HSD10 Regulates Cancer Cell Growth and Resistance to Cell Death

Dysfunction or deregulation of certain cellular processes is commonly used to distinguish known illnesses into separate and unique disease states. Although each cancer type is individually distinct, most cancers initially occur due to genomic mutations of oncogenes and tumor suppressor genes, leading to enhancement or disruption of specific cellular processes, including mitochondrial-mediated events. As an organelle necessary for both cell survival and cell death, the mitochondrion is involved in a variety of diseases, including cancer. Specific alterations to mitochondrial DNA in cancer can result in enhanced proliferation and avoidance of cell death pathways. Thus, alterations to mitochondria function often increase the likelihood of tumor progression. In this dissertation, the role of a mitochondrial enzyme, 17β-hydroxysteroid dehydrogenase type 10 (HSD10), was examined in relation to cancer progression. In rat adrenal gland tumor cells, upregulation of HSD10 correlated with increased cell growth rate and tumor growth in mice, enhanced energy metabolism, and protection against oxidative stress-induced cell death. Downregulation of HSD10 in the rat adrenal gland tumor cells resulted in decreased cell growth rate, reduced mitochondrial bioenergetics, and increased vulnerability to cell death induction under both baseline and oxidative stress conditions. Reductions in cell growth rate and energy metabolism were also observed upon HSD10 knockdown in T47D human breast cancer cells, which supports the role of HSD10 in cancer across two different cancer types and species. Furthermore, overexpression of HSD10 did not transform MCF10A breast cells, providing evidence that HSD10 may not be a tumor-initiating factor. Together, the data suggest that upregulation of HSD10 promotes cell growth and resistance to stress-induced cell death specifically in cancer cells

Designing and Building an Inverted Microscope

Iowa Stonybrook Lasers And DNA Course Embedded Research (ISLAND CURE) is a new research collaboration group that is focused on undergraduate research for both the students and the professors. The goal of this research collaboration was to create physics apparatuses to make biochemical measurements. One of the tools we are developing is an infrared optical tweezing system. This requires an inverted microscope to facilitate the trap. To observe one of these measurements, an inverted microscope is required to observe the sample. Inverted microscopes can be expensive, and our budget is limited. To overcome this issue, our research group decided to create our own inverted microscope with the minimal budget we had. This microscope can now be used for optical tweezing and observation of a live sample

From a Cell’s Viewpoint: Targeting Mitochondria in Alzheimer’s disease

Mitochondria are well-known cellular organelles widely studied in relation to a variety of disease states, including Alzheimer’s disease. With roles in several metabolic processes, numerous signal transduction pathways, and overall cell maintenance and survival, mitochondria are essential to understanding the inner workings of cells. As mitochondria are able to be utilized by diverse illnesses to increase the likelihood of disease progression, targeting specific processes in these organelles could provide beneficial therapeutic options

Mitochondrial permeability transition pore is a potential drug target for neurodegeneration

Mitochondrial permeability transition pore (mPTP) plays a central role in alterations of mitochondrial structure and function leading to neuronal injury relevant to aging and neurodegenerative diseases including Alzheimer’s disease (AD). mPTP putatively consists of the voltage-dependent anion channel (VDAC) and the adenine nucleotide translocator (ANT). Cyclophilin D (CypD) and reactive oxygen species (ROS) increase intra-cellular calcium and enhance the formation of mPTP that leads to neuronal cell death in AD. CypD-dependent mPTP can play a crucial role in ischemia/reperfusion injury. The interaction of amyloid beta peptide (Aβ) with CypD potentiates mitochondrial and neuronal perturbation. This interaction triggers the formation of mPTP, resulting in decreased mitochondrial membrane potential, impaired mitochondrial respiration function, increased oxidative stress, release of cytochrome c, and impaired axonal mitochondrial transport. Thus, the CypD-dependent mPTP is directly linked to the cellular and synaptic perturbations observed in the pathogenesis of AD. Designing small molecules to block this interaction would lessen the effects of Aβ neurotoxicity. This review summarizes the recent progress on mPTP and its potential therapeutic target for neurodegenerative diseases including AD

Mitochondrial permeability transition pore is a potential drug target for neurodegeneration

Mitochondrial permeability transition pore (mPTP) plays a central role in alterations of mitochondrial structure and function leading to neuronal injury relevant to aging and neurodegenerative diseases including Alzheimer’s disease (AD). mPTP putatively consists of the voltage-dependent anion channel (VDAC) and the adenine nucleotide translocator (ANT). Cyclophilin D (CypD) and reactive oxygen species (ROS) increase intra-cellular calcium and enhance the formation of mPTP that leads to neuronal cell death in AD. CypD-dependent mPTP can play a crucial role in ischemia/reperfusion injury. The interaction of amyloid beta peptide (Aβ) with CypD potentiates mitochondrial and neuronal perturbation. This interaction triggers the formation of mPTP, resulting in decreased mitochondrial membrane potential, impaired mitochondrial respiration function, increased oxidative stress, release of cytochrome c, and impaired axonal mitochondrial transport. Thus, the CypD-dependent mPTP is directly linked to the cellular and synaptic perturbations observed in the pathogenesis of AD. Designing small molecules to block this interaction would lessen the effects of Aβ neurotoxicity. This review summarizes the recent progress on mPTP and its potential therapeutic target for neurodegenerative diseases including AD

Enhancing Social Skills in Adolescents with High Functioning Autism using Motor-based Role-play Intervention

