Growth in utero and cognitive function in adult life: follow up study of people born between 1920 and 1943.

OBJECTIVES--To examine the relation between fetal growth and cognitive function in adult life. DESIGN--A follow up study of men and women whose birth weights and other measurements of body size had been recorded at birth. SETTING--Hertfordshire, Preston, and Sheffield. SUBJECTS--1576 men and women born in Hertfordshire, Sheffield, or Preston between 1920 and 1943. MAIN OUTCOME MEASURES--Intelligence quotient as measured by the AH4 test and amount of decline in cognitive function with age as estimated by the difference between score on the Mill Hill vocabulary test and score on the AH4 test. RESULTS--Score on the intelligence test was higher in people who had a large biparietal head diameter at birth, but it was not related to any other measure of body size or proportions. No association was found between decline in cognitive function and any measure of size or proportions at birth. CONCLUSION--Impaired fetal growth was not associated with poorer cognitive performance in adult life. Adaptations made by the fetus in response to conditions that retard its growth seem to be largely successful in maintaining brain development.     

Human papilloma virus E6/E7 genes can expand the lifespan of human corneal fibroblasts

Summary Human corneal fibroblasts were infected with a retroviral delivery vector containing the E6 and E7 genes from human Papilloma virus type 16 in order to produce cell lines that have an expanded lifespan in culture. Morphologically, some of the trasfected corneal fibroblast lines appeared to have the normal spindle-shape morphology of diploid fibroblasts, whereas other lines appeared to have a more elongated morphology. All the cell lines were anchorage-dependent. Cells that had a normal morphology grew at a rate similar to normal diploid human corneal fibroblasts and had a population doubling time of 48 h. All E6/E7 expressing cell lines, regardless of morphology, produce types I, III, and V collagen, at levels similar to those observed in the parent corneal diploid fibroblast. These corneal fibroblast lines will be a usefulin vitro system to study collagen expression and fibril formation, as well as normal stroma development. These results also demonstrate that the use of E6/E7 genes to expand a cell’s lifespan can be a powerful tool because it does not appear to alter either the growth rate of the cell or collagen expression.     

Structural evolution of wheat chromosomes 4A, 5A,and 7B and its impact on recombination

The construction of comparative genetic maps of chromosomes 4A^m and 5A^m of Triticum monococcum and chromosomes of homoeologous groups 4, 5 and 7 of T. aestivum has provided insight into the evolution of these chromosomes. The structures of chromosomes 4A, 5A and 7B of modern-day hexaploid bread wheat can be explained by a 4AL/5AL translocation that occurred at the diploid level and is present both in T. monococcum and T. aestivum. Three further rearrangements, a 4AL/7BS translocation, a pericentric inversion and a paracentric inversion, have taken place in the tetraploid progenitor of hexaploid wheat. These structural rearrangements and the evolution of chromosomes 4A, 5A and 7B of bread wheat are discussed. The presence of the 4AL/5AL translocation in several Triticeae genomes raises two questions — which state is the more primitive, and is the translocation of mono- or poly-phylogenetic origin? The rearrangements that have occurred in chromosome 4A resulted in segments of both arms having different positions relative to the telomere, compared to 4A^m and to 4B and 4D. Comparisons of map length in these regions indicate that genetic length is a function of distance from the telomere, with the distal regions showing the highest recombination.     

Mapping quantitative trait loci for downy mildew resistance in pearl millet

Quantitative trait loci (QTLs) for resistance to pathogen populations of Scelerospora graminicola from India, Nigeria, Niger and Senegal were mapped using a resistant x susceptible pearl millet cross. An RFLP map constructed using F₂ plants was used to map QTLs for traits scored on F₄ families. QTL analysis was carried out using the interval mapping programme Mapmaker/QTL. Independent inheritance of resistance to pathogen populations from India, Senegal, and populations from Niger and Nigeria was shown. These results demonstrate the existence of differing virulences in the pathogen populations from within Africa and between Africa and India. QTLs of large effect, contributing towards a large porportion of the variation in resistance, were consistently detected in repeated screens. QTLs of smaller and more variable effect were also detected. There was no QTLs that were effective against all four pathogen populations, demonstrating that pathotype-specific resistance is a major mechanism of downy mildew resistance in this cross. For all but one of the QTLs, resistance was inherited from the resistant parent and the inheritance of resistance tended to be the result of dominance or over-dominance. The implications of this research for pearl millet breeding are discussed.     

Vaccination against Babesia bovis: T cells from protected and unprotected animals show different cytokine profiles

Vaccination of cattle against the haemoprotozoun parasite, Babesia bovis, with the recombinant antigen 11C5 resulted in 9 of 15 cattle being protected against challenge infection. The cellular immune responses of protected and unprotected cattle were compared in order to identify differences in response. No differences were observed in the pattern of change in various blood leukocyte populations throughout challenge infection. FACScan analysis revealed an increase in the proportion of cells bearing the CD2 marker in both protected and unprotected cattle over the course of infection. There were no observable differences in the frequency of various cell-surface markers between the unprotected and protected cattle. During the period of patent parasitaemia, in vitro cultures of peripheral blood mononuclear cells (PBMC) from protected cattle produced significantly more TNF- (P < 0.05) than cultures from unprotected cattle. TNF- concentrations remained at pre-challenge levels until day 10, when levels in the unvaccinated control and vaccinated/unprotected animals dropped. By peak parasitaemia, TNF- production in vitro was siguificantly greater (P < 0.05) in cultures of PBMCs from protected cattle. Interferon production showed an initial peak at day 5 in all cattle, followed by a decrease and a second peak at days 10–13 in protected cattle only, which coincided with resolution of the infection.     

