Activity Ball Monitoring Activity and Climate Impact in Market Hogs

Design and fabricate a container to collect market hog activity data through the use of an existing sensor package. The container must maximize stability of the system while testing in the field and minimize amount of interference when collecting data. The system will automatically report the data as an IoT device

Feedlot Performance and Carcass Characteristics of Ram Lambs Slaughtered at Different Weights

Food Scienc

Expression and regulation of type 2A protein phosphatases and alpha4 signalling in cardiac health and hypertrophy

Abstract Cardiac physiology and hypertrophy are regulated by the phosphorylation status of many proteins, which is partly controlled by a poorly defined type 2A protein phosphatase-alpha4 intracellular signalling axis. Quantitative PCR analysis revealed that mRNA levels of the type 2A catalytic subunits were differentially expressed in H9c2 cardiomyocytes (PP2ACb[PP2ACa[PP4C[PP6C), NRVM (PP2ACb[PP2ACa = PP4C = PP6C), and adult rat ventricular myocytes (PP2ACa[ PP2ACb[PP6C[PP4C). Western analysis confirmed that all type 2A catalytic subunits were expressed in H9c2 cardiomyocytes; however, PP4C protein was absent in adult myocytes and only detectable following 26S proteasome inhibition. Short-term knockdown of alpha4 protein expression attenuated expression of all type 2A catalytic subunits. Pressure overload-induced left ventricular (LV) hypertrophy was associated with an increase in both PP2AC and alpha4 protein expression. Although PP6C expression was unchanged, expression of PP6C regulatory subunits (1) Sit4-associated protein 1 (SAP1) and (2) ankyrin repeat domain (ANKRD) 28 and 44 proteins was elevated, whereas SAP2 expression was reduced in hypertrophied LV tissue. Co-immunoprecipitation studies demonstrated that the interaction between alpha4 and PP2AC or PP6C subunits was either unchanged or reduced in hypertrophied LV tissue, respectively. Phosphorylation status of phospholemman (Ser63 and Ser68) was significantly increased by knockdown of PP2ACa, PP2ACb, or PP4C protein expression. DNA damage assessed by histone H2A.X phosphorylation (cH2A.X) in hypertrophied tissue remained unchanged. However, exposure of cardiomyocytes to H2O2 increased levels of cH2A.X which was unaffected by knockdown of PP6C expression, but was abolished by the short-term knockdown of alpha4 expression. This study illustrates the significance and altered activity of the type 2A protein phosphatase-alpha4 complex in healthy and hypertrophied myocardium

Doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, or doxorubicin alone as a first‐line treatment for advanced leiomyosarcoma: A propensity score matching analysis from the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group

Background The optimal treatment for advanced leiomyosarcoma is still debated. Given histotype‐specific prospective controlled data lacking, this study retrospectively evaluated doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone as first‐line treatments for advanced/metastatic leiomyosarcoma treated at European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC‐STBSG) sites. Methods The inclusion criteria were a confirmed histological diagnosis, treatment between January 2010 and December 2015, measurable disease (Response Evaluation Criteria in Solid Tumors 1.1), an Eastern Cooperative Oncology Group performance status ≤2, and an age ≥ 18 years. The endpoints were progression‐free survival (PFS), overall survival (OS), and overall response rate (ORR). PFS was analyzed with methods for interval‐censored data. Patients were matched according to their propensity scores, which were estimated with a logistic regression model accounting for histology, grade, age, sex, performance status, tumor site, and tumor extent. Results Three hundred three patients from 18 EORTC‐STBSG sites were identified. One hundred seventeen (39%) received doxorubicin plus dacarbazine, 71 (23%) received doxorubicin plus ifosfamide, and 115 (38%) received doxorubicin. In the 2:1:2 propensity score–matched population (205 patients), the estimated median PFS was 9.2 months (95% confidence interval [CI], 5.2‐9.7 months), 8.2 months (95% CI, 5.2‐10.1 months), and 4.8 months (95% CI, 2.3‐6.0 months) with ORRs of 30.9%, 19.5%, and 25.6% for doxorubicin plus dacarbazine, doxorubicin plus ifosfamide, and doxorubicin alone, respectively. PFS was significantly longer with doxorubicin plus dacarbazine versus doxorubicin (hazard ratio [HR], 0.72; 95% CI, 0.52‐0.99). Doxorubicin plus dacarbazine was associated with longer OS (median, 36.8 months; 95% CI, 27.9‐47.2 months) in comparison with both doxorubicin plus ifosfamide (median, 21.9 months; 95% CI, 16.7‐33.4 months; HR, 0.65; 95% CI, 0.40‐1.06) and doxorubicin (median, 30.3 months; 95% CI, 21.0‐36.3 months; HR, 0.66; 95% CI, 0.43‐0.99). Adjusted analyses retained an effect for PFS but not for OS. None of the factors selected for multivariate analysis had a significant interaction with the received treatment for both PFS and OS. Conclusions This is the largest retrospective study of first‐line treatment for advanced leiomyosarcoma. In the propensity score–matched population, doxorubicin and dacarbazine showed favorable activity in terms of both ORR and PFS and warrants further evaluation in prospective trials

Identificatie van PPP2R4 als nieuwe kandidaat tumor suppressor: een studie in PTPA deficiënte muizen en humane tumoren.

