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Horseshoe crabs represent the most ancestral chelicerate lineage characterized by marine ecology and the possession of lateral compound eyes. While considered living fossils, recent studies reported an unusual number of Pax6 genes in the Atlantic horseshoe crab Limulus polyphemus. Pax genes encode ancient metazoan transcription factors, which comprise seven subfamilies. Among these, the members of the Pax6 subfamily confer critical functions in the development of the head, the visual system, and further body plan components. Arthropods are generally characterized by two Pax6 subfamily homologs that were discovered in Drosophila and named eyeless (ey) and twin of eyeless (toy). However, whole genome sequence searches uncovered three homologs of ey and two homologs of toy in L. polyphemus. These numbers are explained by the occurrence of likely three whole genome duplications in the lineage to the last common ancestor of L. polyphemus and the three additional members of the extant horseshoe crab species cluster. Here, we report that all five L. polyphemus Pax6 paralogs are conserved in the approximately 135-million-year-old horseshoe crab species cluster and that they evolve under strong purifying selection. Largely homogenous protein sequence diversification rates of ey and toy paralogs suggest subfunctionalization as the likeliest preservation trajectory. However, our studies further revealed evidence that the horseshoe crab ey1 and ey2 paralogs share a derived splice isoform that encodes a unique five amino acid-long insertion in helix 3 of the homeodomain. This suggests that the exceptional expansion of the horseshoe crab Pax6 gene family repertoire was also associated with regulatory diversification and possibly innovation. [ABSTRACT FROM AUTHOR]

Simple Summary: Hemiptera is one of the largest and most diverse insect orders, yet our knowledge about visual opsin evolution in this group remains preliminary. This study provides an updated survey of visual opsin genes in the Hemiptera, which reveals that the subfamily of blue-sensitive opsin receptor genes has been independently lost in planthoppers and aphids. Moreover, in both groups, tandem duplication of UV-sensitive opsins produced sister paralogs that diverged by maintaining ancestral UV sensitivity versus shifting to blue sensitivity and thereby likely compensating for the loss of the blue-sensitive opsin subfamily. The study further shows that these parallel trajectories at the level of gene family evolution are associated with mostly convergent changes at the level of protein sequence evolution. Expanding on previous efforts to survey the visual opsin repertoires of the Hemiptera, this study confirms that homologs of the UV- and LW-opsin subfamilies are conserved in all Hemiptera, while the B-opsin subfamily is missing from the Heteroptera and subgroups of the Sternorrhyncha and Auchenorrhyncha, i.e., aphids (Aphidoidea) and planthoppers (Fulgoroidea), respectively. Unlike in the Heteroptera, which are characterized by multiple independent expansions of the LW-opsin subfamily, the lack of B-opsin correlates with the presence of tandem-duplicated UV-opsins in aphids and planthoppers. Available data on organismal wavelength sensitivities and retinal gene expression patterns lead to the conclusion that, in both groups, one UV-opsin paralog shifted from ancestral UV peak sensitivity to derived blue sensitivity, likely compensating for the lost B-opsin. Two parallel bona fide tuning site substitutions compare to 18 non-corresponding amino acid replacements in the blue-shifted UV-opsin paralogs of aphids and planthoppers. Most notably, while the aphid blue-shifted UV-opsin clade is characterized by a replacement substitution at one of the best-documented UV/blue tuning sites (Rhodopsin site 90), the planthopper blue-shifted UV-opsin paralogs retained the ancestral lysine at this position. Combined, the new findings identify aphid and planthopper UV-opsins as a new valuable data sample for studying adaptive opsin evolution. [ABSTRACT FROM AUTHOR]

There is general agreement about the Jesuits' alertness to media, their crucial role in early modern printing, and their engagement in promoting the sanctity of some of their members through print publication. Despite several efforts to establish central control, most of the Society's media production remained decentralized. Moreover, there was no pre-conceived publication strategy of hagiographical activities. As a result, the production of hagiographies often sprung up locally and with little initial awareness of each other. Hence, it was nearly unavoidable that projects overlapped and that competition between them arose. Examining two early hagiographic accounts of the life of Peter Canisius, the article sheds light on the Jesuits' production and publication of hagiographical literature by linking the publication history of both projects to an investigation of the underlying manuscripts. As the paper demonstrates, early modern Jesuit print and manuscript culture cannot be separated. [ABSTRACT FROM AUTHOR]

Pioneering molecular work on chelicerate visual system development in the horseshoe crab Limulus polyphemus surprised with the possibility that this process may not depend on the deeply conserved retinal determination function of Pax6 transcription factors. Genomic, transcriptomic, and developmental studies in spiders now reveal that the arthropod Pax6 homologs eyeless and twin of eyeless act as ancestral determinants of the ocular head segment in chelicerates, which clarifies deep gene regulatory and structural homologies and recommends more unified terminologies in the comparison of arthropod visual systems. Following this phylotypic stage, chelicerate visual system development differs fundamentally from other arthropods during the compartmentalization of the ocular segment in that eye and optic neuropil primordia originate independently from each other. Comparative analyses of this phase identified further gene regulatory homologies but also major differences, most notably the possibly compensatory replacement of Pax6 by Pax2 in lateral eye specification. Also see the video abstract here: https://youtu.be/Hdfr3z5kEXU [ABSTRACT FROM AUTHOR]

The goal of this document is to survey existing methods for recovering or extracting CSG (Constructive Solid Geometry) representations from unstructured data such as 3D point-clouds or polygon meshes. We review and discuss related topics such as the segmentation and fitting of the input data. We cover techniques from solid modeling for the conversion of a polyhedron to a CSG expression and for the conversion of a B-rep to a CSG expression. We look at approaches coming from program synthesis, evolutionary techniques (such as genetic programming or genetic algorithm), and deep learning. Finally, we conclude our survey with a discussion of techniques for the generation of computer programs involving higher-level constructs, representations, and operations for representing solids. • A study of the complexity within the solution space of the CSG conversion problem. • A review of classical techniques for converting B-reps to CSG expressions. • A survey of techniques for extracting CSG expressions from unstructured data. • A review of recent techniques from program synthesis and neurosymbolic models (integration of symbolic reasoning with neural networks) for learning procedural models from unstructured data. • A chronologically based organization and presentation of the existing techniques. [ABSTRACT FROM AUTHOR]

