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Background: Temperature is an important determinant of developmental and reproductive rates in insects. Here, we investigated the physiological responses of adult beet webworm, Loxostege sticticalis L. (Lepidoptera: Crambidae), to three temperatures (16, 23 and 30 °C) focusing on trehalose metabolism., Results: Exposure of moths to 30 °C accelerated eclosion and ovarian development, but shortened the oviposition period and adult longevity, whereas exposure to 16 °C had opposite effects. Transcriptome analysis revealed that vitellogenin (VG) and vitellogenin receptor (VR) genes were up-regulated at 30 °C, as were numerous genes related to energy metabolism, including those involved in the insulin signaling pathway, the tricarboxylic acid (TCA) cycle, and glycolysis. Expression of the trehalose transporter gene TRET1 was also induced at high temperature, primarily in the ovaries, where trehalose content increased, accompanied by lipid degradation in the fat body. Treatment with the trehalase inhibitor validamycin A reduced female fecundity and longevity at 23 °C, but enhanced the expression of genes related to stress resistance and reproduction, mimicking the effect of high temperature., Conclusion: Besides their practical utility for predicting the oviposition behavior and geographic distribution of L. sticticalis in the field, these results elucidate the various physiological roles of trehalose in L. sticticalis during exposure of moths to high temperature and may provide insights into the relationship between stress resistance and reproduction in insects more generally. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The stink bugs Acrosternum arabicum Wagner and Brachynema germari Kolenati (Hemiptera: Pentatomidae) damage developing pistachio nuts in Iran. Ooencyrtus egeria Huang and Noyes (Hymenoptera: Encyrtidae) parasitizes eggs of both species, alternating between them seasonally. We compared the biological and life history attributes of O. egeria reared for 3 generations on each host species with those that had been transferred to the alternate host for 2 generations. We also tested female responses to host egg density. Eggs of B. germari were parasitized at higher rates and yielded faster wasp development, heavier female progeny with greater fecundity, and a more female-biased sex ratio, than eggs of A. arabicum. Rearing on A. arabicum did not diminish wasp fitness on B. germari, and the F1 progeny of wasps switched to A. arabicum inherited some beneficial parental effects from rearing on B. germari. Regardless of host species, females parasitized fewer eggs in 8 h as density increased from 10 to 30 eggs, but progeny sex ratio (% female) increased. The anomalous response to host density appears to arise from a combination of behavioral and egg load constraints. Females mature only 10-12 eggs per day. Carefully inspect egg clusters before selecting the most suitable eggs for oviposition, a more time-consuming process for large clusters. Our results indicate that rearing O. egeria on eggs of A. arabicum, which are more convenient and cost-effective to produce than those of B. germari, will not diminish its performance on B. germari following augmentative release, beyond a slight reduction in female fecundity., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Quality assessment of pome fruits (i.e. apples and pears) is used not only for determining the optimal harvest time but also for the progression of fruit-quality attributes during storage. Therefore, it is typical to repeatedly evaluate fruits during the course of a postharvest experiment. This evaluation often includes careful visual assessments of fruit for apparent defects and physiological symptoms. A general best practice for quality assessment is to rate fruit using the same individual rater or group of individual raters to reduce bias. However, such consistency across labs, facilities, and experiments is often not feasible or attainable. Moreover, while these visual assessments are critical empirical data, they are often coarse-grained and lack consistent objective criteria. Granny, is a tool designed for rating fruit using machine-learning and image-processing to address rater bias and improve resolution. Additionally, Granny supports backward compatibility by providing ratings compatible with long-established standards and references, promoting research program continuity. Current Granny ratings include starch content assessment, rating levels of peel defects, and peel color analyses. Integrative analyses enhanced by Granny's improved resolution and reduced bias, such as linking fruit outcomes to global scale -omics data, environmental changes, and other quantitative fruit quality metrics like soluble solids content and flesh firmness, will further enrich our understanding of fruit quality dynamics. Lastly, Granny is open-source and freely available., Competing Interests: The authors do not have any conflict of interests to declare., (© 2024 The Author(s). Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

The two-spotted spider mite, Tetranychus urticae Koch (TSSM), is an important cosmopolitan pest of agricultural crops that is often managed in greenhouses by augmentation of predatory mites in combination with acaricides. Here we examined the transgenerational effects of low lethal concentrations of a widely-used acaricide, Oberon Speed® (a combination of spiromesifen and abamectin), on the life history traits and population growth of T. urticae and two of its predators, Phytoseiulus persimilis Athias-Henriot and Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae). The concentrations employed corresponded to the LC 10 , LC 20 and LC 30 values estimated for TSSM protonymphs 48 h post-exposure in a topical bioassay, which yielded an LC 50 value of 207.2 ppm. Parental exposure of TSSM to all three low concentrations increased the total developmental time of progeny; both the LC 20 and LC 30 treatments reduced adult longevity and number of oviposition days, but only the LC 30 treatment increased the preoviposition period. Similarly, both the LC 20 and LC 30 treatments significantly reduced life table parameters (r, R 0 , λ, and GRR), and increased generation time (T) and population doubling time (DT). Although maternal exposure to the acaricide had various impacts on progeny life history, A. swirskii was less affected than P. persimilis, suggesting the former species would be more compatible for integration with Oberon Speed® for control of T. urticae in greenhouse vegetable production., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: In septic arthritis, joint lavage can be performed using arthrocentesis (articular needle aspiration) or arthrotomy. The use of fluoroscopy to guide the puncture involves radiation. Ultrasound (US) guidance is still little recommended to guide the treatment of septic arthritis in children. We wanted to know whether treating septic arthritis in children was feasible and safe under ultrasound (US) guidance., Methods: We retrospectively included 67 children (mean age, 3.0 years; range: 1 month-12 years) treated for septic arthritis of the hip, shoulder, or ankle using arthrocentesis or arthrotomy under US or fluoroscopic guidance (non-US group) with at least two years of follow-up., Results: We found no significant difference between the groups. After arthrocentesis, patients in the US group remained in hospital for 0.8 days longer than those in the non-US group, but the difference was not significant. After arthrotomy, the arthrotomy-US group required 0.4 more days of hospitalization than the non-US group, but the difference was not significant. Patients in the US group exhibited higher initial CRP and WBC values than patients treated without US, although the differences were not significant. The WBC values of the arthrocentesis-US groups were higher than those of the non-US groups initially and at 72 h, but non significantly so; they became similar on day 5. Three puncture failures required arthrotomy (two under US guidance). Three patients required early revision surgery: one had undergone arthrocentesis with US, one arthrocentesis without US, and one arthrotomy without US. At the last follow-up, there were no clinical sequelae but two hip arthrotomies (one US and one non-US child) showed asymptomatic calcifications., Conclusions: US guidance is feasible and safe for treating septic arthritis in children, visualizing structures not shown by X-rays and avoiding radiation exposure during surgery., Level of Evidence: IV (case series)., Trial Registration: IRB-MTP_2021_05_202100781., (© 2024. The Author(s).)

