A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11.

DiGeorge syndrome (DGS), a developmental field defect of the third and fourth pharyngeal pouches, is characterized by aplasia or hypoplasia of the thymus and parathyroid glands and by conotruncal cardiac malformations. Cytogenetic studies support the presence of a DGS critical region in band 22q11. In the present study, we report the results of clinical, cytogenetic, and molecular studies of 14 patients with DGS. Chromosome analysis, utilizing high-resolution banding techniques, detected interstitial deletions in five probands and was inconclusive for a deletion in three probands. The remaining six patients had normal karyotypes. In contrast, molecular analysis detected DNA deletions in all 14 probands. Two of 10 loci tested, D22S75 and D22S259, are deleted in all 14 patients. A third locus, D22S66, is deleted in the eight DGS probands tested. Physical mapping using somatic cell hybrids places D22S66 between D22S75 and D22S259, suggesting that it should be deleted in the remaining six cases. Parent-of-origin studies were performed in five families. Four probands failed to inherit a maternal allele, and one failed to inherit a paternal allele. On the basis of these families, and of six maternally and five paternally derived unbalanced-translocation DGS probands in the literature, parent of origin or imprinting does not appear to play an important role in the pathogenesis of DGS. Deletion of the same three loci in all 14 DGS probands begins to delineate the region of chromosome 22 critical for DGS and confirms the hypothesis that submicroscopic deletions of 22q11 are etiologic in the vast majority of cases.     

INVITED SPECIAL PAPER: History of the botanical teaching laboratory in the United States

The establishment of teaching laboratories for botany in the United States was strongly influenced in the early part of the 19th century by the founding of a laboratory of natural history at the Rensselaer School by Amos Eaton who inspired numerous educators, particularly women. By midcentury and later, botany programs were established at land-grant colleges and the so-called “new Botany” movement spread from them. In the latter part of the century additional changes were brought about by the influence of German laboratory activity and botanists’ reactions to the introduction of the Huxley-Martin biology programs to America. During these times, Americans were improving their own manufactured microscopes, laboratory supplies, and equipment capabilities. By the beginning of the 20th century, laboratory teaching of botanical subjects was widely accepted as normal in universities and colleges, as well as in some high schools.     

Molecular characterization of the marker chromosome associated with cat eye syndrome.

Cat eye syndrome (CES) is associated with a supernumerary bisatellited marker chromosome which is derived from duplicated regions of 22pter-22q11.2. In this study we have used dosage and RFLP analyses on 10 CES patients with marker chromosomes, by using probes to five loci mapped to 22q11.2. The sequences recognized by the probes D22S9, D22S43, and D22S57 are in four copies in all patients, but the sequences at the more distal loci, D22S36 and D22S75, are duplicated only in some individuals. D22S36 is present in three copies in some individuals, and D22S75 is present in two copies in the majority of cases. Only three individuals have a duplication of the most distal locus examined (D22S75), and these individuals have the largest marker chromosomes identified in this study. From the dosage analysis it was found that the marker chromosomes are variable in size and can be asymmetric in nature. There is no obvious correlation between the severity of the phenotype and the size of the duplication. The distal boundary of the CES critical region (D22S36) is proximal to that of DiGeorge syndrome, a contiguous-gene-deletion syndrome of 22q11.2.     

Eco-evolution from deep time to contemporary dynamics: The role of timescales and rate modulators

Eco-evolutionary dynamics, or eco-evolution for short, are often thought to involve rapid demography (ecology) and equally rapid heritable phenotypic changes (evolution) leading to novel, emergent system behaviours. We argue that this focus on contemporary dynamics is too narrow: Eco-evolution should be extended, first, beyond pure demography to include all environmental dimensions and, second, to include slow eco-evolution which unfolds over thousands or millions of years. This extension allows us to conceptualise biological systems as occupying a two-dimensional time space along axes that capture the speed of ecology and evolution. Using Hutchinson's analogy: Time is the ‘theatre’ in which ecology and evolution are two interacting ‘players’. Eco-evolutionary systems are therefore dynamic: We identify modulators of ecological and evolutionary rates, like temperature or sensitivity to mutation, which can change the speed of ecology and evolution, and hence impact eco-evolution. Environmental change may synchronise the speed of ecology and evolution via these rate modulators, increasing the occurrence of eco-evolution and emergent system behaviours. This represents substantial challenges for prediction, especially in the context of global change. Our perspective attempts to integrate ecology and evolution across disciplines, from gene-regulatory networks to geomorphology and across timescales, from today to deep time.     

The active site of the P99 beta-lactamase from Enterobacter cloacae.

