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This article explores the rapidly advancing innovation to endow robots with social intelligence capabilities in the form of multilingual and multimodal emotion recognition, and emotion-aware decision-making capabilities, for contextually appropriate robot behaviours and cooperative social human–robot interaction for the healthcare domain. The objective is to enable robots to become trustworthy and versatile social robots capable of having human-friendly and human assistive interactions, utilised to better assist human users’ needs by enabling the robot to sense, adapt, and respond appropriately to their requirements while taking into consideration their wider affective, motivational states, and behaviour. We propose an innovative approach to the difficult research challenge of endowing robots with social intelligence capabilities for human assistive interactions, going beyond the conventional robotic sense-think-act loop. We propose an architecture that addresses a wide range of social cooperation skills and features required for real human–robot social interaction, which includes language and vision analysis, dynamic emotional analysis (long-term affect and mood), semantic mapping to improve the robot’s knowledge of the local context, situational knowledge representation, and emotion-aware decision-making. Fundamental to this architecture is a normative ethical and social framework adapted to the specific challenges of robots engaging with caregivers and care-receivers.

As a contribution to the more general discussion on causes of language endangerment and death, we describe the language ecologies of four related languages (Bà Mambila [mzk]/[mcu], Sombә (Somyev or Kila) [kgt], Oumyari Wawa [www], Njanga (Kwanja) [knp]) of the Cameroon-Nigeria borderland to reach an understanding of the factors and circumstances that have brought two of these languages, Sombә and Njanga, to the brink of extinction; a third, Oumyari, is unstable/eroded, while Bà Mambila is stable. Other related languages of the area, also endangered and in one case extinct, fit into our discussion, though with less focus. We argue that an understanding of the language ecology of a region (or of a given language) leads to an understanding of the vitality of a language. Language ecology seen as a multilayered phenomenon can help explain why the four languages of our case studies have different degrees of vitality. This has implications for how language change is conceptualised: we see multilingualism and change (sometimes including extinction) as normative.

Multilinear Grammar provides a framework for integrating the many different syntagmatic structures of language into a coherent semiotically based Rank Interpretation Architecture, with default linear grammars at each rank. The architecture defines a Sui Generis Condition on ranks, from discourse through utterance and phrasal structures to the word, with its sub-ranks of morphology and phonology. Each rank has unique structures and its own semantic-pragmatic and prosodic-phonetic interpretation models. Default computational models for each rank are proposed, based on a Procedural Plausibility Condition: incremental processing in linear time with finite working memory. We suggest that the Rank Interpretation Architecture and its multilinear properties provide systematic design features of human languages, contrasting with unordered lists of key properties or single structural properties at one rank, such as recursion, which have previously been been put forward as language design features. The framework provides a realistic background for the gradual development of complexity in the phylogeny and ontogeny of language, and clarifies a range of challenges for the evaluation of realistic linguistic theories and applications. The empirical objective of the paper is to demonstrate unique multilinear properties at each rank and thereby motivate the Multilinear Grammar and Rank Interpretation Architecture framework as a coherent approach to capturing the complexity of human languages in the simplest possible way.

Fulvia fulva and Dothistroma septosporum are closely related apoplastic pathogens with similar lifestyles but different hosts: F. fulva is a pathogen of tomato, whilst D. septosporum is a pathogen of pine trees. In 2012, the first genome sequences of these pathogens were published, with F. fulva and D. septosporum having highly fragmented and near-complete assemblies, respectively. Since then, significant advances have been made in unravelling their genome architectures. For instance, the genome of F. fulva has now been assembled into 14 chromosomes, 13 of which have synteny with the 14 chromosomes of D. septosporum, suggesting these pathogens are even more closely related than originally thought. Considerable advances have also been made in the identification and functional characterization of virulence factors (e.g., effector proteins and secondary metabolites) from these pathogens, thereby providing new insights into how they promote host colonization or activate plant defence responses. For example, it has now been established that effector proteins from both F. fulva and D. septosporum interact with cell-surface immune receptors and co-receptors to activate the plant immune system. Progress has also been made in understanding how F. fulva and D. septosporum have evolved with their host plants, whilst intensive research into pandemics of Dothistroma needle blight in the Northern Hemisphere has shed light on the origins, migration, and genetic diversity of the global D. septosporum population. In this review, we specifically summarize advances made in our understanding of the F. fulva-tomato and D. septosporum-pine pathosystems over the last 10 years., (© 2023 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

