bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered fMRI resting‐state connectivity in individuals with fibromyalgia on acute pain stimulation
Authors: Ichesco E. , Puiu T. , Hampson J.P. , Kairys A.E. , Clauw D.J. , Harte S.E. , Peltier S.J. , Harris R.E. , Schmidt‐Wilcke T.
Published: January 2016

Background

Fibromyalgia is a chronic widespread pain condition, with patients commonly reporting other symptoms such as sleep difficulties, memory complaints and fatigue. The use of magnetic resonance imaging (MRI) in fibromyalgia has allowed for the detection of neural abnormalities, with alterations in brain activation elicited by experimental pain and alterations in resting state connectivity related to clinical pain.

Methods

In this study, we sought to monitor state changes in resting brain connectivity following experimental pressure pain in fibromyalgia patients and healthy controls. Twelve fibromyalgia patients and 15 healthy controls were studied by applying discrete pressure stimuli to the thumbnail bed during MRI. Resting‐state functional MRI scanning was performed before and immediately following experimental pressure pain. We investigated changes in functional connectivity to the thalamus and the insular cortex.

Results

Acute pressure pain increased insula connectivity to the anterior cingulate and the hippocampus. Additionally, we observed increased thalamic connectivity to the precuneus/posterior cingulate cortex, a known part of the default mode network, in patients but not in controls. This connectivity was correlated with changes in clinical pain.

Conclusions

These data reporting changes in resting‐state brain activity following a noxious stimulus suggest that the acute painful stimuli may contribute to the alteration of the neural signature of chronic pain.

What does this study/add?

In this study acute pain application shows an echo in functional connectivity and clinical pain changes in chronic pain.
Individual and joint effects of risk factors for onset widespread pain and obesity – a population‐based prospective cohort study
Authors: Magnusson K. , Hagen K.B. , Natvig B.
Published: January 2016

Background

Widespread musculoskeletal pain (WSP) and obesity frequently co‐occur and may have shared risk factors. We aimed to investigate whether four dichotomized risk factors individually or jointly increase the risk for the onset of WSP and onset of obesity.

Methods

Persons aged 34–76 years in 2004 living in Ullensaker municipality, Norway, responded to questionnaires in 2004 and 2010 (n = 1553). Using causal interaction analyses, we examined whether baseline obesity and WSP, poor sleep quality, mental distress and poor physical fitness jointly increased the risk of new onset WSP (≥3 pain sites leading to disability the last year) and new onset obesity (self‐reported BMI ≥30 kg/m2) in persons without WSP (n = 1270) or without obesity (n = 1300) at baseline respectively.

Results

The mean (SD) age was 51 (12.1) years and 56% were female. The incidence of WSP and obesity were 9.1% and 5.4%. Mental distress and poor sleep quality individually and jointly with poor physical fitness increased WSP onset risk (relative excess risk due to interaction [RERI] = 1.90, 95% CI, 0.39–3.42 and RERI = 1.43, 95% CI, 0.10–2.76). Poor physical fitness individually increased the risk for new onset obesity, and baseline WSP and poor sleep quality jointly (RERI = 1.87, 95% CI, 0.49–3.24). The presence of more risk factors was dose‐dependently associated with onset WSP and to a lesser extent with onset obesity.

Conclusion

The onset of WSP and the onset of obesity were results of joint effects of exposures. Poor physical fitness was a key covariate in increasing the risk for both conditions.

What does this study add?

In a general population, the new onset of widespread pain and new onset of obesity were results of joint effects of risk factors and particularly poor physical fitness.

The study may aid in the identification of patients at risk of future disability.
Causal effects of threat and challenge appraisals on coping and pain perception
Authors: Wang Y. , Jackson T. , Cai L.
Published: January 2016

Background

Numerous studies have found appraisals of pain as a source of potential threat or tissue damage influence pain perception and coping. Conversely, causal effects of challenge appraisals reflecting potential future benefits of bearing pain have received little attention. This experiment was designed to elucidate effects of appraising laboratory pain as a source of potential threat and challenge on pain perception and coping.

Methods

Before engaging in a cold pressor test (CPT), young adult women (N = 112) and men (N = 49) were randomly assigned to one of three conditions: a higher threat group in which participants read an orienting passage describing symptoms and consequences of frostbite (pain as a signal for nociception), a lower threat group in which participants read about CPT safety (pain independent of nociception) or a challenge appraisal group in which participants read a passage describing how persistence in the face of discomfort predicts future life success and satisfaction.

Results

The higher threat group had lower pain tolerance and catastrophized more during the task than lower threat and challenge appraisal groups. Conversely, the challenge appraisal group reported using more cognitive strategies (ignoring, diverting attention, coping self‐statements) in managing pain than either threat group. Structural equation modelling indicated paths of subjective threat and challenge appraisals with pain tolerance were fully mediated by individual differences in reported cognitive coping and/or pain catastrophizing.

Conclusions

Findings underscore causal effects of pain appraisals on coping responses and pain perception.

What does this study add?

Effects of challenge appraisals of pain as a source of potential future growth or development have not been considered in experimental pain research.

