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Cell cycle progression into S phase requires the induction of histone gene expression to package newly synthesized DNA as chromatin. Cyclin E stimulation of CDK2 at the Restriction point late in G1 controls both histone gene expression by the p220NPAT/HiNF-P pathway and initiation of DNA replication through the pRB/E2F pathway. The three CDK inhibitors (CKIs) p21CIP1/WAF1, p27KIP1, and p57KIP2 attenuate CDK2 activity. Here we find that γ-irradiation induces p21CIP1/WAF1 but not the other two CKIs, while reducing histone H4 mRNA levels but not histone H4 gene promoter activation by the p220NPAT/HiNF-P complex. We also show that p21CIP1/WAF1 is less effective than p27KIP1 and p57KIP2 in inhibiting the CDK2 dependent phosphorylation of p220NPAT at subnuclear foci and transcriptional activation of histone H4 genes. The greater effectiveness of p57KIP2 in blocking the p220NPAT/HiNF-P pathway is attributable in part to its ability to form a specific complex with p220NPAT that may suppress CDK2/cyclin E phosphorylation through direct substrate inhibition. We conclude that CKIs selectively control stimulation of the histone H4 gene promoter by the p220NPAT/HiNF-P complex. J. Cell. Physiol. 219: 438–448, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The reaction of the N-heterocyclic substrates with carbene complex (II) produces azaisobenzofuran intermediates. [ABSTRACT FROM AUTHOR]

Mammalian UDP-glucuronosyltransferase (UGT) isozymes detoxify a vast number of critical drugs, toxins, dietary constituents, and environmental chemicals by conjugation with glucuronic acid. Because UGTs are endoplasmic reticulum-bound making purification and biochemical analyses difficult, the mechanism of UGT conversion of innumerable chemicals is not understood. Recently, we uncovered that UGT isozymes require phosphorylation for activity. Phosphorylation, regulated via signaling, occurs on both serine/threonine and tyrosine residues. PKC phosphorylation is shown to determine substrate specificity of a human UGT isozyme; Src tyrosine kinase phosphorylation of another UGT is shown to control detoxification of catechol estrogens, linked to breast cancer. Moreover, we have evidence that UGT phosphorylation can be targeted transiently to reduce premature clearance of therapeutic drugs (e.g mycophenolic acid), suggesting inhibition of glucuronidation can greatly improve efficacy. [ABSTRACT FROM AUTHOR]

Two mixed-valent tetranuclear MnII/III complexes of formula [Mn4(L)4(OAc)2(OMe)4] ·2H2O ( 1) and [Mn4(L)4(OAc)2(OMe)4] ( 2), in which HL = 9-hydroxyphenalenone, were synthesized by a solvothermal method and magnetostructurally characterized. Complex 1 crystallizes in the monoclinic space group P21/ c with a = 12.69 Å, b = 15.51 Å, c = 15.40 Å, β = 114.35° and Z = 2. Complex 2 crystallizes in the triclinic space group P $\bar {1}$ with a = 8.74 Å, b = 12.06 Å, c = 13.89 Å, α = 114.23° β = 102.16°, γ = 98.54° and Z = 1. Both 1 and 2 are products of the same reaction and have the same molecular formula except for the solvent of crystallization. X-ray crystallographic studies show that 1 and 2 have six coordinated MnII and MnIII ions and almost the same tetranuclear core, which resembles a rhomboidal 'butterfly motif' except that the MnIII ions are at the 'wing-tip' and MnII ions in the 'body' positions. The MnII/III ions that form the metal core in 1 and 2 have two μ3-Oalkoxo and four μ2-Oalkoxo bridges along with two carboxylate anions that bridge the MnII and MnIII centres situated at the 'body' and the 'wing-tip' positions. Complex 1 shows intermolecular π ···π and C-H ···π interactions. Detailed direct current (DC) magnetic susceptibility studies in the temperature range 2-300 K suggest that 1 and 2 are antiferromagnetically coupled. The exchange coupling constants and g values were estimated by theoretical fitting of the magnetic susceptibility data. We find that it is difficult to determine a model with three different coupling constants ( J1, J2, J3) unambiguously from the magnetic susceptibility data. Nevertheless, the bonding parameters of the metal core for 1 and 2 suggest a simplification to two exchange coupling constants ( Jbb and Jwb) with a reasonably good fit. In addition, the theoretical fitting of the magnetic data when correlated to the structure shows good agreement for complexes with similar cores in the literature and it appears that the exchange coupling constants correlate with the solid angle formed by the μ3-O(alk)oxo bonded to the MnII/III ions. [ABSTRACT FROM AUTHOR]

