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Plant roots integrate environmental signals with development using exquisite spatiotemporal control. This is apparent in the deposition of suberin, an apoplastic diffusion barrier, which regulates flow of water, solutes and gases, and is environmentally plastic. Suberin is considered a hallmark of endodermal differentiation but is absent in the tomato endodermis. Instead, suberin is present in the exodermis, a cell type that is absent in the model organism Arabidopsis thaliana. Here we demonstrate that the suberin regulatory network has the same parts driving suberin production in the tomato exodermis and the Arabidopsis endodermis. Despite this co-option of network components, the network has undergone rewiring to drive distinct spatial expression and with distinct contributions of specific genes. Functional genetic analyses of the tomato MYB92 transcription factor and ASFT enzyme demonstrate the importance of exodermal suberin for a plant water-deficit response and that the exodermal barrier serves an equivalent function to that of the endodermis and can act in its place.

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BACKGROUND: Cisplatin is a primary chemotherapy choice for various solid tumors. DNA damage caused by cisplatin results in apoptosis of tumor cells. Cisplatin-induced DNA damage, however, may also result in mutations in normal cells and the initiation of secondary malignancies. In the current study, we have used the erythrocyte PIG-A assay to evaluate mutagenesis in non-tumor hematopoietic tissue of cancer patients receiving cisplatin chemotherapy. METHODS: Twenty-one head and neck cancer patients undergoing treatment with cisplatin were monitored for the presence of PIG-A mutant total erythrocytes and the young erythrocytes, reticulocytes (RETs), in peripheral blood for up to five and a half months from the initiation of the anti-neoplastic chemotherapy. RESULTS: PIG-A mutant frequency (MF) in RETs increased at least two-fold in 15 patients at some point of the monitoring, while the frequency of total mutant RBCs increased at least two-fold in 6 patients. A general trend for an increase in the frequency of mutant RETs and total mutant RBCs was observed in 19 and 18 patients, respectively. Only in one patient did both RET and total RBC PIG-A MFs did not increase at any time-point over the monitoring period. CONCLUSION: Cisplatin chemotherapy induces moderate increases in the frequency of PIG-A mutant erythrocytes in head and neck cancer patients. Mutagenicity measured with the flow cytometric PIG-A assay may serve as a tool for predicting adverse outcomes of genotoxic antineoplastic therapy.

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Lipomas are benign soft tissue tumors frequently observed throughout the body. Lipomas rarely cause health concerns; however, when symptomatic, it is often related to their location and size. A 65-year-old male patient presented with a non-tender, enlarging mass in the anterior floor of the mouth, which was otherwise asymptomatic. Computed tomography evaluation revealed an unusually large hypolucent mass, posterior to the inner table of the right anterior mandible. Surgical excision was uncomplicated. Upon follow-up, the right anterior floor of the mouth wound healed without compromise of the lingual or hypoglossal nerves or Wharton's duct. This discussion highlights the infrequent occurrence of lipomas in the oral cavity, particularly in the floor of the mouth, including patient presentation, preoperative evaluation, and surgical planning.

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Bioinformatic and experimental data show that bacteriophages are ubiquitous in human enteric microbiomes. However, there are gaps in understanding the contribution of these viruses in shaping the bacterial strain and species composition of the gut microbiome and how these phages are maintained over time. To address these questions, we adapted and analyzed the properties of a mathematical model of the population and evolutionary dynamics of bacteria and phage and performed experiments with Escherichia coli and phages isolated from four fecal microbiota transplantation (FMT) doses as representative samples of non-dysbiotic enteric microbiota. Our models predict and experiments confirm that due to production of the O antigen, E. coli in the enteric microbiome are likely to be resistant to infection with co-occurring phages. However, phages can be maintained in these populations in high densities due to high rates of transition between resistant and sensitive states, which we call leaky resistance. Based on these models and observations, we postulate that the phages found in the human gut are likely to play little role in shaping the composition of E. coli in the enteric microbiome in healthy individuals. How general this is for other species of bacteria in enteric microbiota is not yet clear, although O antigen production is broadly conserved across many taxa.

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BACKGROUND: Patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA alterations have poor outcomes. MAGNITUDE found patients with homologous recombination repair gene alterations (HRR+), particularly BRCA1/2, benefit from first-line therapy with niraparib plus abiraterone acetate and prednisone (AAP). Here we report longer follow-up from the second prespecified interim analysis (IA2). PATIENTS AND METHODS: Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1 : 1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints [time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival (OS)] were assessed. RESULTS: Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n = 113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival {rPFS; blinded independent central review; median rPFS 19.5 versus 10.9 months; hazard ratio (HR) = 0.55 [95% confidence interval (CI) 0.39-0.78]; nominal P = 0.0007} consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population [HR = 0.76 (95% CI 0.60-0.97); nominal P = 0.0280; median follow-up 26.8 months]. Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR of 0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies, demonstrated an HR of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed. CONCLUSIONS: MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients.

