The contrasting roles of ICE family proteases and interleukin-1beta in apoptosis induced by trophic factor withdrawal and by copper/zinc superoxide dismutase down-regulation.

We compare here the mechanisms of apoptotic death of PC12 cells induced by down-regulation of Cu2+,Zn2+ superoxide dismutase (SOD1) and withdrawal of trophic support (serum/nerve growth factor). Our previous results indicated that the initiating causes of death are different in each paradigm. However, bcl-2 rescues cells in either paradigm, suggesting common downstream elements to the cell death pathway. To determine whether the ICE [interleukin 1beta converting enzyme] family of proteases, which is required for apoptosis on trophic factor withdrawal, is also required for apoptosis induced by oxidative stress, we have developed a novel peptide inhibitor that mimics the common catalytic site of these enzymes and thereby blocks their access to substrates. This differs from the more usual pseudosubstrate approach to enzyme inhibition. Blockade of ICE family proteases by either this inhibitor or by a permeant competitive ICE family antagonist rescues PC12 cells from apoptotic death following apoptosis induced by down-regulation of SOD1, as well as from trophic factor/nerve growth factor deprivation. SOD1 down-regulation results in an increase in interleukin 1beta (IL- 1beta) production by the cells, and cell death under these conditions can be prevented by either blocking antibodies against IL-1beta or the IL-1 receptor antagonist (IL-1Ralpha). In contrast, trophic factor withdrawal does not increase IL-1beta secretion, and the blocking antibody failed to protect PC12 cells from trophic factor withdrawal, whereas the receptor antagonist was only partially protective at very high concentrations. There were substantial differences in the concentrations of pseudosubstrate inhibitors which rescued cells from SOD1 down-regulation and trophic factor deprivation. These results suggest the involvement of different members of the ICE family, different substrates, or both in the two different initiating causes of cell death.

Suppression of apoptosis by basement membrane requires three-dimensional tissue organization and withdrawal from the cell cycle.

The basement membrane (BM) extracellular matrix induces differentiation and suppresses apoptosis in mammary epithelial cells, whereas cells lacking BM lose their differentiated phenotype and undergo apoptosis. Addition of purified BM components, which are known to induce beta-casein expression, did not prevent apoptosis, indicating that a more complex BM was necessary. A comparison of culture conditions where apoptosis would or would not occur allowed us to relate inhibition of apoptosis to a complete withdrawal from the cell cycle, which was observed only when cells acquired a three-dimensional alveolar structure in response to BM. In the absence of this morphology, both the GI cyclin kinase inhibitor p21/WAF-1 and positive proliferative signals including c-myc and cyclin DI were expressed and the retinoblastoma protein (Rb) continued to be hyperphosphorylated. When we overexpressed either c-myc in quiescent cells or p21 when cells were still cycling, apoptosis was induced. In the absence of three-dimensional alveolar structures, mammary epithelial cells secrete a number of factors including transforming growth factor alpha and tenascin, which when added exogenously to quiescent cells induced expression of c-myc and interleukin-beta1-converting enzyme (ICE) mRNA and led to apoptosis. These experiments demonstrate that a correct tissue architecture is crucial for long-range homeostasis, suppression of apoptosis, and maintenance of differentiated phenotype.

Decreased brain reward produced by ethanol withdrawal.

Abstinence from chronic administration of various drugs of abuse such as ethanol, opiates, and psychostimulants results in withdrawal syndromes largely unique to each drug class. However, one symptom that appears common to these withdrawal syndromes in humans is a negative affective/motivational state. Prior work in rodents has shown that elevations in intracranial self-stimulation (ICSS) reward thresholds provide a quantitative index that serves as a model for the negative affective state during withdrawal from psychostimulants and opiates. The current study sought to determine whether ICSS threshold elevations also accompany abstinence from chronic ethanol exposure sufficient to induce physical dependence. Rats prepared with stimulating electrodes in the lateral hypothalamus were trained in a discrete-trial current-intensity ICSS threshold procedure; subsequently they were subjected to chronic ethanol administration in ethanol vapor chambers (average blood alcohol level of 197 mg/dl). A time-dependent elevation in ICSS thresholds was observed following removal from the ethanol, but not the control, chambers. Thresholds were significantly elevated for 48 hr after cessation of ethanol exposure, with peak elevations observed at 6-8 hr. Blood alcohol levels were directly correlated with the magnitude of peak threshold elevation. Ratings of traditional overt signs of withdrawal showed a similar time course of expression and resolution. The results suggest that decreased function of reward systems (elevations in reward thresholds) is a common element of withdrawal from chronic administration of several diverse classes of abused drugs.