SQSTM1/p62, as a major autophagy receptor, forms droplets that are critical for cargo recognition, nucleation, and clearance. p62 droplets also function as liquid assembly platforms to allow the formation of autophagosomes at their surfaces. It is unknown how p62-droplet formation is regulated under physiological or pathological conditions. Here, we report that p62-droplet formation is selectively blocked by inflammatory toxicity, which induces cleavage of p62 by caspase-6 at a novel cleavage site D256, a conserved site across human, mouse, rat, and zebrafish. The N-terminal cleavage product is relatively stable, whereas the C-terminal product appears undetectable. Using a variety of cellular models, we show that the p62 N-terminal caspase-6 cleavage product (p62-N) plays a dominant-negative role to block p62-droplet formation. In vitro p62 phase separation assays confirm this observation. Dominant-negative regulation of p62-droplet formation by caspase-6 cleavage attenuates p62 droplets dependent autophagosome formation. Our study suggests a novel pathway to modulate autophagy through the caspase-6-p62 axis under certain stress stimuli., (© 2021. The Author(s).)

Introduction: Traumatic brain injuries (TBIs) are life-threatening, and air transport of patients with TBI requires additional considerations. To mitigate the risks of complications associated with altitude, some patients fly with a cabin altitude restriction (CAR) to limit the altitude at which an aircraft's cabin is maintained. The goal of this study was to examine the effects of CARs on patients with TBI transported out of theater via Critical Care Air Transport Teams., Materials and Methods: We conducted a retrospective chart review of patients with moderate-to-severe TBI evacuated out of combat theater to Landstuhl Regional Medical Center via Critical Care Air Transport Teams. We collected demographics, flight and injury information, procedures, oxygenation, and outcomes (discharge disposition and hospital/ICU/ventilator days). We categorized patients as having a CAR if they had a documented CAR or maximum cabin altitude of 5,000 feet or lower in their Critical Care Air Transport Teams record. We calculated descriptive statistics and constructed regression models to evaluate the association between CAR and clinical outcomes., Results: We reviewed the charts of 435 patients, 31% of which had a documented CAR. Nineteen percent of the sample had a PaO2 lower than 80 mm Hg, and 3% of patients experienced a SpO2 lower than 93% while in flight. When comparing preflight and in-flight events, we found that the percentage of patients who had a SpO2 of 93% or lower increased for the No CAR group, whereas the CAR group did not experience a significant change. However, flying without a CAR was not associated with discharge disposition, mortality, or hospital/ICU/ventilator days. Further, having a CAR was not associated with these outcomes after adjusting for additional flights, injury severity, injury type, or preflight head surgery., Conclusions: Patients with TBI who flew with a CAR did not differ in clinical outcomes from those without a CAR., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2020.)