The arthropod compound eye represents one of two major eye types in the animal kingdom and has served as an essential experimental paradigm for defining fundamental mechanisms underlying sensory organ formation, function, and maintenance. One of the most distinguishing features of the compound eye is the highly regular array of lens facets that define individual eye (ommatidial) units. These lens facets are produced by a deeply conserved quartet of cuticle-secreting cells, called Semper cells (SCs). Also widely known as cone cells, SCs were originally identified for their secretion of the dioptric system, i.e. the corneal lens and underlying crystalline cones. Additionally, SCs are now known to execute a diversity of patterning and glial functions in compound eye development and maintenance. Here, we present an integrated account of our current knowledge of SC multifunctionality in the Drosophila compound eye, highlighting emerging gene regulatory modules that may drive the diverse roles for these cells. Drawing comparisons with other deeply conserved retinal glia in the vertebrate single lens eye, this discussion speaks to glial cell origins and opens new avenues for understanding sensory system support programs. [Display omitted] • Drosophila Semper cells, also known as cone cells, are highly multifunctional. • Semper cells direct the differentiation of all three tissue types in the compound eye. • Semper cells serve homeostatic support roles in the adult compound eye. • Semper cells share many characteristics with vertebrate retinal Muller glia. • Conserved gene regulatory modules are associated with specific Semper cell functions. [ABSTRACT FROM AUTHOR]

Pax6 transcription factors are essential upstream regulators in the developing anterior brain and peripheral visual system of most bilaterian animals. While a single homolog is in charge of these functions in vertebrates, two Pax6 genes are in Drosophila : eyeless ( ey ) and twin of eyeless ( toy ). At first glance, their co-existence seems sufficiently explained by their differential involvement in the specification of two types of insect visual organs: the lateral compound eyes ( ey ) and the dorsal ocelli ( toy ). Less straightforward to understand, however, is their genetic redundancy in promoting defined early and late growth phases of the precursor tissue to these organs: the eye-antennal imaginal disc. Drawing on comparative sequence, expression, and gene function evidence, I here conclude that this gene regulatory network module dates back to the dawn of arthropod evolution, securing the embryonic development of the ocular head segment. Thus, ey and toy constitute a paradigm to explore the organization and functional significance of longterm conserved genetic redundancy of duplicated genes. Indeed, as first steps in this direction, recent studies uncovered the shared use of binding sites in shared enhancers of target genes that are under redundant ( string ) and, strikingly, even subfunctionalized control by ey and toy ( atonal ). Equally significant, the evolutionarily recent and paralog-specific function of ey to repress the transcription of the antenna fate regulator Distal-less offers a functionally and phylogenetically well-defined opportunity to study the reconciliation of shared, partitioned, and newly acquired functions in a duplicated developmental gene pair. [ABSTRACT FROM AUTHOR]

The article presents a report from a June 10, 2017 conference in Mannheim, Germany on the history of competitive cycling hosted by the Institut für Sportgeschichte Baden-Württemberg e.V. sports history society and the Stadtarchiv Mannheim-Institut für Stadtgeschichte and Landesarchiv Baden-Württemberg archives. Topics of presentations delivered included the technological history of the bicycle from the invention of the draisienne, the formation of cycling clubs in Mannheim, and cycling and the working class.

Light represents one of the most reliable environmental cues in the biological world. In this review we focus on the evolutionary consequences to changes in organismal photic environments, with a specific focus on the class Insecta. Particular emphasis is placed on transitional forms that can be used to track the evolution from (1) diurnal to nocturnal (dim-light) or (2) surface to subterranean (aphotic) environments, as well as (3) the ecological encroachment of anthropomorphic light on nocturnal habitats (artificial light at night). We explore the influence of the light environment in an integrated manner, highlighting the connections between phenotypic adaptations (behaviour, morphology, neurology and endocrinology), molecular genetics and their combined influence on organismal fitness. We begin by outlining the current knowledge of insect photic niches and the organismal adaptations and molecular modifications that have evolved for life in those environments. We then outline concepts and guidelines for future research in the fields of natural history, ethology, neurology, morphology and particularly the advantages that high throughput sequencing provides to these aspects of investigation. Finally, we highlight that the power of such integrative science lies in its ability to make phylogenetically robust comparative assessments of evolution, ones that are grounded by empirical evidence derived from a concrete understanding of organismal natural history. [ABSTRACT FROM AUTHOR]

This essay approaches the history of data by looking at research practices of early modern genealogists. Genealogy was (and is) a data-intensive enterprise. It requires the accumulation, management, organization, and display of vast amounts of personal data reaching back many generations. While recent research has studied in detail the social and political functions of premodern genealogy, and while the staging of genealogical information for purposes of representation has been investigated carefully, next to nothing is known about the work invested in actually researching family lines and dynastic relations. Yet the research strategies and practices, the constraints, and the possibilities of genealogical study had a crucial impact on the shape and understanding of genealogical information. By looking particularly carefully at archives as sites of genealogical data production, this essay attempts to shed light on this understudied question and contributes to the premodern history of data. [ABSTRACT FROM AUTHOR]