Whole brain neuroanatomy using tera‐voxel light‐microscopic data sets is of much current interest. A fundamental problem in this field is the mapping of individual brain data sets to a reference space. Previous work has not rigorously quantified in‐vivo to ex‐vivo distortions in brain geometry from tissue processing. Further, existing approaches focus on registering unimodal volumetric data; however, given the increasing interest in the marmoset model for neuroscience research and the importance of addressing individual brain architecture variations, new algorithms are necessary to cross‐register multimodal data sets including MRIs and multiple histological series. Here we present a computational approach for same‐subject multimodal MRI‐guided reconstruction of a series of consecutive histological sections, jointly with diffeomorphic mapping to a reference atlas. We quantify the scale change during different stages of brain histological processing using the Jacobian determinant of the diffeomorphic transformations involved. By mapping the final image stacks to the ex‐vivo post‐fixation MRI, we show that (a) tape‐transfer assisted histological sections can be reassembled accurately into 3D volumes with a local scale change of 2.0 ± 0.4% per axis dimension; in contrast, (b) tissue perfusion/fixation as assessed by mapping the in‐vivo MRIs to the ex‐vivo post fixation MRIs shows a larger median absolute scale change of 6.9 ± 2.1% per axis dimension. This is the first systematic quantification of local metric distortions associated with whole‐brain histological processing, and we expect that the results will generalize to other species. These local scale changes will be important for computing local properties to create reference brain maps. [ABSTRACT FROM AUTHOR]

An in‐depth understanding of the genetics and evolution of brain function and behavior requires a detailed mapping of gene expression in functional brain circuits across major vertebrate clades. Here we present the Zebra finch Expression Brain Atlas (ZEBrA; www.zebrafinchatlas.org, RRID: SCR_012988), a web‐based resource that maps the expression of genes linked to a broad range of functions onto the brain of zebra finches. ZEBrA is a first of its kind gene expression brain atlas for a bird species and a first for any sauropsid. ZEBrA's >3,200 high‐resolution digital images of in situ hybridized sections for ~650 genes (as of June 2019) are presented in alignment with an annotated histological atlas and can be browsed down to cellular resolution. An extensive relational database connects expression patterns to information about gene function, mouse expression patterns and phenotypes, and gene involvement in human diseases and communication disorders. By enabling brain‐wide gene expression assessments in a bird, ZEBrA provides important substrates for comparative neuroanatomy and molecular brain evolution studies. ZEBrA also provides unique opportunities for linking genetic pathways to vocal learning and motor control circuits, as well as for novel insights into the molecular basis of sex steroids actions, brain dimorphisms, reproductive and social behaviors, sleep function, and adult neurogenesis, among many fundamental themes. [ABSTRACT FROM AUTHOR]

Traditionally, the dorsal lateral geniculate nucleus (LGN) and the inferior pulvinar (IPul) nucleus are considered as anatomically and functionally distinct thalamic nuclei. However, in several primate species it has also been established that the koniocellular (K) layers of LGN and parts of the IPul have a shared pattern of immunoreactivity for the calcium‐binding protein calbindin. These calbindin‐rich cells constitute a thalamic matrix system which is implicated in thalamocortical synchronisation. Further, the K layers and IPul are both involved in visual processing and have similar connections with retina and superior colliculus. Here, we confirmed the continuity between calbindin‐rich cells in LGN K layers and the central lateral division of IPul (IPulCL) in marmoset monkeys. By employing a high‐throughput neuronal tracing method, we found that both the K layers and IPulCL form comparable patterns of connections with striate and extrastriate cortices; these connections are largely different to those of the parvocellular and magnocellular laminae of LGN. Retrograde tracer‐labelled cells and anterograde tracer‐labelled axon terminals merged seamlessly from IPulCL into LGN K layers. These results support continuity between LGN K layers and IPulCL, providing an anatomical basis for functional congruity of this region of the dorsal thalamic matrix and calling into question the traditional segregation between LGN and the inferior pulvinar nucleus. [ABSTRACT FROM AUTHOR]

