HIV Subtypes B and C gp120 and Methamphetamine Interaction: Dopaminergic System Implicates Differential Neuronal Toxicity

HIV subtypes or clades differentially induce HIV-associated neurocognitive disorders (HAND) and substance abuse is known to accelerate HIV disease progression. The HIV-1 envelope protein gp120 plays a major role in binding and budding in the central nervous system (CNS) and impacts dopaminergic functions. However, the mechanisms utilized by HIV-1 clades to exert differential effects and the methamphetamine (METH)-associated dopaminergic dysfunction are poorly understood. We hypothesized that clade B and C gp120 structural sequences, modeling based analysis, dopaminergic effect, and METH potentiate neuronal toxicity in astrocytes. We evaluated the effect of clade B and C gp120 and/or METH on the DRD-2, DAT, CaMKs and CREBP transcription. Both the structural sequence and modeling studies demonstrated that clade B gp120 in V1-V4, α -2 and N-glycosylated sites are distinct from clade C gp120. The distinct structure and sequence variation of clade B gp120 differentially impact DRD-2, DAT, CaMK II and CaMK IV mRNA, protein and intracellular expression compared to clade C gp120. However, CREB transcription is upregulated by both clade B and C gp120, and METH co-treatment potentiated these effects. In conclusion, distinct structural sequences of HIV-1 clade B and C gp120 differentially regulate the dopaminergic pathway and METH potentiates neurotoxicity

1′-Methyl-4′-(1-naphth­yl)-1′′,2′′,3′′,4′′-tetra­hydro­indane-2-spiro-2′-pyrrolidine-3′-spiro-2′′-naphthalene-1,3,1′′-trione

In the title compound, C32H25NO3, the pyrrolidine ring adopts an envelope conformation, whereas the cyclo­hexa­none ring in the tetra­hydro­naphthalene fused-ring system adopts a half-chair conformation. The indanedione unit is oriented at an angle of 58.9 (1)° with respect to the naphthyl ring system. Three intra­molecular C—H⋯O close contacts and an intra­molecular C—H⋯π inter­action are observed. In the crystal, mol­ecules associate via C—H⋯O hydrogen bonds, forming a helical chain with a C(10) motif along the b axis

Puckering behavior in six new phosphoric triamides containing aliphatic six- and seven-membered ring groups and a database survey of analogous ring-containing structures

The influence of a N heteroatom on the ring conformations of six- and seven- membered aliphatic rings in six new C(O)NHP(O)-based phosphoric triamide structures (analysed by X-ray crystallography) is investigated. Additionally the influence of steric and crystal packing effects is also studied by the analysis of Hirshfeld surfaces. The results are compared to analogous structures with three- to seven- aliphatic membered rings deposited in the Cambridge Structural Database. In the newly determined structures, the six-membered rings only show the near-chair conformation with a maximum deviation of the θ puckering parameter of 4.4° from the ideal chair value of 0°/180°, while the seven-membered rings are found in different conformations such as near-chair, twist chair and twist sofa

Commandeering a biological pathway using aptamer-derived molecular adaptors

Induction of molecular proximity can mediate a discrete functional response in biological systems. Therefore, creating new and specific connectivity between non-interacting proteins is a means of imposing rational control over biological processes. According to this principle, here we use composite RNA aptamers to generate molecular adaptors that link various ‘target’ molecules to a common ‘utility’ molecule, with the utility molecule being an entry point to a pathway conscripted to process the target molecule. In particular, we created a bi-functional aptamer that simultaneously binds to the green fluorescent protein (serving as a surrogate extracellular target) and the opsonin C3b/iC3b (serving as the utility molecule). This bi-functional aptamer enabled us to commandeer the C3-based opsonization-phagocytosis pathway to selectively transport an extracellular target into the lysosome for degradation. This novel strategy has the potential for powerful therapeutic applications with extracellular proteins involved in tumor development or surface markers on cancer cells as the target molecules

