bluuebunny/crossref_metadata_2025 huggingface dataset:
Directed Evolution of DNA Polymerases: Construction and Screening of DNA Polymerase Mutant Libraries
Authors: Gloeckner Christian , Kranaster Ramon , Marx Andreas
Published: January 2015

The protocols in this article describe the construction of a mutant DNA polymerase library using error‐prone PCR (epPCR) as a method for gene randomization, followed by screening of the library using two different approaches. The examples described use an N‐terminally truncated form of the thermostable DNA polymerase I of Thermus aquaticus (Taq DNA polymerase), namely Klentaq (KTQ), and protocols are included for the identification of variants with (1) increased DNA lesion‐bypass ability and (2) enhanced selectivity for DNA match/mismatch recognition. The screening assays are based on double‐stranded DNA detection (using SYBR Green I) which can be carried out using standard laboratory equipment. The described assays are designed for use in a 384‐well plate format to increase screening throughput and reduce material costs. For improved accuracy and ease of liquid handling, the use of an automated liquid handling device is recommended. Curr. Protoc. Chem Biol. 2:89‐109. © 2010 by John Wiley & Sons, Inc.
Hematology Testing in Mice
Authors: Lundberg Pontus , Skoda Radek
Published: January 2015

The mouse is an increasingly important system for the study of both normal and aberrant hematopoiesis. As a model organism, the mouse recapitulates much of human hematopoiesis; however, there are some important differences. Here, the basic approaches for analyzing hematopoiesis in mice are described. In particular, methods are provided for the collection and analysis of peripheral blood, flow cytometry analysis of peripheral blood, bone marrow, and spleen cells, and isolation and transplantation of bone marrow stem cells. Curr. Protoc. Mouse Biol. 1:323‐346 © 2011 by John Wiley & Sons, Inc.
Systematic Evaluation of Skeletal Mechanical Function
Authors: Smith Lauren , Bigelow Erin M.R. , Jepsen Karl J.
Published: January 2015

Many genetic and environmental perturbations lead to measurable changes in bone morphology, matrix composition, and matrix organization. Here, straightforward biomechanical methods are described that can be used to determine whether a genetic or environmental perturbation affects bone strength. A systematic method is described for evaluating how bone strength is altered in the context of morphology and tissue‐level mechanical properties, which are determined in large part from matrix composition, matrix organization, and porosity. The methods described include computed tomography, whole‐bone mechanical tests (bending and compression), tissue‐level mechanical tests, and determination of ash content, water content, and bone density. This strategy is intended as a first step toward screening mice for phenotypic effects on bone and establishing the associated biomechanical mechanism by which function has been altered, and can be conducted without a background in engineering. The outcome of these analyses generally provides insight into the next set of experiments required to further connect cellular perturbation with functional change. Curr. Protoc. Mouse Biol. 3:39‐67 © 2013 by John Wiley & Sons, Inc.
Blood Collection from Mice and Hematological Analyses on Mouse Blood
Authors: Rathkolb Birgit , Fuchs Helmut , Gailus‐Durner Valérie , Aigner Bernhard , Wolf Eckhard , Hrabě de Angelis Martin
Published: January 2015

Basic phenotyping of inbred mouse strains and genetically modified mouse models usually includes the determination of blood‐based parameters as a diagnostic screen for genotype effects on metabolism and organ function. A broad range of analytes, including hematological parameters, can be reliably determined in mouse blood, if appropriate samples are available. Here we describe recommended techniques for blood collection from mice and the considerations that have to be taken into account to get adequate samples for hematological investigations. Furthermore, we describe established methods used in the German Mouse Clinic (GMC) to determine hematological parameters in the mouse. Curr. Protoc. Mouse Biol. 3:101‐119 © 2013 by John Wiley & Sons, Inc.
Does Combined Clinical and Ultrasound Assessment Allow Selection of Individuals With Rheumatoid Arthritis for Sustained Reduction of Anti–Tumor Necrosis Factor Therapy?
Authors: Marks Jonathan L. , Holroyd Christopher R. , Dimitrov Borislav D. , Armstrong Ray D. , Calogeras Antonia , Cooper Cyrus , Davidson Brian K. , Dennison Elaine M. , Harvey Nicholas C. , Edwards Christopher J.
Published: January 2015

Objective

To investigate whether a strategy combining clinical and ultrasound (US) assessment can select individuals with rheumatoid arthritis (RA) for sustained dose reduction of anti–tumor necrosis factor (anti‐TNF) therapies.

Methods

As part of a real‐world approach, patients with RA receiving anti‐TNF therapies were reviewed in a dedicated biologic therapy clinic. Patients not taking oral corticosteroids with both Disease Activity Score in 28 joints (DAS28) remission (≤2.6) and absent synovitis on power Doppler US (PDUS 0) for >6 months were invited to reduce their anti‐TNF therapy dose by one‐third.

Results

Between January 2012 and February 2014, a total of 70 patients underwent anti‐TNF dose reduction. Combined DAS28 and PDUS remission was maintained by 96% of patients at 3 months followup, 63% at 6 months, 37% at 9 months, and 34% at 18 months followup. However, 88% of patients maintained at least low disease activity (LDA) with DAS28 <3.2 and PDUS ≤1 at 6 months. The addition of PDUS identified 8 patients (25% of those that flared) in DAS28 remission, with subclinically active disease. Those who maintained dose reduction were more likely to be rheumatoid factor (RF) negative (46% versus 17%; P = 0.03) and have lower DAS28 scores at biologic therapy initiation (5.58 versus 5.96; P = 0.038).

