bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model-Based Re-Examination of the Effectiveness of Tumor/Immunohistochemistry and Direct-to-Sequencing Protocols for Lynch Syndrome Case Finding in Endometrial Cancer
Authors: Gudgeon James M. , Varner Michael W. , Hao Jing , Williams Marc S. 
Published: April 2021

PURPOSE: Despite widespread provision of Lynch syndrome (LS) screening programs, questions remain about the most effective and efficient protocol for LS case finding. The purpose of this study was to explore the performance of the two protocols widely shown to be the most efficient and effective, respectively: immunohistochemical (IHC) staining of tumor and direct-to-sequencing (DtS) in endometrial cancer populations. METHODS: Simulation models were developed to explore performance of the IHC and DtS protocols, updated to reflect current evidence. Analyses explicitly account for protocol complexity and failure points, as well as decreased sequencing costs. Key outcomes are percent of LS cases identified, total protocol costs and efficiency, and break-even analyses of sequencing costs. All costs are in 2020 US dollars (USD). RESULTS: Under plausible conditions, the IHC protocol is expected to identify 40%-78% of LS cases and DtS protocol from 49% to 97%. When the key variable success in proceeding to sequencing is fixed for both protocols at 50%, 75%, and 100%, the DtS protocol is 9%, 12%, and 16% better at case finding, respectively, than the IHC protocol. The break-even cost of sequencing is about $488 USD when the outcome is total direct testing protocol costs; it is about $670 USD when the outcome is cost per LS case detected. CONCLUSION: This study quantifies the plausible differences in the clinical effectiveness and cost-effectiveness of the two LS case-finding protocols. We demonstrate the large influence of success in proceeding to sequencing and potential impact of decreasing sequencing prices.
Pseudoautosomal genes in man
Authors: Goodfellow P. J. , Darling S. , Banting G. , Pym B. , Mondello C. , Goodfellow P. N. 
Published: April 2021

ABSTRACT
MIC2, which encodes the 12E7 antigen, is the only well-defined pseudoautosomal gene in man. We have isolated cDNA and genomic sequences corresponding to MIC2 and have produced monoclonal antibodies reacting with the 12E7 antigen. These molecular tools have been used to investigate the genetics and biochemistry of the MIC2 system. Recent results suggest that MIC2 is the most proximal of the currently defined pseudoautosomal markers and that the escape of M1C2 from X-inactivation may be intrinsic to an associated HTF island found at the 5’ end of the gene. Investigation of the inter-relationship between M1C2 and the XG locus has led us to postulate the existence of a second pseudoautosomal gene in man.
The use of Y-chromosome-specific repeated DNA sequences in the analysis of testis development in an XX/XY mouse
Authors: Singh Lalji , Matsukuma Shoichi , Jones K. W. 
Published: April 2021

ABSTRACT
A study, by means of Y-chromosome-specific repeated DNA probes, of mouse (ST) with small testes is reviewed. Mouse ST was shown to be a somatic mosaic of 10 % XY and 90 % XX cells. The cellular composition of the azoospermie testis reflected the overall proportions of XX and XY cells but it was found that XY cells predominated in the Sertoli cells of the testis tubules. These findings have been interpreted to indicate a fundamental role for the Sertoli cell in inducing testis organization in the indifferent gonadal rudiment, involving the expression of the Y chromosome.
The Y-chromosomal and autosomal testis-determining genes
Authors: De La Chapelle Albert 
Published: April 2021

