The role of intravascular ultrasound imaging in vascular brachytherapy

Intracoronary brachytherapy has recently emerged as a new therapy to prevent restenosis. Initial experimental work was achieved in animal models and the results were assessed by histomorphometry. Initial clinical trials used angiography to guide dosimetry and to assess efficacy. Intravascular ultrasound (IVUS) permits tomographic examination of the vessel wall, elucidating the true morphology of the lumen and transmural components, which cannot be investigated on the lumenogram obtained by angiography. This paper reviews the use of IVUS in the clinical studies of brachytherapy conducted to date. IVUS allows clinicians to make a thorough assessment of the remodeling of the vessel and appears to have a major role to play in facilitating understanding of the underlying mechanisms of action in this emerging field. The authors propose that state-of-the-art IVUS techniques should be employed to further knowledge of the mechanisms of action of brachytherapy in atherosclerotic human coronary arteries.     

A Single Genetic Determinant that Prevents Sex Reversal in C57BL-YPOS Congenic Mice

Sex determination in the mammalian embryo begins with the activation of a gene on the Y chromosome which triggers a cascade of events that lead to male development. The mechanism by which this gene, designated SRY in humans and Sry in mice (sex determining region of the Y chromosome), is activated remains unknown. Likewise, the downstream target genes for Sry remain unidentified at present. C57BL mice carrying a Y chromosome from Mus musculus musculus or molossinus develop normally as males. In contrast, C57BL/6 mice with the Y chromosome from M. m. domesticus often show sex reversal, i.e., develop as XY females. It has been documented that C57BL mice with the Y chromosome from Poschiavinus (Y^POS), a domesticus subtype, always develop as females or hermaphrodites. This suggests that a C57BL gene either up- or downstream of Sry is ineffective in interacting with Sry, which then compromises the processes that lead to normal male sex development. Nonetheless, by selective breeding, we have been able to generate a sex reversal-resistant C57BL/6-congenic strain of mice in which the XY^POS individuals consistently develop as normal males with bilateral testes. Because the resistance to sex reversal was transferred from strain 129S1/Sv (nonalbino) by simple selection over 13 backcross generations, it is inferred that a single autosomal gene or chromosomal region confers resistance to the sex reversal that would otherwise result. XY^POS normal males generated in these crosses were compared to XY^POS abnormal individuals and to C57BL/6 controls for sexual phenotype, gonadal weight, serum testosterone, and major urinary protein (MUP) level. A clear correlation was found among phenotypic sex, MUP level, and testis weight in the males and in the incompletely masculinized XY^POS mice. The fully masculinized males of the congenic strain resemble C57BL/6 males in the tested parameters. DNA analysis confirmed that these males, in fact, carry the Y^POS Sry gene.     

Improving model construction of profile HMMs for remote homology detection through structural alignment

Background  

Remote homology detection is a challenging problem in Bioinformatics. Arguably, profile Hidden Markov Models (pHMMs) are one of the most successful approaches in addressing this important problem. pHMM packages present a relatively small computational cost, and perform particularly well at recognizing remote homologies. This raises the question of whether structural alignments could impact the performance of pHMMs trained from proteins in the Twilight Zone, as structural alignments are often more accurate than sequence alignments at identifying motifs and functional residues. Next, we assess the impact of using structural alignments in pHMM performance.     

Testing for Hardy-Weinberg equilibrium in samples with related individuals

When the classical chi(2) goodness-of-fit test for Hardy-Weinberg (HW) equilibrium is used on samples with related individuals, the type I error can be greatly inflated. In particular the test is inappropriate in population isolates where the individuals are related through multiple lines of descent. In this article, we propose a new test for HW (the QL-HW test) suitable for any sample with related individuals, including large inbred pedigrees, provided that their genealogy is known. Performed conditional on the pedigree structure, the QL-HW test detects departures from HW that are not due to the genealogy. Because the computation of the QL-HW test becomes intractable for very polymorphic loci in large inbred pedigrees, a simpler alternative, the GCC-HW test, is also proposed. The statistical properties of the QL-HW and GCC-HW tests are studied through simulations considering a sample of independent nuclear families, a sample of extended outbred genealogies, and samples from the Hutterite population, a North American highly inbred isolate. Finally, the method is used to test a set of 143 biallelic markers spanning 82 genes in this latter population.     

Rise and fall of cotton aphid (Hemiptera: Aphididae) populations in southeastern cotton production systems

The impact of natural enemies on cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae), populations in cotton, Gossypium hirsutum L., production systems in the southeastern United States was evaluated over 3 yr in irrigated commercial cotton fields. Fungal epizootics caused by the entomopathogen Neozygites fresenii (Nowakowski) Batko reduced aphid numbers to subthreshold levels in 1999, 2000, and 2001 and occurred consistently in early to mid-July in all 3 yr. Scymnus spp. were the most abundant aphidophagous predators, although other coccinellid species and generalist predators such as spiders, fire ants, heteropterans, and neuropterans also were present. Studies using arthropod exclusion cages demonstrated little impact of predators or parasitoids on aphid populations before fungal epizootics. Arthropod natural enemies were most abundant after epizootics and may have suppressed aphid populations late in the season. Seed cotton yield, and lint quality were not affected by aphicide applications in any year of the study. Implications of these findings for aphid management in the southeastern United States are discussed.     

Reconstitution of a developmental clock in vitro: a critical role for astrocytes in the timing of oligodendrocyte differentiation

The rat optic nerve contains three types of macroglial cells: type 1 astrocytes first appear at embryonic day 16 (E16), oligodendrocytes at birth (E21), and type 2 astrocytes between postnatal days 7 and 10. The oligodendrocytes and type 2 astrocytes develop from a common, bipotential O-2A progenitor cell. We show here that although O-2A progenitor cells in E17 optic nerve prematurely stop dividing and differentiate into oligodendrocytes within 2 days in culture, when cultured on a monolayer of type 1 astrocytes, they continue to proliferate; moreover, the first cells differentiate into oligodendrocytes after 4 days in vitro, which is equivalent to the time that oligodendrocytes first appear in vivo. Our findings suggest that the timing of oligodendrocyte differentiation depends on an intrinsic clock in the O-2A progenitor cell that counts cell divisions that are driven by a growth factor (or factors) produced by type 1 astrocytes.