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Developmental and genomic insight into the origin of the tardigrade body plan.

Tardigrada is an ancient lineage of miniaturized animals. As an outgroup of the well-studied Arthropoda and Onychophora, studies of tardigrades hold the potential to reveal important insights into body plan evolution in Panarthropoda. Previous studies have revealed interesting facets of tardigrade development and genomics that suggest that a highly compact body plan is a derived condition of this lineage, rather than it representing an ancestral state of Panarthropoda. This conclusion was based on studies of several species from Eutardigrada. We review these studies and expand on them by analyzing the publicly available genome and transcriptome assemblies of Echiniscus testudo, a representative of Heterotardigrada. These new analyses allow us to phylogenetically reconstruct important features of genome evolution in Tardigrada. We use available data from tardigrades to interrogate several recent models of body plan evolution in Panarthropoda. Although anterior segments of panarthropods are highly diverse in terms of anatomy and development, both within individuals and between species, we conclude that a simple one-to-one alignment of anterior segments across Panarthropoda is the best available model of segmental homology. In addition to providing important insight into body plan diversification within Panarthropoda, we speculate that studies of tardigrades may reveal generalizable pathways to miniaturization.

Animals

The genomic origin of the unique chaetognath body plan.

The emergence of animal phyla, each with their unique body plan, was a rapid event in the history of animal life, yet its genomic underpinnings are still poorly understood1. Here we investigate at the genomic, regulatory and cellular levels, the origin of one of the most distinctive animal phyla, the chaetognaths, whose organismal characteristics have historically complicated their phylogenetic placement2,3. We show that these characteristics are reflected at the cell-type level by the expression of genes that originated in the chaetognath lineage, contributing to adaptation to planktonic life at the sensory and structural levels4. Similarly to other members of gnathiferans (which also include rotifers and several other microscopic phyla)5,6, chaetognaths have undergone accelerated genomic evolution with gene loss and chromosomal fusions7,8. Furthermore, they secondarily duplicated thousands of genes9,10, without evidence for a whole-genome duplication, yielding, for instance, tandemly expanded Hox genes, as well as many phylum-specific genes. We also detected repeat-rich highly methylated neocentromeres and a simplified DNA methylation toolkit that is involved in mobile element repression rather than transcriptional control. Consistent with fossil evidence11,12, our observations suggest that chaetognaths emerged after a phase of morphological simplification through a reinvention of organ systems paralleled by massive genomic reorganization, explaining the uniqueness of their body plan.

Animals

Evolution of Orthonectida body plan.

Orthonectida is an enigmatic group of animals with still uncertain phylogenetic position. Orthonectids parasitize various marine invertebrates. Their life cycle comprises a parasitic plasmodium and free-living males and females. Sexual individuals develop inside the plasmodium; after egress from the host they copulate in the external environment, and the larva, which has developed inside the female infects a new host. In a series of studied orthonectid species simplification of free-living sexual individuals can be clearly traced. The number of longitudinal and transverse muscle fibers is gradually reduced. In the nervous system, simplification is even more pronounced. The number of neurons constituting the ganglion is dramatically reduced from 200 in Rhopalura ophiocomae to 4-6 in Intoshia variabili. The peripheral nervous system undergoes gradual simplification as well. The morphological simplification is accompanied with genome reduction. However, not only genes are lost from the genome, it also undergoes compactization ensured by extreme reduction of intergenic distances, short intron sizes, and elimination of repetitive elements. The main trend in orthonectid evolution is simplification and miniaturization of free-living sexual individuals coupled with reduction and compactization of the genome.

Animals

Phoronida-A small clade with a big role in understanding the evolution of lophophorates.

