Inwardly rectifying K+ channels bind intracellular magnesium and polyamines to generate inward rectification. We have examined the architecture of the inner pore of Kir2.1 channels by covalently attaching a constrained number (from one to four) of positively charged moieties of different sizes to the channel. Our results indicate that the inner pore is formed solely by the second transmembrane segment and is unprecedentedly wide. At a position critical for inward rectification (D172), the pore is sufficiently wide to bind three Mg2+ ions or polyamine molecules simultaneously. Single-channel recordings directly demonstrate that partially modified channels exhibit distinct subconductance levels. Such a wide inner pore may greatly facilitate ion permeation and high-affinity binding of multiple pore blockers to generate strong inward rectification.

Using a strategy based on reverse transcription and the polymerase chain reaction, we have determined the order of splicing of the four introns of the endogenous adenine phosphoribosyltransferase (aprt) gene in Chinese hamster ovary cells. The method involves a pairwise comparison of molecules that retain one intron and have either retained or spliced another intron(s). A highly preferred order of removal was found: intron 3 > 2 > 4 = 1. This order did not represent a linear progression from one end of the transcript to the other, nor did it correlate with the conformity of the splice site sequences to the consensus sequences or to the calculated energy of duplex formation with Ul small nuclear RNA. By using actinomycin D to inhibit RNA synthesis, the in vivo rate of the first step in splicing was estimated for all four introns; a half-life of 6 min was found for introns 2, 3, and 4. Intron 1 was spliced more slowly, with a 12-min half-life. A substantial amount of RNA that retained intron 1 as the sole intron was exported to the cytoplasm. In the course of these experiments, we also determined that intron 3, but not intron 4, is spliced before 3'-end formation is complete, probably on nascent transcripts. This result is consistent with the idea that polyadenylation is required for splicing of the 3'-most intron. We applied a similar strategy to determine the last intron to be spliced in a very large transcript, that of the endogenous dihydrofolate reductase (dhfr) gene in Chinese hamster ovary cells (25 kb). Here again, intron 1 was the last intron to be spliced.Most mammalian genes contain multiple introns. Although great progress has been made in determining the chemistry of splicing, it is still not well understood how the splicing machinery selects the correct pairs of splice sites and how a multi-intron pre-mRNA is accurately spliced without deleting exons. The recognition of correct splice sites could involve specific sequences, preferred higher-order RNA structures, or both. The relative homology of the 5' and 3' splice sites to the consensus sequences is critical but insufficient to specify a splice site; many sequences that conform closely to the consensus sequence are not selected (46,52).Several models have been proposed to help explain splice site selection. In the scanning model, splice sites might be recognized by a linear scanning process initiating at one end of the pre-mRNA. However, the experimental predictions of this model have not been borne out (26,50). In the firstcome-first-served model, spliceosome assembly may initiate on the nascent transcript as soon as the necessary RNA sequences have been synthesized, with splicing taking place at some later time (2). In the exon definition model, exons are somehow recognized as units of splicing during assembly of the splicing machinery by factors that first bind to the 5' and 3' ends (51).Another mechanism that could contribute to splice site selection is the order of splicing: removal of one intron may facilitate the subsequent splicing of anoth...

The evolution of South China involved accretion-collision of multiple terranes from the Proterozoic to the Mesozoic. Zircon U-Pb ages, Hf data, and structural data indicate that the Cathaysia block consists of two terranes, West Cathaysia and East Cathaysia, separated by a newly recognized major strike-slip fault. We propose that West Cathaysia was part of a microcontinent that originated from a Grenvillian-aged orogen in the Rodinia supercontinent, East Cathaysia originated from an Indosinian-aged orogen in the Paleo-Tethyan regime to the south and was translated to the east of West Cathaysia through strike-slip motion, and the early Paleozoic Wuyi-Yunkai orogeny was a result of direct collision of West Cathaysia with a yet-unidentified terrane that rifted away after the collision. We conclude that a multiterrane Wilson cycle (multi-terrane accretion-collision, large-scale strike-slip motion, and separation of two terranes by post-collisional rifting along the suture zone) characterizes the history of South China and may be a common feature of orogens.*

Purpose -The purpose of this paper is to examine the drivers of outward foreign direct investment (OFDI) from the emerging economies and if there exists a positive role for home governments to coordinate them. The backdrop is the recent increases in OFDI from emerging economies and the emergence of several emerging economy firms, which have caught up to become global leaders in several industries. The paper focuses particularly on experiences from Asian economies. Design/methodology/approach -The paper applies a multi method approach and relies on literature studies, investment statistics, government reports, press reports, company reports, and interviews with public officials. Findings -Extending the motive-based business theory, the paper first establishes the pronouncement of a third wave of OFDI from the mid-1990s. Whereas the typical motives have remained important, the technology-seeking motive has become significantly more important during the third wave. Typical policy prescriptions to liberalize government regulations have been called into question. Many home emerging country governments have acted to coordinate their activities by regulating proactively investment outflows. The evidence also shows that the successful investment outflows have benefited significantly from home governments addressing the characteristics and motives of target industries and locations abroad. Practical implications -The analysis shows that contrary to mainstream prescriptions many home governments have successfully regulated strongly OFDI from the emerging economies. However, it is important for home governments to consider the broader interest of promoting capital flows to ensure the long-term development of economies rather than narrow national interests. Home and host governments should seek to establish common and specific collaboration platforms to raise information flows and coordinate better the negotiations and execution of investment projects. Originality/value -The paper provides a more thorough analysis of the implications for home country policies of the increasing outward investment flows from emerging economies and the increasing competitiveness and capabilities of their transnational firms. It proposes augmentations to prior frameworks of drivers and motives of OFDI and pushes deeper the home policy implications of increasing outward investment flows.

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