoVs from Erinaceus europaeus (European hedgehog). We suppose MOW-BatCoV could have arisen as a result of recombination between ancestral viruses of bats and hedgehogs. Molecular docking analysis of MOW-BatCoV/15-22 spike glycoprotein binding to DPP4 receptors of different mammals predicted the highest binding ability with DPP4 of the Myotis brandtii bat (docking score -320.15) and the E. europaeus (docking score -294.51). Hedgehogs are widely kept as pets and are commonly found in areas of human habitation. As this novel bat-CoV is likely capable of infecting hedgehogs, we suggest hedgehogs can act as intermediate hosts between bats and humans for other bat-CoVs.

PMID:36834395 | DOI:10.3390/ijerph20043702

Genes (Basel). 2023 Jan 20;14(2):269. doi: 10.3390/genes14020269.

ABSTRACT

Context: Inferring gene regulatory networks (GRN) from high-throughput gene expression data is a challenging task for which different strategies have been developed. Nevertheless, no ever-winning method exists, and each method has its advantages, intrinsic biases, and application domains. Thus, in order to analyze a dataset, users should be able to test different techniques and choose the most appropriate one. This step can be particularly difficult and time consuming, since most methods' implementations are made available independently, possibly in different programming languages. The implementation of an open-source library containing different inference methods within a common framework is expected to be a valuable toolkit for the systems biology community. Results: In this work, we introduce GReNaDIne (Gene Regulatory Network Data-driven Inference), a Python package that implements 18 machine learning data-driven gene regulatory network inference methods. It also includes eight generalist preprocessing techniques, suitable for both RNA-seq and microarray dataset analysis, as well as four normalization techniques dedicated to RNA-seq. In addition, this package implements the possibility to combine the results of different inference tools to form robust and efficient ensembles. This package has been successfully assessed under the DREAM5 challenge benchmark dataset. The open-source GReNaDIne Python package is made freely available in a dedicated GitLab repository, as well as in the official third-party software repository PyPI Python Package Index. The latest documentation on the GReNaDIne library is also available at Read the Docs, an open-source software documentation hosting platform. Contribution: The GReNaDIne tool represents a technological contribution to the field of systems biology. This package can be used to infer gene regulatory networks from high-throughput gene expression data using different algorithms within the same framework. In order to analyze their datasets, users can apply a battery of preprocessing and postprocessing tools and choose the most adapted inference method from the GReNaDIne library and even combine the output of different methods to obtain more robust results. The results format provided by GReNaDIne is compatible with well-known complementary refinement tools such as PYSCENIC.

PMID:36833196 | DOI:10.3390/genes14020269

Genes (Basel). 2023 Jan 19;14(2):267. doi: 10.3390/genes14020267.

ABSTRACT

The GPRO suite is an in-progress bioinformatic project for -omics data analysis. As part of the continued growth of this project, we introduce a client- and server-side solution for comparative transcriptomics and analysis of variants. The client-side consists of two Java applications called "RNASeq" and "VariantSeq" to manage pipelines and workflows based on the most common command line interface tools for RNA-seq and Variant-seq analysis, respectively. As such, "RNASeq" and "VariantSeq" are coupled with a Linux server infrastructure (named GPRO Server-Side) that hosts all dependencies of each application (scripts, databases, and command line interface software). Implementation of the Server-Side requires a Linux operating system, PHP, SQL, Python, bash scripting, and third-party software. The GPRO Server-Side can be installed, via a Docker container, in the user's PC under any operating system or on remote servers, as a cloud solution. "RNASeq" and "VariantSeq" are both available as desktop (RCP compilation) and web (RAP compilation) applications. Each application has two execution modes: a step-by-step mode enables each step of the workflow to be executed independently, and a pipeline mode allows all steps to be run sequentially. "RNASeq" and "VariantSeq" also feature an experimental, online support system called GENIE that consists of a virtual (chatbot) assistant and a pipeline jobs panel coupled with an expert system. The chatbot can troubleshoot issues with the usage of each tool, the pipeline jobs panel provides information about the status of each computational job executed in the GPRO Server-Side, while the expert system provides the user with a potential recommendation to identify or fix failed analyses. Our solution is a ready-to-use topic specific platform that combines the user-friendliness, robustness, and security of desktop software, with the efficiency of cloud/web applications to manage pipelines and workflows based on command line interface software.