Causal effects of primary appraisals of laboratory pain as a source of potential threat and challenge were elucidated in relation to pain perception and coping.
Development of a Biosensor Based on Phosphotriesterase and n‐Channel ISFET for Detection of Pesticides
Authors: Andrianova M. S. , Gubanova O. V. , Komarova N. V. , Kuznetsov E. V. , Kuznetsov A. E.
Published: January 2016

A biosensor for the direct determination of organophosphorus pesticides (OPs) is described. It utilizes an ion‐selective field‐effect transistor and phosphotriesterase enzyme (PTE), which provides cleavage of OPs. The sensitivity of the biosensor was increased after PTE immobilization on the surface of the transistor. Packaging of the integrated circuit and creation of a microfluidic system for analyte delivery stabilized the signal. This system was able to detect 0.1 µM paraoxon and 0.5 µM parathion and methyl parathion and was stable for at least 1 month (PBS, 1°), and could thus provide the basis for a portable device for analyzing OPs in water.
On two‐liquid AC electroosmotic system for thin films
Authors: Navarkar Abhishek , Amiroudine Sakir , Demekhin Evgeny A.
Published: January 2016

Lab‐on‐chip devices employ EOF for transportation and mixing of liquids. However, when a steady (DC) electric field is applied to the liquids, there are undesirable effects such as degradation of sample, electrolysis, bubble formation, etc. due to large magnitude of electric potential required to generate the flow. These effects can be averted by using a time‐periodic or AC electric field. Transport and mixing of nonconductive liquids remain a problem even with this technique. In the present study, a two‐liquid system bounded by two rigid plates, which act as substrates, is considered. The potential distribution is derived by assuming a Boltzmann charge distribution and using the Debye–Hückel linearization. Analytical solution of this time‐periodic system shows some effects of viscosity ratio and permittivity ratio on the velocity profile. Interfacial electrostatics is also found to play a significant role in deciding velocity gradients at the interface. High frequency of the applied electric field is observed to generate an approximately static velocity profile away from the Electric Double Layer (EDL).
Electrophoretic separation method for membrane pore‐forming proteins in multilayer lipid membranes
Authors: Okamoto Yukihiro , Tsujimoto Yusuke , Umakoshi Hiroshi
Published: January 2016

In this paper, we report on a novel electrophoretic separation and analysis method for membrane pore‐forming proteins in multilayer lipid membranes (MLMs) in order to overcome the problems related to current separation and analysis methods of membrane proteins, and to obtain a high‐performance separation method on the basis of specific properties of the lipid membranes. We constructed MLMs, and subsequently characterized membrane pore‐forming protein behavior in MLMs. Through the use of these MLMs, we were able to successfully separate and analyze membrane pore‐forming proteins in MLMs. To the best of our knowledge, this research is the first example of membrane pore‐forming protein separation in lipid membranes. Our method can be expected to be applied for the separation and analysis of other membrane proteins including intrinsic membrane proteins and to result in high‐performance by utilizing the specific properties of lipid membranes.
The challenge of scaling up photobioreactors: Modeling and approaches in small scale
Authors: Socher Maria Lisa , Löser Christian , Schott Carolin , Bley Thomas , Steingroewer Juliane
Published: January 2016

Commercial large‐scale application of photobiotechnology calls for acceptable rates and high cell densities. The latter results in self‐shading and a temporally declining growth rate, making the process inefficient. Upscaling phototrophic processes requires knowledge of the reaction kinetics with special attention on the μ‐I relation. Model‐based calculations for studying the effect of self‐shading on growth were performed for three μ(I) concepts. The nonrealistic μ(I0) concept results in exponential growth without limit, the widely used concept exhibits a growth behavior that significantly deviates from real processes, but the sophisticated concept describes real processes best. A Respiration Activity Monitoring System (RAMOS) with CultiLux unit was tested regarding its applicability for exploring the μ‐I dependency of Arthrospira platensis. The results were not satisfactory because of self‐shading due to a high cell density (which was essential for yielding detectable oxygen‐evolution signals). An innovative cultivation system in which self‐shading does not interfere with phototrophic growth was required. A flat‐panel system was constructed (designed by CFD, short light path of 1 cm, uniform planar light supply by LED and OLED units), allowing continuous cultivation of phototrophic microbes at varied light intensities.
A Thermally Stable, Combustion‐Resistant, and Highly Ion‐Conductive Separator for Lithium‐Ion Batteries Based on Electrospun Fiber Mats of Crosslinked Polybenzoxazine
Authors: Li Hsieh‐Yu , Li Guo‐An , Lee Yun‐Yang , Tuan Hsing‐Yu , Liu Ying‐Ling
Published: January 2016

Porous and thermally stable membranes are attractive materials as separators in lithium‐ion batteries. This work reports a new class of high‐performance separators for Li‐ion batteries based on a crosslinked polybenzoxazine electrospun fiber mat (CR‐PBz‐FbM). The CR‐PBz‐FbM separator shows a high ion conductivity of 2.92 mS cm−1 (5.2 times the value recorded for Celgard 2300), a low MacMullin number of 3.35, ultrahigh electrolyte uptake (≈825 %), and near‐zero shrinkage at 150 °C. Consequently, the CR‐PBz‐FbM separator shows a high C‐rate capacity and good cycle retention in the half‐cell test. At a C‐rate of 2.0, the CR‐PBz‐FbM‐based Li‐ion cell only exhibits a capacity loss of 16 % compared to a 40 % capacity loss found with the cell based on Celgard 2300. The results demonstrate that CR‐PBz‐FbM is an inexpensive, non‐shutdown‐type, thermally stable, and highly ion‐conductive separator for Li‐ion batteries.
Characterization of partially purified milk‐clotting enzyme from sunflower (Helianthus annuus) seeds
Authors: Nasr Assia I. A. M. , Mohamed Ahmed Isam A. , Hamid Omer I. A.
Published: January 2016

