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Fas‐associated death domain protein (FADD) is an apoptotic adapter molecule that recruits caspases and facilitates the formation of death‐inducing signaling complexes in mammals. In lower animals, FADD forms a complex with immune deficiency and death‐related ced‐3/Nedd2‐like caspase to elicit antimicrobial responses. In this study, we characterized the FADD sequence of Tenebrio molitor (TmFADD) using molecular informatics to understand its role in immune surveillance of the host against microorganisms. The 618 bp open reading frame of TmFADD encodes a polypeptide of 204 amino acids. The protein includes two promiscuous domains, the death‐effector domain and the death domain, found at the N‐ and C‐termini, respectively. TmFADD is clustered with the coleopteran FADD sequences in the phylogenetic tree. Homology‐based structural analysis showed an α‐helical model with a QMEAN score of 0.58. The expression of TmFADD mRNA was conspicuous in the larval and early pupal stages. TmFADD mRNA was distributed in the immune tissues of the larva and was found predominately in the gut of the adult. Infection of the host with Candida albicans, Escherichia coli or Staphylococcus aureus increased the expression of TmFADD mRNA, suggesting that these microorganisms trigger the innate immunity of the host. The silencing of TmFADD transcripts resulted in an increased susceptibility of T. molitor larvae to infection with E. coli, but not to infection with C. albicans or S. aureus. Hence, these results indicate that FADD plays a role in the defense of T. molitor and could open avenues for understanding insect immunity. [ABSTRACT FROM AUTHOR]

Edible insects such as the mealworm (Tenebrio molitor) are emerging as an alternative animal protein resource to meet the needs of a growing global population. However, despite the successful mass production of edible insects, research into practical compound feed for edible insect is still insufficient. In this study, mealworms were fed wheat bran, layer chicken feed mash, chicken pellets and cattle pellets for 1 to 36 days, after which their body length was measured. In the groups fed with chicken feed mash, chicken pellets or cattle pellets, the mean body lengths were 2.88, 2.92 and 2.95 cm, respectively, similar to the 2.95 cm of the control T. molitor fed with wheat bran. Individual weight measurements yielded similar results: control, 7.87 g; chicken feed mash, 7.43 g; chicken pellets, 7.60 g; and cattle pellets, 7.63 g. Analysis of livestock feed intake showed that the intake was 290.4 g in control insects, 137.7 g in insects fed chicken feed mash, 220.2 g in insects fed chicken pellets and 230.3 g in insects fed cattle pellets. In the excretion analysis, the excretion of the control insects (161.60 g) was larger than that of the insects fed with chicken feed mash (93.37 g), chicken pellets (93.40 g) or cattle pellets (133.87 g). An analysis of the nutritional content of T. molitor based on nine major nutrients showed no significant differences between the control and the test groups. These results can be used to improve the price competitiveness and quality of T. molitor for commercial development. [ABSTRACT FROM AUTHOR]

Selective herbicides are used to control undesirable vegetation or weeds in fields without harming crops. Herbicide use for weed management can directly impact the densities of insect pests in agricultural communities as a result of insect mortality during and immediately after application. In insects, the glutathione S‐transferase (GST) enzyme is involved in both the detoxification process and the defense of cellular membranes against oxidative damage. In this study, two TmGSTs (TmGST‐iso1 and TmGST‐iso2) were identified and characterized to elucidate the GST family in Tenebrio molitor. Among the developmental stages of T. molitor, eggs had the highest expression levels of TmGST‐iso1. TmGST‐iso2 expression was highest in the pre‐pupal stage. TmGST‐iso1 expression was high in the guts of early and late larvae, whereas TmGST‐iso2 expression was not observed in early larvae. Adults, both male and female, had the highest levels of TmGST‐iso1 mRNA expression in the gut and reproductive organs, and the highest levels of TmGST‐iso2 expression in the reproductive organs. Quantitative polymerase chain reaction was used to investigate the impact of treatment with butachlor on the mRNA expression of TmGST‐iso1 and TmGST‐iso2 in larvae. TmGST‐iso1 expression increased in the butachlor‐treated group after 3 and 24 h, whereas TmGST‐iso2 expression peaked at 24 h after treatment. This study provides vital information about the detoxifying activities of T. molitor. [ABSTRACT FROM AUTHOR]