Opioid use disorder (OUD) has emerged as a severe, ongoing public health emergency. Current, frontline addiction treatment strategies fail to produce lasting abstinence in most users. This underscores the lasting effects of chronic opioid exposure and emphasizes the need to understand the molecular mechanisms of drug seeking and taking, but also how those alterations persist through acute and protracted withdrawal. Here, we used RNA sequencing in post-mortem human tissue from males (n=10) and females (n=10) with OUD and age and sex-matched comparison subjects. We compared molecular alterations in the nucleus accumbens (NAc) and dorsolateral prefrontal cortex (DLPFC) between humans with OUD and rodent models across distinct stages of opioid use and withdrawal (acute and prolonged) using differential gene expression and network-based approaches. We found that the molecular signature in the NAc of females with OUD mirrored effects seen in the NAc of female mice at all stages of exposure. Conversely, males with OUD showed strong overlap in expression profile with rats in acute withdrawal. Co-expression networks involved in post-transcriptional modification of RNA and epigenetic modification of chromatin state. This study provides fundamental insight into the converging molecular pathways altered by opioids across species. Further, this work helps to disentangle which alterations observed in humans with OUD are driven by acute drug exposure and which alterations are consequences of chronic exposure., Competing Interests: Declarations Competing Interests The authors have nothing to disclose.

Background: Childhood neurodegenerative diseases often pose a challenge to clinicians to diagnose because of the degree of genetic heterogeneity and variable presentations. Here, we present a child with progressive neurodegeneration consisting of spasticity, dystonia, and ataxia in which postmortem pathological analysis led to the diagnosis of interferon regulatory factor 2 binding protein like (IRF2BPL)-related disorder., Methods: Detailed postmortem gross and histological examination was conducted, and findings consistent with dentatorubral-pallidoluysian atrophy (DRPLA) and included polyglutamine (polyQ) inclusions. Follow up testing for the CAG repeat expansion at ATN1 was non-diagnostic., Results: Subsequent exome sequencing reanalysis of the research exome identified a pathogenic de novo IRF2BPL variant. The IRF2BPL c.562C>T, p.(Arg188Ter) variant, distal to the polyQ repeat tract, results in variable mRNA levels depending on the cell type examined with decreased mRNA in the brain, as well as destabilization of the protein product and corresponding downstream molecular abnormalities in patient derived cells., Conclusion: We provide the first detailed pathological description for IRF2BPL-related disorder, termed NEDAMSS (neurodevelopmental disorder with regression, abnormal movements, loss of speech and seizures; Mendelian Inheritance in Man, 618088) and evidence for the inclusion of this condition in the differential diagnosis of spastic-ataxic neurodegenerative conditions, reminiscent of DRPLA. Although the individuals with NEDAMSS do not carry an expansion, the polyQ repeat tract may play a role in the pathological inclusions that would represent a novel disease mechanism for polyQ repeats. © 2024 International Parkinson and Movement Disorder Society., (© 2024 International Parkinson and Movement Disorder Society.)

Background: Lepidopteran pest control in agriculture has become heavily dependent on cultivars that express Bacillus thuringiensis (Bt) toxins as 'plant-incorporated protectants'. However, populations of Spodoptera frugiperda (Smith) in Brazil appear resistant to the Bt traits currently available in commercial soybean cultivars., Results: This study evaluated S. frugiperda life history when feeding on three different Bt soybean cultivars. Cultivars expressing Cry1Ac + Cry1F and Cry1A.105 + Cry2Ab2 + Cry1Ac Bt toxins caused 100% larval mortality in S. frugiperda. Both non-Bt and Cry1Ac-expressing soybean induced transgenerational effects that increased the survival of subsequent generations. A Cry1Ac soybean diet reduced the generation time (T) of S. frugiperda relative to non-Bt soybean, resulting in shorter generation time and more rapid population growth., Conclusion: The implications of these results revealed how diet can alter aspects of insect life history and biology, and have important implications for sustainable management of S. frugiperda on soybean. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Integrated pest management relies upon mutual compatibility among pest control tactics. The fruit-boring moths Carposina sasakii and Grapholita molesta can be devastating pests of pome and stone fruit production. Trichogramma dendrolimi parasitizes the eggs of these pests, preventing their eclosion, but its efficacy can be reduced by other pest control tactics. We tested T. dendrolimi attraction to five colors, and moth attraction to six colors, in laboratory choice tests, and thereafter deployed yellow sticky cards in tandem with releases of T. dendrolimi in field trials in a pear orchard. Yellow sticky cards deployed at high density trapped T. dendrolimi and reduced their numbers post-release. They also trapped adult G. molesta , which appeared to compensate for reduced egg parasitism on this species, but not on C. sasakii , which had higher abundance in plots with yellow sticky cards. The cards also captured adult lacewings, likely reducing their numbers in the field, but did not capture large numbers of lady beetles. The results suggest that yellow sticky cards can be used at high density to control aphids, psyllids and leafhoppers in early spring (March and April) when natural enemies are in low numbers, then removed in May so as not to interfere with augmentative releases of T. dendrolimi that must be timed to coincide with peak flights of fruit-boring moths. This strategy should enhance the compatibility of yellow sticky cards with egg parasitoid releases.

Increasing evidence suggests that the muscle stem cell (MuSC) pool is heterogeneous. In particular, a rare subset of PAX7-positive MuSCs that has never expressed the myogenic regulatory factor MYF5 displays unique self-renewal and engraftment characteristics. However, the scarcity and limited availability of protein markers make the characterization of these cells challenging. Here, we describe the generation of StemRep reporter mice enabling the monitoring of PAX7 and MYF5 proteins based on equimolar levels of dual nuclear fluorescence. High levels of PAX7 protein and low levels of MYF5 delineate a deeply quiescent MuSC subpopulation with an increased capacity for asymmetric division and distinct dynamics of activation, proliferation, and commitment. Aging primarily reduces the MYF5 Low MuSCs and skews the stem cell pool toward MYF5 High cells with lower quiescence and self-renewal potential. Altogether, we establish the StemRep model as a versatile tool to study MuSC heterogeneity and broaden our understanding of mechanisms regulating MuSC quiescence and self-renewal in homeostatic, regenerating, and aged muscles., Competing Interests: Declaration of interests Except S.C.S., all authors are or were employees of Société des Produits Nestlé SA., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction/background: Bladder exstrophy epispadias complex (BEEC) is a rare congenital anomaly of unknown etiology, although, genetic and environmental factors have been associated with its development. Variants in several genes expressed in the urogenital pathway have been reported as causative for bladder exstrophy in human and murine models. The expansion of next-generation sequencing and molecular genomics has improved our ability to identify the underlying genetic causes of similarly complex diseases and could thus assist with the investigation of the molecular basis of BEEC., Objective: The objective was to identify the presence of rare heterozygous variants in genes previously implicated in bladder exstrophy and correlate them with the presence or absence of bladder regeneration in our study population., Patients and Methods: We present a case series of 12 patients with BEEC who had bladder biopsies performed by pediatric urology during bladder neck reconstruction or bladder augmentation. Cases were classified as "sufficient" or "insufficient" (n = 5 and 7, respectively) based on a bladder volume of greater than or less than 40% of expected bladder size. Control bladder tissue specimens were obtained from patients (n = 6) undergoing biopsies for conditions other than bladder exstrophy. Whole exome sequencing was performed on DNA isolated from the bladder specimens. Based on the hypothesis of de novo mutations, as well as the potential implications of autosomal dominant conditions with incomplete penetrance, each case was evaluated for autosomal dominant variants in a set of genes previously implicated in BEEC., Results: Our review of the literature identified 44 genes that have been implicated in human models of bladder exstrophy. Our whole exome sequencing data analysis identified rare variants in two of these genes among the cases classified as sufficient, and seven variants in five of these genes among the cases classified as insufficient., Conclusion: We identified rare variants in seven previously implicated genes in our BEEC specimens. Additional research is needed to further understand the cellular signaling underlying this potentially genetically heterogeneous embryological condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Jelin, Sopko, Sobreira, Boyadjiev, Wohler, Morrill, Witmer, Michaud, Valle, Gearhart and Dicarlo.)