Conclusion

Combined clinical and US assessment identifies individuals in remission who may be suitable for anti‐TNF dose reduction and enhances safe monitoring for subclinical disease flares. Despite longstanding severe RA, a subset of our cohort sustained prolonged DAS28 and PDUS remission. LDA at biologic therapy initiation and RF status appeared predictive of sustained remission.
Oxide Formation, Morphology, and Nanohardness of Laser‐Patterned Steel Surfaces
Authors: Rosenkranz Andreas , Reinert Leander , Gachot Carsten , Aboufadl Hisham , Grandthyll Samuel , Jacobs Karin , Müller Frank , Mücklich Frank
Published: January 2015

A large variety of tribological research studies dealt with the effect of laser induced surface textures and the respective parameters such as depth, feature diameter, and area density on the tribological efficiency. However, only few studies have examined chemical and microstructural changes induced by the laser‐patterning process, which can have a significant impact on the tribological properties. The aim of this study is to analyze the surface chemistry of laser‐induced line‐like patterns with a structural wavelength of 18 mm on steel surfaces (AISI 304), i.e., oxide scale thickness and morphology, prior to and after laser processing. X‐ray photoelectron spectroscopy combined with an Argon ion sputtering facility was used to measure depth profiles of the iron‐ and chromium oxide layer. A subsequent analysis performed by atom probe tomography demonstrated that the laser interference patterning leads to an increased iron‐ and chromium oxide layer by a factor of 8 compared to the polished unpatterned reference surface and to a change in the oxide morphology from a solid solution in the reference to a layered structure in the laser‐patterned state. Nanoindentation experiments revealed that the nano‐hardness in the laser‐intensity maximum position is two times larger than in the reference position. Finally, hardness calculations assuming a bilayer model correlate the observed nano‐hardness with the measured surface chemistry.
Enhanced Mechanical Properties of Microalloyed Austenitic Stainless Steel Produced by Martensite Treatment
Authors: Shirdel Mohammad , Mirzadeh Hamed , Parsa Mohammad Habibi
Published: January 2015

A thermomechanical treatment based on the reversion of strain‐induced martensite (SIM) was employed to produce ultrafine‐grained structures in a microalloyed austenitic stainless steel (ASS). The smallest average grain size of ≈480 nm was achieved by annealing the heavily‐rolled samples at 650 °C for 240 min while an outstanding combination of strength and ductility was acquired by annealing at 850 °C for 1 min due to the synergic effects of the following phenomena: refinement of austenite matrix grains down to an average grain size of 620 nm, presence of small amount of thermally‐induced martensite, formation of a bimodal grain size distribution by primary and secondary recrystallization processes, and dislocation accumulation. The kinetics of strain‐induced martensitic transformation was studied and the classical rule of mixtures was used to elucidate the hardening contribution of martensite. Subsequently, it was shown that the Hall–Petch relation is valid for a wide range of grain size for AISI 304 type stainless steel.
Energy Level Offsets at Lead Halide Perovskite/Organic Hybrid Interfaces and Their Impacts on Charge Separation
Authors: Wang Qian‐Kun , Wang Rong‐Bin , Shen Peng‐Fei , Li Chi , Li Yan‐Qing , Liu Li‐Jia , Duhm Steffen , Tang Jian‐Xin
Published: January 2015

Lead halide perovskites are currently attracting a great deal of attentions due to their great promise as light absorbers in high‐efficiency hybrid organic–inorganic solid‐state solar cells. The reliable information about interface energetics of lead halide perovskite‐based interfaces is indispensable to unraveling the photon harvesting and charge separation process for this emerging photovoltaic technology. Here, we provide the direct evidence on energy level alignments at the hybrid interfaces between lead halide perovskite and organic hole‐transport materials (HTMs) using in situ ultraviolet and X‐ray photoemission techniques. The measured alignment schemes at perovskite/HTM hybrid interfaces reveal four entirely different energy level offsets with respect to the variation of HTMs, including spiro‐OMeTAD, NPB, F16CuPc, HATCN, and MoO3, and their impacts on charge separation are also elucidated. It is identified that the staggered‐gap heterojunction in contact with a HTM of higher‐lying occupied molecular orbital can facilitate the interfacial hole extraction. Our experimental findings provide the guideline of not only understanding the interfacial charge separation mechanisms but also optimizing the HTMs in perovskite‐based solar cells.
Altitude effect on birth weight and prematurity in the Province of Catamarca (Argentina)
Authors: Candelas Nieves , Terán José Manuel , López Barbancho Diego , Díaz María Cristina , Lomaglio Delia Beatriz , Marrodán María Dolores
Published: January 2015

Objectives

To analyze the effect of altitude on weight and prematurity at birth in the Province of Catamarca (Argentina), between the years 1994 and 2003.

Methods

Records of 22,628 newborns were collected from the vital statistics of the census of Catamarca. Weight was recategorized to include low birth weight (<2,500 g), and gestational age was divided into births that had occurred before or after 37 weeks (preterm or at term births). Altitude was also recategorized (<1,500 m, 1,500–2,000 m, and > 2,000 m). Nonparametric statistical tests were performed.

Results

Differences were found in birth weight between sexes and in the incidence of low birth weight depending on altitude. This pattern changed according to gestational age, because those sexual differences were nonexistent or lower in preterm neonates with certain advantages for females. Moreover, it was found that the effects of hypoxia were not reflected in birth weight until later stages of intrauterine development.

