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Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor and bi-functional lipid and protein phosphatase. We report that the metabolic regulator pyruvate dehydrogenase kinase1 (PDHK1) is a synthetic-essential gene in PTEN-deficient cancer and normal cells. The PTEN protein phosphatase dephosphorylates nuclear factor κB (NF-κB)-activating protein (NKAP) and limits NFκB activation to suppress expression of PDHK1, a NF-κB target gene. Loss of the PTEN protein phosphatase upregulates PDHK1 to induce aerobic glycolysis and PDHK1 cellular dependence. PTEN-deficient human tumors harbor increased PDHK1, a biomarker of decreased patient survival. This study uncovers a PTEN-regulated signaling pathway and reveals PDHK1 as a potential target in PTEN-deficient cancers.

Although aquaria are common features of homes and other buildings, little is known about how environmental perturbations (i.e., tank cleaning, water changes, addition of habitat features) impact the diversity and succession of aquarium microbial communities. In this study, we sought to evaluate the hypotheses that newly established aquaria show clear microbial successional patterns over time and that common marine aquarium-conditioning practices, such as the addition of ocean-derived "live rocks" (defined as any "dead coral skeleton covered with crustose coralline algae" transferred into an aquarium from open ocean habitats) impact the diversity of microbial populations as well as nitrogen cycling in aquaria. We collected water chemistry data alongside water and sediment samples from two independent and newly established saltwater aquaria over a 3-month period. Microbial communities in samples were assessed by DNA extraction, amplification of the 16S rRNA gene, and Illumina MiSeq sequencing. Our results showed clear and replicable patterns of community succession in both aquaria, with the existence of multiple stable states for aquarium microbial assemblages. Notably, our results show that changes in aquarium microbial communities do not always correlate with water chemistry measurements and that operational taxonomic unit (OTU)-level patterns relevant to nitrogen cycling were not reported as statistically significant. Overall, our results demonstrate that aquarium perturbations have a substantial impact on microbial community profiles of aquarium water and sediment and that the addition of live rocks improves nutrient cycling by shifting aquarium communities toward a more typical saltwater assemblage of microbial taxa.IMPORTANCE Saltwater aquaria are living systems that support a complex biological community of fish, invertebrates, and microbes. The health and maintenance of saltwater tanks are pressing concerns for home hobbyists, zoos, and professionals in the aquarium trade; however, we do not yet understand the underlying microbial species interactions and community dynamics which contribute to tank setup and conditioning. This report provides a detailed view of ecological succession and changes in microbial community assemblages in two saltwater aquaria which were sampled over a 3-month period, from initial tank setup and conditioning with "live rocks" through subsequent tank cleanings and water replacement. Our results showed that microbial succession appeared to be consistent and replicable across both aquaria. However, changes in microbial communities did not always correlate with water chemistry measurements, and aquarium microbial communities appear to have shifted among multiple stable states without any obvious buildup of undesirable nitrogen compounds in the tank environment.

Metastasis is the leading cause of death in people with lung cancer, yet the molecular effectors underlying tumor dissemination remain poorly defined. Through the development of an in vivo spontaneous lung cancer metastasis model, we show that the developmentally regulated transcriptional repressor Capicua (CIC) suppresses invasion and metastasis. Inactivation of CIC relieves repression of its effector ETV4, driving ETV4-mediated upregulation of MMP24, which is necessary and sufficient for metastasis. Loss of CIC, or an increase in levels of its effectors ETV4 and MMP24, is a biomarker of tumor progression and worse outcomes in people with lung and/or gastric cancer. Our findings reveal CIC as a conserved metastasis suppressor, highlighting new anti-metastatic strategies that could potentially improve patient outcomes.