The Mammalian Protein (rbet1) Homologous to Yeast Bet1p Is Primarily Associated with the Pre-Golgi Intermediate Compartment and Is Involved in Vesicular Transport from the Endoplasmic Reticulum to the Golgi Apparatus

Yeast Bet1p participates in vesicular transport from the endoplasmic reticulum to the Golgi apparatus and functions as a soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) associated with ER-derived vesicles. A mammalian protein (rbet1) homologous to Bet1p was recently identified, and it was concluded that rbet1 is associated with the Golgi apparatus based on the subcellular localization of transiently expressed epitope-tagged rbet1. In the present study using rabbit antibodies raised against the cytoplasmic domain of rbet1, we found that the majority of rbet1 is not associated with the Golgi apparatus as marked by the Golgi mannosidase II in normal rat kidney cells. Rather, rbet1 is predominantly associated with vesicular spotty structures that concentrate in the peri-Golgi region but are also present throughout the cytoplasm. These structures colocalize with the KDEL receptor and ERGIC-53, which are known to be enriched in the intermediate compartment. When the Golgi apparatus is fragmented by nocodazole treatment, a significant portion of rbet1 is not colocalized with structures marked by Golgi mannosidase II or the KDEL receptor. Association of rbet1 in cytoplasmic spotty structures is apparently not altered by preincubation of cells at 15°C. However, upon warming up from 15 to 37°C, rbet1 concentrates into the peri-Golgi region. Furthermore, rbet1 colocalizes with vesicular stomatitis virus G-protein en route from the ER to the Golgi. Antibodies against rbet1 inhibit in vitro transport of G-protein from the ER to the Golgi apparatus in a dose-dependent manner. This inhibition can be neutralized by preincubation of antibodies with recombinant rbet1. EGTA is known to inhibit ER-Golgi transport at a stage after vesicle docking but before the actual fusion event. Antibodies against rbet1 inhibit ER-Golgi transport only when they are added before the EGTA-sensitive stage. These results suggest that rbet1 may be involved in the docking process of ER- derived vesicles with the cis-Golgi membrane.     

Characterization of progenies of Triticum aestivum- Psathyrostachys juncea derivatives by using genomic in-situ hybridization

Using genomicin-situ hybridization (GISH) technique, 7 translocation-addition lines, 6 translocation and translocation-addition lines, 2 ditelosomic addition lines and 1 translocation line were identified fromTriticum aestivum L. -Psathyrostachys juncea (Fisch.) Nevski intergeneric hybrids, of which translocation-addition and translocation and translocation-addition lines were not found in other reports. No substitutions and disornic additions were detected in the, hybrids and breakages occurred in allP. juncea chromosomes studied. Results have shown that the improved GISH technique is a rapid and economical method for use in this field.     

Binding of simple carbohydrates and some N-acetyllactosamine-containing oligosaccharides to Erythrina cristagalli agglutinin as followed with a fluorescent indicator ligand

Erythrina cristagalli agglutinin, a dimeric lectin [J. L. Iglesias, et al. (1982) Eur. J. Biochem.123, 247–252] was shown by equilibrium dialysis to be bivalent for 4-methylumbelliferyl-β-d-galactoside. Upon binding to the lectin, this ligand showed a difference absorption spectrum with two maxima (at 322 and 336 nm) of equal intensity (Δ? = 1.2 × 10³m^?1 cm^?1). A similar spectrum with a comparable value of Δ? was obtained with 4-methylumbelliferyl-N-acetyl-β-d-galactosaminide. Binding of methyl-α-d-galactoside, lactose, and N-acetyllactosamine all produced small but equally intense protein difference spectra with a maximum (Δ? = 2.8 × 10² M^?1 cm^?1) at 291.6 nm. Upon binding of N-dansyl-d-galactosamine to the lectin, there was a fivefold increase in fluorescence intensity of this ligand. The association constant for N-dansyl-d-galactosamine was caused by a very favorable ΔS° of the dansyl group without affecting the strictly carbohydrate-specific character of binding. N-Dansyl-d-galactosamine was employed as a fluorescent indicator ligand in substitution titrations. This involved the use of simple carbohydrates, N-acetyllactosamine, and oligosaccharides which occur in the carbohydrate units of N-glycoproteins; the latter were Gal(β → 4)GlcNAc(β1 → 2)Man, Gal(β1 → 4)GlcNAc(β1 → 6)Man, and Gal(β1 → 4)GlcNAc(β1 → 6)[Gal(β1 → 4)GlcNAc(β1 → 2)]Man. The titrations were performed at two temperatures to determine the thermodynamic parameters. In the series N-acetyl-d-galactosamine, methyl-α-d-galactoside, and lactose, ?ΔH° increased from 24 to 41 kJ mol^?1; it increased further for N-acetyllactosamine and then remained unchanged for the N-acetyllactosamine-containing oligosaccharides (55 ± 1 kJ mol^?1). This indicated that the site specifically accommodated the disaccharide structure with an important contribution of the 2-acetamido group in the penultimate sugar. Beyond this, no additional contacts seemed to be formed. This conclusion also followed from considerations of ΔS° values which became more unfavorable in the above series (?23 to ?101 ± 4 J mol^?1 K^?1); the most negative value of ΔS° was observed with N-acetyllactosamine and the three N-acetyllactosamine-containing oligosaccharides.