ABSTRACT
It has been conclusively shown that a majority of XX males has acquired Y-chromosome-specific DNA (Y-DNA) sequences from their father’s Y chromosome. Testicular differentiation in these XX males is very likely induced by the testis-determining factor, TDF, normally located on Yp. The phenotypic expression of TDF in the presence of two X chromosomes is a male habitus, dysgenetic scrotal testes and no ambiguity of the genitalia.
Among those XX males who do not have Y-DNA detectable by presently used methods, some, but not all have ambiguity of the genitalia with or without hypospadias. XX true hermaphrodites are characterized by the presence of both testicular and ovarian tissue and have ambiguous genitalia. They do not have Y-DNA.
Several instances of familial XX maleness are critically analysed. In these pedigrees, most of the affected individuals are true hermaphrodites or XX males with ambiguous genitalia; in at least one family no Y-DNA occurred in these individuals. Typical autosomal dominant inheritance of XX testicular differentiation occurs in informative pedigrees. The suggested conclusion is that an autosomal dominant testis-determining factor, TDFA, exists. TDFA shows somewhat variable expression in XX individuals often causing genital ambiguity or true hermaphrodism. TDFA has no phenotypic effect on XY individuals. It is argued that XX males without presently detectable Y-DNA are caused either by TDF or TDFA.
Regeneration in the medial–lateral axis of the insect thoracic segment
Authors: French Vernon , Rowlands Tamara F. 
Published: April 2021

Abstract
We have studied pattern regulation in the medial-lateral axis of the insect segment by grafting legs of beetle larvae (Tenebrio molitor) in different orientations into different positions medial and lateral to the leg site. The Boundary Model and Polar Coordinate Model of the insect appendage predict various patterns of supernumerary leg regeneration, and these grafts were designed to test the predictions.
When a larval leg is grafted with normal anterior-posterior orientation medial to the normal leg, larvae and subsequent adults bear the graft plus a super-numerary leg. This is located where the lateral edge of the grafted leg confronted medial thorax (from the leg base across to the midline) and is orientated as a mirror image of the graft. The tarsal structure of supernumeraries resulting from grafts of the mesothoracic leg onto the metathorax shows that the supernumeraries may be derived from the graft, the host site or from both sources. Similarly, when a leg is grafted lateral to the leg site, a supernumerary forms at the confrontation between the medial edge of the graft and lateral thorax (from leg base across to the dorsal tergite). These results agree with the pre-dictions of both models and would indicate that the compartments or the positional values extend out from the leg to the midline and the edge of the tergite.
The two models differ in their predictions for the number, position and orientation of supernumeraries following 180° rotation of the grafted leg. When the rotated graft is placed lateral to the leg, larvae and adults form a single supernumerary which, in accordance with the Polar Coordinate Model, is lateral to the graft and orientated as a mirror image of it. However, the results of the corresponding medial graft cannot be readily explained by either model. Larvae form a single supernumerary either posterior or medial to the graft, suggesting a modified model with unequally spaced positional values, but the subsequent adult supernumeraries are almost all located medially.
Experiments involving a graft placed medial to the leg site frequently show duplication of the adult midline suture, an extra branch forming between the thorax and the graft or supernumerary leg. In this case, as in the regeneration of the dorsal midline, the extreme medial structure is formed between two more lateral regions, which need not come from opposite sides of the body, but must have opposite mediolateral polarities.
At present, no model can adequately explain all the results of grafting and extirpation on the insect ventral thorax.
Murine A type retroviruses promote high levels of gene expression in embryonal carcinoma cells
Authors: Morgan Richard A. , Christy Robert J. , Huang Ru Chih C. 
Published: April 2021

Abstract
The expression of Intracisternal A Particle (IAP) genes in the mouse embryonal carcinoma cell line PCC3 was investigated by cDNA cloning and transient gene expression assays. A group of 26 IAP cDNA clones, products of transcriptionally active IAP proviruses, were selected from a cDNA library made from undifferentiated PCC3 cell RNA. Several of these clones were characterized by restriction enzyme mapping and DNA sequence analysis. The DNA sequence in both the promoter and structural regions of two cDNAs closely resembles those of IAP genomic clones. Three new sequence elements were identified within the U3 region, an Spl transcription-factor-binding site, an adenovirus Ela enhancer sequence and a region of homology to a promoter element of adenovirus E4 gene. Hybrid constructs were made that place the U3/R region of the IAP cDNAs immediately 5’ to the chloramphenicol acetyl transferase (CAT) gene. IAP-CAT constructs were transfected into PCC3 cells, and cell extracts prepared and analysed for CAT enzyme activity and CAT RNA levels. IAP-CAT transfected cells were shown to contain substantial levels of CAT enzyme activity and to accumulate much greater levels of CAT RNA than two standard promoters, pRSVcat and pSVlcat. The ability of these A type retroviral promoters to function in PCC3 cells is in direct contrast to the near total restriction of normal C type retroviral expression in EC cells.
The role of diffusible molecules in regulating the cellular differentiation ofDictyostelium discoideum
Authors: Williams Jeffrey G. 
Published: April 2021

