213 research outputs found
Dipentylammonium Binds to the Sigma-1 Receptor and Protects Against Glutamate Toxicity, Attenuates Dopamine Toxicity and Potentiates Neurite Outgrowth in Various Cultured Cell Lines
Alzheimer’s disease is a neurodegenerative disease that affects 44 million people worldwide, costing the world $605 billion to care for those affected not taking into account the physical and psychological costs for those who care for Alzheimer’s patients. Dipentylammonium is a simple amine, which is structurally similar to a number of other identified sigma-1 receptor ligands with high affinities such as (2R-trans)-2butyl-5-heptylpyrrolidine, stearylamine and dodecylamine. This study investigates whether dipentylammonium is able to provide neuroprotective effects similar to those of sigma-1 receptor agonists such as PRE-084. Here we identify dipentylammonium as a sigma-1 receptor ligand with nanomolar affinity. We have found that micromolar concentrations of dipentylammonium protect from glutamate toxicity and prevent NFκB activation in HT-22 cells. Micromolar concentrations of dipentylammonium also protect stably expressing amyloid precursor protein Swedish mutant (APP/Swe) Neuro2A cells from toxicity induced by 150 μM dopamine, suggesting that dipentylammonium may be useful for the treatment of Parkinsonian symptoms in Alzheimer’s patients which are often associated with a more rapid deterioration of cognitive and physical ability. Finally, we found that low micromolar concentrations of dipentylammonium could out preform known sigma-1 receptor agonist PRE-084 in potentiating neurite outgrowth in Neuro2A cells, further suggesting that dipentylammonium has a potential use in the treatment of neurodegenerative diseases and could be acting through the sigma-1 receptor
Ligand-specific regulation and signalling by the neuromedin U 2 receptor
Neuromedin U receptor 2 (NMU2) is a Family A, G protein-coupled receptor (GPCR) for both neuromedin U (NmU) and neuromedin S (NmS), particularly within the CNS where effects include the suppression of feeding behaviour and increased energy expenditure suggesting an anti-obesity target. Although NMU2 preferentially activates Gαq/11, it is unclear which signalling underlies physiological outcomes or if the ligands generate different responses. Here, NMU2 signalling and regulation have been explored, including using a protocol of brief ligand exposure to match exposure patterns of peptidergic receptors in vivo.In HEK293 cells stably expressing human (h) NMU2, hNmU-25 and hNmS-33 evoked similar Ca2+ signalling, although resensitisation required only 6 h following brief (5 min) exposure to hNmU-25 but more than 6 h following hNmS-33. Activation of the mitogen-activated protein kinases (MAPKs) ERK, P38 and JNK, was more sustained following brief exposure to hNmS-33 compared to hNmU-25. NMU2 phosphorylation was increased by both ligands and inhibition of protein kinase C (PKC) reduced this by ~50%. Phosphorylation was more sustained following brief exposure to hNmS-33 than hNmU-25. Sustained challenge with either ligand sustained the recruitment of arrestin 2 and 3 to NMU2. Ligand removal resulted in loss of arrestin interaction that was slower for arrestin 2 but similar for the two ligands. This suggests that following brief exposure to hNmS-33, sustained NMU2 phosphorylation does not sustain arrestin recruitment and arrestin recruitment is not responsible for sustained MAPK activation. Five phosphorylated serine or threonine residues were identified in the C-terminus of NMU2 by mass spectrometry. Mutation of these reduced phosphorylation by both ligands and phosphorylation was abolished by PKC inhibition. Mutation of seven other serine/threonine residues reduced phosphorylation by hNmU-25 more than hNmS-33, suggesting different phosphorylation patterns. Mutation of all fourteen C-terminal serine/threonine residues abolished agonist-dependent phosphorylation. These data highlight ligand-dependent NMU2 signalling and regulation, particularly following brief ligand exposure. Such ligand dependence may be relevant to other GPCRs but their consequence to physiology and implications for drug discovery require further study.</div
Aversive feelings of therapists to clients and ways of dealing with them
TITLE: Aversive feelings of therapists to clients and ways of dealing with them AUTHOR: Bc. Simona Kozlová DEPARTMENT: Department of psychology SUPERVISOR: PhDr. David Heider, PhD. ABSTRACT: The aim of this thesis is to gain insight aversive feelings experienced by therapists to the clients. Determine the causal characteristics of aversive feeling and their processing. The task is to examine whether there are links between the detected phenomena. The method of data collection, are interviews with a group of psychotherapists. When analyzing the responses I used qualitative methodology, specifically the Strauss and Corbin's grounded theory. The work is divided into theoretical part and empirical part. The theoretical part describes aspects affecting the therapeutic process, as well as forms of aversive feelings and their possible consequences on the therapeutic relationship. In the empirical part are presented and interpreted data obtained from interviews, which are analyzed. The main results include: aversive feelings experienced by the therapists include helplessness, frustration, anger, and frustration, exhaustion, disgust, fear and threats, abuse and failure. Aversive feelings occur depending on situational and personal characteristics of therapists and clients. A significant factor that contributes to..
