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In Drosophila melanogaster, successful development relies on the precise coordination of both spatial and temporal regulatory axes. The temporal axis governs stage-specific identity and developmental transitions through a number of genes, collectively forming the Metamorphic Gene Network. Among these, Ecdysone inducible protein 93F (E93) serves as the critical determinant for adult specification, but its mechanism of action remains unclear. Here, we found that, rather than acting mainly as an instructive signal, E93 promotes adult differentiation through the repression of the pupal specifier broad (br). In the absence of E93, sustained high levels of Br during the pupal stage strongly represses pupal-specific enhancers that are essential for the terminal differentiation of the wing. Notably, RNA-seq analysis confirmed that the majority of E93-dependent transcriptomic changes in pupal wings are primarily driven by br repression. In addition, we also show that Br represses the pupal-enhancers during the larval and prepupal stages preventing the premature implementation of the adult genetic program, and that it also dampens the activity of larval enhancers during the latter stages of larval development. This mechanism of action seems to be a derived feature acquired in Diptera, as in the coleopteran Tribolium castaneum, repression of br by E93 is not sufficient to allow adult differentiation. In summary, our study elucidates the crucial role of the intricate interplay between E93 and Br as the governing mechanism in the process of terminal differentiation in Drosophila. This finding holds significant implications for advancing our understanding of the evolution of insect metamorphosis. [ABSTRACT FROM AUTHOR]

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Epithelial cells form continuous membranous structures for organ formation, and these cells are classified into three major morphological categories: cuboidal, columnar, and squamous. It is crucial that cells transition between these shapes during the morphogenetic events of organogenesis, yet this process remains poorly understood. All three epithelial cell shapes can be found in the follicular epithelium of Drosophila egg chamber during oogenesis. Squamous cells (SCs) are initially restricted to the anterior terminus in cuboidal shape. They then rapidly become flattened to assume squamous shape by stretching and expansion in 12 ​h during midoogenesis. Previously, we reported that Notch signaling activated a zinc-finger transcription factor Broad (Br) at the end of early oogenesis. Here we report that ecdysone and JAK/STAT pathways subsequently converge on Br to serve as an important spatiotemporal regulator of this dramatic morphological change of SCs. The early uniform pattern of Br in the follicular epithelium is directly established by Notch signaling at stage 5 of oogenesis. Later, ecdysone and JAK/STAT signaling activities synergize to suppress Br in SCs from stage 8 to 10a, contributing to proper SC squamous shape. During this process, ecdysone signaling is essential for SC stretching, while JAK/STAT regulates SC clustering and cell fate determination. This study reveals an inhibitory role of ecdysone signaling in suppressing Br in epithelial cell remodeling. In this study we also used single-cell RNA sequencing data to highlight the shift in gene expression which occurs as Br is suppressed and cells become flattened. [Display omitted] • Notch, ecdysone and JAK/STAT signaling controls Broad to change the epithelial shape. • Ecdysone signaling regulates follicle cell stretching and dispersion. • JAK/STAT ensures proper spacing between cells to prevent clustering. • Single-cell RNA sequencing data reveal genes expressed during cell shape change. [ABSTRACT FROM AUTHOR]

Copyright of Athar alrafedain is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The brutal toll of another viral pandemic can be blunted by investing now in research that uncovers mechanisms of broad-based immunity so we may have vaccines and therapeutics at the ready. We do not know exactly what pathogen may trigger the next wave or next pandemic. We do know, however, that the human immune system must respond and must be bolstered with effective vaccines and other therapeutics to preserve lives and livelihoods. These countermeasures must focus on features conserved among families of pathogens in order to be responsive against something yet to emerge. Here, we focus on immunological approaches to mitigate the impact of the next emerging virus pandemic by developing vaccines that elicit both broadly protective antibodies and T cells. Identifying human immune mechanisms of broad protection against virus families with pandemic potential will be our best defense for humanity in the future. Saphire and Sette discuss potential approaches for vaccine development against the broad array of SARS-CoV-2 variants and other viruses of pandemic potential. Approaches that elicit both humoral and cellular responses are considered and are expected to be synergistic with each other, providing humanity with the best chance to defend against the next pandemic. [ABSTRACT FROM AUTHOR]

The molecular control of insect metamorphosis from larva to pupa to adult has long been a mystery. The Broad and E93 transcription factors, which can modify chromatin domains, are known to direct the production of the pupa and the adult, respectively. We now show that chinmo, a gene related to broad, is essential for the repression of these metamorphic genes. Chinmo is strongly expressed during the formation and growth of the larva and its removal results in the precocious expression of broad and E93 in the first stage larva, causing a shift from larval to premetamorphic functions. This trinity of Chinmo, Broad, and E93 regulatory factors is mutually inhibitory. The interaction of this network with regulatory hormones likely ensures the orderly progression through insect metamorphosis. [ABSTRACT FROM AUTHOR]