This study was aimed to extract milk‐clotting enzyme from sunflower seeds and to determine its potentiality for manufacturing white soft cheese from cows and goats milk. The seeds were blended and extracted using two types of buffers and milk‐clotting and proteolytic activities were evaluated. The enzyme was partially purified using ammonium sulfate fractionation techniques. Results indicated that sunflower seeds extracted with 5% NaCl in 50 mmol/L acetate buffer, pH 5.0, had the highest milk‐clotting activity (MCA) and lowest coagulation time compared to that extracted with only acetate buffer (pH 5.0). Ammonium sulfate at 30–50% saturation purified the enzyme to 4.3 folds with MCA of 241.0 U/mL and final enzyme yield of 10.9%. The partially purified enzyme was characterized by SDS–PAGE that showed two bands with molecular weight of 120 and 62 kDa. When compared with other plant enzymes, the partially purified sunflower enzyme was found to have higher milk‐clotting activity and lower proteolytic activity. Also, both milk sources and enzyme types significantly affected the cheese yield and curd formation time. The cheese made from cow milk using sunflower enzyme had higher yield compared to that obtained using commercial rennet, whereas the opposite was observed when using goat milk.
CDS Inferred Stock Volatility
Authors: Guo Biao
Published: January 2016

Both CDS and out‐of‐money put option can protect investors against downside risk, so they are related while not being mutually replaceable. This study provides a straightforward linkage between corporate CDS and equity option by inferring stock volatility from CDS spread and, thus, enables a direct analogy with the implied volatility from option price. I find CDS inferred volatility (CIV) and option implied volatility (OIV) are complementary, both containing some information that is not captured by the other. CIV dominates OIV in forecasting stock future realized volatility. Moreover, a trading strategy based on the CIV–OIV mean reverting spreads generates significant risk‐adjusted return. These findings complement existing empirical evidence on cross‐market analysis. © 2016 Wiley Periodicals, Inc. Jrl Fut Mark 36:745–757, 2016
ALK‐rearranged renal cell carcinomas in children
Authors: Cajaiba Mariana M. , Jennings Lawrence J. , Rohan Stephen M. , Perez‐Atayde Antonio R. , Marino‐Enriquez Adrian , Fletcher Jonathan A. , Geller James I. , Leuer Katrin M. C. , Bridge Julia A. , Perlman Elizabeth J.
Published: January 2016

Knowledge of the clinicopathological and molecular spectrum of pediatric renal cell carcinomas (RCC) remains limited, and approximately 16%–24% of these neoplasms cannot be classified into specific subtypes. In this review of 168 pediatric RCC prospectively registered on Children's Oncology Group AREN03B2 protocol, six RCC (3.5%) that demonstrated a unique epithelioid morphology and a peculiar immunophenotypic profile that includes expression of ALK, TFE3, and retention of INI1 was identified. Further investigation revealed ALK rearrangements in all cases, manifested molecularly by fusion transcripts of either VCL‐ALK (3 patients all with sickle cell trait which had been previously reported) or TPM3‐ALK (3 patients, none with sickle cell trait). Based on the shared unique morphologic, immunophenotypic, and genetic features, it was proposed that these neoplasms belonged to a distinct subgroup of RCC frequently occurring in pediatric patients, which they have termed as ALK‐rearranged RCC. Importantly, additional therapeutic options may be available for these patients. © 2016 Wiley Periodicals, Inc.
HRAS mutation prevalence and associated expression patterns in pheochromocytoma
Authors: Stenman Adam , Welander Jenny , Gustavsson Ida , Brunaud Laurent , Bäckdahl Martin , Söderkvist Peter , Gimm Oliver , Juhlin C. Christofer , Larsson Catharina
Published: January 2016

Pheochromocytomas (PCC) and abdominal paragangliomas (PGL) display a highly diverse genetic background and recent gene expression profiling studies have shown that PCC and PGL (together PPGL) alter either kinase signaling pathways or the pseudo‐hypoxia response pathway dependent of the genetic composition. Recurrent mutations in the Harvey rat sarcoma viral oncogene homolog (HRAS) have recently been verified in sporadic PPGLs. In order to further establish the HRAS mutation frequency and to characterize the associated expression profiles of HRAS mutated tumors, 156 PPGLs for exon 2 and 3 hotspot mutations in the HRAS gene was screened, and compared with microarray‐based gene expression profiles for 93 of the cases. The activating HRAS mutations G13R, Q61R, and Q61K were found in 10/142 PCC (7.0%) and a Q61L mutation was revealed in 1/14 PGL (7.1%). All HRAS mutated cases included in the mRNA expression profiling grouped in Cluster 2, and 21 transcripts were identified as altered when comparing the mutated tumors with 91 HRAS wild‐type PPGL. Somatic HRAS mutations were not revealed in cases with known PPGL susceptibility gene mutations and all HRAS mutated cases were benign. The HRAS mutation prevalence of all PPGL published up to date is 5.2% (49/950), and 8.8% (48/548) among cases without a known PPGL susceptibility gene mutation. The findings support a role of HRAS mutations as a somatic driver event in benign PPGL without other known susceptibility gene mutations. HRAS mutated PPGL cluster together with NF1‐ and RET‐mutated tumors associated with activation of kinase‐signaling pathways. © 2016 The Authors Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.
Frequent BCOR aberrations in extranodal NK/T‐Cell lymphoma, nasal type
Authors: Dobashi Akito , Tsuyama Naoko , Asaka Reimi , Togashi Yuki , Ueda Kyoko , Sakata Seiji , Baba Satoko , Sakamoto Kana , Hatake Kiyohiko , Takeuchi Kengo
Published: January 2016

