\u3cem\u3ePlasmodium falciparum\u3c/em\u3e SSB Tetramer Wraps Single-Stranded DNA with Similar Topology but Opposite Polarity to \u3cem\u3eE. coli\u3c/em\u3e SSB

Single-stranded DNA binding (SSB) proteins play central roles in genome maintenance in all organisms. Plasmodium falciparum, the causative agent of malaria, encodes an SSB protein that localizes to the apicoplast and likely functions in the replication and maintenance of its genome. P. falciparum SSB (Pf-SSB) shares a high degree of sequence homology with bacterial SSB proteins but differs in the composition of its C-terminus, which interacts with more than a dozen other proteins in Escherichia coli SSB (Ec-SSB). Using sedimentation methods, we show that Pf-SSB forms a stable homo-tetramer alone and when bound to single-stranded DNA (ssDNA). We also present a crystal structure at 2.1 Å resolution of the Pf-SSB tetramer bound to two (dT)35 molecules. The Pf-SSB tetramer is structurally similar to the Ec-SSB tetramer, and ssDNA wraps completely around the tetramer with a “baseball seam” topology that is similar to Ec-SSB in its “65 binding mode”. However, the polarity of the ssDNA wrapping around Pf-SSB is opposite to that observed for Ec-SSB. The interactions between the bases in the DNA and the amino acid side chains also differ from those observed in the Ec-SSB–DNA structure, suggesting that other differences may exist in the DNA binding properties of these structurally similar proteins

Intrinsically Disordered C-Terminal Tails of \u3cem\u3eE. coli\u3c/em\u3e Single-Stranded DNA Binding Protein Regulate Cooperative Binding to Single-Stranded DNA

The homotetrameric Escherichia coli single-stranded DNA binding protein (SSB) plays a central role in DNA replication, repair and recombination. E. coli SSB can bind to long single-stranded DNA (ssDNA) in multiple binding modes using all four subunits [(SSB)65 mode] or only two subunits [(SSB)35 binding mode], with the binding mode preference regulated by salt concentration and SSB binding density. These binding modes display very different ssDNA binding properties with the (SSB)35 mode displaying highly cooperative binding to ssDNA. SSB tetramers also bind an array of partner proteins, recruiting them to their sites of action. This is achieved through interactions with the last 9 amino acids (acidic tip) of the intrinsically disordered linkers (IDLs) within the four C-terminal tails connected to the ssDNA binding domains. Here, we show that the amino acid composition and length of the IDL affects the ssDNA binding mode preferences of SSB protein. Surprisingly, the number of IDLs and the lengths of individual IDLs together with the acidic tip contribute to highly cooperative binding in the (SSB)35 binding mode. Hydrodynamic studies and atomistic simulations suggest that the E. coli SSB IDLs show a preference for forming an ensemble of globular conformations, whereas the IDL from Plasmodium falciparum SSB forms an ensemble of more extended random coils. The more globular conformations correlate with cooperative binding

The Effect of a Femoral Fracture Sustained before Skeletal Maturity on Bone Mineral Density: A Long-Term Follow-Up Study

Peer reviewe

Forecasting the cost of processing multi-join queries via hashing for main-memory databases (Extended version)

Database management systems (DBMSs) carefully optimize complex multi-join queries to avoid expensive disk I/O. As servers today feature tens or hundreds of gigabytes of RAM, a significant fraction of many analytic databases becomes memory-resident. Even after careful tuning for an in-memory environment, a linear disk I/O model such as the one implemented in PostgreSQL may make query response time predictions that are up to 2X slower than the optimal multi-join query plan over memory-resident data. This paper introduces a memory I/O cost model to identify good evaluation strategies for complex query plans with multiple hash-based equi-joins over memory-resident data. The proposed cost model is carefully validated for accuracy using three different systems, including an Amazon EC2 instance, to control for hardware-specific differences. Prior work in parallel query evaluation has advocated right-deep and bushy trees for multi-join queries due to their greater parallelization and pipelining potential. A surprising finding is that the conventional wisdom from shared-nothing disk-based systems does not directly apply to the modern shared-everything memory hierarchy. As corroborated by our model, the performance gap between the optimal left-deep and right-deep query plan can grow to about 10X as the number of joins in the query increases.Comment: 15 pages, 8 figures, extended version of the paper to appear in SoCC'1