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We used diffuse reflectance spectroscopy to quantify tissue absorption and scattering-based parameters in similarly sized tumors derived from a panel of four isogenic murine breast cancer cell lines (4T1, 4T07, 168FARN, 67NR) that are each capable of accomplishing different steps of the invasion-metastasis cascade. We found lower tissue scattering, increased hemoglobin concentration, and lower vascular oxygenation in indolent 67NR tumors incapable of metastasis compared with aggressive 4T1 tumors capable of metastasis. Supervised learning statistical approaches were able to accurately differentiate between tumor groups and classify tumors according to their ability to accomplish each step of the invasion-metastasis cascade. We investigated whether the inhibition of metastasis-promoting genes in the highly metastatic 4T1 tumors resulted in measurable optical changes that made these tumors similar to the indolent 67NR tumors. These results demonstrate the potential of diffuse reflectance spectroscopy to noninvasively evaluate tumor biology and discriminate between indolent and aggressive tumors.

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Technical advances in artificial intelligence (AI) in cardiac imaging are rapidly improving the reproducibility of this approach and the possibility to reduce time necessary to generate a report. In cardiac computed tomography angiography (CCTA) the main application of AI in clinical practice is focused on detection of stenosis, characterization of coronary plaques, and detection of myocardial ischemia. In cardiac magnetic resonance (CMR) the application of AI is focused on post-processing and particularly on the segmentation of cardiac chambers during late gadolinium enhancement. In echocardiography, the application of AI is focused on segmentation of cardiac chambers and is helpful for valvular function and wall motion abnormalities. The common thread represented by all of these techniques aims to shorten the time of interpretation without loss of information compared to the standard approach. In this review we provide an overview of AI applications in multimodality cardiac imaging.

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The accurate analytical characterization of metastatic phenotype at primary tumor diagnosis and its evolution with time are critical for controlling metastatic progression of cancer. Here, we report a label-free optical strategy using Raman spectroscopy and machine learning to identify distinct metastatic phenotypes observed in tumors formed by isogenic murine breast cancer cell lines of progressively increasing metastatic propensities. Methods: We employed the 4T1 isogenic panel of murine breast cancer cells to grow tumors of varying metastatic potential and acquired label-free spectra using a fiber probe-based portable Raman spectroscopy system. We used MCR-ALS and random forests classifiers to identify putative spectral markers and predict metastatic phenotype of tumors based on their optical spectra. We also used tumors derived from 4T1 cells silenced for the expression of TWIST, FOXC2 and CXCR3 genes to assess their metastatic phenotype based on their Raman spectra. Results: The MCR-ALS spectral decomposition showed consistent differences in the contribution of components that resembled collagen and lipids between the non-metastatic 67NR tumors and the metastatic tumors formed by FARN, 4T07, and 4T1 cells. Our Raman spectra-based random forest analysis provided evidence that machine learning models built on spectral data can allow the accurate identification of metastatic phenotype of independent test tumors. By silencing genes critical for metastasis in highly metastatic cell lines, we showed that the random forest classifiers provided predictions consistent with the observed phenotypic switch of the resultant tumors towards lower metastatic potential. Furthermore, the spectral assessment of lipid and collagen content of these tumors was consistent with the observed phenotypic switch. Conclusion: Overall, our findings indicate that Raman spectroscopy may offer a novel strategy to evaluate metastatic risk during primary tumor biopsies in clinical patients.

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[This corrects the article DOI: 10.3389/fvets.2022.788289.].

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Debates around fishes' ability to feel pain concern sentience: do reactions to tissue damage indicate evaluative consciousness (conscious affect), or mere nociception? Thanks to Braithwaite's discovery of trout nociceptors, and concerns that current practices could compromise welfare in countless fish, this issue's importance is beyond dispute. However, nociceptors are merely necessary, not sufficient, for true pain, and many measures held to indicate sentience have the same problem. The question of whether fish feel pain - or indeed anything at all - therefore stimulates sometimes polarized debate. Here, we try to bridge the divide. After reviewing key consciousness concepts, we identify "red herring" measures that should not be used to infer sentience because also present in non-sentient organisms, notably those lacking nervous systems, like plants and protozoa (P); spines disconnected from brains (S); decerebrate mammals and birds (D); and humans in unaware states (U). These "S.P.U.D. subjects" can show approach/withdrawal; react with apparent emotion; change their reactivity with food deprivation or analgesia; discriminate between stimuli; display Pavlovian learning, including some forms of trace conditioning; and even learn simple instrumental responses. Consequently, none of these responses are good indicators of sentience. Potentially more valid are aspects of working memory, operant conditioning, the self-report of state, and forms of higher order cognition. We suggest new experiments on humans to test these hypotheses, as well as modifications to tests for "mental time travel" and self-awareness (e.g., mirror self-recognition) that could allow these to now probe sentience (since currently they reflect perceptual rather than evaluative, affective aspects of consciousness). Because "bullet-proof" neurological and behavioral indicators of sentience are thus still lacking, agnosticism about fish sentience remains widespread. To end, we address how to balance such doubts with welfare protection, discussing concerns raised by key skeptics in this debate. Overall, we celebrate the rigorous evidential standards required by those unconvinced that fish are sentient; laud the compassion and ethical rigor shown by those advocating for welfare protections; and seek to show how precautionary principles still support protecting fish from physical harm.

