bluuebunny/crossref_metadata_2025 huggingface dataset:
EGFR regulation of epidermal barrier function
Authors: Tran Quynh T. , Kennedy Lawrence H. , Leon Carrion Sandra , Bodreddigari Sridevi , Goodwin Shirlean B. , Sutter Carrie H. , Sutter Thomas R.
Published: March 2012

Keratinocyte terminal differentiation is the process that ultimately forms the epidermal barrier that is essential for mammalian survival. This process is controlled, in part, by signal transduction and gene expression mechanisms, and the epidermal growth factor receptor (EGFR) is known to be an important regulator of multiple epidermal functions. Using microarray analysis of a confluent cell density-induced model of keratinocyte differentiation, we identified 2,676 genes that are regulated by epidermal growth factor (EGF), a ligand of the EGFR. We further discovered, and separately confirmed by functional assays, that EGFR activation abrogates all of the known essential processes of keratinocyte differentiation by 1) decreasing the expression of lipid matrix biosynthetic enzymes, 2) regulating numerous genes forming the cornified envelope, and 3) suppressing the expression of tight junction proteins. In organotypic cultures of skin, EGF acted to impair epidermal barrier integrity, as shown by increased transepidermal water loss. As defective epidermal differentiation and disruption of barrier function are primary features of many human skin diseases, we used bioinformatic analyses to identify genes that are known to be associated with skin diseases. Compared with non-EGF-regulated genes, EGF-regulated genes were significantly enriched for skin disease genes. These results provide a systems-level understanding of the actions of EGFR signaling to inhibit keratinocyte differentiation, providing new insight into the role of EGFR imbalance in skin pathogenesis.
Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction
Authors: Livraghi-Butrico Alessandra , Grubb Barbara R. , Kelly Elizabeth J. , Wilkinson Kristen J. , Yang Huifang , Geiser Marianne , Randell Scott H. , Boucher Richard C. , O'Neal Wanda K.
Published: March 2012

Mucus clearance is an important airway innate defense mechanism. Airway-targeted overexpression of the epithelial Na+channel β-subunit [encoded by sodium channel nonvoltage gated 1, beta subunit ( Scnn1b)] in mice [ Scnn1b-transgenic (Tg) mice] increases transepithelial Na+absorption and dehydrates the airway surface, which produces key features of human obstructive lung diseases, including mucus obstruction, inflammation, and air-space enlargement. Because the first Scnn1b-Tg mice were generated on a mixed background, the impact of genetic background on disease phenotype in Scnn1b-Tg mice is unknown. To explore this issue, congenic Scnn1b-Tg mice strains were generated on C57BL/6N, C3H/HeN, BALB/cJ, and FVB/NJ backgrounds. All strains exhibited a two- to threefold increase in tracheal epithelial Na+absorption, and all developed airway mucus obstruction, inflammation, and air-space enlargement. However, there were striking differences in neonatal survival, ranging from 5 to 80% (FVB/NJ<BALB/cJ<C3H/HeN<C57BL/6N), which correlated with the incidence of upper airway mucus plugging and the levels of Muc5b in bronchoalveolar lavage. The strains also exhibited variable Clara cell necrotic degeneration in neonatal intrapulmonary airways and a variable incidence of pulmonary hemorrhage and lung atelectasis. The spontaneous occurrence of a high surviving BALB/cJ line, which exhibited delayed onset of Na+hyperabsorption, provided evidence that: 1) air-space enlargement and postnatal death were only present when Na+hyperabsorption occurred early, and 2) inflammation and mucus obstruction developed whenever Na+hyperabsorption was expressed. In summary, the genetic context and timing of airway innate immune dysfunction critically determines lung disease phenotype. These mouse strains may be useful to identify key modifier genes and pathways.
Peromyscusas a Mammalian Epigenetic Model
Authors: Shorter Kimberly R. , Crossland Janet P. , Webb Denessia , Szalai Gabor , Felder Michael R. , Vrana Paul B.
Published: March 2012

