Molecular analysis of 24 Alagille syndrome families identifies a single submicroscopic deletion and further localizes the Alagille region within 20p12.

Alagille syndrome (AGS) is a clinically defined disorder characterized by cholestatic liver disease with bile duct paucity, peculiar facies, structural heart defects, vertebral anomalies, and ocular abnormalities. Multiple patients with various cytogenetic abnormalities involving 20p12 have been identified, allowing the assignment of AGS to this region. The presence of interstitial deletions of varying size led to the hypothesis that AGS is a contiguous gene deletion syndrome. This molecular analysis of cytogenetically normal AGS patients was performed in order to test this hypothesis and to refine the localization of the known AGS region. Investigation of inheritance of simple tandem repeat polymorphism alleles in 67 members of 24 cytogenetically normal Alagille families led to the identification of a single submicroscopic deletion. The deletion included loci D20S61, D20S41, D20S186, and D20S188 and presumably intervening uninformative loci D20S189 and D20S27. The six deleted loci are contained in a single YAC of 1.9 Mb. The additional finding of multiple unrelated probands who are heterozygous at each locus demonstrates that microdeletions at known loci within the AGS region are rare in cytogenetically normal patients with this disorder. This suggests that the majority of cases of AGS may be the result of a single gene defect rather than a contiguous gene deletion syndrome.     

Methionine Sulfoximine Effects on C4 Plant Leaf Discs: Comparison with C3 Species

Methionine sulfoximine caused ammonia accumulation and photosyntheticrate inhibition in leaf discs from two C₄ species, Zea maysL. cv. F. M. Cross (Hybrid) and Sorghum bicolor L. Moench cv.NC-70X, as well as one C₃ plant species, Datura stramonium L.cv. stramonium. Similar results were obtained earlier with theC₃ species Spinacia oleracea L. The effect occurred in the absenceof inorganic nitrogen reduction and was light dependent. Ammoniaaccumulation rates were similar in all four species examined.The results support a role for glutamine synthetase in leafammonia recycling in both C₄ and C₃ leaves. ¹ Current address: Cetus Madison Corporation, 2208 Parview Road,Middleton, WI 53562, U.S.A. (Received November 2, 1981; Accepted April 28, 1982)     

Adherent cell requirement for PWM-stimulated factor suppression of natural killer cytotoxicity

Natural killer cytotoxicity is enhanced in a 5-day mixed-leukocyte culture (MLC). This augmentation of NK can be suppressed by factor released from pokeweed-mitogen (PWM)-activated peripheral blood cells. To maximize activity, the PWM-soluble factor must be present within the first 6 hr of the MLC, and is required to be in the culture for at least 4 hr. The affect of the PWM factor is not due to the destruction of either effector or stimulator cells. This factor does, however, require the presence of an adherent, non-T cell in the effector population. Directly incubating adherent cells with the PWM-induced soluble factor activates this population to mediate suppression. Thus the adherent cells are required for the PWM-induced suppression of NK cytotoxicity, indicating a possible regulatory mechanism for this cytotoxicity.     

The mitogenic properties of rabbit anti-mouse brain serum

The mitogenic activity of heterologous rabbit anti-mouse brain sera (RAMB) was investigated. By complement-dependent cytotoxicity and indirect immunofluorescence, RAMB was T-cell specific. Mitogenic activity was assessed by determination of [³H]thymidine incorporation into DNA. RAMB was mitogenic for spleen cells for Thy 1.1- and Thy 1.2-positive mouse strains. Maximal mitogenic responsiveness to RAMB occurred on Day 3 of culture. The incorporation of [³H]uridine into RNA and [³H]leucine into protein and percentage of blast cells in culture were also significantly increased following RAMB stimulation. The mitogenic activity of RAMB was abrogated by adsorption of the sera with BALB/c or AKR thymocytes or brains or with RL♂ 1.3+, a Thy 1.2-bearing T-cell lymphoma of BALB/c origin. In contrast, the mitogenic activity was not removed when RAMB sera were absorbed with RL♂ 1.4?, a variant of RL♂ 1 which appears to specifically lack cell surface Thy 1 determinants. These data suggest that the mitogenic activity of RAMB is Thy 1 directed. RAMB mitogenicity is T-cell dependent. Spleen cells from normal and heterologous nu/+ mice respond to RAMB, while spleen cells from nu/nu mice do not respond. Normal thymocytes and cortisone-resistant thymocytes do not respond mitogenically to RAMB. The response of unseparated spleen cells to RAMB is also macrophage dependent. Nylon-wool column-purified splenic T cells respond to high concentrations of RAMB in the absence of exogenous macrophages but do not respond to lower concentrations of RAMB unless exogenous macrophages are added to the cultures. Nylon-wool-adherent cells, which are B-cell enriched and relatively T-cell depleted, also respond to RAMB, suggesting that in the presence of even small numbers of T cells, B cells can be recruited into the response.     