The marmoset is an emerging animal model for large-scale attempts to understand primate brain connectivity, but achieving this aim requires the development and validation of procedures for normalization and integration of results from many neuroanatomical experiments. Here we describe a computational pipeline for coregistration of retrograde tracing data on connections of cortical areas into a 3D marmoset brain template, generated from Nissl-stained sections. The procedure results in a series of spatial transformations that are applied to the coordinates of labeled neurons in the different cases, bringing them into common stereotaxic space. We applied this procedure to 17 injections, placed in the frontal lobe of nine marmosets as part of earlier studies. Visualizations of cortical patterns of connections revealed by these injections are supplied as Supplementary Materials. Comparison between the results of the automated and human-based processing of these cases reveals that the centers of injection sites can be reconstructed, on average, to within 0.6 mm of coordinates estimated by an experienced neuroanatomist. Moreover, cell counts obtained in different areas by the automated approach are highly correlated ( r = 0.83) with those obtained by an expert, who examined in detail histological sections for each individual. The present procedure enables comparison and visualization of large datasets, which in turn opens the way for integration and analysis of results from many animals. Its versatility, including applicability to archival materials, may reduce the number of additional experiments required to produce the first detailed cortical connectome of a primate brain. J. Comp. Neurol. 524:2161-2181, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene-structure-function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system 'maps' comprising molecular, anatomical, and physiological data. This research will identify which neural features are likely to generalize across species, and which are unlikely to be broadly conserved. It will also suggest causal relationships between genes, development, adult anatomy, physiology, and, ultimately, behavior. These causal hypotheses can then be tested experimentally. Finally, insights from comparative research can inspire and guide technological development. To promote this research agenda, we recommend that teams of investigators coalesce around specific research questions and select a set of 'reference species' to anchor their comparative analyses. These reference species should be chosen not just for practical advantages, but also with regard for their phylogenetic position, behavioral repertoire, well-annotated genome, or other strategic reasons. We envision that the nervous systems of these reference species will be mapped in more detail than those of other species. The collected data may range from the molecular to the behavioral, depending on the research question. To integrate across levels of analysis and across species, standards for data collection, annotation, archiving, and distribution must be developed and respected. To that end, it will help to form networks or consortia of researchers and centers for science, technology, and education that focus on organized data collection, distribution, and training. These activities could be supported, at least in part, through existing mechanisms at NSF, NIH, and other agencies. It will also be important to develop new integrated software and database systems for cross-species data analyses. Multidisciplinary efforts to develop such analytical tools should be supported financially. Finally, training opportunities should be created to stimulate multidisciplinary, integrative research into brain structure, function, and evolution. J. Comp. Neurol. 522:1445-1453, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT We describe a set of new comprehensive, high-quality, high-resolution digital images of histological sections from the brain of male zebra finches ( Taeniopygia guttata) and make them publicly available through an interactive website (http://zebrafinch.brainarchitecture.org/). These images provide a basis for the production of a dimensionally accurate and detailed digital nonstereotaxic atlas. Nissl- and myelin-stained brain sections are provided in the transverse, sagittal, and horizontal planes, with the transverse plane approximating the more traditional Frankfurt plane. In addition, a separate set of brain sections in this same plane is stained for tyrosine hydroxylase, revealing the distribution of catecholaminergic neurons (dopaminergic, noradrenergic, and adrenergic) in the songbird brain. For a subset of sagittal sections we also prepared a corresponding set of drawings, defining and annotating various nuclei, fields, and fiber tracts that are visible under Nissl and myelin staining. This atlas of the zebra finch brain is expected to become an important tool for birdsong research and comparative studies of brain organization and evolution. J. Comp. Neurol. 521:3702-3715, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The marmoset is an emerging animal model for large-scale attempts to understand primate brain connectivity, but achieving this aim requires the development and validation of procedures for normalization and integration of results from many neuroanatomical experiments. Here we describe a computational pipeline for coregistration of retrograde tracing data on connections of cortical areas into a 3D marmoset brain template, generated from Nissl-stained sections. The procedure results in a series of spatial transformations that are applied to the coordinates of labeled neurons in the different cases, bringing them into common stereotaxic space. We applied this procedure to 17 injections, placed in the frontal lobe of nine marmosets as part of earlier studies. Visualizations of cortical patterns of connections revealed by these injections are supplied as Supplementary Materials. Comparison between the results of the automated and human-based processing of these cases reveals that the centers of injection sites can be reconstructed, on average, to within 0.6 mm of coordinates estimated by an experienced neuroanatomist. Moreover, cell counts obtained in different areas by the automated approach are highly correlated ( r = 0.83) with those obtained by an expert, who examined in detail histological sections for each individual. The present procedure enables comparison and visualization of large datasets, which in turn opens the way for integration and analysis of results from many animals. Its versatility, including applicability to archival materials, may reduce the number of additional experiments required to produce the first detailed cortical connectome of a primate brain. J. Comp. Neurol. 524:2161-2181, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

An abstract of the article "Ligand-Free Copper-Catalyzed Efficient One-Pot Access of Benzo[b]pyrido[3,2-f][1,4]oxazepinones Through O-Heteroarylation-Smiles Rearrangement-Cyclization Cascade" by N. C. Ganguly, P. Mondal and colleagues is presented.