Objectives: Fever occurs in up to 50% of critically-ill patients with acute neurological injury. Small temperature elevations have been correlated with increased morbidity and mortality in this patient population. We sought to evaluate a novel single-use surface cooling system for the treatment of fever in patients with acute brain injury., Patients and Methods: We conducted a retrospective analysis of a prospective product evaluation using the EMCOOLS Flex.Pad™ system for acute fever (≥38.3 °C) in our 16-bed neuro-ICU. Four refrigerated pads (-18 °C) were applied to the chest, back, and anterior thighs. Core temperature (bladder) was continuously recorded over 4 h, and the highest Bedside Shivering Assessment Scale (BSAS) score was recorded hourly., Results: Twelve subjects were included in the analysis. Mean age was 55 ± 9 years, 9 patients were men, and mean weight was 85 ± 12 kg. The most common primary diagnoses were subarachnoid (N = 5) and intracerebral (N = 4) hemorrhage. Application of the EMCOOLS system resulted in a linear 1.3 ± 0.6 °C drop (T 0avg  = 38.9 ⁰C, T 90avg  = 37.6 ⁰C, P = 0.0032) in mean temperature over 90 min, followed by a plateau with only one subject rebounding to >38 °C within 4 h. Normothermia (<38.0 ⁰C) was achieved in all but one patient (92%) in an average of 65 min. Comatose patients displayed a non-significantly higher degree of cooling at 90 min than did awake subjects (ΔT coma  = 1.74 °C vs ΔT awake  = 0.74 °C hr -1 , P = 0.067). There was no observed skin irritation upon removal of the device for any patients., Conclusion: The EMCOOLs system is a well-tolerated, safe and effective short-term intervention for control of fever in neurological patients. Future studies are needed to compare efficacy of the EMCOOLs to other devices and interventions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Pigments and phytotoxins are crucial for the survival and spread of plant pathogenic fungi. The genome of the tomato biotrophic fungal pathogen Cladosporium fulvum contains a predicted gene cluster (CfPKS1, CfPRF1, CfRDT1 and CfTSF1) that is syntenic with the characterized elsinochrome toxin gene cluster in the citrus pathogen Elsinoë fawcettii. However, a previous phylogenetic analysis suggested that CfPks1 might instead be involved in pigment production. Here, we report the characterization of the CfPKS1 gene cluster to resolve this ambiguity. Activation of the regulator CfTSF1 specifically induced the expression of CfPKS1 and CfRDT1, but not of CfPRF1. These co-regulated genes that define the CfPKS1 gene cluster are orthologous to genes involved in 1,3-dihydroxynaphthalene (DHN) melanin biosynthesis in other fungi. Heterologous expression of CfPKS1 in Aspergillus oryzae yielded 1,3,6,8-tetrahydroxynaphthalene, a typical precursor of DHN melanin. Δcfpks1 deletion mutants showed similar altered pigmentation to wild type treated with DHN melanin inhibitors. These mutants remained virulent on tomato, showing this gene cluster is not involved in pathogenicity. Altogether, our results showed that the CfPKS1 gene cluster is involved in the production of DHN melanin and suggests that elsinochrome production in E. fawcettii likely involves another gene cluster., Competing Interests: The authors have declared that no competing interests exist.

Tomato leaf mold disease is caused by the biotrophic fungus Cladosporium fulvum. During infection, C. fulvum produces extracellular small secreted protein (SSP) effectors that function to promote colonization of the leaf apoplast. Resistance to the disease is governed by Cf immune receptor genes that encode receptor-like proteins (RLPs). These RLPs recognize specific SSP effectors to initiate a hypersensitive response (HR) that renders the pathogen avirulent. C. fulvum strains capable of overcoming one or more of all cloned Cf genes have now emerged. To combat these strains, new Cf genes are required. An effectoromics approach was employed to identify wild tomato accessions carrying new Cf genes. Proteomics and transcriptome sequencing were first used to identify 70 apoplastic in planta-induced C. fulvum SSPs. Based on sequence homology, 61 of these SSPs were novel or lacked known functional domains. Seven, however, had predicted structural homology to antimicrobial proteins, suggesting a possible role in mediating antagonistic microbe-microbe interactions in planta. Wild tomato accessions were then screened for HR-associated recognition of 41 SSPs, using the Potato virus X-based transient expression system. Nine SSPs were recognized by one or more accessions, suggesting that these plants carry new Cf genes available for incorporation into cultivated tomato.

The Cf-5 gene of tomato confers resistance to strains of the fungal pathogen Cladosporium fulvum carrying the avirulence gene Avr5. Although Cf-5 has been cloned, Avr5 has remained elusive. We report the cloning of Avr5 using a combined bioinformatic and transcriptome sequencing approach. RNA-Seq was performed on the sequenced race 0 strain (0WU; carrying Avr5), as well as a race 5 strain (IPO 1979; lacking a functional Avr5 gene) during infection of susceptible tomato. Forty-four in planta-induced C. fulvum candidate effector (CfCE) genes of 0WU were identified that putatively encode a secreted, small cysteine-rich protein. An expressed transcript sequence comparison between strains revealed two polymorphic CfCE genes in IPO 1979. One of these conferred avirulence to IPO 1979 on Cf-5 tomato following complementation with the corresponding 0WU allele, confirming identification of Avr5. Complementation also led to increased fungal biomass during infection of susceptible tomato, signifying a role for Avr5 in virulence. Seven of eight race 5 strains investigated escape Cf-5-mediated resistance through deletion of the Avr5 gene. Avr5 is heavily flanked by repetitive elements, suggesting that repeat instability, in combination with Cf-5-mediated selection pressure, has led to the emergence of race 5 strains deleted for the Avr5 gene.