Protein Phosphatase 2A (PP2A) complexes counteract diverse kinase-driven oncogenic pathways. Accumulating clinical evidence further underscoresimpaired PP2A function/activity in diverse cancers, sustaining its suspected tumor suppressor function. Nevertheless, whether loss of PP2A activity is sufficient for tumorigenesis in vivo has remained elusive. Here, we describe development of spontaneous malignancies in mice (haplo)deficient for Ppp2r4, encoding a PP2A chaperone (PTPA) essential for generation of active PP2A holoenzymes. PTPA-deficient tissues show reduced PP2A activity and methylation, selectively affecting specific PP2Aholoenzymes. Complementary analyses of protein phosphorylation and geneexpression revealed heterogeneous activation of diverse oncogenic signaling pathways in the tumors, underscoring that decreased PP2A activity affects multiple targets. Importantly, cancer database surveys revealed heterozygous PPP2R4 deletion at strikingly high frequency in several human cancer types. Furthermore, cancer-derived PPP2R4 mutants showing impaired PP2A-C binding in cellulo or impaired PTPA activity in vitro were unable to rescue transformation of PTPA-depleted human HEK-TER cells. Our data provide the first compelling in vivo evidence that impaired PP2A activity is sufficient to promote tumor development and establish PPP2R4 as a novel haploinsufficient tumor suppressor gene in multiple human cancers. These findings ultimately validate PP2A as a bona fide tumor suppressor and target for tumor suppressor reactivation therapies.nrpages: 161status: publishe

EVALUATION OF THE CRITICAL COMMUNICATION PROCESS IN THE U.S. ARMY FOOD DEFENSE PROGRAM

Master of Public HealthPublic Health Interdepartmental ProgramJustin J. KastnerAccording to its website, the United States Army Public Health Command (USAPHC) serves “to promote health and prevent disease, injury and disability in Soldiers and retirees, their family members, and Army civilians, and to assure effective execution of full-spectrum veterinary services for the Army and Department of Defense.” Within this organization, the Veterinary Services Portfolio manages the Animal Medicine and Food Protection Programs. The Health Risk Management Portfolio contains the Health Risk Communication Program, which provides training and consultation services throughout the Department of Defense on how to effectively communicate scientific and technical information to lay persons on an interpersonal level. This report describes the capstone project completed at the interface of the Food Protection Program and the Health Risk Communication Program in order to evaluate the critical communication process that should occur within the U.S. Army Food Defense program. My field experience with the USAPHC, coursework, and supplemental experiences have collectively educated me on and provided me unique experiences with infectious disease control, international trade, border security, weapons of mass destruction, food defense, global health, social behavior, and risk communication

Activity Ball Monitoring Activity and Climate Impact in Market Hogs

Design and fabricate a container to collect market hog activity data through the use of an existing sensor package. The container must maximize stability of the system while testing in the field and minimize amount of interference when collecting data. The system will automatically report the data as an IoT device.</p

The basic biology of PP2A in hematologic cells and malignancies

Reversible protein phosphorylation plays a crucial role in regulating cell signaling. In normal cells, phosphoregulation is tightly controlled by a network of protein kinases counterbalanced by several protein phosphatases. Deregulation of this delicate balance is widely recognized as a central mechanism by which cells escape external and internal self-limiting signals, eventually resulting in malignant transformation. A large fraction of hematologic malignancies is characterized by constitutive or unrestrained activation of oncogenic kinases. This is in part achieved by activating mutations, chromosomal rearrangements, or constitutive activation of upstream kinase regulators, in part by inactivation of their anti-oncogenic phosphatase counterparts. Protein phosphatase 2A (PP2A) represents a large family of cellular serine/threonine phosphatases with suspected tumor suppressive functions. In this review, we highlight our current knowledge about the complex structure and biology of these phosphatases in hematologic cells, thereby providing the rationale behind their diverse signaling functions. Eventually, this basic knowledge is a key to truly understand the tumor suppressive role of PP2A in leukemogenesis and to allow further rational development of therapeutic strategies targeting PP2A.status: publishe

The biogenesis of active Protein Phosphatase 2A holoenzymes: a tightly regulated process creating phosphatase specificity

Protein Phosphatase type 2A (PP2A) enzymes comprise a large family of Ser/Thr phosphatases with multiple functions in cellular signaling and physiology. The composition of heterotrimeric PP2A holoenzymes, resulting from the combinatorial assembly of a catalytic C, structural A and regulatory B-type subunit, provides the essential determinants for substrate specificity, subcellular targeting and fine-tuning of phosphatase activity, largely explaining why PP2A is functionally involved in so many diverse physiological processes, sometimes in seemingly opposing ways. In this review, we highlight how PP2A holoenzyme biogenesis and enzymatic activity are controlled by a sophisticatedly coordinated network of five PP2A modulators, consisting of α4, PTPA, LCMT1, PME-1 and potentially TIPRL1, which serve to prevent promiscuous phosphatase activity until the holoenzyme is completely assembled. Likewise, these modulators may come into play when PP2A holoenzymes are disassembled following particular cellular stresses. Malfunctioning of these cellular control mechanisms contributes to human disease. The potential therapeutic benefits or pitfalls of interfering with these regulatory mechanisms will be briefly discussed.status: publishe