Extranodal natural killer/T cell lymphoma (ENKTL) is a rare subtype of lymphoma. Recurrent mutations in the JAK‐STAT pathway, recently reported in ENKTL cases, are interesting in terms of both pathogenesis and inhibitor therapy. However, the frequencies of these mutations are low and variable among reports, and other pathognomonic mutations in ENKTL remain to be elucidated. In the present study, targeted capture sequencing of 602 cancer‐related genes from 25 frozen ENKTL samples was performed, 11 of which were matched to normal samples. Several recurrent somatic mutations involving BCOR (32%), TP53 (16%), DDX3X (12%), FAT4 (8%), NRAS (8%), MLL3 (12%), and MIR17HG (8%) were identified. The pattern of BCOR aberrations (1 nonsense and 5 frame‐shift mutations, a mutation leading to a splicing error, and gene loss) suggested that loss of function of BCOR was the functionally important outcome of such changes. The literature was reviewed and the public data on BCOR aberrations was reanalyzed and it was found that the aberrations were frequently found in myeloid neoplasms, but, interestingly, were highly specific to ENKTL among lymphoid malignancies. Given the high frequency and pattern of aberration, BCOR is likely to play an important role in ENKTL pathogenesis as a tumor suppressor gene. © 2016 Wiley Periodicals, Inc.
Patterns and frequencies of acquired and constitutional uniparental isodisomies in pediatric and adult B‐cell precursor acute lymphoblastic leukemia
Authors: Lundin Kristina B. , Olsson Linda , Safavi Setareh , Biloglav Andrea , Paulsson Kajsa , Johansson Bertil
Published: January 2016

Single nucleotide polymorphism (SNP) arrays are increasingly being used in clinical routine for genetic analysis of pediatric B‐cell precursor acute lymphoblastic leukemias (BCP ALL). Because constitutional DNA is not readily available as a control at the time of diagnosis, it is important to be able to distinguish between acquired and constitutional aberrations in a diagnostic setting. In the present study we focused on uniparental isodisomies (UPIDs). SNP array analyses of 143 pediatric and 38 adult B‐cell precursor acute lymphoblastic leukemias and matched remission samples revealed acquired whole chromosome or segmental UPIDs (wUPIDs, sUPIDs) in 32 cases (18%), without any age‐ or gender‐related frequency differences. Acquired sUPIDs were larger than the constitutional ones (mean 35.3 Mb vs. 10.7 Mb; P < 0.0001) and were more often terminally located in the chromosomes (69% vs. 4.5%; P < 0.0001). Chromosomes 3, 5, and 9 were most often involved in acquired wUPIDs, whilst recurrent acquired sUPIDs targeted 6p, 9p, 9q, and 14q. The majority (56%) of sUPID9p was associated with homozygous CDKN2A deletions. In pediatric ALL, all wUPIDs were found in high hyperdiploid (51–67 chromosomes) cases and an extended analysis, also including unmatched diagnostic samples, revealed a higher frequency of wUPID‐positivity in higher modal number (56–67 chromosomes) than in lower modal number (51–55 chromosomes) high hyperdiploid cases (34% vs. 11%; P = 0.04), suggesting different underlying mechanisms of formation of these subtypes of high hyperdiploidy. © 2016 Wiley Periodicals, Inc.
Guidelines for genomic array analysis in acquired haematological neoplastic disorders
Authors: Schoumans Jacqueline , Suela Javier , Hastings Ros , Muehlematter Dominique , Rack Katrina , van den Berg Eva , Berna Beverloo H. , Stevens‐Kroef Marian
Published: January 2016

Genetic profiling is important for disease evaluation and prediction of prognosis or responsiveness to therapy in neoplasia. Microarray technologies, including array comparative genomic hybridization and single‐nucleotide polymorphism‐detecting arrays, have in recent years been introduced into the diagnostic setting for specific types of haematological malignancies and solid tumours. It can be used as a complementary test or depending on the neoplasia investigated, also as a standalone test. However, comprehensive and readable presentation of frequently identified complex genomic profiles remains challenging. To assist diagnostic laboratories, standardization and minimum criteria for clinical interpretation and reporting of acquired genomic abnormalities detected through arrays in neoplastic disorders are presented. © 2016 Wiley Periodicals, Inc.
Parameterising User Uptake in Economic Evaluations: The role of discrete choice experiments
Authors: Terris‐Prestholt Fern , Quaife Matthew , Vickerman Peter
Published: January 2016

Model‐based economic evaluations of new interventions have shown that user behaviour (uptake) is a critical driver of overall impact achieved. However, early economic evaluations, prior to introduction, often rely on assumed levels of uptake based on expert opinion or uptake of similar interventions. In addition to the likely uncertainty surrounding these uptake assumptions, they also do not allow for uptake to be a function of product, intervention, or user characteristics.

