Sci Rep. 2023 Jul 5;13(1):10895. doi: 10.1038/s41598-023-37721-w.

ABSTRACT

Diaphorina citri Kuwayama, also known as the Asian citrus psyllid (ACP), can vector the bacterium Candidatus Liberibacter asiaticus (CLas), agent of Huanglongbing (HLB): an incurable disease affecting citrus trees worldwide. In citrus growing regions where ACP and HLB are absent, such as Australia, the risk of an incursion and consequent economic damage to citrus industries make this psyllid one of the top-priority pests. Due to ACP's small dimensions and the generally poorly studied native psylloid fauna worldwide, morphological identification of this insect to distinguish it from harmless species is challenging, especially in the field, and with immature, partial or damaged specimens. To allow rapid and efficient detection of ACP in the field, we designed and optimised a new Loop-mediated isothermal amplification (LAMP) assay for the detection of D. citri based on the mitochondrial 16S locus. The optimised ACP 16S LAMP assay produced amplification from D. citri samples within 13.3 ± 3.6 min, with an anneal derivative of ~ 78.5 °C. A synthetic gBlock gene fragment was also developed to be used as positive control for the new LAMP assay with a different anneal derivative of ~ 83 °C. An existing commercially available LAMP assay for detection of the bacterium CLas was also tested in this study on ACP DNA. The ACP 16S LAMP assay we developed and tested here provides a valuable new in-field compatible tool that can allow early detections of ACP, enabling a quick biosecurity response, and could potentially be adopted by a wide range of users, from farmers to agronomists and from researchers to industry.

PMID:37407637 | DOI:10.1038/s41598-023-37721-w

Nat Commun. 2023 Jul 5;14(1):3966. doi: 10.1038/s41467-023-39591-2.

ABSTRACT

KRAS is a frequent driver in lung cancer. To identify KRAS-specific vulnerabilities in lung cancer, we performed RNAi screens in primary spheroids derived from a Kras mutant mouse lung cancer model and discovered an epigenetic regulator Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1). In human lung cancer models UHRF1 knock-out selectively impaired growth and induced apoptosis only in KRAS mutant cells. Genome-wide methylation and gene expression analysis of UHRF1-depleted KRAS mutant cells revealed global DNA hypomethylation leading to upregulation of tumor suppressor genes (TSGs). A focused CRISPR/Cas9 screen validated several of these TSGs as mediators of UHRF1-driven tumorigenesis. In vivo, UHRF1 knock-out inhibited tumor growth of KRAS-driven mouse lung cancer models. Finally, in lung cancer patients high UHRF1 expression is anti-correlated with TSG expression and predicts worse outcomes for patients with KRAS mutant tumors. These results nominate UHRF1 as a KRAS-specific vulnerability and potential target for therapeutic intervention.

PMID:37407562 | DOI:10.1038/s41467-023-39591-2

Dev Biol. 2023 Jul 3:S0012-1606(23)00109-4. doi: 10.1016/j.ydbio.2023.06.010. Online ahead of print.

NO ABSTRACT

PMID:37407371 | DOI:10.1016/j.ydbio.2023.06.010

Mol Biol Evol. 2023 Jul 5;40(7):msad141. doi: 10.1093/molbev/msad141.

ABSTRACT

Angiosperms have a complex history of whole-genome duplications (WGDs), with varying numbers and ages of WGD events across clades. These WGDs have greatly affected the composition of plant genomes due to the biased retention of genes belonging to certain functional categories following their duplication. In particular, regulatory genes and genes encoding proteins that act in multiprotein complexes have been retained in excess following WGD. Here, we inferred protein-protein interaction (PPI) networks and gene regulatory networks (GRNs) for seven well-characterized angiosperm species and explored the impact of both WGD and small-scale duplications (SSDs) in network topology by analyzing changes in frequency of network motifs. We found that PPI networks are enriched in WGD-derived genes associated with dosage-sensitive intricate systems, and strong selection pressures constrain the divergence of WGD-derived genes at the sequence and PPI levels. WGD-derived genes in network motifs are mostly associated with dosage-sensitive processes, such as regulation of transcription and cell cycle, translation, photosynthesis, and carbon metabolism, whereas SSD-derived genes in motifs are associated with response to biotic and abiotic stress. Recent polyploids have higher motif frequencies than ancient polyploids, whereas WGD-derived network motifs tend to be disrupted on the longer term. Our findings demonstrate that both WGD and SSD have contributed to the evolution of angiosperm GRNs, but in different ways, with WGD events likely having a more significant impact on the short-term evolution of polyploids.

