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Journal of Integrative Neuroscience May 2024To explore the time-frequency structure and cross-scale coupling of electroencephalography (EEG) signals during seizure in juvenile myoclonic epilepsy (JME),...
BACKGROUND
To explore the time-frequency structure and cross-scale coupling of electroencephalography (EEG) signals during seizure in juvenile myoclonic epilepsy (JME), correlations between different leads, as well as dynamic evolution in epileptic discharge, progression and end of seizure were examined.
METHODS
EEG data were obtained for 10 subjects with JME and 10 normal controls and were decomposed using gauss continuous wavelet transform (CWT). The phase amplitude coupling (PAC) relationship between the 11th (4.57 Hz) and 17th (0.4 Hz) scale was investigated. Correlations were examined between the 11th and 17th scale EEG signals in different leads during seizure, using multi-scale cross correlation analysis.
RESULTS
The time-frequency structure of JME subjects showed strong rhythmic activity in the 11th and 17th scales and a close PAC was identified. Correlation analysis revealed that the ictal JME correlation first increased in the anterior head early in seizure and gradually expanded to the posterior head.
CONCLUSION
PAC was exhibited between the 11th and 17th scales during JME seizure. The results revealed that the correlation in the anterior leads was higher than the posterior leads. In the perictal period, the 17th scale EEG signal preceded the 11th scale signal and remained for some time after a seizure. This suggests that the 17th scale signal may play an important role in JME seizure.
Topics: Humans; Myoclonic Epilepsy, Juvenile; Electroencephalography; Male; Female; Young Adult; Adult; Adolescent; Wavelet Analysis; Brain; Brain Waves; Signal Processing, Computer-Assisted
PubMed: 38812390
DOI: 10.31083/j.jin2305097 -
Insects May 2024Starvation is a complex physiological state that induces changes in protein expression to ensure survival. The insect midgut is sensitive to changes in dietary content...
Starvation is a complex physiological state that induces changes in protein expression to ensure survival. The insect midgut is sensitive to changes in dietary content as it is at the forefront of communicating information about incoming nutrients to the body via hormones. Therefore, a DIA proteomics approach was used to examine starvation physiology and, specifically, the role of midgut neuropeptide hormones in a representative lepidopteran, . Proteomes were generated from midguts of fourth-instar caterpillars, starved for 24 h and 48 h, and compared to fed controls. A total of 3047 proteins were identified, and 854 of these were significantly different in abundance. KEGG analysis revealed that metabolism pathways were less abundant in starved caterpillars, but oxidative phosphorylation proteins were more abundant. In addition, six neuropeptides or related signaling cascade proteins were detected. Particularly, neuropeptide F1 (NPF1) was significantly higher in abundance in starved larvae. A change in juvenile hormone-degrading enzymes was also detected during starvation. Overall, our results provide an exploration of the midgut response to starvation in and validate DIA proteomics as a useful tool for quantifying insect midgut neuropeptide hormones.
PubMed: 38786882
DOI: 10.3390/insects15050325 -
BMC Biology May 2024Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation...
BACKGROUND
Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown.
RESULTS
In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for the biosynthesis of JHB3 and JH III in D. melanogaster. The Cyp6g2 is predominantly expressed in the corpus allatum (CA), concurring with the expression pattern of jhamt, another well-studied gene that is crucial in the last steps of JH biosynthesis. Mutation in Cyp6g2 leads to severe disruptions in larval-pupal metamorphosis and exhibits reproductive deficiencies, exceeding those seen in jhamt mutants. Notably, Cyp6g2::jhamt double mutants all died at the pupal stage but could be rescued through the topical application of JH analogs. JH titer analyses revealed that both Cyp6g2 mutant and jhamt mutant lacking JHB3 and JH III, while overexpression of Cyp6g2 or jhamt caused a significant increase in JHB3 and JH III titer.
CONCLUSIONS
These findings collectively established that Cyp6g2 as the major JH epoxidase in the higher dipterans and laid the groundwork for the further understanding of JH biosynthesis. Moreover, these findings pave the way for developing specific Cyp6g2 inhibitors as insect growth regulators or insecticides.
