Dog-appeasing pheromone collars reduce sound-induced fear and anxiety in beagle dogs: a placebo-controlled study.

The objective of the study was to assess the effects of a dog-appeasing pheromone (DAP) collar in reducing sound-induced fear and anxiety in a laboratory model of thunderstorm simulation. Twenty-four beagle dogs naïve to the current test were divided into two treatment groups (DAP and placebo) balanced on their fear score in response to a thunderstorm recording. Each group was then exposed to two additional thunderstorm simulation tests on consecutive days. Dogs were video-assessed by a trained observer on a 6-point scale for active, passive and global fear and anxiety (combined). Both global and active fear and anxiety scores were significantly improved during and following thunder compared with placebo on both test days. DAP significantly decreased global fear and anxiety across 'during' and 'post' thunder times when compared with baseline. There was no significant improvement in the placebo group from baseline on the test days. In addition, the DAP group showed significantly greater use of the hide box at any time with increased exposure compared with the placebo group. The DAP collar reduced the scores of fear and anxiety, and increased hide use in response to a thunder recording, possibly by counteracting noise-related increased reactivity.

Zipper-interacting protein kinase is involved in regulation of ubiquitination of the androgen receptor, thereby contributing to dynamic transcription complex assembly.

We have recently identified apoptosis-antagonizing transcription factor (AATF), tumor-susceptibility gene 101 (TSG101) and zipper-interacting protein kinase (ZIPK) as novel coactivators of the androgen receptor (AR). The mechanisms of coactivation remained obscure, however. Here we investigated the interplay and interdependence between these coactivators and the AR using the endogenous prostate specific antigen (PSA) gene as model for AR-target genes. Chromatin immunoprecipitation in combination with siRNA-mediated knockdown revealed that recruitment of AATF and ZIPK to the PSA enhancer was dependent on AR, whereas recruitment of TSG101 was dependent on AATF. Association of AR and its coactivators with the PSA enhancer or promoter occurred in cycles. Dissociation of AR-transcription complexes was due to degradation because inhibition of the proteasome system by MG132 caused accumulation of AR at enhancer/promoter elements. Moreover, inhibition of degradation strongly reduced transcription, indicating that continued and efficient transcription is based on initiation, degradation and reinitiation cycles. Interestingly, knockdown of ZIPK by siRNA had a similar effect as MG132, leading to reduced transcription but enhanced accumulation of AR at androgen-response elements. In addition, knockdown of ZIPK, as well as overexpression of a dominant-negative ZIPK mutant, diminished polyubiquitination of AR. Furthermore, ZIPK cooperated with the E3 ligase Mdm2 in AR-dependent transactivation, assembled into a single complex on chromatin and phosphorylated Mdm2 in vitro. These results suggest that ZIPK has a crucial role in regulation of ubiquitination and degradation of the AR, and hence promoter clearance and efficient transcription.

Beta-amyloid deposition and tau phosphorylation in clinically characterized aged cats.

The current study describes both Abeta and tau abnormalities that accumulate in the brains of aged (16-21 years), but not young (<4 years) clinically characterized cats. Diffuse plaques that were morphologically different from what is typically observed in the human brain could be detected with 4G8 (Abeta17-24) or an Abeta1-42-specific antibody but not with N-terminal Abeta or an Abeta1-40-specific antibody. SELDI-TOF mass spectrometry experiments indicated that cat brain Abeta consisted almost entirely of Abeta1-42. Markers of tau hyperphosphorylation (AT8 and PHF-1) labeled a subset of neurons in two aged animals. In the hilus of the hippocampus, a subset of AT8 positive neurons showed a sprouting morphology similar to that observed in human brain. Western blot analysis with antibodies against hyperphosphorylated tau indicated that tau is hyperphosphorylated in the aged cat and contains many of the same epitopes found in Alzheimer's disease (AD) brain. Thus, the aged cat brain develops AD-related lesions with important morphological and biochemical differences compared to human brain.

Black holes at the Large Hadron Collider.

If the scale of quantum gravity is near TeV, the CERN Large Hadron Collider will be producing one black hole (BH) about every second. The decays of the BHs into the final states with prompt, hard photons, electrons, or muons provide a clean signature with low background. The correlation between the BH mass and its temperature, deduced from the energy spectrum of the decay products, can test Hawking's evaporation law and determine the number of large new dimensions and the scale of quantum gravity.

Cloning and characterization of Dlk, a novel serine/threonine kinase that is tightly associated with chromatin and phosphorylates core histones.