In insects, the production of antimicrobial peptides is considered to be the solo arm of the innate immune response. The Toll and immune deficiency pathways are two major signaling pathways that lead to the production of antimicrobial peptides as final effectors. The dynamic functions of Toll/Toll‐like receptors have been thoroughly reviewed in mammals and Drosophila. During the last decade, we have attempted to clarify the immunological roles of different Toll receptor variants and their ligands in Tenebrio molitor. Accordingly, we showed that TmToll‐8, −9, and −10 mRNA transcripts are induced following systemic injections of Gram‐negative, Gram‐positive, and fungal infections. Our data revealed harmonic expression patterns of TmToll‐8, −9, and −10 throughout the developmental stages of healthy individuals and in response to infections in the examined tissues (Malpighian tubules, gut, fat bodies, and hemolymph), illustrating similar evolutionary conversions of different Toll receptor variants in T. molitor. Taken together, our findings highlight the immunological actions of TmToll‐8, −9, and −10 in response to pathogenic insults in T. molitor. [ABSTRACT FROM AUTHOR]

Agricultural intensification has led to significant increases in production, but the overuse of pesticides and associated hazards pose threats to biodiversity and ecological functions. Catalase (CAT), a key antioxidant enzyme, plays a crucial role in alleviating oxidative stress by directly interacting with toxins. In this study, we identified three CAT isoforms in Tenebrio molitor (TmCAT‐iso1, TmCAT‐iso2 and TmCAT‐iso3). These CATs possess a CAT domain, tetramer interface sites and a heme‐binding pocket. We examined the expression of Tm catalases across all developmental stages and in specific tissues using quantitative real time polymerase chain reaction (qRT‐PCR) experiments. Our findings demonstrate that TmCAT‐iso1 and TmCAT‐iso3 exhibit peak expression in young and late larval stages, respectively, whereas TmCAT‐iso2 shows peak expression during the egg and pre‐pupal stages. Tissue distribution analysis revealed the high expression of TmCAT‐iso1 and TmCAT‐iso2 in larval hemocytes, whereas TmCAT‐iso3 is predominantly expressed in larval Malpighian tubules. Furthermore, injection with chlorantraniliprole significantly elevated mRNA expression levels of TmCAT‐iso1, TmCAT‐iso2, and TmCAT‐iso3 in larval groups, compared with control groups. Our study highlights the distinct developmental stages and tissues where TmCATs are expressed. We also elucidated the effects of pesticide application on the expression of each TmCAT, revealing the physiological characteristics of CATs in response to these pesticides, which are dose‐ and time‐dependent in T. molitor. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are considered to be candidate effectors for eliciting humoral immune responses against infectious pathogens in the host. Cecropins are α‐helical peptides of 30–40 amino acids, which are known to permeabilize bacterial membranes, and play authoritative roles in the innate immune system of insects. In the present study, we identified the full‐length open reading frame (ORF) encoding the Tenebrio molitor cecropin‐2 (TmCec2) gene using the Tribolium castaneum cecropin‐2 (TcCec2) gene to query a T. molitor Rnaseq database. Phylogenetic analysis revealed close identity of TmCec2 with TcCec2. TmCec2 was ubiquitously expressed in the insect during all developmental stages, with the highest expression observed in the adult. Tissue‐specific TmCec2 expression was highest in larval hemocytes and in the adult integument and hemocytes. Microbial challenge experiments revealed that TmCec2 was highly induced in response to gram‐positive and gram‐negative bacteria, and fungi. These data provide credible evidence for a putative role of TmCec2 in insect innate immunity against a plethora of pathogens. [ABSTRACT FROM AUTHOR]

