Posted by: kelsijo97 | January 24, 2014

January 2014

Bhuiyan, M. S., Pattison, J. Scott, Osinska, H., James, J., Gulick, J., McLendon, P. M., . . . Robbins, J. (2013). Enhanced autophagy ameliorates cardiac proteinopathy. Journal of Clinical Investigation, 123(12), 5284-5297.

Basal autophagy is a crucial mechanism in cellular homeostasis, underlying both normal cellular recycling and the clearance of damaged or misfolded proteins, organelles and aggregates. We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). To increase levels of basal autophagy, we generated an inducible Tg mouse expressing autophagy-related 7 (Atg7), a critical and rate-limiting autophagy protein. Hearts from these mice had enhanced autophagy, but normal morphology and function. We crossed these mice with CryAB(R120G) mice, a model of DRC in which autophagy is significantly attenuated in the heart, to test the functional significance of autophagy activation in a proteotoxic model of heart failure. Sustained Atg7-induced autophagy in the CryAB(R120G) hearts decreased interstitial fibrosis, ameliorated ventricular dysfunction, decreased cardiac hypertrophy, reduced intracellular aggregates and prolonged survival. To determine whether different methods of autophagy upregulation have additive or even synergistic benefits, we subjected the autophagy-deficient CryAB(R120G) mice and the Atg7-crossed CryAB(R120G) mice to voluntary exercise, which also upregulates autophagy. The entire exercised Atg7-crossed CryAB(R120G) cohort survived to 7 months. These findings suggest that activating autophagy may be a viable therapeutic strategy for improving cardiac performance under proteotoxic conditions.

Basic Biomedical Sciences, Vermillion Campus.

Canguo, Zhao, Shouting, Liu, Changshan, Yang, Xiaofen, Li, Hongbiao, Huang, Ningning, Liu, . . . Jinbao, Liu. (2013). Gambogic acid moderates cardiac responses to chronic hypoxia likely by acting on the proteasome and NF-κB pathway. American Journal of Cardiovascular Disease, 3(3), 135-145.

Gambogic acid (GA) is the principal active ingredient of gamboges. GA was reported to exert anti-tumor and anti-inflammatory effects both in vitro and in vivo. Previously, we have shown that GA is a more tissue-specific proteasome inhibitor than bortezomib and it is less toxic to peripheral white blood cells compared to bortezomib. Ubiquitous proteasome inhibition was shown by some reports, but not by others, to prevent cardiac remodeling in response to pressure overload by blocking the NF-κB pathway; however, whether GA modulates the development of chronic hypoxia-induced right ventricular hypertrophy has not been investigated yet. Here we report that GA can significantly attenuate right ventricular hypertrophy induced by chronic hypoxia, reduce cardiac fibrosis, and remarkably block the reactivation of bona fide fetal genes in the cardiac tissue. Furthermore, we also investigated the potential molecular targets of GA on right ventricular hypertrophy. The results showed that GA could accumulate the IκB levels associated with decreased proteasomal activity, block the translocation of NF-κB from the cytoplasm to the nucleus, decrease NF-κB DNA-binding activity, and reduce IL-2 levels. In conclusion, GA is capable of preventing the development of chronic hypoxia-induced right ventricular hypertrophy. GA has great potential to be developed into an effective anti-hypertrophy agent.

Basic Biomedical Sciences, Vermillion Campus.

Novick, Andrew M., Miiller, Leah C., Forster, Gina L., & Watt, Michael J. (2013). Adolescent social defeat decreases spatial working memory performance in adulthood. Behavioral and Brain Functions, 9.

