Role of TATATAA element in the regulation of tRNA(1)(Gly) gene expression in Bombyx mori is position dependent

Transcription of tRNA genes by RNA polymerase III is controlled by the internal conserved sequences within the coding region and the immediate upstream flanking sequences. A highly transcribed copy of glycyl tRNA gene tRNA1(Gly)-1 from Bombyx mori is down regulated by sequences located much farther upstream in the region -150 to -300 nucleotides (nt), with respect to the +1 nt of tRNA. The negative regulatory effect has been narrowed down to a sequence motif 'TATATAA', a perfect consensus recognised by the TATA binding protein, TBP. This sequence element, when brought closer to the transcription start point, on the other hand, exerts a positive effect by promoting transcription of the gene devoid of other cis regulatory elements. The identity of the nuclear protein interacting with this 'TATATAA' element to TBP has been established by antibody and mutagenesis studies. The 'TATATAA' element thus influences the transcription of tRNA genes positively or negatively in a position-dependent manner either by recruitment or sequestration of TBP from the transcription machinery.

Identification of putative regulatory motifs in the upstream regions of co-expressed functional groups of genes in Plasmodium falciparum

Background: Regulation of gene expression in Plasmodium falciparum (Pf) remains poorly understood. While over half the genes are estimated to be regulated at the transcriptional level, few regulatory motifs and transcription regulators have been found. Results: The study seeks to identify putative regulatory motifs in the upstream regions of 13 functional groups of genes expressed in the intraerythrocytic developmental cycle of Pf. Three motif-discovery programs were used for the purpose, and motifs were searched for only on the gene coding strand. Four motifs – the 'G-rich', the 'C-rich', the 'TGTG' and the 'CACA' motifs – were identified, and zero to all four of these occur in the 13 sets of upstream regions. The 'CACA motif' was absent in functional groups expressed during the ring to early trophozoite transition. For functional groups expressed in each transition, the motifs tended to be similar. Upstream motifs in some functional groups showed 'positional conservation' by occurring at similar positions relative to the translational start site (TLS); this increases their significance as regulatory motifs. In the ribonucleotide synthesis, mitochondrial, proteasome and organellar translation machinery genes, G-rich, C-rich, CACA and TGTG motifs, respectively, occur with striking positional conservation. In the organellar translation machinery group, G-rich motifs occur close to the TLS. The same motifs were sometimes identified for multiple functional groups; differences in location and abundance of the motifs appear to ensure different modes of action. Conclusion: The identification of positionally conserved over-represented upstream motifs throws light on putative regulatory elements for transcription in Pf.

A pilot study in different unstable designs on the biomechanical effect of gait characteristics

The purpose of this study was to compare kinematics and kinetics during walking for healthy subjects using unstable shoes with different designs. Ten subjects participated in this study, and foot biomechanical data during walking were quantified using motion analysis system and a force plate. Data were collected for unstable shoes condition after accommodation period of one week. With soft material added in the heel region, the peak impact force was effectively reduced when compared among similar shapes. In addition, the soft material added in the rocker bottom showed more to be in dorsiflexed position during the initial stance. The shoe with three rocker curves design reduced the contact area in the heel strike, which may result in increasing human body forward speed. Further studies shall be carried out after adapting to long periods of wearing unstable shoes.

Construction, installation, and performance of two repacked weighing lysimeters

Weighing lysimeters are the standard method for directly measuring evapotranspiration (ET). This paper discusses the construction, installation, and performance of two (1.52 m × 1.52 m × 2.13-m deep) repacked weighing lysimeters for measuring ET of corn and soybean in West Central Nebraska. The cost of constructing and installing each lysimeter was approximately US $12,500, which could vary depending on the availability and cost of equipment and labor. The resolution of the lysimeters was 0.0001 mV V-1, which was limited by the data processing and storage resolution of the datalogger. This resolution was equivalent to 0.064 and 0.078 mm of ET for the north and south lysimeters, respectively. Since the percent measurement error decreases with the magnitude of the ET measured, this resolution is adequate for measuring ET for daily and longer periods, but not for shorter time steps. This resolution would result in measurement errors of less than 5% for measuring ET values of ≥3 mm, but the percent error rapidly increases for lower ET values. The resolution of the lysimeters could potentially be improved by choosing a datalogger that could process and store data with a higher resolution than the one used in this study.