Bladder exstrophy epispadias complex (BEEC) encompasses a spectrum of conditions ranging from mild epispadias to the most severe form: omphalocele-bladder exstrophy-imperforate anus-spinal defects (OEIS). BEEC involves abnormalities related to anatomical structures that are proposed to have a similar underlying etiology and pathogenesis. In general, BEEC, is considered to arise from a sequence of events in embryonic development and is believed to be a multi-etiological disease with contributions from genetic and environmental factors. Several genes have been implicated and mouse models have been generated, including a knockout model of p63, which is involved in the synthesis of stratified epithelium. Mice lacking p63 have undifferentiated ventral urothelium. MNX1 has also been implicated. In addition, cigarette smoking, diazepam and clomid have been implied as environmental factors due to their relative association. By in large, the etiology and pathogenesis of human BEEC is unknown. We performed de novo analysis of whole exome sequencing (WES) of germline samples from 31 unrelated trios where the probands have a diagnosis of BEEC syndrome. We also evaluated the DECIPHER database to identify copy number variants (CNVs) in genes in individuals with the search terms "bladder exstrophy" in an attempt to identify additional candidate genes within these regions. Several de novo variants were identified; however, a candidate gene is still unclear. This data further supports the multi-etiological nature of BEEC., (© 2023 Wiley Periodicals LLC.)

Impaired skeletal muscle stem cell (MuSC) function has long been suspected to contribute to the pathogenesis of muscular dystrophy (MD). Here, we showed that defects in the endothelial cell (EC) compartment of the vascular stem cell niche in mouse models of Duchenne MD, laminin α2-related MD, and collagen VI-related myopathy were associated with inefficient mobilization of MuSCs after tissue damage. Using chemoinformatic analysis, we identified the 13-amino acid form of the peptide hormone apelin (AP-13) as a candidate for systemic stimulation of skeletal muscle ECs. Systemic administration of AP-13 using osmotic pumps generated a pro-proliferative EC-rich niche that supported MuSC function through angiocrine factors and markedly improved tissue regeneration and muscle strength in all three dystrophic mouse models. Moreover, EC-specific knockout of the apelin receptor led to regenerative defects that phenocopied key pathological features of MD, including vascular defects, fibrosis, muscle fiber necrosis, impaired MuSC function, and reduced force generation. Together, these studies provide in vivo proof of concept that enhancing endogenous skeletal muscle repair by targeting the vascular niche is a viable therapeutic avenue for MD and characterized AP-13 as a candidate for further study for the systemic treatment of MuSC dysfunction.

We introduce a mathematical model of cultural evolution to study cultural traits that shape how individuals exchange information. Current theory focuses on traits that influence the reception of information (receiver traits), such as evaluating whether information represents the majority or stems from a trusted source. Our model shifts the focus from the receiver to the sender of cultural information and emphasizes the role of sender traits, such as communicability or persuasiveness. Here, we show that sender traits are probably a stronger driving force in cultural evolution than receiver traits. While receiver traits evolve to curb cultural transmission, sender traits can amplify it and fuel the self-organization of systems of mutually supporting cultural traits, including traits that cannot be maintained on their own. Such systems can reach arbitrary complexity, potentially explaining uniquely human practical and mental skills, goals, knowledge and creativity, independent of innate factors. Our model incorporates social and individual learning throughout the lifespan, thus connecting cultural evolutionary theory with developmental psychology. This approach provides fresh insights into the trait-individual duality, that is, how cultural transmission of single traits is influenced by individuals, who are each represented as an acquired system of cultural traits.

The carob moth, Ectomyelois ceratoniae (Zeller) (Lepidoptera: Pyralidae), is an important pest of pistachio causing direct damage to nuts during ripening, and in storage. We examined the tritrophic effects of 5 pistachio cultivars, representing the full range of kernel suitability for E. ceratoniae, on 2 larval parasitoids, Habrobracon hebetor (Say) (Hymenoptera: Braconidae), a gregarious, synovigenic, idiobiont, ectoparasitoid, and Venturia canescens Gravenhorst (Hymenoptera: Ichneumonidae), a solitary, pro-ovigenic, koinobiont, endoparasitoid. The suitability of pistachio cultivars for development and reproduction of the 2 parasitoids was closely correlated, despite their divergent lifestyles and developmental patterns, and paralleled variation in kernel suitability for host larvae. Although kernels of the most resistant cultivar reduced demographic parameters of the parasitoids, the potential impact on numerical responses was minor. Successful biological control of carob moth within the vulnerable period of nut ripening will likely depend on the functional responses of earlier generations of adult parasitoids emerging from other fruit and nut crops, or those released in an augmentation program., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: With the recent interest in hip-spine relationship, the link between femoroacetabular impingement (FAI) and the lumbar-pelvic-femoral complex (LPFC) appears decisive. The objectives of this study were (1) to compare the pelvic version, as well as (2) all the parameters of the LPFC between two populations of healthy subjects, comparing those with radiological signs of FAI to those without and finally, (3) to evaluate the LPFC parameters according to the type of FAI., Hypothesis: Asymptomatic subjects with radiological signs of FAI had superior pelvic anteversion., Materials and Method: This retrospective study was based on a prospective cohort of 118 voluntary asymptomatic patients including 62 men (52.5%) with a mean age of 25.6 years±4.4 (19-39). The following parameters: pelvic version (PV), pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), hip flexion, intrinsic (IER) and extrinsic (EER) extension reserve were measured using EOS imaging™ in the reference standing position and the lunge position. The radiological signs of FAI (cam, pincer, mixed) were identified on these acquisitions then separated into 2 groups. The first was the group presenting with one or more images of FAI (FAI+) and the second group with no images of FAI (FAI-)., Results: There were 143 hips in the FAI+ group compared to 93 hips in the FAI- group. There were 36.4% cams and 45% pincers. With an average of 9.08°±7.81 (-11.0; 27.0) versus 12.33°±8.94 (-5.0; 55.0), the PV was significantly lower (p=0.022) in the FAI+ group compared to the FAI- group. A post-hoc power analysis on the primary outcome (PV) confirmed sufficient power (1-β=0.809). Compared to the FAI- group, the cam group presented a significantly lower IER and EER (respectively p=0.014 and p=0.047). The comparative analysis between the FAI- and pincer groups found a significant difference in PI (p=0.001), PV (p<0.001), IER (p=0.017) and hip flexion (p<0.001), SS in lunge position (p=0.031) and EER (p=0.039)., Conclusion: Asymptomatic subjects with radiographic signs of FAI present with weak pelvic version when standing. This pelvic hyper-anteversion is mainly found in the event of a radiological pincer sign., Level of Evidence: III, retrospective comparative study., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Intercrops can lower pest densities by increasing plant diversity, altering chemical communication in the arthropod community, and integrating well with other IPM tactics. We used two years of field observations and Y-tube olfactometer assays to explore the effects of intercropping a pear orchard with okra and castor bean on the cosmopolitan fruit-boring pest Grapholita molesta (Lepidoptera: Tortricidae). Intercropping okra reduced G. molesta trap catches in the pear orchard in both years, and intercropping with castor bean reduced them in the second year. Hydrocarbons, phenols, and ketones predominated in the GC-MS assay of okra volatiles, whereas castor bean volatiles were rich in aldehydes, ketones, and esters. Five of the commercially available volatiles released by these plants exhibited repellency to G. molesta in olfactometer trials, especially cinnamaldehyde, dibutyl phthalate, and thymol; the former compound also exhibited attraction to the egg parasitoid Trichogamma dendrolimi (Hymenoptera: Trichogrammatidae). In addition to their repellent properties, okra and castor bean may enhance integrated control of G. molesta in orchards by hosting prey that support populations of generalist predators that either provide biological pest control services within the orchard ecosystem or generate non-consumptive effects that contribute to pest deterence. Among the plant volatiles evaluated, cinnamaldehyde has the best potential for deployment in orchards to repel G. molesta without disrupting augmentative releases of T. dendrolimi .