PMID:36833195 | DOI:10.3390/genes14020267

Genes (Basel). 2023 Jan 18;14(2):249. doi: 10.3390/genes14020249.

ABSTRACT

The history of Alu retroposons has been choreographed by the systematic accumulation of inherited diagnostic nucleotide substitutions to form discrete subfamilies, each having a distinct nucleotide consensus sequence. The oldest subfamily, AluJ, gave rise to AluS after the split between Strepsirrhini and what would become Catarrhini and Platyrrhini. The AluS lineage gave rise to AluY in catarrhines and to AluTa in platyrrhines. Platyrrhine Alu subfamilies Ta7, Ta10, and Ta15 were assigned names based on a standardized nomenclature. However, with the subsequent intensification of whole genome sequencing (WGS), large scale analyses to characterize Alu subfamilies using the program COSEG identified entire lineages of subfamilies simultaneously. The first platyrrhine genome with WGS, the common marmoset (Callithrix jacchus; [caljac3]), resulted in Alu subfamily names sf0 to sf94 in an arbitrary order. Although easily resolved by alignment of the consensus sequences, this naming convention can become increasingly confusing as more genomes are independently analyzed. In this study, we reported Alu subfamily characterization for the platyrrhine three-family clade of Cebidae, Callithrichidae, and Aotidae. We investigated one species/genome from each recognized family of Callithrichidae and Aotidae and of both subfamilies (Cebinae andSaimiriinae) of the family Cebidae. Furthermore, we constructed a comprehensive network of Alu subfamily evolution within the three-family clade of platyrrhines to provide a working framework for future research. Alu expansion in the three-family clade has been dominated by AluTa15 and its derivatives.

PMID:36833175 | DOI:10.3390/genes14020249

Entropy (Basel). 2023 Feb 9;25(2):319. doi: 10.3390/e25020319.

ABSTRACT

Communication between cells enables the coordination that drives structural and functional complexity in biological systems. Both single and multicellular organisms have evolved diverse communication systems for a range of purposes, including synchronization of behavior, division of labor, and spatial organization. Synthetic systems are also increasingly being engineered to utilize cell-cell communication. While research has elucidated the form and function of cell-cell communication in many biological systems, our knowledge is still limited by the confounding effects of other biological phenomena at play and the bias of the evolutionary background. In this work, our goal is to push forward the context-free understanding of what impact cell-cell communication can have on cellular and population behavior to more fully understand the extent to which cell-cell communication systems can be utilized, modified, and engineered. We use an in silico model of 3D multiscale cellular populations, with dynamic intracellular networks interacting via diffusible signals. We focus on two key communication parameters: the effective interaction distance at which cells are able to interact and the receptor activation threshold. We found that cell-cell communication can be divided into six different forms along the parameter axes, three asocial and three social. We also show that cellular behavior, tissue composition, and tissue diversity are all highly sensitive to both the general form and specific parameters of communication even when the cellular network has not been biased towards that behavior.

PMID:36832685 | DOI:10.3390/e25020319

Biosensors (Basel). 2023 Feb 14;13(2):271. doi: 10.3390/bios13020271.

ABSTRACT

This study reports the synthesis of a nanocomposite consisting of spongin and its applicability in the development of an aptasensing platform with high performance. The spongin was carefully extracted from a marine sponge and decorated with copper tungsten oxide hydroxide. The resulting spongin-copper tungsten oxide hydroxide was functionalized by silver nanoparticles and utilized in electrochemical aptasensor fabrication. The nanocomposite covered on a glassy carbon electrode surface amplified the electron transfer and increased active electrochemical sites. The aptasensor was fabricated by loading of thiolated aptamer on the embedded surface via thiol-AgNPs linkage. The applicability of the aptasensor was tested in detecting the Staphylococcus aureus bacterium as one of the five most common causes of nosocomial infectious diseases. The aptasensor measured S. aureus under a linear concentration range of 10-108 colony-forming units per milliliter and a limit of quantification and detection of 12 and 1 colony-forming unit per milliliter, respectively. The highly selective diagnosis of S. aureus in the presence of some common bacterial strains was satisfactorily evaluated. The acceptable results of the human serum analysis as the real sample may be promising in the bacteria tracking in clinical samples underlying the green chemistry principle.