In fungi, genes involved in the production of secondary metabolites are generally clustered at one location. There are some exceptions, such as genes required for synthesis of dothistromin, a toxin that is a chemical analog of the aflatoxin precursor versicolorin A and made by the pine needle pathogen Dothistroma septosporum. The availability of the D. septosporum genome sequence enabled identification of putative dothistromin genes, including an ortholog of the aflatoxin regulatory gene AflR, and revealed that most of the genes are spread over six separate regions (loci) on chromosome 12 (1.3 Mb). Here we show that levels of expression of the widely dispersed genes in D. septosporum are not correlated with gene location with respect to their distance from a telomere, but that AflR regulates them. The production of dothistromin by D. septosporum in which the AflR gene was knocked out (ΔDsAflR) was drastically reduced, but still detectable. This is in contrast to orthologous ΔAflR mutants in Aspergillus species that lack any aflatoxin production. Expression patterns in ΔDsAflR mutants helped to predict the complete set of genes involved in dothistromin production. This included a short-chain aryl alcohol dehydrogenase (NorB), which is located on chromosome 11 rather than chromosome 12, but was 24-fold down regulated in ΔDsAflR. An orthologous set of dothistromin genes, organized in a similar fragmented cluster arrangement to that seen in D. septosporum, was found in the closely related tomato pathogen Cladosporium fulvum even though this species does not produce dothistromin. In C. fulvum, pseudogenization of key biosynthetic genes explains the lack of dothistromin production. The fragmented arrangement of dothistromin genes provides an example of coordinated control of a dispersed set of secondary metabolite genes; it also provides an example where loss of dothistromin production might have allowed adaptation to a new pathogenic lifestyle., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We sequenced and compared the genomes of the Dothideomycete fungal plant pathogens Cladosporium fulvum (Cfu) (syn. Passalora fulva) and Dothistroma septosporum (Dse) that are closely related phylogenetically, but have different lifestyles and hosts. Although both fungi grow extracellularly in close contact with host mesophyll cells, Cfu is a biotroph infecting tomato, while Dse is a hemibiotroph infecting pine. The genomes of these fungi have a similar set of genes (70% of gene content in both genomes are homologs), but differ significantly in size (Cfu >61.1-Mb; Dse 31.2-Mb), which is mainly due to the difference in repeat content (47.2% in Cfu versus 3.2% in Dse). Recent adaptation to different lifestyles and hosts is suggested by diverged sets of genes. Cfu contains an α-tomatinase gene that we predict might be required for detoxification of tomatine, while this gene is absent in Dse. Many genes encoding secreted proteins are unique to each species and the repeat-rich areas in Cfu are enriched for these species-specific genes. In contrast, conserved genes suggest common host ancestry. Homologs of Cfu effector genes, including Ecp2 and Avr4, are present in Dse and induce a Cf-Ecp2- and Cf-4-mediated hypersensitive response, respectively. Strikingly, genes involved in production of the toxin dothistromin, a likely virulence factor for Dse, are conserved in Cfu, but their expression differs markedly with essentially no expression by Cfu in planta. Likewise, Cfu has a carbohydrate-degrading enzyme catalog that is more similar to that of necrotrophs or hemibiotrophs and a larger pectinolytic gene arsenal than Dse, but many of these genes are not expressed in planta or are pseudogenized. Overall, comparison of their genomes suggests that these closely related plant pathogens had a common ancestral host but since adapted to different hosts and lifestyles by a combination of differentiated gene content, pseudogenization, and gene regulation., Competing Interests: The authors have declared that no competing interests exist.