Background: Baculoviruses such as Helicoverpa armigera nucleopolyhedrovirus (HearNPV) infect their lepidopteran hosts via the larval midgut where they interact with host immune responses and gut microbiota. Here we demonstrate that gut microbiota proliferating in response to HearNPV infection promote larval immune responses which impede the infection process., Results: The microbial load of the larval midgut increased following HearNPV infection, due primarily to increases in Enterococcus spp., whereas most other bacterial genera declined, with Firmicutes replacing Proteobacteria as the dominant phylum. Injection of abdominal prolegs of infected larvae with H 2 O 2 promoted viral infection, diminished microbial abundance, and accelerated larval death, mimicking the effects of HearNPV infection, which up-regulated dual oxidase (Duox) expression, increasing H 2 O 2 levels in the midgut. Knockdown of Duox with RNAi reduced H 2 O 2 production in the guts of infected larvae, increased bacterial loads, decreased viral replication, and improved larval survival. Germ-free larvae were more susceptible to HearNPV than control larvae, exhibiting greater expression of Duox, higher levels of H 2 O 2 , and lower survival. Replenishment of gut bacteria in germ-free larvae restored the base-line immunity to HearNPV observed in normal larvae. Enterococcus spp., Levilactobacillus brevis, and Lactobacillus sp. bacteria were isolated and implicated in immunity restoration via replenishment in germ-free larvae., Conclusion: These findings illuminate how gut microbiota play important roles in larval defense against oral baculovirus infection, and suggest novel avenues of investigation to enhance the efficacy of baculoviruses and improve control of lepidopteran pests. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Introduction: Bladder capacity (BC) is an important metric in the management of patients with classic bladder exstrophy (CBE). BC is frequently used to determine eligibility for surgical continence procedures, such as bladder neck reconstruction (BNR), and is associated with the likelihood of achieving urinary continence., Objective: To use readily available parameters to develop a nomogram that could be used by patients and pediatric urologists to predict BC in patients with CBE., Study Design: An institutional database of CBE patients was reviewed for those who have undergone annual gravity cystogram 6 months after bladder closure. Candidate clinical predictors were used to model BC. Linear mixed effects models with random intercept and slope were used to construct models predicting log transformed BC and were compared with adjusted R 2 , Akaike Information Criterion (AIC), and cross-validated mean square error (MSE). Final model evaluated via K-fold cross-validation. Analyses were performed using R version 3.5.3 and the prediction tool was developed with ShinyR., Results: In total, 369 patients (107 female, 262 male) with CBE had at least one BC measurement after bladder closure. Patients had a median of 3 annual measurements (range 1-10). The final nomogram includes outcome of primary closure, sex, log-transformed age at successful closure, time from successful closure, and interaction between outcome of primary closure and log-transformed age at successful closure as the fixed effects with random effect for patient and random slope for time since successful closure (Extended Summary)., Discussion: Using readily accessible patient and disease related information, the bladder capacity nomogram in this study provides a more accurate prediction of bladder capacity ahead of continence procedures when compared to the age-based Koff equation estimates. A multi-center study using this web-based CBE bladder growth nomogram (https://exstrophybladdergrowth.shinyapps.io/be&#95;app/) will be needed for widespread application., Conclusion: Bladder capacity in those with CBE, while known to be influenced by a broad swath of intrinsic and extrinsic factors, may be modeled by the sex, outcome of primary bladder closure, age at successful bladder closure and age at evaluation., Competing Interests: Conflicts of interest The authors have no financial or personal relationships with other people or organizations that could inappropriately influence their work., (Copyright © 2023 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objectives: Integrin α1β1 protects against osteoarthritis (OA) when it is upregulated in the superficial zone of cartilage in the early stages of disease. However, the mechanism behind this protection is unknown. Integrin α1β1 moderates transforming growth factor β receptor II (TGFBR2) signalling, a critical regulator of chondrocyte anabolic activity. To this end, mice lacking integrin α1β1 have increased baseline activation of TGFBR2 signalling and overall fibrosis. The purpose of this study was to evaluate the interplay between integrin α1β1 and TGFBR2 in the development of spontaneous OA. We hypothesized that dampening TGFBR2 signalling in the cartilage of itga1 -null mice would attenuate OA., Methods: Behavioural and histological manifestations of spontaneous knee OA were measured at 4, 8, 12 and 16 months in mice with and without a ubiquitous itga1 deletion and with and without a tamoxifen-induced cartilage specific TGFBR2 depletion., Results: Knee cartilage degeneration, collateral ligament ossification and pain responses increased with age. Itga1 -null mice with intact TGFBR2 signalling developed earlier and more severe OA compared to controls. In agreement with our hypothesis, depleting TGFBR2 signalling in the cartilage of itga1 -null mice attenuated OA progression., Conclusion: Intact TGFBR2 signalling drives early and worse knee OA in itga1 -null mice. This result supports the hypothesis that the increased expression of integrin α1β1 by superficial zone chondrocytes early in OA development dampens TGFBR2 signalling and thus protects against degeneration., Competing Interests: None of the authors declare any conflict of interest., (© 2023 The Author(s).)

Spinocerebellar ataxia 34 (SCA34) is a late-onset progressive ataxia caused by a mutation in ELOVL4, a gene involved in the biosynthesis of very long-chain fatty acids (VLCFAs). We performed post-mortem neuropathological examinations on four SCA34 patients with the ELOVL4 L168F mutation and compared the findings to age-matched controls. Specific gross findings of SCA34 were limited to pontocerebellar atrophy. On light microscopy, pontine base showed neuronal loss and storage of an autofluorescent lipopigment positive on oil red O, PAS and Hale's colloidal iron and negative on Alcian blue and Luxol fast blue (LFB). Among the swollen neurons were abundant CD68+ /CD163+ /IBA1- macrophages laden with a material with similar histochemical profile as in neurons except for the lack of autofluorescence and oil red O positivity and the presence of needle-like birefringent inclusions. Normal resting IBA1 + microglia were generally absent from pontine base nuclei but present in normal numbers elsewhere in the pons. In dentate nucleus neurons, atrophy was milder than in the pontine base and the coarser storage material was LFB-positive, closely resembling lipofuscin. On electron microscopy, dentate nucleus neurons showed neuronal storage of tridimensionally organized trilaminar spicules within otherwise normal lipofuscin, while in the more affected pontine base neurons, lipofuscin was almost completely replaced by the storage material. Storage macrophages were tightly packed with stacks of unorganized trilaminar spicules, reminiscent of the storage material seen in peroxisomal disorders and thought to represent VLCFAs incorporated in complex polar lipids. In summary, we provide histochemical and ultrastructural evidence that SCA34 is a lipid storage disease, the first among the currently known SCAs, and that the storage lipid is accumulating within neuronal lipofuscin. Our findings suggest that the storage lipid is similar to the one accumulating in non-neuronal cells in peroxisomal disorders and provide the first ultrastructural description of this type of material within neurons., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

