Dan forms condensates in neuroblasts and regulates nuclear architecture and progenitor competence in vivo.

Genome organization is thought to underlie cell type specific gene expression, yet how it is regulated in progenitors to produce cellular diversity is unknown. In Drosophila, a developmentally-timed genome reorganization in neural progenitors terminates competence to produce early-born neurons. These events require downregulation of Distal antenna (Dan), part of the conserved pipsqueak DNA-binding superfamily.

Complexin Mutants Reveal Partial Segregation between Recycling Pathways That Drive Evoked and Spontaneous Neurotransmission.

Unlabelled: Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals.

A Drosophila model of Huntington disease-like 2 exhibits nuclear toxicity and distinct pathogenic mechanisms from Huntington disease.

Huntington disease-like 2 (HDL2) and Huntington disease (HD) are adult-onset neurodegenerative diseases characterized by movement disorders, psychiatric disturbances and cognitive decline. Brain tissue from HD and HDL2 patients shows degeneration of the striatum and ubiquitinated inclusions immunoreactive for polyglutamine (polyQ) antibodies. Despite these similarities, the diseases result from different genetic mutations.

Shank Modulates Postsynaptic Wnt Signaling to Regulate Synaptic Development.

Unlabelled: Prosap/Shank scaffolding proteins regulate the formation, organization, and plasticity of excitatory synapses. Mutations in SHANK family genes are implicated in autism spectrum disorder and other neuropsychiatric conditions. However, the molecular mechanisms underlying Shank function are not fully understood, and no study to date has examined the consequences of complete loss of all Shank proteins in vivo Here we characterize the single Drosophila Prosap/Shank family homolog.

Phosphorylation of Complexin by PKA Regulates Activity-Dependent Spontaneous Neurotransmitter Release and Structural Synaptic Plasticity.

Synaptic plasticity is a fundamental feature of the nervous system that allows adaptation to changing behavioral environments. Most studies of synaptic plasticity have examined the regulated trafficking of postsynaptic glutamate receptors that generates alterations in synaptic transmission. Whether and how changes in the presynaptic release machinery contribute to neuronal plasticity is less clear.

Postsynaptic actin regulates active zone spacing and glutamate receptor apposition at the Drosophila neuromuscular junction.

Synaptic communication requires precise alignment of presynaptic active zones with postsynaptic receptors to enable rapid and efficient neurotransmitter release. How transsynaptic signaling between connected partners organizes this synaptic apparatus is poorly understood. To further define the mechanisms that mediate synapse assembly, we carried out a chemical mutagenesis screen in Drosophila to identify mutants defective in the alignment of active zones with postsynaptic glutamate receptor fields at the larval neuromuscular junction.

Association of housing first implementation and key outcomes among homeless persons with problematic substance use.

Objectives: Housing First is a supportive housing model for persons with histories of chronic homelessness that emphasizes client-centered services, provides immediate housing, and does not require treatment for mental illness or substance abuse as a condition of participation. Previous studies of Housing First have found reduced governmental costs and improved personal well-being among participants. However, variations in real-world program implementation require better understanding of the relationship between implementation and outcomes.

Genetic analysis of the Complexin trans-clamping model for cross-linking SNARE complexes in vivo.

Complexin (Cpx) is a SNARE-binding protein that regulates neurotransmission by clamping spontaneous synaptic vesicle fusion in the absence of Ca(2+) influx while promoting evoked release in response to an action potential. Previous studies indicated Cpx may cross-link multiple SNARE complexes via a trans interaction to function as a fusion clamp. During Ca(2+) influx, Cpx is predicted to undergo a conformational switch and collapse onto a single SNARE complex in a cis-binding mode to activate vesicle release.

Complexin controls spontaneous and evoked neurotransmitter release by regulating the timing and properties of synaptotagmin activity.

Neurotransmitter release following synaptic vesicle (SV) fusion is the fundamental mechanism for neuronal communication. Synaptic exocytosis is a specialized form of intercellular communication that shares a common SNARE-mediated fusion mechanism with other membrane trafficking pathways. The regulation of synaptic vesicle fusion kinetics and short-term plasticity is critical for rapid encoding and transmission of signals across synapses.

Comparative analysis of Drosophila and mammalian complexins as fusion clamps and facilitators of neurotransmitter release.