Conclusions

To be female appears to be a benefit under conditions of prematurity and high altitude. The increased incidence of prematurity due to altitude increase may reflect an adaptive advantage of preterm birth under these conditions. Am. J. Hum. Biol. 27:526–529, 2015. © 2015 Wiley Periodicals, Inc.
Is human mating for height associated with fertility? Results from a british national cohort study
Authors: Krzyżanowska Monika , Mascie‐Taylor C.G. Nicholas , Thalabard Jean‐Christophe
Published: January 2015

Objectives

Very few studies have investigated whether spousal similarity for height is related to fertility. This study examined the relationship between mating for height and fertility after correction for spousal age, social class, education, and region.

Methods

The data used were collected as part of the British National Child Development Study and 6,535 husband–wife pairs for whom data were available on measured height, spousal age, education, social class, region, and the number of children were studied.

Results

Fertility varied between the regions with the highest fertility in Scotland. Fertility tended to increase from more to less educated and from higher to lower social classes in both sexes. These relationships remained significant after correction for mean age. A negative association between husband's height in relation to fertility was noted as well as the negative and the quadratic term for wife's height. Both the linear as well as the quadratic effects of parental height difference were significantly related to fertility, but after removing the effects of mean age, age difference and mean height these effects disappeared. Analysis of region, mean age, social class, education, height, and differences in age, social class, education, and height together revealed that 32.4% of variation in fertility was explained but only mean age, mean social class and mean height and difference in social class remained significant.

Conclusions

The results did not provide any evidence that differential fertility was associated with spousal height difference after taking into account age, social class, education and region. Am. J. Hum. Biol. 27:553–563, 2015. © 2015 Wiley Periodicals, Inc.
Characterizing occupational heat‐related mortality in the United States, 2000–2010: An analysis using the census of fatal occupational injuries database
Authors: Gubernot Diane M. , Anderson G. Brooke , Hunting Katherine L.
Published: January 2015

Background

Occupational heat‐related mortality is not well studied and risk factors remain largely unknown. This paper describes the epidemiological characteristics of heat‐related deaths among workers in the US 2000–2010.

Methods

Fatality data were obtained at the Bureau of Labor Statistics from the confidential on‐site Census of Fatal Occupational Injuries database. Fatality rates and risk ratios with 95% confidence intervals were calculated by year, sex, age group, ethnicity, race, state, and industry.

Results

Between 2000 and 2010, 359 occupational heat‐related deaths were identified in the U.S., for a yearly average fatality rate of 0.22 per 1 million workers. Highest rates were found among Hispanics, men, the agriculture and construction industries, the state of Mississippi, and very small establishments.

Conclusions

This study provides the first comprehensive national profile of heat‐related deaths in the U.S. workplace. Prevention efforts should be directed at small businesses and at industries and individuals with the highest risk. Am. J. Ind. Med. 58:203–211, 2015. © 2015 Wiley Periodicals, Inc.
Workplace cohort studies in times of economic instability
Authors: Cherniack Martin , Dussetschleger Jeffrey , Farr Dana , Dugan Alicia ,   The CPH‐NEW Team
Published: January 2015

Background

A prospective study directed to musculoskeletal health in the manufacturing workforce.

Methods

A 36‐month longitudinal study using mixed method; surveys with work and non‐work psychosocial variables, physiologic measurements physical performance, interviews and focus groups, and direct observation of work activity.

Results

Changing economic conditions introduced barriers requiring recruiting a larger number of study sites. Study adherence was unexpectedly high. Coincident with their economic concerns, participants perceived an increase in workplace stress, but not physical demand. New instruments were added to assess economic effects on retirement planning and the physical and emotional costs of caregiving responsibilities.

Conclusions

The economic conditions required adaptive alterations in design due to workforce volatility but presented opportunities for studying the link between working conditions and health. Nevertheless, study size expectations were met through an adaptive approach that suggests a potential effect of the economy on health and well‐being. Am. J. Ind. Med. 58:138–151, 2015. © 2015 Wiley Periodicals, Inc.
Nonlocal effects in black body radiation
Authors: Bremm Guilherme N. , Falciano Felipe T.
Published: January 2015

Nonlocal electrodynamics is a formalism developed to include nonlocal effects in the measurement process in order to account for the impossibility of instantaneous measurement of physical fields. This theory modifies Maxwell's electrodynamics by eliminating the hypothesis of locality that assumes an accelerated observer simultaneously equivalent to a comoving inertial frame of reference. In this scenario, the transformation between an inertial and accelerated observer is generalized which affects the properties of physical fields. In particular, we analyze how an uniformly accelerated observer perceives a homogeneous and isotropic black body radiation. We show that all nonlocal effects are transient and most relevant in the first period of acceleration.