PMID:37405949 | DOI:10.1093/molbev/msad141

STAR Protoc. 2023 Jul 4;4(3):102401. doi: 10.1016/j.xpro.2023.102401. Online ahead of print.

ABSTRACT

RNA-binding proteins (RBPs) can bind and mediate RNA-RNA contacts. However, identifying specific RBP-organized RNA-RNA contacts remains challenging. Here, we present a capture RIC-seq (CRIC-seq) technique to map specific RBP-associated RNA-RNA contacts globally. We describe steps for formaldehyde cross-linking to fix RNA in situ conformation, pCp-biotin labeling to mark RNA juncture, and in situ proximity ligation to join proximal RNAs. We then detail immunoprecipitation to isolate specific RBP-associated RNA-RNA contacts, biotin-streptavidin selection to enrich chimeric RNAs, and library construction for paired-end sequencing. For complete information on the generation and use of this protocol, please refer to Ye et al.1.

PMID:37405924 | DOI:10.1016/j.xpro.2023.102401

Front Mol Biosci. 2023 Jun 19;10:1164220. doi: 10.3389/fmolb.2023.1164220. eCollection 2023.

ABSTRACT

Introduction: Coronavirus disease 2019 (COVID-19) has become a global pandemic and poses a serious threat to human health. Many studies have shown that pre-existing nonalcoholic steatohepatitis (NASH) can worsen the clinical symptoms in patients suffering from COVID-19. However, the potential molecular mechanisms between NASH and COVID-19 remain unclear. To this end, key molecules and pathways between COVID-19 and NASH were herein explored by bioinformatic analysis. Methods: The common differentially expressed genes (DEGs) between NASH and COVID-19 were obtained by differential gene analysis. Enrichment analysis and protein-protein interaction (PPI) network analysis were carried out using the obtained common DEGs. The key modules and hub genes in PPI network were obtained by using the plug-in of Cytoscape software. Subsequently, the hub genes were verified using datasets of NASH (GSE180882) and COVID-19 (GSE150316), and further evaluated by principal component analysis (PCA) and receiver operating characteristic (ROC). Finally, the verified hub genes were analyzed by single-sample gene set enrichment analysis (ssGSEA) and NetworkAnalyst was used for the analysis of transcription factor (TF)-gene interactions, TF-microRNAs (miRNA) coregulatory network, and Protein-chemical Interactions. Results: A total of 120 DEGs between NASH and COVID-19 datasets were obtained, and the PPI network was constructed. Two key modules were obtained via the PPI network, and enrichment analysis of the key modules revealed the common association between NASH and COVID-19. In total, 16 hub genes were obtained by five algorithms, and six of them, namely, Kruppel-like factor 6 (KLF6), early growth response 1 (EGR1), growth arrest and DNA-damage-inducible 45 beta (GADD45B), JUNB, FOS, and FOS-like antigen 1 (FOSL1) were confirmed to be closely related to NASH and COVID-19. Finally, the relationship between hub genes and related pathways was analyzed, and the interaction network of six hub genes was constructed with TFs, miRNAs, and compounds. Conclusion: This study identified six hub genes related to COVID-19 and NASH, providing a new perspective for disease diagnosis and drug development.

PMID:37405258 | PMC:PMC10315682 | DOI:10.3389/fmolb.2023.1164220

Drug Des Devel Ther. 2023 Jun 28;17:1933-1943. doi: 10.2147/DDDT.S417563. eCollection 2023.