In Drosophila melanogaster, loss of regenerative capacity in wing imaginal discs coincides with an increase in systemic levels of the steroid hormone ecdysone, a key coordinator of their developmental progression. Regenerating discs release the relaxin hormone Dilp8 (Drosophila insulin-like peptide 8) to limit ecdysone synthesis and extend the regenerative period. Here, we describe how regenerating tissues produce a biphasic response to ecdysone levels: lower concentrations of ecdysone promote local and systemic regenerative signaling, whereas higher concentrations suppress regeneration through the expression of broad splice isoforms. Ecdysone also promotes the expression of wingless during both regeneration and normal development through a distinct regulatory pathway. This dual role for ecdysone explains how regeneration can still be completed successfully in dilp8- mutant larvae: higher ecdysone levels increase the regenerative activity of tissues, allowing regeneration to reach completion in a shorter time. From these observations, we propose that ecdysone hormone signaling functions to coordinate regeneration with developmental progression. [ABSTRACT FROM AUTHOR]

• Generating neutralizing mAbs against EV-As by co-immunization with EVA71 and CVA16. • An IgM antibody M20 shows potent and broad neutralizing ability against tetra-EV-A. • M20 binds to the GH loop of VP1, may be a candidate for universal vaccines design. To determine the potent and broad neutralizing monoclonal antibody (mAb) against enterovirus A (EV-A) in vitro and in vivo induced by enterovirus A71(EVA71) and coxsackievirus 16 (CVA16) co-immunization. The mAb was Generated by co-immunization with EVA71 and CVA16 through hybridomas technology. The characteristics and neutralizing ability of mAb were analysed in vitro and in mice. We screened three mAb, the IgM antibody M20 and IgG antibody B1 and C31. All three antibodies showed cross-reactivity against tetra-EV-As. However, M20 showed potent and broad neutralizing ability against tetra-EV-As than B1 and C31. Meanwhile, M20 provided cross-antiviral efficacy in tetra-EV-As orally infected mice. Moreover, M20 binds to a conserved neutralizing epitope within the GH loop of tetra-EV-As VP1. M20 and its property exhibited potent and broad antiviral activity against tetra-EV-As, and that is expected to be a potential preventive and therapeutic candidate against EV-As. [ABSTRACT FROM AUTHOR]

Brain development requires the generation of the right number, and type, of neurons and glial cells at the right time. The Drosophila optic lobe, like mammalian brains, develops from simple neuroepithelia; they first divide symmetrically to expand the progenitor pool and then differentiate into neuroblasts, which divide asymmetrically to generate neurons and glial cells. Here, we investigate the mechanisms that control neuroepithelial growth and differentiation in the optic lobe. We find that the Broad/Tramtrack/ Bric a brac-zinc finger protein Broad, which is dynamically expressed in the optic lobe neuroepithelia, promotes the transition of neuroepithelial cells to medulla neuroblasts. Loss of Broad function causes neuroepithelial cells to remain highly proliferative and delays neuroepithelial cell differentiation into neuroblasts, which leads to defective lamina and medulla. Conversely, Broad overexpression induces neuroepithelial cells to prematurely transform into medulla neuroblasts. We find that the ecdysone receptor is required for neuroepithelial maintenance and growth, and that Broad expression in neuroepithelial cells is repressed by the ecdysone receptor. Our studies identify Broad as an important cell-intrinsic transcription factor that promotes the neuroepithelial-cell-to-neuroblast transition. [ABSTRACT FROM AUTHOR]

Developmental, genetic and endocrine data from diverse taxa provide insight into the evolution of insect metamorphosis. We equate the larva–pupa–adult of the Holometabola to the pronymph–nymph–adult of hemimetabolous insects. The hemimetabolous pronymph is a cryptic embryonic stage with unique endocrinology and behavioural modifications that probably served as preadaptations for the larva. It develops in the absence of juvenile hormone (JH) as embryonic primordia undergo patterning and morphogenesis, the processes that were arrested for the evolution of the larva. Embryonic JH then drives tissue differentiation and nymph formation. Experimental treatment of pronymphs with JH terminates patterning and induces differentiation, mimicking the processes that occurred during the evolution of the larva. Unpatterned portions of primordia persist in the larva, becoming imaginal discs that form pupal and adult structures. Key transcription factors are associated with the holometabolous life stages: Krüppel-homolog 1 (Kr-h1) in the larva, broad in the pupa and E93 in the adult. Kr-h1 mediates JH action and is found whenever JH acts, while the other two genes direct the formation of their corresponding stages. In hemimetabolous forms, the pronymph has low Broad expression, followed by Broad expression through the nymphal moults, then a switch to E93 to form the adult. This article is part of the theme issue 'The evolution of complete metamorphosis'. [ABSTRACT FROM AUTHOR]