Background: Adolescent social stress is associated with increased incidence of mental illnesses in adulthood that are characterized by deficits in cognitive focus and flexibility. Such enhanced vulnerability may be due to psychosocial stress-induced disruption of the developing mesocortical dopamine system, which plays a fundamental role in facilitating complex cognitive processes such as spatial working memory. Adolescent rats exposed to repeated social defeat as a model of social stress develop dopaminergic hypofunction in the medial prefrontal cortex as adults. To evaluate a direct link between adolescent social stress and later deficits in cognitive function, the present study tested the effects of adolescent social defeat on two separate tests of spatial working memory performance. Methods: Adult rats exposed to adolescent social defeat and their controls were trained on either the delayed win-shift task or the delayed alternating T-Maze task and then challenged with various delay periods. To evaluate potential differences in motivation for the food reward used in memory tasks, consumption and conditioned place preference for sweetened condensed milk were tested in a separate cohort of previously defeated rats and controls. Results: Compared to controls, adult rats defeated in adolescence showed a delay-dependent deficit in spatial working memory performance, committing more errors at a 90 s and 5 min delay period on the T-maze and win-shift tasks, respectively. Observed memory deficits were likely independent of differences in reward motivation, as conditioned place preference for the palatable food used on both tasks was similar between the adolescent social defeat group and control. Conclusions: The results demonstrate that severe social stressors during adolescence can produce long term deficits in aspects of cognitive function. Given the dependence of spatial working memory on prefrontal dopamine, pharmacologically reversing dopaminergic deficiencies caused by adolescent social stress has the potential to treat such cognitive deficits.

Basic Biomedical Sciences, Vermillion Campus.

Rajagopalan, Viswanathan, Mingming, Zhao, Reddy, Sushma, Fajardo, Giovanni, Xuejun, Wang, Dewey, Shannamar, . . . Bernstein, Daniel. (2013). Altered ubiquitin-proteasome signaling in right ventricular hypertrophy and failure. American Journal of Physiology: Heart & Circulatory Physiology, 305(4), H551-H562.

Alterations in the ubiquitin-proteasome system (UPS) have been described in left ventricular hypertrophy and failure, although results have been inconsistent. The role of the UPS in right ventricular (RV) hypertrophy (RVH) and RV failure (RVF) is unknown. Given the greater percent increase in RV mass associated with RV afterload stress, as present in many congenital heart lesions, we hypothesized that alterations in the UPS could play an important role in RVH/RVF. UPS expression and activity were measured in the RV from mice with RVH/RVF secondary to pulmonary artery constriction (PAC). Epoxomicin and MG132 were used to inhibit the proteasome, and overexpression of the 11S PA28a subunit was used to activate the proteasome. PAC mice developed RVH (109.3% increase in RV weight to body weight), RV dilation with septal shift, RV dysfunction, and clinical RVF. Proteasomal function (26S ß5 chymotrypsin-like activity) was decreased 26% (P < 0.05). Protein expression of 19S subunit Rpt5 (P < 0.05), UCHL1 deubiquitinase (P < 0.0001), and Smurf1 E3 ubiquitin ligase (P < 0.01) were increased, as were polyubiquitinated proteins (P < 0.05) and free-ubiquitins (P = 0.05). Pro-apoptotic Bax was increased (P < 0.0001), whereas anti-apoptotic Bcl-2 decreased (P < 0.05), resulting in a sixfold increase in the Bax/Bcl-2 ratio. Proteasomal inhibition did not accelerate RVF. However, proteasome enhancement by cardiac-specific proteasome overexpression partially improved survival. Proteasome activity is decreased in RVH/RVF, associated with upregulation of key UPS regulators and pro-apoptotic signaling. Enhancement of proteasome function partially attenuates RVF, suggesting that UPS dysfunction contributes to RVF.

Basic Biomedical Sciences, Vermillion Campus.

Yuan, Sharleen, & Burrell, Brian D. (2013). Nonnociceptive afferent activity depresses nocifensive behavior and nociceptive synapses via an endocannabinoid-dependent mechanism. Journal of Neurophysiology, 110(11), 2607-2616.

Previously, low-frequency stimulation (LFS) of a nonnociceptive touch-sensitive neuron has been found to elicit endocannabinoid-dependent long-term depression (eCB-LTD) in nociceptive synapses in the leech central nervous system (CNS) that requires activation of a presynaptic transient receptor potential vanilloid (TRPV)-like receptor by postsynaptically synthesized 2-arachidonoyl glycerol (2-AG). This capacity of nonnociceptive afferent activity to reduce nociceptive signaling resembles gate control of pain, albeit longer lasting in these synaptic experiments. Since eCB-LTD has been observed at a single sensory-motor synapse, this study examines the functional relevance of this mechanism, specifically whether this form of synaptic plasticity has similar effects at the behavioral level in which additional, intersegmental neural circuits are engaged. Experiments were carried out using a semi-intact preparation that permitted both synaptic recordings and monitoring of the leech whole body shortening, a defensive withdrawal reflex that was elicited via intracellular stimulation of a single nociceptive neuron (the N cell). The same LFS of a nonnociceptive afferent that induced eCB-LTD in single synapses also produced an attenuation of the shortening reflex. Similar attenuation of behavior was also observed when 2-AG was applied. LFS-induced behavioral and synaptic depression was blocked by tetrahydrolipstatin (THL), a diacylglycerol lipase inhibitor, and by SB366791, a TRPV1 antagonist. The effects of both THL and SB366791 were observed following either bath application of the drug or intracellular injection into the presynaptic (SB366791) or postsynaptic (THL) neuron. These findings demonstrate a novel, endocannabinoid-based mechanism by which nonnociceptive afferent activity may modulate nocifensive behaviors via action on primary afferent synapses.

