Objective: Alfaxalone is a commonly used anesthetic agent in small animals. In cats, alfaxalone can be administered as an IM agent to achieve clinically useful sedation or anesthesia, negating the need for IV injection in difficult patients. The molecular structure of alfaxalone is similar to the hormone progesterone (P4).
View Article and Find Full Text PDFTay-Sachs disease (TSD) is a fatal neurodegenerative disorder caused by a deficiency of the enzyme hexosaminidase A (HexA). TSD also occurs in sheep, the only experimental model of TSD that has clinical signs of disease. The natural history of sheep TSD was characterized using serial neurological evaluations, 7 Tesla magnetic resonance imaging, echocardiograms, electrodiagnostics, and cerebrospinal fluid biomarkers.
View Article and Find Full Text PDFWe describe a metal-free, photocatalytic hydrodefluorination (HDF) of polyfluoroarenes (FA) using pyrene-based photocatalysts (Py). The weak "π-hole-π" interaction between Py and FA promotes the electron transfer against unfavorable energetics (ΔG up to 0.63 eV) and initiates the subsequent HDF.
View Article and Find Full Text PDFWe describe a new strategy to generate non-coordinating anions using zwitterionic metal-organic frameworks (MOFs). By assembly of anionic inorganic secondary building blocks (SBUs) ([In(CO2)4](-)) with cationic metalloporphyrin-based organic linkers, we prepared zwitterionic MOFs in which the complete internal charge separation effectively prevents the potential binding of the counteranion to the cationic metal center. We demonstrate the enhanced Lewis acidity of Mn(III)- and Fe(III)-porphyrins in the zwitterionic MOFs in three representative electrocyclization reactions: [2 + 1] cycloisomerization of enynes, [3 + 2] cycloaddition of aziridines and alkenes, and [4 + 2] hetero-Diels-Alder cycloaddition of aldehydes with dienes.
View Article and Find Full Text PDFTwo non-interpenetrated zirconium metal-organic frameworks (Zr-MOFs), NPF-200 and NPF-201, were synthesized via the assembly of elongated tetrahedral linkers with Zr6 and Zr8 clusters. They represent the first examples of MOFs to have the β-UH3-like, 4,12,12T1 topology. Upon activation, NPF-200 exhibits the largest BET surface area (5463 m(2) g(-1)) and void volume (81.
View Article and Find Full Text PDFAdeno-associated viral (AAV) vectors have shown promise as a platform for gene therapy of neurological disorders. Achieving global gene delivery to the central nervous system (CNS) is key for development of effective therapies for many of these diseases. Here we report the isolation of a novel CNS tropic AAV capsid, AAV-B1, after a single round of in vivo selection from an AAV capsid library.
View Article and Find Full Text PDFEffective gene delivery to the central nervous system (CNS) is vital for development of novel gene therapies for neurological diseases. Adeno-associated virus (AAV) vectors have emerged as an effective platform for in vivo gene transfer, but overall neuronal transduction efficiency of vectors derived from naturally occurring AAV capsids after systemic administration is relatively low. Here, we investigated the possibility of improving CNS transduction of existing AAV capsids by genetically fusing peptides to the N-terminus of VP2 capsid protein.
View Article and Find Full Text PDFAn anionic indium porphyrin framework (UNLPF-10) consisting of rare Williams β-tetrakaidecahedral cages was constructed using an octatopic ligand linked with 4-connected [In(COO)4](-) SBUs. Remarkably, the extent of indium metalation of porphyrin macrocycles in UNLPF-10 can be facilely tuned in situ depending on the M/L ratio during synthesis, resulting in a controllable framework charge density and photocatalytic activity toward the selective oxygenation of sulfides.
View Article and Find Full Text PDFMetal-organic frameworks (MOFs) are emerging microporous materials that are promising for capture and sequestration of CO2 due to their tailorable binding properties. However, it remains a grand challenge to pre-design a MOF with a precise, multivalent binding environment at the molecular level to enhance CO2 capture. Here, we report the design, synthesis, and direct X-ray crystallographic observation of a porphyrinic MOF, UNLPF-2, that contains CO2-specific single molecular traps.
View Article and Find Full Text PDFProgressive debilitating neurological defects characterize feline G(M1) gangliosidosis, a lysosomal storage disease caused by deficiency of lysosomal β-galactosidase. No effective therapy exists for affected children, who often die before age 5 years. An adeno-associated viral vector carrying the therapeutic gene was injected bilaterally into two brain targets (thalamus and deep cerebellar nuclei) of a feline model of G(M1) gangliosidosis.
View Article and Find Full Text PDFA "pillar-free", highly porous metalloporphyrinic framework (UNLPF-1) exhibiting eclipsed porphyrin arrays has been constructed from an octacarboxylate ligand connected with paddlewheel secondary building units. UNLPF-1 possesses two types of open metal sites and exhibits an efficient selectivity toward capture of CO2 over N2.
View Article and Find Full Text PDFThree pediatric chimpanzees and one pediatric gibbon were anesthetized for routine physical examination. Anesthesia was maintained with inhalant delivered via a laryngeal mask airway (LMA). The LMA was easy to insert, provided adequate control of the airway for ventilation, and caused no tracheal stimulation.
View Article and Find Full Text PDFObjective: To characterize the antinociceptive action of IM-administered butorphanol, buprenorphine, or a combination of both by use of a thermal threshold method in cats.
Animals: 2 male and 4 female domestic cats.
Procedures: In a controlled, masked, randomized, crossover study design, thermal thresholds were measured by use of a thermal threshold-testing device developed for cats.