This article focuses on Pierre Camille Le Moine (1723–1800), an archivist and the author of the first printed French monograph entirely devoted to archives and archival management and description, the influential Diplomatique pratique (1765). The article investigates the strategies that archivists such as Le Moine used to acquire employment. A labour market for archival expertise came into being in mid-eighteenth-century France, and several episodes from Le Moine’s professional life illustrate the mechanisms used both by potential employers and employees to attract interest. Next, the article investigates Le Moine’s understanding of himself as an archivist and his assumptions about the status of archival work, both in relation to his family life and in relation to the wider cultural changes at the time. While able to use enlightened rhetoric and showing at least some superficial acquaintance with the new sociability of the philosophes, Le Moine in many ways remained anchored in a culture more akin to the world of the traditional antiquarian. Clearly, his constant concern for archives gave him a preservationist bias. What made the author most famous was the publication of Le Diplomatique pratique, a serious attempt to combine erudite diplomatics in the Maurist style with a manual for the practicalities of everyday archival life. The last section of the article studies the nature of daily archival experiences in eighteenth-century France, including daily routines regarding the production, content, structure and function of inventories. [ABSTRACT FROM AUTHOR]

Superficial fungal infections affect 20-25% of people worldwide and can cause considerable morbidity, particularly if an inflammatory component is present. As superficial fungal infections can be diverse, the treatment should be tailored to the individual needs of the patient and several factors should be taken into account when deciding on the most appropriate treatment option. These include the type, location and surface area of the infection, patient age, degree of inflammation and underlying comorbidities. Although several meta-analyses have shown that there are no significant differences between the numerous available topical antifungal agents with regard to mycological cure, agents differ in their specific intrinsic properties, which can affect their clinical use. The addition of a corticosteroid to an antifungal agent at the initiation of treatment can attenuate the inflammatory symptoms of the infection and is thought to increase patient compliance, reduce the risk of bacterial superinfection and enhance the efficacy of the antifungal agent. However, incorrect use of antifungal-corticosteroid therapy may be associated with treatment failure and adverse effects. This review summarises available treatment options for superficial fungal infections and provides general treatment recommendations based on the consensus outcomes of an Expert Panel meeting on the topical treatment of superficial mycoses. [ABSTRACT FROM AUTHOR]

The essay focuses on the professionalisation of archivists, sometimes referred to as feudistes, in France in the mid eighteenth-century. Such men needed to understand previously used handwriting, Latin language, chronological systems, and seals for organizing and referencing French seigneurial archives. Other topics include the work "La Pratique universelle pour la rénovation des terriers et des droits seigneuriaux," by Edme de la Poix de Fréminville, feudal record keeping, and the social history of archives.

Simple Summary: Programmed cell death is a universal mechanism in animal development and tissue maintenance, which facilitates the elimination of surplus or poorly functioning cells. Many conserved regulators of programmed cell death have been identified in model organisms including the fruit fly Drosophila melanogaster. In the latter, the four members of the RHG gene family function as critical inducers of programmed cell death. Despite this important role, RHG genes had thus far only been found in a surprisingly small number of insect groups, i.e., other flies and butterflies. This study reports the much deeper conservation of RHG genes in winged insects, ranging from cockroaches to beetles. In addition to opening new opportunities to study programmed cell death in a wide range of insects, the bioinformatic search strategy developed for this work will be of general use for studying gene families with challenging sequence evolution dynamics. Together with sickle (skl), the Drosophila paralogs reaper (rpr), head involution defective (hid), and grim (RHG) control a critical switch in the induction of programmed cell death. RHG homologs have been identified in other dipteran and lepidopteran species but not beyond. Revisiting this issue with a "taxon hopping" BLAST search strategy in current genome and transcriptome resources, I detected high confidence RHG homologs in Coleoptera, Hymenoptera, Hemiptera, and Dictyoptera. Analyses of gene structure and protein sequence conservation revealed aconserved splicing pattern and highly conserved amino acid residues at both the N- and C-terminal ends that identify hid as the most ancestrally organized RHG gene family member in Drosophila. hid-like RHG homologs were also detected in mosquitoes, redefining their michelob_x (mx) genes as an expansion of derived RHG homologs. Only singleton homologs were detected in the large majority of other insect clades. Lepidopteran RHG homologs, however, stand out by producing an evolutionarily-derived splice isoform, identified in previous work, in addition to the newly detected hid-like isoform. Exceptional sequence diversification of select RHG homologs at the family- and genus-level explain their previous elusiveness in important insect genome model species like the red flour beetle Tribolium castaneum and the pea aphid Acyrthosiphon pisum. Combined, these findings expand the minimal age of the RHG gene family by about 100 million years and open new avenues for molecular cell death studies in insects. [ABSTRACT FROM AUTHOR]

Cave-adapted animals are characterized by extreme reduction or complete absence of eyes, reflecting their lack of exposure to daylight. Given the overall constancy of abiotic variables in the cave environment, one would also expect the relaxation and eventual loss of circadian rhythms, and with it, the regressive evolution of the underlying genetic biological clock. Remarkably, however, recent behavioral and molecular studies converge with earlier evidence that the biological clock remains conserved in cave-adapted species. Reviewing the structural and behavioral data on the relationship between the visual system and the biological clock in cave species, I assess the potential of deep sequencing for elucidating their evolutionary conservation and adaptive significance in the subterranean fauna. The combined evidence confirms the widespread conservation both of the visual system and of the behavior regulated by the biological clock in cave species. The data from over 40 vertebrate and arthropod species further reveal that the absence of activity rhythms is correlated with the regression of the visual system. At the same time, the network of biological clock genes is likely to be generally conserved in cave species, regulating rhythmic behaviors in response to non-visual cycling variables as well as organismal homeostasis. Arrhythmic, eyeless species of cave beetles emerge as the most stringent choice for using deep-sequencing approaches to test and explore the conservation of the biological clock, independently of the visual system. [ABSTRACT FROM PUBLISHER]

The value of mitochondrial versus nuclear gene sequence data in phylogenetic analysis has received much attention without yielding definitive conclusions. Theoretical arguments and empirical data suggest a lower phylogenetic utility than equivalent nuclear gene sequences, but there are many examples of important progress made using mitochondrial sequences. We undertook a systematic performance analysis of mitochondrial and nuclear sequence partitions taken from a representative sample of dipteran species. When analysed alone, mitochondrial genes generally performed less well than nuclear genes; however, these genes resolved some branches for which nuclear genes failed. Moreover, the combined use of mitochondrial and nuclear sequences produced superior results without artifacts for nodes where mitochondrial and nuclear gene data generated conflicting topologies. These findings strongly advocate the inclusion of mitochondrial sequences, even in deep phylogeny reconstruction. Comparison of tree support between our and previous analyses identified robustly supported high-confidence clades in the Diptera, but also revealed problematic groupings in need of further analysis. [ABSTRACT FROM AUTHOR]