This letter proposes using uptake projections from discrete choice experiments (DCE) to better parameterize uptake and substitution in cost‐effectiveness models. A simple impact model is developed and illustrated using an example from the HIV prevention field in South Africa. Comparison between the conventional approach and the DCE‐based approach shows that, in our example, DCE‐based impact predictions varied by up to 50% from conventional estimates and provided far more nuanced projections. In the absence of observed uptake data and to model the effect of variations in intervention characteristics, DCE‐based uptake predictions are likely to greatly improve models parameterizing uptake solely based on expert opinion. This is particularly important for global and national level decision making around introducing new and probably more expensive interventions, particularly where resources are most constrained.
Development of a Health Screening Package Under the Universal Health Coverage: The Role of Health Technology Assessment
Authors: Teerawattananon Yot , Kingkaew Pritaporn , Koopitakkajorn Tanunya , Youngkong Sitaporn , Tritasavit Nattha , Srisuwan Patsri , Tantivess Sripen
Published: January 2016

This study reports the systematic development of a population‐based health screening package for all Thai people under the universal health coverage (UHC). To determine major disease areas and health problems for which health screening could mitigate health burden, a consultation process was conducted in a systematic, participatory, and evidence‐based manner that involved 41 stakeholders in a half‐day workshop. Twelve diseases/health problems were identified during the discussion. Subsequently, health technology assessments, including systematic review and meta‐analysis of health benefits as well as economic evaluations and budget impact analyses of corresponding population‐based screening interventions, were completed. The results led to advice against elements of current clinical practice, such as annual chest X‐rays and particular blood tests (e.g. kidney function test), and indicated that the introduction of certain new population‐based health screening programs, such as for chronic hepatitis B, would provide substantial health and economic benefits to the Thais. The final results were presented to a wide group of stakeholders, including decision‐makers at the Ministry of Public Health and the public health insurance schemes, to verify and validate the findings and policy recommendations. The package has been endorsed by the Thai UHC Benefit Package Committee for implementation in fiscal year 2016. © 2016 The Authors. Health Economics published by John Wiley & Sons Ltd.
Methodological Issues to Consider When Collecting Data to Estimate Poverty Impact in Economic Evaluations in Low‐income and Middle‐income Countries
Authors: Sweeney Sedona , Vassall Anna , Foster Nicola , Simms Victoria , Ilboudo Patrick , Kimaro Godfather , Mudzengi Don , Guinness Lorna
Published: January 2016

Out‐of‐pocket spending is increasingly recognized as an important barrier to accessing health care, particularly in low‐income and middle‐income countries (LMICs) where a large portion of health expenditure comes from out‐of‐pocket payments. Emerging universal healthcare policies prioritize reduction of poverty impact such as catastrophic and impoverishing healthcare expenditure. Poverty impact is therefore increasingly evaluated alongside and within economic evaluations to estimate the impact of specific health interventions on poverty. However, data collection for these metrics can be challenging in intervention‐based contexts in LMICs because of study design and practical limitations. Using a set of case studies, this letter identifies methodological challenges in collecting patient cost data in LMIC contexts. These components are presented in a framework to encourage researchers to consider the implications of differing approaches in data collection and to report their approach in a standardized and transparent way. © 2016 The Authors. Health Economics published by John Wiley & Sons Ltd.
Transparency for Whom? Impacts of Accountability Movements for Institutional Researchers and Beyond
Authors: Chen P. Daniel , Haynes R. Michael
Published: January 2016

To whom should higher education institutions provide data, and what is the impact of transparency on institutions?
Growth of Burden in Federal and State Reporting
Authors: Henderson Angela E.
Published: January 2016

This chapter provides context for understanding external reporting burdens and a brief examination of the ongoing shift in institutional reporting demands.
Burden in the Eye of the Beholder: Why Should Administration Care?
Authors: Ma Yanli , Kulich James , Hu Shouping
Published: January 2016

This chapter focuses on perspectives of external data reporting and their implications for institutional research offices and campuses as a whole. The authors examine a variety of uses for externally reported data and explore opportunities for using these data more fully across the institution.
Maximizing Institutional Research Impact Through Building Relationships and Collaborating Within the Institution
Authors: Kirby Yvonne Kochera , Floyd Nancy D.
Published: January 2016

Building and maintaining relationships within the institution with shared goals for preserving compliance and presenting an accurate portrait of the institution is critical for effective external reporting. It can also provide immeasurable internal benefit to information stakeholders.
Easing the Burden of External Reporting
Authors: LoGrasso Marc F.
Published: January 2016

In this chapter, the author presents suggestions for improving the effectiveness of external reporting while minimizing burden. Recommendations include repurposing existing internal reports to address the needs of external reports.
Benchmarking—Current Availability, Possible New National Alternatives, and Making a Contribution to the Discussion
Authors: Atchison Eric S. , Hosch Braden J.
Published: January 2016

This chapter synthesizes the national discussion on other solutions to the Integrated Postsecondary Education Data System (IPEDS), such as a national student record system, and complications. The authors will briefly examine the pros and cons of IPEDS while primarily focusing on national alternatives, as well providing specific examples for institutional researchers to make a contribution to the field.
Future of External Reporting
Authors: Powers Kristina
Published: January 2016

This chapter builds on prior chapters and focuses on higher education trends on the horizon and the resulting impact on external reporting for institutional researchers. Three practical recommendations and examples for institutional researchers are also presented.
Skeletal Mineralization Deficits and Impaired Biogenesis and Function of Chondrocyte-Derived Matrix Vesicles in Phospho1–/– and Phospho1/Pit1 Double-Knockout Mice
Authors: Yadav Manisha C , Bottini Massimo , Cory Esther , Bhattacharya Kunal , Kuss Pia , Narisawa Sonoko , Sah Robert L , Beck Laurent , Fadeel Bengt , Farquharson Colin , Millán José Luis
Published: January 2016