Thermoneutral housing has been shown to promote more accurate and robust development of several pathologies in mice. Raising animal housing temperatures a few degrees may create a relatively straightforward opportunity to improve translatability of mouse models. In this commentary, we discuss the changes of physiology induced in mice housed at thermoneutrality, and review techniques for measuring systemic thermogenesis, specifically those affecting storage and mobilization of lipids in adipose depots. Environmental cues are a component of the information integrated by the brain to calculate food consumption and calorie deposition. We show that relative humidity is one of those cues, inducing a rapid sensory response that is converted to a more chronic susceptibility to obesity. Given high inter-institutional variability in the regulation of relative humidity, study reproducibility may be improved by consideration of this factor. We evaluate a "humanized" environmental cycling protocol, where mice sleep in warm temperature housing, and are cool during the wake cycle. We show that this protocol suppresses adaptation to cool exposure, with consequence for adipose-associated lipid storage. To evaluate systemic cues in mice housed at thermoneutral temperatures, we characterized the circulating lipidome, and show that sera are highly depleted in some HDL-associated phospholipids, specifically phospholipids containing the essential fatty acid, 18:2 linoleic acid, and its derivative, arachidonic acid (20:4) and related ether-phospholipids. Given the role of these fatty acids in inflammatory responses, we propose they may underlie the differences in disease progression observed at thermoneutrality., (Copyright © 2022 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Background and Objectives: Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of dementia. Oral anticoagulants (OACs) are essential for stroke prevention in NVAF, and studies have shown a possible protective effect on dementia. However, findings have been inconsistent and hampered by methodological limitations. Thus, we assessed whether the use of OACs is associated with a decreased incidence of dementia in patients with NVAF. In addition, we explored the impact of the cumulative duration of OAC use on the incidence of dementia., Methods: Using the UK Clinical Practice Research Datalink, we formed a cohort of all patients aged 50 years or older with an incident diagnosis of NVAF between 1988 and 2017 and no prior OAC use, with a follow-up until 2019. Patients were considered unexposed until 6 months after their first OAC prescription for latency considerations and exposed thereafter until the end of follow-up. We used time-dependent Cox regression models to estimate hazard ratios (HRs), adjusted for 54 covariates, with 95% CIs for dementia associated with OAC use, compared with nonuse. We also assessed whether the risk varied with the cumulative duration of OAC use, compared with nonuse, by comparing prespecified exposure categories defined in a time-varying manner and by modeling the HR using a restricted cubic spline., Results: The cohort included 142,227 patients with NVAF, with 8,023 cases of dementia over 662,667 person-years of follow-up (incidence rate 12.1, 95% CI 11.9-12.4 per 1,000 person-years). OAC use was associated with a decreased risk of dementia (HR 0.88, 95% CI 0.84-0.92) compared with nonuse. A restricted cubic spline also indicated a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. Moreover, OAC use decreased the risk in patients aged 75 years and older (HR 0.84, 95% CI 0.80-0.89), but not in younger patients (HR 0.99, 95% CI 0.90-1.10)., Discussion: In patients with incident NVAF, OACs were associated with a decreased risk of dementia, particularly in elderly individuals. This warrants consideration when weighing the risks and benefits of anticoagulation in this population., Classification of Evidence: This study provides Class II evidence that in patients with NVAF, OAC use (vs nonuse) is associated with a decreased risk of dementia., (© 2022 American Academy of Neurology.)

Traumatic brain injury (TBI) is now recognized as an insult triggering a dynamic process of degeneration and regeneration potentially evolving for years with chronic traumatic encephalopathy (CTE) as one major complication. Neurons are at the center of the clinical manifestations, both in the acute and chronic phases. Yet, in the acute phase, conventional neuropathology detects abnormalities predominantly in the axons, if one excludes contusions and hypoxic ischemic changes. We report the finding of ballooned neurons, predominantly in the anterior cingulum, in three patients who sustained severe TBI and remained comatose until death, 2 ½ weeks to 2 ½ months after the traumatic impact. All three cases showed severe changes of traumatic diffuse axonal injury in line with acceleration/deceleration forces. The immunohistochemical profile of the ballooned neurons was like that described in neurodegenerative disorders like tauopathies which were used as controls. The presence of αB-crystallin positive ballooned neurons in the brain of patients who sustained severe craniocerebral trauma and remained comatose thereafter has never been reported. We postulate that the co-occurrence of diffuse axonal injury in the cerebral white matter and ballooned neurons in the cortex is mechanistically reminiscent of the phenomenon of chromatolysis. Experimental trauma models with neuronal chromatolytic features emphasized the presence of proximal axonal defects. In our three cases, proximal swellings were documented in the cortex and subcortical white matter. This limited retrospective report should trigger further studies in order to better establish, in recent/semi-recent TBI, the frequency of this neuronal finding and its relationship with the proximal axonal defects., (© 2023. The Author(s).)

Baculoviruses are highly evolved parasites that genetically reprogram the developing phenotype of their host insect to produce a vessel for virus replication and dispersal. Here we show that larvae of Helicoverpa armigera infected with HearNPV accumulate glucose in the midgut, which reduces food consumption and alters the dynamics of pathways governing metabolism and immunity. We used transcriptomics to demonstrate the role of the insulin signalling pathway in regulating the HearNPV infection process. Dietary restriction decreased mortality of infected larvae and reduced viral replication prior to death, whereas dietary supplementation with glucose produced the opposite effects. The expression of most tricarboxylic acid cycle (TCA) and energy metabolism-related genes was reduced in infected larvae, whereas the expression of immunity-, glycolysis- and insulin-related genes was enhanced. Treatment of infected larvae with insulin increased their survival, reduced viral replication and inhibited climbing behaviour compared to a control treatment with DMSO, whereas RNAi suppression of the insulin receptor gene produced the opposite effects. Inhibition of glycolysis with dichloroacetate (DCA) promoted viral replication and accelerated larval death, but inhibition of the TCA cycle with 2-deoxyglucose (2-DG) did not, although both diminished climbing behaviour. This work demonstrates that successful baculovirus infections hinge on metabolic reprogramming of the host and concurrent suppression of immune responses in the larval midgut, with the insulin signalling pathway mediating a trade-off between glucose metabolism and virus resistance., (© 2022 John Wiley & Sons Ltd.)