The purpose of this pilot study was to collect pilot data evaluating whether a motor-based role-play intervention using a canine animal assistant can enhance social skill use in two adolescents with HFA. A single subject ABA design across two participants was used. The intervention consisted of four 1-hour sessions over 4 weeks. The quality of social interaction was measured by the Evaluation of Social Interaction (ESI) administered at baseline and the 3-month probe. Frequency of targeted social skill use was measured during baseline, intervention, and probe phases. Participant 1 experienced statistically significant increases in both ESI scores (p = .012, t = -5.488) from baseline to the 3-month probe. Participant 2 also experienced a statistically significant increase in ESI scores from baseline to probe (p = .002, t = -10.167), but he was unable to fully maintain these gains at the 3-month probe. This pilot study’s findings suggest that the intervention produced positive effects in both participants and warrant further investigation

Overexpression of 17β-hydroxysteroid dehydrogenase type 10 increases pheochromocytoma cell growth and resistance to cell death

Background: 17β-hydroxysteroid dehydrogenase type 10 (HSD10) has been shown to play a protective role in cells undergoing stress. Upregulation of HSD10 under nutrient-limiting conditions leads to recovery of a homeostatic state. Across disease states, increased HSD10 levels can have a profound and varied impact, such as beneficial in Parkinson’s disease and harmful in Alzheimer’s disease. Recently, HSD10 overexpression has been observed in some prostate and bone cancers, consistently correlating with poor patient prognosis. As the role of HSD10 in cancer remains underexplored, we propose that cancer cells utilize this enzyme to promote cancer cell survival under cell death conditions. Methods: The proliferative effect of HSD10 was examined in transfected pheochromocytoma cells by growth curve analysis and a xenograft model. Fluctuations in mitochondrial bioenergetics were evaluated by electron transport chain complex enzyme activity assays and energy production. Additionally, the effect of HSD10 on pheochromocytoma resistance to cell death was investigated using TUNEL staining, MTT, and complex IV enzyme activity assays. Results: In this study, we examined the tumor-promoting effect of HSD10 in pheochromocytoma cells. Overexpression of HSD10 increased pheochromocytoma cell growth in both in vitro cell culture and an in vivo xenograft mouse model. The increases in respiratory enzymes and energy generation observed in HSD10-overexpressing cells likely supported the accelerated growth rate observed. Furthermore, cells overexpressing HSD10 were more resistant to oxidative stress-induced perturbation. Conclusions: Our findings demonstrate that overexpression of HSD10 accelerates pheochromocytoma cell growth, enhances cell respiration, and increases cellular resistance to cell death induction. This suggests that blockade of HSD10 may halt and/or prevent cancer growth, thus providing a promising novel target for cancer patients as a screening or therapeutic option

Solution Focused Financial Therapy: A Brief Report of a Pilot Study

The financial counseling, financial planning, and financial therapy fields are hampered by a conceptual and empirical paucity of clinical and experimental evidence-based research. In an attempt to decrease this gap in the literature, a pilot study was developed to test the implementation of a solution-focused financial therapy client intervention approach, in which solution-focused therapy techniques were applied in a financial counseling setting. This paper reports findings from a clinical intervention study of college students (N = 8) who presented a variety of financial issues related to budgeting, investing, and debt repayment problems. Data were gathered prior to the start of treatment, after treatment ended, and three months later. Participants’ psychological well-being and financial behaviors improved, while financial distress decreased. The solution-focused financial therapy approach used is discussed

Aquatic biosurvey of the Lovell River on UNH land

We assessed the physical, chemical and biological conditions at two sites along the Lovell River on University of New Hampshire (UNH) -owned conservation land. The discharge was 4.4 m3 s-1 at Site 1 and 5.7 m3 s -1 downstream at Site 2. Canopy coverage ranged from 8-25%. Canopy was dominated by Eastern Hemlock (79-84%). Much of the stream was strewn with large boulders and the substrate consisted of rocks of highly variable sizes ( 3-549 cm dia.). Specific conductivity (22.1-23.3 µS), pH (6.4) and temperature (7.9-8.3 °C) varied little between sites. Macro-invertebrate bio-indices indicated either excellent water quality with no apparent organic pollution (3.0/10) or good water quality with possible slight organic pollution (4.4/10)

Identification of Human ABAD Inhibitors for Rescuing Aβ-Mediated Mitochondrial Dysfunction

Amyloid beta (Aβ) binding alcohol dehydrogenase (ABAD) is a cellular cofactor for promoting (Aβ)-mediated mitochondrial and neuronal dysfunction, and cognitive decline in transgenic Alzheimer's disease (AD) mouse models. Targeting mitochondrial ABAD may represent a novel therapeutic strategy against AD. Here, we report the biological activity of small molecule ABAD inhibitors. Using in vitro surface plasmon resonance (SPR) studies, we synthesized compounds with strong binding affinities for ABAD. Further, these ABAD inhibitors (ABAD-4a and 4b) reduced ABAD enzyme activity and administration of phosphonate derivatives of ABAD inhibitors antagonized calcium-mediated mitochondrial swelling. Importantly, these compounds also abolished Aβ-induced mitochondrial dysfunction as shown by increased cytochrome c oxidase and adenosine-5′-triphosphate levels, suggesting protective mitochondrial function effects of these synthesized compounds. Thus, these compounds are potential candidates for further pharmacologic development to target ABAD to improve mitochondrial function