FGF-4 signaling is involved in mir-206 expression in developing somites of chicken embryos.

The microRNAs (miRNAs) are recently discovered short, noncoding RNAs, that regulate gene expression in metazoans. We have cloned short RNAs from chicken embryos and identified five new chicken miRNA genes. Genome analysis identified 17 new chicken miRNA genes based on sequence homology to previously characterized mouse miRNAs. Developmental Northern blots of chick embryos showed increased accumulation of most miRNAs analyzed from 1.5 days to 5 days except, the stem cell-specific mir-302, which was expressed at high levels at early stages and then declined. In situ analysis of mature miRNAs revealed the restricted expression of mir-124 in the central nervous system and of mir-206 in developing somites, in particular the developing myotome. In addition, we investigated how miR-206 expression is controlled during somite development using bead implants. These experiments demonstrate that fibroblast growth factor (FGF) -mediated signaling negatively regulates the initiation of mir-206 gene expression. This may be mediated through the effects of FGF on somite differentiation. These data provide the first demonstration that developmental signaling pathways affect miRNA expression. Thus far, miRNAs have not been studied extensively in chicken embryos, and our results show that this system can complement other model organisms to investigate the regulation of many other miRNAs.     

Sex determination and the maternal dominance hypothesis

The maternal dominance hypothesis has been derived from workwith humans which shows that women who are more dominant thanother women are more likely to conceive sons. In both animalsand humans dominance is a characteristic or personality trait,underpinned by testosterone and responsive to a range of environmentalchanges: physical, social and psychological. Studies of thesex ratio in the social sciences and animal behaviour eithersupport or are compatible with the idea that the sex-determiningrole of X- and Y-chromosome bearing spermatozoa may be precededby factors under maternal control which provide for differentialaccess of spermatozoa. Findings in reproductive physiology andphysiological psychology suggest that folh'cular testosteroneor a related hormone may play a critical role. Reproductivephysiologists have already identified maternal mechanisms whichcould provide the context for such a model.     

Analytical fan-beam and cone-beam reconstruction algorithms with uniform attenuation correction for SPECT

In this paper, we developed an analytical fan-beam reconstruction algorithm that compensates for uniform attenuation in SPECT. The new fan-beam algorithm is in the form of backprojection first, then filtering, and is mathematically exact. The algorithm is based on three components. The first one is the established generalized central-slice theorem, which relates the 1D Fourier transform of a set of arbitrary data and the 2D Fourier transform of the backprojected image. The second one is the fact that the backprojection of the fan-beam measurements is identical to the backprojection of the parallel measurements of the same object with the same attenuator. The third one is the stable analytical reconstruction algorithm for uniformly attenuated Radon data, developed by Metz and Pan. The fan-beam algorithm is then extended into a cone-beam reconstruction algorithm, where the orbit of the focal point of the cone-beam imaging geometry is a circle. This orbit geometry does not satisfy Tuy's condition and the obtained cone-beam algorithm is an approximation. In the cone-beam algorithm, the cone-beam data are first backprojected into the 3D image volume; then a slice-by-slice filtering is performed. This slice-by-slice filtering procedure is identical to that of the fan-beam algorithm. Both the fan-beam and cone-beam algorithms are efficient, and computer simulations are presented. The new cone-beam algorithm is compared with Bronnikov's cone-beam algorithm, and it is shown to have better performance with noisy projections.     

The use of computer-assisted diagnosis in cardiac perfusion nuclear medicine studies: A review (part 3)

Computer-assisted diagnosis (CAID) is commonly used to evaluate cardiac nuclear medicine studies such as thallium perfusion scans. Part 1 of this series (Journal of Digital Imaging, 5:209–222, 1992) reviewed the basic theory underlying CAID in nuclear medicine and its use in planar thallium imaging. Part 2 discussed the application of CAID to SPECT perfusion studies (Journal of Digital Imaging, 6:1–15, 1993). This article reviews new variations of CAID programs for SPECT imaging and the application of expert systems and neural networks to CAID of nuclear medicine perfusion studies.     