Cytosolic and organelle-based heat-shock protein (HSP) chaperones ensure proper folding and function of nascent and injured polypeptides to support cell growth. Under conditions of cellular stress, including oncogenic transformation, proteostasis components maintain homeostasis and prevent apoptosis. Although this cancer-relevant function has provided a rationale for therapeutically targeting proteostasis regulators (e.g., HSP90), cancer-subtype dependencies upon particular proteostasis components are relatively undefined. Here, we show that human rhabdomyosarcoma (RMS) cells, but not several other cancer cell types, depend upon heat-shock protein 70 kDA (HSP70) for survival. HSP70-targeted therapy (but not chemotherapeutic agents) promoted apoptosis in RMS cells by triggering an unfolded protein response (UPR) that induced PRKR-like endoplasmic reticulum kinase (PERK)-eukaryotic translation initiation factor α (eIF2α)-CEBP homologous protein (CHOP) signaling and CHOP-mediated cell death. Intriguingly, inhibition of only cytosolic HSP70 induced the UPR, suggesting that the essential activity of HSP70 in RMS cells lies at the endoplasmic reticulum-cytosol interface. We also found that increased CHOP mRNA in clinical specimens was a biomarker for poor outcomes in chemotherapy-treated RMS patients. The data suggest that, like human epidermal growth factor receptor 2 (HER2) amplification in breast cancer, increased CHOP in RMS is a biomarker of decreased response to chemotherapy but enhanced response to targeted therapy. Our findings identify the cytosolic HSP70-UPR axis as an unexpected regulator of RMS pathogenesis, revealing HSP70-targeted therapy as a promising strategy to engage CHOP-mediated apoptosis and improve RMS treatment. Our study highlights the utility of dissecting cancer subtype-specific dependencies on proteostasis networks to uncover unanticipated cancer vulnerabilities.

One strategy for combating cancer-drug resistance is to deploy rational polytherapy up front that suppresses the survival and emergence of resistant tumor cells. Here we demonstrate in models of lung adenocarcinoma harboring the oncogenic fusion of ALK and EML4 that the GTPase RAS-mitogen-activated protein kinase (MAPK) pathway, but not other known ALK effectors, is required for tumor-cell survival. EML4-ALK activated RAS-MAPK signaling by engaging all three major RAS isoforms through the HELP domain of EML4. Reactivation of the MAPK pathway via either a gain in the number of copies of the gene encoding wild-type K-RAS (KRAS(WT)) or decreased expression of the MAPK phosphatase DUSP6 promoted resistance to ALK inhibitors in vitro, and each was associated with resistance to ALK inhibitors in individuals with EML4-ALK-positive lung adenocarcinoma. Upfront inhibition of both ALK and the kinase MEK enhanced both the magnitude and duration of the initial response in preclinical models of EML4-ALK lung adenocarcinoma. Our findings identify RAS-MAPK dependence as a hallmark of EML4-ALK lung adenocarcinoma and provide a rationale for the upfront inhibition of both ALK and MEK to forestall resistance and improve patient outcomes.

A novel, Gram-negative, non-spore-forming, pleomorphic yellow-orange bacterial strain was isolated from a stadium seat. Strain Coronado(T) falls within the Erythrobacteraceae family and the genus Porphyrobacter based on 16S rRNA phylogenetic analysis. This strain has Q-10 as the predominant respiratory lipoquinone, as do other members of the family. The fatty acid profile of this strain is similar to other Porphyrobacter, however Coronado(T) contains predominately C18:1ω7cis and C16:0, a high percentage of the latter not being observed in any other Erythrobacteraceae. This strain is catalase-positive and oxidase-negative, can grow from 4 to 28 °C, at NaCl concentrations 0.1-1.5%, and at pH 6.0-8.0. On the basis of phenotypic and phylogenetic data presented in this study, strain Coronado(T) represents a novel species in the Porphyrobacter genus for which the name Porphyrobacter mercurialis sp. nov. is proposed; the type strain is Coronado(T) (=DSMZ 29971, =LMG 28700).

Here we present the draft genome of an actinobacterium, Curtobacterium flaccumfaciens strain UCD-AKU, isolated from a residential carpet. The genome assembly contains 3,692,614 bp in 130 contigs. This is the first member of the Curtobacterium genus to be sequenced.

Deans and faculty at Association to Advance Collegiate Schools of Business-accredited colleges of business were surveyed on the extent and impact of the occurrence of undeserved authorships in business journal articles. Eighty percent of the deans and faculty responding acknowledged the occurrence of undeserved authorships in published business journal articles. There were disagreements on the extent of occurrence, with the deans reporting a lower rate of occurrence than faculty. Deans also indicated less impact of undeserved authorships on promotions, tenure awards, and merit increases than did faculty. With the strong increase in pressure to publish in order to be promoted, colleges of business need to be aware of the possibility of undeserved authorships.