Copyright of Electronic Components & Materials is the property of Electronic Components & Materials and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Insect growth and development are mainly regulated via synchronization of many extrinsic and intrinsic factors such as nutrition and hormones. Previously we have demonstrated that larval growth period influences the effect of insulin on the accumulation of glycogen in the fat body of Bombyx larvae. In the present study we demonstrate that Bombyx larvae at the terminal growth period (TGP, after critical weight) had a significantly greater increase in the expression level of Akt in the fat body than at the active growth period (AGP, before critical weight). The larvae at TGP also showed an increase in the expression level of ecdysone receptors ( EcRB1 and USP1 ) and ecdysone-induced early genes ( E75A and broad ). The treatment of bovine insulin and methoprene to larvae at AGP induced the transcript levels of Akt , irrespective of the nutritional status of the larvae. However, in larvae at TGP, insulin repressed the transcript level of Akt . On contrary, 20-hydroxyecdysone (20E) induced the expression level of Akt in TGP larvae, but at feeding only. Insulin and 20E thus showed an antagonistic action on the Akt expression level in TGP larvae under feeding. The studies thus showed that larval growth period influences the expression level of Akt and ecdysone receptors in Bombyx . Further, the growth period and nutrition modulate the effect of exogenous hormones on Akt expression. [ABSTRACT FROM AUTHOR]

Serological Diagnosis of Sudano-Sahelian Isolates of Rice Yellow Mottle Virus (RYMV). Rice Yellow Mottle Virus (RYMV) is the most damaging virus infecting rice in Africa. Serology is a suitable detection method for RYMV but most available anti-RYMV polyclonal antibodies react poorly with some isolates of the virus, which undermine the reliability of the method. A broad-spectrum polyclonal antibody was raised against Rice Yellow Mottle Virus (RYMV) in order to improve the serological detection of the virus. This antibody was used to diagnose the virus in field samples collected from both irrigated and upland rice and wild host plants in five West and Central African countries (Burkina Faso, Cameroon, Chad, Mali and Togo). RYMV was readily detected in about 500 samples whereas a new natural host species (Eragrostis atrovirens) collected from Mali was identified. The viral isolates gathered in this study constitute the starting point for a reference collection of plant viruses in the Sudano-Sahelian region. This collection will be particularly useful for the assessment of RYMV variability which is a key factor in developing rice varieties with stable resistance to the virus.

Background: Broad-range fungal inter spacer region (ITS) polymerase chain reaction (PCR) has been evaluated for the detection and identification of fungi in clinical specimens from severely immunocompromised patients, but not in non-selected patients. Thus, the aim of this study was to compare the diagnostic performance of ITS PCR with that of fungal culture and to investigate its clinical impact on the diagnosis of fungal infections in non-immunocompromised patients. The corresponding patients' data were retrieved by detailed medical chart reviews. Results: Results from 251 specimens showed a high concordance of 89.6 % for ITS PCR and fungal culture. The analytical sensitivity and specificity of ITS PCR considering culture as gold standard were 87.7 and 90.3 %, respectively, the positive and negative predictive value (PPV and NPV) were 76 and 95.5 %, respectively. Assessing the clinical probability of a fungal infection based on detailed chart reviews, PCR had a clinical sensitivity of 88.9 %, a specificity of 86.3 %, a PPV of 64.0 % and a NPV of 96.6 %. The overall performance of fungal broad-range PCR was similar to that of culture. Conclusions: Our data show that, in non-selected and non-immunocompromised patients, the performance of ITS PCR is similar to that of culture for detecting fungal infections, not the least because sensitivity of culture in patients under antifungal treatment is surprisingly high. Compared to culture, PCR has the advantage of a rapid time-to-result (approximately two working days), proper identification of rare pathogens, prompt initiation of a species-targeted antifungal treatment, and prospects for automation. [ABSTRACT FROM AUTHOR]

Many problems in the translation industry revolve around customer dissatisfaction with someone’s translation quality and disputes between translators when one is revising the work of the other. To determine whether someone has attained translation quality, one must be able to measure it. To measure translation quality, one must be able to define it. And to define translation quality, one must be able to define both translation and quality. Our two prior articles have addressed these terms respectively. Those articles do not resolve disagreements about these terms; indeed, we authors have unresolved disagreements among ourselves. However, the articles outline how different definitions can radically affect people’s expectations about translation and quality. This third article builds on the first two and presents two contrasting definitions of translation quality, a narrow one and a broad one. The narrow definition matches with the narrow definition of translation in the first article and an emphasis on the transcendent view of quality in the second article, while the broad definition matches with the broad definition of translation the first article and an integration of the five approaches in quality management from the second article. The authors strongly disagree about which definition of translation quality is better for the translation industry. Rather than pretending to be the end of this discussion, it hopes to encourage a continuation of the debate that has taken place among the authors.