Evaluation of three storage systems used for chilling and holding swordfish

Swordfish are kept chilled, not frozen, for up to 15 days before being unloaded at Australian ports. Swordfish landed alive, and to a lesser extent prerigor, have better quality when unloaded. Warmer fishing waters did not lead to poorer quality at unloading. There was a serious loss of quality during long fishing trips. Sex had no influence on swordfish quality. Three methods of chilling were evaluated: refrigerated seawater (RSW) chilling for up to 2 days followed by storage under ice, refrigerated brine (seawater with extra salt added) for up to 2 days followed by storage in a freshwater ice slurry, and ice slurry (freshwater ice mixed with seawater) for up to 2 days followed by storage under ice only. Two fishing trips were monitored for each method. The freshness indicator K value was used to determine which method produced the best quality swordfish when unloaded at the factory. Storage method played a larger role in quality loss than capture conditions. Refrigerated brine produced the best quality swordfish when the machinery functioned properly closely followed by RSW. Ice slurry chilling of large fish such as swordfish exhibited initial delays in the reduction of core temperature which led to lower quality. This method could be improved with the addition of mechanical circulation. Mechanical problems, which resulted in minor increases of temperature during brine storage, led to a much larger loss of quality than would be expected.

Growth and physiological response of six Australian rainforest tree species to a light gradient

An understanding of growth and photosynthetic potential of subtropical rainforest species to variations in light environment can be useful for determining the sequence of species introductions in rainforest restoration projects and mixed species plantations. We examined the growth and physiology of six Australian subtropical rainforest tree species in a greenhouse consisting of three artificial light environments (10%, 30%, and 60% full sunlight). Morphological responses followed the typical sun-shade dichotomy, with early and late secondary species (Elaeocarpus grandis, Flindersia brayleyana, Flindersia schottiana, and Gmelina leichhardtii) displaying higher relative growth rate (RGR) compared to mature stage species (Cryptocarya erythroxyion and Heritiera trifoliolatum). Growth and photosynthetic performance of most species reached a maximum in 30-60% full sunlight. Physiological responses provided limited evidence of a distinct dichotomy between early and late successional species. E. grandis and F brayleyana, provided a clear representation of early successional species, with marked increase in Am in high light and an ability to down regulate photosynthetic machinery in low light conditions. The remaining species (F. schottiana, G. leichhardtii, and H. trifoliolatum) were better represented as failing along a shade-tolerant continuum, with limited ability to adjust physiologically to an increase or decrease in light, maintaining similar A(max) across all light environments. Results show that most species belong to a shade-tolerant constituency, with an ability to grow and persist across a wide range of light environments. The species offer a wide range of potential planting scenarios and silvicultural options, with ample potential to achieve rapid canopy closure and rainforest restoration goals.

Effect of Crowding Agents, Signal Peptide, and Chaperone SecB on the Folding and Aggregation of E. coli Maltose Binding Protein

SecB, a soluble cytosolic chaperone component of the Secexport pathway, binds to newly synthesized precursor proteins and prevents their premature aggregation and folding and subsequently targets them to the translocation machinery on the membrane. PreMBP, the precursor form of maltose binding protein, has a 26-residue signal sequence attached to the N-terminus of MBP and is a physiological substrate of SecB. We examine the effect of macromolecular crowding and SecB on the stability and refolding of denatured preMBP and MBP. PreMBP was less stable than MBP (ΔTm =7( 0.5 K) in both crowded and uncrowded solutions. Crowding did not cause any substantial changes in the thermal stability ofMBP(ΔTm=1(0.4 K) or preMBP (ΔTm=0(0.6 K), as observed in spectroscopically monitored thermal unfolding experiments. However, both MBP and preMBP were prone to aggregation while refolding under crowded conditions. In contrast to MBP aggregates, which were amorphous, preMBP aggregates form amyloid fibrils.Under uncrowded conditions, a molar excess of SecB was able to completely prevent aggregation and promote disaggregation of preformed aggregates of MBP. When a complex of the denatured protein and SecB was preformed, SecB could completely prevent aggregation and promote folding of MBP and preMBP even in crowded solution. Thus, in addition to maintaining substrates in an unfolded, export-competent conformation, SecB also suppresses the aggregation of its substrates in the crowded intracellular environment. SecB is also able to promote passive disaggregation of macroscopic aggregates of MBP in the absence of an energy source such as ATP or additional cofactors. These experiments also demonstrate that signal peptide can reatly influence protein stability and aggregation propensity.