AbstractA central problem in developmental biology is to understand how morphogenetic fields are created and how they act to direct regionalized cellular differentiation. This goal is being pursued in organisms as diverse as moulds, worms, flies, frogs and mice. Each organism has evolved its own solution to the challenge of multicellularity but there appear to be common underlying principles and, once pattern formation is fully understood in any system, some general truths seem certain to be revealed. As a non-obligate metazoan, Dictyostelium discoideum has proven a particularly tractable system in which to identify and characterize cellular morphogens. Cyclic AMP and ammonia stimulate prespore cell differentiation and ammonia plays an additional role in repressing terminal cellular differentiation. Differentiation Inducing Factor (DIF) acts to direct prestalk cell differentiation and adenosine may play a synergistic role in repressing prespore cell differentiation. This review summarizes the evidence for these interactions and describes a number of models which show how this small repertoire of diffusible molecules, acting in concert, may direct the formation of a differentiated structure.
Microamputation of somatic embryos of the domestic carrot reveals apical control of axis elongation and root regeneration
Authors: Schiavone F. Mark 
Published: April 2021

Abstract
Somatic heart- and torpedo-stage embryos of the domesticated carrot, Daucus carota L., were severed at their midlengths to produce two halves termed apical and basal pieces. These pieces may be grafted or kept separate. Grafted embryos developed normally, with the exception that they tended to mature earlier than uncut control embryos. If kept separate, the apices grew at rates similar to grafted apices, while the basal ends, behaving as if they had been released from an inhibition of growth, rapidly elongated and matured (e.g. produced root hairs and a root cap) 3–4 days earlier than uncut controls. Grafted embryos treated with the transport inhibitor TIBA (2,3,5triiodobenzoic acid) had basal sections that behaved as if the sections had been kept separate. Additionally, resupplying IAA (indole-3-acetic acid) via a novel wick-bridge forced isolated basal pieces to behave as if the embryo apex were present. This apparent inhibition of root growth by the apex appears to be controlled by either the polar transport of auxin, and/or the accumulation of auxin at the root end. These experiments suggest that polar auxin transport has a greater influence on root, rather than on apex, development in these embryos.
Transcripts of α-cardiac and α-skeletal actins are early markers for myogenesis in the mouse embryo
Authors: Sassoon David A. , Garner Ian , Buckingham Margaret 
Published: April 2021

ABSTRACT
Among the first tissues to differentiate in the mammalian embryo are cardiac and subsequently skeletal striated muscle. We have developed specific cRNA probes corresponding to the 5′ noncoding regions of α-cardiac and α-skeletal actin mRNAs in order to investigate myogenesis in the mouse embryo. Transcripts coding for cardiac actin which is the major isoform of the adult heart can first be detected between 7·5 and 7·8 days p.c. in the developing heart and are observed in all somites as they are formed. In addition, α-skeletal actin transcripts are accumulated at much lower levels in cardiac tissue and newly formed somites; both heart and skeletal muscle show co expression of this actin gene pair at all stages of development examined. The fact that cardiac actin transcripts can be observed in the myotomal portion of the somite prior to muscle fibre differentiation indicates that cardiac actin transcripts (and to a lesser extent skeletal actin transcripts) are markers not only of striated muscle tissue, but also of earlier stages of the myogenic programme in vivo.
Calcium localization duringAcetabulariawhorl formation: evidence supporting a two-stage hierarchical mechanism
Authors: Harrison Lionel G. , Graham Keith T. , Lakowski Bernard C. 
Published: April 2021

