The common understanding of proton-neutron pairing, whose fingerprints are currently investigated in N = Z nuclei, relies on Cooper pair mechanism and BCS-type models. In the present thesis we present an alternative approach which, contrary to BCS models, conserves exactly the particle number and the isospin. In this approach the ground state of N=Z nuclei is described as a condensate of alpha-like quartets built by two neutrons and two protons coupled to the total isospin T=0 and total spin J=0. The comparison with exact shell model calculations shows that the quartet condensation model (QCM) gives a very accurate description of pairing correlations in N=Z nuclei, much better than the BCS models. It is also shown that proton-neutron pairing and alpha-type condensation are important not only for N=Z nuclei but also for nuclei with excess neutrons. In the latter case the condensate of alpha-like quartets coexist with the condensate of the neutron pairs in excess relative to the N=Z isotope. Using the framework of QCM we have also studied the competition between the isovector and the isoscalar proton-neutron pairing in nuclei with N=Z. Our results indicate that the contribution of isoscalar pairing to the ground state pairing correlations is very small compared to the isovector pairing.

No description available.

With approximately 7% of the adult population reporting to have taken illicit substances over the course of a year and the chronically relapsing nature of substance use disorders there is a great need for effective forms of treatment and therapies to reduce relapse. Deep brain stimulation (DBS) is a process of neuromodulation where electrodes are implanted in a target region to modulate the electrophysiological activity of the target region. DBS has been postulated as a potential therapy for treatment-refractory addiction, with a great deal of focus on the nucleus accumbens (NAc). Forty male Long Evans rats were implanted with unilateral stimulating electrodes within the right NAc prior to exposure to chronic cocaine self-administration (0.5 mg/kg/infusion). Following self administration, the animals were withdrawn from cocaine and treated with 14 consecutive days of sham, low frequency (LF, 20 Hz) or high frequency (HF, 160 Hz) stimulation sessions (30 min/day). The animals underwent drug seeking tests on days 1, 15 and 30 of the withdrawal phase with context-induced relapse paired with a drug challenge (5 mg/kg i.p). Relapse rates were highest on day 15 after withdrawal, with both LF and HF attenuating cocaine during this drug-seeking test, however this was not the case for tests on days 1 and 30. Motivation to respond for saccharin solution (0.1 %) remained intact following both LF and HF stimulation intake sessions. These results demonstrate that unilateral DBS of the NAc effectively attenuated cocaine-seeking following chronic exposure to stimulation although these beneficial effects appeared to diminish following cessation of daily treatment with stimulation. The results obtained in this experiment provide support for DBS as a potential therapy for patients with treatment-resistant cases of substance use disorders.

Impulsive choice refers to the inability to delay gratification and is associated with increased drug abuse vulnerability. Understanding the underlying neural mechanisms linking impulsive choice and drug abuse can contribute to improved treatment options for individuals with substance use disorders. Evidence suggests a major role for nucleus accumbens core (NAcc) in impulsive choice and the reinforcing effects of drugs of abuse. The neurotransmitters glutamate (Glu) and dopamine (DA) are implicated in the neural adaptations observed in drug addiction; however, the role of intra-NAcc Glu and DA in impulsive choice is unclear. Rats were trained in a delay discounting task, in which animals chose between a small, immediate reinforcer and large, delayed reinforcer. Consistently choosing the small, immediate reinforcer was considered to reflect increased impulsivity. Following delay discounting, in vitro receptor autoradiography was performed to quantify the number of N-methyl-D-aspartate (NMDA) receptors and dopamine transporters (DAT) in NAcc and nucleus accumbens shell (NAcSh). In a separate experiment, rats were trained in delay discounting and were implanted with guide cannulae into NAcc. Following surgery, rats received microinfusions of either a) the Glu-selective ligands MK-801 (noncompetitive NMDA receptor channel blocker; 0, 0.3, and 1.0 μg), AP-5 (competitive NMDA receptor antagonist; 0, 0.3, and 1.0 μg), ifenprodil (NMDA NR2B subunit antagonist; 0, 0.3, and 1.0 μg), and CNQX (AMPA receptor antagonist; 0, 0.2, and 0.5 μg) or b) the DA-selective ligands SKF 38393 (D1-like receptor agonist; 0, 0.03, and 0.1 μg), SCH 23390 (D1-like receptor antagonist; 0, 0.3, and 1.0 μg), quinpirole (D2-like receptor agonist; 0, 0.3, and 1.0 μg), and eticlopride (D2-like receptor antagonist; 0, 0.3, and 1.0 μg). In NAcc and NAcSh, NMDA receptor and DAT expression did not differ between high and low impulsive rats. Furthermore, intra-NAcc administration of NDMA and DA receptor ligands did not significantly alter impulsive choice. These results suggest that Glu and DA systems within NAcc do not directly mediate impulsive decision making. Future work is needed to determine the precise role of NAcc in mediating impulsive choice.