Design and Development of an In-Vehicle Human Machine Interface to Improve Fuel Efficiency & Safety

Road transport plays a significant role in various industries and mobility services around the globe and has a vital impact on our daily lives. However it also has serious impacts on both public health and the environment. In-vehicle feedback systems are a relatively new approach to encouraging driver behaviour change for improving fuel efficiency and safety in automotive environments. While many studies claim that the adoption of eco-driving practices, such as eco-driving training programs and in-vehicle feedback to drivers, has the potential to improve fuel efficiency, limited research has integrated safety and eco-driving. Therefore, this research seeks to use human factors related theories and practices to inform the design and evaluation of an in-vehicle Human Machine Interface (HMI) providing real-time driver feedback with the aim of improving both fuel efficiency and safety.

Row spacing and planting density effects on the growth and yield of sugarcane. 2. Strategies for the adoption of controlled traffic.

Controlled traffic (matching wheel and row spacing) is being promoted as a means to manage soil compaction in the Australian sugar industry. However, machinery limitations dictate that wider row spacings than the standard 1.5-m single row will need to be adopted to incorporate controlled traffic and many growers are reluctant to widen row spacing for fear of yield penalties. To address these concerns, contrasting row configuration and planting density combinations were investigated for their effect on cane and sugar yield in large-scale experiments in the Gordonvale, Tully, Ingham, Mackay, and Bingera (near Bundaberg) sugarcane-growing regions of Queensland, Australia. The results showed that sugarcane possesses a capacity to compensate for different row configurations and planting densities through variation in stalk number and individual stalk weight. Row configurations ranging from 1.5-m single rows (the current industry standard) to 1.8-m dual rows (50 cm between duals), 2.1-m dual (80 cm between duals) and triple ( 65 cm between triples) rows, and 2.3-m triple rows (65 cm between triples) produced similar yields. Four rows (50 cm apart) on a 2.1-m configuration (quad rows) produced lower yields largely due to crop lodging, while a 1.8-m single row configuration produced lower yields in the plant crop, probably due to inadequate resource availability (water stress/limited radiation interception). The results suggest that controlled traffic can be adopted in the Australian sugar industry by changing from a 1.5-m single row to 1.8-m dual row configuration without yield penalty. Further, the similar yields obtained with wider row configurations (2 m or greater with multiple rows) in these experiments emphasise the physiological and environmental plasticity that exists in sugarcane. Controlled traffic can be implemented with these wider row configurations (>2 m), although it will be necessary to carry out expensive modifications to the current harvester and haul-out equipment. There were indications from this research that not all cultivars were suited to configurations involving multiple rows. The results suggest that consideration be given to assessing clones with different growth habits under a range of row configurations to find the most suitable plant types for controlled traffic cropping systems.

Playing alone, playing with others: Differences in player experience and indicators of wellbeing

Video game play is becoming an increasingly social experience, yet we have little understanding of how social and solitary modes of play differ in terms of the player experience or interact with player wellbeing. An online survey (n = 446) collected data on players' current mode of play, their game play experience, social capital gained from game play and wellbeing. The results indicate that social and solitary players differ in terms of degree of autonomy, presence and relatedness experienced, while the different types of social play are associated with differences in relatedness and social capital experienced. Different predictors of wellbeing were also present across solitary and social player samples. People who play games on their own experience greater wellbeing when experiencing in-game autonomy. Social players experience greater wellbeing when playing with strangers, and when experiencing in-game bridging social capital. All players experienced increased wellbeing with age and decreased wellbeing with greater amounts of play.

Characterization of the mitochondrial active-site serine protein LACTB: filaments in the mitochondrial intermembrane space

