The bacterial SRP receptor, FtsY, is activated on binding to the translocon.

Proteins are inserted into the bacterial plasma membrane cotranslationally after translating ribosomes are targeted to the translocon in the membrane via the signal recognition particle (SRP) pathway. The targeting pathway involves an interaction between SRP and the SRP receptor, FtsY. Here we focus on the role of FtsY and its interaction with the translocon in controlling targeting.

Electrostatics and Intrinsic Disorder Drive Translocon Binding of the SRP Receptor FtsY.

Integral membrane proteins in bacteria are co-translationally targeted to the SecYEG translocon for membrane insertion via the signal recognition particle (SRP) pathway. The SRP receptor FtsY and its N-terminal A domain, which is lacking in any structural model of FtsY, were studied using NMR and fluorescence spectroscopy. The A domain is mainly disordered and highly flexible; it binds to lipids via its N terminus and the C-terminal membrane targeting sequence.

Lateral opening of the bacterial translocon on ribosome binding and signal peptide insertion.

Proteins are co-translationally inserted into the bacterial plasma membrane via the SecYEG translocon by lateral release of hydrophobic transmembrane segments into the phospholipid bilayer. The trigger for lateral opening of the translocon is not known. Here we monitor lateral opening by photo-induced electron transfer (PET) between two fluorophores attached to the two SecY helices at the rim of the gate.

Interplay between trigger factor and other protein biogenesis factors on the ribosome.

Nascent proteins emerging from translating ribosomes in bacteria are screened by a number of ribosome-associated protein biogenesis factors, among them the chaperone trigger factor (TF), the signal recognition particle (SRP) that targets ribosomes synthesizing membrane proteins to the membrane and the modifying enzymes, peptide deformylase (PDF) and methionine aminopeptidase (MAP). Here, we examine the interplay between these factors both kinetically and at equilibrium. TF rapidly scans the ribosomes until it is stabilized on ribosomes presenting TF-specific nascent chains.

Dynamic switch of the signal recognition particle from scanning to targeting.

Ribosomes synthesizing inner membrane proteins in Escherichia coli are targeted to the membrane by the signal recognition particle (SRP) pathway. By rapid kinetic analysis we show that after initial binding to the ribosome, SRP undergoes dynamic fluctuations in search of additional interactions. Non-translating ribosomes, or ribosomes synthesizing non-membrane proteins, do not provide these contacts, allowing SRPs to dissociate rapidly.

A United Nations General Assembly Special Session for mental, neurological, and substance use disorders: the time has come.

Mental, neurological, and substance use (MNS) disorders are leading causes of the global burden of disease and profoundly impact the social and economic well-being of individuals and communities. The majority of people affected by MNS disorders globally do not have access to evidence-based interventions and many experience discrimination and abuses of their human rights. A United Nations General Assembly Special Session (UNGASS) is needed to focus global attention on MNS disorders as a core development issue requiring commitments to improve access to care, promote human rights, and strengthen the evidence on effective prevention and treatment.

Trends in mental health and substance abuse services at the nation's community health centers: 1998-2003.

Objective: We examined trends in delivery of mental health and substance abuse services at the nation's community health centers.

Methods: Analyses used data from the Health Resources and Services Administration (HRSA), Bureau of Primary Care's (BPHC) 1998 and 2003 Uniform Data System, merged with county-level data.

Results: Between 1998 and 2003, the number of patients diagnosed with a mental health/substance abuse disorder in community health centers increased from 210,000 to 800,000.

Signal sequence-independent membrane targeting of ribosomes containing short nascent peptides within the exit tunnel.

Ribosomes synthesizing inner membrane proteins in Escherichia coli are targeted to the translocon in the plasma membrane by the signal recognition particle (SRP) and the SRP receptor, FtsY. Here we show using a purified system that membrane targeting does not require an exposed signal-anchor sequence, as SRP-dependent targeting takes place with ribosomes containing short nascent peptides, with or without a signal-anchor sequence, within the peptide exit tunnel. Signaling from inside the tunnel involves ribosomal protein L23, which constitutes part of the SRP binding site.

Trends in Mental Health and Substance Abuse Services at the Nation's Community Health Centers: 1998-2003.

Objective: We examined trends in delivery of mental health and substance abuse services at the nation's community health centers.

Methods: Analyses used data from the Health Resources and Services Administration (HRSA), Bureau of Primary Care's (BPHC) 1998 and 2003 Uniform Data System, merged with county-level data.

Results: Between 1998 and 2003, the number of patients diagnosed with a mental health/substance abuse disorder in community health centers increased from 210,000 to 800,000.

The Carter Center Mental Health Program: addressing the public health crisis in the field of mental health through policy change and stigma reduction.

Some of the most pervasive and debilitating illnesses are mental illnesses, according to World Health Organization's The World Health Report 2001--Mental Health: New Understanding, New Hope. Neuropsychiatric conditions account for four of the top five leading causes of years of life lived with disability in people aged 15 to 44 in the Western world. Many barriers prevent people with mental illnesses from seeking care, such as prohibitive costs, lack of insurance, and the stigma and discrimination associated with mental illnesses.

A survey of mental health leaders one year after the President's New Freedom Commission report.

As part of the 19th annual Rosalynn Carter Symposium on Mental Health Policy, held in 2003, an anonymous online survey of symposium participants was conducted to gain insight into participants' perceptions of the impact on their organizations of the President's New Freedom Commission and its recommendations. The participants were national mental health leaders representing a broad range of mental health agencies and organizations. The results of the survey suggest that the New Freedom Commission has had a substantial impact on the organizations represented at the symposium.