Identification of mastitis pathogens. A laboratory procedure for the veterinary practitioner
A simple procedure that can be used by veterinary practitioners for identification of mastitis pathogens is outlined. It consists of using plates of blood agar or 2 selective agars (TK/FC and MacConkey), the catalase test and Gram staining to identify major udder pathogens in milk samples. When the type of mastitis infection is known, the veterinary practitioner can recommend the most effective method for controlling the infection..RE: 5 ref.; SC: ZA; CA; VE; BE; 0D; 0ISource type: Electronic(1) http://upei-resolver.asin-risa.ca?sid=SP:CABI&id=pmid:&id=&issn=0362-8140&isbn=&volume=62&issue=7&spage=531&pages=531-536&date=1981&title=Modern%20Veterinary%20Practice&atitle=Identification%20of%20mastitis%20pathogens.%20A%20laboratory%20procedure%20for%20the%20veterinary%20practitioner.&aulast=%20Heider&pid=%3Cauthor%3ESears%20P%20M%3bHeider%2c%20L%20E%3C%2Fauthor%3E%3CAN%3E19820473631%3C%2FAN%3E%3CDT%3EJournal%20article%3C%2FDT%3
Experimental molecular structures in the gas phase at the upper size limit: The case of Si6Tip6.
Vishnevskiy Y, Heider Y, Scheschkewitz D. Experimental molecular structures in the gas phase at the upper size limit: The case of Si6Tip6. The Journal of chemical physics. 2024;161(5): 054307.Currently, the largest (ramax = 19.9A) and by far the most complicated (234 atoms, C1 symmetry, 696 independent geometrical parameters, and 27261 interatomic terms) experimental molecular structure of a cage-type Si6Tip6 (Tip = 2,4,6-iPr3C6H2) isomer has been investigated in the gas phase by the electron diffraction method (Tav = 645K) supplemented with theoretical simulations. A detailed analysis of the current possibilities for experimentally investigating large molecular structures is performed. A series of density functional theory approximations and the role of dispersion interactions have been benchmarked using the obtained data. Based on the refined geometry of Si6Tip6, various quantum-chemical methods have been applied for the investigation of the electronic structure of its Si6 core. In particular, natural bond orbital, quantum theory of atoms in molecules, interacting quantum atoms, fractional occupation number weighted density, and complete active space self-consistent field (CASSCF) methods were utilized. The diradical character of the molecule has been assessed by the UHF and CASSCF approximations. The problem of bonding between the hemispheroidal silicon atoms has been investigated. © 2024 Author(s). Published under an exclusive license by AIP Publishing
Calls for marketing methods to promote veterinary medicine - response
PT: J; NR: 0; TC: 1; J9: J AMER VET MED ASSN; PG: 2; GA: 634PXSource type: Electronic(1
Francisco Suárez on Pain and Touch
In the study the author aims at two main things. First, he points out an (at least) potential doctrinal incoherence in Suárez’s statements concerning the issue of the proper sensible object of touch. While in the context of his treatment of the sense of touch in DA VII, 13-14 Suárez restricts the total object of touch to external (tangent) qualities, in DA XI, 2, when treating the issue of emotions, the Jesuit includes also the qualitas dolorifera, i.e., a quality inherent in the percipient’s body. The author states that Suárez’s inconsistence is more urgent if his formulations are compared with those of Francisco de Oviedo. Second, the author indicates that Suárez’s «mixed view of pain», combining both the perceptual and the affective aspects in the single experience of pain, is a kind of theory that can be regarded as an up-to-date position even in the contemporary debate among analytic philosophers
Epidemiologic considerations in reporting herd somatic cell counts