We have previously shown that ablation of either the Phospho1 or Alpl gene, encoding PHOSPHO1 and tissue-nonspecific alkaline phosphatase (TNAP) respectively, lead to hyperosteoidosis, but that their chondrocyte-derived and osteoblast-derived matrix vesicles (MVs) are able to initiate mineralization. In contrast, the double ablation of Phospho1 and Alpl completely abolish initiation and progression of skeletal mineralization. We argued that MVs initiate mineralization by a dual mechanism: PHOSPHO1-mediated intravesicular generation of inorganic phosphate (Pi) and phosphate transporter-mediated influx of Pi. To test this hypothesis, we generated mice with col2a1-driven Cre-mediated ablation of Slc20a1, hereafter referred to as Pit1, alone or in combination with a Phospho1 gene deletion. Pit1col2/col2 mice did not show any major phenotypic abnormalities, whereas severe skeletal deformities were observed in the [Phospho1–/–; Pit1col2/col2] double knockout mice that were more pronounced than those observed in the Phospho1–/– mice. Histological analysis of [Phospho1–/–; Pit1col2/col2] bones showed growth plate abnormalities with a shorter hypertrophic chondrocyte zone and extensive hyperosteoidosis. The [Phospho1–/–; Pit1col2/col2] skeleton displayed significant decreases in BV/TV%, trabecular number, and bone mineral density, as well as decreased stiffness, decreased strength, and increased postyield deflection compared to Phospho1–/– mice. Using atomic force microscopy we found that ∼80% of [Phospho1–/–; Pit1col2/col2] MVs were devoid of mineral in comparison to ∼50% for the Phospho1–/– MVs and ∼25% for the WT and Pit1col2/col2 MVs. We also found a significant decrease in the number of MVs produced by both Phospho1–/– and [Phospho1–/–; Pit1col2/col2] chondrocytes. These data support the involvement of phosphate transporter 1, hereafter referred to as PiT-1, in the initiation of skeletal mineralization and provide compelling evidence that PHOSPHO1 function is involved in MV biogenesis. © 2016 American Society for Bone and Mineral Research.
IRS-1 Functions as a Molecular Scaffold to Coordinate IGF-I/IGFBP-2 Signaling During Osteoblast Differentiation
Authors: Xi Gang , Shen Xinchun , Rosen Clifford J , Clemmons David R
Published: January 2016

Insulin like growth factor I (IGF-I) and insulin like growth factor binding protein-2 (IGFBP-2) function coordinately to stimulate AKT and osteoblast differentiation. IGFBP-2 binding to receptor protein tyrosine phosphatase β (RPTPβ) stimulates polymerization and inactivation of phosphatase activity. Because phosphatase and tensin homolog (PTEN) is the primary target of RPTPβ, this leads to enhanced PTEN tyrosine phosphorylation and inactivation. However RPTPβ inactivation also requires IGF-I receptor activation. The current studies were undertaken to determine the mechanism by which IGF-I mediates changes in RPTPβ function in osteoblasts. IGFBP-2/IGF-I stimulated vimentin binding to RPTPβ and this was required for RPTPβ polymerization. Vimentin serine phosphorylation mediated its binding to RPTPβ and PKCζ was identified as the kinase that phosphorylated vimentin. To determine the mechanism underlying IGF-I stimulation of PKCζ-mediated vimentin phosphorylation, we focused on insulin receptor substrate–1 (IRS-1). IGF-I stimulated IRS-1 phosphorylation and recruitment of PKCζ and vimentin to phospho-IRS-1. IRS-1 immunoprecipitates containing PKCζ and vimentin were used to confirm that activated PKCζ directly phosphorylated vimentin. PKCζ does not contain a SH-2 domain that is required to bind to phospho-IRS-1. To determine the mechanism of PKCζ recruitment we analyzed the role of p62 (a PKCζ binding protein) that contains a SH2 domain. Exposure to differentiation medium plus IGF-I stimulated PKCζ/p62 association. Subsequent analysis showed the p62/PKCζ complex was co-recruited to IRS-1. Peptides that disrupted p62/PKCζ or p62/IRS-1 inhibited IGF-I/IGFBP-2 stimulated PKCζ activation, vimentin phosphorylation, PTEN tyrosine phosphorylation, AKT activation, and osteoblast differentiation. The importance of these signaling events for differentiation was confirmed in primary mouse calvarial osteoblasts. These results demonstrate the cooperative interaction between RPTPβ and the IGF-I receptor leading to a coordinated series of signaling events that are required for osteoblast differentiation. Our findings emphasize the important role IRS-1 plays in modulating these signaling events and confirm its essential role in facilitating osteoblast differentiation. © 2016 American Society for Bone and Mineral Research.
Transcription Factors and Medium Suitable for Initiating the Differentiation of Human‐Induced Pluripotent Stem Cells to the Hepatocyte Lineage
Authors: Tomizawa Minoru , Shinozaki Fuminobu , Motoyoshi Yasufumi , Sugiyama Takao , Yamamoto Shigenori , Ishige Naoki
Published: January 2016