Insect juvenile hormone (JH) agonists have been utilized as insect growth regulators for pest management against several pest insect species. We investigated insecticidal activity and the induction ratios of two JH-inducible genes, Krüppel homolog 1 (Kr-h1) and broad (br), using 12 test compounds in the western flower thrips Frankliniella occidentalis (Pergande). In insecticidal assays against propupae to inhibit metamorphosis to the adult, the activities of pyriproxyfen, KF-13, ETB, and KF-31 were potent at 10 mM, while those of the other 8 test chemicals were not. In quantitative RT-PCR, these 4 chemicals up-regulated the transcript levels of Kr-h1 and br, while the induction of transcription by chemicals with lower insecticidal activities was relatively small. Thus, the induction ratios of Kr-h1 and br correlated with insecticidal activity. Assessments of the induction ratios of these genes may be a useful method in the preliminary screening of JH agonists. [ABSTRACT FROM AUTHOR]

Bone Morphogenetic Proteins (BMPs) signal by activating Smad transcription factors to control a number of decisions during animal development. In Drosophila , signaling by the BMP ligand Decapentaplegic (Dpp) involves the activity of brinker ( brk ) which, in most contexts, is repressed by Dpp. Brk encodes a transcription factor which represses BMP signaling output by antagonizing Smad-dependent target gene activation. Here, we study BMP-dependent gene regulation during Drosophila oogenesis by following the signal transmission from Dpp to its target broad ( br ), a gene with a crucial function in eggshell patterning. We identify regulatory sequences that account for expression of both brk and br , and connect these to the transcription factors of the pathway. We show that Dpp directly regulates brk transcription through Smad- and Schnurri (Shn)-dependent repression. Brk is epistatic to Dpp in br expression and activates br indirectly, through removal of a repressor, which is yet to be identified. Our work provides first cis -regulatory insights into transcriptional interpretation of BMP signaling in eggshell morphogenesis and defines a transcriptional cascade that connects Dpp to target gene regulation. [ABSTRACT FROM AUTHOR]

Abstract: During Drosophila oogenesis, activation of Notch signaling in the follicular epithelium (FE) around stage 6 of oogenesis is essential for entry into the endocycle and a series of other changes such as cell differentiation and migration of subsets of the follicle cells. Notch induces the expression of zinc finger protein Hindsight and suppresses homeodomain protein Cut to regulate the mitotic/endocycle (ME) switch. Here we report that broad (br), encoding a small group of zinc-finger transcription factors resulting from alternative splicing, is a transcriptional target of Notch nuclear effector Suppressor of Hairless (Su(H)). The early pattern of Br in the FE, uniformly expressed except in the polar cells, is established by Notch signaling around stage 6, through the binding of Su(H) to the br early enhancer (brE) region. Mutation of the Su(H) binding site leads to a significant reduction of brE reporter expression in follicle cells undergoing the endocycle. Chromatin immunoprecipitation results further confirm Su(H) binding to the br early enhancer. Consistent with its expression in follicle cells during midoogenesis, loss of br function results in a delayed entry into the endocycle. Our findings suggest an important role of br in the timing of follicle cell development, and its transcriptional regulation by the Notch pathway. [Copyright &y& Elsevier]

Human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin stalk of group 1 influenza A viruses (IAVs) are biased for IGHV1-69 alleles that use phenylalanine (F54) but not leucine (L54) within their CDRH2 loops. Despite this, we demonstrated that both alleles encode for human IAV bnAbs that employ structurally convergent modes of contact to the same epitope. To resolve differences in lineage expandability, we compared F54 versus L54 as substrate within humanized mice, where antibodies develop with human-like CDRH3 diversity but are restricted to single V H genes. While both alleles encoded for bnAb precursors, only F54 IGHV1-69 supported elicitation of heterosubtypic serum bnAbs following immunization with a stalk-only nanoparticle vaccine. L54 IGHV1-69 was unproductive, co-encoding for anergic B cells and autoreactive stalk antibodies that were cleared from B cell memory. Moreover, human stalk antibodies also demonstrated L54-dependent autoreactivity. Therefore, IGHV1-69 polymorphism, which is skewed ethnically, gates tolerance and vaccine expandability of influenza bnAbs. [Display omitted] • Both F54 and L54 IGHV1-69 alleles encode for human bnAbs against influenza virus • Only F54 IGHV1-69 can provide a substrate for vaccine-amplifying bnAbs to high titer • L54 IGHV1-69 co-endows for poly/autoreactive B cells, which become tolerized • Immune cell checkpoint inhibitors can restore L54 IGHV1-69 antibody responses Human broadly neutralizing antibodies (bnAbs) against the influenza virus preferentially use F54 IGHV1-69 as opposed to the L54 allele of this antibody V H gene. Sangesland et al. show that although both alleles encode for affinity to the same target, L54 IGHV1-69 also imparts autoreactivity, dampening vaccine expandability in a humanized mouse model. [ABSTRACT FROM AUTHOR]