Ladybirds (Coleoptera: Coccinellidae) provide services that are critical to food production, and they fulfill an ecological role as a food source for predators. The richness, abundance, and distribution of ladybirds, however, are compromised by many anthropogenic threats. Meanwhile, a lack of knowledge of the conservation status of most species and the factors driving their population dynamics hinders the development and implementation of conservation strategies for ladybirds. We conducted a review of the literature on the ecology, diversity, and conservation of ladybirds to identify their key ecological threats. Ladybird populations are most affected by climate factors, landscape composition, and biological invasions. We suggest mitigating actions for ladybird conservation and recovery. Short-term actions include citizen science programs and education, protective measures for habitat recovery and threatened species, prevention of the introduction of non-native species, and the maintenance and restoration of natural areas and landscape heterogeneity. Mid-term actions involve the analysis of data from monitoring programs and insect collections to disentangle the effect of different threats to ladybird populations, understand habitat use by taxa on which there is limited knowledge, and quantify temporal trends of abundance, diversity, and biomass along a management-intensity gradient. Long-term actions include the development of a worldwide monitoring program based on standardized sampling to fill data gaps, increase explanatory power, streamline analyses, and facilitate global collaborations., (© 2022 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Soluble fragments of peptidoglycan called muropeptides are released from the cell wall of bacteria as part of their metabolism or as a result of biological stresses. These compounds trigger immune responses in mammals and plants. In bacteria, they play a major role in the induction of antibiotic resistance. The development of efficient methods to produce muropeptides is, therefore, desirable both to address their mechanism of action and to design new antibacterial and immunostimulant agents. Herein, we engineered the peptidoglycan recycling pathway of Escherichia coli to produce N-acetyl-β-D-glucosaminyl-(1→4)-1,6-anhydro-N-acetyl-β-D-muramic acid (GlcNAc-anhMurNAc), a common precursor of Gram-negative and Gram-positive muropeptides. Inactivation of the hexosaminidase nagZ gene allowed the efficient production of this key disaccharide, providing access to Gram-positive muropeptides through subsequent chemical peptide conjugation. E. coli strains deficient in both NagZ hexosaminidase and amidase activities further enabled the in vivo production of Gram-negative muropeptides containing meso-diaminopimelic acid, a rarely available amino acid., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background: Fluoroscopy guided interventions are widely used procedures in the treatment of musculoskeletal conditions. Understanding the movement of the needle is part of a resident's initial training when performing these procedures. Needle navigation training is largely gained with fluoroscopy., Objective: The purpose of this study is to determine whether the use of ultrasound training can lead to a decrease in time to reach a target under fluoroscopy., Methods: 32 medical students or residents. Exposure of one group of trainees to a practice session of needle navigation using ultrasound. The control group did not participate in ultrasound training. Time to reach the target during a fluoroscopy guided needle navigation test was measured in both groups., Results: The mean time to reach the target under fluoroscopy of the students unexposed to an ultrasound training (group 1 control group) was 183 ​s (standard deviation ​= ​160 ​s), while that after ultrasound training (group 2 experimental group) was 150,81 ​s (standard deviation ​= ​96 ​s) (p ​= ​0,483)., Conclusion: Fluoroscopy needle navigation training was not improved by a 1-h group practice session with in-plane ultrasound needle navigation practice. Further studies need to be done with exposure for residents to a group practice session longer than 1-h., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2022 Published by Elsevier Inc. on behalf of Spine Intervention Society.)

The widespread adoption of Bt crops expressing insecticidal proteins derived from Bacillus thuringiensis has created a need to assess the potential effects of these toxins on non-target organisms, especially species such as Arma custos, a generalist predator that provides important biological control services in many field crops in Asia. Direct dietary exposure of A. custos to Cry1Ah and Vip3Aa proteins produced no adverse effects on life history traits, despite continuous exposure throughout development and early adult life to concentrations significantly higher than the Bt protein concentration likely encountered by A.custos in the field, even when feeding directly on Bt plants. Enzyme-linked immunosorbent assay confirmed the presence of Bt proteins in A. custos midguts, but quantitative real-time PCR analysis of 12 genes associated with detoxification, antioxidative responses, immune responses, and metabolism revealed no significant changes in expression in adult bugs. Indirect exposure to these toxins via consumption of intoxicated prey, larvae of Helicoverpa armigera (Hübner), likewise produced no negative impacts on survival, development, adult weight, or female fecundity in either the F0 (exposed) or F1 (unexposed) generation, but female fresh weight was reduced in the F0 generation by the Cry1Ah (50 μg/g) treatment. Finally, a competitive binding assay with labelled protein and a ligand blotting assay both demonstrated that the Cry1Ah protein could not bind to receptors on the midgut brush border membrane vesicles (BBMVs) of A. custos adults. Therefore, we conclude that Cry1Ah and Vip3Aa proteins are unlikely to have significant negative effects on A. custos populations if employed as plant-incorporated protectants in field crops., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We examined differences in the physiology and life history between dimorphs of the common pistachio psyllid, Agonoscena pistaciae (Burckhardt and Lauterer) (Hemiptera: Aphalaridae), and how they differ in elicitating host plant production of key metabolites and volatile compounds involved in the recruitment of herbivores and natural enemies. Summer morphs had higher activities of glutathione S-transferase, carboxylesterase, acetylcholinesterase, and cytochrome P450 monooxygenase, superoxide dismutase, catalase, peroxidase, phenoloxidase, and a higher total protein content compared to winter morphs, whereas the latter had higher amounts of lipid, carbohydrate, and glycogen. Winter morphs were heavier, with a higher chitin content and longer preoviposition period, but greater fecundity and longevity than summer morphs. A lower LC50 to thiamethoxam for winter morphs resulted in higher mortality following exposure to the recommended rate of this insecticide in a greenhouse trial. Feeding by winter morphs elicited more strongly the release of volatile compounds known to be attractive to other herbivores, whereas feeding by summer morphs elicited more strongly the release of volatiles implicated in the attraction of natural enemies. Feeding by psyllids increased the concentrations of nitrogenous compounds, carbohydrates, vitamins, and amino acids in plants, the winter morph eliciting larger changes and more improved host plant quality. We conclude that winter morphs are more vulnerable targets for chemical control in early spring, whereas management of summer morphs could rely more on conservation biological control., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

As an intermediate molecule in the Insulin/Insulin-like growth factor signalling pathway (IIS), the insulin receptor (IR) plays vital roles linking nutritional signals to the downstream regulation of metabolic homeostasis, development, metamorphosis, reproduction and stress responses. In the present study, we describe the molecular characteristics of IR in the cosmopolitan fruit boring pest, Grapholita molesta, and its predicted posttranscription regulator miR-982490, and elucidate its regulatory roles in glucolipid homeostasis and metamorphosis. Phylogenetic and domain analyses indicate that lepidopteran IRs normally cluster within families, and that four main domains are conserved in GmIR and those of other Lepidoptera. Bio-informatic prediction, synchronic expression profile evaluation and dual luciferase reporter assays indicated negative regulation of GmIR by miR-982490. Injection of miR-982490 agomir into fifth instar larvae yielded effects similar to dsGmIR injection, resulting in enhanced levels of trehalose and triglyceride in haemolymph, and reduced pupation success and pupal weight, both of which could be rescued by co-injection of dsGmIR and miR-982490 antagomir. We infer that GmIR regulates glucolipid homeostasis and affects G. molesta metamorphosis via interactions with its posttranscriptional regulator miR-982490. This study expands our understanding of the regulatory network of IIS in insect nutritional homeostasis and development., (© 2022 Royal Entomological Society.)

