Effects of the Antidepressant/Antipanic Drug Phenelzine on Alanine and Alanine Transaminase in Rat Brain

1. Phenelzine (PLZ) is an antidepressant with anxiolytic properties. Acute and chronic PLZ administration increase brain GABA levels, an effect due, at least in part, to an inhibition of the activity of the GABA metabolizing enzyme, GABA transaminase (GABA-T).2. Previous preliminary reports have indicated that acute PLZ treatment also elevates brain alanine levels. As with GABA, the metabolism of alanine involves a pyridoxal phosphate-dependent transaminase.3. In the study reported here, the effects of acute PLZ treatment on the levels of various amino acids, some of which are also metabolized by pyridoxal phosphate-dependent transaminases were compared in rat whole brain. Of the 6 amino acids investigated, only GABA and alanine levels were elevated (in a time- and dose-dependent manner).4. The elevation in brain alanine levels could be explained, at least in part, by a time- and dose-dependent inhibitory effect of PLZ on alanine transaminase (ALA-T), although as with GABA the increases are higher than expected from the degree of enzyme inhibition produced. In addition, we also showed that the elevation in alanine levels and the inhibition of alanine transaminase in the brain are retained after 14 days of PLZ treatment, and that PLZ produces a marked increase in extracellular levels of alanine.5. These results are discussed in terms of their relevance to synaptic function and to the pharmacological profile of PLZ.     

Myocardial protection of the homograft II cold coronary perfusion

In the search for minimizing post-transplantation cardiac failure, the protective effect of cold coronary perfusion was tested by evaluation of the postoperative left ventricular function. In a control group, seven hearts were excised from dogs, immediately cooled in physiological saline at 4 °C, and homografted. In a second group of five dogs, immediately after cardiectomy the coronary bed of the homograft was perfused with cold extracellular solution (5 °C) for a period of 10 min and transplanted. Cardiac function of all animals was evaluated at rest 3, 24, and 48 hr postoperatively. In group I, the myocardial temperature was lowered to 13 °C in 12 min. In group II, the hypothermia induced by coronary perfusion was more rapid and deeper (11 °C within 10 min). Three hours postoperatively, cardiac function of group II was superior to that of group I as demonstrated by the increase of cardiac index (19%), stroke volume index (38%), mean systolic ejection rate index (17%), maximum systolic flow index (21%), stroke power index (31%), stroke work index (48%). Twenty-four hours postoperatively, the functional state of the two groups was improved; however, cardiac function of group II remained slightly superior on the whole: CI (14%), SVI (14%), MSERI (10%), M_XSFI (25%), SPI (18%), and SWI (9.4%). Forty-eight hours later, cardiac performance were similar in the two groups. These results demonstrate that cold coronary perfusion increases protection of the homograft during the initial period of implantation. The rapidity of cooling and the degree of deep hypothermia are most likely responsible for this beneficial effect.     

First multi-proxy record of Jurassic wildfires from Gondwana: Evidence from the Middle Jurassic of the Neuquén Basin,Argentina

Wildfires play a crucial role in recent and ancient ecosystem modeling but their detailed history on the Earth is still not well recorded or understood. The co-occurrence of charcoal and pyrolytic polycyclic aromatic hydrocarbons (PAHs) is used for the recognition of wildfires in geological record that may have implications for the analysis of the terrestrial environment, ecosystems, climate and the level of atmospheric oxygen. Here we present the first multi-proxy evidence of wildfires on the Gondwana continent during the Jurassic, based on the occurrence of charcoal and pyrolytic PAHs in the Middle Jurassic of the Neuquén Basin, Argentina. This is the first evidence of wildfire in the Aalenian, the lowest stage of the Middle Jurassic, and one of the few records of wildfires in the Bathonian. Temperature interpretations, derived from charcoal reflectance data, show that charcoals formed in low temperature surface fires that only sporadically reached the higher temperatures, possibly related to crown fires. The occurrence of charcoals in the Middle Jurassic deposits confirms recent results that the atmospheric oxygen level reached at least 15% during the Middle Jurassic times.     