Obligatory cave species exhibit dramatic trait modifications such as eye reduction, loss of pigmentation and an increase in touch receptors. As molecular studies of cave adaptation have largely concentrated on vertebrate models, it is not yet possible to probe for genetic universalities underlying cave adaptation. We have therefore begun to study the strongly cave-adapted small carrion beetle Ptomaphagus hirtus. For over 100 years, this flightless signature inhabitant of Mammoth Cave, the world's largest known cave system, has been considered blind despite the presence of residual lens structures. By deep sequencing of the adult head transcriptome, we discovered the transcripts of all core members of the phototransduction protein machinery. Combined with the absence of transcripts of select structural photoreceptor and eye pigmentation genes, these data suggest a reduced but functional visual system in P. hirtus. This conclusion was corroborated by a negative phototactic response of P. hirtus in light/dark choice tests. We further detected the expression of the complete circadian clock gene network in P. hirtus, raising the possibility of a role of light sensation in the regulation of oscillating processes. We speculate that P. hirtus is representative of a large number of animal species with highly reduced but persisting visual capacities in the twilight zone of the subterranean realm. These can now be studied on a broad comparative scale given the efficiency of transcript discovery by next-generation sequencing. [ABSTRACT FROM AUTHOR]

Evolutionary developmental biology focuses heavily on the constructive evolution of body plan components, but there are many instances such as parasitism, cave adaptation, or postembryonic growth rate optimization where evolutionary regression is of adaptive value. This is particularly true in the nervous system because of its massive energy costs. However, comparatively little effort has thus far been made to understand the evolutionary developmental trajectories of adaptive nervous system reduction. This review focuses on the organization and evolution of the Drosophila larval brain, which represents an exceptional example of miniaturization, most dramatically in the visual system. It is specifically discussed how the dependency of outer optic lobe development on retinal innervation can be assumed to have facilitated a first evolutionary phase of larval visual system reduction. Afferent input-contingent development of neu- ral compartments very likely plays a widespread role in adaptive brain evolution. Understanding the complete deconstruction of the larval optic neuropiles in Drosophila awaits expanded comparative analysis but has the promise to inform about further developmental trajectories and mechanisms underlying regressive evolution of the brain. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article focuses on the paired box (Pax) transcription factor subfamilies in the last common ancestor (LCA) of bilaterian animals. Topics include the importance of the DNA-binding protein as the developmental genetic tool kit animal body plan diversity, reconstruction of Pax gene tree, and evolutionary and functional complexity of the modular transcription factor gene family.

This paper uses the Society of Jesus as a case study to examine important developments in the early modern history of administration. It starts by analyzing the conceptual framework of Jesuit government, especially its centralized government. From here, the article moves on to examine the routines of administrative information-management, including the different forms of letter writing and the use of printed questionnaires. Special attention is then paid to every-day decision-making and the information acquired through it. The order's central archive is treated in a separate section. The archive is regarded as a key element of Jesuit administration, both in theory and daily routines. To balance the 'central' perspective of the first sections, the paper finally focuses on several critical voices that were part of a larger Jesuit administrative counter-discourse. [ABSTRACT FROM AUTHOR]

The article discusses the molecular genetic study of the mechanism which controls the differential opsin expression and cell fate determination in Drosophila larval eyes. It says that the drosophila larval and adult eyes use the same mechanism for the regulation of the opsin expression and photoreceptor cell specification. Moreover, significant lessons in the construction of homology between neural cell types and gene regulatory network evolution are being delivered by drosophila larval eyes.

Runx gene family transcription factors play important regulatory roles in metazoan development. The Drosophila genome contains four Runx genes, two of which are well studied ( runt and lozenge) and two of which have not been explored in depth yet ( CG42267 and CG34145). In the absence of paralog-specific orthologs in vertebrates, we investigated the evolutionary conservation of the Drosophila Runx genes in the genomes of mosquito, red flour beetle, honeybee, and distantly related Bilateria. All four Drosophila Runx genes are conserved in other endopterygote insects. Strikingly, their genetic linkage and genomic arrangement is also highly conserved despite past recombination events in the same genomic region. The preservation of Runx gene cluster organization for at least 300 million years resembles that of insect Hox and selected Wnt genes. We propose a model for the conserved cluster organization of developmental gene family paralogs based on differential coduplication of regulatory elements that act over long distances. [ABSTRACT FROM AUTHOR]

Dermatomycoses are contagious superficial fungal infections, which are highly prevalent in developed and developing countries. Caused by a range of Epidermophyton, Microsporum and Trichophyton species, dermatomycoses manifest on glabrous skin as ‘ringworm’, an annular scaly lesion with a variable inflammatory component. Itch is the chief subjective symptom, particularly in tinea cruris. Unless lesions are extensive or resistant to local therapy, dermatomycoses of glabrous skin are treated with topical antifungal agents, such as imidazoles and allylamines. Studies show, however, that the addition of a topical corticosteroid to imidazole therapy increases the bioavailability and prolongs the activity of the antimycotic, while rapidly reducing inflammatory symptoms. Travocort® is a combination of 1% isoconazole nitrate (ISN), a broad-spectrum imidazole with established antimicrobial activity and antimycotic efficacy, and 0.1% diflucortolone valerate (DFV), a potent topical corticosteroid with low systemic absorption and therefore a low risk of systemic glucocorticoid side-effects. In randomised, double-blind controlled clinical trials, Travocort® therapy showed a more rapid onset of action, faster relief of itch and other inflammatory symptoms, improved overall therapeutic benefits and better mycological cure rate during the first 2 weeks of treatment compared with ISN monotherapy. Travocort® is well tolerated and, because of prolonged ISN retention in the skin, provides antifungal protection against reinfection for some weeks after therapy. [ABSTRACT FROM AUTHOR]