Transcription factors and culture media were investigated to determine the condition to initiate the differentiation of human‐induced pluripotent stem (iPS) cells most efficiently. The expression of genes in human adult liver was compared with that in 201B7 cells (iPS cells) using cDNA microarray analysis. Episomal plasmids expressing transcription factors were constructed. 201B7 cells were transfected with the episomal plasmids and cultured in ReproFF (feeder‐free media maintaining pluripotency), Leibovitz‐15 (L15), William's E (WE), or Dulbecco's modified Eagle medium/Nutrient F‐12 Ham (DF12) for 7 days. RNA was isolated and subjected to real‐time quantitative PCR to analyze the expression of alpha‐feto protein (AFP) and albumin. cDNA microarray analysis revealed 16 transcription factors that were upregulated in human adult liver relative to that in 201B7 cells. Episomal plasmids expressing these 16 genes were transfected into 201B7 cells. CCAAT/enhancer‐binding protein alpha (CEBPA), CCAAT/enhancer‐binding protein beta (CEBPB), forkhead box A1 (FOXA1), and forkhead box A3 (FOXA3) up‐regulated AFP and down‐regulated Nanog. These four genes were further analyzed. The expression of AFP and albumin was the highest in 201B7 cells transfected with the combination of CEBPA, CEBPB, FOXA1, and FOXA3 and cultured in WE. The combination of CEBPA, CEBPB, FOXA1, and FOXA3 was suitable for 201B7 cells to initiate differentiation to the hepatocyte lineage and WE was the most suitable medium for culture after transfection. J. Cell. Biochem. 117: 2001–2009, 2016. © 2016 Wiley Periodicals, Inc.
CJD and Scrapie Require Agent‐Associated Nucleic Acids for Infection
Authors: Botsios Sotirios , Manuelidis Laura
Published: January 2016

Unlike Alzheimer's and most other neurodegenerative diseases, Transmissible Spongiform Encephalopathies (TSEs) are all caused by actively replicating infectious particles of viral size and density. Different strain‐specific TSE agents cause CJD, kuru, scrapie and BSE, and all behave as latent viruses that evade adaptive immune responses and can persist for years in lymphoreticular tissues. A foreign viral structure with a nucleic acid genome best explains these TSE strains and their endemic and epidemic spread in susceptible species. Nevertheless, it is widely believed that host prion protein (PrP), without any genetic material, encodes all these strains. We developed rapid infectivity assays that allowed us to reproducibly isolate infectious particles where >85% of the starting titer separated from the majority of host components, including PrP. Remarkably, digestion of all forms of PrP did not reduce brain particle titers. To ask if TSE agents, as other viruses, require nucleic acids, we exposed high titer FU‐CJD and 22L scrapie particles to potent nucleases. Both agent‐strains were propagated in GT1 neuronal cells to avoid interference by complex degenerative brain changes that can impede nuclease digestions. After exposure to nucleases that are active in sarkosyl, infectivity of both agents was reproducibly reduced by ≥99%. No gold‐stained host proteins or any form of PrP were visibly altered by these nucleases. In contrast, co‐purifying protected mitochondrial DNA and circular SPHINX DNAs were destroyed. These findings demonstrate that TSE agents require protected genetic material to infect their hosts, and should reopen investigation of essential agent nucleic acids. J. Cell. Biochem. 117: 1947–1958, 2016. © 2016 Wiley Periodicals, Inc.
TGF‐β Signaling in Cancer
Authors: Syed Viqar
Published: January 2016

The transforming growth factor‐β (TGF‐β) is a family of structurally related proteins that comprises of TGF‐β, activins/inhibins, and bone morphogenic proteins (BMPs). Members of the TGF‐β family control numerous cellular functions including proliferation, apoptosis, differentiation, epithelial‐mesenchymal transition (EMT), and migration. The first identified member, TGF‐β is implicated in several human diseases, such as vascular diseases, autoimmune disorders, and carcinogenesis. Activation of the TGF‐β receptor by its ligands induces the phosphorylation of serine/threonine residues and triggers phosphorylation of the intracellular effectors, SMADs. Upon activation, SMAD proteins translocate to the nucleus and induce transcription of their target genes, regulating several cellular functions. TGF‐β dysregulation has been implicated in carcinogenesis. In early stages of cancer, TGF‐β exhibits tumor suppressive effects by inhibiting cell cycle progression and promoting apoptosis. However, in late stages TGF‐β exerts tumor promoting effects, increasing tumor invasiveness, and metastasis. Furthermore, the TGF‐β signaling pathway communicates with other signaling pathways in a synergistic or antagonistic manner and regulates cellular functions. Elevated TGF‐β activity has been associated with poor clinical outcome. Given the pivotal role of TGF‐β in tumor progression, this pathway is an attractive target for cancer therapy. Several therapeutic tools such as TGF‐β antibodies, antisense oligonucleotides, and small molecules inhibitors of TGF‐β receptor‐1 (TGF‐βR1) have shown immense potential to inhibit TGF‐β signaling. Finally, in the interest of developing future therapies, further studies are warranted to identify novel points of convergence of TGF‐β with other signaling pathways and oncogenic factors in the tumor microenvironment. J. Cell. Biochem. 117: 1279–1287, 2016. © 2016 Wiley Periodicals, Inc.
Extracellular Matrix Stiffness Controls VEGF Signaling and Processing in Endothelial Cells
Authors: Sack Kelsey D. , Teran Madelane , Nugent Matthew A.
Published: January 2016