The acetylcholinesterase genes of C. elegans: identification of a third gene (ace-3) and mosaic mapping of a synthetic lethal phenotype

In C. elegans, the newly identified ace-3 is the third gene affecting acetylcholinesterase (AChE) activity. ace-3 II specifically affects class C AChE and is unlinked to ace-1 X or ace-2 I, which affect the other two AChE classes (A and B, respectively). Strains homozygous for an ace-3 mutation have no apparent behavioral or developmental defect; ace-1 ace-3 and ace-2 ace-3 double mutants are also nearly wild type. In contrast, ace-1 ace-2 ace-3 triple mutant animals are paralyzed and developmentally arrested; their embryonic development is relatively unimpaired, but they are unable to grow beyond the hatching stage. Based on the analysis of genetic mosaics, we conclude that in the absence of ace-2 and ace-3 function, the expression of ace-1(+) in muscle cells, but not in neurons, is essential for postembryonic viability.     

Two-phase strategy of controlling motor coordination determined by task performance optimality

A quantitative model of optimal coordination between hand transport and grip aperture has been derived in our previous studies of reach-to-grasp movements without utilizing explicit knowledge of the optimality criterion or motor plant dynamics. The model’s utility for experimental data analysis has been demonstrated. Here we show how to generalize this model for a broad class of reaching-type, goal-directed movements. The model allows for measuring the variability of motor coordination and studying its dependence on movement phase. The experimentally found characteristics of that dependence imply that execution noise is low and does not affect motor coordination significantly. From those characteristics it is inferred that the cost of neural computations required for information acquisition and processing is included in the criterion of task performance optimality as a function of precision demand for state estimation and decision making. The precision demand is an additional optimized control variable that regulates the amount of neurocomputational resources activated dynamically. It is shown that an optimal control strategy in this case comprises two different phases. During the initial phase, the cost of neural computations is significantly reduced at the expense of reducing the demand for their precision, which results in speed-accuracy tradeoff violation and significant inter-trial variability of motor coordination. During the final phase, neural computations and thus motor coordination are considerably more precise to reduce the cost of errors in making a contact with the target object. The generality of the optimal coordination model and the two-phase control strategy is illustrated on several diverse examples.     

WEIGHT AND CULMEN CHANGES IN

Summers, R.W. &; Kaletja-Summers, B. 1996. Seasonal use of sandflats and saltmarshes by waders at low and high tide at Langebaan Lagoon, South Africa. Ostrich 67:72-79.