Mitochondria have evolved from endosymbiotic alpha-proteobacteria. During the endosymbiotic process early eukaryotes dumped the major component of the bacterial cell wall, the peptidoglycan layer. Peptidoglycan is synthesized and maintained by active-site serine enzymes belonging to the penicillin-binding protein and the β-lactamase superfamily. Mammals harbor a protein named LACTB that shares sequence similarity with bacterial penicillin-binding proteins and β-lactamases. Since eukaryotes lack the synthesis machinery for peptidoglycan, the physiological role of LACTB is intriguing. Recently, LACTB has been validated in vivo to be causative for obesity, suggesting that LACTB is implicated in metabolic processes. The aim of this study was to investigate the phylogeny, structure, biochemistry and cell biology of LACTB in order to elucidate its physiological function. Phylogenetic analysis revealed that LACTB has evolved from penicillin binding-proteins present in the bacterial periplasmic space. A structural model of LACTB indicates that LACTB shares characteristic features common to all penicillin-binding proteins and β-lactamases. Recombinat LACTB protein expressed in E. coli was recovered in significant quantities. Biochemical and cell biology studies showed that LACTB is a soluble protein localized in the mitochondrial intermembrane space. Further analysis showed that LACTB preprotein underwent proteolytic processing disclosing an N-terminal tetrapeptide motif also found in a set of cell death-inducing proteins. Electron microscopy structural studies revealed that LACTB can polymerize to form stable filaments with lengths ranging from twenty to several hundred nanometers. These data suggest that LACTB filaments define a distinct microdomain in the intermembrane space. A possible role of LACTB filaments is proposed in the intramitochondrial membrane organization and microcompartmentation. The implications of these findings offer novel insight into the evolution of mitochondria. Further studies of the LACTB function might provide a tool to treat mitochondria-related metabolic diseases.

Mitochondrial Malfunction in Tumor Formation and Neuromuscular Diseases : Consequences of defects in fumarate hydratase and in the respiratory chain

The mitochondrion is an organelle of outmost importance, and the mitochondrial network performs an array of functions that go well beyond ATP synthesis. Defects in mitochondrial performance lead to diseases, often affecting nervous system and muscle. Although many of these mitochondrial diseases have been linked to defects in specific genes, the molecular mechanisms underlying the pathologies remain unclear. The work in this thesis aims to determine how defects in mitochondria are communicated within - and interpreted by - the cells, and how this contributes to disease phenotypes. Fumarate hydratase (FH) is an enzyme of the citrate cycle. Recessive defects in FH lead to infantile mitochondrial encephalopathies, while dominant mutations predispose to tumor formation. Defects in succinate dehydrogenase (SDH), the enzyme that precedes FH in the citrate cycle, have also been described. Mutations in SDH subunits SDHB, SDHC and SDHD are associated with tumor predisposition, while mutations in SDHA lead to a characteristic mitochondrial encephalopathy of childhood. Thus, the citrate cycle, via FH and SDH, seems to have essential roles in mitochondrial function, as well as in the regulation of processes such as cell proliferation, differentiation or death. Tumor predisposition is not a typical feature of mitochondrial energy deficiency diseases. However, defects in citrate cycle enzymes also affect mitochondrial energy metabolism. It is therefore necessary to distinguish what is specific for defects in citrate cycle, and thus possibly associated with the tumor phenotype, from the generic consequences of defects in mitochondrial aerobic metabolism. We used primary fibroblasts from patients with recessive FH defects to study the cellular consequences of FH-deficiency (FH-). Similarly to the tumors observed in FH- patients, these fibroblasts have very low FH activity. The use of primary cells has the advantage that they are diploid, in contrast with the aneuploid tumor cells, thereby enabling the study of the early consequences of FH- in diploid background, before tumorigenesis and aneuploidy. To distinguish the specific consequences of FH- from typical consequences of defects in mitochondrial aerobic metabolism, we used primary fibroblasts from patients with MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) and from patients with NARP (neuropathy, ataxia and retinitis pigmentosa). These diseases also affect mitochondrial aerobic metabolism but are not known to predispose to tumor formation. To study in vivo the systemic consequences of defects in mitochondrial aerobic metabolism, we used a transgenic mouse model of late-onset mitochondrial myopathy. The mouse contains a transgene with an in-frame duplication of a segment of Twinkle, the mitochondrial replicative helicase, whose defects underlie the human disease progressive external ophthalmoplegia. This mouse model replicates the phenotype in the patients, particularly neuronal degeneration, mitochondrial myopathy, and subtle decrease of respiratory chain activity associated with mtDNA deletions. Due to the accumulation of mtDNA deletions, the mouse was named deletor. We first studied the consequences of FH- and of respiratory chain defects for energy metabolism in primary fibroblasts. To further characterize the effects of FH- and respiratory chain malfunction in primary fibroblasts at transcriptional level, we used expression microarrays. In order to understand the in vivo consequences of respiratory chain defects in vivo, we also studied the transcriptional consequences of Twinkle defects in deletor mice skeletal muscle, cerebellum and hippocampus. Fumarate accumulated in the FH- homozygous cells, but not in the compound heterozygous lines. However, virtually all FH- lines lacked cytoplasmic FH. Induction of glycolysis was common to FH-, MELAS and NARP fibroblasts. In deletor muscle glycolysis seemed to be upregulated. This was in contrast with deletor cerebellum and hippocampus, where mitochondrial biogenesis was in progress. Despite sharing a glycolytic pattern in energy metabolism, FH- and respiratory chain defects led to opposite consequences in redox environment. FH- was associated with reduced redox environment, while MELAS and NARP displayed evidences of oxidative stress. The deletor cerebellum had transcriptional induction of antioxidant defenses, suggesting increased production of reactive oxygen species. Since the fibroblasts do not represent the tissues where the tumors appear in FH- patients, we compared the fibroblast array data with the data from FH- leiomyomas and normal myometrium. This allowed the determination of the pathways and networks affected by FH-deficiency in primary cells that are also relevant for myoma formation. A key pathway regulating smooth muscle differentiation, SRF (serum response factor)-FOS-JUNB, was found to be downregulated in FH- cells and in myomas. While in the deletor mouse many pathways were affected in a tissue-specific basis, like FGF21 induction in the deletor muscle, others were systemic, such as the downregulation of ALAS2-linked heme synthesis in all deletor tissues analyzed. However, interestingly, even a tissue-specific response of FGF21 excretion could elicit a global starvation response. The work presented in this thesis has contributed to a better understanding of mitochondrial stress signalling and of pathways interpreting and transducing it to human pathology.