The SNARE-binding protein complexin (Cpx) has been demonstrated to regulate synaptic vesicle fusion. Previous studies are consistent with Cpx functioning either as a synaptic vesicle fusion clamp to prevent premature exocytosis, or as a facilitator to directly stimulate release. Here we examined conserved roles of invertebrate and mammalian Cpx isoforms in the regulation of neurotransmitter release using the Drosophila neuromuscular junction as a model synapse.

"Empty" sac in pregnant women with bleeding: are measurements answering the right question?

Purpose: To assess the percentage of first-trimester pregnancies with bleeding that demonstrate a visible sac but lack an identifiable embryo and have a mean sac diameter (MSD) in the controversial range of 16-20 mm.

Methods: Retrospective study of all first-trimester sonograms among women with vaginal bleeding during a 4-year interval.

Results: The study cohort consisted of 546 first- trimester sonograms.

Second trimester prenatal ultrasound for the detection of pregnancies at increased risk of Trisomy 18 based on serum screening.

Objective: To describe ultrasound findings in fetuses with Trisomy 18.

Methods: Prospective population-based cohort study of second trimester ultrasound among Californian women who were at increased risk of chromosome abnormality based on serum screening between November 1999 and April 2001. Structural anomalies plus the following soft markers were assessed: nuchal fold thickening, choroid plexus cyst (CPC), echogenic intracardiac focus, echogenic bowel, renal pyelectasis, clenched hands; clinodactyly; short femur, short humerus and a single umbilical artery (SUA).

Five-millimeter and smaller embryos without embryonic cardiac activity: outcomes in women with vaginal bleeding.

Objective: The purpose of this study was to assess outcomes in embryos with a crown-rump length (CRL) of 5 mm or less without embryonic cardiac activity (ECA) among pregnant women with vaginal bleeding in the first trimester.

Methods: A retrospective study of all first-trimester sonograms in women with vaginal bleeding from 1999 to 2002 was conducted.

Results: Thirty-seven embryos without detectable ECA that had a CRL of 5 mm or less were identified.

mGluR1/5-dependent long-term depression requires the regulated ectodomain cleavage of neuronal pentraxin NPR by TACE.

Matrix metalloproteases (MMPs) play a role in remodeling the extracellular matrix during brain development and have been implicated in synaptic plasticity. Here, we report that a member of the neuronal pentraxin (NP) family, neuronal pentraxin receptor (NPR), undergoes regulated cleavage by the MMP tumor necrosis factor-alpha converting enzyme (TACE). NPR is enriched at excitatory synapses where it associates with AMPA-type glutamate receptors (AMPAR) and enhances synaptogenesis.

Interaction of the N-terminal domain of the AMPA receptor GluR4 subunit with the neuronal pentraxin NP1 mediates GluR4 synaptic recruitment.

Synaptogenesis requires recruitment of neurotransmitter receptors to developing postsynaptic specializations. We developed a coculture system reconstituting artificial synapses between neurons and nonneuronal cells to investigate the molecular components required for AMPA-receptor recruitment to synapses. With this system, we find that excitatory axons specifically express factors that recruit the AMPA receptor GluR4 subunit to sites of contact between axons and GluR4-transfected nonneuronal cells.

Neuronal pentraxins mediate synaptic refinement in the developing visual system.

Neuronal pentraxins (NPs) define a family of proteins that are homologous to C-reactive and acute-phase proteins in the immune system and have been hypothesized to be involved in activity-dependent synaptic plasticity. To investigate the role of NPs in vivo, we generated mice that lack one, two, or all three NPs. NP1/2 knock-out mice exhibited defects in the segregation of eye-specific retinal ganglion cell (RGC) projections to the dorsal lateral geniculate nucleus, a process that involves activity-dependent synapse formation and elimination.

Narp and NP1 form heterocomplexes that function in developmental and activity-dependent synaptic plasticity.

Narp is a neuronal immediate early gene that plays a role in excitatory synaptogenesis. Here, we report that native Narp in brain is part of a pentraxin complex that includes NP1. These proteins are covalently linked by disulfide bonds into highly organized complexes, and their relative ratio in the complex is dynamically dependent upon the neuron's activity history and developmental stage.