ABSTRACT

Moving a new drug from bench to bedside is a long and arduous process. The tactic of drug repurposing, which solves "new" diseases with "old" existing drugs, is more efficient and economical than conventional ab-initio way for drug development. Information technology has dramatically changed the paradigm of biomedical research in the new century, and drug repurposing studies have been significantly accelerated by implementing informatics techniques related to genomics, systems biology and biophysics during the past few years. A series of remarkable achievements in this field comes with the practical applications of in silico approaches including transcriptomic signature matching, gene-connection-based scanning, and simulated structure docking in repositioning drug therapies against breast cancer. In this review, we systematically curated these impressive accomplishments with summarization of the main findings on potentially repurposable drugs, and provide our insights into the current issues as well as future directions of the field. With the prospective improvement in reliability, the computer-assisted repurposing strategy will play a more critical role in drug research and development.

PMID:37405253 | PMC:PMC10315146 | DOI:10.2147/DDDT.S417563

J Res Med Sci. 2023 May 29;28:43. doi: 10.4103/jrms.jrms_702_22. eCollection 2023.

ABSTRACT

BACKGROUND: Diabetic kidney disease has substantial burden and limited therapeutic options. An inadequate understanding of the complex gene regulatory circuits underlying this disorder contributes to the insufficiency of current treatment strategies. MicroRNAs (miRNAs) play a crucial role as regulators of functionally related gene networks. Previously, mmu-mir-802-5p was identified as the sole dysregulated miRNA in both the kidney cortex and medulla of diabetic mice. This study aims to investigate the role of miR-802-5p in diabetic kidney disease.

MATERIALS AND METHODS: The validated and predicted targets of miR-802-5p were identified using miRTarBase and TargetScan databases, respectively. The functional role of this miRNA was inferred using gene ontology enrichment analysis. The expression of miR-802-5p and its selected targets were assessed by qPCR. The expression of the angiotensin receptor (Agtr1a) was measured by ELISA.

RESULTS: miR-802-5p exhibited dysregulation in both the kidney cortex and medulla of diabetic mice, with two- and four-fold over-expressions, respectively. Functional enrichment analysis of the validated and predicted targets of miR-802-5p revealed its involvement in the renin-angiotensin pathway, inflammation, and kidney development. Differential expression was observed in the Pten transcript and Agtr1a protein among the examined gene targets.

CONCLUSION: These findings suggest that miR-802-5p is a critical regulator of diabetic nephropathy in the cortex and medulla compartments, contributing to disease pathogenesis through the renin-angiotensin axis and inflammatory pathways.

PMID:37405075 | PMC:PMC10315408 | DOI:10.4103/jrms.jrms_702_22

Front Bioeng Biotechnol. 2023 Jun 19;11:1202836. doi: 10.3389/fbioe.2023.1202836. eCollection 2023.

ABSTRACT

The optimization of genetically engineered biological constructs is a key step to deliver high-impact biotechnological applications. The use of high-throughput DNA assembly methods allows the construction of enough genotypic variants to successfully cover the target design space. This, however, entails extra workload for researchers during the screening stage of candidate variants. Despite the existence of commercial colony pickers, their high price excludes small research laboratories and budget-adjusted institutions from accessing such extensive screening capability. In this work we present COPICK, a technical solution to automatize colony picking in an open-source liquid handler Opentrons OT-2. COPICK relies on a mounted camera to capture images of regular Petri dishes and detect microbial colonies for automated screening. COPICK's software can then automatically select the best colonies according to different criteria (size, color and fluorescence) and execute a protocol to pick them for further analysis. Benchmark tests performed for E. coli and P. putida colonies delivers a raw picking performance over pickable colonies of 82% with an accuracy of 73.4% at an estimated rate of 240 colonies/h. These results validate the utility of COPICK, and highlight the importance of ongoing technical improvements in open-source laboratory equipment to support smaller research teams.

PMID:37404684 | PMC:PMC10315574 | DOI:10.3389/fbioe.2023.1202836

Front Neurosci. 2023 Jun 19;17:1198243. doi: 10.3389/fnins.2023.1198243. eCollection 2023.