Topics: Animals; Drosophila melanogaster; Juvenile Hormones; Drosophila Proteins; Cytochrome P-450 Enzyme System; Larva; Metamorphosis, Biological; Corpora Allata; Pupa; Oxidoreductases
PubMed: 38741075
DOI: 10.1186/s12915-024-01910-4 -
Pediatric Rheumatology Online Journal May 2024Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used... (Randomized Controlled Trial)
Randomized Controlled Trial
Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial.
BACKGROUND
Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial.
METHODS
92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m/week.
RESULTS
32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4-10), median 10 months (7-16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6-9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group.
CONCLUSIONS
Escalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety.
TRIAL REGISTRATION
Dutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585 .
Topics: Humans; Arthritis, Juvenile; Etanercept; Female; Male; Child; Antirheumatic Agents; Methotrexate; Drug Therapy, Combination; Child, Preschool; Dose-Response Relationship, Drug; Treatment Outcome; Prednisolone; Sulfasalazine
PubMed: 38730442
DOI: 10.1186/s12969-024-00989-x -
Integrative Organismal Biology (Oxford,... 2024Stressful experiences in early life can have phenotypic effects that persist into, or manifest during, adulthood. In vertebrates, such carryover effects can be driven by...
Stressful experiences in early life can have phenotypic effects that persist into, or manifest during, adulthood. In vertebrates, such carryover effects can be driven by stress-induced secretion of glucocorticoid hormones, such as corticosterone, which can lead to developmental reprogramming of hypothalamic-pituitary-adrenal/interrenal axis activity and behavior. Nutritional stress in the form of early life nutrient restriction is well known to modify later life behaviors and stress activity through corticosterone-related mechanisms. However, it is not known whether corticosterone is also mechanistically involved in carryover effects induced by a different form of nutritional variation: the use of alternate or entirely novel types of dietary resources. The plains spadefoot () presents an excellent system for testing this question, since larvae of this species have evolved to use 2 alternate diet types: an ancestral detritus-based diet and a more novel diet of live shrimp. While previous work has shown that feeding on the novel shrimp diet influences juvenile (i.e., post-metamorphic) behavior and corticosterone levels, it is unclear whether these diet-induced carryover effects are mediated by diet-induced corticosterone itself. To test for the mechanistic role of corticosterone in diet-induced carryover effects, we experimentally treated larvae with exogenous corticosterone and measured subsequent effects on juvenile behavior and corticosterone levels. We found that while shrimp-fed larvae had elevated corticosterone levels, treatment of larvae with corticosterone itself had effects on juvenile behavior that partially resembled those carryover effects induced by the shrimp diet, such as altered food seeking and higher locomotor activity. However, unlike carryover effects caused by the shrimp diet, larval corticosterone exposure did not affect juvenile corticosterone levels. Overall, our study shows that corticosterone-related mechanisms are likely involved in carryover effects induced by a novel diet, yet such diet-induced carryover effects are not driven by corticosterone alone.
PubMed: 38707679
DOI: 10.1093/iob/obae012 -
Scientific Reports Apr 2024Intestinal stem cells (ISCs) of the fruit fly, Drosophila melanogaster, offer an excellent genetic model to explore homeostatic roles of ISCs in animal physiology. Among...
Intestinal stem cells (ISCs) of the fruit fly, Drosophila melanogaster, offer an excellent genetic model to explore homeostatic roles of ISCs in animal physiology. Among available genetic tools, the escargot (esg)-GAL4 driver, expressing the yeast transcription factor gene, GAL4, under control of the esg gene promoter, has contributed significantly to ISC studies. This driver facilitates activation of genes of interest in proximity to a GAL4-binding element, Upstream Activating Sequence, in ISCs and progenitor enteroblasts (EBs). While esg-GAL4 has been considered an ISC/EB-specific driver, recent studies have shown that esg-GAL4 is also active in other tissues, such as neurons and ovaries. Therefore, the ISC/EB specificity of esg-GAL4 is questionable. In this study, we reveal esg-GAL4 expression in the corpus allatum (CA), responsible for juvenile hormone (JH) production. When driving the oncogenic gene, Ras, esg-GAL4 induces overgrowth in ISCs/EBs as reported, but also increases CA cell number and size. Consistent with this observation, animals alter expression of JH-response genes. Our data show that esg-GAL4-driven gene manipulation can systemically influence JH-mediated animal physiology, arguing for cautious use of esg-GAL4 as a "specific" ISC/EB driver to examine ISC/EB-mediated animal physiology.