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The influence of Ni/Nd‐based Ziegler–Natta catalyst on microstructure configurations and properties of butadiene rubber
Authors: Chatarsa Chansuree , Prasassarakich Pattarapan , Rempel Garry L. , Hinchiranan Napida
Published: January 2015

Neodymium (Nd)‐based Ziegler–Natta catalyst has been well known for preparing polybutadiene rubber (BR) containing high, about 98%, cis−1,4 configuration with extremely low gel content providing superior resistance to low‐temperature fatigue and abrasion. However, its cost is more expensive than a conventional nickel (Ni)‐based catalyst. The Nd‐BR has poor processability with high cold flow due to its high linearity and molecular weight. To compare with a traditional process, the BR produced by Ni‐based catalyst has higher level of branching resulting in the better processability, but it contains medium amount of gel. To balance the catalyst cost and the BR properties, this article reported the influence of a solution containing Ni‐ and Nd‐based Ziegler–Natta catalyst (Ni/Nd) using diethyl aluminum chloride and triethyl aluminum as co‐catalysts on 1,3‐butadiene (BD) conversion and physical properties of the elastomeric materials based on obtained rubber (Ni/Nd‐BR). In the presence of toluene, the increase in the Ni/Nd molar ratio from 0.0/1.0 to 0.4/0.6 yielded Ni/Nd‐BR containing cis−1,4 units of 95%–96% with significantly decreasing both levels of vinyl−1,2 and trans−1,4 configurations from 0.26% to 0.13% and 4.44% to 3.07%, respectively. When cyclohexane was applied as the reaction media, 100% BD conversion was achieved and the Ni/Nd‐BR had very low content of vinyl−1,2 unit (0.07%). The mechanical properties in terms of tensile properties and abrasion resistance of the elastomer based on Ni/Nd‐BR having high cis‐1,4 and relatively higher trans−1,4 configurations were superior to elastomers based on commercial BRs produced by using Ni‐ and Nd‐based catalyst systems. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41834.
Effect of interfacial pretreatment on the properties of montmorillonite/poly(vinyl alcohol) nanocomposites
Authors: Shori Shailesh , Chen Xiaoming , Peralta Michael , Gao Hongsheng , zur Loye Hans‐Conrad , Ploehn Harry J.
Published: January 2015

This work explores the factors that control the dispersion of exfoliated montmorillonite (MMT) in poly(vinyl alcohol) (PVOH) during solution blending and solvent evaporation. Nanocomposite films were prepared by solution blending of aqueous PVOH solutions with dilute suspensions of fully exfoliated MMT platelets (as confirmed by AFM). Dynamic light scattering (DLS) indicates that addition of MMT suspensions to PVOH solutions results in undesired particle aggregation and thus poor MMT dispersion in cast films (as evidenced by transmission electron microscopic images and gas permeation measurements). We believe that PVOH bridging induces MMT platelet aggregation. To counteract bridging aggregation, we explore the novel idea of pretreating the MMT surface with a small amount of compatible polymer prior to solution blending with PVOH. We hypothesize that “pretreating” the MMT platelet surfaces with adsorbed polymer in dilute suspensions will protect the platelets from bridging aggregation during solution blending and solvent evaporation. MMT/PVOH composite films have been prepared using low‐molecular‐weight PVOH as the pretreatment polymer; and low‐, medium‐, and high‐molecular‐weight PVOH as the matrix polymer. A PEO‐PPO‐PEO triblock copolymer (F108 from the Pluronics® family) was also evaluated as the pretreatment polymer. DLS shows that pretreated MMT platelets are less susceptible to aggregation during blending with PVOH solutions. Results compare the crystalline structure, thermal properties, dynamic mechanical properties, gas permeability, and dissolution behavior of MMT/PVOH films incorporating untreated versus pretreated MMT. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41867.
Synthesis and stability research of reproducible aqueous polyurethane micelles with low de‐blocking temperature
Authors: Wu Hongchuan , Li Zhiguo , Zhu Libin , Gu Jiyou
Published: January 2015

Aqueous polyurethane micelles from 2,4,6‐trichlorphenol blocking terminal‐isocynate pre‐polymer were prepared which could be de‐blocked at low temperature. The prepared aqueous blocked polyurethane micelles (BPUMs) were uniform and spherical micro‐particles. The particle size was decreased with increase of the DMPA content, while it was enlarged at first and then gradually decreased by increasing R‐value. The stability of the micelles was affected by the R value, blocked efficiency and DMPA content. HDI‐BPUMs were more stable than HDI‐BPUMs at the same condition. The stability was further researched by the zeta potential combining with technique and viscosity tracking method, and the initial zeta potential be used as the stability criterion. In addition, a stabilization mechanism of the micelles was proposed. TCP‐blocked TDI‐BPUMs could be initially de‐blocked at about 75°C and TCP‐blocked HDI‐BPUMs was de‐blocked at about 80°C. The de‐blocking temperature could be further reduced in the presence of catalyst, but it was scarcely affected by the change of R‐value and DMPA content. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41908
Effects of polycaprolactone molecular weights on thermal and mechanical properties of polybenzoxazine
Authors: Tiptipakorn Sunan , Keungputpong Noppawat , Phothiphiphit Somruthai , Rimdusit Sarawut
Published: January 2015

Polymer blends of polybenzoxazine (PBA‐a) and polycaprolactone (PCL) of different molecular weights (Mn = 10,000, 45,000, and 80,000 Da) were prepared at various PBA‐a/PCL mass ratios and their properties were characterized. The results from dynamic mechanical analyzer (DMA) revealed two glass transition temperatures implying phase separation of the two polymers in the studied range of the PCL contents. Moreover, a synergistic behavior in glass transition temperature (Tg) was evidently observed in these blends with a maximumTgvalue of 281°C compared with theTgvalue of 169°C of the PBA‐a and about −50°C of the PCL used. The blends with higherMnof PCL tended to provide greaterTgvalue than those with lower Mnof PCL. The modulus and hardness values of PBA‐a were decreased while the elongation at break and area under the stress−strain curve were increased with an increase of the content andMnof PCL, suggesting an enhancement of toughness of the PBA‐a. Scanning electron micrographs (SEM) of the sample fracture surface are also used to confirm the improvement in toughness of the blends. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2015,132, 41915.
Brief Report: Chikungunya Viral Arthritis in the United States: A Mimic of Seronegative Rheumatoid Arthritis
Authors: Miner Jonathan J. , Aw Yeang Han Xian , Fox Julie M. , Taffner Samantha , Malkova Olga N. , Oh Stephen T. , Kim Alfred H. J. , Diamond Michael S. , Lenschow Deborah J. , Yokoyama Wayne M.
Published: January 2015