We cloned a cDNA coding for a novel serine/threonine kinase, Dlk, a protein of 448 amino acids with a predicted molecular weight of 51.3 kDa. The kinase domain shows 81% amino acid sequence identity to the recently identified DAP kinase (death associated protein kinase) (Deiss et al., Genes & Dev., 9, 15-30, 1995), therefore, the new kinase was called Dlk, for DAP like kinase. Northern analyses revealed a single mRNA species of 1.7 kb which was ubiquitously expressed. However, expression levels varied considerably in different cell lines and tissues. Moreover, expression was downregulated upon UV irradiation. Dlk exhibited autophosphorylation activity, predominantly towards threonine residues and phosphorylated the regulatory subunit of myosin light chain, but in this case exclusively at serine residues. Dlk seems to be tightly associated with insoluble nuclear structures, presumably chromatin, since it was resistant to various rigorous extraction procedures but it was partially released upon DNase I digestion of nuclei. Consistent with this, purified Dlk phosphorylated core histones H3, H2A and H4 as exogenous substrates and endogenous histone H3 in kinase assays with nuclear extracts. Expression as GFP-fusion protein revealed a diffuse as well as a speckled nuclear staining suggesting an association with replication or transcription centers.

The impact of managed care on community mental health outpatient services in New York State.

This article explores the impact of managed care on community mental health outpatient services in New York State. A survey was sent to directors of all the licensed mental health organizations to obtain information about staff composition, services provided, training, funding, managed care affiliations, and advertising. The survey focus was on changes that had taken place in the past 4 years and those anticipated in the future due to managed care. Results indicate that managed care has led to changes in the aforementioned areas and that these changes varied by agency size, region, and type.

Geriatric behavioral problems.

Behavior problems in older pets may be due to many of the same causes as in younger pets. However, the effects of aging on the pet's body may cause a dramatic decline or deterioration in organ and sensory function, which may have a profound impact on the pet's behavior. A decline in cognitive function may also afflict older pets, in many instances due to the occurrence of Alzheimer's disease brain pathology, especially beta amyloid plaque formation. Correlation of geriatric behavior problems, therefore, entails first diagnosing and treating any underlying medical problems. Behavior modification techniques and drug therapy may then be required, with modifications and adjustments made to suit the specific needs of the older pet.

The cycle of violence and victimization: a study of the school-based intervention of a multidisciplinary youth violence-prevention program.

This article reports on the school-based intervention component of a multidisciplinary program intended to reduce and prevent youth violence in the East New York neighborhood of Brooklyn. This intervention is based on three theories. The first theory posits that modifying beliefs, attitudes, and norms will help youths develop behaviors that support nonviolence. The second theoretical construct asserts that enhancing relationships with peers and family will buffer youths from the effects of exposure to violence. Finally, the third theory suggests that changing aspects of the setting and climate that contribute to violent behavior will prevent violence. The school-based intervention, the Safe Harbor, is a victim-assistance and violence-prevention program. The Safe Harbor offers activities including a 20-lesson violence-prevention and victim-assistance curriculum, counseling, parent involvement, teacher training, and school-change campaigns. The evaluation design is a panel study, with cohorts surveyed longitudinally at nonequivalent intervals. One hundred and fifteen seventh- and eighth-grade students who receive the curriculum and other services are the experimental group; the other 879 students in the seventh and eighth grades serve as the comparison group. Baseline data were collected through a survey of the entire school before the program's implementation in January 1995. Subsequent data collection will include interviews and focus groups; future analysis will address how participation in other parts of the Safe Harbor program or other programs in the school affects outcomes. The participation rate for the baseline survey in the experimental group was 86%, in the comparison group 76%. Responses to the survey questions were virtually identical between the two groups. Preliminary analyses reflect a climate of pervasive violence in the school, family, and community. More than half of the sample reported witnessing a severe beating in the school or their community within the past four months. Forty-four percent witnessed someone being attacked with a weapon in their neighborhood. The psychological consequences of exposure to violence were severe-51% of the sample reported post-traumatic stress disorder (PTSD) symptoms. A number of lessons have been learned from implementing and evaluating this project, including the importance of fostering community partnership and strong relationships with the school, and addressing both reactions to victimization and norms and beliefs about aggression.

UV irradiation leads to transient changes in phosphorylation and stability of tumor suppressor protein p53.