Labelling the beta-lactamase of Enterobacter cloacae P99 with a poor substrate or a mechanism-based inactivator points to an active-site serine residue in a sequence closely resembling that of the ampC beta-lactamase. These results establish the P99 enzyme as a class-C beta-lactamase, and the concurrence of the two approaches helps to confirm the reliability of determining active-site sequences with the aid of mechanism-based inactivators.     

Isolation of lysine codon suppressors inEscherichia coli

Starting with anEscherichia coli strain containingglyT56, a glycine transfer RNA suppressor of the arginine codons AGA and AGG, and atrpA mutant containing lysine at position 211 of the tryptophan synthetase alpha chain, we have isolated AAG-suppressors that fall into two classes. In class 1 are dominant suppressors that arose with the simultaneous loss ofglyT56 activity. They are approximately 50% cotransducible withargE, as isglyT, and appear to be derived fromglyT56. Class 2 suppressors, located betweenpurE andtrp on theE. coli map, are not near any glycine tRNA genes, and may represent novel missense suppressors.     

Ultrastructural changes during encystment and germination of Bdellovibrio sp.

Under proper conditions, Bdellovibrio sp. strain W cells develop into bdellocysts in appropriate prey bacteria. After attachment and penetration of the prey cell, the encysting bdellovibrio began to accumulate inclusion material and increase in size, and was surrounded by an outer layer of amorphous electrondense material. The cytoplasm of the encysting cell appeared more electron dense, and nuclear areas appeared more compact. During germination of bdellocysts, the outer wall was uniformly broken down the inclusion material changed shape and affinity for the heavy metal stain, and the nuclear areas expanded. As the outer wall was dissolved, outgrowth began with the elongation of the germinant as it emerged from the prey ghost as an actively motile cell.     

Characterization of iron-sulfur clusters in rat liver submitochondrial particles by electron paramagnetic resonance spectroscopy. Alterations produced by chronic ethanol consumption

Iron-sulfur clusters present in rat liver submitochondrial particles were characterized by ESR at temperatures between 30 and 5.5 K combined with potentiometric titrations. The spectral and thermodynamic characteristics of the iron-sulfur clusters were generally similar to those previously reported for pigeon or bovine heart submitochondrial particles. Clusters N-1a, N-1b, N-2, N-3 and N-4 of NADH dehydrogenase had midpoint oxidation-reduction potentials at pH 7.5 of ?425, ?265, ?85, ?240 and ?260 mV, respectively. Clusters S-1 and S-3 of succinate dehydrogenase had midpoint potentials of 0 and +65 mV, respectively. The iron-sulfur cluster of electron-transferring flavoprotein-ubiquinone oxidoreductase exhibited the g_z signal at g = 2.08 and had a midpoint potential of +30 mV. This signal was relatively prominent in rat liver compared to pigeon or bovine heart.Submitochondrial particles from rats chronically treated with ethanol (36% of total calories, 40 days) showed decreases of 20–30% in amplitudes of signals due to clusters N-2, N-3 and N-4 compared to those from pair-fed control rats. Signals from clusters N-1b, S-1, S-3 and electron-transferring flavoprotein-ubiquinone oxidoreductase were unaffected. Microwave power-saturation behavior was similar for both submitochondrial particle preparations, suggesting that the lower signal amplitudes reflected a lower content of these particular clusters. NADH dehydrogenase activity was significantly decreased (46%), whilst succinate dehydrogenase activity was elevated (25%), following chronic ethanol consumption. The results indicate that chronic ethanol treatment leads to an alteration of the structure and function of the NADH dehydrogenase segment of the electron transfer chain. This alteration is one of the factors contributing to the lower respiration rates observed following chronic ethanol administration.     

WOMEN IN NINETEENTH CENTURY AMERICAN BOTANY; A GENERALLY UNRECOGNIZED CONSTITUENCY

Botany was thought to be a suitable study for young women in schools and an amateur avocation in the Nineteenth Century. A surprisingly large number of American women identified themselves as being seriously interested in botany. For example, in the first published directory of American botanists in 1873, 13 percent of the 599 names are women's and that increased to 16 percent of the 982 names in 1878. In this paper, 1,185 women have been identified as a sample of those actively interested in botany during the century. Less than 2% of them were active before 1870, and most of them, 67%, resided in New England and the Middle Atlantic States. Almost three quarters of them were unmarried, and only 10% had higher educational degrees although 15% had some identifiable profession. Some particular individuals are noted for their contributions to science, their activity as plant collectors, and their support of botanical societies. Though few American women became professional botanists in the Nineteenth Century, they constitute an important overlooked constituency for the developing profession of botany.