Activation of Ras signaling by the receptor tyrosine kinase Sevenless plays important roles during retinal patterning and male germline development in Drosophila. Sevenless is orthologous to the vertebrate receptor tyrosine kinase c-ros. Remarkably, vertebrate ligands of c-Ros as well as non- Drosophila orthologs of the Sevenless ligand Bride of sevenless have remained elusive. Using newly available insect genome sequence information, we investigated the evolutionary conservation of the seven transmembrane domain protein gene bride of sevenless. Single orthologs were identified in the genomes of mosquito, flour beetle, and honeybee due to strong sequence conservation in the seven transmembrane domain. The extracellular region, however, is only detectably conserved within but not outside Diptera. Analysis of domain-specific substitution rates demonstrates correlated fast rates of evolutionary change in the extracellular domains of both bride of sevenless and sevenless. The rapid pace of sequence change explains why Sevenless ligands are difficult to detect by sequence similarity in distantly related phyla. Second, the conservation of bride of sevenless in flour beetle and honeybee raises the possibility of conserved Sevenless signaling controlled patterning processes in endopterygote insects. [ABSTRACT FROM AUTHOR]

Abstract: Key mechanisms of development are strongly constrained, and hence often shared in the formation of highly diversified homologous organs. This diagnostic is applied to uncovering ancient gene activities in the control of visual sense organ development by comparing the gene networks, which regulate larval eye, ocellus and compound eye specification in Drosophila. The comparison reveals a suite of shared aspects that are likely to predate the diversification of arthropod visual sense organs and, consistent with this, have notable similarities in the developing vertebrate visual system: (I) Pax-6 genes participate in the patterning of primordia of complex visual organs. (II) Primordium determination and differentiation depends on formation of a transcription factor complex that contains the products of the selector genes Eyes absent and Sine oculis. (III) The TGF-β signaling factor Decapentaplegic exerts transcriptional activation of eyes absent and sine oculis. (IV) Canonical Wnt signaling contributes to primordium patterning by repression of eyes absent and sine oculis. (V) Initiation of determination and differentiation is controlled by hedgehog signaling. (VI) Egfr signaling drives retinal cell fate specification. (VII) The proneural transcription factor atonal regulates photoreceptor specification. (VII) The zinc finger gene glass regulates photoreceptor specification and differentiation. [Copyright &y& Elsevier]

Abstract: Holometabolous insects like Drosophila proceed through two phases of visual system development. The embryonic phase generates simple eyes of the larva. The postembryonic phase produces the adult specific compound eyes during late larval development and pupation. In primitive insects, by contrast, eye development persists seemingly continuously from embryogenesis through the end of postembryogenesis. Comparative literature suggests that the evolutionary transition from continuous to biphasic eye development occurred via transient developmental arrest. This review investigates how the developmental arrest model relates to the gene networks regulating larval and adult eye development in Drosophila, and embryonic compound eye development in primitive insects. Consistent with the developmental arrest model, the available data suggest that the determination of the anlage of the rudimentary Drosophila larval eye is homologous to the embryonic specification of the juvenile compound eye in directly developing insects while the Drosophila compound eye primordium is evolutionarily related to the yet little studied stem cell based postembryonic eye primordium of primitive insects. [Copyright &y& Elsevier]

The selectin family of vascular cell adhesion molecules is comprised of structurally related carbohydrate binding proteins, which mediate the initial rolling of leukocytes on the activated vascular endothelium. Because this process is one of the crucial events in initiating and maintaining inflammation, selectins are proposed to be an attractive target for the development of new antiinflammatory therapeutics. Here, we demonstrate that the synthetic pan-selectin antagonist bimosiamose is effective in pre-clinical models of psoriasis as well as in psoriatic patients. In vitro bimosiamose proved to be inhibitory to E- or P-selectin dependent lymphocyte adhesion under flow conditions. Using xenogeneic transplantation models, bimosiamose reduced disease severity as well as development of psoriatic plaques in symptomless psoriatic skin. The administration of bimosiamose in patients suffering from psoriasis resulted in a reduction of epidermal thickness and lymphocyte infiltration. The clinical improvement was statistically significant ( P=0.02) as analyzed by comparison of psoriasis area and severity index before and after treatment. Assessment of safety parameters showed no abnormal findings. These data suggest that pan-selectin antagonism may be a promising strategy for the treatment of psoriasis and other inflammatory diseases. [ABSTRACT FROM AUTHOR]

The signaling factor Wingless regulates multiple steps during the postembryonic development of theDrosophilaeye. To obtain insight into the molecular regulation of embryonic eye development in primitive insects, we studied the expression ofwgand genes projected to interact withwgin the grasshopperSchistocerca americana. We find that the dynamic and complex expression ofwgin the early grasshopper procephalon results in three paired expression domains with relevance to eye primordium development. By comparison withDrosophila, these domains are compatible with a conserved function ofwgduring anteroposterior and dorsoventral axis formation by repression of retinal differentiation and stimulation of tissue proliferation. This is further supported by the expression of grasshopper orthologs of the retina determination genessine oculisandeyes absent, and by inhibition of retina differentiation in grasshopper eye primordia cultured with LiCl. Surprisingly, the expression ofwgand the grasshopper orthologs ofpannier,fringe,Delta, andIroquois complexis inconsistent with induction of midline centered Notch signaling activity, which is essential forDrosophilaretina development. Similarly substantial evolutionary divergence is found concerning the control of retina versus head epidermis specification. The transcription factorExtradenticle(Exd), which cooperates withwgin specifying theDrosophilahead epidermis, is not detected outside the labral and antennal primordia in the embryonic grasshopper head. Our results, which provide the first insight into the molecular control of eye primordium formation in primitive insects, suggest substantial modification of this process during the evolution of theDrosophilamode of postembryonic eye development. [ABSTRACT FROM AUTHOR]