ABSTRACT

INTRODUCTION: The human brain comprises heterogeneous cell types whose composition can be altered with physiological and pathological conditions. New approaches to discern the diversity and distribution of brain cells associated with neurological conditions would significantly advance the study of brain-related pathophysiology and neuroscience. Unlike single-nuclei approaches, DNA methylation-based deconvolution does not require special sample handling or processing, is cost-effective, and easily scales to large study designs. Existing DNA methylation-based methods for brain cell deconvolution are limited in the number of cell types deconvolved.

METHODS: Using DNA methylation profiles of the top cell-type-specific differentially methylated CpGs, we employed a hierarchical modeling approach to deconvolve GABAergic neurons, glutamatergic neurons, astrocytes, microglial cells, oligodendrocytes, endothelial cells, and stromal cells.

RESULTS: We demonstrate the utility of our method by applying it to data on normal tissues from various brain regions and in aging and diseased tissues, including Alzheimer's disease, autism, Huntington's disease, epilepsy, and schizophrenia.

DISCUSSION: We expect that the ability to determine the cellular composition in the brain using only DNA from bulk samples will accelerate understanding brain cell type composition and cell-type-specific epigenetic states in normal and diseased brain tissues.

PMID:37404460 | PMC:PMC10315586 | DOI:10.3389/fnins.2023.1198243

iScience. 2023 Jun 20;26(7):107187. doi: 10.1016/j.isci.2023.107187. eCollection 2023 Jul 21.

ABSTRACT

Tissue-residential natural killer (trNK) cells act as pioneering responders during infectious challenges. However, their discrimination with conventional NK (cNK) cells is still an issue. Through an integrative transcriptome comparison of the two NK subgroups from different tissues, we have defined two genesets capable of efficiently distinguishing them. Based on the two genesets, a fundamental difference between the activation of trNK and cNK is identified and further confirmed. Mechanistically, we have discovered a particular role of chromatin landscape in regulating the trNK activation. In addition, IL-21R and IL-18R are respectively highly expressed by trNK and cNK, indicating a role of cytokine milieu in determining their differential activation. Indeed, IL-21 is particularly critical in accessorily promoting trNK activation using a bunch of bifunctional transcription factors. Together, this study sheds light on the bona fide difference between trNK and cNK, which will further expand our knowledge about their distinct functionalities during immune responses.

PMID:37404378 | PMC:PMC10316664 | DOI:10.1016/j.isci.2023.107187

iScience. 2023 Jun 12;26(7):107101. doi: 10.1016/j.isci.2023.107101. eCollection 2023 Jul 21.

ABSTRACT

Cancer is a leading cause of mortality and morbidity globally. Sex differences in cancer are evident in death rates and treatment responses in several cancers. Asian patients have unique cancer epidemiology influenced by their genetic ancestry and sociocultural factors in the region. In this review, we show molecular associations that potentially mediate sex disparities observed in cancer in Asian populations. Differences in sex characteristics are evident at the cytogenetic, genetic, and epigenetic levels mediating processes that include cell cycle, oncogenesis, and metastasis. Larger clinical and in vitro studies that explore mechanisms can confirm the associations of these molecular markers. In-depth studies of these markers can reveal their importance as diagnostics, prognostics, and therapeutic efficacy markers. Sex differences should be considered in designing novel cancer therapeutics in this era of precision medicine.

PMID:37404373 | PMC:PMC10316661 | DOI:10.1016/j.isci.2023.107101

Appl Environ Microbiol. 2023 Jul 5:e0017723. doi: 10.1128/aem.00177-23. Online ahead of print.