Circadian clocks are responsible for daily rhythms in gastrointestinal function which are vital for normal digestive rhythms and health. The present study examines the roles of the circadian pacemaker, the suprachiasmatic nuclei (SCN), and the sympathetic nervous system in regulation of circadian gastrointestinal rhythms in Mus musculus. Surgical ablation of the SCN abolishes circadian locomotor, feeding, and stool output rhythms when animals are presented with food ad libitum, while restricted feeding reestablishes these rhythms temporarily. In intact mice, chemical sympathectomy with 6- hydroxydopamine has no effect on feeding and locomotor rhythmicity, but attenuates stool output rhythms. Again, restricted feeding reestablishes these rhythms. Ex vivo, intestinal tissue from mPer2LUC knockin mice expresses circadian rhythms of luciferase bioluminescence. 6-hydroxydopamine has little effect upon these rhythms, but timed administration of β−adrenergic agonist isoproterenol causes a phase-dependent phase shift in PERIOD2 expression rhythms. Collectively, the data suggest the SCN are required to maintain feeding, locomotor and stool output rhythms during ad libitum conditions, acting at least in part through daily activation of sympathetic activity. Even so, this input is not necessary for entrainment to timed feeding, which may be the province of oscillators within the intestines themselves or other components of the gastrointestinal system.

This missiological study is to precede from the reformation Theology tradition. The Theological methodology used in this study in formulating theoretical indicators from scripture will follow the hermeneutics of Biblical Theology as set out by Scobie (2003), Lexicons such as Louw and Nida (1988), the grammatical - historical method (Du Toit & Roberts 1979:58), along with other relevant scholarly works will be consulted. This study focuses on the task of the Missionary church and therefore qualitative research is preferable over quantitative research. This study is limited by the fact that morality is a very wide area. There are a lot of interrelated issues that this type of study cannot address and that call for further research e.g. the task of the state towards moral regeneration and the relationship with the church and religion in general, the influence of postmodernism on the church. The context of this study is limited to South African context and covers the post 1994 democratic elections. This study will focus on the Mission focused family because it is the cornerstone of society. Chapter one presented the limites of the study on theSouth African context and cover the post the 1994 democratic elections. Secondly, the second chapter focused on the Missionary church their task to morall regeneration: begining with the church in the area such as self–introspection, repentance, confession of sins, forgiveness an faith in God and in the message of the church. Firstly, the chapter reviewed the history of South Africa and how the past Apartheid era impacted on the present situation as well as the church’s response to Moral Regeneration. Finally, the chapter looks at how the Church can come with practical development through the re–humanization of our people. Similarly, chapter four looked at the matter of Mission focused families as cornerstones for Moral Regeneration. Initially, I provided a comprehensive definition of Mission focused families in the light of, amongst other things, Deut 6: 1–25 and Eph 5: 22–23 . Finally, the fifth chapter delved on the question of the South African Missionary church and the challenges she faces as an agent of hope for moral regeneration. I analysed in detail the challenges facing the Missionary Church today, and on how the Missionary Church deals with those challenges. Most importantly, the chapter focused on the Missionary Church’s prophetic voice on moral regeneration. / Thesis (M.A. (Missiology))--North-West University, Potchefstroom Campus, 2012.

Females are disproportionately affected by stress- related mood disorders. Child abuse is the single greatest environmental risk factor for mood disorders. An animal model of child abuse, juvenile social subjugation (JSS), was used to determine whether males and females differentially process stress, specifically in the bed nucleus of the stria terminalis (BST). Rats (n=36) were randomly assigned to one of three conditions: JSS, Benign Control (BC) or Handled Control (HC). Following this procedure, brains were processed for Fos, which indicates neural activity. It was hypothesized that the JSS condition would evoke more neural activation than other conditions and would do so more in females. Across both sexes, we hypothesized there would be significantly more activation in the posterior BST than in the anterior BST. Based on earlier research, we hypothesized there would be and a sex difference in total neuron number, favoring males, in the posterior BST.

This missiological study is to precede from the reformation Theology tradition. The Theological methodology used in this study in formulating theoretical indicators from scripture will follow the hermeneutics of Biblical Theology as set out by Scobie (2003), Lexicons such as Louw and Nida (1988), the grammatical - historical method (Du Toit & Roberts 1979:58), along with other relevant scholarly works will be consulted. This study focuses on the task of the Missionary church and therefore qualitative research is preferable over quantitative research. This study is limited by the fact that morality is a very wide area. There are a lot of interrelated issues that this type of study cannot address and that call for further research e.g. the task of the state towards moral regeneration and the relationship with the church and religion in general, the influence of postmodernism on the church. The context of this study is limited to South African context and covers the post 1994 democratic elections. This study will focus on the Mission focused family because it is the cornerstone of society. Chapter one presented the limites of the study on theSouth African context and cover the post the 1994 democratic elections. Secondly, the second chapter focused on the Missionary church their task to morall regeneration: begining with the church in the area such as self–introspection, repentance, confession of sins, forgiveness an faith in God and in the message of the church. Firstly, the chapter reviewed the history of South Africa and how the past Apartheid era impacted on the present situation as well as the church’s response to Moral Regeneration. Finally, the chapter looks at how the Church can come with practical development through the re–humanization of our people. Similarly, chapter four looked at the matter of Mission focused families as cornerstones for Moral Regeneration. Initially, I provided a comprehensive definition of Mission focused families in the light of, amongst other things, Deut 6: 1–25 and Eph 5: 22–23 . Finally, the fifth chapter delved on the question of the South African Missionary church and the challenges she faces as an agent of hope for moral regeneration. I analysed in detail the challenges facing the Missionary Church today, and on how the Missionary Church deals with those challenges. Most importantly, the chapter focused on the Missionary Church’s prophetic voice on moral regeneration. / Thesis (M.A. (Missiology))--North-West University, Potchefstroom Campus, 2012.

