Maximizing the Benefit of Life-Saving Treatments for Pompe Disease, Spinal Muscular Atrophy, and Duchenne Muscular Dystrophy Through Newborn Screening: Essential Steps.

Importance: Newborn screening (NBS) identifies infants with specific congenital disorders for which earlier intervention cannot only prevent a lifetime of chronic disability but also, most importantly, save lives. In this article, we discuss complexities associated with NBS processes in the United States, with a focus on challenges in neuromuscular disorders.

Observations: As new interventions for neuromuscular disorders become available, the clinical community must prepare to overcome the challenges of adding new diseases to screening panels and understand the rigorous evidence review at the federal level and the complex process of state-level implementation.

Metabotropic glutamate receptor 1 (mGluR1): antibody specificity and receptor expression in cultured primary neurons.

The availability of high quality, well-characterized antibodies for molecular and cellular neuroscience studies is important. However, not all available antibodies are rigorously evaluated, nor are limitations of particular antibodies often reported. We have examined a panel of currently available mGluR1 antibodies and have identified which ones are selective for use by western blots and immunocytochemistry.

Decreased Lin7b expression in layer 5 pyramidal neurons may contribute to impaired corticostriatal connectivity in huntington disease.

Motor dysfunction, cognitive impairment, and regional cortical atrophy indicate cerebral cortical involvement in Huntington disease (HD). To address the hypothesis that abnormal corticostriatal connectivity arises from polyglutamine-related alterations in cortical gene expression, we isolated layer 5 cortical neurons by laser-capture microdissection and analyzed transcriptome-wide mRNA changes in them. Enrichment of transcription factor mRNAs including foxp2, tbr1, and neuroD6, and neurotransmission- and plasticity-related RNAs including sema5A, pclo, ntrk2, cntn1, and Lin7b were observed.

Phosphorylation of the homer-binding domain of group I metabotropic glutamate receptors by cyclin-dependent kinase 5.

Phosphorylation of neurotransmitter receptors can modify their activity and regulate neuronal excitability. Cyclin-dependent kinase 5 (cdk5) is a proline-directed serine/threonine kinase involved not only in neuronal development, but also in synaptic function and plasticity. Here we demonstrate that group I metabotropic glutamate receptors (mGluRs), which modulate post-synaptic signaling by coupling to intracellular signal transduction pathways, are phosphorylated by cdk5.

Interactions between metabotropic glutamate 5 and adenosine A2A receptors in normal and parkinsonian mice.

Evidence for heteromeric receptor complexes comprising adenosine A2A and metabotropic glutamate 5 (mGlu5) receptors in striatum has raised the possibility of synergistic interactions between striatal A2A and mGlu5 receptors. We investigated the role of striatal A2A receptors in the locomotor stimulant and antiparkinsonian properties of mGlu5 antagonists using complementary pharmacologic and genetic approaches. Locomotion acutely stimulated by the mGlu5 antagonist [2-methyl-6-(phenylethynyl)-pyridine (MPEP)] was absent in mGlu5 knock-out (KO) mice and was potentiated by an A2A antagonist KW-6002 [(E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methylxanthine], both in normal and in dopamine-depleted (reserpinized) mice.

The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner.

Cyclin-dependent kinase 5 (Cdk5) is a critical regulator of neuronal migration in the developing CNS, and recent studies have revealed a role for Cdk5 in synaptogenesis and regulation of synaptic transmission. Deregulation of Cdk5 has been linked to the pathology of neurodegenerative diseases such as Alzheimer's disease. Activation of Cdk5 requires its association with a regulatory subunit, and two Cdk5 activators, p35 and p39, have been identified.

Small Heteroborane Cluster Systems. 6. Mössbauer Effect Study of Iron Substituted Small Metallaborane Clusters.

The Mössbauer effect spectra for a series of small [Fe(eta(5)-C(5)H(5))(CO)(x)()] substituted metallaborane complexes are reported, where x = 1 or 2. The pentaborane cage in compounds [Fe(eta(5)-C(5)H(5))(CO)(2)B(5)H(7)P(C(6)H(5))(2)] (1), [Fe(eta(5)-C(5)H(5))(CO)(2)B(5)H(8)] (2), and [(Fe(eta(5)-C(5)H(5))(CO)(2))(2)B(5)H(7)] (3) was found to act as a significantly better donor ligand than the ligands in a comparison group of previously reported [Fe(eta(5)-C(5)H(5))(CO)LX] complexes, where L = CO or PPh(3) and X = halide, pseudohalide, or alkyl ligands. These metallaborane complexes were found to most resemble their silyl analogues in Mössbauer spectral parameters and the electronic distribution around the iron centers.