Basic Biomedical Sciences, Vermillion Campus.

Zou, Jianqiu, Rezvani, Khosrow, Wang, Hongmin, Lee, K. S., & Zhang, Dong. (2013). BRCA1 downregulates the kinase activity of Polo-like kinase 1 in response to replication stress. Cell Cycle, 12(14), 2255-2265.

In response to DNA damage or replication stress, proliferating cells are arrested at different cell cycle stages for DNA repair by downregulating the activity of both the cyclin-dependent kinases (CDKs) and other important cell cycle kinases, including Polo-like kinase 1 (PLK1) . The signaling pathway to inhibit CDKs is relatively well understood, and breast cancer gene 1 (BRCA1) and other DNA damage response (DDR) factors play a key role in this process. However, the DNA damage-induced inhibition of PLK1 is still largely a mystery. Here we show that DNA damage and replication stress stimulate the association between BRCA1 and PLK1. Most importantly, we demonstrate that BRCA1 downregulates the kinase activity of PLK1 by modulating the dynamic interactions of Aurora A, hBora, and PLK1. Together with previous findings, we propose that in response to replication stress and DNA damage, BRCA1 plays a critical role in downregulating the kinase activity of both CDKs and PLK1.

Basic Biomedical Sciences, Vermillion Campus.

Ghosh, Suvankar, & Li, X. L. (2013). A Real Options Model for Generalized Meta-Staged Projects-Valuing the Migration to SOA. Information Systems Research, 24(4), 1011-1027.

This paper develops an innovative real options (RO) model for valuing multistage information technology (IT) projects that can be viewed as comprising meta stages. In RO literature, multistage investment programs have been treated as either interproject or intraproject programs, with intraproject programs being evaluated using n-fold Geske compound options and interproject programs valued using the so-called “subsidy-to-exercise price” logic. Our innovative RO model integrates the Geske compound option model with the subsidy-to-exercise price approach to value sequential investment programs that are neither purely interproject nor purely intraproject in nature but are composed of meta-stages. A meta-stage as a whole can be considered an interproject stage resulting in cash flows, but internally it consists of several intraproject stages that do not result in cash flows. We show that a key problem in IT, which is migrating to a Service-Oriented Architecture (SOA) for integrating a firm’s many disparate applications, systems, data, and business processes, is best viewed as an investment program comprising meta-stages. Examining SOA migration from an RO lens is particularly apt at this time not only because of the importance of SOA but also because doubts have surfaced about the value of SOA. We illustrate our RO model by applying it to the simulated case of a firm migrating to SOA. We also develop a software tool based on the Mathematica T computational platform so that practitioners can easily apply our innovative options pricing model to determine the true value of SOA in their business contexts.

Beacom School of Business.

Brown, Jennifer, & Kerby, Jacob. (2013). Batrachochytrium dendrobatidis in South Dakota, USA Amphibians. Herpetological Review, 44(3), 457-458.

Biology Department.

Bubak, Andrew N., Renner, Kenneth J., & Swallow, John G. (2014). Heightened serotonin influences contest outcome and enhances expression of high-intensity aggressive behaviors. Behavioural Brain Research, 259, 137-142.

Highlights: [•] We pharmacologically altered brain 5-HT levels using the precursor 5-HTP. [•] We found heightened 5-HT increased the probability of winning aggressive contests. [•] High-intensity behaviors and retreat threshold are influenced by 5-HT. [•] Other biogenic amines including octopamine remained unaltered following fights.