Defensins are a major family of antimicrobial peptides that serve as the innate immune defense of both vertebrates and invertebrates. Due to their antimicrobial, chemotactic, and regulatory activities, Defensins have been exploited for their therapeutic potential. Insect Defensins are cysteine‐rich and contain an N‐terminal loop, α‐helix, and antiparallel β‐sheet, forming a "cysteine‐stabilized alpha beta (CSαβ)" or "loop–helix‐sheet" structure. In this study, we identified the full‐length open reading frame (ORF) sequences of Defensin (TmDef) and Defensin‐like (TmDef‐like) genes from the mealworm beetle Tenebrio molitor using in silico methods. TmDef and TmDef‐like genes encode the peptides of 72 and 71 amino acid residues, respectively. TmDefensin is comprised of a Defensin domain and the TmDefensin‐like is comprised of a signal peptide of 21 amino acid residues. Phylogenetic analysis revealed close similarities of TmDefensin with the Defensin of Acalolepta luxuriosa of the longhorn beetle family. The expression of TmDef mRNA was found to be greater than that of TmDef‐like mRNA and was mostly expressed in the pupal and adult stages. Tissue distribution showed high expression of TmDef‐like mRNA in larval hemocytes, gut, integument, and fat body, while in adults, the expression was high in gut and hemocytes. Following bacterial and fungal stimulation in vivo, TmDef was upregulated at 24 h post‐infection in whole body, fat body, and hemocytes of the larvae. Even TmDef‐like mRNA was upregulated in the gut and hemocytes at 12 and 9 h post‐infection respectively. These results suggest that TmDef and TmDef‐like genes play important roles in protecting T. molitor from microbial contact. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are effector candidates that elicit humoral immunity in invertebrates. AMPs facilitate bacterial clearance by either physically disrupting the microbial membranes or the intracellular targets. In the Coleopteran pest, Tenebrio molitor, transcriptional regulation of AMPs has been studied in the context of innate immune signaling cascades and antimicrobial immunity. Here, we report the transcriptional response of three AMP genes, Coleoptericin A, B, and C (TmCole A, B and C) in T. molitor in response to bacterial (Escherichia coli, Staphylococcus aureus), and fungal (Candida albicans) challenges. These genes were expressed essentially in the gut and hemocytes followed by the integument tissue of the T. molitor larva. Further, these genes were highly expressed in the late‐larval, pupal, and early adult stages. Furthermore, while all of these transcripts were highly upregulated in the fat body and Malpighian tubules after bacterial challenge, TmCole B and TmCole C were induced in the gut after E. coli challenge. Fungal stimulation was not required for the upregulation of the transcription of Coleoptericin genes in T. molitor. [ABSTRACT FROM AUTHOR]

We generated a Burkholderia mutant, which is deficient of an N -acetylmuramyl- l -alanine amidase, AmiC, involved in peptidoglycan degradation. When non-motile Δ amiC mutant Burkholderia cells harboring chain form were orally administered to Riptortus insects, Δ amiC mutant cells were unable to establish symbiotic association. But, Δ amiC mutant complemented with amiC gene restored in vivo symbiotic association. Δ amiC mutant cultured in minimal medium restored their motility with single-celled morphology. When Δ amiC mutant cells harboring single-celled morphology were administered to the host insect, this mutant established normal symbiotic association, suggesting that bacterial motility is essential for the successful symbiosis between host insect and Burkholderia symbiont. [ABSTRACT FROM AUTHOR]