DInSAR monitoring of aquifer compaction due to water withdrawal: Vegas Baja and Media of the Segura river (SE, Spain) case study

This study was partially financed by the Spanish Ministry of Education and Science and EU FEDER under project TEC2005-06863, by the Valencia Regional Government under projects GV006/179 and ACOMP07/087, and by the University of Alicante under projects VIGROB2004102, VIGROB-053, and VIGROB-114.

Community Size in Youth Sport Settings: Examining Developmental Assets and Sport Withdrawal

Despite the popularity of youth sport programs, little research has examined the psychosocial benefits assumed to stem from involvement. Some studies suggest birthplace influences the development of elite athletes, but little work has examined other influences of community contexts. The purpose of this study was to examine relationships between young athletes’ community size, developmental assets, and sport involvement. Current and recently withdrawn competitive swimmers (N = 181) completed the Developmental Assets Profile (Search Institute, 2004). Athletes from smaller cities had significantly higher developmental asset scores for support, commitment to learning, and boundaries/expectations. Further, community size was a significant predictor of withdrawal. Findings suggest community context should be given additional attention in youth sport literature.

Is Withdrawal from the European Union a Manageable Option? A Review of Economic and Legal Complexities. Bruges European Economic Policy (BEEP) Briefing 28/2013

Withdrawal from the EU is no more a taboo subject. However, the process by which it can happen is unclear and potentially complex. The purpose of this paper is to show that a withdrawing Member State will not only rid itself from the constraints and obligations of EU rules, but it will also have to re-invent many policies and institutions to fill the gap left by the non-application of EU rules. The paper examines closely the case of the UK and Scotland and concludes that outright exit is not the best option for a withdrawing Member State. The best, but possibly the least feasible, option is an intermediate arrangement falling between full membership and complete separation from the EU. The exact position between the two extremes can only be determined by the exit negotiations and will be influenced by the political climate that will prevail at that time. While the final destination of an acceding country is well known [full adoption of the obligations of EU membership], the exiting country will be embarking on a trip with unknown destination and full of surprises.

The impact of the withdrawal from Afghanistan on Russia’s security. Egmont Security Policy Brief No. 54, March 2014

ISAF’s withdrawal from Afghanistan in 2014 will directly impact the wider region. Not only is there a risk of instability spilling over to Central Asia, but the drawdown will also accelerate the ongoing shift in the balance of power in Central Asia towards China. Should a spillover occur, the burden will mainly fall on Russia and China. Russia will, however, only continue playing the dominant role in the security of the former Soviet Central Asia (FSCA) until China takes on responsibility for the security of its direct sphere of influence or “dingwei”. Russia’s Near Abroad, however, overlaps both with the EU’s Eastern Neighbourhood in Europe and China’s dingwei in Central Asia and the Far East. It is, therefore, necessary to approach Russian reactions to these encroachments on its historical spheres of influence in a single context, taking into account the interrelationship between these three.

Adult attention-deficit/hyperactivity disorder and nicotine withdrawal: a qualitative study of patient perceptions

Background: Nicotine use has been reported to ameliorate symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). Furthermore, adults with ADHD have a relatively high prevalence of cigarette smoking and greater difficulty abstaining from smoking. Overall, though, there is scant literature investigating the beliefs, perceptions and experiences of smokers with ADHD regarding smoking cessation and withdrawal. Methods: Our participants (n = 20) fulfilling criteria for ADHD and a past or current dependence from nicotine were recruited from the in- and outpatient clinic of the Zurich University Psychiatric Hospital and the Psychiatric Services Aargau (Switzerland). We conducted in-depth interviews to explore their motivations to quit, past experiences with and expectations about quitting using a purposeful sampling plan. The sample was selected to provide diversity in relation to level of nicotine dependence, participation in a smoking-cessation program, gender, age, martial status and social class. Mayring’s qualitative content analysis approach was used to evaluate findings. Results: Adult smokers with ADHD had made several attempts to quit, experienced intense withdrawal symptoms, and relapsed early and often. They also often perceived a worsening of ADHD symptoms with nicotine abstinence. We identified three motives to quit smoking: 1) health concerns, 2) the feeling of being addicted, and 3) social factors. Most participants favored a smoking cessation program specifically designed for individuals with ADHD because they thought ADHD complicated their nicotine withdrawal and that an ADHD-specific smoking cessation program should address specific symptoms of this disorder. Conclusions: Since treatment initiation and adherence associate closely with perception, we hope these findings will result in better cessation interventions for the vulnerable subgroup of smokers with ADHD. Keywords: ADHD, Nicotine, Withdrawal, Subjective, Qualitative, Narrative

Fundamental diagnostic hematology : the bleeding and clotting disorders /

Includes index.

Report on impact of intelligence reassessment on withdrawal of U.S. troops from Korea /

Mode of access: Internet.