Indicators of wellbeing in recreational video game players

Video game play is a popular entertainment choice, yet we have a limited understanding of the potential wellbeing benefits associated with recreational play. An online survey (final sample, n = 297) addresses this by investigating how the player experience related to wellbeing. The impact of amount of play, game genre, mode of play (social or solitary play) and the psychological experience of play (flow and need satisfaction) on a multi-dimensional measure of wellbeing (emotional, psychological and social) was examined via hierarchical regression. Age, gender, the play of casual games compared to shooters, and in-game experiences of flow, autonomy and relatedness were associated with increases in dimensions of wellbeing.

Testing the effectiveness of the SKIM foam fractionator to reduce nutrient levels in prawn farm effluent

To experimentally investigate the effect of the “SKIM” mechanical foam fractionator on suspended material and the nutrient levels in prawn farm effluent, a series of standardised short-term treatments were applied to various effluent types in a static 10,000-litre water body. Prawn pond effluents were characterised by watercolour and dominance of phytoplankton species. Three effluent types were tested, namely 1) particulate-rich effluent with little apparent phytoplankton, 2) green mircoalgal bloom predominately made up of single celled phytoplankton, and 3) brown microalgal bloom with higher prevalence of diatoms. The effluent types were similar (P>0.05) in non-volatile particulate material, and nitrate/nitrite but varied from each other in the following ways: 1) The particulate-rich effluents were lower (P<0.05) in volatile solids (compared to brown blooms), total Kjeldahl nitrogen, dissolved organic nitrogen, dissolved organic phosphorus and chlorophyll a (compared to both green and brown blooms). 2) The brown blooms were higher (P<0.05) in ammonia (compared to green blooms), total nitrogen and total phosphorus (compared to both green and particulate-rich effluent), but were lower (P<0.05) in inorganic phosphorus (compared to both green and particulate-rich effluent). 3) The green blooms were higher (P<0.05) in dissolved (both organic and inorganic) phosphorus (compared to both brown and particulate-rich effluents). Although the effluent types varied significantly in these aspects the effect of the Skim treatment was similar for all parameters measured except total phosphorus. Bloom type and Skim-treatment period significantly (P<0.05) affected total Kjeldahl phosphorus concentrations. For all effluent types there was a continuous significant reduction (P<0.05) in total Kjeldahl phosphorus during the initial 6-hour treatment period. Levels of total suspended solids and volatile suspended solids in all effluent types were significantly (P<0.05) reduced in the first 2 hours but not thereafter. Non-volatile suspended solids were also significantly (P<0.05) reduced in the first 2 hours (30 to 40 % reduction) and a further 40% reduction occurred in the particulate-rich effluent over the next 2 hours. Mean values for total ammonia, dissolved organic nitrogen, total Kjeldahl nitrogen, total nitrogen, chlorophyll a and dissolved organic or inorganic phosphorus levels were not significantly (P>0.05) affected by the Skim unit in any bloom type during the initial 6 hours of testing. Nevertheless, non-significant nitrogen reductions did occur. Foam production by the Skim unit varied with different blooms, resulting in different concentrate volumes and different end points for separate experiments. Concentrate volumes were generally high for the particulate-rich and green blooms (175 – 370 litres) and low for the brown blooms (25 – 80 litres). This was due to the low tendency of the brown bloom to produce foam. This generated higher nutrient concentrations in the associated condensed foam, but may have limited the treatment efficiency. The results suggest that in this application, the Skim unit did not remove micro-algae as effectively as was anticipated. However, it was effective at removing other suspended solids. Considering these attributes and the other uses of this machinery documented by the manufactures, the unit’s oxygenation mixing capacities coupled with inorganic solids removal may provide a suitable mechanism for construction of a continuously mixed bioreactor that utilises the filtration and profit making abilities of bivalves.