Background: Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist known to delay gastric emptying. Despite a growing body of evidence, its peri-operative safety profile remains uncertain, particularly with regard to the risk of increased residual gastric content and aspiration of gastric contents during anaesthesia. We hypothesised that semaglutide interruption of ≤ 10 days before elective surgical procedures is insufficient to reduce or normalise the residual gastric content, despite fasting intervals that comply with current guidelines., Methods: In this prospective observational study, we recruited patients who received pre-operative once-weekly subcutaneous semaglutide within 10 days of the procedure (semaglutide group) and control patients who had not been exposed to semaglutide (non-semaglutide group). On the day of surgery, all patients underwent pre-operative point-of-care gastric ultrasound to evaluate their residual gastric content. Increased residual gastric content was defined as any solid content or > 1.5 ml.kg -1 of clear fluids as assessed by gastric ultrasound., Results: We recruited 220 patients, 107 in the semaglutide group and 113 in the non-semaglutide group. Increased residual gastric content was found in 43/107 patients (40%) in the semaglutide group and 3/113 (3%) in the non-semaglutide group (p < 0.001). In propensity-weighted analysis, semaglutide use (OR 36.97, 95%CI 16.54-99.32), age (OR 0.95, 95%CI 0.93-0.98) and male sex (OR 2.28, 95%CI 1.29-4.06) were significantly associated with increased residual gastric content. There were no cases of pulmonary aspiration of gastric contents., Conclusion: Pre-operative semaglutide use within 10 days of elective surgical procedures was independently associated with increased risk of residual gastric content on pre-operative gastric ultrasound assessment., (© 2024 The Author(s). Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Disruptions in circadian rhythms are risk factors for excessive alcohol drinking. The ethanol-sensitive adenosine equilibrative nucleoside transporter type 1 (ENT1, slc29a1) regulates ethanol-related behaviors, sleep, and entrainment of circadian rhythms. However, the mechanism underlying the increased ethanol consumption in ENT1 knockout (KO) mice in constant light (LL) and whether there are sex differences in ethanol consumption in ENT1 mice are less studied. Here, we investigated the effects of loss of ENT1, LL, and sex on ethanol drinking using two-bottle choice. In addition, we monitored the locomotor activity rhythms. We found that LL increased ethanol drinking and reduced accumbal ENT1 expression and adenosine levels in male but not female mice, compared with control mice. Interestingly, only LL-exposed male, not female, ENT1 KO mice exhibited higher ethanol drinking and a longer circadian period with a higher amplitude compared with wild-type (WT) mice. Furthermore, viral-mediated rescue of ENT1 expression in the NAc of ENT1 KO mice reduced ethanol drinking, demonstrating a possible causal link between ENT1 expression and ethanol drinking in males. Together, our findings indicate that deficiency of ENT1 expression contributes to excessive ethanol drinking in a sex-dependent manner., (© 2019 Society for the Study of Addiction.)