Phoronids, together with brachiopods and bryozoans, form the animal clade Lophophorata. Modern lophophorates are quite diverse-some can biomineralize while others are soft-bodied, they could be either solitary or colonial, and they develop through various eccentric larval stages that undergo different types of metamorphoses. The diversity of this clade is further enriched by numerous extinct fossil lineages with their own distinct body plans and life histories. In this review, I discuss how data on phoronid development, genetics, and morphology can inform our understanding of lophophorate evolution. The actinotrocha larvae of phoronids is a well documented example of intercalation of the new larval body plan, which can be used to study how new life stages emerge in animals with biphasic life cycle. The genomic and embryonic data from phoronids, in concert with studies of the fossil lophophorates, allow the more precise reconstruction of the evolution of lophophorate biomineralization. Finally, the regenerative and asexual abilities of phoronids can shed new light on the evolution of coloniality in lophophorates. As evident from those examples, Phoronida occupies a central role in the discussion of the evolution of lophophorate body plans and life histories.

Animals

The gastropod Lottia peitaihoensis as a model to study the body patterning of trochophore larvae.

The body patterning of trochophore larvae is important for understanding spiralian evolution and the origin of the bilateral body plan. However, considerable variations are observed among spiralian lineages, which have adopted varied strategies to develop trochophore larvae or even omit a trochophore stage. Some spiralians, such as patellogastropod mollusks, are suggested to exhibit ancestral traits by producing equal-cleaving fertilized eggs and possessing "typical" trochophore larvae. In recent years, we developed a potential model system using the patellogastropod Lottia peitaihoensis (= Lottia goshimai). Here, we introduce how the species were selected and establish sources and techniques, including gene knockdown, ectopic gene expression, and genome editing. Investigations on this species reveal essential aspects of trochophore body patterning, including organizer signaling, molecular and cellular processes connecting the various developmental functions of the organizer, the specification and behaviors of the endomesoderm and ectomesoderm, and the characteristic dorsoventral decoupling of Hox expression. These findings enrich the knowledge of trochophore body patterning and have important implications regarding the evolution of spiralians as well as bilateral body plans.

Animals

Use of body scanner in radiotherapy treatment planning.

CT body scans obtained on 98 patients before, during, and after radiotherapy were evaluated for their utility in radiotherapy treatment planning and in follow-up after radiotherapy. Twenty-two patients were studied after irradiation. Four received additional treatment, and continuing or planned treatment was withheld from another four on the basis of CT data. Tumor extent was clearly delineated on CT scan in 48/76 cases (63%), suggestive in 25/76 (33%), and not seen in only three (4%). Utilizing CT data relative to all other available tests, in 75 patients, total treatment volume was altered in 34 (45%), tumor coverage was marginal or inadequate in 35 (47%), and volume of normal tissue irradiated was changed in 34 (45%). CT scan data was judged essential for treatment planning in 41, or 55%, of patients studied. Unsuspected areas of tumor involvement were seen in 32 of 75 cases (43%). Use of the CT scan as a patient contour for radiotherapy treatment planning and alternative techniques for inputting the CT data to treatment planning computers are discussed. A simple inexpensive device to accomplish this is described. Speculations are made regarding the impact of CT scanners on transverse axial tomography units and treatment simulators as well as the potential application of the technique in brachytherapy dose computation.

Abdominal Neoplasms

Homes or hospitals? Contradictions of the urban crisis.

Medical expansion is threatening to eliminate many urban residential areas, despite criticisim that argues for comprehensive planning, reduced costs, less concentrated power in the health sector, and a reversal of "medicalization." Our research on expansion, which grew partly from personal participation in a local struggle against expanding institutions in Boston, revealed certain tensions in combining sociomedical research with concrete political practice. From events in Boston and from an exploratory review of periodicals, we recognized that medical expansion and community conflict occur frequently in cities throughtout the United States. Based on general theoretical perspectives from organizational analysis and political economy, we made several hypotheses that we tested through a questionnaire sent to all hospitals in the 20 largest cities of the United States and through other data available on the same hospitals. In large part, this empirical study confirmed our theoretical expectations that (a) larger medical centers show a greater tendency toward territorial growth than smaller hospitals; (b) bureaucratic and administrative dynamics lead to facilities that do not necessarily enhance patient care; (c) despite short-term cycles of expansion and contraction in public hospital growth, expansion projects are widespread and generate considerable political conflict; (d) because of the state's contradictory roles in regulation and social capital expenditures, opposition to medical expansion comes more from community organizations than from governmental monitoring or planning bodies; and (e) the needs of capital determine that medical expansion has a more detrimental impact on housing than on commercial or industrial facilities. Future expansion of private medical facilities is more likely than that of public facilities, although much private expansion may receive public subsidization. As ideologic patterns are demystified, the contradictions between medical expansion and housing needs can provide a focus for successful community organizing.