Deer mice (Peromyscus) offer an opportunity for studying the effects of natural genetic/epigenetic variation with several advantages over other mammalian models. These advantages include the ability to study natural genetic variation and behaviors not present in other models. Moreover, their life histories in diverse habitats are well studied.Peromyscusresources include genome sequencing in progress, a nascent genetic map, and >90,000 ESTs. Here we review epigenetic studies and relevant areas of research involvingPeromyscusmodels. These include differences in epigenetic control between species and substance effects on behavior. We also present new data on the epigenetic effects of diet on coat-color using aPeromyscusmodel of agouti overexpression. We suggest that in terms of tying natural genetic variants with environmental effects in producing specific epigenetic effects,Peromyscusmodels have a great potential.
Mobilisation versus Bed Rest after Skin Grafting Pretibial Lacerations: A Meta-Analysis
Authors: Southwell-Keely James , Vandervord John
Published: March 2012

Pretibial lacerations are problematic and best managed by surgical debridement, then skin grafting. Traditional postoperative care involves bed rest to optimise graft survival. This meta-analysis assesses early mobilisation versus bed rest for skin graft healing of these wounds. Medline, Embase, Cochrane, Cinahl, and Google Scholar databases were searched. Analyses were performed on appropriate clinical trials. Four trials met with the inclusion criteria. No difference was demonstrated in split skin graft healing between patients mobilised early compared to patients admitted to hospital for postoperative bed rest at either 7 (OR 0.86 CI 0.29–2.56) or 14 days (OR 0.74 CI 0.31–1.79). There was a statistically significant delay in healing in patients treated with systemic corticosteroids (OR 8.20 CI 0.99–15.41). There was no difference in postoperative haematoma, bleeding, graft infection, or donor site healing between the comparison groups. In the available literature, there is no difference between early mobilisation and bed rest for the healing of skin grafts to pretibial wounds. Corticosteroids exert a negative effect on skin graft healing unlike early mobilisation, which does not cause increased haematoma, bleeding, infection, or delayed donor site healing. Modality of anaesthesia does not affect skin graft healing.
Nonlinear Vibration of a Multirotor System Connected by a Flexible Coupling Subjected to the Holonomic Constraint of Dynamic Angular Misalignment
Authors: Li M.
Published: March 2012

This paper proposes a mathematical model of the multirotor system with a flexible coupling on spring supports on Lagrange′s approach, which has taken into account the effects of dynamic angular misalignment and mass unbalance. Then its nonlinear dynamic behaviors of the system are discussed based on the method of multiple scales and numerical technique, respectively. The results show that the responses of the system in lateral directions contain a similar component to that of the mass unbalanced system on both the vibrating frequency and amplitude and involve the typical nonlinear components such as the ones from some combined frequencies; the results also reveal that the numerical agreements on the above‐mentioned methods are perfect for the transient responses.
Essential Role of Mast Cells in the Visceral Hyperalgesia Induced byT. spiralisInfection and Stress in Rats
Authors: Yang Chang-Qing , Wei Yan-Yu , Zhong Chan-Juan , Duan Li-Ping
Published: March 2012

Mast cells (MCs) deficient rats (Ws/Ws) were used to investigate the roles of MCs in visceral hyperalgesia. Ws/Ws and wild control (+/+) rats were exposed toT. spiralisor submitted to acute cold restraint stress (ACRS). Levels of proteinase-activated receptor 2 (PAR2) and nerve growth factor (NGF) were determined by immunoblots and RT-PCR analysis, and the putative signal pathways including phosphorylated extracellular-regulated kinase (pERK1/2) and transient receptor potential vanilloid receptor 1 (TRPV1) were further identified. Visceral hyperalgesia triggered by ACRS was observed only in+/+rats. The increased expression of PAR2 and NGF was observed only in+/+rats induced byT. spiralisand ACRS. The activation of pERK1/2 induced by ACRS occurred only in+/+rats. However, a significant increase of TRPV1 induced byT. spiralisand ACRS was observed only in+/+rats. The activation of PAR2 and NGF via both TRPV1 and pERK1/2 signal pathway is dependent on MCs in ACRS-induced visceral hyperalgesia rats.
Global Stability of Multigroup Dengue Disease Transmission Model
Authors: Ding Deqiong , Wang Xueping , Ding Xiaohua
Published: March 2012