Sex hormones play an important role in establishing sex-distinctive brain structural and functional variations that could contribute to the sex differences in alcohol consumption behavior. Here, we systematically reviewed articles that studied sex hormone impacts on alcohol consumption and alcohol use disorder (AUD). An extensive literature search conducted in MEDLINE, PubMed, Scopus and CINAHL databases identified 776 articles, which were then evaluated for pre-specified criteria for relevance and quality assurance. A total of 50 articles, including 19 human studies and 31 animal studies, were selected for this review. Existing evidence supports the association of increased testosterone level and increased risk for alcohol use and AUD in males but results are inconclusive in females. In contrast, the evidence supports the association of increased estrogen level and increased alcohol use in females, with mixed findings reported in males. Much less is known about the impact of progestins on alcohol use and misuse in human subjects. Future observational and experimental studies conducted in both sexes with a comprehensive hormone panel are needed to elucidate the impact of the interplay between various sex hormone levels during various developmental stages on alcohol use-related phenotypes and AUD., (© 2017 The Authors.Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Background: Major depression is one of the most prevalent psychiatry comorbidities of alcohol use disorders (AUD). As negative emotions can trigger craving and increase the risk of relapse, treatments that target both conditions simultaneously may augment treatment success. Previous studies showed a potential synergistic effect of Food and Drug Administration approved medication for AUD acamprosate and the antidepressant escitalopram. In this study, we investigated the effects of combining acamprosate and escitalopram on ethanol (EtOH) consumption in stress-induced depressed mice., Methods: Forty singly housed C57BL/6J male mice were subjected to chronic unpredictable stress. In parallel, 40 group-housed male mice were subjected to normal husbandry. After 3 weeks, depressive- and anxiety-like behaviors and EtOH consumption were assessed. For the next 7 days, mice were injected with saline, acamprosate (200 mg/kg; twice/d), escitalopram (5 mg/kg; twice/d), or their combination (n = 9 to 11/drug group/stress group). Two-bottle choice limited-access drinking of 15% EtOH and tap water was performed 3 hours into dark phase immediately after the daily dark phase injection. EtOH drinking was monitored for another 7 days without drug administration., Results: Mice subjected to the chronic unpredictable stress paradigm for 3 weeks showed apparent depression- and anxiety-like behaviors compared to their nonstressed counterparts including longer immobility time in the forced swim test and lower sucrose preference. Stressed mice also displayed higher EtOH consumption and preference in a 2-bottle choice drinking test. During the drug administration period, the escitalopram-only and combined drug groups showed significant reduction in EtOH consumption in nonstressed mice, while only the combined drug group showed significantly reduced consumption in stressed mice. However, such reduction did not persist into the postdrug administration period., Conclusions: The combination of acamprosate and escitalopram suppressed EtOH intake in both nonstressed and stressed mice; hence, this combination is potentially helpful for AUD individuals with or without comorbid depression to reduce alcohol use., (Copyright © 2016 by the Research Society on Alcoholism.)

T-helper cells that produce IL-17 (Th17 cells) are a subset of CD4(+) T-cells with pathological roles in autoimmune diseases including systemic lupus erythematosus (SLE), and ETS1 is a negative regulator of Th17 cell differentiation. Our previous work on genome-wide association study (GWAS) identified two variants in the ETS1 gene (rs10893872 and rs1128334) as being associated with SLE. However, like many other risk alleles for complex diseases, little is known on how these genetic variants might affect disease pathogenesis. In this study, we examined serum IL-17 levels from 283 SLE cases and observed a significant correlation between risk variants in ETS1 and serum IL-17 concentration in patients, which suggests a potential mechanistic link between these variants and the disease. Furthermore, we found that the two variants act synergistically in influencing IL-17 production, with evidence of significant genetic interaction between them as well as higher correlation between the haplotype formed by the risk alleles and IL-17 level in patient serum. In addition, the correlation between ETS1 variants and IL-17 level seems to be more significant in SLE patients manifesting renal involvement, dsDNA autoantibody production or early-onset., (© 2013 John Wiley & Sons Ltd/University College London.)

Continuous central pressure monitoring and simultaneous continuous infusion via the same central venous catheter are sometimes necessary. Based on theoretical calculations and experimental measurements, we have determined that pressure monitoring is essentially unaffected if the continuous infusion rate is 50 ml.h(-1) or less for an adult and a paediatric central catheter. At rates > 200 ml.h(-1), the central venous pressure is exaggerated by up to 4 mmHg and 8 mmHg for the adult and paediatric catheters, respectively.

There is increasing interest in the use of cuffed paediatric tracheal tubes, these tubes have a number of advantages and disadvantages. One disadvantage is the decreased margin of safety associated with the use of cuffed tracheal tubes. When using an uncuffed tube, the margin of safety is approximately the length of the trachea, however, for a cuffed tube, this margin is reduced and is the length of the trachea minus the distance between the proximal edge of the cuff and the and the tip of the tube. We have found that, compared with traditional uncuffed tubes, cuffed tubes may be associated with a reduced margin of safety of approximately 50% or more.

A theoretical one-compartment pharmacokinetic model is described, the aim of which is to guide factor VIII replacement therapy in patients with haemophilia A suffering from significant and ongoing haemorrhage. Based on our calculations, plasma factor VIII concentrations can decrease at a rapid rate even with non-severe blood loss.