Background: Grasshopper serves as important model system in neuroscience, development and evolution. Representatives of this primitive insect group are also highly relevant targets of pest control efforts. Unfortunately, the lack of genetics or gene specific molecular manipulation imposes major limitations to the study of grasshopper biology. Results: We investigated whether juvenile instars of the grasshopper species chistocerca americana are conducive to gene silencing via the systemic RNAi pathway. Injection of dsRNA corresponding to the eye colour gene vermilion into first instar nymphs triggered suppression of ommochrome formation in the eye lasting through two instars equivalent to 10-14 days in absolute time. QRT-PCR analysis revealed a two fold decrease of target transcript levels in affected animals. Control injections of EGFP dsRNA did not result in detectable phenotypic changes. RT-PCR and in situ hybridization detected ubiquitous expression of the grasshopper homolog of the dsRNA channel protein gene sid-1 in embryos, nymphs and adults. Conclusion: Our results demonstrate that systemic dsRNA application elicits specific and long-term gene silencing in juvenile grasshopper instars. The conservation of systemic RNAi in the grasshopper suggests that this pathway can be exploited for gene specific manipulation of juvenile and adult instars in a wide range of primitive insects. [ABSTRACT FROM AUTHOR]

While non-arthropod orthologues have been found for many Drosophila eye developmental genes, this has not been the case for the glass (gl) gene, which encodes a zinc finger transcription factor required for photoreceptor cell specification, differentiation, and survival. This study reports sequence and expression analysis of the gl orthologue of the flour beetle Tribolium castaneum. A strongly conserved C-terminal zinc finger binding region and a moderately conserved N-terminal transcriptional activation domain characterize the putative Tribolium gl protein. Tribolium gl transcripts were detected in the developing photoreceptors of the larval and adult visual system, the corpora cardiaca, and subsets of cells in the developing brain. This suggests that the gl function of specifying predominantly neuronal cells is strongly conserved. Using gl as a marker for the onset of larval photoreceptor differentiation, we studied the embryonic development of the Tribolium visual system. We find that the Tribolium larval eyes originate at the posterior margin of the embryonic eye lobes as defined by eye-field-specific wingless expression domains. This is consistent with the hypothesis that the larval visual organs (stemmata) of holometabolous insects were derived from and are therefore homologous to the posterior-most ommatidia of the adult retina in primitive nonholometabolous insects. [Copyright &y& Elsevier]

Ultraviolet irradiation represents a well-established treatment modality for inflammatory skin diseases. The aim of this study was to investigate the mechanisms of ultraviolet B radiation-induced keratinocyte insensitivity towards interferon-γ. Flow cytometric analyses indicated that ultraviolet B radiation temporarily inhibits the interferon-γ-induced activation of primary keratinocyte and HaCaT cells as measured by reduced intercellular adhesion molecule-1 (CD54) and HLA-DR upregulation. Western blot experiments have suggested that this is mediated by the ultraviolet B radiation-induced inhibition of signal transduction and transcription factor-1 phosphorylation. Neither interleukin-10 neutralization nor interleukin-10 addition had any effect on the ultraviolet B radiation-induced inhibition of interferon-γ induced intercellular adhesion molecule-1 expression. Furthermore, the supernatant from ultraviolet B-irradiated cells failed to inhibit the interferon-γ-induced CD54 and HLA-DR upregulation in nonradiated HaCaT cells. Moreover, irradiated cells from whom the supernatant was withdrawn 4 h after irradiation still showed a diminished interferon-γinduced response after 24 h. Thus, not soluble but intracellular factors might be involved in the ultraviolet B radiation-induced inhibition of interferon-γ-induced keratinocyte activation. Therefore, we analyzed the expression of members of suppressors of cytokine-signaling (SOCS) molecules using real-time polymerase chain reaction. We found a fast and strong upregulation of SOCS1 and SOCS3 but not of SOCS2 after ultraviolet B radiation. Similarly, ultraviolet B radiation induced the expression of these particular SOCS molecules in lesional psoriatic skin. As SOCS molecules are known inhibitors of signal transduction and transcription factor phosphorylation, which is essential for interferon-γ-induced intercellular adhesion molecule-1 and HLA-DR upregulation, this may explain the interferon-γ unresponsiveness after ultraviolet B radiation. [ABSTRACT FROM AUTHOR]

The molecular genetic dissection of Drosophila eye development led to the exciting discovery of a surprisingly large panel of genes and gene activities, which are functionally conserved across phyla. Little effort has yet been made towards pinpointing non-conserved gene functions in the developing Drosophila eye. This neglects the fact that Drosophila visual system development is a highly derived process. The comparative analysis of Drosophila eye development within insects can be expected to enhance resolution and accuracy of between phyla comparisons of eye development, and to reveal molecular developmental changes that facilitated the evolutionary transition from hemimetabolous to holometabolous insect development. Here we review aspects of early Drosophila eye development, which are likely to have diverged from the situation in more primitive insects, as indicated by results from work in the flour beetle Tribolium castaneum and the grasshopper Schistocerca americana. [ABSTRACT FROM AUTHOR]

We describe the first complete mitochondrial genome sequence from a representative of the insect order Coleoptera, the flour beetle Tribolium castaneum. The 15,881 bp long Tribolium mitochondrial genome encodes 13 putative proteins, two ribosomal RNAs and 22 tRNAs canonical for animal mitochondrial genomes. Their arrangement is identical to that in Drosophila melanogaster, which is considered ancestral for insects and crustaceans (Boore et al., 1998; ). Nucleotide composition, amino acid composition, and codon usage fall within the range of values observed in other insect mitochondrial genomes. Most notable features are the use of TCT as tRNASer(AGN) anticodon instead of GCT, which is used in most other arthropod species, and the relative scarcity of special sequence motifs in the 1431 bp long control region. Phylogenetic analysis confirmed resolving power in the conserved regions of the mitochondrial proteome regarding diversification events, which predate the emergence of pterygote insects, while little resolution was obtained at the level of basal perygote diversification. The partition of faster evolving amino acid sites harbored strong support for joining Lepidoptera with Diptera, which is consistent with a monophyletic Mecopterida. [Copyright &y& Elsevier]