We investigate a class of multigroup dengue epidemic
model. We show that the global dynamics are determined by the basic reproductive
number R0. We present that when R0 ≤ 1, there is a unique disease‐free
equilibrium which is globally asymptotically stable; when R0 > 1, there exists a
unique endemic equilibrium and it is globally asymptotically stable proved by a
graph‐theoretic approach to the method of global Lyapunov function.
The Physiological Role of Mitophagy: New Insights into Phosphorylation Events
Authors: Hirota Yuko , Kang Dongchon , Kanki Tomotake
Published: March 2012

Mitochondria play an essential role in oxidative phosphorylation, fatty acid oxidation, and the regulation of apoptosis. However, this organelle also produces reactive oxygen species (ROS) that continually inflict oxidative damage on mitochondrial DNA, proteins, and lipids, which causes further production of ROS. To oppose this oxidative stress, mitochondria possess quality control systems that include antioxidant enzymes and the repair or degradation of damaged mitochondrial DNA and proteins. If the oxidative stress exceeds the capacity of the mitochondrial quality control system, it seems that autophagy degrades the damaged mitochondria to maintain cellular homeostasis. Indeed, recent evidence from yeast to mammals indicates that the autophagy-dependent degradation of mitochondria (mitophagy) contributes to eliminate dysfunctional, aged, or excess mitochondria. In this paper, we describe the molecular processes and regulatory mechanisms of mitophagy in yeast and mammalian cells.
Sporadic Infection ofWolbachiain a Recently Established Population ofFormica fusca
Authors: Ingram Krista K. , Hoadley Andrew P. , Iandoli Matt , Kahler John , Marion Stacey , Peteru Swetha , Sabo Emily , So Jee Won
Published: March 2012

This study examines the distribution and invasion dynamics ofWolbachiain a recently establishedFormica fuscapopulation. Preliminary data revealed the intermittent infection ofWolbachiaacross colonies, providing the opportunity to test for ecological factors affecting the acquisition and spread of the parasite. Only 35% of colonies are infected in this population. Both infected and noninfected nests have similar dispersion patterns that approximate a random distribution, suggesting that transmission ofWolbachiabetween adjacent colonies is not common. There is no difference in the infection rate between workers and brood, indicating that workers are not actively eliminating the infection. Our results show no significant association betweenWolbachiainfection and nest size; however, infected colonies tend to be larger than noninfected colonies. Finally,Wolbachiainfection was not associated with queen number. Overall, our results suggest no large fitness differences between infected and noninfected colonies, although small fitness effects cannot be ruled out for this population.
Fisheye‐Lens‐Based Visual Sun Compass for Perception of Spatial Orientation
Authors: Wang Liang , Duan Fuqing , Lv Ke
Published: March 2012

In complex aeronautical and space engineering systems, conventional sensors used for environment perception fail to determine the orientation because of the influences of the special environments, wherein geomagnetic fields are exceptional and the Global Positioning System is unavailable. This paper presents a fisheye‐lens‐based visual sun compass that is efficient in determining orientation in such applications. The mathematical model is described, and the absolute orientation is identified by image processing techniques. For robust detection of the sun in the image of the visual sun compass, a modified maximally stable extremal region algorithm and a method named constrained least squares with pruning are proposed. In comparison with conventional sensors, the proposed visual sun compass can provide absolute orientation with a tiny size and light weight in especial environments. Experiments are carried out with a prototype validating the efficiency of the proposed visual sun compass.
Nanostructures for Medical Diagnostics
Authors: Bellah Md. Motasim , Christensen Shawn M. , Iqbal Samir M.
Published: March 2012

Nanotechnology is the art of manipulating materials on atomic or molecular scales especially to build nanoscale structures and devices. The field is expanding quickly, and a lot of work is ongoing in the design, characterization, synthesis, and application of materials, structures, devices, and systems by controlling shape and size at nanometer scale. In the last few years, much work has been focused on the use of nanostructures toward problems of biology and medicine. In this paper, we focus on the application of various nanostructures and nanodevices in clinical diagnostics and detection of important biological molecules. The discussion starts by introducing some basic techniques of micro‐/nanoscale fabrication that have enabled reproducible production of nanostructures. The prospects, benefits, and limitations of using these novel techniques in the fields of biodetection and medical diagnostics are then discussed. Finally, the challenges of mass production and acceptance of nanotechnology by the medical community are considered.
Low Prevalence ofTP53Mutations andMDM2Amplifications in Pediatric Rhabdomyosarcoma
Authors: Ognjanovic Simona , Martel Ghyslaine , Manivel Carlos , Olivier Magali , Langer Erica , Hainaut Pierre
Published: March 2012