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PURPOSE: Inflammatory breast cancer is a deadly and aggressive type of breast cancer. A key challenge relates to the need for a more detailed, formal, objective definition of IBC, the lack of which compromises clinical care, hampers the conduct of clinical trials, and hinders the search for IBC-specific biomarkers and treatments because of the heterogeneity of patients considered to have IBC. METHODS: Susan G. Komen, the Inflammatory Breast Cancer Research Foundation, and the Milburn Foundation convened patient advocates, clinicians, and researchers to review the state of IBC and to propose initiatives to advance the field. After literature review of the defining clinical, pathologic, and imaging characteristics of IBC, the experts developed a novel quantitative scoring system for diagnosis. RESULTS: The experts identified through consensus several "defining characteristics" of IBC, including factors related to timing of onset and specific symptoms. These reflect common pathophysiologic changes, sometimes detectable on biopsy in the form of dermal lymphovascular tumor emboli and often reflected in imaging findings. Based on the importance and extent of these characteristics, the experts developed a scoring scale that yields a continuous score from 0 to 48 and proposed cut-points for categorization that can be tested in subsequent validation studies. CONCLUSION: To move beyond subjective 'clinical diagnosis' of IBC, we propose a quantitative scoring system to define IBC, based on clinical, pathologic, and imaging features. This system is intended to predict outcome and biology, guide treatment decisions and inclusion in clinical trials, and increase diagnostic accuracy to aid basic research; future validation studies are necessary to evaluate its performance.

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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the key tobacco-specific nitrosamines that plays an important role in human lung carcinogenesis. Repeated dose inhalation toxicity data on NNK, particularly relevant to cigarette smoking, however, is surprisingly limited. Hence, there is a lack of direct information available on the carcinogenic and potential non-carcinogenic effects of NNK via inhalational route exposure. In the present study, the subchronic inhalation toxicity of NNK was evaluated in Sprague Dawley rats. Both sexes (9-10 weeks age; 23 rats/sex/group) were exposed by nose-only inhalation to air, vehicle control (75% propylene glycol), or 0.2, 0.8, 3.2, or 7.8 mg/kg body weight (BW)/day of NNK (NNK aerosol concentrations: 0, 0, 0.0066, 0.026, 0.11, or 0.26 mg/L air) for 1 h/day for 90 consecutive days. Toxicity was evaluated by assessing body weights; food consumption; clinical pathology; histopathology; organ weights; blood, urine, and tissue levels of NNK, its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and their glucuronides (reported as total NNK, tNNK, and total NNAL, tNNAL, respectively); tissue levels of the DNA adduct O6-methylguanine; blood and bone marrow micronucleus (MN) frequency; and bone marrow DNA strand breaks (comet assay). The results showed that NNK exposure caused multiple significant adverse effects, with the most sensitive endpoint being non-neoplastic lesions in the nose. Although the genotoxic biomarker O6-methylguanine was detected, genotoxicity from NNK exposure was negative in the MN and comet assays. The Lowest-Observed-Adverse-Effect-Level (LOAEL) was 0.8 mg/kg BW/day or 0.026 mg/L air of NNK for 1 h/day for both sexes. The No-Observed-Adverse-Effect-Level (NOAEL) was 0.2 mg/kg BW/day or 0.0066 mg/L air of NNK for 1 h/day for both sexes. The results of this study provide new information relevant to assessing the human exposure hazard of NNK.

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The sequencing of the Arabidopsis thaliana genome 21 years ago ushered in the genomics era for plant research. Since then, an incredible variety of bioinformatic tools permit easy access to large repositories of genomic, transcriptomic, proteomic, epigenomic and other '-omic' data. In this review, we cover some more recent tools (and highlight the 'classics') for exploring such data in order to help formulate quality, testable hypotheses, often without having to generate new experimental data. We cover tools for examining gene expression and co-expression patterns, undertaking promoter analyses and gene set enrichment analyses, and exploring protein-protein and protein-DNA interactions. We will touch on tools that integrate different data sets at the end of the article.

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In order to investigate the possibility that treatment age affects the genotoxic response to ethyl methane sulfonate (EMS) exposure, we dosed gpt-delta neonatal mice on postnatal days 1-28 with 5-100 mg/kg/day of EMS and measured micronucleus (MN) induction in peripheral blood and gpt gene mutation in liver, lung, bone marrow, small intestine, spleen, and kidney. The data were compared to measurements from similarly exposed adult gpt-delta mice. Our results indicate that the peripheral blood MN frequencies in mice treated as neonates are not substantially different from those measured in mice treated as adults. There were, however, differences in tissue-specific gpt mutation responses in mice treated with EMS as neonates and adults. Greater mutant frequencies were seen in DNA isolated from kidney of mice treated as neonates, whereas the mutant frequencies in bone marrow, liver, and spleen were greater in the animals treated as adults. Benchmark dose potency ranking indicated that the differences for kidney were significant. Our data indicate that there are differences in EMS-induced genotoxicity between mice treated as adults and neonates; the differences, however, are relatively small.

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