The ability of interleukin-10 therapy to reduce the severity of exacerbated psoriasis has been demonstrated recently. Considering the immunobiologic properties of this cytokine we investigated the effects of long-term interleukin-10 application on the immune system and duration of psoriasis remission. We performed a placebo-controlled, double-blind, phase II trial using interleukin-10 in patients with chronic plaque psoriasis in remission. Patients received subcutaneous injections with either interleukin-10 (10 µg per kg body weight; n = 7) or placebo (n = 10) three times per week until relapse or study termination after 4 months. The treatment was well tolerated. In the placebo group almost all patients (90%) showed a relapse during the observation period. In contrast to this, only two of seven patients (28.6%) relapsed in the interleukin-10-treated group. Kaplan–Meier analysis revealed a significantly lower relapse incidence in the interleukin-10 than in the placebo group (p = 0.02). The mean relapse-free interval time was 101.6 ± 12.6 d in the interleukin-10 group in comparison with 66.4 ± 10.4 d in the placebo group. Immunologic activity of interleukin-10 application was indicated by an increase in soluble interleukin-2 receptor plasma levels and higher ex vivo interleukin-4 secretion capacities. Remarkably, a significant negative correlation was demonstrated between the interleukin-4 secretion capacity and Psoriasis Area and Severity Index score (r = -0.36, p < 0.01). Our data suggest that interleukin-10 therapy is immunologic effective, decreases the incidence of relapse and prolongs the disease-free interval in psoriasis. Its value should be further determined in larger trials and for the prevention of re-exacerbation of other inflammatory disorders with a similar immunologic profile. [ABSTRACT FROM AUTHOR]

Interleukin-10 is an important anti-inflammatory and immunosuppressive cytokine with major impact on several immune reactions, including regulatory mechanisms in the skin. Recently, we performed a phase II trial in psoriatic patients receiving subcutaneously interleukin-10 over 7 wk. The clinical response suggested that interleukin-10 might represent a novel anti-psoriatic drug. In order to understand better the mode of action and to elucidate the effects of systemic interleukin-10 treatment on the skin immune system, skin punch biopsies from sites different from interleukin-10 injection were analyzed. Biopsies were obtained from the patients before, at the end, and 3 wk after interleukin-10 therapy. The results are reported here. Histologic examination showed a decrease of several parameters reflecting the psoriatic disease activity as acanthosis and extension of the horny layer. Immunohistologic examination demonstrated decreasing numbers of infiltrating T cells, dermal CD1a+ cells, and a diminished proliferation of epidermal cells. Using a novel, quantitative reverse transcriptase–polymerase chain reaction approach a significant shift within the cytokine pattern was found. Interleukin-10 therapy led to a decrease of cutaneous interleukin-8 and interleukin-10 mRNA expression. Whereas no significant changes of interleukin-6, tumor necrosis factor-α, and interferon-γ expression were found, interleukin-4 was strongly upregulated suggesting a shift from a type 1 towards a type 2 cytokine pattern. The changes within the local cytokine pattern seem to be disease-related, as an inverse course was found in a single interleukin-10 nonresponding patient. Our findings demonstrate considerable effects of systemic interleukin-10 application on the skin immune systems, which might contribute to the anti-psoriatic activity of interleukin-10. [ABSTRACT FROM AUTHOR]

Indolent, primary cutaneous T-cell lymphomas (CTCL) are characterized by hyper-proliferation of malignant T-helper cells in the skin with a favorable prognosis in the early stages. Cytotoxic T cells (CTLs) are believed to be of major importance for tumor surveillance, but there is not yet sufficient evidence for a systemic anti-tumor response in mycosis fungoides (MF). On the contrary, there are hints of systemic immunodepression. We wondered whether signs of a systemic anti-tumor response were demonstrable in peripheral blood of patients with MF and CD30+ pleomorphic T cell lymphoma. Using multiparameter flow cytometry, we investigated blood samples from 39 CTCL patients at different stages and compared them with those from patients with psoriasis, atopic dermatitis, and healthy volunteers. In CTCL patients, an elevated number of lymphocytes expressing natural killer cell markers were found, as well as considerable T-cell activation, indicated by increased percentages of T cells expressing HLA-DR, IL-2 receptor α-chain, and transferrin receptor. The CD8+ T cells, which were the most strongly activated T-cell subset, were of polyclonal origin, as shown by their usage of different T-cell receptor families. The enhanced expression of activation antigens was associated with an increased proportion of CDS+ T cells with high expression of the adhesion molecule LFA-1, demonstrating the capacity for migration of these cells. These CD8+ effector cells are suspected to be CTLs and may be responsible for the favorable prognosis of indolent, primary CTCL. Interestingly, a stage-dependent decrease in T-cell activation antigen expression was observed, suggesting the development of a lack in tumor surveillance in advanced MF stages. Further investigations are necessary to verify whether any of the parameters determined are of predictive value for prognosis and response to therapy in CTCL. [ABSTRACT FROM AUTHOR]

Undetected tinea pedis in a patient with diabetes can lead to serious bacterial infections with potentially serious consequences, such as foot amputations. Here we report on a 60-year-old patient with diabetes presenting with pain, severe pruritus, and malodour in the foot's interdigital area, and subsequently, diagnosed with inflammatory tinea pedis with bacterial superinfection. The patient was successfully treated with Travocort cream containing isoconazole nitrate 1% and diflucortolone valerate 0.1%; marked improvement occurred within 5 days. [ABSTRACT FROM AUTHOR]

Examines the phylogenetic relationships of arthropods using sequence information from the nuclear ribosomal genes of taxa that cover most of the evolutionary divergence of each of the four major extant arthropod subgroups. Implications for the course of land colonization by the different arthropod groups; Interpretation of primitive features of arthropod morphology.