Biology Department.

Siler, Cameron D., Welton, Luke J., Rock, Ashley A., & Brown, Rafe M. (2013). Population Genetic Structure and Revised Geographic Range for the Tridactyl Skink (Brachymeles muntingkamay) from Luzon Island, Philippines. Herpetological Review, 44(1), 30-33.

Biology Department.


Wetland habitats in the Prairie Pothole Region of North America have been greatly reduced since European settlement, but the availability of managed wetlands has increased. The relative efficacy of these two habitats for meeting energetic demands of migrating shorebirds is unknown. To assess the relative suitability of stopover sites, we measured plasma metabolites and creatine kinase in Least Sandpipers (Calidris minutilla), Semipalmated Sandpipers (C. pusilla), and Pectoral Sandpipers (C. melanotos) at natural and managed wetland sites during fall migration in northeastern South Dakota and west-central Minnesota. We used stepwise multiple regression to identify significant effectors of plasma metabolite levels, followed by analysis of covariance to compare metabolite values between birds in the two habitat types. Plasma metabolite levels generally did not differ significantly between birds in the two habitat types, with two exceptions. Plasma triglycerides of Pectoral Sandpipers were 2.6x higher at managed than at natural wetlands, suggesting higher rates of fattening at managed sites, but this was not supported by plasma glycerol levels, which did not differ significantly between birds in the two habitat types, or by body mass, which was greater for adult males in natural wetlands. Plasma creatine kinase levels of Least Sandpipers were 75% higher at managed than at natural wetlands, which suggests that repair of flight-induced muscle damage may be slower for this species at managed wetlands. The general absence of significant differences in plasma metabolites among shorebirds in the two wetland types suggests that natural and managed wetlands serve as similarly effective stopover habitat for fall-migrating shorebirds in the Prairie Pothole Region.

Biology Department.

Wu, Chia-Ming, Peng, Rui, Dimitrijevic, Nada M., Rajh, Tijana, & Koodali, Ranjit T. (2014). Preparation of TiO2–SiO2 aperiodic mesoporous materials with controllable formation of tetrahedrally coordinated Ti4+ ions and their performance for photocatalytic hydrogen production. International Journal of Hydrogen Energy, 39(1), 127-136.

Abstract: The efficiency of photocatalytic water splitting for TiO2 dispersed on four SiO2 aperiodic porous supports is discussed in this work. The four TiO2–SiO2 composite materials were prepared via a sol–gel method and then subjected to supercritical drying, natural drying, rotatory vapor drying, or hydrothermal synthesis and the materials were subsequently calcined under identical conditions. These synthetic strategies result in differences in textural properties (specific surface area, pore diameter etc.) and in the amount of tetrahedrally coordinated Ti4+ ions. The TiO2–SiO2 materials were thoroughly characterized by powder X-ray diffraction (XRD), UV–Vis diffuse reflectance spectra (DRS), nitrogen adsorption studies, FT-IR spectroscopy, transmission electron microscopic (TEM) studies, and electron paramagnetic resonance (EPR) studies. The photocatalytic activity for hydrogen production is maximum when the amount of tetrahedrally coordinated Ti4+ ions is high. Thus, this work provides guidance towards the preparation of photoactive materials for generating hydrogen from water.

Chemistry Department.

Bersamin, Melina M., Zamboanga, Byron L., Schwartz, Seth J., ….., & Caraway, S. Jean. (2014). Risky Business: Is There an Association between Casual Sex and Mental Health among Emerging Adults? Journal of Sex Research, 51(1), 43-51.

A multiethnic sample of single, heterosexual, emerging-adult college students (N = 3,907) ages 18 to 25, from 30 institutions across the United States, participated in a study about identity, culture, psychological well-being, and risky behaviors. Given ongoing debates about the connection between casual sex and psychological adjustment, in the current study we assessed the cross-sectional association of participation in casual sex with psychological well-being and distress. A greater proportion of men (18.6%) compared to women (7.4%) reported having had casual sex in the month prior to assessment. Structural equation modeling indicated that casual sex was negatively associated with well-being (ß = .20,p < .001) and positively associated with psychological distress (ß = .16,p < .001). Gender did not moderate these associations. For emerging-adult college students, engaging in casual sex may elevate risk for negative psychological outcomes.