The tumor suppressor geneTP53is the most commonly mutated gene in human cancer. The reported prevalence of mutations in rhabdomyosarcoma (RMS) varies widely, with recent larger studies suggesting thatTP53mutations in pediatric RMS may be extremely rare. Overexpression of MDM2 also attenuates p53 function. We have performedTP53mutation/MDM2amplification analyses in the largest series analyzed thus far, including DNA isolated from 37 alveolar and 38 embryonal RMS tumor samples obtained from the Cooperative Human Tissue Network (CHTN). Available samples were frozen tumor tissues (N=48) and histopathology slides.TP53mutations in exons 4–9 were analyzed by direct sequencing in all samples, andMDM2amplification analysis was performed by differential PCR on a subset of 22 samples. We found only one sample (1/75, 1.3%) carrying aTP53mutation at codon 259 (p.D259Y) and noMDM2amplification. Two SNPs in theTP53pathway, associated with accelerated tumor onset in germlineTP53mutation carriers, (TP53SNP72 (rs no. 1042522) and MDM2 SNP309 (rs no. 2279744)), were not found to confer earlier tumor onset. In conclusion, we confirm the extremely low prevalence ofTP53mutations/MDM2amplifications in pediatric RMS (1.33% and 0%, respectively). The possible inactivation of p53 function by other mechanisms thus remains to be elucidated.
Three Positive Periodic Solutions to Nonlinear Neutral Functional Differential Equations with Parameters on Variable Time Scales
Authors: Li Yongkun , Wang Chao
Published: March 2012

Using two successive reductions: B‐equivalence of the system on a variable time scale to a system on a time scale and a reduction to an impulsive differential equation and by Leggett‐Williams fixed point theorem, we investigate the existence of three positive periodic solutions to the nonlinear neutral functional differential equation on variable time scales with a transition condition between two consecutive parts of the scale , (t, x) ∈ 𝕋0(x),, , where and are parameters, 𝕋0(x) is a variable time scale with (ω, p)‐property, c(t),   a(t), vj(t), and fj(t, x)   (j = 1,2, …, n) are ω‐periodic functions of t, Bi+p = Bi,   Ji+p(x) = Ji(x) uniformly with respect to i ∈ ℤ.
Circulating Leukotriene B4 Identifies Respiratory Complications after Trauma
Authors: Auner Birgit , Geiger Emanuel V. , Henrich Dirk , Lehnert Mark , Marzi Ingo , Relja Borna
Published: March 2012

Background. Leukotriene B4 (LTB4), a proinflammatory lipid mediator correlates well with the acute phase of Acute Respiratory Distress Syndrome (ARDS). Therefore, LTB4-levels were investigated to determine whether they might be a useful clinical marker in predicting pulmonary complications (PC) in multiply traumatized patients. Methods: Plasma levels of LTB4 were determined in 100 patients on admission (ED) and for five consecutive days (daily). Twenty healthy volunteers served as control. LTB4-levels were measured by ELISA. Thirty patients developed PC (pneumonia, respiratory failure, acute lung injury (ALI), ARDS, pulmonary embolism) and 70 had no PC (ØPC).Results. LTB4-levels in the PC-group [127.8 pg/mL, IQR: 104–200pg/ml] were significantly higher compared to the ØPC-group on admission [95.6 pg/mL, IQR: 55–143 pg/mL] or control-group [58.4 pg/mL, IQR: 36–108 pg/mL]. LTB4 continuously declined to basal levels from day 1 to 5 without differences between the groups. The cutoff to predict PC was calculated at 109.6 pg/mL (72% specificity, 67% sensitivity). LTB4 was not influenced by overall or chest injury severity, age, gender or massive transfusion. Patients with PC received mechanical ventilation for a significantly longer period of time, and had prolonged intensive care unit and overall hospital stay.Conclusion. High LTB4-levels indicate risk for PC development in multiply traumatized patients.
Measurement and Analysis of Microwave Frequency Signals Transmitted through the Breast
Authors: Bourqui Jeremie , Garrett John , Fear Elise
Published: March 2012