Recent large-scale studies of opsin gene contents in representatives of the largest order of insects, the Coleoptera (beetles), revealed that the blue wavelength-sensitive (B) opsin subfamily is absent in this clade, while the ultraviolet- (UV) and long wavelength-sensitive (LW) opsin subfamilies are broadly conserved with gene duplications possibly reintroducing blue sensitivity in select subclades. Little is known yet, however, how opsin genes are expressed in the compound eyes of beetles. In a previous study, we analyzed opsin gene expression in the red flour beetle Tribolium castaneum, a member of the family of darkling beetles (Tenebrionidae), and found that a singleton LW opsin homolog is homogeneously expressed in all photoreceptors of the compound eye retina with a singleton UV opsin homolog being co-expressed in the R7 subtype photoreceptors. To probe for the evolutionary conservation of these expression patterns, we isolated complete opsin transcript sequences from three additional species in the subfamily Tenebrionidae (Tribolium confusum, Tenebrio molitor, Zophobas morio) and studied their expression via whole mount in situ hybridization in the pupal retina. These experiments revealed very similar, if not identical, photoreceptor subtype-specific expression patterns in all three species compared with T. castaneum. Documenting a deep conservation of photoreceptor subtype-specific opsin gene expression in this range of darkling beetles, our study provides a first point of reference for broader comparative studies of retinal organization in the Coleoptera. [ABSTRACT FROM AUTHOR]

Small carrion beetles (Coleoptera: Leiodidae: Cholevinae) are members of cave communities around the world and important models for understanding the colonization of caves, adaptation to cave life, and the diversification of cave-adapted lineages. We developed a molecular phylogeny to examine the diversification of the hirtus-group of the small carrion beetle genus Ptomaphagus. The hirtus-group has no surfacedwelling members; it consists of 19 short-range endemic cave- and soil-dwelling species in the central and southeastern United States of America. Taxonomic, phylogenetic and biogeographic data were previously interpreted to suggest the hirtus-group diversified within the past 350,000 years through a series of cave colonization and speciation events related to Pleistocene climate fluctuations. However, our time-calibrated molecular phylogeny resulting from the analysis of 2,300 nucleotides from five genes across three mitochondrial regions (cox1, cytb, rrnL-trnL-nad1) for all members of the clade paints a different picture. We identify three stages of diversification in the hirtus-group: (1) ~10 million years ago (mya), the lineage that develops into P. shapardi, a soil-dwelling species from the Ozarks, diverged from the lineage that gives rise to the 18 cave-obligate members of the group; (2) between 8.5 mya and 6 mya, seven geographically distinct lineages diverged across Kentucky, Tennessee, Alabama and Georgia; six of these lineages represent a single species today, whereas (3) the 'South Cumberlands' lineage in Tennessee and Alabama diversified into 12 species over the past ~6 my. While the events triggering diversification during the first two stages remain to be determined, the distributions, phylogenetic relationships and divergence times in the South Cumberlands lineage are consistent with populations being isolated by vicariant events as the southern Cumberland Plateau eroded and fragmented over millions of years. [ABSTRACT FROM AUTHOR]

Background: Having conquered water surfaces worldwide, the semi-aquatic bugs occupy ponds, streams, lakes, mangroves, and even open oceans. The diversity of this group has inspired a range of scientific studies from ecology and evolution to developmental genetics and hydrodynamics of fluid locomotion. However, the lack of a representative water strider genome hinders our ability to more thoroughly investigate the molecular mechanisms underlying the processes of adaptation and diversification within this group. Results: Here we report the sequencing and manual annotation of the Gerris buenoi (G. buenoi) genome; the first water strider genome to be sequenced thus far. The size of the G. buenoi genome is approximately 1,000 Mb, and this sequencing effort has recovered 20,949 predicted protein-coding genes. Manual annotation uncovered a number of local (tandem and proximal) gene duplications and expansions of gene families known for their importance in a variety of processes associated with morphological and physiological adaptations to a water surface lifestyle. These expansions may affect key processes associated with growth, vision, desiccation resistance, detoxification, olfaction and epigenetic regulation. Strikingly, the G. buenoi genome contains three insulin receptors, suggesting key changes in the rewiring and function of the insulin pathway. Other genomic changes affecting with opsin genes may be associated with wavelength sensitivity shifts in opsins, which is likely to be key in facilitating specific adaptations in vision for diverse water habitats. Conclusions: Our findings suggest that local gene duplications might have played an important role during the evolution of water striders. Along with these findings, the sequencing of the G. buenoi genome now provides us the opportunity to pursue exciting research opportunities to further understand the genomic underpinnings of traits associated with the extreme body plan and life history of water striders. [ABSTRACT FROM AUTHOR]

Examines the role of pentoxifylline drug on the reduction of side effect of fumaric acid ester (FAE) therapy on patients with Psoriasis. Influence of releasing of tumor necrosis factor-alpha during initial phase of therapy on the adverse effect of FAE; Standard doses of FAE for treatment; Symptoms of the disease.

We present a mixed-integer linear program (MILP) for line planning with mode and route choice. In contrast to existing approaches, the mode and route decisions of passengers are modeled depending on the line plan and commercial solvers can be applied to solve the corresponding MILP. The model aims at finding line plans that maximize the profit for the railway operator while estimating the corresponding passenger demand with aggregate choice models. Hence, the resulting line plans are not only profitable for operators but also attractive to passengers. By suitable preprocessing we are able to apply any aggregate choice model for mode choices using linear constraints. We provide and test means to improve the computational performance. Our experiments on the Intercity network of the Randstad, a metropolitan area in the Netherlands, show that models which assume a fixed passenger assignment to modes cannot attract the passenger numbers they were designed for and therefore lead to inferior profit compared with our new model. Supplemental Material: The online appendices are available at https://doi.org/10.1287/trsc.2022.1171. [ABSTRACT FROM AUTHOR]