Objective

Chikungunya virus (CHIKV) is an arthritogenic mosquito‐transmitted alphavirus that spread to the Caribbean in 2013 and to the US in 2014. CHIKV‐infected patients develop inflammatory arthritis that can persist for months or years, but little is known about the rheumatologic and immunologic features of CHIKV‐related arthritis in humans, particularly as compared to rheumatoid arthritis (RA). The purpose of this study was to describe these features in a group of 10 American travelers who were nearly simultaneously infected while visiting Haiti in June 2014.

Methods

Patient history was obtained and physical examination and laboratory tests were performed. All patients with CHIKV‐related arthritis had detectable levels of anti‐CHIKV IgG. Using cytometry by time‐of‐flight (CyTOF), we analyzed peripheral blood mononuclear cells in CHIKV‐infected patients, healthy controls, and patients with untreated, active RA.

Results

Among 10 CHIKV‐infected individuals, 8 developed persistent symmetric polyarthritis that met the American College of Rheumatology/European League Against Rheumatism 2010 criteria for (seronegative) RA. CyTOF analysis revealed that RA and CHIKV‐infected patients had greater percentages of activated and effector CD4+ and CD8+ T cells than healthy controls.

Conclusion

In addition to similar clinical features, patients with CHIKV infection and patients with RA develop very similar peripheral T cell phenotypes. These overlapping clinical and immunologic features highlight a need for rheumatologists to consider CHIKV infection when evaluating patients with new, symmetric polyarthritis.
Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage
Authors: Zelenski Nicole A. , Leddy Holly A. , Sanchez‐Adams Johannah , Zhang Jinzi , Bonaldo Paolo , Liedtke Wolfgang , Guilak Farshid
Published: January 2015

Objective

Mechanical factors play a critical role in the physiology and pathology of articular cartilage, although the mechanisms of mechanical signal transduction are not fully understood. We undertook this study to test the hypothesis that type VI collagen is necessary for mechanotransduction in articular cartilage by determining the effects of type VI collagen knockout on the activation of the mechano‐osmosensitive, calcium‐permeable channel TRPV4 (transient receptor potential vanilloid channel 4) as well as on osmotically induced chondrocyte swelling and pericellular matrix (PCM) mechanical properties.

Methods

Confocal laser scanning microscopy was used to image TRPV4‐mediated calcium signaling and osmotically induced cell swelling in intact femora from 2‐ and 9‐month‐old wild‐type (WT) and type VI collagen–deficient (Col6a1−/−) mice. Immunofluorescence‐guided atomic force microscopy was used to map PCM mechanical properties based on the presence of perlecan.

Results

Hypo‐osmotic stress–induced TRPV4‐mediated calcium signaling was increased in Col6a1−/− mice relative to WT controls at 2 months. Col6a1−/− mice exhibited significantly increased osmotically induced cell swelling and decreased PCM moduli relative to WT controls at both ages.

Conclusion

In contrast to our original hypothesis, type VI collagen was not required for TRPV4‐mediated Ca2+ signaling; however, knockout of type VI collagen altered the mechanical properties of the PCM, which in turn increased the extent of cell swelling and osmotically induced TRPV4 signaling in an age‐dependent manner. These findings emphasize the role of the PCM as a transducer of mechanical and physicochemical signals, and they suggest that alterations in PCM properties, as may occur with aging or osteoarthritis, can influence mechanotransduction via TRPV4 or other ion channels.
Th1 and Th17 Cytokines Drive Inflammation in Takayasu Arteritis
Authors: Saadoun D. , Garrido M. , Comarmond C. , Desbois A. C. , Domont F. , Savey L. , Terrier B. , Geri G. , Rosenzwajg M. , Klatzmann D. , Fourret P. , Cluzel P. , Chiche L. , Gaudric J. , Koskas F. , Cacoub P.
Published: January 2015

Objective

Takayasu arteritis (TAK) is a large‐vessel vasculitis that induces damage to the aorta and its branches. Glucocorticoids remain the gold standard of therapy for TAK. The nature of the T cells driving vascular inflammation and the effects of glucocorticoids on the systemic components of TAK are not understood. The aim of this study was to analyze T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta in patients with TAK.

Methods

T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta were analyzed using Luminex analysis, flow cytometry, and immunohistochemical analysis. The study included 41 patients fulfilling the American College of Rheumatology 1990 criteria for the classification of TAK (17 patients with active TAK and 24 patients with disease in remission), 30 patients with giant cell arteritis and 39 patients with Behçet's disease (disease controls), and 20 age‐ and sex‐matched healthy control subjects.