Psychology Department.

Contractor, A. A., Elhai, J. D., Ractliffe, Kendra C., & Forbes, D. (2013). PTSD’s underlying symptom dimensions and relations with behavioral inhibition and activation. Journal of Anxiety Disorders, 27(7), 645-651.

Reinforcement sensitivity theory (RST) stipulates that individuals have a behavioral activation system (BAS) guiding approach (rewarding) behaviors (Gray, 1971, 1981), and behavioral inhibition system (BIS) guiding conflict resolution between approach and avoidance (punishment) behaviors (Gray & McNaughton, 2000). Posttraumatic stress disorder (PTSD) severity overall relates to both BIS (e.g., Myers, VanMeenen, & Servatius, 2012; Pickett, Bardeen, & Orcutt, 2011) and BAS (Pickett et al., 2011). Using a more refined approach, we assessed specific relations between PTSD’s latent factors (Simms, Watson, & Doebbeling, 2002) and observed variables measuring BIS and BAS using 308 adult, trauma-exposed primary care patients. Confirmatory factor analysis and Wald chi-square tests demonstrated a significantly greater association with BIS severity compared to BAS severity for PTSD’s dysphoria, avoidance, and re-experiencing factors. Further, PTSD’s avoidance factor significantly mediated relations between BIS/BAS severity and PTSD’s dysphoria factor. (C) 2013 Elsevier Ltd. All rights reserved.

Psychology Department.

Berdahl, John P., & Jensen, M. P. (2014). The business of refractive laser assisted cataract surgery (ReLACS). Current Opinion in Ophthalmology, 25(1), 62-70.

Purpose of reviewRefractive Laser Assisted Cataract Surgery (ReLACS) combines the femtosecond laser with other noncovered tests and services in an attempt to reduce spectacle dependence in combination with cataract surgery. Significant interest is present among ophthalmologists who are considering adopting this technology, however significant capital outlays and continuing expenses can make the decision to adopt ReLACS foreboding. We review the financial considerations of ReLACS and review the trends seen in early adopters of this technology.Recent findingsRecent findings have shown that ReLACS is a growing segment of cataract surgery. Most practices who have implemented the technology have broken even and have a positive outlook on the financial return of implementing the ReLACS program. The average break-even analysis point for practices is around 230 cases a year.SummaryReLACS is growing and appears to be a financial viable approach for many practices.

Sanford School of Medicine, Sioux Falls Campus.

Doorn, Joshua M., & Kruer, Michael C. (2013). Newly Characterized Forms of Neurodegeneration with Brain Iron Accumulation. Current Neurology and Neuroscience Reports, 13(12).

Neurodegeneration with brain iron accumulation (NBIA) comprises a group of brain iron deposition syndromes that lead to mixed extrapyramidal features and progressive dementia. Historically, there has not been a clearly identifiable molecular cause for many patients with clinical and radiologic features of NBIA. Recent discoveries have shown that mutations in C19orf12 or WDR45 can lead to NBIA. C19orf12 mutations are inherited in an autosomal recessive manner, and lead to a syndrome similar to that caused by mutations in PANK2 or PLA2G6. In contrast, WDR45 mutations lead to a distinct form of NBIA characterized by spasticity and intellectual disability in childhood followed by the subacute onset of dystonia-parkinsonism in adulthood. WDR45 mutations act in an X-linked dominant manner. Although the function of C19orf12 is largely unknown, WDR45 plays a key role in autophagy. Each of these new forms of NBIA thus leads to a distinct clinical syndrome, and together they implicate new cellular pathways in the pathogenesis of these disorders.

Sanford School of Medicine, Sioux Falls Campus.

Hellwig, Thaddaus, & Gulseth, Michael. (2013). Pharmacokinetic and Pharmacodynamic Drug Interactions With New Oral Anticoagulants: What Do They Mean for Patients With Atrial Fibrillation? Annals of Pharmacotherapy, 47(11), 1478-1487.