Fulminant disseminated Varicella Zoster virus infection without skin involvement.

BACKGROUND: Varicella Zoster virus (VZV) infection is potentially very serious in bone marrow transplant recipients, and may manifest as a disseminated visceral infection. This condition is generally accompanied by a vesicular rash. OBJECTIVES: We review here a case of fulminant fatal disseminated VZV infection, not accompanied by skin involvement, and the laboratory approaches currently available to diagnose this disease. STUDY DESIGN: Post mortem tissue samples were subjected to histopathological examination, and tested for herpesviruses by electron microscopy and PCR. RESULTS: Intranuclear inclusions were noted by histological examination in the lungs, liver, kidneys and bone marrow. Particles with a herpesvirus morphology were visualized in liver tissue. VZV DNA was detected in liver and bone marrow by PCR followed by sequencing of the amplicons. Viremia was documented by retrospective testing of the serum by PCR. CONCLUSIONS: A disseminated VZV infection which proved rapidly fatal was demonstrated in a case without skin manifestations. This rare presentation of VZV infection is potentially underdiagnosed. Testing for VZV viremia by PCR can at the very least suggest the diagnosis although whether plasma-associated viremia is truly pathognomonic of visceral disseminated infection remains to be established.     

Regulation of the replication initiator protein p65cdc18 by CDK phosphorylation

Cyclin-dependent kinases (CDKs) promote the initiation of DNA replication and prevent reinitiation before mitosis, presumably through phosphorylation of key substrates at origins of replication. In fission yeast, the p65^cdc18 protein is required to initiate DNA replication and interacts with the origin recognition complex (ORC) and the p34^cdc2 CDK. Here we report that p65^cdc18 becomes highly phosphorylated as cells undergo the G₁→S phase transition. This modification is dependent on p34^cdc2 protein kinase activity, as well as six consensus CDK phosphorylation sites within the p65^cdc18 polypeptide. Genetic interactions between cdc18⁺ and the S-phase cyclin cig2⁺ suggest that CDK-dependent phosphorylation antagonizes cdc18⁺ function in vivo. Using site-directed mutagenesis, we show that phosphorylation at CDK consensus sites directly targets p65^cdc18 for rapid degradation and inhibits its replication activity, as strong expression of a constitutively hypophosphorylated mutant form of p65^cdc18 results in large amounts of DNA over-replication in vivo. Furthermore, the over-replication phenotype produced by this mutant p65^cdc18 is resistant to increased mitotic cyclin/CDK activity, a known inhibitor of over-replication. Therefore, p65^cdc18 is the first example of a cellular initiation factor directly regulated in vivo by CDK-dependent phosphorylation and proteolysis. Regulation of p65^cdc18 by CDK phosphorylation is likely to contribute to the CDK-driven “replication switch” that restricts initiation at eukaryotic origins to once per cell cycle.     

GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies

A major challenge in understanding complex idiopathic generalized epilepsies has been the characterization of their underlying molecular genetic basis. Here, we report that genetic variation within the GABRD gene, which encodes the GABAA receptor delta subunit, affects GABA current amplitude consistent with a model of polygenic susceptibility to epilepsy in humans. We have found a GABRD Glu177Ala variant which is heterozygously associated with generalized epilepsy with febrile seizures plus. We also report an Arg220His allele in GABRD which is present in the general population. Compared with wild-type receptors, alpha1beta2Sdelta GABAA receptors containing delta Glu177Ala or Arg220His have decreased GABAA receptor current amplitudes. As GABAA receptors mediate neuronal inhibition, the reduced receptor current associated with both variants is likely to be associated with increased neuronal excitability. Since delta subunit-containing receptors localize to extra- or peri-synaptic membranes and are thought to be involved in tonic inhibition, our results suggest that alteration of this process may contribute to the common generalized epilepsies.