Results

We observed a marked increase in the expression of Th1 and Th17 cells, which correlated with TAK disease activity. The addition of serum from patients with active TAK to sorted CD4+ T cells from healthy donors in culture medium induced significant production of interferon‐γ (IFNγ) and interleukin‐17A (IL‐17A). We demonstrated the presence of IFNγ‐, IL‐6–, and IL‐17A–producing T cells in vascular inflammatory infiltrates in patients with TAK. Corticosteroid therapy was associated with decreased levels of circulating Th1 cytokines in corticosteroid‐treated patients with TAK compared with steroid‐free patients with TAK (for IL‐2, mean ± SD 5,079 ± 5,300 versus 7,359 ± 3,197 pg/ml; for IFNγ, 2,592 ± 3,072 versus 8,393 ± 3,392 pg/ml; for tumor necrosis factor α, 847 ± 724 versus 1,491 ± 392 pg/ml). However, glucocorticoids had essentially no effect on the frequency of Th17 cytokines (IL‐1 receptor, IL‐17, and IL‐23).

Conclusion

The Th17 and Th1 pathways contribute to the systemic and vascular manifestations of TAK. Glucocorticoid treatment suppresses Th1 cytokines but spares Th17 cytokines in patients with TAK.
Overlap Between Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder: Searching for Distinctive/Common Clinical Features
Authors: Craig Francesco , Lamanna Anna Linda , Margari Francesco , Matera Emilia , Simone Marta , Margari Lucia
Published: January 2015

Recent studies support several overlapping traits between autism spectrum disorders (ASD) and attention‐deficit/hyperactivity disorder (ADHD), assuming the existence of a combined phenotype. The aim of our study was to evaluate the common or distinctive clinical features between ASD and ADHD in order to identify possible different phenotypes that could have a clinical value. We enrolled 181 subjects divided into four diagnostic groups: ADHD group, ASD group, ASD+ADHD group (that met diagnostic criteria for both ASD and ADHD), and control group. Intelligent quotient (IQ), emotional and behavior problems, ADHD symptoms, ASD symptoms, and adaptive behaviors were investigated through the following test: Wechsler Intelligence Scale for Children, Wechsler Preschool and Primary Scale of Intelligence or Leiter International Performances Scale Revised, Child Behavior Checklist, Conners' Rating Scales‐Revised, SNAP‐IV Rating Scale, the Social Communication Questionnaire, Vineland Adaptive Behavior Scales. The ASD+ADHD group differs from ADHD or ASD in some domains such as lower IQ mean level and a higher autistic symptoms severity. However, the ASD+ADHD group shares inattention and hyperactivity deficit and some emotional and behavior problems with the ADHD group, while it shares adaptive behavior impairment with ASD group. These findings provide a new understanding of clinical manifestation of ASD+ADHD phenotype, they may also inform a novel treatment target. Autism Res 2015, 8: 328–337. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Electrodermal Response to Reward and Non‐Reward Among Children With Autism
Authors: Neuhaus Emily , Bernier Raphael A. , Beauchaine Theodore P.
Published: January 2015

Pervasive social difficulties among individuals with autism spectrum disorder (ASD) are often construed as deriving from reduced sensitivity to social stimuli. Behavioral and neurobiological evidence suggests that typical individuals show preferential processing of social (e.g., voices, faces) over nonsocial (e.g., nonvocal sounds, images of objects) information, whereas individuals with ASD may not. This reduction in sensitivity may reflect disrupted reward processing [Dawson & Bernier, ], with significant developmental consequences for affected individuals. In this study, we explore effects of social and monetary reward on behavioral and electrodermal responses (EDRs) among 8‐ to 12‐year‐old boys with (n = 18) and without (n = 18) ASD, with attention to the potential moderating effects of stimulus familiarity. During a simple matching task, participants with and without ASD had marginally slower reactions during social vs. nonsocial reward, and boys with ASD had less accurate responses than controls. Compared to baseline, reward and non‐reward conditions elicited more frequent and larger EDRs for participants as a whole, and both groups showed similar patterns of EDR change within reward blocks. However, boys with and without ASD differed in their EDRs to non‐reward, and response amplitude was correlated with social and emotional functioning. These findings provide some support for altered reward responding in ASD at the autonomic level, and highlight the discontinuation of reward as an important component of reward‐based learning that may play a role in shaping behavior and guiding specialized brain development to subserve social behavior and cognition across the lifespan. Autism Res 2015, 8: 357–370. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Normal P50 Gating in Children with Autism, Yet Attenuated P50 Amplitude in the Asperger Subcategory
Authors: Madsen Gitte Falcher , Bilenberg Niels , Jepsen Jens Richardt , Glenthøj Birte , Cantio Cathriona , Oranje Bob
Published: January 2015

Autism spectrum disorders (ASD) and schizophrenia are separate disorders, but there is evidence of conversion or comorbid overlap. The objective of this paper was to explore whether deficits in sensory gating, as seen in some schizophrenia patients, can also be found in a group of ASD children compared to neurotypically developed children. An additional aim was to investigate the possibility of subdividing our ASD sample based on these gating deficits. In a case–control design, we assessed gating of the P50 and N100 amplitude in 31 ASD children and 39 healthy matched controls (8–12 years) and screened for differences between groups and within the ASD group. We did not find disturbances in auditory P50 and N100 filtering in the group of ASD children as a whole, nor did we find abnormal P50 and N100 amplitudes. However, the P50 amplitude to the conditioning stimulus was significantly reduced in the Asperger subgroup compared to healthy controls. In contrast to what is usually reported for patients with schizophrenia, we found no evidence for sensory gating deficits in our group of ASD children taken as a whole. However, reduced P50 amplitude to conditioning stimuli was found in the Asperger group, which is similar to what has been described in some studies in schizophrenia patients. There was a positive correlation between the P50 amplitude of the conditioning stimuli and anxiety score in the pervasive developmental disorder not otherwise specified group, which indicates a relation between anxiety and sensory registration in this group. Autism Res 2015, 8: 371–378. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Neural Correlates of Set‐Shifting in Children With Autism
Authors: Yerys Benjamin E. , Antezana Ligia , Weinblatt Rachel , Jankowski Kathryn F. , Strang John , Vaidya Chandan J. , Schultz Robert T. , Gaillard William D. , Kenworthy Lauren
Published: January 2015