Aims:  To evaluate the effectiveness and safety of apixaban versus rivaroxaban among patients with nonvalvular atrial fibrillation (NVAF) and type 2 diabetes mellitus (T2DM)., Methods and Results:  Using the United Kingdom's Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository, and the Office for National Statistics database, we identified a cohort of patients with NVAF and T2DM newly treated with apixaban or rivaroxaban between 2013 and 2020. Propensity scores with standardized mortality ratio weighting were used to control for confounding. We used weighted Cox proportional hazards models to estimate separately the hazard ratios (HRs) with 95% confidence intervals (CIs) of ischemic stroke, major bleeding, and major adverse limb events associated with the use of apixaban compared with rivaroxaban. We also evaluated whether the risk was modified by age, sex, duration of diabetes, microvascular and macrovascular complications of diabetes, nephropathy, CHA 2 DS 2 -VASc and HAS-BLED scores, and by dose (standard vs. low dose)., Results:  The cohort included 11,561 apixaban and 8,265 rivaroxaban users. Apixaban was associated with a similar risk of stroke (HR: 0.99, 95% CI: 0.79-1.23), and a 32% reduced risk of major bleeding (HR: 0.68, 95% CI: 0.59-0.78), compared with rivaroxaban. The risk of major adverse limb events was similar between apixaban and rivaroxaban (HR: 0.75, 95% CI: 0.54-1.04). Overall, the risk of ischemic stroke and major bleeding was consistent in stratified analyses., Conclusion:  Among patients with NVAF and T2DM, apixaban was associated with a similar risk of stroke and a lower risk of major bleeding compared with rivaroxaban., Competing Interests: L.A. served as a consultant for Janssen and Pfizer for work unrelated to this study. The other authors have no conflicts of interest to declare., (Thieme. All rights reserved.)

Background: The entomopathogenic fungus Beauveria bassiana and the egg parasitoid Trichogramma dendrolimi can both contribute to biological control of the global fruit borer Grapholita molesta. To derive insights for optimizing their combined application in augmentation programs, we assayed fungal pathogenicity to both G. molesta (eggs, larvae and adults) and adult parasitoids, and assessed wasp acquisition and transmission of fungal spores following their emergence from B. bassiana-treated host eggs., Results: Concentrations of 10 8 conidia mL -1 of B. bassiana and higher caused virtually complete mortality of G. molesta larvae, but less than 30% mortality of eggs, and female moths surviving treatments had reduced fecundity. More than 80% of adult T. dendrolimi survived B. bassiana treatments of 10 7 conidia mL -1 , and more than 60% survived 10 9 conidia mL -1 , with surviving females achieving reproductive success equivalent to controls. Parasitoid females preferred healthy eggs over B. bassiana-infected ones in choice tests; wasps emerging from treated eggs carried about 10 4 conidia each and contributed an additional 11% host mortality in trials combining both agents., Conclusion: Our results indicate that combined applications of B. bassiana and T. dendrolimi can have complimentary impacts on G. molesta, the wasps compensating for low fungal pathogenicity to eggs and their progeny potentially aiding in subsequent disease transmission. Although foraging wasps tended to avoid infected eggs, negative interactions between the two agents might be further mitigated by timing B. bassiana applications from late instar larva to early moth stage, and T. dendrolimi releases several days later to coincide with peak oviposition periods. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Fate decisions in the embryo are controlled by a plethora of microenvironmental interactions in a three-dimensional niche. To investigate whether aspects of this microenvironmental complexity can be engineered to direct myogenic human-induced pluripotent stem cell (hiPSC) differentiation, we here screened murine cell types present in the developmental or adult stem cell niche in heterotypic suspension embryoids. We identified embryonic endothelial cells and fibroblasts as highly permissive for myogenic specification of hiPSCs. After two weeks of sequential Wnt and FGF pathway induction, these three-component embryoids are enriched in Pax7-positive embryonic-like myogenic progenitors that can be isolated by flow cytometry. Myogenic differentiation of hiPSCs in heterotypic embryoids relies on a specialized structural microenvironment and depends on MAPK, PI3K/AKT, and Notch signaling. After transplantation in a mouse model of Duchenne muscular dystrophy, embryonic-like myogenic progenitors repopulate the stem cell niche, reactivate after repeated injury, and, compared to adult human myoblasts, display enhanced fusion and lead to increased muscle function. Altogether, we provide a two-week protocol for efficient and scalable suspension-based 3D derivation of Pax7-positive myogenic progenitors from hiPSCs., (© 2022 The Authors.)

Background: High temperatures will occur more frequently with global warming, with potential impacts on the efficacy of biological control agents. Heat shock proteins (HSPs) are induced by high temperature, but their possible roles in pest resistance to entomopathogens remain unexplored. We investigated the effects of high temperature (35 °C) on Helicoverpa armigera resistance to H. armigera nucleopolyhedrovirus (HearNPV) and the putative roles of HSPs in this process., Results: Even short periods (24 h) of high temperature (35 °C) reduced mortality in HearNPV-infected H. armigera larvae. Sustained 35 °C exposure significantly shortened developmental time, and increased fresh weight and locomotor activity in infected larvae. Moreover, high temperature inhibited virus replication and thickened the epidermis of H. armigera, resulting in reduced spread of infection from cadavers. Real-time polymerase chain reaction (PCR) analysis showed that expression of 11 HSP genes was altered by the 35 °C treatment, and that mostly small heat shock protein (sHSP) genes were up-regulated, the same sHSPs were induced when larvae were infected with HearNPV. Finally, RNA interference (RNAi) suppression of these sHSPs showed that only Hsp24.91 and Hsp21.8 diminished H. armigera defensive responses to HearNPV infection., Conclusion: Even short periods of exposure to high temperature can significantly reduce susceptibility of H. armigera larvae to HearNPV by stimulating the production of sHSPs which enhance immune responses, with important implications for the use of entomopathogens as biological control agents under global warming scenarios. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Fiber-reinforced polymer composites are an excellent choice for bridge decks due to high strength, lightweight, resistance to corrosion, and long-term durability with a 100-year design life. Structural health monitoring is useful for the long-term assessment of the condition of the bridge structure and obtaining a response to complex loads considering environmental conditions. Bridge structures have been studied primarily using distributed fiber optic sensing, such as Brillouin scattering; however, critical events, including damage detection, can be missed due to low spatial resolution. There is also a critical need to conduct a comprehensive study of static and dynamic loading simultaneously for fiber-reinforced composite bridge structures. In this study, a novel approach was implemented using two sensor technologies, optical frequency domain reflectometry and fiber Bragg grating-based sensors, embedded in a glass-fiber-reinforced composite bridge deck to simultaneously monitor the deformation response of the bridge structure. The optical frequency domain reflectometry sensor utilizing Rayleigh scattering provides high spatial strain resolution were positioned strategically based on expected stress distributions to measure strain in the longitudinal, transverse, and diagonal directions along the span of the composite bridge. Furthermore, fiber Bragg grating based sensors are used to monitor the response to dynamic vehicular loading and deformations from an automotive-crash-type event on the bridge structure. To monitor environmental variables such as temperature, a custom wireless configured sensor package was developed for the study and integrated with a composite bridge located in Morgan County, Tennessee. Additionally, a triaxial accelerometer was used to monitor the vehicular dynamic loading of the composite bridge deck in parallel with fiber Bragg grating sensors. When appropriate, mid-point displacements were compared with strain-distribution measurements from the fiber optic sensor-based data.

Background: The orthopaedic surgery residency program website represents a recruitment tool that can be used to demonstrate a program's commitment to diversity and inclusion to prospective applicants. The authors assessed how orthopaedic surgery residency programs demonstrated diversity and inclusion on their program websites and whether this varied based on National Institutes of Health (NIH) funding, top-40 medical school affiliation, university affiliation, program size, or geographic region., Methods: The authors evaluated 187 orthopaedic surgery residency program websites for the presence of 12 elements that represented program commitment to diversity and inclusion values, based on prior work and ACGME recommendations. Mann-Whitney U and Kruskal-Wallis tests were used to assess whether NIH funding and other program characteristics were associated with commitment to diversity and inclusion on affiliated residency websites., Results: Orthopaedic surgery residency websites included a mean of 4.9 ± 2.1 diversity and inclusion elements, with 21% (40/187) featuring a majority (7+) of elements. Top 40 NIH funded programs (5.4 ± 2.0) did not have significantly higher website diversity scores when compared with nontop-40 programs (4.8 ± 2.1) ( P = 0.250). University-based or affiliated programs (5.2 ± 2.0) had higher diversity scores when compared with community-based programs (3.6 ± 2.2) ( P = 0.003)., Conclusions: Most orthopaedic surgery residency websites contained fewer than half of the diversity and inclusion elements studied, suggesting opportunities for further commitment to diversity and inclusion. Inclusion of diversity initiatives on program websites may attract more diverse applicants and help address gender and racial or ethnic disparities in orthopaedic surgery., Level of Evidence: Level V., Competing Interests: The authors report no conflicts of interest.