Boston

Abalone genomics reveals an ancient asymmetry axis and the multifunctionality of the mantle.

Gastropod diversification represents one of the most spectacular evolutionary radiations, underpinned by a fundamentally asymmetric body plan and diverse pigmentation patterns. To understand the genetic underpinnings of these cardinal traits, we constructed a chromosome-level genome assembly for the rainbow abalone, Haliotis iris. Integrating comparative genomics, histoembryology, and molecular assays, we identify a conserved regulatory association between the long non-coding RNA lncRNA1 and pitx that is associated with asymmetric mantle development. In H. iris, this association is supported by chromatin-contact evidence and exploratory data suggesting a possible miRNA-associated post-transcriptional component. Furthermore, we identify a wnt-mitf-tyr framework for melanogenesis and show that the mantle is the primary site of melanin synthesis. Concurrently, we identify mantle-enriched prestin genes that are vibration-responsive, consistent with a possible sensory specialization of the mantle. These findings provide molecular insight into asymmetry, pigmentation, and mantle multifunctionality in gastropods.

Animals

Investigating the Functions of Hox Genes Using Planarian Asexual Reproduction.

Hox genes are highly conserved developmental regulators instrumental to the formation of a wide range of diverse body plans across metazoans. While significant progress in the field of Hox gene research has been made, persistent challenges in unraveling their mechanisms of action and full repertoire of functions remain. To date, investigations of Hox gene function have been primarily conducted in research models belonging to ecdysozoa and vertebrata. Herein we summarize recent findings on Hox genes' roles in the asexual reproduction of the regenerative flatworm planaria, a member of the understudied superphylum Spiralia. We detail our optimized methods for planarian culture, gene perturbation, and induction of asexual reproduction. We aim to provide an experimentally tractable means to dissect Hox gene adult tissue functions underlying planarian asexual reproduction with broader relevance to Hox genes' established and emerging roles in regulating cellular behaviors, developmental patterning, animal behavior, and tissue regeneration.

Animals

Generation of Hoxa11-3XFLAG and Hoxd11-3XFLAG alleles to investigate Hox11 genome-wide binding.

Hox genes encode for evolutionary conserved transcription factors that direct the proper development of the body plan. Despite decades of research, little is known regarding their downstream target genes, especially in vertebrates. The strong evolutionary conservation of their DNA-binding homeodomain, their generic AT-rich binding sites, and the lack of specific antibodies has precluded rigorous examination. To circumvent these limitations, we have generated two mouse models in which a 3XFLAG epitope tag has been inserted into the 5' end of the coding sequence of both Hoxa11 and Hoxd11 loci via Cas9/CRISPR. The alleles have been validated by sequencing, PCR genotyping, western blotting, and protein expression analyses, demonstrating proper targeting and expression. Breeding these alleles in combination produces viable and fertile Hoxa11FLAG/FLAG; Hoxd11FLAG/FLAG animals, with no overt patterning defects unlike Hoxa11/Hoxd11 mutants that are infertile and have severe kidney and limb defects. By performing CUT&RUN and CUT&Tag analyses, we have confirmed DNA binding to a known Six2 enhancer in the developing kidney. These novel alleles will allow characterization of the genome-wide binding profile of Hox11 proteins in vivo.

Animals

A morphogenetic fate map constructed from Habrobracon juglandis gynandromorphs.

A morphogenetic fate map is presented for the parasitic wasp, Habrobracon juglandis. Twenty adult cuticular structures of 1211 haploid-diploid gynandromorphs were placed on the fate map using the sturtoid calculation. The overall shape and organization of the Habrobracon fate map are similar to those of the Drosophila fate mape, both of which approximate the shape of an insect embryo but show structures arranged in a manner resembling the adult body plan. Independent samples of gynandromorphs yield similar maps.