The molecular action of juvenile hormone (JH), a regulator of vital importance to insects, was until recently regarded as a mystery. The past few years have seen an explosion of studies of JH signaling, sparked by a finding that a JH-resistance gene, Methoprene-tolerant ( Met), plays a critical role in insect metamorphosis. Here, we summarize the recently acquired knowledge on the capacity of Met to bind JH, which has been mapped to a particular ligand-binding domain, thus establishing this bHLH-PAS protein as a novel type of an intracellular hormone receptor. Next, we consider the significance of JH-dependent interactions of Met with other transcription factors and signaling pathways. We examine the regulation and biological roles of genes acting downstream of JH and Met in insect metamorphosis. Finally, we discuss the current gaps in our understanding of JH action and outline directions for future research. [ABSTRACT FROM AUTHOR]

Like the mammalian intestine, the Drosophila adult midgut is constantly replenished by multipotent intestinal stem cells (ISCs). Although it is well known that adult ISCs arise from adult midgut progenitors (AMPs), relatively little is known about the mechanisms that regulate AMP specification. Here, we demonstrate that Broad (Br)-mediated hormone signaling regulates AMP specification. Br is highly expressed in AMPs temporally during the larva-pupa transition stage, and br loss of function blocks AMP differentiation. Furthermore, Br is required for AMPs to develop into functional ISCs. Conversely, br overexpression drives AMPs toward premature differentiation. In addition, we found that Br and Notch (N) signaling function in parallel pathways to regulate AMP differentiation. Our results reveal a molecular mechanism whereby Br-mediated hormone signaling directly regulates stem cells to generate adult cells during metamorphosis. [ABSTRACT FROM AUTHOR]

In his classic work The Mind and its Place in Nature published in 1925 at the height of the development of quantum mechanics but several years after the chemists Lewis and Langmuir had already laid the foundations of the modern theory of valence with the introduction of the covalent bond, the analytic philosopher C. D. Broad argued for the emancipation of chemistry from the crass physicalism that led physicists then and later-with support from a rabblement of philosophers who knew as much about chemistry as etymologists-to believe that chemistry reduced to physics. Here Broad's thesis is recast in terms more familiar to chemists. In the hard sell of particle physics, several prominent figures in chemistry-Hoffmann, Primas, and Pauling-have had their views interpreted to imply that they were sympathetic to greedy reductionism when in fact they were not. Indeed, being chemists without physicists as alter egos, they could not but side with Broad's contention that chemistry, as a science that deals primarily in emergent phenomena which are beyond the purview of physicalism, owes no acquiescence to particle physics and its ethereal wares. Historically, among the most widely used expediencies in chemistry and materials science are additivity or mixture rules and their cohort transferability, all of which are devised and used under the mantle of naive reductionism. Here it is argued that while the transfer of functional groups between molecules works empirically to an extent, it is strictly outlawed by the no-cloning theorem of quantum mechanics. Several illustrative examples related to chemistry's irreducibility to physics are presented and discussed. The failure of naive reductionism exhibited by the deep-inelastic scattering of leptons by A > 2 nuclei is traced to the same flawed reasoning that was the original basis of Moffitt's 'atoms in molecules' hypothesis, the neglect of context, nuclei in the case of high-energy physics and molecules in the case of chemistry. A non-exhaustive list of other contexts from physics, chemistry, and molecular biology evidencing similar departures from the ideal of additivity or reductionism is provided for the perusal of philosophers. Had the call by the mathematician J. T. Schwartz for developments in mathematical linguistics possessed of a less single, less literal, and less simple-minded nature been met, perhaps it might have persuaded scientists to abandon their regressive fixation with unphysical reductionism and to adapt to new methodologies that engender a more nuanced handling of ubiquitous emergent phenomena as they arise in Nature than is the case today. [ABSTRACT FROM AUTHOR]