Microwave approaches to breast imaging include the measurement of signals transmitted through and reflected from the breast. Prototype systems typically feature sensors separated from the breast, resulting in measurements that include the effects of the environment and system. To gain insight into transmission of microwave signals through the breast, a system that places sensors in direct contact with the breast is proposed. The system also includes a lossy immersion medium that enables measurement of the signal passing through the breast while significantly attenuating signals traveling along other paths. Collecting measurements at different separations between sensors also provides the opportunity to estimate the average electrical properties of the breast tissues. After validation through simulations and measurements, a study of 10 volunteers was performed. Results indicate symmetry between the right and left breast and demonstrate differences in attenuation, maximum frequency for reliable measurement, and average properties that likely relate to variations in breast composition.
Potential Uses of Cord Blood in Cardiac Surgery
Authors: Mosca Ralph S.
Published: March 2012

Despite advances in the fields of prevention, medical intervention and surgical therapy, cardiovascular disease remains a major public healthcare issue. A promising area of research is the potential application of regenerative therapies with pluripotential stem cells to reduce the burden of heart disease and its sequelae. Umbilical cord blood, a rich source of multiple populations of nonembryonic stem cells, will be a valuable resource and has the potential to advance therapeutic options for patients with acquired and congenital heart disease.
Block Least Mean Squares Algorithm over Distributed Wireless Sensor Network
Authors: Panigrahi T. , Pradhan P. M. , Panda G. , Mulgrew B.
Published: March 2012

In a distributed parameter estimation problem, during each sampling instant, a typical sensor node communicates its estimate either by the diffusion algorithm or by the incremental algorithm. Both these conventional distributed algorithms involve significant communication overheads and, consequently, defeat the basic purpose of wireless sensor networks. In the present paper, we therefore propose two new distributed algorithms, namely, block diffusion least mean square (BDLMS) and block incremental least mean square (BILMS) by extending the concept of block adaptive filtering techniques to the distributed adaptation scenario. The performance analysis of the proposed BDLMS and BILMS algorithms has been carried out and found to have similar performances to those offered by conventional diffusion LMS and incremental LMS algorithms, respectively. The convergence analyses of the proposed algorithms obtained from the simulation study are also found to be in agreement with the theoretical analysis. The remarkable and interesting aspect of the proposed block-based algorithms is that their communication overheads per node and latencies are less than those of the conventional algorithms by a factor as high as the block size used in the algorithms.
Bayesian Assessment of Newborn Brain Maturity from Two-Channel Sleep Electroencephalograms
Authors: Jakaite Livija , Schetinin Vitaly , Maple Carsten
Published: March 2012

Newborn brain maturity can be assessed by expert analysis of maturity-related patterns recognizable in polysomnograms. Since 36 weeks most of these patterns become recognizable in EEG exclusively, particularly, in EEG recorded via the two central-temporal channels. The use of such EEG recordings enables experts to minimize the disturbance of sleep, preparation time as well as the movement artifacts. We assume that the brain maturity of newborns aged 36 weeks and older can be automatically assessed from the 2-channel sleep EEG as accurately as by expert analysis of the full polysomnographic information. We use Bayesian inference to test this assumption and assist experts to obtain the full probabilistic information on the EEG assessments. The Bayesian methodology is feasibly implemented with Monte Carlo integration over areas of high posterior probability density, however the existing techniques tend to provide biased assessments in the absence of prior information required to explore a model space in detail within a reasonable time. In this paper we aim to use the posterior information about EEG features to reduce possible bias in the assessments. The performance of the proposed method is tested on a set of EEG recordings.
Dental Erosion and Its Growing Importance in Clinical Practice: From Past to Present
Authors: Johansson Ann-Katrin , Omar Ridwaan , Carlsson Gunnar E. , Johansson Anders
Published: March 2012