Topics: Animals; Drosophila melanogaster; Drosophila Proteins; Stem Cells; Transcription Factors; Juvenile Hormones; Intestines; Gene Expression Regulation; Animals, Genetically Modified
PubMed: 38671036
DOI: 10.1038/s41598-024-60269-2 -
Journal of the American Mosquito... Jun 2024The Salt Lake City Mosquito Abatement District (SLCMAD) detected a 20,000-fold resistance to Lysinibacillus sphaericus (Lsph) in Culex pipiens occurring in catch basins...
The Salt Lake City Mosquito Abatement District (SLCMAD) detected a 20,000-fold resistance to Lysinibacillus sphaericus (Lsph) in Culex pipiens occurring in catch basins of Salt Lake City during 2016. In response, SLCMAD suspended use of Lsph and rotated use of spinosyn and s-methoprene products for the next three years. At the end of the third year, Lsph was evaluated again and efficacy similar to susceptible colony strains. During the second year of Lsph use, technicians observed lack of control of larvae at some urban sites. Bioassays performed during 2021 showed recurrence of some resistance to Lsph to varying degrees across SLCMAD urban areas. The rapidity with which resistant phenotypes reemerged clarifies that SLCMAD cannot in the near future rely on repeated use of Lsph, even after suspending use for three years and using within-season product rotations. Prior reports in other research groups have found long-term selection to Lsph, as is the case at SLCMAD, to not regress in spite of halting use of the products. However, our findings offer some optimism that regression may be relatively quick. More operational review is needed, and future work should characterize resistance alleles in field populations. Collectively, there is a lack of concrete data supporting the prevailing assumptions from adjacent industries that were adopted into mosquito abatement. We provide this short note as additional guidance for mosquito and vector control districts weighing options to remediate Lsph resistance.
Topics: Animals; Culex; Utah; Mosquito Control; Larva; Bacillaceae; Macrolides; Methoprene; Insecticides; Drug Combinations
PubMed: 38660965
DOI: 10.2987/24-7172 -
Journal of Vector Borne Diseases Jan 2024Insect growth regulators (IGRs) are biological hormone analogue or mimics used as pesticides to inhibit the growth of larva during their molting and skin shedding. This...
BACKGROUND OBJECTIVES
Insect growth regulators (IGRs) are biological hormone analogue or mimics used as pesticides to inhibit the growth of larva during their molting and skin shedding. This study aimed to test the effect of IGRs on the eggs hatching and post-hatching inhibition of Aedes mosquitoes and understanding its effect in the mosquito breeding habitats for reduction in adult emergence.
METHODS
Experiments on the evaluation of three insect growth regulators (IGRs) for the control of different stages of Aedes aegypti was carried out during 2020-21. Each experiment consisted of four treatments viz., Pyriproxyfen, Novaluron, and Larvicol at 1.0 ppm and distilled water as a control. All experiments were carried out in completely randomized design (CRD) except eggs which were carried out in factorial design each with three replications.
RESULTS
All tested IGRs performed better in affecting eggs, larval and pupal stages of Ae. aegypti. Highest eggs hatching inhibition (80%) of fresh eggs occurred in Pyriproxyfen followed by Novaluron (66%) and lowest in Larvicol (62%). Eggs hatch inhibition of embryonated eggs was lower than fresh eggs. Pyriproxyfen caused 69%, Novaluron 59% and Larvicol 39% eggs hatch inhibition of embryonated eggs. Both Pyriproxyfen and Novaluron performed better in causing 98-100% larval mortality followed by Larvicol (39%). Larval development to pupal stage was completely prevented by both Pyriproxyfen and Novaluron. Although Larvicol resulted in lowest eggs hatch and larval inhibition but prevented pupae to emerge as adults. Results further showed 70-89% mortality of 3rd instar larvae of Ae. aegypti when exposed to Pyriproxyfen and Novaluron solutions after 30 days storage at lab. temperature (27±2°C), RH 70±5.