Objective: To review pharmacokinetic and pharmacodynamic drug-drug interactions (DDIs) involving new oral anticoagulants for atrial fibrillation. Data Sources: A literature search was conducted via PubMed and the Cochrane database to identify DDI studies using the terms drug interactions, dabigatran, rivaroxaban, and apixaban. Prescribing information and Food and Drug Administration briefing documents were used to supplement published data. Study Selection and Data Extraction: English publications identified on Medline from 2005 up to August 2013 and US prescribing information for approved oral anticoagulants. Data Synthesis: Articles reviewed focused on drugs affecting the permeability glycoprotein (P-gp) efflux transporter protein and/or cytochrome P (CYP) 450 3A4 enzymes, and pharmacodynamic DDIs when drugs are administered concomitantly. Phase I DDI studies have reported pharmacokinetic DDIs mediated by P-gp alone (dabigatran etexilate) or in combination with CYP3A4 enzymes (rivaroxaban and apixaban). Dabigatran etexilate should not be administered with any P-gp inhibitor in patients with severe renal impairment. Briefing documents indicate that rivaroxaban and apixaban should not be used with drugs that are strong inhibitors of both P-gp and CYP3A4. DDI studies involving rifampicin suggest that rivaroxaban and apixaban should be avoided when strong inducers of P-gp and CYP3A4 are used concurrently. Concomitant use of apixaban and strong dual inhibitors of P-gp and CYP3A4 should be avoided or the dose reduced. Five randomized clinical trials report additive effects with rivaroxaban, dabigatran, and apixaban when used concomitantly with antiplatelet agents; bleeding rates have been found to be higher, especially with dual antiplatelet therapy. Conclusions: Awareness of drugs that alter the function of the P-gp efflux transporter protein and CYP3A4 enzymes and provide additive effects should enable prescribers to anticipate and avoid potential DDIs involving the new oral anticoagulants. To this end, briefing documents and prescribing information have applied cautionary measures for individuals treated with these newer anticoagulants.

Sanford SChool of Medicine, Sioux Falls Campus.

Stys, Adam T., Stys, Tomasz P., Rajpurohit, Naveen, & Khan, Muhammed A. (2013). A Novel Application of Guide Liner Catheter for Thrombectomy in Acute Myocardial Infarction: A Case Series. Journal of Invasive Cardiology, 25(11), 620-624.

Angiographically visible thrombus and distal embolization are relatively common during percutaneous coronary intervention (PCI) in myocardial infarction (MI) and correspond to worse outcomes. Several aspiration and thrombectomy devices have been shown to be effective for prevention of distal embolization. We present a technique with successful use of the GuideLiner catheter (Vascular Solutions) for thrombus aspiration after dedicated manual aspiration thrombectomy devices have failed. Our case series includes large thrombus burden in clinical scenarios of ST-elevation MI in a native vessel, non-ST elevation MI in a vein graft, and ST-elevation MI due to native vessel in stent thrombosis.

Sanford School of Medicine, Sioux Falls Campus.

Wysocka, M., Kossenkov, A. V., Benoit, B. M., TroxeI, A. B., ….., Nagata, Satoshi, . . . Rook, A. H. (2014). CD164 and FCRL3 Are Highly Expressed on CD4+CD26-T Cells in Sezary Syndrome Patients. Journal of Investigative Dermatology, 134(1), 229-236.

Sezary syndrome (SS) cells express cell surface molecules also found on normal activated CD4 T cells. In an effort to find a more specific surface marker for malignant SS cells, a nnicroarray analysis of gene expression was performed. Results showed significantly increased levels of mRNA for CD164, a sialomucin found on human CD34+ hematopoietic stem cells, and FCRL3, a molecule present on a subset of human natural T regulatory cells. Both markers were increased in CD4 T cells from SS patients compared with healthy donors (HD). Flow cytometry studies confirmed the increased expression of CD164 and FCRL3 primarily on CD4 + CD26 – T cells of SS patients. Importantly, a statistically significant correlation was found between an elevated percentage of CD4 + CD164+ T cells and an elevated percentage of CD4 + CD26 T cells in all tested SS patients but not in patients with mycosis fungoides and atopic dermatitis or HD. FCRL3 expression was significantly increased only in patients with high tumor burden. CD4 + CD164 + cells displayed cerebriform morphology and their loss correlated with clinical improvement in treated patients. Our results suggest that CD164 can serve as a marker for diagnosis and for monitoring progression of cutaneous T-cell lymphoma (CTCL)/SS and that FCRL3 expression correlates with a high circulating tumor burden.

Sanford School of Medicine, Sioux Falls Campus.


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