ABSTRACT

Bacteriophages (phages), which are viruses that infect bacteria, are the most abundant components of microbial communities and play roles in community dynamics and host evolution. However, the study of phage-host interactions is hindered by a paucity of model systems from natural environments. Here, we investigate phage-host interactions in the "pink berry" consortia, which are naturally occurring, low-diversity, macroscopic bacterial aggregates that are found in the Sippewissett Salt Marsh (Falmouth, MA, USA). We leverage metagenomic sequence data and a comparative genomics approach to identify eight compete phage genomes, infer their bacterial hosts from host-encoded clustered regularly interspaced short palindromic repeats (CRISPRs), and observe the potential evolutionary consequences of these interactions. Seven of the eight phages identified infect known pink berry symbionts, namely, Desulfofustis sp. PB-SRB1, Thiohalocapsa sp. PB-PSB1, and Rhodobacteraceae sp. A2, and they are largely divergent from known viruses. In contrast to the conserved bacterial community structure of pink berries, the distribution of these phages across aggregates is highly variable. Two phages persisted over a period of seven years with high sequence conservation, allowing us to identify gene gain and loss. Increased nucleotide variation in a conserved phage capsid gene that is commonly targeted by host CRISPR systems suggests that CRISPRs may drive phage evolution in pink berries. Finally, we identified a predicted phage lysin gene that was horizontally transferred to its bacterial host, potentially via a transposon intermediary. Taken together, our results demonstrate that pink berry consortia contain diverse and variable phages as well as provide evidence for phage-host coevolution via multiple mechanisms in a natural microbial system. IMPORTANCE Phages, which are viruses that infect bacteria, are important components of all microbial systems, in which they drive the turnover of organic matter by lysing host cells, facilitate horizontal gene transfer (HGT), and coevolve with their bacterial hosts. Bacteria resist phage infection, which is often costly or lethal, through a diversity of mechanisms. One of these mechanisms is CRISPR systems, which encode arrays of phage-derived sequences from past infections to block subsequent infection with related phages. Here, we investigate the bacteria and phage populations from a simple marine microbial community, known as "pink berries", found in salt marshes of Falmouth, Massachusetts, as a model of phage-host coevolution. We identify eight novel phages and characterize a case of putative CRISPR-driven phage evolution as well as an instance of HGT between a phage and its host, together suggesting that phages have large evolutionary impacts in a naturally occurring microbial community.

PMID:37404190 | DOI:10.1128/aem.00177-23

Rev Med Suisse. 2023 Jul 5;19(834):1322-1326. doi: 10.53738/REVMED.2023.19.834.1322.

ABSTRACT

Agent-Based Modelling (ABM) is a computer modelling technique that simulates the behaviour and interactions of autonomous agents within a virtual environment. Applied to health equity, this technique allows for a better understanding of the complex social and economic determinants that contribute to health inequities and enables the evaluation of the potential effects of public policies on the latter. Despite some limitations related to the accessibility and quality of health data and the complexity of the models, ABM appears to be a promising tool in the field of health equity, both for researchers in public or community health and for policy makers.

PMID:37403955 | DOI:10.53738/REVMED.2023.19.834.1322

Mol Omics. 2023 Jul 5. doi: 10.1039/d3mo00049d. Online ahead of print.

ABSTRACT

Molecular crosstalk, the dialogue between different cell types, is attracting more attention in cancer research. On the one hand, the communication between tumor and non-tumor cells in the microenvironment or between different tumor clones has influential consequences for the progression and spread of tumors and response to treatment. On the other hand, novel techniques such as single-cell sequencing or spatial transcriptomics provide detailed information that needs to be interpreted. TALKIEN: crossTALK IntEraction Network is a simple and intuitive online R/shiny application to visualize molecular crosstalk information through the construction and analysis of a protein-protein interaction network. Taking two or more lists of genes or proteins as input, which are representative of cell lineages, TALKIEN extracts information about ligand-receptor interactions, builds a network and analyzes it using systems biology techniques such as centrality measures and component analysis, among others. Moreover, it expands the network displaying pathways downstream receptors. The application allows users to select different graphical layouts, performs functional analysis and gives information about drugs targeting receptors. In conclusion, TALKIEN allows users to detect ligand-receptor interactions generating new in silico predictions of cell-cell communication thus providing a translational rationale for future experiments. It is freely available at https://www.odap-ico.org/talkien.

PMID:37403821 | DOI:10.1039/d3mo00049d

Nucleic Acids Res. 2023 Jul 5:gkad562. doi: 10.1093/nar/gkad562. Online ahead of print.