ABSTRACTThe giant single-celled marine alga Acetabularia mediterranea (or A. acetabulum) repeatedly generates whorls of hairs at its growing tip. Theoretical considerations, and physicochemical analysis of the effect of extracellular calcium concentration on hair spacing, have suggested a two-stage mechanism, in which whorl pattern is preceded by a simple annular pattern. This analysis requires that, at the time of whorl determination, morphogenetically related calcium should still be distributed in the first-stage annular pattern. This paper reports studies of calcium distribution at closely spaced developmental stages from unpatterned growing tip to whorl expression. The sequence observed is that expected from the theoretical analysis. The fluorescence chelate used, chloro tetracycline, is believed to be specific for membrane-bound calcium. The results therefore suggest, but do not prove, that morphogenetically related calcium is attached to membrane-bound structures rather than Intracellular ones.
IGF-2 receptors are first expressed at the 2-cell stage of mouse development
Authors: Harvey Mark B. , Kaye Peter L. 
Published: April 2021

ABSTRACT
A specific IGF-2 receptor antiserum was used to reveal the presence of IGF-2 receptors during preimplantation development of mice. Receptors were present on 2-, 4- and 8-cell embryos, morulae, blastocysts, and on ICMs isolated prior to staining. There was no evidence for receptors on fertilized eggs. These observations confirm reports of the expression of IGF-2 receptor mRNA as early as the 2-cell stage and refine similar observations in blastocysts to confirm expression in both the TE and ICM. A potential auto/paracrine loop is thus one of the first products of activation of the embryonic genome and is expressed constitutively through preimplantation development.
Survival of XO mouse fetuses: effect of parental origin of the X chromosome or uterine environment?
Authors: Hunt Patricia A. 
Published: April 2021

ABSTRACT
Using a recombinant product from the structurally abnormal Y chromosome, Y*, female mice with a single X of either maternal or paternal origin were generated. The two types of females were produced on the same genetic background and differ only in the origin of the X chromosome. Hence it has been possible to assess the effect of parental origin of the X on survival of females with a single X chromosome. A highly significant prenatal loss of females with a single X of paternal origin, but no comparable loss of females with a single X of maternal origin was observed. The reduced viability of females with a paternally derived X could be mediated by the parental origin of the X (i.e. X chromosome imprinting) or alternatively, since the mothers of females with a single paternally derived X have only a single X chromosome, the effect could be mediated by the genotype of the mother (l.e. maternal uterine effect).
Positional cues governing cell migration in leech neurogenesis
Authors: Torrence Steven A. 
Published: April 2021

ABSTRACT
The stereotyped distribution of identified neurons and glial cells in the leech nervous system is the product of stereotyped cell migrations and rearrangements during embryogenesis. To examine the dependence of longdistance cell migrations on positional cues provided by other tissues, embryos of Theromyzon rude were examined for the effects of selective ablation of various embryonic cell lines on the migration and final distribution of neural and glial precursor cells descended from the bilaterally paired ectodermal cell lines designated q bandlets. The results suggest that neither the commitment of q-bandlet cells to migrate nor the general lateral-to-medial direction of their migration depend on interactions with any other cell line. However, the ability of the migrating cells to follow their normal pathways and to find their normal destinations does depend on interactions with cells of the mesodermal cell line, which appears to provide positional cues that specify the migration pathways.
Developmental and spatial regulation of a Dictyostelium prespore gene: cis-acting elements and a cAMP-induced, developmentally regulated DNA binding activity
Authors: Haberstroh Linda , Galindo Jose , Firtel Richard A. 
Published: April 2021

ABSTRACT
Previously, 5′ deletion analysis revealed three important upstream regions within the regulatory region of the cAMP-induced, prespore gene SP60 of D. discoidium, each of which contains a CA-rich sequence element (CAE: consensus CACACAYYYCACACAAA/T). In this study, we have made site-directed mutations within these CAEs and examined their effect on reporter gene activity (luciferase or lacZ). Point mutations within or deletion of the distal CAE (CAE-1), middle CAE (CAE-2) or proximal CAE (CAE-3) result in substantial decreases in promoter activity at 18 h of development or in response to cAMP. lacZ fusions made with the CAE mutant promoters produced novel β-gal staining patterns that suggest the presence of one or more morphogen gradients within the prespore zone of the slug and indicate that the CAEs are also important in regulating the spatial patterning of SP60 expression in the multicellular aggregate.
Gel mobility shift assays were used to identify activities from crude nuclear extracts that bind oligonucleotides containing the CAEs. One of the binding activities is not observed in extracts from vegetative cells or cells in early development and is induced during multicellular development with kinetics similar to those of SP60 gene expression. This activity is also induced in response to cAMP and specifically binds the wild-type CAE-1- and CAE-2-containing oligonucleotides. CAE-1 and CAE-2 oligonucleotides containing point mutations within the CAE core sequence neither bind to nor compete for the cAMP-induced, developmentally regulated factor(s) and result in substantial reductions in expression levels when substituted for the wild-type CAEs in vivo. The correlation between in vitro binding and in vivo function suggests that the CAE-l/CAE-2 binding activity may be involved in regulating cAMP and developmentally induced expression of SP60. A second, constitutive in vitro binding activity with high affinity to CAE-3 is also described. Models are proposed to relate the binding activities with the effects of the mutations on the spatial patterning of SP60-lacZ expression.
Budding-specific lectin induced in epithelial cells is an extracellular matrix component for stem cell aggregation in tunicates
Authors: Kawamura Kazuo , Fujiwara Shigeki , Sugino Yasuo M. 
Published: April 2021

ABSTRACT
We have examined immunocytochemically the expression, localization and in vivo function of a calciumdependent and galactose-binding 14 ×103Mr lectin purified from the budding tunicate, Polyandrocarpa misakiensis. Lectin granules first appeared in the inner epithelium of a double-walled bud vesicle. Soon after the bud entered the developmental phase, the granules were secreted into the mesenchymal space, where the lectin-positive extracellular matrix (ECM) developed. The lectin was also produced and secreted by granular leucocytes during budding. Hemoblasts, pluripotent stem cells in the blood, were often found in association with the ECM and they aggregated with epithelial cells to form organ rudiments. The lectin showed a high binding affinity for hemoblast precursors. The blockage of epithelial transformation of stem cells by galactose in in vivo bioassay was ineffective in the presence of the lectin. Polyclonal anti-lectin antibody prevented the hemoblasts spreading on the ECM and moving toward the epithelium, but it did not block the cell–cell adhesion of hemoblasts. By three days of bud development, lectin granules and ECM have almost disappeared from the developing bud together with a cessation of hemoblast aggregation. These results show that Polyandrocarpa lectin is a component of the ECM induced specifically in budding and suggest strongly that it plays a role in bud morphogenesis by directing the migration of pluripotent stem cells to the epithelium.
Microinjection of fluorescent tracers to study neural cell lineages
Authors: Wetts Richard , Fraser Scott E. 
Published: April 2021

Abstract
The examination of cell lineages is an important step towards understanding the developmental events that specify the various cell types in the organism. The mechanisms that control which cell types are formed, their locations, and their numbers remain unknown. Analyses of cell lineage in the frog neural retina have revealed that individual precursors are multipotent and are capable of producing almost any combination of cell types. In addition to giving rise to a wide range of phenotypes, the precursors can give rise to a wide range of clone sizes. Cell lineage studies in other systems indicate that some precursors are multipotent, like those in the retina, while others appear to produce a more restricted range of descendants, perhaps even a single phenotype. These differences in the developmental potential of precursor cells suggest that the nervous system uses several strategies for producing its many cell types. Investigation of these strategies, at the cellular and molecular level, requires more than a description of the normal cell lineages. We are now exploiting the frog neural retina to perform the experimental manipulations needed to elucidate these strategies.