Cus2 enforces the first ATP-dependent step of splicing by binding to yeast SF3b1 through a UHM-ULM interaction

ABSTRACTStable recognition of the intron branchpoint by the U2 snRNP to form the pre-spliceosome is the first ATP-dependent step of splicing. Genetic and biochemical data from yeast indicate that Cus2 aids U2 snRNA folding into the stem IIa conformation prior to pre-spliceosome formation. Cus2 must then be removed by an ATP-dependent function of Prp5 before assembly can progress. However, the location from which Cus2 is displaced and the nature of its binding to the snRNP are unknown. Here, we show that Cus2 contains a conserved UHM (U2AF homology motif) that binds Hsh155, the yeast homolog of human SF3b1, through a conserved ULM (U2AF ligand motif). Mutations in either motif block binding and allow pre-spliceosome formation without ATP. A 2.0 Å resolution structure of the Hsh155 ULM in complex with the UHM of Tat-SF1, the human homolog of Cus2, and complementary binding assays show that the interaction is highly similar between yeast and humans. Furthermore, Tat-SF1 enforces ATP-dependence of pre-spliceosome formation in yeast extracts, showing that it can replace Cus2 function. Cus2 is removed before pre-spliceosome formation, and both Cus2 and its Hsh155 ULM binding site are absent from available cryo-EM structure models. However, our data are consistent with the apparent location of the disordered Hsh155 ULM between the U2 stem-loop IIa and the HEAT-repeats of Hsh155 that interact with Prp5. We suggest a model in which Prp5 uses ATP to remove Cus2 from Hsh155 such that extended base pairing between U2 snRNA and the intron branchpoint can occur.

Spatial patterns of a Southern Bell Frog Litoria raniformis population in an agricultural landscape

We investigated changes in the spatial organization of individuals within a population of endangered Southern Bell Frogs Litoria raniformis over an eight-month period. Our results identified strong temporal changes in both spatial organization and the apparent location of L. raniformis within the study site. Ripley's K Function analyses showed that the position of individuals relative to one another shifted from random immediately after the study site was flooded (p < 0.005), to strongly clustered at spatial scales between 0-1500 m during the peak breeding period (p < 0.005). The majority of flooded areas were dry by April and May and individuals again became aggregated within the remaining waterbodies.

A Final Reply to Hutchison and Loomis

While acknowledging that their design and methods were different from the original Proffitt, Stefanucci, Banton, and Epstein (2003) study, Hutchison and Loomis (H&L) continue to argue that their findings qualify our account of energetic influences on distance perception. This reply provides a brief and focused discussion of the methodological differences between their study and ours and why these differences were likely responsible for the different results. It is also argued that the measures employed by H&L are assessments of apparent location, not apparent distance.

Massive Stars Ejected from R136?

We present the observational signature of a statistically significant number of very massive stars around the core of R136 and discuss the evidence for dynamical processes to be responsible for their apparent location. Alternative scenarios are discussed as well.

Pseudo-nonlinearities in engineering structures

A novel theoretical framework is presented for making a given linear system respond to external excitation as if a nonlinearity or fault was present. The type and apparent location of the nonlinearity or pseudo-fault may be specified arbi­trarily. The means of generating the required response is to excite the system with additional inputs, thus exploiting the principle of superposition. The theory is validated using numerical simulation of various lumped parameter systems.

Why do Mirrors Reverse Left/Right and not Up/Down?

Imagine a child′s toy arrow, sticking by its rubber sucker to a mirror′s reflective surface. We can call the direction in which such an arrow would point the finwards direction (forwards into the mirror); and we can call the opposite direction boutwards (backwards out). When we look at things in a mirror, their images are apparently just as far finwards of the mirror as the things themselves are boutwards of it. For example, if we look at the tail of our arrow and cast our glance finwards, we see first the tail, then the head, then the mirror, then the reflection of the head, and finally the reflection of the tail. We can therefore say that a mirror reverses things in the finwards/boutwards dimension. Moreover, the straight line connecting each thing to its image passes perpendicularly through the plane of the mirror. Hence there is no plane, apart from that of the mirror itself, such that the apparent location of each thing′s image is just as far to the one side of that plane as the original is to the other. This means that the reversal in the finwards/ boutwards dimension is the only reversal of its kind to take place. In particular, there is no such reversal in any dimension at right angles to finwards/boutwards.

Dreams and purposes: an analysis of dream narratives in an independent African Church

Opening ParagraphSampling provided the rationale of my previous account of ‘Dreams in an Independent African Church’ (1973). I took a set of ninety-five dream reports, and a handful of visions, as individual events which could be summed and categorised in a variety of ways. I had been able to garner these over a period of five months' study, from the services of this ‘Independent African Church’ (IAC). Beyond considering in general terms the part played by dream-telling and its accompaniments in the services of the Church and in its life more generally, in that article I worked out patterns, categorising the individual dreams in relation to their tellers, to the way they might implicate other named people, to whether they depicted IAC activities, to their apparent location, and so on. I sought to explain the patterns in terms of leadership and its interests, and of the idea that dream-telling was a kind of ‘bidding’, ‘to contribute valuably to the life of the group, and through this for status within it’ (op. cit.: 256). This article moves on from that analysis.