Internal and external signaling dependent changes in cell behavior are directly linked to force-generating remodeling of the actin microfilament system which is juxtaposed to the inside of the plasma membrane. This dynamic filament system is involved in many processes in the cytoplasm and the nucleus of eukaryotic cells.   This thesis studies profilin, a regulator of actin filament dynamics which functions during incorporation of new actin molecules at growing filament ends at the cell periphery. Profilin is also present in the nucleus but its function is less well understood in this compartment. Here I present results concerning profilin and the activity of the transcription factor SRF, which is known to control the expression of actin and many actin-binding proteins in a process requiring the MRTF-A co-factor. MRTF-A binds monomeric actin and is released upon receptor mediated actin polymerization. Depletion of the two profilin isoforms I and IIa reduced MRTF-A/SRF-dependent transcription, most likely since the lack of profilin enable more MRTF-A to bind actin monomers and thereby prevent SRF-transcription. Interestingly profilin depletion also seemed to affect general transcription in the two cell lines investigated. In a separate study, a close connection between profilin, and possibly also profilin:actin, with microtubules was revealed. Microtubules are important for intracellular trafficking of vesicles as well as directional cell migration and the observation made here suggests the existence of a microtubule-associated platform for actin filaments formation. In congruence, the microtubule-associated actin nucleation promoting factor WHAMM was found to interact with profilin. Finally, the intracellular distribution of profilin was investigated by fluorescence microscopy using different peptide specific antibodies. Since these antibodies showed unique but varying results our work emphasizes common problems connected with this technique. / <p>At the time of the doctoral defence the following papers were unpublished and had a status as follows: Paper1: Manuscript; Paper 2: Manuscript; Paper 3: Manuscript</p>

Molecular, cellular, and physiological processes within an organism are set to occur at specific times throughout the day. The timing of these processes is under control of a biological clock. Nearly all organisms on Earth have biological clocks, ranging from unicellular bacteria and fungi to multicellular plants, insects, reptiles, fish, birds, and mammals. The biological clock is an endogenous time-keeping mechanism that generates the onset of many processes and coordinates the phases of processes over 24 hours. While the biological clock allows these organisms to maintain roughly 24-hour, or circadian, timing in daily processes, many organisms have the ability to set their clocks, or entrain them, to changes in light. In mammals, the suprachiasmatic nucleus (SCN) is the master biological clock that entrains daily physiological and behavioral rhythms to the appropriate times of day and night. The SCN is located in the hypothalamus and contains thousands of neurons and glia that function in coordinating system-level physiological rhythms that are entrained to environmental light cues. Many of these neurons and glia are individual circadian oscillators, and the cellular mechanisms that couple them into ensemble oscillations are emerging. Adenosine triphosphate (ATP) is a transmitter involved in local communication among astrocytes and between astrocytes and neurons. ATP released from astrocytes may play a role in SCN cellular communication and synchrony. Extracellular ATP accumulated rhythmically in the rat SCN in vivo, and ATP released from rat SCN astrocytes in vitro was rhythmic, with a periodicity near 24 hours. ATP released from mouse SCN astrocytes was circadian, and disruption of the molecular clock abolished rhythmic extracellular ATP accumulation. SCN astrocyte cultures with disrupted molecular clocks also had marked reductions in total ATP accumulation compared to SCN astrocyte cultures with functional biological clocks. Furthermore, ATP-induced calcium transients were rhythmic, and this rhythmic purinergic sensitivity was abolished in clock mutant astrocytes. Pharmacological blockade of purinergic signaling, with antagonists of both the P2X7 and P2Y1 receptors, led to a gradual reduction in the amplitude of coordinated ATP accumulation over three days. These purinergic receptor antagonists, as expected, led to a reduction in calcium responses of SCN astrocytes to ATP and led to a dampening of clock gene expression rhythms as determined by PER2::LUC bioluminescence reporting in SCN astrocytes. These data demonstrate that astrocytes of the mammalian SCN rhythmically release ATP and are rhythmically sensitive to ATP in a manner dependent on their intrinsic molecular clock. Ensemble rhythmicity of SCN astrocytes is, in turn, dependent on that rhythmic purinergic signaling via both P2X and P2Y classes of ATP receptors. These results are indicative of a functional role for ATP accumulation within the SCN, with astrocytes releasing ATP every 24 hours for continual signaling onto astrocytes and neurons to maintain daily coordinated synchrony of the clocks in these cells.