Primate vocalizations during social separation and aggression: effects of alcohol and benzodiazepines

The most common group of squirrel monkey vocalizations, peeps, are emitted during different social situations including social separation, affiliative interactions, feeding and aggressive confrontations. The present experiments investigated whether peeps and other vocalizations emitted during different social contexts are pharmacologically altered in a similar manner. First, vocalizations were characterized during (1) social separation in juveniles, and (2) "resident-intruder" aggressive confrontations between dominant monkeys from different social groups. Then, the effects of alcohol (EtOH) and the benzodiazepine chlordiazepoxide (CDP) on vocalizations during social separation and during aggression were examined. Isolated juveniles emitted only one type of call, the isolation peep. Resident monkeys primarily emitted peeps, but also emitted cackles, chucks, noisy calls and pulsed calls. Aggressive peeps were similar in structure and frequency (kHz) to isolation peeps, but were shorter in duration. At the same doses, both CDP (0.3-3 mg/kg) and EtOH (0.1-1.0 g/kg) reduced explosive motor behaviors and isolation peeps in juvenile monkeys during social separation and increased threat displays and aggression peeps in resident monkeys during confrontations with an intruder monkey from a different social group. Thus, similarly structured vocalizations that were emitted during social separation and aggression were very sensitive to EtOH and CDP, but the social context determined the direction and magnitude of effects.     

Animal and plant cell lysates share a conserved chaperone system that assembles the glucocorticoid receptor into a functional heterocomplex with hsp90

The hormone-binding domain of the glucocorticoid receptor must be bound to heat shock protein (hsp) 90 for it to have a high-affinity steroid-binding conformation. Cell-free assembly of a glucocorticoid receptor-hsp90 heterocomplex is brought about in reticulocyte lysate by a preformed protein-folding complex containing hsp90, hsp70, and other proteins [Hutchison, K.A., Dittmar, K. D., & Pratt, W.B. (1994) J. Biol. Chem. 269, 27894-27899]. In this "foldosome" system, hsp70 is required for assembly of the receptor-hsp90 complex and concomitant activation of steroid-binding activity [Hutchison, K.A., Dittmar, K.D., Czar, M.J., & Pratt, W.B. (1994) J. Biol. Chem. 269, 22157-22161]. All previous experiments involving cell-free assembly of both receptor-hsp90 and protein kinase-hsp90 heterocomplexes have been carried out with the protein-folding system in rabbit reticulocyte lysate. In this work, we show that concentrated lysates of receptor-free mouse (L cells) and insect (Sf9) cells and also a plant (wheat germ) lysate fold the immunopurified glucocorticoid receptor into a functional (i.e., steroid binding) heterocomplex with hsp90. Receptor heterocomplex formation in animal lysates and in the plant lysate are not identical in that the dynamics of complex assembly are different, but both systems produce a functional complex that binds steroid. Also, in contrast to animal and insect complexes, receptor-plant hsp90 complexes are not stabilized by molybdate. When added to the other lysate, purified plant and animal hsp90s show partial complementarity, in that a receptor-hsp90 complex is formed but the receptor is not converted to the steroid-binding conformation. When added to rabbit reticulocyte lysate that has been depleted of endogenous hsp70, purified wheat germ and mouse hsp70's are equally active in promoting both assembly of receptor-hsp90 heterocomplexes and conversion of receptor to the steroid-binding conformation. Thus, hsp70 from the plant kingdom has conserved the ability to interact functionally with chaperone proteins of the animal kingdom to cooperate in protein folding as evidenced by formation of a functional receptor-hsp90 heterocomplex.     

Radiopharmacology of inhaled 133Xe in skeletal sites containing deposits of Gaucher cells

Gaucher's disease is a lysosomal storage disease in which cells of the reticuloendothelial system accumulate the lipid glucocerebroside. It is characterized by slowly progressive visceral and osseous involvement. One of the latter manifestations includes lipid infiltration of bone marrow. We monitored the rate of inhaled 133Xe uptake and wash-out over diseased and normal metaphyseal and epiphyseal areas of the knee. Twenty-two patients (15 adults, 7 children) with various degrees of previously diagnosed Gaucher's disease were positioned supine under a gamma-camera interfaced to a computer system. All patients rebreathed 133Xe gas from a closed system for 10 min followed by 14 min of wash-out. Digitized images of the lung, liver, spleen, bony sites and soft tissue were obtained at 1 min intervals during the wash-in and wash-out phases. Counts for each ROI were normalized per 100 pixels and plotted as a function (time). Maximum uptake was also calculated by relating the counts/ROI/100 pixels to the 10 min integrated lung count during equilibrium (the administered "dose"). There was essentially no 133Xe uptake in liver and spleen involved with Gaucher's disease. Monophasic uptake and biphasic wash-out curves were observed in the limited investigative population. Skeletal Gaucher deposits released the 133Xe at a greater rate relative to soft tissue.     