ABSTRACT

Cis-regulatory elements (CREs) can be classified by the shapes of their transcription start site (TSS) profiles, which are indicative of distinct regulatory mechanisms. Massively parallel reporter assays (MPRAs) are increasingly being used to study CRE regulatory mechanisms, yet the degree to which MPRAs replicate individual endogenous TSS profiles has not been determined. Here, we present a new low-input MPRA protocol (TSS-MPRA) that enables measuring TSS profiles of episomal reporters as well as after lentiviral reporter chromatinization. To sensitively compare MPRA and endogenous TSS profiles, we developed a novel dissimilarity scoring algorithm (WIP score) that outperforms the frequently used earth mover's distance on experimental data. Using TSS-MPRA and WIP scoring on 500 unique reporter inserts, we found that short (153 bp) MPRA promoter inserts replicate the endogenous TSS patterns of ∼60% of promoters. Lentiviral reporter chromatinization did not improve fidelity of TSS-MPRA initiation patterns, and increasing insert size frequently led to activation of extraneous TSS in the MPRA that are not active in vivo. We discuss the implications of our findings, which highlight important caveats when using MPRAs to study transcription mechanisms. Finally, we illustrate how TSS-MPRA and WIP scoring can provide novel insights into the impact of transcription factor motif mutations and genetic variants on TSS patterns and transcription levels.

PMID:37403796 | DOI:10.1093/nar/gkad562

J Sci Food Agric. 2023 Jul 5. doi: 10.1002/jsfa.12827. Online ahead of print.

ABSTRACT

BACKGROUND: Aroma is an important agronomic trait for strawberries, and the improvement of fruit flavor is a key goal in current strawberry breeding programs. Fragaria vesca (also known as woodland strawberry) has become an excellent model plant with exquisite flavor, a small genome size, and a short life cycle. Thus, the comprehensive identification of fruit volatiles and their accumulation pattern of F. vesca strawberries are very important and necessary to the fruit aroma study. This study examined the volatile profile changes from the fruits of three F. vesca genotypes during maturation using the headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME GC-MS) with multivariate analysis.

RESULTS: A total of 191 putative volatile compounds were identified, while 152, 159, and 175 volatiles were detected in 20-30 dap fruits of Hawaii 4 (HW), Reugen (RG), and Yellow Wonder (YW), respectively. Aldehydes and alcohols predominated in the early time point while esters were predominant during the late time point. Ketones were the dominant compounds from F. vesca strawberries fruits at the ripe stage. Certain genotype-characteristic volatiles were identified, including eugenol, γ-octalactone, and δ-decalactone were only detected in YW, and mesifurane was found in HW.

CONCLUSIONS: RG and YW showed very similar volatile compositions, but YW presented a greater number of volatiles and RG yielded a higher content. Differences in the volatile composition may be primarily due to genetic relationships. The metabolic changes that occurred during fruit ripening and characteristic volatiles will be a useful reference for future strawberry volatile studies. This article is protected by copyright. All rights reserved.

PMID:37403783 | DOI:10.1002/jsfa.12827

J Med Virol. 2023 Jul;95(7):e28900. doi: 10.1002/jmv.28900.

