Survival strategies in a changing practice environment.

A number of forces disrupt normal referral patterns to physicians, driving hospital consolidation, and changing the way medicine is practiced in the United States. Strategies have been implemented to keep services in-network and stem "leakage"-all in the name of population health management, reducing unit costs, and spreading financial risk among the insurers, hospitals, and physicians. To survive in the changing medical environment, independent unintegrated physicians need to consider different practice models. These models include accountable care organizations (ACOs), super groups, specialty networks, co-management agreements, professional service agreements (PSAs), and partnering with local hospitals. Each physician and physician group need to decide what works best for them and their geographical area. Physicians and physician groups may find that one or more of these models will improve their chance of economic survival.

Oncology professional services agreements: a model for hospital affiliation that preserves private practice.

Professional services agreements enable community-based oncology groups to affiliate with local hospitals in a win-win transaction that preserves a significant level of independence for the oncology group. This article describes the business and legal aspects of such agreements.

Mechanism of eIF6-mediated inhibition of ribosomal subunit joining.

During the process of ribosomal assembly, the essential eukaryotic translation initiation factor 6 (eIF6) is known to act as a ribosomal anti-association factor. However, a molecular understanding of the anti-association activity of eIF6 is still missing. Here we present the cryo-electron microscopy reconstruction of a complex of the large ribosomal subunit with eukaryotic eIF6 from Saccharomyces cerevisiae. The structure reveals that the eIF6 binding site involves mainly rpL23 (L14p in Escherichia coli). Based on our structural data, we propose that the mechanism of the anti-association activity of eIF6 is based on steric hindrance of intersubunit bridge formation around the dynamic bridge B6.

Anatomy of a Cancer Center Transaction: Part II.

The second of a two-part series comparing two models for structuring a community-based cancer center on a collaborative basis between oncologists and a hospital.

Anatomy of a Cancer Center Transaction.

The first of a two-part series, this article presents one of two models for structuring a community-based cancer center through collaborative arrangements between oncologists and a hospital.

Following the signal sequence from ribosomal tunnel exit to signal recognition particle.

Membrane and secretory proteins can be co-translationally inserted into or translocated across the membrane. This process is dependent on signal sequence recognition on the ribosome by the signal recognition particle (SRP), which results in targeting of the ribosome-nascent-chain complex to the protein-conducting channel at the membrane. Here we present an ensemble of structures at subnanometre resolution, revealing the signal sequence both at the ribosomal tunnel exit and in the bacterial and eukaryotic ribosome-SRP complexes. Molecular details of signal sequence interaction in both prokaryotic and eukaryotic complexes were obtained by fitting high-resolution molecular models. The signal sequence is presented at the ribosomal tunnel exit in an exposed position ready for accommodation in the hydrophobic groove of the rearranged SRP54 M domain. Upon ribosome binding, the SRP54 NG domain also undergoes a conformational rearrangement, priming it for the subsequent docking reaction with the NG domain of the SRP receptor. These findings provide the structural basis for improving our understanding of the early steps of co-translational protein sorting.

Circulating proteasomes are functional and have a subtype pattern distinct from 20S proteasomes in major blood cells.

BACKGROUND: 20S proteasomes, the proteolytic core particles of the major intracellular protein degradative pathway, are potential disease markers because they are detectable in human plasma as circulating proteasomes and their concentrations are increased in patients suffering from various diseases. To investigate the origin of circulating proteasomes, we compared some of their features with those of proteasomes isolated from major blood cells. METHODS: We isolated circulating proteasomes from the plasma of 2 patients with rheumatoid arthritis and 2 with systemic lupus erythematosus and from human plasma from healthy donors. We purified the proteasomes to apparent homogeneity and then used electron microscopy for imaging and chromatography for subtype spectrum analysis. We compared subtype results with those from 20S proteasomes purified from 4 major blood cell populations. We also tested proteasomes for enzymatic activity and immunosubunit content. RESULTS: Circulating proteasomes from plasma of healthy donors and from patients with autoimmune disease were found to have the same size and shape as erythrocyte proteasomes, be proteolytically active, and contain standard- and immunosubunits. Chromatography revealed 6 circulating proteasome subtype peaks in healthy donor plasma and 7 in patient donor plasma. Proteasomes from erythrocytes had 3 subtype peaks and those of monocytes, T-lymphocytes, and thrombocytes each had 5 different subtype peaks. CONCLUSION: Circulating proteasomes were intact and enzymatically active in plasma from healthy donors and from patients with autoimmune disease. Because the subtype patterns of circulating proteasomes clearly differ from those of proteasomes from blood cells, these cells cannot be regarded as a major source of circulating proteasomes.

Structure of eEF3 and the mechanism of transfer RNA release from the E-site.

Elongation factor eEF3 is an ATPase that, in addition to the two canonical factors eEF1A and eEF2, serves an essential function in the translation cycle of fungi. eEF3 is required for the binding of the aminoacyl-tRNA-eEF1A-GTP ternary complex to the ribosomal A-site and has been suggested to facilitate the clearance of deacyl-tRNA from the E-site. Here we present the crystal structure of Saccharomyces cerevisiae eEF3, showing that it consists of an amino-terminal HEAT repeat domain, followed by a four-helix bundle and two ABC-type ATPase domains, with a chromodomain inserted in ABC2. Moreover, we present the cryo-electron microscopy structure of the ATP-bound form of eEF3 in complex with the post-translocational-state 80S ribosome from yeast. eEF3 uses an entirely new factor binding site near the ribosomal E-site, with the chromodomain likely to stabilize the ribosomal L1 stalk in an open conformation, thus allowing tRNA release.

ERj1p uses a universal ribosomal adaptor site to coordinate the 80S ribosome at the membrane.

Ribosomes translating secretory and membrane proteins are targeted to the endoplasmic reticulum membrane and attach to the protein-conducting channel and ribosome-associated membrane proteins (RAMPs). Recently, a new RAMP, ERj1p, has been identified that recruits BiP to ribosomes and regulates translational activity. Here we present the cryo-EM structure of a ribosome-ERj1p complex, revealing how ERj1p coordinates the ribosome at the membrane and how allosteric effects may mediate ERj1p's regulatory activity.

Exclusive hospital-based service agreements: what radiologists need to know.

This article provides radiologists with the information that they need to know to participate meaningfully in negotiating or renegotiating an exclusive hospital-based radiology service agreement. It discusses the contract negotiation process, including how to identify and prioritize contract objectives, and how to assess and create bargaining leverage. Options for achieving contract longevity, for resolving "turf" issues and for achieving financial objectives are also addressed. The article further explains the key regulatory issues that shape exclusive hospital-based radiology service agreements, including antitrust, fraud and abuse, Stark Law, HIPAA, tax, and Medicare reimbursement considerations. The author discusses the contract negotiation process from both the radiology group and hospital perspectives. He suggests that successful negotiation will depend on "fitting" the group's contracting agenda with the hospital's priorities, organizational structure, culture and resources.