Effects of hypothalamic temperature changes on the sweat rate in Macaca mulatta

The concept of cardiac reconditioning centers for the prevention and rehabilitation of coronary patients has been tremendously successful in Germany over the past 20 years. At least 40 such centers are located throughout the country. Physicians, nurses, and physical therapists work closely together in the various facets of the rehabilitation process. The financial backing for these facilities is primarily through governmental and regional insurance companies, whose officials are apparently convinced that in the long run supporting preventive measures is financially sound. Objective data supporting their convictions come from studies such as that of Brusis, who showed that such as that of 1,500 employees was diminished by nearly 70 percent during a two-year period after cardiac reconditioning, as compared to a similar time period before the rehabilitation experience. Subjective benefits, which are extremely difficult to quantitate in meaningful terms, were nonetheless expressed by nearly all the patients with whom I conversed. Perhaps they have experienced the same feelings that Mark Twain did when he observed that "all frets and worries and chafings sank to sleep in the presence of the benignant serenity of the Alps; the Great Spirit of the Mountains breathed his own peace upon their hurt minds and sore hearts and healed them."     

Organizing Sexuality: Silencing and the Push–Pull Process of Co-sexuality in the Workplace

How human beings think about, talk about, and organize around sexuality is changing. Growing social legitimization for sexual minority relationships and a more fluid social understanding of sexual identities has shifted how we bound “normal” sexuality. In the workplace, these shifting norms affect employees of all sexual identities who must make sense of new policies and complex daily practices. This paper introduces the concept of co-sexuality, the push-and-pull process of communicatively organizing around sexuality. Using this concept, we take a grounded theory approach to exploring how employees of various sexualities and in different occupations understand “normal” sexuality and subsequently organize around it. Ultimately, participants described being silenced or silencing another to maintain sexual “norms” at work.     

Employing CRISPR-Cas9 to Generate CD133 Synthetic Lethal Melanoma Stem Cells

Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MIC) implicated in tumorigenesis, invasion, and drug resistance, and is characterized by the elevated expression of stem cell markers, including CD133. The siRNA knockdown of CD133 enhances apoptosis induced by the MEK inhibitor trametinib in melanoma cells. This study investigates the underlying mechanisms of CD133’s anti-apoptotic activity in patient-derived BAKP and POT cells, harboring difficult-to-treat NRAS^Q61K and NRAS^Q61R drivers, after CRISPR-Cas9 CD133 knockout or Dox-inducible expression of CD133. MACS-sorted CD133(+) BAKP cells were conditionally reprogrammed to derive BAKR cells with sustained CD133 expression and MIC features. Compared to BAKP, CD133(+) BAKR exhibit increased cell survival and reduced apoptosis in response to trametinib or the chemotherapeutic dacarbazine (DTIC). CRISPR-Cas9-mediated CD133 knockout in BAKR cells (BAKR-KO) re-sensitized cells to trametinib. CD133 knockout in BAKP and POT cells increased trametinib-induced apoptosis by reducing anti-apoptotic BCL-xL, p-AKT, and p-BAD and increasing pro-apoptotic BAX. Conversely, Dox-induced CD133 expression diminished apoptosis in both trametinib-treated cell lines, coincident with elevated p-AKT, p-BAD, BCL-2, and BCL-xL and decreased activation of BAX and caspases-3 and -9. AKT1/2 siRNA knockdown or inhibition of BCL-2 family members with navitoclax (ABT-263) in BAKP-KO cells further enhanced caspase-mediated apoptotic PARP cleavage. CD133 may therefore activate a survival pathway where (1) increased AKT phosphorylation and activation induces (2) BAD phosphorylation and inactivation, (3) decreases BAX activation, and (4) reduces caspases-3 and -9 activity and caspase-mediated PARP cleavage, leading to apoptosis suppression and drug resistance in melanoma. Targeting nodes of the CD133, AKT, or BCL-2 survival pathways with trametinib highlights the potential for combination therapies for NRAS-mutant melanoma stem cells for the development of more effective treatments for patients with high-risk melanoma.     

Assessing support alternatives for longwall gateroads subject to changing stress

Longwall gateroad entries are subject to changing horizontal and vertical stress induced by redistribution of loads around the extracted panel. The stress changes can result in significant deformation of the entries that may include roof sag, rib dilation, and floor heave. Mine operators install different types of supports to control the ground response and maintain safe access and ventilation of the longwall face. This paper describes recent research aimed at quantifying the effect of longwall-induced stress changes on ground stability and using the information to assess support alternatives. The research included monitoring of ground and support interaction at several operating longwall mines in the U.S., analysis and calibration of numerical models that adequately represent the bedded rock mass, and observation of the support systems and their response to changes in stress. The models were then used to investigate the impact of geology and stress conditions on ground deformation and support response for various depths of cover and geologic scenarios. The research results were summarized in two regression equations that can be used to estimate the likely roof deformation and height of roof yield due to longwall-induced stress changes. This information is then used to assess the ability of support systems to maintain the stability of the roof. The application of the method is demonstrated with a retrospective analysis of the support performance at an operating longwall mine that experienced a headgate roof fall. The method is shown to produce realistic estimates of gateroad entry stability and support performance, allowing alternative support systems to be assessed during the design and planning stage of longwall operations.     

Environmental radioactivity levels in Malaysian marine species

Radioactivity measurements were carried out on some Malaysian marine species using gross γ‐ray spectrometry. ¹³⁷Cs levels of the order of 7 to 10 Bq/dry kg were detected in the larger‐sized species whereas considerably lower levels were found in the smaller‐sized ones. No other artificial radioisotopes were present in significant concentrations. ⁴⁰K levels ranged from about 70 to 567 Bq/dry kg. The concentration factors for both ^l17Cs and ⁴⁰K in these samples were also reported.