The purpose of this study was to determine whether the ability of freshman college students to identify the founding fathers of free enterprise and of communism has improved. This study is a follow-up to four previous studies. A questionnaire was developed and distributed to College of Business and College of Education & Human Services freshmen who were enrolled in freshmen orientation courses. As in previous studies, a higher percentage of students correctly identified Karl Marx as the founder of Communism than identified Adam Smith as the founder of free enterprise. Nearly 52% of the students were able to identify Karl Marx and approximately 43% of the students correctly identify Adam Smith.

Stereotype threat has primarily been studied with regard to test performance in academic settings, testing aptitude, ability, and intelligence, and it has been found to cause both behavioral and cognitive decrements. Although there is research on stereotype threat in the workplace, this too is usually conducted in upper-level or more academically based job tasks. This article concentrates on how stereotype threat affects those in manual labor workplace settings. This research, however, sought to test subjects on a behavioral task in a workplace setting to see if the results mirror those in academia. Stereotype threat in academic settings has been shown to cause both behavioral and cognitive decrements. It was theorized that stereotype threat would cause performance decrements for the African American participants. Participants were undergraduate students--60 Caucasian and 60 African American. All performed two manual labor tasks, sorting and assembling nuts and bolts, and a math test, half while under stereotype threat and half without stereotype threat manipulation. Results yielded significant differences between the two conditions for African Americans on both the academic and nonacademic/manual labor tasks. (Contains 5 tables and 5 figures.)

It Was the Best Thing I Could Have Done When Darryl Coaston walked out of the county jail in October 2011, it was the start of a very different life. [...]

Objectives: To report results from a quality improvement (QI) project evaluating diagnostic performance, hospital resource use, and patient response data for postoperative contrast‐enhanced ultrasound (CEUS) antegrade nephrostogram after percutaneous nephrolithotomy. Methods: For this Health Insurance Portability and Accountability Act–compliant, Institutional Review Board–approved study, QI data were deidentified and analyzed. On the first postoperative day after percutaneous nephrolithotomy, patients underwent both CEUS and fluoroscopic antegrade nephrostogram. For CEUS, 1.0 mL of Lumason (sulfur hexafluoride lipid type A microspheres; Bracco Diagnostics, Inc, Monroe Township, NJ) was injected via an indwelling nephrostomy tube, with ureteral patency confirmed by identifying intravesical ultrasound (US) contrast. Diagnostic performance for ureteral patency and contrast extravasation was calculated (with fluoroscopy as the reference standard). The examination time, room time, physician time, hospital costs, and patient response data were compared. The mean, standard deviation, 95% confidence interval, differences in mean, and 95% confidence interval of differences were calculated. Results: Eighty‐one examinations were performed in 73 patients during the QI period. The sensitivity and specificity of CEUS for ureteral patency were 96% and 57%, respectively. There was no significant difference in time metrics between modalities, and the cost analysis showed lower direct and indirect costs for CEUS. Patient responses revealed lower levels of comfort for CEUS relative to fluoroscopy, without significant differences in reported pain or effort levels. Conclusions: Contrast‐enhanced US showed very high sensitivity for ureteral patency; the relatively low specificity may have resulted from false‐negative results in fluoroscopy. The hospital costs and resource use of CEUS compared favorably to fluoroscopy. Contrast‐enhanced US also offers inherent advantages, including portability and lack of ionizing radiation. [ABSTRACT FROM AUTHOR]

Lung transplantation can prolong and improve quality of life for patients affected by end-stage lung disease. Potential lung transplant patients undergo a rigorous preoperative assessment that includes multiple medical imaging studies. These studies provide information that help physicians determine whether the patient is a surgical candidate, as well as the surgical technique that should be used during transplantation. Imaging studies also are used in long-term care to detect complications in patients after lung transplantation. [ABSTRACT FROM AUTHOR]

The article discusses the elements with which radiologic technologists should be aware of, which includes urethra anatomy, the pathology of urethral abnormalities, imaging techniques, and special considerations for preoperative and postoperative patients. The symptoms and causes of male urethral stricture disease are listed. The three stages of the conversion of blood plasma into urine are discussed. Non-ionic contrast media are said to be available for urographic studies.