Autism spectrum disorder (ASD) is often associated with high levels of inflexible thinking and rigid behavior. The neural correlates of these behaviors have been investigated in adults and older adolescents, but not children. Prior studies utilized set‐shifting tasks that engaged multiple levels of shifting, and depended on learning abstract rules and establishing a strong prepotent bias. These additional demands complicate simple interpretations of the results. We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of set‐shifting in 20 children (ages 7–14) with ASD and 19 typically developing, matched, control children. Participants completed a set‐shifting task that minimized nonshifting task demands through the use of concrete instructions that provide spatial mapping of stimuli‐responses. The shift/stay sets were given an equal number of trials to limit the prepotent bias. Both groups showed an equivalent “switch cost,” responding less accurately and slower to Switch stimuli than Stay stimuli, although the ASD group was less accurate overall. Both groups showed activation in prefrontal, striatal, parietal, and cerebellum regions known to govern effective set‐shifts. Compared to controls, children with ASD demonstrated decreased activation of the right middle temporal gyrus across all trials, but increased activation in the mid‐dorsal cingulate cortex/superior frontal gyrus, left middle frontal, and right inferior frontal gyri during the Switch vs. Stay contrast. The successful behavioral switching performance of children with ASD comes at the cost of requiring greater engagement of frontal regions, suggesting less efficiency at this lowest level of shifting. Autism Res 2015, 8: 386–397. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
T‐Brain‐1 – A Potential Master Regulator in Autism Spectrum Disorders
Authors: Chuang Hsiu‐Chun , Huang Tzyy‐Nan , Hsueh Yi‐Ping
Published: January 2015

T‐Brain‐1 (TBR1), a causative gene in autism spectrum disorders (ASDs), encodes a brain‐specific T‐box transcription factor. It is therefore possible that TBR1 controls the expression of other autism risk factors. The downstream genes of TBR1 have been identified using microarray and promoter analyses. In this study, we annotated individual genes downstream of TBR1 and investigated any associations with ASDs through extensive literature searches. Of 124 TBR1 target genes, 23 were reported to be associated with ASDs. In addition, one gene, Kiaa0319, is a known causative gene for dyslexia, a disorder frequently associated with autism. A change in expression level in 10 of these 24 genes has been previously confirmed. We further validated the alteration of RNA expression levels of Kiaa0319, Baiap2, and Gad1 in Tbr1 deficient mice. Among these 24 genes, four transcription factors Auts2, Nfia, Nr4a2, and Sox5 were found, suggesting that TBR1 controls a transcriptional cascade relevant to autism pathogenesis. A further five of the 24 genes (Cd44, Cdh8, Cntn6, Gpc6, and Ntng1) encode membrane proteins that regulate cell adhesion and axonal outgrowth. These genes likely contribute to the role of TBR1 in regulation of neuronal migration and axonal extension. Besides, decreases in Grin2b expression and increases in Gad1 expression imply that neuronal activity may be aberrant in Tbr1 deficient mice. These analyses provide direction for future experiments to reveal the pathogenic mechanism of autism. Autism Res 2015, 8: 412–426. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Construction of an antimyoglobin single‐chain variable fragment with rapid reaction kinetics
Authors: Jang Jun‐Hyuck , Kim Dong‐Hyung , Paek Se‐Hwan , Woo Eui‐Jeon , Kim Young‐Wan
Published: January 2015

Antibodies with rapid reaction kinetics (high association and dissociation rates), named reversible antibodies, are used to perform continuous monitoring of sensitive disease biomarkers. In cases of acute myocardial infarction (AMI), continuous monitoring and early diagnosis are important. Human myoglobin (Myo) is a useful biomarker for AMI during the early stage after the onset of symptoms. In this study, a single‐chain variable fragment (scFv) specific to Myo was derived from an IgG antibody that has rapid reaction kinetics. Enzyme‐linked immunosorbent assay revealed that recombinant scFv exhibited 3.8‐fold reduced affinity compared with the parent IgG antibody based on the antibody concentration necessary for 50% of the maximum signal. The scFv retained the rapid reaction kinetic mode with average kon and koff of 2.63 × 105 M−1 Sec−1 and 3.25 × 10−3 Sec−1, respectively, which were reduced to 10‐ and 2.3‐fold compared with those of the parent antibody. The equilibrium constant for the association of the scFv (KA = 8.09 × 107 M−1) was 4.6‐fold lower than that of its parent IgG antibody. This scFv may be a starting point for further mutagenesis/kinetic and structural analyses providing valuable insight into the mechanism of reversible antibodies.
Thermostable α‐amylase immobilization: Enhanced stability and performance for starch biocatalysis
Authors: Kumar Gudi Satheesh , Rather Gulam Mohmad , Gurramkonda Chandrasekhar , Reddy Bontha Rajasekhar
Published: January 2015