Migrant and resident waders were counted on sandflats and saltmarshes at low and high tide during two summers (197576 and 1976–77) and two winters (1975 and 1976) at Langebaan Lagoon. Intertidal sandflats supported higher densities of waders than saltmarshes at low tide in summer (18.7 and 17.2 waders ha' on sandflats compared with 0.4 and 2.9 waders ha' on saltmarshes) and winter (0.9 and 3.1 compared with 0.6 and 1.9 waders ha I for the two years). At high tide, most waders moved onto saltmarshes, attaining densities of 70.4 and 53.6 waders ha' in the two summers, and 5.7 and 15.6 birds ha' in the two winters. Resident waders comprised 0.3 and 0.8% of the wader community in the two summers and 41 and 5% in the two winters. They were also at higher densities in winter than in summer. The composition of wader communities on the different sandflats varied little in summer and Curlew Sandpipers were the most abundant species on all sandflats. Minor variations in species composition included proportionately more Turnstones at the mouth of the lagoon, more Sanderlings and Whimbrels in the mid sections and more Terek Sandpipers, Greenshanks and Curlews in the upper part. Larger percentages of waders were foraging on the sandflats at low tide in both summer (96 and 92% for the two summers) and winter (85 and 94% for the two winters) compared with the saltmarshes (73 and 79% in the two summers and 60 and 81% in the two winters). A larger proportion of small waders were foraging on sandflats at low tide compared with large waders. At high tide on the saltmarshes, the percent of foraging birds was lower in summer (29% for both summers) than in winter (36 and 78% for the two winters), perhaps reflecting seasonal changes in energy requirements.     

High‐Voltage Photogeneration Exclusively via Aggregation‐Induced Triplet States in a Heavy‐Atom‐Free Nonplanar Organic Semiconductor

The electron–hole recombination kinetics of organic photovoltaics (OPVs) are known to be sensitive to the relative energies of triplet and charge‐transfer (CT) states. Yet, the role of exciton spin in systems having CT states above 1.7 eV—like those in near‐ultraviolet‐harvesting OPVs—has largely not been investigated. Here, aggregation‐induced room‐temperature intersystem crossing (ISC) to facilitate exciton harvesting in OPVs having CT states as high as 2.3 eV and open‐circuit voltages exceeding 1.6 V is reported. Triplet excimers from energy‐band splitting result in ultrafast CT and charge separation with nonradiative energy losses of <250 meV, suggesting that a 0.1 eV driving force is sufficient for charge separation, with entropic gain via CT state delocalization being the main driver for exciton dissociation and generation of free charges. This finding can inform engineering of next‐generation active materials and films for near‐ultraviolet OPVs with open‐circuit voltages exceeding 2 V. Contrary to general belief, this work reveals that exclusive and efficient ISC need not require heavy‐atom‐containing active materials. Molecular aggregation through thin‐film processing provides an alternative route to accessing 100% triplet states on photoexcitation.     

Analysis of Caenorhabditis elegans acetylcholine synthesis mutants reveals a temperature-sensitive requirement for cholinergic neuromuscular function

In Caenorhabditis elegans, the cha-1 gene encodes choline acetyltransferase (ChAT), the enzyme that synthesizes the neurotransmitter acetylcholine. We have analyzed a large number of cha-1 hypomorphic mutants, most of which are missense alleles. Some homozygous cha-1 mutants have approximately normal ChAT immunoreactivity; many other alleles lead to consistent reductions in synaptic immunostaining, although the residual protein appears to be stable. Regardless of protein levels, neuromuscular function of almost all mutants is temperature-sensitive, i.e., neuromuscular function is worse at 25° than at 14°. We show that the temperature effects are not related to acetylcholine release, but specifically to alterations in acetylcholine synthesis. This is not a temperature-dependent developmental phenotype, because animals raised at 20° to young adulthood and then shifted for 2 h to either 14° or 25° had swimming and pharyngeal pumping rates similar to animals grown and assayed at either 14° or 25°, respectively. We also show that the temperature-sensitive phenotypes are not limited to missense alleles; rather, they are a property of most or all severe cha-1 hypomorphs. We suggest that our data are consistent with a model of ChAT protein physically, but not covalently, associated with synaptic vesicles; and there is a temperature-dependent equilibrium between vesicle-associated and cytoplasmic (i.e., soluble) ChAT. Presumably, in severe cha-1 hypomorphs, increasing the temperature would promote dissociation of some of the mutant ChAT protein from synaptic vesicles, thus removing the site of acetylcholine synthesis (ChAT) from the site of vesicular acetylcholine transport. This, in turn, would decrease the rate and extent of vesicle-filling, thus increasing the severity of the behavioral deficits.