Tumor suppressor protein p53 is thought to play a crucial role in maintaining the integrity of the genome. DNA damage caused by genotoxic drugs, UV or gamma-irradiation leads to accumulation of p53 and activation of its DNA binding and transcriptional activities and subsequently to cell cycle arrest or apoptosis. We investigated whether the apparent activation of p53 might be due to post-translational modification. The rat fibroblast cell lines REF52, 208F, and rat1 were irradiated with W-A and the synthesis, stability and phosphorylation state of p53 were investigated by pulse chase experiments, SDS-PAGE and two-dimensional phosphopeptide mapping. The three cell lines exhibited different sensitivities and biological responses to UV irradiation, REF52 cells responded with a growth arrest whereas 208F and rat1 cells underwent apoptosis. The fate of p53 was similar in all cases. Both the stability of p53 and its phosphorylation increased instantaneously but transiently. However, the amount of p53 that accumulated after UV treatment was much higher in 208F and rat1 than in REF52 cells. Interestingly, p53 that was synthesized early after irradiation was stable for more than 14 h whereas molecules synthesized 8 or more hours post irradiation were increasingly susceptible to degradation. Moreover, between 14 and 20 h after treatment, the rate of synthesis of p53 decreased to a level lower than in untreated cells suggesting negative feed back control. The expression of different p53-responsive genes, waf1/cip1, Gadd45, and bax was investigated by protein analyses. Surprisingly, p21(waf1) was expressed only in REF52 cells but not in the others. Furthermore, UV irradiation led only to a moderate increase of p21(waf1) expression. Expression of Gadd45 and box was detectable in both cell types but its expression did not change significantly upon UV treatment. Our results suggest i) that both cell types share a common pathway which upon UV irradiation results in enhanced stability and phosphorylation of p53 and ii) that the decision whether a cell undergoes a growth arrest or apoptosis may be determined independent of p53 by the cellular environment i.e. the expression patterns of genes that mediate the response.

County mental health directors' evaluation of a statewide intensive case management program: the New York State experience.

Case management is increasingly recommended as part of an overall strategy for serving individuals with severe mental illness. The New York State Office of Mental Health developed such a program in 1988, with county mental health directors the key players in its development and operationalization. This article reports the results of a statewide survey administered by the authors to these directors 3 1/2 years after the program's implementation to determine its degree of success. Overall, the program was viewed as effective for individual clients, particularly those most in need of services. However, with respect to overall systems change, there was more variability in results. In general, a combination of strategies to reduce fragmentation within the mental health system and increase collaboration between service providers should be considered by state mental health authorities.

Enhanced kinase-activity in sv40-transformed cells may be compensated by enhanced phosphatase-activity in revertants as reflected by phosphorylation of p53.

Transformation of rat cells with SV40 large T antigen results in activation of protein kinases and hyperphosphorylation of the tumor suppressor protein p53. In searching for cellular targets involved in SV40-mediated transformation, flat revertants of SV40-transformed rat cells had been isolated carrying a presumptive defect in a cellular gene (Bauer et al: J Virol 61: 1821, 1987). In this investigation, we asked whether the phosphorylation state of p53 might be affected in the revertants. Two-dimensional phosphopeptide analyses revealed indeed a characteristic reduction of phosphorylation of p53 compared to the parental transformed cells. However, when we employed the phosphatase inhibitor okadaic acid in vivo hyperphosphorylation of p53 resumed indicating that the kinases involved in phosphorylation of p53 were fully active but counterbalanced by enhanced phosphatase activity. Indeed, the phosphate turnover of p53 in vivo and phosphatase activity towards p53 in vitro was higher in the revertants than in the parental transformants. These findings demonstrate that the transformation state of a cell correlates with the phosphorylation state of p53 which in turn can be regulated in different ways, enhanced kinase activity in transformed cells may be counteracted by enhanced phosphatase activity in revertant cells.

Feline scratching and destruction and the effects of declawing.

Scratching is an inherited, normal behavior in cats that is used as a visual and olfactory territorial mark and as a stretching exercise for the forelegs. In addition, it serves to condition the claws by removing the old, worn-out external sheath and exposing the healthy, new claw. When scratching occurs indoors, it often is disruptive and undesirable unless it can be directed to an acceptable object such as a scratching post. During playing, jumping, climbing, and aggressive displays, cats also may injure people with their claws. With appropriate behavior modification techniques, most undesirable scratching can be prevented or eliminated. Although somewhat controversial, declawing is another alternative for those owners who are unwilling or unable to control the undesirable scratching. Declawing can successfully correct most scratching problems with no adverse behavioral effects; in fact, most owners of declawed cats indicate that there is an improved relationship (bonding) between cat and owner. On the other hand, declawing is often unnecessary, because appropriate behavior modification techniques can be used to correct most scratching problems successfully.