Baculoviruses can induce climbing behaviour in their caterpillar hosts to ensure they die at elevated positions to enhance virus transmission, providing an excellent model to study parasitic manipulation of host behaviour. Here, we demonstrate that climbing behaviour occurred mostly during daylight hours, and that the height at death of Helicoverpa armigera single nucleopolyhedrovirus (HearNPV)-infected larvae increases with the height of the light source. Phototaxic and electroretinogram (ERG) responses were enhanced after HearNPV-infection in host larvae, and ablation of stemmata in infected larvae prevented both phototaxis and climbing behaviour. Through transcriptome and quantitative PCR, we confirmed that two opsin genes (a blue light-sensitive gene, HaBL; and a long wave-sensitive gene, HaLW) as well as the TRPL (transient receptor potential-like channel protein) gene, all integral to the host's visual perception pathway, were significantly upregulated after HearNPV infection. Knockout of HaBL, HaLW, or TRPL genes using the CRISPR/Cas9 system resulted in significantly reduced ERG responses, phototaxis, and climbing behaviour in HearNPV-infected larvae. These results reveal that HearNPV alters the expression of specific genes to hijack host visual perception at fundamental levels-photoreception and phototransduction-in order to induce climbing behaviour in host larvae., (© 2022 John Wiley & Sons Ltd.)

Entomopathogenic fungi produce extracellular enzymes to facilitate host infection, and these can also reduce metal ions to produce nanoparticles. In the present study, three isolates of Beauveria bassiana (JS1, JS2 and KA75) and one isolate of Metarhizium anisopliae (TT1) were evaluated for their ability to biosynthesize silver nanoparticles (AgNPs). In general, the best yields and smallest NP sizes were obtained at 60 °C and pH 7.0. Nanoparticle properties were studied using UV-visible spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy. Biosynthesized AgNPs ranged from 23 to 101 nm across, the smallest being produced by KA75, and the largest by TT1. UV-visible spectroscopy confirmed peak absorption of AgNPs in the range of 420-454 nm. AgNP antibacterial activity was highest against the gram-negative bacteria Pectobacterium carotovorum and Erwinia amylovora, and lower against the gram-positive Bacillus sp. AF1. JS1-AgNPs caused the greatest growth restriction of P. carotovorum at a concentration of 75 µL/mL at lower OD 600 (0.25). Smaller AgNPs generally had better antifungal activities against B. bassiana, M. anisopliae, and the plant-pathogenic Rhizoctonia solani. Complete inhibition of vegetative growth of the JS2 fungus was obtained with TT1-synthesized AgNPs at 15 µL/mL, a control level similar to half the field rate of benomyl. Generally, fungal sporulation was more inhibited than vegetative growth, and all AgNPs showed good compatibility with the fungi at low concentrations. We conclude that AgNPs mycosynthesized by these entomopathogens have promising antibacterial and antifungal properties with potential for various applications., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Helicoverpa armigera single nucleopolyhedrovirus (HearNPV) has a long coevolutionary history with its host, exerting profound effects on larval development, physiology and immune responses, although the mechanisms mediating these effects remain unclear. We demonstrate that HearNPV infection constrains the growth and development of larvae by inducing high levels of reactive oxygen species (ROS), which increase the expression of forkhead box O transcription factor (FoxO). FoxO upregulates the expression of peroxiredoxin 1 (Prx1) which serves to regulate larval development and immune responses following HearNPV infection. Collectively, our results provide novel insights into the role of Prx1 in larval development and immunity subsequent to HearNPV infection. Further investigation of the oxidative stress induced by HearNPV in H. armigera and its interactions with host immunity could yield novel insights useful in agricultural pest control., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specific cell populations. Here, we describe a method for the encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging in vivo independent of heterogeneous short-range tissue interactions. We observed that circulating long-range signaling factors in the old systemic environment lead to an activation of Myc and E2F transcription factors, induce senescence, and suppress myogenic differentiation. Importantly, in vitro profiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus, in vivo transcriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy., Competing Interests: OM, XH, JM, GL, CB, FD, SM, FR, PD, NB, JF, CB Presently or previously employed by the Société des Produits Nestlé S.A., Switzerland, EM Presently or previously employed by the Société des Produits Nestlé; S.A., Switzerland, EL, JC, JI, PM No competing interests declared, (© 2022, Mashinchian et al.)

Aphids parasitized in later instars can give birth to several nymphs before their reproduction is curtailed by the developing parasitoid. We examined the life histories of Aphis fabae Scopoli born to mothers parasitized by Lysiphlebus fabarum Marshall, and their suitability as subsequent hosts, to test the 'fecundity compensation' hypothesis. Maternal parasitism negatively impacted life history parameters, resulting in reduced estimates of population increase (rm, R0, and λ), and increased generation time (GT) and doubling time (DT). These impacts were greater when the larva developing in the mother turned out to be female rather than male, and greater still when mothers were superparasitized. Maternal parasitism produced aphids with shorter hind tibia (HTL), at birth and at maturity, but their developmental time was unaffected. Although female L. fabarum readily accepted such aphids for oviposition, rates of mummification and wasp emergence were lower, and more so when the maternal parasitoid was female. The resulting parasitoids took longer to develop than progeny from control wasps, had shorter HTLs, lower egg loads, smaller eggs, and produced fewer mummies with lower rates of adult emergence, all differences that were more pronounced when the maternal parasitoid was female. The progeny of these wasps exhibited similar impairments to these biological parameters as their parents, demonstrating that the negative impacts of development in maternally parasitized hosts extended for at least two generations. Thus, our results do not support fecundity compensation, but suggest that any benefits of post-parasitism reproduction will be offset by reduced fitness in both aphid progeny and the parasitoids that develop in them.

Aphid cornicles are abdominal appendages that secrete an array of volatile and nonvolatile compounds with diverse ecological functions. The emission of alarm pheromones yields altruistic benefits for clone-mates in the aphid colony, which is essentially a superorganism with a collective fate. Secreted droplets also contain unsaturated triglycerides, fast-drying adhesives that can be lethal when smeared on natural enemies but more often impede their foraging efficiency. The longest cornicles have evolved in aphids that feed in exposed locations and are likely used to scent-mark colony intruders. Reduced cornicles are associated with reliance on alternative defenses, such as the secretion of protective waxes or myrmecophily. Root-feeding and gall-forming lifestyles provide protected feeding sites and are associated with an absence of cornicles. In some eusocial gall-formers, soldier morphs become repositories of cornicle secretion used to defend the gall, either as menopausal apterae that defend dispersing alatae or as sterile first instars that dispatch predators with their stylets and use cornicle secretions as a construction material for gall repair. Collectively, the evidence is consistent with an adaptive radiation of derived cornicle functions molded by the ecological lifestyle of the aphid lineage.