gamma-Glutamyl transpeptidase (GGT) is normally absent from adult rat hepatocytes but is induced by a range of xenobiotics, including carcinogens and chemoprotective agents. As many as six mRNA species for this enzyme have been described in both rat and mouse, with various degrees of tissue specificity. These originate from one gene and have separate promoters within alternative 5' untranslated sequences. By using a cDNA-derived sequence specific for GGT mRNA III to screen a rat genomic library, a clone that contains the promoter region for this mRNA was isolated and characterized. The transcriptional start site lay some 3.5 kb upstream from that already characterized for mRNA II in rat kidney. Luciferase activity was obtained after transfection of rat hepatoma-derived cell lines with constructs containing the putative promoter III fused to a luc reporter. Although this promoter lacks a TATA box, a sequence close to the start site that binds the transcription factor TFIID in vitro was identified. By using PCR techniques, mRNA III (homologous to both mouse III and IV) and an mRNA (IV) with homology to VI in mouse were found in ethoxyquin- and aflatoxin B1-treated rat liver and kidney as well as in a hepatoma-derived cell line. No evidence was found for a product homologous to mRNA from promoter V described in the mouse.

A clone containing the entire protein-coding region of gamma glutamyl transpeptidase (GGT) from ethoxyquin- (EQ) treated rat liver has been isolated from a cDNA library. DNA sequence analysis showed that the protein-coding and 3' untranslated regions are almost identical to rat kidney GGT, but the sequences differ in the 5' untranslated region. Southern blot data suggest a single gene for GGT in the rat, hence the different mRNAs may originate by differential transcriptional and/or posttranscriptional processing.

Infection of mouse BALB/c 3T3 cells by adenovirus 5 resulted in at least 1000-fold lowered yields of virus compared to human cells. The molecular basis of this restriction was analysed at the level of viral gene expression. Steady-state levels of viral DNA and RNA were greatly reduced in infected mouse, compared to human cells. Both early region 1A (E1A) and E1B mRNAs were decreased in mouse cells and their protein products were barely detectable by metabolic labelling of infected cells. The E2A-72 kDa protein and the hexon protein were detected by metabolic labelling, and immunocytochemical analysis showed that they were correctly located in nuclei of infected mouse cells. Only a minor proportion of infected mouse 3T3 cells expressed the E2A-72 kDa or hexon proteins. Low yields of virus were obtained by infection of SV40 transformed BALB/c 3T3 cells showing that SV40 does not provide a helper function for adenovirus 5 growth in this cell system.

Glutathione-dependent enzymes play a central role in the protection of cells from cytotoxic chemicals and have been implicated in the intrinsic and acquired resistance of tumors to cytotoxic drugs. We have generated a Chinese hamster ovary line resistant to bifunctional nitrogen mustards and in this report have characterized and isolated the protein that represents the major observable phenotypic difference between the drug-sensitive and drug-resistant cell lines. This purified protein is shown to be an alpha class glutathione S-transferase comprising YcYc subunits and possessing a pI value of approximately 8.0. The intracellular level of the Yc subunit is elevated greater than 40-fold in the drug-resistant cell line, which could account for the increase in glutathione S-transferase (RX:glutathione R-transferase; EC 2.5.1.18) activity toward both 1-chloro-2,4-dinitrobenzene and cumene hydroperoxide. Other glutathione S-transferase subunits within this gene family are also elevated. These changes are accompanied by a significant elevation in alpha class mRNA levels. Southern analysis indicates that the genes coding for these proteins are amplified 4- to 8-fold in the drug-resistant cell line. In addition, gamma-glutamyl transpeptidase [(5-glutamyl)-peptide:amino acid 5-glutamyltransferase; EC 2.3.2.2] activity is increased 3.6-fold in the drug-resistant Chinese hamster ovary cell line, which may explain the increase in cellular glutathione level. In this case no gene amplification was seen. These data indicate that gene amplification may be important in drug resistance toward alkylating agents and also that other enzymes in glutathione homeostasis are involved.

We have studied the induction of rat liver gamma-glutamyl transpeptidase (GGT) mRNA by the antioxidant ethoxyquin and during aflatoxin B1-induced carcinogenesis. Using a rat kidney GGT cDNA probe, Northern blot analysis revealed that GGT mRNA induced in liver by either compounds was slightly larger than that found in untreated kidney. GGT mRNA was not detected in untreated liver or freshly isolated hepatocytes, but induction of the message in treated tissues correlated with the increase in enzymic activity observed by histochemistry and quantitative assay. Slot-blot analysis of poly(A)+ mRNA indicated that constitutive GGT mRNA levels in kidney were at least 5-fold greater than those in the most GGT-positive liver-derived tissue examined.