Bridging Neuroscience and Clinical Practice: Accelerating Stroke Recovery in a Pontine Infarction Case Through Neuroplasticity-Based Rehabilitation.

Foundational neuroscience is crucial to locating lesions, understanding current functional limitations, making correct prognoses, and designing holistic and realistic treatment plans for stroke patients. A model bridging neuroscience knowledge and clinical practice was assessed through a rare pontine infarction case. A 76-year-old patient suffered two consecutive right-sided pontine ischemic strokes, leading to significant motor and sensory abnormalities on the left side.

Primary severe acute respiratory syndrome coronavirus infection limits replication but not lung inflammation upon homologous rechallenge.

Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days.

Respiratory syncytial virus impairs macrophage IFN-alpha/beta- and IFN-gamma-stimulated transcription by distinct mechanisms.

Macrophages are the primary lung phagocyte and are instrumental in maintenance of a sterile, noninflamed microenvironment. IFNs are produced in response to bacterial and viral infection, and activate the macrophage to efficiently counteract and remove pathogenic invaders. Respiratory syncytial virus (RSV) inhibits IFN-mediated signaling mechanisms in epithelial cells; however, the effects on IFN signaling in the macrophage are currently unknown.

Transactivation of lung lysozyme expression by Ets family member ESE-1.

Epithelial-specific Ets (ESE) transcription factors, consisting of ESE-1, ESE-2, and ESE-3, are constitutively expressed in distinct epithelia of mucosal tissues, including the lung. Each ESE member exhibits alternative splicing and yields at least two isoforms (a and b) with transcriptional targets largely unidentified. The studies described herein define a novel role for ESE transcription factors in transactivation of the human lysozyme gene (LYZ), an essential component of innate defense in lung epithelia.

Positive and negative regulation of c-Myb by cyclin D1, cyclin-dependent kinases, and p27 Kip1.

The c-Myb transcription factor controls differentiation and proliferation in hematopoietic and other cell types and has latent transforming activity, but little is known about its regulation during the cell cycle. Here, c-Myb was identified as part of a protein complex from human T cells containing the cyclin-dependent kinase (CDK) CDK6. Assays using model reporter constructs as well as endogenous target genes showed that the activity of c-Myb was inhibited by cyclin D1 plus CDK4 or CDK6 but stimulated by expression of the CDK inhibitors p16 Ink4a, p21 Cip1, or p27 Kip1.

Positive and negative determinants of target gene specificity in myb transcription factors.

The A-Myb and c-Myb transcription factors share a highly conserved DNA-binding domain and activate the same promoters in reporter gene assays. However, the two proteins have distinct biological activities, and expressing them individually in human cells leads to the activation of distinct sets of endogenous genes, suggesting that each protein has a unique transcriptional specificity. Here, the structural and functional features of the Myb proteins were compared, using assays of endogenous gene expression to measure changes in specificity.

Pim-1 phosphorylates the DNA binding domain of c-Myb.

The c-Myb transcription factor regulates cellular differentiation and proliferation and is regulated by complex mechanisms that control its repressed oncogenic activity. The transcriptional activity of c-Myb is regulated by the serine/threonine protein kinase Pim-1. Here, we show that Pim-1 is able to interact with c-Myb and the closely related transcription factor A-Myb, via direct interactions with the highly conserved Myb DNA binding domain.

Distinct changes in gene expression induced by A-Myb, B-Myb and c-Myb proteins.

The c-Myb, A-Myb and B-Myb transcription factors have nearly identical DNA-binding domains, activate the same reporter gene constructs in animal cells, but have different biological roles. The Myb proteins are often coexpressed in the same cells, raising questions about whether they activate similar or distinct gene expression profiles, and whether they cooperate or compete in regulating the same promoters. Here, recombinant adenoviruses were used to express each protein in human mammary cells, and then microarray assays were used to assess global changes in gene expression.