Vascular endothelial growth factor A (VEGF) drives endothelial cell maintenance and angiogenesis. Endothelial cell behavior is altered by the stiffness of the substrate the cells are attached to suggesting that VEGF activity might be influenced by the mechanical cellular environment. We hypothesized that extracellular matrix (ECM) stiffness modifies VEGF‐cell‐matrix tethering leading to altered VEGF processing and signaling. We analyzed VEGF binding, internalization, and signaling as a function of substrate stiffness in endothelial cells cultured on fibronectin (Fn) linked polyacrylamide gels. Cell produced extracellular matrices on the softest substrates were least capable of binding VEGF, but the cells exhibited enhanced VEGF internalization and signaling compared to cells on all other substrates. Inhibiting VEGF‐matrix binding with sucrose octasulfate decreased cell‐internalization of VEGF and, inversely, heparin pre‐treatment to enhance Fn‐matrix binding of VEGF increased cell‐internalization of VEGF regardless of matrix stiffness. β1 integrins, which connect cells to Fn, modulated VEGF uptake in a stiffness dependent fashion. Cells on hard surfaces showed decreased levels of activated β1 and inhibition of β1 integrin resulted in a greater proportional decrease in VEGF internalization than in cells on softer matrices. Extracellular matrix binding is necessary for VEGF internalization. Stiffness modifies the coordinated actions of VEGF‐matrix binding and β1 integrin binding/activation, which together are critical for VEGF internalization. This study provides insight into how the microenvironment may influence tissue regeneration and response to injury and disease. J. Cell. Physiol. 231: 2026–2039, 2016. © 2016 Wiley Periodicals, Inc.
Conversion of Prostate Adenocarcinoma to Small Cell Carcinoma‐Like by Reprogramming
Authors: Borges Gisely T. , Vêncio Eneida F. , Quek Sue‐Ing , Chen Adeline , Salvanha Diego M. , Vêncio Ricardo Z.N. , Nguyen Holly M. , Vessella Robert L. , Cavanaugh Christopher , Ware Carol B. , Troisch Pamela , Liu Alvin Y.
Published: January 2016

The lineage relationship between prostate adenocarcinoma and small cell carcinoma was studied by using the LuCaP family of xenografts established from primary neoplasm to metastasis. Expression of four stem cell transcription factor (TF) genes, LIN28A, NANOG, POU5F1, SOX2, were analyzed in the LuCaP lines. These genes, when force expressed in differentiated cells, can reprogram the recipients into stem‐like induced pluripotent stem (iPS) cells. Most LuCaP lines expressed POU5F1, while LuCaP 145.1, representative of small cell carcinoma, expressed all four. Through transcriptome database query, many small cell carcinoma genes were also found in stem cells. To test the hypothesis that prostate cancer progression from “differentiated” adenocarcinoma to “undifferentiated” small cell carcinoma could involve re‐expression of stem cell genes, the four TF genes were transduced via lentiviral vectors into five adenocarcinoma LuCaP lines—70CR, 73CR, 86.2, 92, 105CR—as done in iPS cell reprogramming. The resultant cells from these five transductions displayed a morphology of small size and dark appearing unlike the parentals. Transcriptome analysis of LuCaP 70CR* (“*” to denote transfected progeny) revealed a unique gene expression close to that of LuCaP 145.1. In a prostate principal components analysis space based on cell‐type transcriptomes, the different LuCaP transcriptome datapoints were aligned to suggest a possible ordered sequence of expression changes from the differentiated luminal‐like adenocarcinoma cell types to the less differentiated, more stem‐like small cell carcinoma types, and LuCaP 70CR*. Prostate cancer progression can thus be molecularly characterized by loss of differentiation with re‐expression of stem cell genes. J. Cell. Physiol. 231: 2040–2047, 2016. © 2016 Wiley Periodicals, Inc.
It is also in our nature: Genetic influences on work characteristics and in explaining their relationships with well‐being
Authors: Li Wen‐Dong , Zhang Zhen , Song Zhaoli , Arvey Richard D.
Published: January 2016

Work design research typically views employee work characteristics as being primarily determined by the work environment and has thus paid less attention to the possibility that the person may also influence employee work characteristics and in turn accounts for the work characteristics–well‐being relationships through selection. Challenging this conventional view, we investigated the role of a fundamental individual difference variable—people's genetic makeup—in affecting work characteristics (i.e., job demands, job control, social support at work, and job complexity) and in explaining why work characteristics relate to subjective and physical well‐being. Our findings based on a national US twin sample show sizable genetic influences on job demands, job control, and job complexity, but not on social support at work. Such genetic influences were partly attributed to genetic factors associated with core self‐evaluations. Both genetic and environmental influences accounted for the relationships between work characteristics and well‐being, but to varying degrees. The results underscore the importance of the person, in addition to the work environment, in influencing employee work characteristics and explaining the underlying nature of the relationships between employee work characteristics and their well‐being. Copyright © 2016 John Wiley & Sons, Ltd.
Protein turnover analysis in Salmonella Typhimurium during infection by dynamic SILAC, Topograph, and quantitative proteomics
Authors: Wang Zhe , Han Qiang‐Qiang , Zhou Mao‐Tian , Chen Xi , Guo Lin
Published: January 2016

Protein turnover affects protein abundance and phenotypes. Comprehensive investigation of protein turnover dynamics has the potential to provide substantial information about gene expression. Here we report a large‐scale protein turnover study in Salmonella Typhimurium during infection by quantitative proteomics. Murine macrophage‐like RAW 264.7 cells were infected with SILAC labeled Salmonella. Bacterial cells were extracted after 0, 30, 60, 120, and 240 min. Mass spectrometry analyses yielded information about Salmonella protein turnover dynamics and a software program named Topograph was used for the calculation of protein half lives. The half lives of 311 proteins from intracellular Salmonella were obtained. For bacteria cultured in control medium (DMEM), the half lives for 870 proteins were obtained. The calculated median of protein half lives was 69.13 and 99.30 min for the infection group and the DMEM group, respectively, indicating an elevated protein turnover at the initial stage of infection. Gene ontology analyses revealed that a number of protein functional groups were significantly regulated by infection, including proteins involved in ribosome, periplasmic space, cellular amino acid metabolic process, ion binding, and catalytic activity. The half lives of proteins involved in purine metabolism pathway were found to be significantly shortened during infection.