PMID:36832038 | DOI:10.3390/bios13020271

Biosensors (Basel). 2023 Jan 26;13(2):187. doi: 10.3390/bios13020187.

ABSTRACT

Nowadays, morphology and molecular analyses at the single-cell level have a fundamental role in understanding biology better. These methods are utilized for cell phenotyping and in-depth studies of cellular processes, such as mitosis. Fluorescence microscopy and optical spectroscopy techniques, including Raman micro-spectroscopy, allow researchers to examine biological samples at the single-cell level in a non-destructive manner. Fluorescence microscopy can give detailed morphological information about the localization of stained molecules, while Raman microscopy can produce label-free images at the subcellular level; thus, it can reveal the spatial distribution of molecular fingerprints, even in live samples. Accordingly, the combination of correlative fluorescence and Raman microscopy (CFRM) offers a unique approach for studying cellular stages at the single-cell level. However, subcellular spectral maps are complex and challenging to interpret. Artificial intelligence (AI) may serve as a valuable solution to characterize the molecular backgrounds of phenotypes and biological processes by finding the characteristic patterns in spectral maps. The major contributions of the manuscript are: (I) it gives a comprehensive review of the literature focusing on AI techniques in Raman-based cellular phenotyping; (II) via the presentation of a case study, a new neural network-based approach is described, and the opportunities and limitations of AI, specifically deep learning, are discussed regarding the analysis of Raman spectroscopy data to classify mitotic cellular stages based on their spectral maps.

PMID:36831953 | DOI:10.3390/bios13020187

Cancers (Basel). 2023 Feb 17;15(4):1297. doi: 10.3390/cancers15041297.

ABSTRACT

Oncolytic virus (OV)-based immunotherapy is mainly dependent on establishing an efficient cell-mediated antitumor immunity. OV-mediated antitumor immunity elicits a renewed antitumor reactivity, stimulating a T-cell response against tumor-associated antigens (TAAs) and recruiting natural killer cells within the tumor microenvironment (TME). Despite the fact that OVs are unspecific cancer vaccine platforms, to further enhance antitumor immunity, it is crucial to identify the potentially immunogenic T-cell restricted TAAs, the main key orchestrators in evoking a specific and durable cytotoxic T-cell response. Today, innovative approaches derived from systems biology are exploited to improve target discovery in several types of cancer and to identify the MHC-I and II restricted peptide repertoire recognized by T-cells. Using specific computation pipelines, it is possible to select the best tumor peptide candidates that can be efficiently vectorized and delivered by numerous OV-based platforms, in order to reinforce anticancer immune responses. Beyond the identification of TAAs, system biology can also support the engineering of OVs with improved oncotropism to reduce toxicity and maintain a sufficient portion of the wild-type virus virulence. Finally, these technologies can also pave the way towards a more rational design of armed OVs where a transgene of interest can be delivered to TME to develop an intratumoral gene therapy to enhance specific immune stimuli.

PMID:36831638 | DOI:10.3390/cancers15041297

Cancers (Basel). 2023 Feb 11;15(4):1166. doi: 10.3390/cancers15041166.

ABSTRACT

(1) Background: Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Wide application of prostate specific antigen test has historically led to over-treatment, starting from excessive biopsies. Risk calculators based on molecular and clinical variables can be of value to determine the risk of PCa and as such, reduce unnecessary and invasive biopsies. Urinary molecular studies have been mostly focusing on sampling after initial intervention (digital rectal examination and/or prostate massage). (2) Methods: Building on previous proteomics studies, in this manuscript, we aimed at developing a biomarker model for PCa detection based on urine sampling without prior intervention. Capillary electrophoresis coupled to mass spectrometry was applied to acquire proteomics profiles from 970 patients from two different clinical centers. (3) Results: A case-control comparison was performed in a training set of 413 patients and 181 significant peptides were subsequently combined by a support vector machine algorithm. Independent validation was initially performed in 272 negative for PCa and 138 biopsy-confirmed PCa, resulting in an AUC of 0.81, outperforming current standards, while a second validation phase included 147 PCa patients. (4) Conclusions: This multi-dimensional biomarker model holds promise to improve the current diagnosis of PCa, by guiding invasive biopsies.

PMID:36831508 | DOI:10.3390/cancers15041166