Background: Tip surgery probably is the most challenging objective in modern rhinoplasty. The Goldman technique, despite its 50 years of history and its many variations proposed in the past, still remains a powerful tool for the surgeon who has to deal with an overprojected or broad nasal tip. Methods: A retrospective review was performed for all the patients who underwent surgery with the Goldman technique by the senior author from 2004 to 2009 for correction of the broad or overprojected nasal tip. The clinical and pathologic findings of these patients were reviewed, and an independent observer evaluated the pre- and postoperative photos of the patients using five parameters: projection, rotation, symmetry, shape, and distance of the tip-defining points. The evaluation was performed using a scale of −1 to +1 for each of the five parameters. Results: Of the 205 patients who underwent the technique, 115 (56%) were patients with overprojected tips, and 90 (44%) were patients with broad (boxy) tips. A total of 189 cases (92.2%) involved primary rhinoplasties, and 16 cases (7.8%) involved revision. The mean follow-up period was 3 years (range, 1-5 years). During this period, complications were observed in five patients (2.4%), who underwent revision rhinoplasty with a successful result. The average score for the five parameters already mentioned for primary rhinoplasties according to the scale of −5 to +5 (resulting from the summation of all the parameters) showed a significant postoperative improvement (score, +4.3). The revision rhinoplasties showed significant improvement as well (score, +4.5). Conclusion: The Goldman technique is safe when performed by experienced surgeons and according to specific indications. This conclusion is indicated by the low rate of complications in the large series of patients in this study. When performed correctly, the Goldman technique provides a long-term aesthetic, functional, and natural result, which is the goal of modern functional rhinoplasty. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the seismic responses of base-isolated broad and slender cylindrical liquid storage ground tanks are investigated. Three types of isolation systems are considered. The seismic responses are compared with the corresponding responses of non-isolated tanks. Moreover, a parametric study was conducted to evaluate the effect of tank aspect ratio, isolation period, and friction coefficient of the FPS system on key responses of the tank. It was found that, base isolation is quite effective in reducing the earthquake response of ground liquid storage tanks. Generally speaking, 50–90% reductions in both base shear and impulsive displacement responses were observed. The convective displacement was observed to be 20–70% higher than that associated with fixed base tanks leading to an essential need of increasing the clear height above the liquid surface. Base isolation was found to be more effective for slender tanks in comparison with broad tanks. [ABSTRACT FROM AUTHOR]

Abstract: In holometabolous insects, Krüppel homolog 1 (Kr-h1) and broad (br) are key players in the juvenile hormone (JH) regulation of metamorphosis: Kr-h1 is an early JH-response gene, while br is a transcription factor that directs pupal development. Thrips (Thysanoptera) are classified as hemimetabolous insects that develop directly from nymph to adult, but they have quiescent and non-feeding stages called propupa and pupa. We analyzed the developmental profiles of br and Kr-h1 in the western flower thrips Frankliniella occidentalis (Thripidae) that has one propupal instar and one pupal instar, and Haplothrips brevitubus (Phlaeothripidae) that has one propupal instar and two pupal instars, i.e. pupa I and pupa II. In F. occidentalis, the br mRNA levels were moderate in the embryonic stage, high at the larva-propupa transition, and low in the pre-final larval instar and the pupal stage, while Kr-h1 mRNA levels were high in the embryonic stage, remained at a moderate level in the larval and propupal stages, and low in the pupal stage. The expression profiles in H. brevitubus were very similar to those in F. occidentalis, except that the increase of br expression in the final larval stage occurs more slowly in H. brevitubus, and that the mRNA levels of br and Kr-h1 remained high in pupa I of H. brevitubus and then decreased. These profiles of br and Kr-h1 were comparable to those in holometabolous insects, although br expression found in thrips’ embryogenesis is reminiscent of several hemimetabolous species. Treatment with an exogenous JH mimic (JHM) in distinct developmental stages consistently resulted in lethality as pupa of F. occidentalis or pupa II of H. brevitubus. Treatment with JHM to newly molted propupae caused prolonged expression of Kr-h1 and br in both species, suggesting that Kr-h1 and br could be involved in mediating anti-metamorphic signals of JHM. [ABSTRACT FROM AUTHOR]

Abstract: The exoskeleton of insects (cuticle) is an assembly of chitin and cuticle proteins. Its physical properties are determined largely by the proteins it contains, and vary widely with developmental stages and body regions. The genes encoding cuticle proteins are therefore good models to study the molecular mechanisms of signalling by ecdysteroids and juvenile hormones, which regulate molting and metamorphosis in insects. This review summarizes the studies of hormonal regulation of insect cuticle protein genes, and the recent progress in the analysis of the regulatory sequences and transcription factors important for their expression. [Copyright &y& Elsevier]

Broad (BR), an ecdysone-inducible transcription factor, is a major determinant of the pupal stage. The misexpression of BR-Z1 isoform ( BR-Z1) during adult development of Drosophila melanogaster prevents the expression of the adult cuticle protein 65A gene ( Acp65A). We found that the proximal 237 bp of the 5′ flanking region of Acp65A were sufficient to mediate this suppression. A targeted point mutation of a putative BR-Z1 response element (BRE) within this region showed that it was not involved. Drosophila hormone receptor-like 38 (DHR38) is required for Acp65A expression. We found that BR-Z1 repressed DHR38 expression and that BR's inhibition of Acp65A expression was rescued by exogenous expression of DHR38. Thus, BR-Z1 suppresses Acp65A expression by preventing the normal up-regulation of DHR38 at the time of adult cuticle formation. [ABSTRACT FROM AUTHOR]

