Alternative splicing of the rat sodium/bile acid transporter changes its cellular localization and transport properties

Bile secretion involves the structural and functional interplay of hepatocytes and cholangiocytes, the cells lining the intrahepatic bile ducts. Hepatocytes actively secrete bile acids into the canalicular space and cholangiocytes then transport bile acids in a vectorial manner across their apical and basolateral plasma membranes. The initial step in the transepithelial transport of bile acids across rat cholangiocytes is apical uptake by a Na+-dependent bile acid transporter (ASBT). To date, the molecular basis of the obligate efflux mechanism for extrusion of bile acids across the cholangiocyte basolateral membrane remains unknown. We have identified an exon-2 skipped, alternatively spliced form of ASBT, designated t-ASBT, expressed in rat cholangiocytes, ileum, and kidney. Alternative splicing causes a frameshift that produces a 154-aa protein. Antipeptide antibodies detected the ≈19 kDa t-ASBT polypeptide in rat cholangiocytes, ileum, and kidney. The t-ASBT was specifically localized to the basolateral domain of cholangiocytes. Transport studies in Xenopus oocytes revealed that t-ASBT can function as a bile acid efflux protein. Thus, alternative splicing changes the cellular targeting of ASBT, alters its functional properties, and provides a mechanism for rat cholangiocytes and other bile acid-transporting epithelia to extrude bile acids. Our work represents an example in which a single gene appears to encode via alternative splicing both uptake and obligate efflux carriers in a bile acid-transporting epithelial cell.

Broken symmetry and critical transport properties of random metals

Recent experimental data on the conductivity σ+(T), T → 0, on the metallic side of the metal–insulator transition in ideally random (neutron transmutation-doped) 70Ge:Ga have shown that σ+(0) ∝ (N − Nc)μ with μ = ½, confirming earlier ultra-low-temperature results for Si:P. This value is inconsistent with theoretical predictions based on diffusive classical scaling models, but it can be understood by a quantum-directed percolative filamentary amplitude model in which electronic basis states exist which have a well-defined momentum parallel but not normal to the applied electric field. The model, which is based on a new kind of broken symmetry, also explains the anomalous sign reversal of the derivative of the temperature dependence in the critical regime.

Critical transport properties of random metals in large magnetic fields

The threshold behavior of the transport properties of a random metal in the critical region near a metal–insulator transition is strongly affected by the measuring electromagnetic fields. In spite of the randomness, the electrical conductivity exhibits striking phase-coherent effects due to broken symmetry, which greatly sharpen the transition compared with the predictions of effective medium theories, as previously explained for electrical conductivities. Here broken symmetry explains the sign reversal of the T → 0 magnetoconductance of the metal–insulator transition in Si(B,P), also previously not understood by effective medium theories. Finally, the symmetry-breaking features of quantum percolation theory explain the unexpectedly very small electrical conductivity temperature exponent α = 0.22(2) recently observed in Ni(S,Se)2 alloys at the antiferromagnetic metal–insulator transition below T = 0.8 K.

Charge transfer and transport in DNA

We explore charge migration in DNA, advancing two distinct mechanisms of charge separation in a donor (d)–bridge ({Bj})–acceptor (a) system, where {Bj} = B1,B2, … , BN are the N-specific adjacent bases of B-DNA: (i) two-center unistep superexchange induced charge transfer, d*{Bj}a → d∓{Bj}a±, and (ii) multistep charge transport involves charge injection from d* (or d+) to {Bj}, charge hopping within {Bj}, and charge trapping by a. For off-resonance coupling, mechanism i prevails with the charge separation rate and yield exhibiting an exponential dependence ∝ exp(−βR) on the d-a distance (R). Resonance coupling results in mechanism ii with the charge separation lifetime τ ∝ Nη and yield Y ≃ (1 + δ̄ Nη)−1 exhibiting a weak (algebraic) N and distance dependence. The power parameter η is determined by charge hopping random walk. Energetic control of the charge migration mechanism is exerted by the energetics of the ion pair state d∓B1±B2 … BNa relative to the electronically excited donor doorway state d*B1B2 … BNa. The realization of charge separation via superexchange or hopping is determined by the base sequence within the bridge. Our energetic–dynamic relations, in conjunction with the energetic data for d*/d− and for B/B+, determine the realization of the two distinct mechanisms in different hole donor systems, establishing the conditions for “chemistry at a distance” after charge transport in DNA. The energetic control of the charge migration mechanisms attained by the sequence specificity of the bridge is universal for large molecular-scale systems, for proteins, and for DNA.

Long-range transport of mineral dust in the global atmosphere: Impact of African dust on the environment of the southeastern United States

Soil dust is a major constituent of airborne particles in the global atmosphere. Dust plumes frequently cover huge areas of the earth; they are one of the most prominent and commonly visible features in satellite imagery. Dust is believed to play a role in many biogeochemical processes, but the importance of dust in these processes is not well understood because of the dearth of information about the global distribution of dust and its physical, chemical, and mineralogical properties. This paper describes some features of the large-scale distribution of dust and identifies some of the geological characteristics of important source areas. The transport of dust from North Africa is presented as an example of possible long-range dust effects, and the impact of African dust on environmental processes in the western North Atlantic and the southeastern United States is assessed. Dust transported over long distances usually has a mass median diameter <10 μm. Small wind-borne soil particles show signs of extensive weathering; consequently, the physical and chemical properties of the particles will greatly depend on the weathering history in the source region and on the subsequent modifications that occur during transit in the atmosphere (typically a period of a week or more). To fully understand the role of dust in the environment and in human health, mineralogists will have to work closely with scientists in other disciplines to characterize the properties of mineral particles as an ensemble and as individual particles especially with regard to surface characteristics.

Electrical and synaptic properties of embryonic luteinizing hormone-releasing hormone neurons in explant cultures.

Voltage- and ligand-activated channels in embryonic neurons containing luteinizing hormone-releasing hormone (LHRH) were studied by patch-pipette, whole-cell current and voltage clamp techniques. LHRH neurons were maintained in explant cultures derived from olfactory pit regions of embryonic mice. Cells were marked intracellularly with Lucifer yellow following recording. Sixty-two cells were unequivocally identified as LHRH neurons by Lucifer yellow and LHRH immunocytochemistry. The cultured LHRH neurons had resting potentials around -50 mV, exhibited spontaneous discharges generated by intrinsic and/or synaptic activities and contained a time-dependent inward rectifier (Iir). Voltage clamp analysis of ionic currents in the LHRH neuron soma revealed a tetrodotoxin-sensitive Na+ current (INa) and two major types of K+ currents, a transient current (IA), a delayed rectifier current (IK) and low- and high-voltage-activated Ca2+ currents. Spontaneous depolarizing synaptic potentials and depolarizations induced by direct application of gamma-aminobutyrate were both inhibited by picrotoxin or bicuculline, demonstrating the presence of functional gamma-aminobutyrate type A synapses on these neurons. Responses to glutamate were found in LHRH neurons in older cultures. Thus, embryonic LHRH neurons not yet positioned in their postnatal environment in the forebrain contained a highly differentiated repertoire of voltage- and ligand-gated channels.