Diet of the Omani Owl,Strix butleri,near Nakhal,Oman

The diet of the Omani Owl, Strix butleri, was studied for the first time based on re- cently collected pellets. A total of 22 individual prey items represented three mam- mals (all rodents), at least two undetermined gecko species and one scorpion. By fre- quency, Acomys cahirinus constituted 31.8% and lizards 27.3%, while Gerbillus nanus and G. dasyurus were the least consumed prey items (4.5% each).     

A comprehensive calorimetric investigation of an entropically driven T cell receptor-peptide/major histocompatibility complex interaction

The alphabeta T cell receptor (TCR) is responsible for recognizing peptides bound and "presented" by major histocompatibility complex (MHC) molecules. We recently reported that at 25 degrees C the A6 TCR, which recognizes the Tax peptide presented by the class I MHC human leukocyte antigen-A*0201 (HLA-A2), binds with a weak DeltaH degrees , a favorable DeltaS degrees , and a moderately negative DeltaC(p). These observations were of interest given the unfavorable binding entropies and large heat capacity changes measured for many other TCR-ligand interactions, suggested to result from TCR conformational changes occurring upon binding. Here, we further investigated the A6-Tax/HLA-A2 interaction using titration calorimetry. We found that binding results in a pK(a) shift, complicating interpretation of measured binding thermodynamics. To better characterize the interaction, we measured binding as a function of pH, temperature, and buffer ionization enthalpy. A global analysis of the resulting data allowed determination of both the intrinsic binding thermodynamics separated from the influence of protonation as well as the thermodynamics associated with the pK(a) shift. Our results indicate that intrinsically, A6 binds Tax/HLA-A2 with a very weak DeltaH degrees , an even more favorable DeltaS degrees than previously thought, and a relatively large negative DeltaC(p). Comparison of these energetics with the makeup of the protein-protein interface suggests that conformational adjustments are required for binding, but these are more likely to be structural shifts, rather than disorder-to-order transitions. The thermodynamics of the pK(a) shift suggest protonation may be linked to an additional process such as ion binding.     

Prodrugs of CL316243: a selective beta3-adrenergic receptor agonist for treating obesity and diabetes.

CL316243 is a highly selective and potent beta3-adrenergic receptor agonist, and has been shown in rodent models to be an effective agent for treating obesity and Type II diabetes. To improve the oral absorption and pharmacokinetic profiles of CL316243, a number of prodrugs have been synthesized and evaluated. Several ester-type prodrugs show significant improvements in oral bioavailability in both rodent and primate models.     

Grooming decisions by damselflies, age-specific colonisation by water mites, and the probability of successful parasitism.

We examined whether host damselflies (Ischnura verticalis) in different stages of development were differentially susceptible to parasitism by larval water mites (Arrenurus pseudosuperior). We found that mites were successful in reaching the parasitic phase more often if they colonised hosts closer to emergence. Thus, we predicted that more mites should colonise damselflies closer to emergence and damselflies closer to emergence should spend more time defending against mites. We found that mites colonised damselflies closer to emergence in one of two experiments, but that damselflies in different stages of development did not differ in time spent defending against mites.     

Variation in female life-history traits among Alaskan populations of the threespine stickleback, Gasterosteus aculeatus L. (Pisces: Gasterosteidae)