Abstract: Juvenile hormone (JH) prevents ecdysone-induced metamorphosis in insects. However, our knowledge of the molecular mechanisms of JH action is still fragmented. Krüppel homolog 1 (Kr-h1) is a JH-inducible transcription factor in Drosophila melanogaster (Minakuchi, C., Zhou, X., Riddiford, L.M., 2008b. Krüppel homolog 1 (Kr-h1) mediates juvenile hormone action during metamorphosis of Drosophila melanogaster. Mech. Dev. 125, 91–105). Analysis of expression of the homologous gene (TcKr-h1) in the beetle Tribolium castaneum showed that its transcript was continuously present in the larval stage but absent in the pupal stage. Artificial suppression of JH biosynthesis in the larval stage caused a precocious larval–pupal transition and a down-regulation of TcKr-h1 mRNA. RNAi-mediated knockdown of TcKr-h1 in the larval stage induced a precocious larval–pupal transition. In the early pupal stage, treatment with an exogenous JH mimic (JHM) caused formation of a second pupa, and a rapid and large induction of TcKr-h1 transcription. JHM-induced formation of a second pupa was counteracted by the knockdown of TcKr-h1. RNAi experiments in combination with JHM treatment demonstrated that in the larval stage TcKr-h1 works downstream of the putative JH receptor Methoprene-tolerant (TcMet), and in the pupal stage it works downstream of TcMet and upstream of the pupal specifier broad (Tcbr). Therefore, TcKr-h1 is an early JH-response gene that mediates JH action linking TcMet and Tcbr. [Copyright &y& Elsevier]

Abstract: At the beginning of the final larval (fifth) instar of Manduca sexta, imaginal precursors including wing discs and eye primordia initiate metamorphic changes, such as pupal commitment, patterning and cell proliferation. Juvenile hormone (JH) prevents these changes in earlier instars and in starved final instar larvae, but nutrient intake overcomes this effect of JH in the latter. In this study, we show that a molecular marker of pupal commitment, broad, is up-regulated in the wing discs by feeding on sucrose or by bovine insulin or Manduca bombyxin in starved final instar larvae. This effect of insulin could not be prevented by JH. In vitro insulin had no effect on broad expression but relieved the suppression of broad expression by JH. This effect of insulin was directly on the disc as shown by its reduction in the presence of insulin receptor dsRNA. In starved penultimate fourth instar larvae, broad expression in the wing disc was not up-regulated by insulin. The discs became responsive to this action of insulin during the molt to the fifth instar together with the ability to become pupally committed in response to 20-hydroxyecdysone. Thus, the Manduca bombyxin acts as a metamorphosis-initiating factor in the imaginal precursors. [Copyright &y& Elsevier]

Abstract: Drosophila egg development is an established model for studying epithelial patterning and morphogenesis, but the connection between signaling pathways and egg morphology is still incompletely understood. We have identified a non-classical cadherin, Cad74A, as a putative adhesion gene that bridges epithelial patterning and morphogenesis in the follicle cells. Starting in mid-oogenesis, Cad74A is expressed in the follicle cells that contact the oocyte, including the border cells and most of the columnar follicle cells. However, Cad74A is repressed in two dorsolateral patches of follicle cells, which participate in the formation of tubular respiratory appendages. We show genetically that Cad74A is downstream of the EGFR and BMP signaling pathways and is repressed by the Zn-finger transcription factor Broad. The correlation of Cad74A repression in the cells that bend out of the plane of the follicular epithelium is preserved across Drosophila species and mutant backgrounds exhibiting a range of eggshell phenotypes. Complete removal of Cad74A from the follicle cells causes defects in dorsal appendage formation. Ectopic expression of Cad74A in the roof cells results in shortened, flattened appendages due to the hindered migration of the roof cells. Based on these results, we propose that Cad74A is part of the adhesive machinery that enables robust dorsal appendage formation, and as such provides a link between the patterning of the follicle cells and eggshell morphogenesis. [Copyright &y& Elsevier]

Abstract: During the pupal metamorphosis in insects, cellular commitment for pupal differentiation must precede before its differentiation. The pupal commitment of Bombyx mori epidermis occurred from day 3 to day 6 last (5th) instar larvae in response to the gradual increase in ecdysteroid titer in the presence of a small amount of juvenile hormone (JH). Yet the concealed preparatory process of the commitment had begun in the newly synthesized 5th instar larval epidermis (∼6h before the ecdysis) as a competence phase, in which pupal commitment in vitro was induced by 20-hydroxyecdysone (20E) but inhibited by JH. This competence phase continued until day 2 5th instar, and the decrease and increase in cellular sensitivity to JH and 20E, respectively, occurred gradually during this period. In early day 3, autonomous pupal commitment began in vitro and 20E stimulated the commitment, but JH could only partially prevent the commitment in both cases. This apparent reversible to irreversible transition ended in early day 6 by the completion of pupal commitment, when the cells completely lost their sensitivity to JH and no longer expressed the larval cuticle protein gene 30. The expression of the transcription factor, broad, closely followed the commitment, so that we could use this gene expression as a molecular marker for pupal commitment. These results indicate that exposure to 20E and loss of the sensitivity of the epidermal cells to JH are required for the completion of pupal commitment, and suggest that the unusually long process over 3days could be due to the presence of the detectable JH during the commitment. [Copyright &y& Elsevier]