ABSTRACT

Antibodies triggering Fc-mediated NK cell activity may contribute to protection against disease caused by SARS-CoV-2 infection in humans. However, how these Fc-mediated humoral responses compare between individuals displaying hybrid immunity (Vac-ex) and those fully vaccinated with no history of SARS-CoV-2 infection (Vac-n) and whether they correlate with neutralizing antibody (NtAb) responses remains largely undetermined. In this retrospective study serum samples from 50 individuals (median age, 44.5 years; range, 11-85; 25 males), 25 Vac-ex and 25 Vac-n were studied. A flow-cytometry-based antibody-mediated NK-cell activation assay was used to quantitate effector NK-cells stimulated to express LAMP1 (lysosomal associated membrane protein 1), MIP1 (Macrophage inflammatory protein 1), and interferon-γ (IFNγ); NK cells isolated from two donors (D1 and D2) were used. NtAb levels targeting the Spike protein of Wuhan-Hu-1 and Omicron BA.1 SARS-CoV-2 variants were quantitated using a SARS-CoV-2 S pseudotyped neutralization assay. Regardless of the SARS-CoV-2 variant S antigen used in the NK-cell activation assay, the frequency of NK cells stimulated to express LAMP-1, MIP1β, and IFNγ was higher in Vac-ex compared with Vac-n (p values ranging from 0.07 to 0.006) for D1; this was only seen for BA.1 when NK cells from D2 were employed. The frequency of functional NK cells activated by antibody binding to either Wuhan-Hu-1 or Omicron BA.1 S protein was not significantly different for both VAC-ex and VAC-n. In contrast, NtAb titers against BA.1 were around 10-fold lower than that against Wuhan-Hu-1. Vac-ex displayed higher NtAb titers against both (sub)variants than Vac-n. NK-cell responses correlated poorly with NtAb titers (ρ ≤ 0.30). The data demonstrate higher cross-reactivity across variants of concern for antibodies triggering Fc-mediated NK cell than for NtAb. Moreover, Vac-Ex seemed to display more robust functional antibody responses as compared with Vac-n.

PMID:37403730 | DOI:10.1002/jmv.28900

Cancer Prev Res (Phila). 2023 Jul 5;16(7):365-367. doi: 10.1158/1940-6207.CAPR-23-0081.

ABSTRACT

Nearly all cancers have identifiable histologically defined precursors known as precancers. These precancers offer a window of opportunity to intercept the neoplastic process to prevent its development into invasive cancer. However, lack of knowledge regarding the evolution of precancers and the microenvironmental pressures shaping them precludes efforts to intercept them. Technological developments over the past decade have facilitated the study of precancers at a previously unattainable resolution. Calls for a national PreCancer Atlas effort incorporating these technologies were heeded in 2018, with the launch of the Human Tumor Atlas Network (HTAN) as part of the Beau Biden National Cancer Moonshot. Since then, five funded HTAN groups have focused their efforts on profiling precancers from breast, colon, skin, and lung. In this time, what progress has been made? What is next for HTAN and the field of premalignant biology? And are there lessons that individual investigators and the larger prevention field can learn from this initial effort to accelerate the development of novel early detection methods, risk prediction biomarkers, and interception agents? A special collection of invited reviews by experts in cancer evolution, systems biology, immunology, cancer genetics, preventive agent development, among other areas, attempts to answer these questions.

PMID:37403656 | DOI:10.1158/1940-6207.CAPR-23-0081

BJPsych Open. 2023 Jul 5;9(4):e120. doi: 10.1192/bjo.2023.507.

ABSTRACT

BACKGROUND: Poor air quality is associated with poor health. Little attention is given to the complex array of environmental exposures and air pollutants that affect mental health during the life course.

AIMS: We gather interdisciplinary expertise and knowledge across the air pollution and mental health fields. We seek to propose future research priorities and how to address them.

METHOD: Through a rapid narrative review, we summarise the key scientific findings, knowledge gaps and methodological challenges.

RESULTS: There is emerging evidence of associations between poor air quality, both indoors and outdoors, and poor mental health more generally, as well as specific mental disorders. Furthermore, pre-existing long-term conditions appear to deteriorate, requiring more healthcare. Evidence of critical periods for exposure among children and adolescents highlights the need for more longitudinal data as the basis of early preventive actions and policies. Particulate matter, including bioaerosols, are implicated, but form part of a complex exposome influenced by geography, deprivation, socioeconomic conditions and biological and individual vulnerabilities. Critical knowledge gaps need to be addressed to design interventions for mitigation and prevention, reflecting ever-changing sources of air pollution. The evidence base can inform and motivate multi-sector and interdisciplinary efforts of researchers, practitioners, policy makers, industry, community groups and campaigners to take informed action.

CONCLUSIONS: There are knowledge gaps and a need for more research, for example, around bioaerosols exposure, indoor and outdoor pollution, urban design and impact on mental health over the life course.

PMID:37403494 | DOI:10.1192/bjo.2023.507