Background Femoroacetabular impingement (FAI) is commonly seen in young or middle-aged patients. Early detection and correction of FAI-related bony deformities or pelvic realignment are essential to prevent the development or progression of hip osteoarthritis. Discussion Computed tomography (CT) and magnetic resonance (MR) imaging are the reference standards for the evaluation of bony anatomy and treatable internal derangement findings of the hip, respectively. Surgeons prefer CT imaging for preoperative bone delineation because of its 3-D isotropic capabilities and excellent multiplanar reconstructions. Three-Tesla (3T) MR scans enable high-resolution 3-D MR reconstructions for bone depiction similar to 3-D CT reconstructions and have the potential to eliminate the need for duplicate (CT and MR) scanning. Conclusion This technical report illustrates the feasibility of such an approach and compares bone rendering obtained using isotropic data from 3-D MR with 3-D CT in the same patient. [ABSTRACT FROM AUTHOR]

With the dramatic advancements in technology, both academia and the workplace have been dramatically impacted. From the increase of online business degree programs to corporate online training, the question of the effectiveness of online courses has been front and center. Do these once primarily live-taught courses successfully transfer to online-only formats without losing the message, the increased productivity, and the desired results? Research was concerned with evaluating the efficacy, measured by junior and senior level business student performance, and results looked at the finals grades in undergraduate business statistics courses taught online classes, as compared to traditional, live-taught classes and web-enhanced courses. Results showed significantly lower scores online versus live-taught, especially with women, and women had lower overall online scores online that men online. [ABSTRACT FROM AUTHOR]

With the dramatic increase of online business degree programs, the question of the effectiveness of online courses has been front and center. Do these once primarily face-to-face courses successfully transfer to online-only formats without losing student productivity? Do the new formats still reach students, and is it reflected in final grades? Research was focused on evaluating the efficacy, measured by student performance, of undergraduate business statistics courses taught online classes, as compared to traditional, face-to-face classes and web-enhanced courses. Are there differences in how male and female students perform in both class formats? Performance in the classroom is traditionally measured by the grades, namely the final grade. This study looked at the impact of online learning facilities in a course with traditionally difficult content for undergraduates with regard to gender. Results found that students overall performed better in face-to-face business statistics courses than in online. When gender was analyzed, the final grade for female students were significantly decreased from face-to-face to online courses, as compared to male students, whose grades were not significantly different in the two course formats. [ABSTRACT FROM AUTHOR]

The theoretical and empirical literatures do not give a clear answer about the superiority of flexible exchange rate regime over fixed exchange rate regime when purchasing power parity (PPP) condition fails to hold. The flexible exchange rate regime is generally shown to be superior, assuming PPP. This study is a fresh examination of the popular assertion that Flexible Exchange Rate regime outperforms other Exchange Rate regimes. We analyze the effect of the violation of purchasing power parity combined with deviations in output target and real exchange rate from their long-run equilibrium values on government's decision domain, which we call government's loss function. This study uses a government loss function, for the most part derived from Barrow and Gordon (1983), to compare two exchange rate regimes under different PPP conditions. The results of this study confirm that a flexible exchange rate system indeed performs better if PPP holds. However, this implication may not be true when PPP doesn't hold, even if the cost of exchange rate change is zero. A major finding of this study, in sharp contrast to Obstfeld (1996), is that, if PPP does not hold, the flexible exchange rate system cannot be guaranteed to perform better unless two additional conditions are met: (a) output target is fully adjusted to its long-run equilibrium value; and (b) the long-run real exchange rate is lower than its long-run equilibrium value. If these conditions are not met, the result is ambiguous. Since the above two conditions may not always hold, the implication of this study is quite significant and offers the opportunity for future empirical research. [ABSTRACT FROM AUTHOR]

Stereotype threat, the threat of being stereotyped against (Steele & Aronson, 1995), regardless of the legitimacy of the stereotype, can impact not only productivity, but goals, behavior, and ultimately attitudes. Stereotype threat impacts not only racial groups but men and women as well, each group impacted by the negative stereotypes about their intellectual and/or work performance. As the workplace becomes more and more diverse, managers must understand and brace for the impact stereotypes have on their workers. This study looks at the impact of stereotype threat on male and female business majors in the workplace and future entrepreneurs. The impact of stereotype was measured in their ranking of their own management skills, how they thought others would rank their management skills, and their goals in the workplace. [ABSTRACT FROM AUTHOR]