Since the mid-1990s, the focus of studies on tooth wear has steadily shifted from the general condition towards the more specific area of dental erosion; equally, a shift has occurred from studies in adults to those in children and adolescents. During this time, understanding of the condition has increased greatly. This paper attempts to provide a critical overview of the development of this body of knowledge, from earlier perceptions to the present. It is accepted that dental erosion has a multifactorial background, in which individual and lifestyle factors have great significance. Notwithstanding methodological differences across studies, data from many countries confirm that dental erosion is common in children and young people, and that, when present, it progresses rapidly. That the condition, and its ramifications, warrants serious consideration in clinical dentistry, is clear. It is important for the oral healthcare team to be able to recognize its early signs and symptoms and to understand its pathogenesis. Preventive strategies are essential ingredients in the management of patients with dental erosion. When necessary, treatment aimed at correcting or improving its effects might best be of a minimally invasive nature. Still, there remains a need for further research to forge better understanding of the subject.
A Hardware Efficient Random Number Generator for Nonuniform Distributions with Arbitrary Precision
Authors: de Schryver Christian , Schmidt Daniel , Wehn Norbert , Korn Elke , Marxen Henning , Kostiuk Anton , Korn Ralf
Published: March 2012

Nonuniform random numbers are key for many technical applications, and designing efficient hardware implementations of non-uniform random number generators is a very active research field. However, most state-of-the-art architectures are either tailored to specific distributions or use up a lot of hardware resources. At ReConFig 2010, we have presented a new design that saves up to 48% of area compared to state-of-the-art inversion-based implementation, usable for arbitrary distributions and precision. In this paper, we introduce a more flexible version together with a refined segmentation scheme that allows to further reduce the approximation error significantly. We provide a free software tool allowing users to implement their own distributions easily, and we have tested our random number generator thoroughly by statistic analysis and two application tests.
Oral Tolerance Induced by Transfer of Food Antigens via Breast Milk of Allergic Mothers Prevents Offspring from Developing Allergic Symptoms in a Mouse Food Allergy Model
Authors: Yamamoto Takeshi , Tsubota Yuma , Kodama Toshihisa , Kageyama-Yahara Natsuko , Kadowaki Makoto
Published: March 2012

We examined whether maternal exposure to food antigens during lactation and maternal allergic status would affect the development of food allergy in offspring. OVA-sensitized or OVA-nonsensitized BALB/c female mice were exposed or unexposed to OVA during lactation. After weaning, their offspring were systemically sensitized twice with OVA and repeatedly given OVA by oral intubation. While 97.1% of the mice breastfed by OVA-nonsensitized and OVA-unexposed mothers developed allergic diarrhea, 59.7% of the mice breastfed by OVA-exposed nonallergic mothers during lactation and 24.6% of the mice breastfed by OVA-exposed allergic mothers during lactation developed food allergy. Furthermore, OVA was detected in breast-milk from OVA-exposed nonallergic mothers during lactation (4.6±0.5 μg/mL). In addition, OVA-specific IgG1 titers were markedly increased in breast milk from allergic mothers (OVA-sensitized and OVA-unexposed mother:11.0±0.5, OVA-sensitized and OVA-exposed mother:12.3±0.3). Our results suggest that oral tolerance induced by breast milk-mediated transfer of dietary antigens along with their specific immunoglobulins to offspring leads to antigen-specific protection from food allergy.
On-Farm Management ofVitellaria paradoxaC. F. Gaertn. in Amuria District, Eastern Uganda
Authors: Okiror Paul , Agea Jacob Godfrey , Okia Clement Akais , Okullo John Bosco Lamoris
Published: March 2012