FB1, a monoclonal antibody reacting with a keratin 14 epitope, stains only a small subset of psoriatic basal keratinocytes

Abstract
A murine monoclonal antibody, FB1, reacted with the basal keratinocytes of human stratified epithelia. One-dimensional and two-dimensional immunoblotting assays, performed on keratins extracted from HaCat cells and normal human keratinocytes, showed that FBI recognizes K14. When LL002, another K14 monoclonal antibody is added, the FB1 stained area in the 2D-immunoblot seems to cover a fraction of the LL002 spot. Immunohistochemical data obtained from studies on normal human tissues supported the K14 specificity of FB1, but when compared with two other monoclonal antibodies, LL002 and RCK107 reacting with K14, some differences appeared. These differences were mainly seen in sweat glands, hair follicles, psoriatic epidermis and salivary glands. In psoriatic epidermis, FB1 showed a heterogeneous pattern of staining of the basal cell compartment. Intense reactivity was only observed at the bottom of the rete ridges. Staining diminished and finally disappeared in the basal cells above the dermal papillae. This observation supports the view that an increased germinative cell population in psoriasis involves a partially differentiated amplifying compartment in which the number of cell divisions is increased.     

Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function

Endo- β-N-acetylgucosaminidases (ENGases) are the enzymes that catalyze both hydrolysis and transglycosylation reactions. It is of interest to study ENGases because of their ability to synthesize glycopeptides. Homology models of Human, Arabidopsis thaliana and Sorghum ENGases were developed and their active sites marked based on information available from Arthrobacter protophormiae (PDB ID: 3FHQ) ENGase. Further, these models were docked with the natural substrate GlcNAc-Asn and the inhibitor Man₃GlcNAc-thiazoline. The catalytic triad of Asn, Glu and Tyr (N171, E173 and Y205 of bacteria) were found to be conserved across the phyla. The crucial Y299F mutation showing 3 times higher transglycosylation activity than in wild type Endo-A is known. The hydrolytic activity remained unchanged in bacteria, while the transglycosylation activity increased. This Y to F change is found to be naturally evolved and should be attributing higher transglycosylation rates in human and Arabidopsis thaliana ENGases. Ligand interactions Ligplots revealed the interaction of amino acids with hydrophobic side chains and polar uncharged side chain amino acids. Thus, structure based molecular model-ligand interactions provide insights into the catalytic mechanism of ENGases and assist in the rational engineering of ENGases.     

Environmental variables that ameliorate extinction learning deficits in the 129S1/SvlmJ mouse strain

Fear conditioning is an associative learning process by which organisms learn to avoid environmental stimuli that are predictive of aversive outcomes. Fear extinction learning is a process by which avoidance of fear‐conditioned stimuli is attenuated when the environmental stimuli is no longer predictive of the aversive outcome. Aberrant fear conditioning and extinction learning are key elements in the development of several anxiety disorders. The 129S1 inbred strain of mice is used as an animal model for maladaptive fear learning because this strain has been shown to generalize fear to other nonaversive stimuli and is less capable of extinguishing fear responses relative to other mouse strains, such as the C57BL/6. Here we report new environmental manipulations that enhance fear and extinction learning, including the ability to discriminate between an aversively paired tone and a neutral tone, in both the 129S1 and C57BL/6 strains of mice. Specifically, we show that discontinuous (“pipped”) tone stimuli significantly enhance within‐session extinction learning and the discrimination between neutral and aversively paired stimuli in both strains. Furthermore, we find that extinction training in novel contexts significantly enhances the consolidation and recall of extinction learning for both strains. Cumulatively, these results underscore how environmental changes can be leveraged to ameliorate maladaptive learning in animal models and may advance cognitive and behavioral therapeutic strategies.