The uses of thermostable starch hydrolytic biocatalysts are steadily increasing for the industrial application because of their obvious need for biocatalytic performance at elevated temperatures. The starch liquefaction and saccharification can be carried out simultaneously by the use of thermostable starch hydrolytic biocatalysts, thus minimizing the unit operations, time, and efforts. The cost factor hampers the industrialization of expensive soluble (free) enzymes for biocatalytic applications and the immobilization of enzymes offers promising alternative to the hurdle. The present investigation was aimed for immobilization of thermostable α‐amylase using calcium alginate, and statistical optimization studies were carried out for enhanced biocatalytic performance. Initially, one‐parameter at a time optimization studies were carried out for identification of significant factors influencing the immobilization. Furthermore, a statistical approach, response surface methodology, was applied for immobilization of α‐amylase. The immobilized α‐amylase in alginate microbeads showed enhanced stability to temperature and reusable property for up to seven cycles (with the retention of 50% initial activity). Finally, the kinetic behavior of free and immobilized enzyme showed the Km value of 1.2% and 2.6% (w/v) and Vmax of 1,020 and 1,030 U, respectively. Fifty percent reduction in affinity of the immobilized enzyme toward substrate was compensated by its longer stability.
Gut microbial metabolism and colon cancer: Can manipulations of the microbiota be useful in the management of gastrointestinal health?
Authors: Belcheva Antoaneta , Irrazabal Thergiory , Martin Alberto
Published: January 2015

The gut microbiota is an important component of the human body and its immune‐modulating and metabolic activities are critical to maintain good health. Gut microbes, however, are sensitive to changes in diet, exposure to antibiotics, or infections, all of which cause transient disruptions in the microbial composition, a phenomenon known as dysbiosis. It is now recognized that microbial dysbiosis is at the root of many gastrointestinal disorders. However, the mechanisms through which bacterial dysbiosis initiates disease are not fully understood. Microbially‐derived metabolites and their role in disease have also attracted significant attention. Identification of cancer‐associated bacteria and understanding the contributions of microbial metabolism in health and disease are exciting but challenging areas that will allow defining microbial biomarkers for predicting gastrointestinal disorders. Understanding the complex interactions between gut microbiota, diet, host immune system and host genetics will be critical to developing more personalized therapies and approaches to treat disease.
Reinforcer Variation in a Token Economy
Authors: Becraft Jessica L. , Rolider Natalie U.
Published: January 2015

We evaluated whether generalized conditioned reinforcers mitigate the effects of satiation with an individual with intellectual disabilities. Previous research indicates that generalized conditioned reinforcers are not sensitive to satiation effects. However, this effect has not been investigated on varying classes of backup reinforcers. First, we established a highly preferred (HP) edible as a reinforcer. Then, we provided presession access to the HP edible, and, in a multi‐element comparison, the participant could either earn tokens for only the HP edible, for edibles that were similar to the HP edible, for edibles that were dissimilar to the HP edible, or earn no tokens. A decreasing trend in responding for the HP edible was observed following presession access. Furthermore, the participant completed the task at a high rate when backup reinforcers were dissimilar to the HP edible. Results suggest that varying the classes of stimuli that are used as backup reinforcers may increase the effectiveness of generalized conditioned reinforcers. Copyright © 2015 John Wiley & Sons, Ltd.
Trends in breast biopsy pathology diagnoses among women undergoing mammography in the United States: A report from the Breast Cancer Surveillance Consortium
Authors: Allison Kimberly H. , Abraham Linn A. , Weaver Donald L. , Tosteson Anna N. A. , Nelson Heidi D. , Onega Tracy , Geller Berta M. , Kerlikowske Karla , Carney Patricia A. , Ichikawa Laura E. , Buist Diana S. M. , Elmore Joann G.
Published: January 2015

BACKGROUND

Current data on the pathologic diagnoses of breast biopsy after mammography can inform patients, clinicians, and researchers about important population trends.

METHODS

Breast Cancer Surveillance Consortium data on 4,020,140 mammograms between 1996 and 2008 were linked to 76,567 pathology specimens. Trends in diagnoses in biopsies by time and risk factors (patient age, breast density, and family history of breast cancer) were examined for screening and diagnostic mammography (performed for a breast symptom or short‐interval follow‐up).

RESULTS

Of the total mammograms, 88.5% were screening and 11.5% diagnostic; 1.2% of screening and 6.8% of diagnostic mammograms were followed by biopsies. The frequency of biopsies over time was stable after screening mammograms, but increased after diagnostic mammograms. For biopsies obtained after screening, frequencies of invasive carcinoma increased over time for women ages 40‐49 and 60‐69, Ductal carcinoma in situ (DCIS) increased for those ages 40‐69, whereas benign diagnoses decreased for all ages. No trends in pathology diagnoses were found following diagnostic mammograms. Dense breast tissue was associated with high‐risk lesions and DCIS relative to nondense breast tissue. Family history of breast cancer was associated with DCIS and invasive cancer.

CONCLUSIONS

Although the frequency of breast biopsy after screening mammography has not changed over time, the percentages of biopsies with DCIS and invasive cancer diagnoses have increased. Among biopsies following mammography, women with dense breasts or family history of breast cancer were more likely to have high‐risk lesions or invasive cancer. These findings are relevant to breast cancer screening and diagnostic practices. Cancer 2015;121:1369–1378. © 2015 American Cancer Society.