The population of shea butter tree (Vitellaria paradoxaC. F. Gaertn.)—a priority tree with enormous economic and cultural values to the parkland communities in Uganda, is rapidly declining due to rapid human population growth, increasing land fragmentation, and high demand for woodfuel especially charcoal. Reversing this trend will depend on the rural community involvement in the planting, facilitating natural regeneration, and tending of shea trees on farm. As such a survey was conducted in Amuria district, eastern Uganda, to assess local strategies and constraints to on-farm management of shea trees, and document socio-demographic factors influencing the on-farm conservation. About 93% of the households protected naturally regeneratedV. paradoxatrees mainly on farms.V. paradoxawas mostly propagated through coppices and seedlings. Although insecure land tenure, insecurity, pests, disease, and shortage of planting materials were reported as major hindrances, farmsize, family size, and gender significantly (P≤0.05) influenced people’s willingness to conserveV. paradoxa. Byelaws and policies on shea conservation need to be properly enforced, and further propagation research is required especially towards shortening the juvenile period ofV. paradoxaso that more farmers can start propagating the tree other than relying on its natural regeneration.
Consumers' Attitudes towards Edible Wild Plants: A Case Study of Noto Peninsula, Ishikawa Prefecture, Japan
Authors: Chen Bixia , Qiu Zhenmian
Published: March 2012

This study explored the rural revitalizing strategy in FAO's Globally Important Agricultural Heritage System (GIAHS) site in Noto Peninsula, Ishikawa Prefecture of Japan, using a case study of edible wild plants. This study assessed the current and possible future utilization of edible wild plants as one important NTFP by clarifying the attitudes of consumers and exploring the challenges of harvesting edible wild plants. Traditional ecological knowledge associated with edible wild plants and the related attitudes of consumers towards wild plants was documented. A questionnaire survey found that a majority of the respondents held positive attitude towards edible wild plants as being healthy, safe food, part of traditional dietary culture. Increasing demand of edible wild plants from urban residents aroused conflicts with local residents’ interest given that around 86% of the forested hills are private in Noto Region. Non timber forest products (NTFP) extraction can be seen as a tool for creating socioeconomic relationships that are dependent on healthy, biodiverse ecosystems. It was suggested that Japanese Agricultural Cooperatives (JA) and Forestry Cooperatives (FCA) could be involved with GIAHS process. As important traditional dietary and ecological system, edible wild plants should be a part of GIAHS project for rural revitalization.
Endothelial Expression of TNF Receptor-1 Generates a Proapoptotic Signal Inhibited by Integrin α6β1 in Glioblastoma
Authors: Huang Ping , Rani M.R. Sandhya , Ahluwalia Manmeet S. , Bae Eunnyung , Prayson Richard A. , Weil Robert J. , Nowacki Amy S. , Hedayat Hirad , Sloan Andrew E. , Lathia Justin D. , Rich Jeremy N. , Tipps Russell , Gladson Candece L.
Published: March 2012

Activation of TNF receptor 1 (TNF-R1) can generate signals that promote either apoptosis or survival. In this study, we show that these signals can be determined by the character of the extracellular matrix in the tumor microenvironment. Specifically, through studies of glioblastoma, we showed that TNFα stimulation induced apoptosis of primary brain endothelial cells (EC) attached to collagen or fibronectin (which engage integrins α2β1/α3β1 and α5β1, respectively), but did not induce apoptosis of ECs attached to laminin (which engages integrins α6β1 and α3β1). TNF-R1 expression was significantly higher in ECs in glioblastoma (GBM) tumors compared with ECs in normal brain specimens. TNFα was also expressed in GBM tumor-associated ECs, which was associated with longer patient survival. ECs plated on anti-integrin α2 or α3 antibody were susceptible to TNFα-induced apoptosis, whereas those plated on anti-integrin α6 antibody were not. Moreover, the ECs plated on laminin, but not collagen, expressed cellular FLICE inhibitory protein (cFLIP) and TNFα stimulation of laminin-attached cells in which cFLIP had been downregulated resulted in the induction of apoptosis. In contrast, attachment to laminin did not induce cFLIP expression in GBM tumor stem cells. Together, our findings indicate that the laminin receptor integrin α6β1 promotes the survival of brain ECs by inhibiting prodeath signaling by TNF-R1, in part by inducing cFLIP expression. Cancer Res; 72(6); 1428–37. ©2012 AACR.
Estrogen Receptor Alpha Mediates Progestin-Induced Mammary Tumor Growth by Interacting with Progesterone Receptors at the Cyclin D1/MYC Promoters
Authors: Giulianelli Sebastián , Vaqué José P. , Soldati Rocío , Wargon Victoria , Vanzulli Silvia I. , