Keeping a lid on nodal : transcriptional and translational repression of nodal signalling

Nodal is an evolutionarily conserved member of the transforming growth factor-β (TGF-β) superfamily of secreted signalling factors. Nodal factors are known to play key roles in embryonic development and asymmetry in a variety of organisms ranging from hydra and sea urchins to fish, mice and humans. In addition to embryonic patterning, Nodal signalling is required for maintenance of human embryonic stem cell pluripotency and mis-regulated Nodal signalling has been found associated with tumour metastases. Therefore, precise and timely regulation of this pathway is essential. Here, we discuss recent evidence from sea urchins, frogs, fish, mice and humans that show a role for transcriptional and translational repression of Nodal signalling during early development

Panic and persecution: witch-hunting in East Lothian, 1628-1631

The Project is a regional case study of East Lothian during the national witchcraft panic of 1628-30. Events in East Lothian are considered, as are important individuals involved with cases in the county, some of whom may also have been involved in investigations further afield, particularly in Berwickshire. The project attempts to catalogue events as they occurred during the development, main body and decline of the panic. Using the evidence uncovered for this regional hunt, existing historiographical arguments will be discussed and larger topics of enquiry will be considered. Specific questions include: How do trial records reflect elite and common beliefs in witchcraft? What evidence is there for the existence of belief in fairies and the witch's familiar? Why did the panic develop and end when it did? What is the role of religious authorities compared to their secular counterparts? Does the witch stereotype break down in a period of intense hunting? The primary goal is to analyse events in East Lothian in order to determine how the trials in this region reveal more about the characteristics of witchhunting during a panic period, when trials take on a serial quality

Targeted gene disruption of the endogenous c-abl locus by homologous recombination with DNA encoding a selectable fusion protein

We have introduced a substitution mutation into the c-abl locus of murine embryonic stem cells by homologous recombination between exogenously added DNA and the endogenous gene. Model constructs were initially generated that consisted of a promoterless selectable neomycin resistance marker inserted into the v-abl gene of the complete Abelson murine leukemia virus genome, designed to be expressed either as a fusion protein or by translational restart. Tests of these viral genomes for transmission of v-abl and neo markers showed more stable coexpression in a protein fusion construct. The neo fusion was subcloned from this v-abl construct into a promoterless c-abl fragment, and the resulting DNA was used to transform embryonic stem cells. Direct screening of genomic DNAs showed that a high proportion of drug-resistant clones arose from homologous recombination into the endogenous c-abl locus

Smad4-dependent pathways control basement membrane deposition and endodermal cell migration at early stages of mouse development

<p>Abstract</p> <p>Background</p> <p>Smad4 mutant embryos arrest shortly after implantation and display a characteristic shortened proximodistal axis, a significantly reduced epiblast, as well as a thickened visceral endoderm layer. Conditional rescue experiments demonstrate that bypassing the primary requirement for Smad4 in the extra-embryonic endoderm allows the epiblast to gastrulate. Smad4-independent TGF-β signals are thus sufficient to promote mesoderm formation and patterning. To further analyse essential Smad4 activities contributed by the extra-embryonic tissues, and characterise Smad4 dependent pathways in the early embryo, here we performed transcriptional profiling of Smad4 null embryonic stem (ES) cells and day 4 embryoid bodies (EBs).</p> <p>Results</p> <p>Transcripts from wild-type versus Smad4 null ES cells and day 4 EBs were analysed using Illumina arrays. In addition to several known TGF-β/BMP target genes, we identified numerous Smad4-dependent transcripts that are mis-expressed in the mutants. As expected, mesodermal cell markers were dramatically down-regulated. We also observed an increase in non-canonical potency markers (<it>Pramel7</it>, <it>Tbx3</it>, <it>Zscan4</it>), germ cell markers (<it>Aire</it>, <it>Tuba3a</it>, <it>Dnmt3l</it>) as well as early endoderm markers (<it>Dpp4</it>, <it>H19</it>, <it>Dcn</it>). Additionally, expression of the extracellular matrix (ECM) remodelling enzymes <it>Mmp14 </it>and <it>Mmp9 </it>was decreased in Smad4 mutant ES and EB populations. These changes, in combination with increased levels of <it>laminin alpha1</it>, cause excessive basement membrane deposition. Similarly, in the context of the Smad4 null E6.5 embryos we observed an expanded basement membrane (BM) associated with the thickened endoderm layer.</p> <p>Conclusion</p> <p>Smad4 functional loss results in a dramatic shift in gene expression patterns and in the endodermal cell lineage causes an excess deposition of, or an inability to breakdown and remodel, the underlying BM layer. These structural abnormalities probably disrupt reciprocal signalling between the epiblast and overlying visceral endoderm required for gastrulation.</p

Correspondence to General William Robertson Boggs, 1860s: October 28, 1867 - February 18, 1869

Box 1, Folder 1: W.R. Boggs Family Papers Correspondence to General William Robertson Boggs, 1860s: October 28, 1867 - February 18, 1869https://digitalcommons.wofford.edu/littlejohnboggs/1000/thumbnail.jp

Effect of Single Set Dynamic and Static Stretching Exercise on Jump Height in College Age Recreational Athletes

This study examined the effects of single set dynamic and static stretching on vertical jump height and hip and knee range of motion in a sample of college age recreational males. Forty-two males (aged 18-24) healthy, physically active volunteers participated as subjects in this investigation and were randomly assigned to one of three groups (1 set of 20 seconds dynamic stretch, 1 set of 20 second static stretch, or control). The knee and hip range of motion, sit and reach, and jump height were measured before and after the treatment condition. The same measures were performed on the control group that sat for 12 minutes. All subjects began with a five minute warm-up on a cycle ergometer. Following the warm-up period, subjects immediately began their stretching program. Results of the investigation showed significant changes from pre-to-post for all dependent measures (p \u3c 0.05). A significant difference between groups was found for sit and reach in the SS + DS groups (p \u3c 0.05). However, there were no significant differences between groups for jump height or knee and hip range of motion. The results of the present study suggest that static and dynamic stretching for 20 seconds prior to a vertical jump can improve vertical jump height and hip and knee range of motion in a sample of male college age recreational athletes. Future research is needed to investigate the effect of single set stretching exercise prior to activities requiring maximal force production that includes athletes and female subjects

The Effect of an Early Education Program on Adult Health: The Carolina Abecedarian Project Randomized Controlled Trial

Objectives. We explored whether a successful randomized controlled trial of early education, the Carolina Abecedarian Project (ABC), which enrolled infants from 1972 to 1977 at the Frank Porter Graham Child Development Institute in Chapel Hill, North Carolina, improved health outcomes and behaviors by 21 years of age. Methods. ABC randomized 111 infants to receive an intensive early education program or nutritional supplements and parental counseling alone; participants have been followed to the present day. We examined the effect of ABC on health outcomes and behavioral risk factors when participants were aged 21 years, and then explored the mediators of this relationship. Results. Relative to the control group, the ABC treatment group was previously found to have improved cognition and educational attainment. We found that the intervention also improved heath (P = .05) and health behaviors (P = .03) when participants were aged 21 years. These improvements in behaviors were not mediated by IQ, math and reading scores at 15 years of age, educational attainment, or health insurance. Conclusions. Effective early education programs may improve health and reduce risky health behaviors in adulthood