Life-history characteristics of female threespine stickleback (Gasterosteus aculeatus) were examined in 12 populations, 11 freshwater and one anadromous, within the Cook Inlet region of Alaska. Because this area has been deglaciated during the last 20 000 years, the freshwater populations are recently derived, probably independendy, from the local marine or anadromous stickleback. Freshwater threespine stickleback have undergone considerable morphological evolution within this region, apparently in response to environmental factors including predatory regimes and environmental productivity. Our freshwater study populations were selected to sample this range of morphological variation in order to determine whether life-history traits and morphologies have followed similar evolutionary trajectories. Freshwater populations could be categorized generally into one of three ecomorphotypes: those inhabiting relatively productive lakes having one or more piscivorous fishes present, and in which the stickleback exhibit a fully developed pelvic girdle; those inhabiting low-calcium lakes that lack piscivorous fishes, and in which the pelvic structures are incomplete; those living in streams with piscivorous fishes, in which the stickleback have fully developed pelvic girdles. The anadromous population constituted a fourth ecomorphotype that lives in marine waters, and is robusdy armored. The freshwater populations showed considerable variation in all life-history traits assessed, and this variation generally corresponded to our ecomorphological classifications. Nevertheless, within each ecomorphotype there was sufficient variation to suggest that morphological and life-history traits may not always respond in the same manner in response to the same selective regime.     

Metabolism of Some “Second”– and “Fourth”–Generation Antidepressants: Iprindole, Viloxazine, Bupropion, Mianserin, Maprotiline, Trazodone, Nefazodone, and Venlafaxine

1. This review summarizes the major known aspects of the metabolism of second-generation (iprindole, viloxazine, bupropion, mianserin, maprotiline, and trazodone) and fourth-generation (nefazodone and venlafaxine) antidepressants.2. Discussions about specific enzymes involved and about possible pharmacokinetic drug–drug interactions, particularly as they relate to cytochrome P450 enzymes, are provided.     

Adaptive Changes in Postsynaptic Dopamine Receptors Despite Unaltered Dopamine Dynamics in Mice Lacking Monoamine Oxidase B

Monoamine oxidase (MAO) B is considered a key enzyme in dopamine metabolism. The present studies, conducted in MAO B knockout mice, show that lack of MAO B does not alter extracellular levels of dopamine in striatum. Similarly, the synthesis, storage, uptake, and release of dopamine are also unaltered. However, autoradiography revealed a significant up-regulation of the D2-like dopamine receptors in the striatum of MAO B knockout mice. Mutant mice also exhibit a functional supersensitivity of D1-dopamine receptors in the nucleus accumbens. Thus, the agonist SKF 38,393-induced c-Fos immunoreactivity was significantly increased in knockout mice as compared with wild-type controls. In view of the apparently normal basal dopamine dynamics observed in MAO B knockout mice, we hypothesize that a dopamine-independent mechanism underlies adaptations in dopamine receptor function that occur as a consequence of MAO B depletion. Finally, these findings suggest that chronic administration of MAO inhibitors, as occurs in the treatment of Parkinson's disease and depression, may be associated with an increased responsiveness of CNS neurons to dopamine receptor ligands.     

Elevated cytokines and chemokines in peripheral blood of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma

The global SARS-CoV-2 coronavirus pandemic continues to be devastating in many areas. Treatment options have been limited and convalescent donor plasma has been used by many centers to transfer passive neutralizing antibodies to patients with respiratory involvement. The results often vary by institution and are complicated by the nature and quality of the donor plasma itself, the timing of administration and the clinical aspects of the recipients. SARS-CoV-2 infection is known to be associated with an increase in the blood concentrations of several inflammatory cytokines/chemokines, as part of the overall immune response to the virus and consequential to mediated lung pathology. Some of these correlates contribute to the cytokine storm syndrome and acute respiratory distress syndrome, often resulting in fatality. A Phase IIa clinical trial at our institution using high neutralizing titer convalescent plasma transfer gave us the unique opportunity to study the elevations of correlates in the first 10 days after infusion. Plasma recipients were divided into hospitalized COVID-19 pneumonia patients who did not (Track 2) or did (Track 3) require mechanical ventilation. Several cytokines were elevated in the patients of each Track and some continued to rise through Day 10, while others initially increased and then subsided. Furthermore, elevations in MIP-1α, MIP-1β and CRP correlated with disease progression of Track 2 recipients. Overall, our observations serve as a foundation for further study of these correlates and the identification of potential biomarkers to improve upon convalescent plasma therapy and to drive more successful patient outcomes.