Abstract: Juvenile hormone (JH) given at pupariation inhibits bristle formation and causes pupal cuticle formation in the abdomen of Drosophila melanogaster due to its prolongation of expression of the transcription factor Broad (BR). In a microarray analysis of JH-induced gene expression in abdominal integument, we found that Krüppel homolog 1 (Kr-h1) was up-regulated during most of adult development. Quantitative real-time PCR analyses showed that Kr-h1 up-regulation began at 10h after puparium formation (APF), and Kr-h1 up-regulation occurred in imaginal epidermal cells, persisting larval muscles, and larval oenocytes. Ectopic expression of Kr-h1 in abdominal epidermis using T155-Gal4 to drive UAS-Kr-h1 resulted in missing or short bristles in the dorsal midline. This phenotype was similar to that seen after a low dose of JH or after misexpression of br between 21 and 30h APF. Ectopic expression of Kr-h1 prolonged the expression of BR protein in the pleura and the dorsal tergite. No Kr-h1 was seen after misexpression of br. Thus, Kr-h1 mediates some of the JH signaling in the adult abdominal epidermis and is upstream of br in this pathway. We also show for the first time that the JH-mediated maintenance of br expression in this epidermis is patterned and that JH delays the fusion of the imaginal cells and the disappearance of Dpp in the dorsal midline. [Copyright &y& Elsevier]

Some of the speech databases and large spoken language corpora that have been collected during the last fifteen years have been (at least partly) annotated with a broad phonetic transcription. Such phonetic transcriptions are often validated in terms of their resemblance to a handcrafted reference transcription. However, there are at least two methodological issues questioning this validation method. First, no reference transcription can fully represent the phonetic truth. This calls into question the status of such a transcription as a single reference for the quality of other phonetic transcriptions. Second, phonetic transcriptions are often generated to serve various purposes, none of which are considered when the transcriptions are compared to a reference transcription that was not made with the same purpose in mind. Since phonetic transcriptions are often used for the development of automatic speech recognition (ASR) systems, and since the relationship between ASR performance and a transcription’s resemblance to a reference transcription does not seem to be straightforward, we verified whether phonetic transcriptions that are to be used for ASR development can be justifiably validated in terms of their similarity to a purpose-independent reference transcription. To this end, we validated canonical representations and manually verified broad phonetic transcriptions of read speech and spontaneous telephone dialogues in terms of their resemblance to a handcrafted reference transcription on the one hand, and in terms of their suitability for ASR development on the other hand. Whereas the manually verified phonetic transcriptions resembled the reference transcription much closer than the canonical representations, the use of both transcription types yielded similar recognition results. The difference between the outcomes of the two validation methods has two implications. First, ASR developers can save themselves the effort of collecting expensive reference transcriptions in order to validate phonetic transcriptions of speech databases or spoken language corpora. Second, phonetic transcriptions should preferably be validated in terms of the application they will serve because a higher resemblance to a purpose-independent reference transcription is no guarantee for a transcription to be better suited for ASR development. [ABSTRACT FROM AUTHOR]

Abstract: The Drosophila egg chamber provides an excellent model for studying the link between patterning and morphogenesis. Late in oogenesis, a portion of the flat follicular epithelium remodels to form two tubes; secretion of eggshell proteins into the tube lumens creates the dorsal appendages. Two distinct cell types contribute to dorsal appendage formation: cells expressing the rhomboid-lacZ (rho-lacZ) marker form the ventral floor of the tube and cells expressing high levels of the transcription factor Broad form a roof over the rho-lacZ cells. In mutants that produce defective dorsal appendages (K10, Ras and ectopic decapentaplegic) both cell types are specified and reorganize to occupy their stereotypical locations within the otherwise defective tubes. Although the rho-lacZ and Broad cells rearrange to form a tube in wild type and mutant egg chambers, they never intermingle, suggesting that a boundary exists that prevents mixing between these two cell types. Consistent with this hypothesis, the Broad and rho-lacZ cells express different levels of the homophilic adhesion molecule Fasciclin 3. Furthermore, in the anterior of the egg, ectopic rhomboid is sufficient to induce both cell types, which reorganize appropriately to form an ectopic tube. We propose that signaling across a boundary separating the rho-lacZ and Broad cells choreographs the cell shape-changes and rearrangements necessary to transform an initially flat epithelium into a tube. [Copyright &y& Elsevier]