INTERPRETATION CONCLUSION
None of the IGRs was more effective at the pupal stage but showed carry-on activity of growth inhibition and mortality of the successive stages of development when used against eggs stages. Therefore, we recommend early application of IGRs at mosquito habitats during the beginning and onset of the season when very early stages of mosquitoes are available in the field.
Topics: Animals; Aedes; Juvenile Hormones; Larva; Mosquito Control; Pyridines; Phenylurea Compounds; Pupa; Female; Nitriles; Insecticides; Ovum
PubMed: 38648415
DOI: 10.4103/0972-9062.392257 -
Endocrinology Mar 2024We examined the effect of the puberty blocker, leuprolide acetate, on sex differences in juvenile rough-and-tumble play behavior and anxiety-like behavior in adolescent...
We examined the effect of the puberty blocker, leuprolide acetate, on sex differences in juvenile rough-and-tumble play behavior and anxiety-like behavior in adolescent male and female rats. We also evaluated leuprolide treatment on gonadal and pituitary hormone levels and activity-regulated cytoskeleton-protein messenger RNA levels within the adolescent amygdala, a region important both for rough-and-tumble play and anxiety-like behavior. Our findings suggest that leuprolide treatment lowered anxiety-like behavior during adolescent development, suggesting that the maturation of gonadotropin-releasing hormone systems may be linked to increased anxiety. These data provide a potential new model to understand the emergence of increased anxiety triggered around puberty. Leuprolide also reduced masculinized levels of rough-and-tumble play behavior, lowered follicle-stimulating hormone, and produced a consistent pattern of reducing or halting sex differences of hormone levels, including testosterone, growth hormone, thyrotropin, and corticosterone levels. Therefore, leuprolide treatment not only pauses sexual development of peripheral tissues, but also reduces sex differences in hormones, brain, and behavior, allowing for better harmonization of these systems following gender-affirming hormone treatment. These data contribute to the intended use of puberty blockers in stopping sex differences from developing further with the potential benefit of lowering anxiety-like behavior.
Topics: Animals; Leuprolide; Male; Female; Anxiety; Rats; Behavior, Animal; Sexual Maturation; Sex Characteristics; Amygdala; Corticosterone; Rats, Sprague-Dawley; Testosterone
PubMed: 38597659
DOI: 10.1210/endocr/bqae046 -
Veterinary Parasitology Jun 2024The control of the sheep blowfly relies on the use of insecticides. There have been several reports of in vitro and in vivo resistance to the most widely-used flystrike...
The control of the sheep blowfly relies on the use of insecticides. There have been several reports of in vitro and in vivo resistance to the most widely-used flystrike control chemical, dicyclanil. A recent report also described in vitro resistance to imidacloprid in a strain collected from a single property over three consecutive seasons that also showed resistance to dicyclanil. The present study aimed to use in vitro assays to examine five field-collected blowfly strains to determine if this co-occurrence of resistance to dicyclanil and imidacloprid was present more widely in field strains and to also measure resistance patterns to the other currently-used flystrike control chemicals. Each of the strains showed significant levels of resistance to both dicyclanil and imidacloprid: resistance factors at the IC of 9.1-23.8 for dicyclanil, and 8.7-14.1 for imidacloprid. Resistance factors at the IC ranged from 16.5 to 53.7, and 14.6-24.3 for dicyclanil and imidacloprid, respectively. Resistance factors were up to 8.5 for cyromazine at the IC. Resistance to dicyclanil and imidacloprid was suppressed by co-treatment with the cytochrome P450 inhibitor, aminobenzotriazole, implicating this enzyme system in the observed resistances. We discuss the implications of the co-occurrence of resistance to dicyclanil and imidacloprid on insecticide rotation strategies for blowfly control. We also discuss the roles of insecticide resistance, environmental factors (e.g. rainfall), operational factors (e.g. insecticide application technique) and other animal health issues (e.g. scouring / diarrhoea) that together will impact on the likelihood of flystrike occurring at an earlier time point than expected after insecticide application.
Topics: Animals; Insecticide Resistance; Insecticides; Neonicotinoids; Nitro Compounds; Diptera; Sheep; Sheep Diseases; Juvenile Hormones; Triazines
PubMed: 38569277
DOI: 10.1016/j.vetpar.2024.110178