An Expedient Synthesis of Flexible Nucleosides through Enzymatic Glycosylation of Proximal and Distal Fleximer Bases

The structurally unique “fleximer” nucleosides were originally designed to investigate how flexibility in a nucleobase could potentially affect receptor–ligand recognition and function. Recently they have been shown to have low-to-sub-micromolar levels of activity against a number of viruses, including coronaviruses, filoviruses, and flaviviruses. However, the synthesis of distal fleximers in particular has thus far been quite tedious and low yielding. As a potential solution to this issue, a series of proximal fleximer bases (flex-bases) has been successfully coupled to both ribose and 2′-deoxyribose sugars by using the N-deoxyribosyltransferase II of Lactobacillus leichmannii (LlNDT) and Escherichia coli purine nucleoside phosphorylase (PNP). To explore the range of this facile approach, transglycosylation experiments on a thieno-expanded tricyclic heterocyclic base, as well as several distal and proximal flex-bases were performed to determine whether the corresponding fleximer nucleosides could be obtained in this fashion, thus potentially significantly shortening the route to these biologically significant compounds. The results of those studies are reported herein.     

Commercial Milk Enzyme‐Linked Immunosorbent Assay (ELISA) Kit Reactivities to Purified Milk Proteins and Milk‐Derived Ingredients

Numerous commercial enzyme‐linked immunosorbent assay (ELISA) kits exist to quantitatively detect bovine milk residues in foods. Milk contains many proteins that can serve as ELISA targets including caseins (α‐, β‐, or κ‐casein) and whey proteins (α‐lactalbumin or β‐lactoglobulin). Nine commercially‐available milk ELISA kits were selected to compare the specificity and sensitivity with 5 purified milk proteins and 3 milk‐derived ingredients. All of the milk kits were capable of quantifying nonfat dry milk (NFDM), but did not necessarily detect all individual protein fractions. While milk‐derived ingredients were detected by the kits, their quantitation may be inaccurate due to the use of different calibrators, reference materials, and antibodies in kit development. The establishment of a standard reference material for the calibration of milk ELISA kits is increasingly important. The appropriate selection and understanding of milk ELISA kits for food analysis is critical to accurate quantification of milk residues and informed risk management decisions.     

Recombinant adeno-associated virus targets passenger gene expression to cones in primate retina

Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy of photoreceptor-based diseases. Previous studies have demonstrated that rAAV serotypes 2 and 5 can transduce both rod and cone photoreceptors in rodents and dogs, and it can target rods, but not cones in primates. Here we report that using a human cone-specific enhancer and promoter to regulate expression of a green fluorescent protein (GFP) reporter gene in an rAAV-5 vector successfully targeted expression of the reporter gene to primate cones, and the time course of GFP expression was able to be monitored in a living animal using the RetCam II digital imaging system.     

Occurrence, synthesis, and mammalian cell cytotoxicity and genotoxicity of haloacetamides: an emerging class of nitrogenous drinking water disinfection byproducts

The haloacetamides, a class of emerging nitrogenous drinking water disinfection byproduct (DBPs), were analyzed for their chronic cytotoxicity and for the induction of genomic DNA damage in Chinese hamster ovary cells. The rank order for cytotoxicity of 13 haloacetamides was DIAcAm > IAcAm > BAcAm > TBAcAm > BIAcAm > DBCAcAm > CIAcAm > BDCAcAm > DBAcAm > BCAcAm > CAcAm > DCAcAm > TCAcAm. The rank order of their genotoxicity was TBAcAm > DIAcAm approximately equal to IAcAm > BAcAm > DBCAcAm > BIAcAm > BDCAcAm > CIAcAm > BCAcAm > DBAcAm > CAcAm > TCAcAm. DCAcAm was not genotoxic. Cytotoxicity and genotoxicity were primarily determined by the leaving tendency of the halogens and followed the order I > Br > > Cl. With the exception of brominated trihaloacetamides, most of the toxicity rank order was consistent with structure-activity relationship expectations. For di- and trihaloacetamides, the presence of at least one good leaving halogen group (I or Br but not Cl) appears to be critical for significant toxic activity. Log P was not a factor for monohaloacetamides but may play a role in the genotoxicity of trihaloacetamides and possible activation of dihaloacetamides by intracellular GSH and -SH compounds.     

Why some capuchin monkeys (Cebus apella) use probing tools (and others do not).

Tufted capuchins (Cebus apella) were provided with a task that facilitated the use and modification of sticks as probing tools. It was found that subjects aged 10 years or older at initial task exposure were less likely to use tools than were younger subjects. Furthermore, juveniles whose mothers died before the subjects were aged 3 years were less likely to use tools than were juveniles whose mothers survived through this period. The ability to use tools was not related to subject sex or to access to the tool site or raw tool materials. Subjects modified tools both before and during their use, and the relative percentage of tools modified increased with subject age. Thus, it appears that capuchins most readily acquire tool use before the age of 10 years and that early disruption of the mother–infant relationship has deleterious effects on the emergence of instrumental behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Depressed writing: Cognitive distortions in the works of depressed and nondepressed poets and writers.

Previous research has consistently found that poets and writers suffer from higher rates of psychological disturbance than the general population; what is lacking in the research is analysis of the works themselves. This study examined cognitive distortions, a known indicator of depression, in writing samples of 36 eminent depressed authors and 36 eminent nondepressed authors. Results indicate that depressed authors have more cognitive distortions in their writings than nondepressed authors. However, greater significance was found between poets and prose writers, with poets having substantially more cognitive distortions in their works. An interaction effect was found between study group (depressed or control) and medium (poetry or prose) indicating that nondepressed prose writers had significantly fewer cognitive distortions than nondepressed poets, depressed poets, and depressed writers. Differences in gender and time period are explored as well. Findings suggest a general acceptance of depressive thinking and writing for poets that is not present for prose writers. Implications for the effectiveness of writing as a form of psychotherapy are also discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interparental conflict, negative parenting, and children's adjustment: Bridging links between parents' depression and children's psychological distress.

Pathways linking parental depressive symptoms, adult relationship insecurity, interparental conflict, negative parenting, and children's psychological adjustment (internalizing symptoms and externalizing problems) were assessed using a 3-wave longitudinal research design. Two-parent families (N = 352) with 11- to 13-year-old children (179 boys, 173 girls) participated in the study. Maternal and paternal depressive symptoms were associated with insecurity in adult close relationships assessed 12 months later, which was concurrently related to heightened levels of interparental conflict. Controlling for children's initial symptom levels, interparental conflict was related to child appraisals of father and mother rejection assessed an additional 12 months later, which were related to children's internalizing symptoms and externalizing problems, respectively. Results are discussed with regard to the implications for understanding the complex interplay between adult depressive symptoms, attributions in close adult relationships, interparental conflict, negative parenting, and children's psychological adjustment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)