The reporting of herd summaries of individual cow somatic cell counts (SCC) differs between the 9 Dairy Records Processing Centers. Estimates of central tendency and frequency distributions are the most commonly used herd summary statistics for SCC. Analyses of the frequency distributions are less widely available. Potential uses of herd SCC are: to measure one aspect of herd milk quality; to estimate the prevalence of mastitis; to analyse mastitis patterns within the herd; and to investigate new areas for mastitis control research. The best available methods for these applications appear to be: bulk tank SCC or weighted arithmetic means for gauging milk quality; frequency distributions for estimating mastitis prevalence; analyses of frequency distributions or mean linear score by lactation and stage of lactation for identifying mastitis patterns within a herd; and frequency distributions or estimated incidence rates, adjusted for differences in age and stage of lactation, for investigating new areas for mastitis control research..RE: 14 ref.; SC: ZA; CA; VE; BE; 0D; 0I; 0VSource type: Electronic(1) http://upei-resolver.asin-risa.ca?sid=SP:CABI&id=pmid:&id=&issn=0022-0302&isbn=&volume=69&issue=7&spage=1987&pages=1987-1995&date=1986&title=Journal%20of%20Dairy%20Science&atitle=Epidemiologic%20considerations%20in%20reporting%20herd%20somatic%20cell%20counts.&aulast=Hueston&pid=%3Cauthor%3EHueston%2c%20W%20D%3bHeider%2c%20L%20E%3C%2Fauthor%3E%3CAN%3E19860411288%3C%2FAN%3E%3CDT%3EJournal%20article%3C%2FDT%3
Detection of mastitis
PT: J; CR: 1978, CURRENT CONCEPTS BOV BROWN RW, 1969, MICROBIOLOGICAL PROC CARTER GR, 1978, DIAGNOSTIC PROCEDURE ERNO H, 1973, ACT VET SC, V14, P436 GRAY DM, 1962, AM J VET RES, V23, P541 JACKSON ER, 1980, VET REC, V107, P37 JASPER DE, 1977, J AM VET MED ASS, V197, P1168 JASPER DE, 1980, CALIF VET, V4, P24 KLASTRUP O, 1970, 6 P INT C CATTL DIS KOWALSKI JJ, 1974, 7TH P ANN CONV AM AS, P119 KOWALSKI JJ, 1977, J AM VET MED ASSOC, V197, P1175 MCDONALD JS, 1973, 12TH ANN NATL MAST C, P28 MCDONALD JS, 1976, AM J VET RES, V37, P377 MEEK AH, 1980, J FOOD PROTECT, V43, P10 PHILPOT WN, 1967, J DAIRY SCI, V50, P975 ROBERTS SJ, 1969, J AM VET MED ASS 1, V155, P157 SCHALM OW, 1971, BOVINE MASTITIS SCHNEIDER R, 1966, AM J VET RES, V27, P1169; NR: 18; TC: 4; J9: VET CLIN N AMER-LARGE ANIM; PG: 20; GA: MW924Source type: Electronic(1
The effect of freezing of milk samples on the cultural results
152 quarter milk samples were examined microbiologically before and after storing at -80 deg C for 7 and 14 days. The total number of isolates from fresh milk (107) was higher than from frozen milk stored for 7 or 14 days (97 and 94 resp.). Similar numbers of staphylococci were isolated from fresh and frozen milk samples, whereas numbers of streptococci were slightly reduced in the frozen milk. The number of coliform isolates was not affected by freezing the milk samples. Examination of 158 composite milk samples for streptococci before and after freezing showed that of the 37 Streptococcus agalactiae, 7 Str. dysgalactiae and 3 Str. uberis strains isolated from fresh milk, 37 and 14 Str. agalactiae, 5 and 5 Str. dysgalactiae and 2 and 1 Str. uberis strains were isolated after 7 and 14 days resp. at -80 deg C. It is concluded that milk samples can be preserved at low temp. (-80 deg C) for 14 days without any change in the number of samples identified as positive for mastitis..RE: 10 ref.; SC: ZA; CA; VE; BE; 0D; 0I; 0VSource type: Electronic(1) http://upei-resolver.asin-risa.ca?sid=SP:CABI&id=pmid:&id=&issn=&isbn=&volume=26&issue=1&spage=1&pages=1-6&date=1979&title=Zentralblatt%20fur%20Veterinarmedizin%2c%20B&atitle=The%20effect%20of%20freezing%20of%20milk%20samples%20on%20the%20cultural%20results.&aulast=Bashandy&pid=%3Cauthor%3EBashandy%2c%20E%20Y%3bHeider%2c%20L%20E%3C%2Fauthor%3E%3CAN%3E19790450952%3C%2FAN%3E%3CDT%3EJournal%20article%3C%2FDT%3
- …