Animals

Electron microscopical studies on onchocerciasis. III. The onchocerca-nodule.

Six onchocerca-nodules from five Liberian patients were examined by electron microscopy. The bulk of cells in the centre of the nodules consists of lymphocytes and macrophages. The lymphocytes can be observed in various stages of differentiation. A major part of the macrophages shows degenerative changes with decrease of lysosomes and increase of fatty vacuoles. Near the worms epithelioid cells and giant cells can be found. Other cells in the nodule include polymorphonuclear neutrophils, eosinophils, plasma cells, and mast cells. Adult Onchocerca volvulus show the basic nematode body plan. The cuticle is subdivided into cortex and two layers with differently arranged fibrillar structures. The characteristics of the hypodermal cells are best seen in the lateral chords, in the interchordal regions the hypodermis is flattened by a muscle layer. The intestine typically contains pigment granules, the cells of the epithelium have folds of their cell membranes forming a basal labyrinth. The uterus consists of two tubes in which the development of the microfilariae from the early embryonic forms to the mature stages is examined.

Adult

Further progress in CT scanning and computerized radiation therapy treatment planning.

Total body computed tomography has introduced a unique method of obtaining body contours as well as anatomical representations for radiation therapy treatment planning. CT scanning combined with computerized radiation therapy treatment planning has improved accuracy and contributed greatly to the solution of complex treatment problems. CT scans can also be used to evaluate the progress of patients undergoing radiation therapy.

Computers

[Whole body computer tomography in the planning and follow-up of radiation therapy (author's transl)].

Whole body computer tomography provides accurate transverse sections of the areas to be irradiated in the position used for irradiation. The method has been used in 167 patients with malignant tumours in various parts of the body on a routine basis. Actual-size cuts allowed accurate delineation of the tumour or of the area to be irradiated with its neighbouring organs in 135 patients; in 66 patients CT scanning probided additional information regarding the extent of the tumour. Follow-up examinations carried out in 29 patients proved effective in showing the results of treatment. The introduction of the whole body scanner into radiation therapy has improbed radiation planning when compared with conventional methods because of the more accurate delineation of the area to be irradiated and of the surrounding organs.

Bone Neoplasms

Foreign body removal with the flexible fiberoptic bronchoscope.

Intrabronchial foreign bodies are occasionally encountered in adults but most available information in humans consists only of reports evaluating one or two cases. We surveyed our experience and found seven patients with intrabronchial foreign bodies who had been examined with the flexible fiberoptic bronchoscope, six of whom were managed successfully. Nine cases have been identified in the literature. Although there were no major complications in either our cases or those in the literature, several problems were identified which under other circumstances could have caused significant complications. We assessed all of these cases for situations which presented potential risk to the patient. These risks were grouped into the following problem categories: 1. selection of appropriate bronchoscope, 2. availability of appropriate instruments, 3. control of the foreign body, and 4. unexpected foreign bodies. Endoscopists planning to use the FFB in foreign body removal should be aware of the problems and hazards which may ensue if improperly managed, and should attempt to gain experience either in the animal laboratory or in models prior to approaching patients with foreign bodies with the flexible fiberoptic bronchoscope.

Adolescent

[Computed tomography of the whole body as a means of radiation planning (author's transl)].

Computed tomography of the whole body offers the first possibility to obtain individual tomographs with high resolution and in correct scale from all regions of the body. Using the "Sicograph", large-sized copies are obtained, which are therefore particularly useful for radiation planning. The size and location of tumors relative to critical organs can be determined exactly. The efficacy of radiation therapy in every individual case may be estimated on the basis of the controlled course (radiobiological information), [2,4,6,11,16,17,18,24,30], and the necessary modifications of the therapeutic schedule can be adopted early, allowing the complete utilization of the advantages of the shrinking field technique [8,19,26]. Since ultrasonic tomographs in many cases furnish additional information, we regard the combination of computed and ultrasonic tomography as the best way to obtain an accuracy of radiation planning previously unknown.

Humans