Velocity and processivity of helicase unwinding of double-stranded nucleic acids

Helicases are molecular motors which unwind double-stranded nucleic acids (dsNA) in cells. Many helicases move with directional bias on single-stranded (ss) nucleic acids, and couple their directional translocation to strand separation. A model of the coupling between translocation and unwinding uses an interaction potential to represent passive and active helicase mechanisms. A passive helicase must wait for thermal fluctuations to open dsNA base pairs before it can advance and inhibit NA closing. An active helicase directly destabilizes dsNA base pairs, accelerating the opening rate. Here we extend this model to include helicase unbinding from the nucleic-acid strand. The helicase processivity depends on the form of the interaction potential. A passive helicase has a mean attachment time which does not change between ss translocation and ds unwinding, while an active helicase in general shows a decrease in attachment time during unwinding relative to ss translocation. In addition, we describe how helicase unwinding velocity and processivity vary if the base-pair binding free energy is changed.Comment: To appear in special issue on molecular motors, Journal of Physics - Condensed Matte

ReoptSMART: A Learning Query Plan Cache

The task of query optimization in modern relational database systems is important but can be computationally expensive. Parametric query optimization(PQO) has as its goal the prediction of optimal query execution plans based on historical results, without consulting the query optimizer. We develop machine learning techniques that can accurately model the output of a query optimizer. Our algorithms handle non-linear boundaries in plan space and achieve high prediction accuracy even when a limited amount of data is available for training. We use both predicted and actual query execution times for learning, and are the first to demonstrate a total net win of a PQO method over a state-of-the-art query optimizer for some workloads. ReoptSMART realizes savings not only in optimization time, but also in query execution time, for an over-all improvement by more than an order of magnitude in some cases

Assessing the importance of a self-generated detachment process in river biofilm models

1. Epilithic biofilm biomass was measured for 14 months in two sites, located up- and downstream of the city of Toulouse in the Garonne River (south-west France). Periodical sampling provided a biomass data set to compare with simulations from the model of Uehlinger, Bürher and Reichert (1996: Freshwater Biology, 36, 249–263.), in order to evaluate the impact of hydraulic disturbance. 2. Despite differences in application conditions (e.g. river size, discharge, frequency of disturbance), the base equation satisfactorily predicted biomass between low and high water periods of the year, suggesting that the flood disturbance regime may be considered a universal mechanism controlling periphyton biomass. 3. However modelling gave no agreement with biomass dynamics during the 7-month long low water period that the river experienced. The influence of other biomass-regulating factors (temperature, light and soluble reactive phosphorus) on temporal biomass dynamics was weak. 4. Implementing a supplementary mechanism corresponding to a temperature-dependent self-generated loss because of heterotrophic processes allowed us to accurately reproduce the observed pattern: a succession of two peaks. This case study suggests that during typical summer low water periods (flow stability and favourable temperature) river biofilm modelling requires self-generated detachment to be considered

Intergenerational Continuity of Psychological Violence: Intimate Partner Relationships and Harsh Parenting.

Objective: This prospective, longitudinal investigation examined psychological violence across generations. We examined how parent psychological violence experienced during adolescence influenced the stability of one’s own intimate partner psychological violence perpetration across time and how psychological violence is related to harsh parenting in adulthood. Method: Data came from 193 parents and their adolescent who participated from adolescence through adulthood. Parental psychological violence was assessed in early adolescence. Partner violence was assessed in late adolescence, emerging adulthood, and adulthood. Harsh parenting to their offspring was assessed in adulthood. Results: Parent psychological violence in early adolescence was associated with one’s own intimate partner psychological violence in late adolescence. Partner psychological violence was stable from emerging adulthood to adulthood. Moreover, parental violence was also related to their own harsh parenting in adulthood. Conclusions: Findings suggest that children exposed to parental psychological violence during adolescence may have greater difficulty developing acceptable behaviors in their own romantic relationships over time, as well as parenting their own child in adulthood. Findings highlight the importance for clinicians and policymakers to develop and utilize effective educational and preventive interventions designed toward not only adolescent behaviors, but also that of the parent. Understanding how the family environment impacts current and long-term functioning is important in helping stop the cycle of violence across generations

Initial Vibration Analysis of the Advanced Stirling Radioisotope Generator's (ASRG's) Affect on Spacecraft Instruments

Assess if nominal Advanced Stirling Radioisotope Generator (ASRG) vibration levels are sufficiently benign for unimpeded spacecraft instrument operation