Molecular Mechanisms of Androgen Receptor Interactions

The androgen receptor (AR) mediates the effects of the male sex-steroid hormones (androgens), testosterone and 5?-dihydrotestosterone. Androgens are critical in the development and maintenance of male sexual characteristics. AR is a member of the steroid receptor ligand-inducible transcription factor family. The steroid receptor family is a subgroup of the nuclear receptor superfamily that also includes receptors for the active forms of vitamin A, vitamin D3, and thyroid hormones. Like all nuclear receptors, AR has a conserved modular structure consisting of a non-conserved amino-terminal domain (NTD), containing the intrinsic activation function 1, a highly conserved DNA-binding domain, and a conserved ligand-binding domain (LBD) that harbors the activation function 2. Each of these domains plays an important role in receptor function and signaling, either via intra- and inter-receptor interactions, interactions with specific DNA sequences, termed hormone response elements, or via functional interactions with domain-specific proteins, termed coregulators (coactivators and corepressors). Upon binding androgens, AR acquires a new conformational state, translocates to the nucleus, binds to androgen response elements, homodimerizes and recruits sequence-specific coregulatory factors and the basal transcription machinery. This set of events is required to activate gene transcription (expression). Gene transcription is a strictly modulated process that governs cell growth, cell homeostasis, cell function and cell death. Disruptions of AR transcriptional activity caused by receptor mutations and/or altered coregulator interactions are linked to a wide spectrum of androgen insensitivity syndromes, and to the pathogenesis of prostate cancer (CaP). The treatment of CaP usually involves androgen depletion therapy (ADT). ADT achieves significant clinical responses during the early stages of the disease. However, under the selective pressure of androgen withdrawal, androgen-dependent CaP can progress to an androgen-independent CaP. Androgen-independent CaP is invariably a more aggressive and untreatable form of the disease. Advancing our understanding of the molecular mechanisms behind the switch in androgen-dependency would improve our success of treating CaP and other AR related illnesses. This study evaluates how clinically identified AR mutations affect the receptor s transcriptional activity. We reveal that a potential molecular abnormality in androgen insensitivity syndrome and CaP patients is caused by disruptions of the important intra-receptor NTD/LBD interaction. We demonstrate that the same AR LBD mutations can also disrupt the recruitment of the p160 coactivator protein GRIP1. Our investigations reveal that 30% of patients with advanced, untreated local CaP have somatic mutations that may lead to increases in AR activity. We report that somatic mutations that activate AR may lead to early relapse in ADT. Our results demonstrate that the types of ADT a CaP patient receives may cause a clustering of mutations to a particular region of the receptor. Furthermore, the mutations that arise before and during ADT do not always result in a receptor that is more active, indicating that coregulator interactions play a pivotal role in the progression of androgen-independent CaP. To improve CaP therapy, it is necessary to identify critical coregulators of AR. We screened a HeLa cell cDNA library and identified small carboxyl-terminal domain phosphatase 2 (SCP2). SCP2 is a protein phosphatase that directly interacts with the AR NTD and represses AR activity. We demonstrated that reducing the endogenous cellular levels of SCP2 causes more AR to load on to the prostate specific antigen (PSA) gene promoter and enhancer regions. Additionally, under the same conditions, more RNA polymerase II was recruited to the PSA promoter region and overall there was an increase in androgen-dependent transcription of the PSA gene, revealing that SCP2 could play a role in the pathogenesis of CaP.