Analysis of C3 Suggests Three Periods of Positive Selection Events and Different Evolutionary Patterns between Fish and Mammals

BACKGROUND: The third complement component (C3) is a central protein of the complement system conserved from fish to mammals. It also showed distinct characteristics in different animal groups. Striking features of the fish complement system were unveiled, including prominent levels of extrahepatic expression and isotypic diversity of the complement components. The evidences of the involvement of complement system in the enhancement of B and T cell responses found in mammals indicated that the complement system also serves as a bridge between the innate and adaptive responses. For the reasons mentioned above, it is interesting to explore the evolutionary process of C3 genes and to investigate whether the huge differences between aquatic and terrestrial environments affected the C3 evolution between fish and mammals. METHODOLOGY/PRINCIPAL FINDINGS: Analysis revealed that these two groups of animals had experienced different evolution patterns. The mammalian C3 genes were under purifying selection pressure while the positive selection pressure was detected in fish C3 genes. Three periods of positive selection events of C3 genes were also detected. Two happened on the ancestral lineages to all vertebrates and mammals, respectively, one happened on early period of fish evolutionary history. CONCLUSIONS/SIGNIFICANCE: Three periods of positive selection events had happened on C3 genes during history and the fish and mammals C3 genes experience different evolutionary patterns for their distinct living environments

Real-time procedural modeling of fracture of brittle materials in games

This thesis addresses the problem of dynamically modeling fracture of brittle objects in next-generation games. The challenges of this research are to implement a fracture framework in real-time and that produces results that are visually realistic. An image- based procedural approach is proposed since speed and memory usage are important factors in a commercial game system. The criteria for fracture depend on the strength of the impact force and position of the impact point. The crack patterns are based on a probability texture that defines the weak areas of the object where the crack propagates. The probability textures are different for various materials and are specifically designed by the user. Our technique is unique and allows the user to have more control over the shape of the fragments for different types of objects. The results presented demonstrate that the fragments can be dynamically generated in real-time.MASTER OF ENGINEERING (SCE

2-(exo-Tricyclo[5.2.1.0<SUP>2,6</SUP>]deca-4,8-dien-3-endo-yl)acetaldehyde 2,4-dinitrophenylhydrazone

The six-membered ring of the norbornene moiety in the title compound, C18H18N4O4, is in a slightly distorted boat conformation, and the two five-membered rings within it adopt envelope conformations. The structure is stabilized by inter- and intramolecular N-H⋯O hydrogen bonds

Crystal and Molecular Structure of Desmodin

The crystal structure of the title compound has been determined from X-ray diffraction. The compound crystallizes from benzene in the orthorhombic system, space group P212121, with unit cell parameters: a = 8.485(2), b = 9.816(2), c = 22.597(4) A, Z = 4, V = 1881.9(7) A3. The structure was determined by direct methods and refined to a final R-factor of 0.04. Six membered rings B and E are planar. Ring A and ring C are in slightly distorted sofa conformation. Ring D is in envelope conformation. The structure is stabilised by weak intermolecular C-H...O hydrogen bond

Dicyclohexylammonium O,O’-Diphenyl Phosphate, [(C6H11)2NH2][(C6H5O)2P(O)(O)]: Spectroscopic Study, Crystal Structure, and Hirshfeld Surface Analysis

The title salt, [(C6H11)2NH2][(C6H5O)2P(O)(O)], crystallizes in the chiral space group P212121, composed of achiral cation and anion components. The strong charge-assisted N–H…O hydrogen bonds build a linear assembly along the a axis, including a non-centrosymmetric C22(6) chain graph-set motif. The intra and intermolecular C–H…O interactions as well as the C–H…π-electron ring interactions also exist in the crystal structure. Fingerprint plots are used for a detailed investigation of intermolecular interactions participating in the crystal packing. The spectroscopic features (IR, 1H NMR, 13C{1H} NMR, 31P{1H} NMR, and mass) are studied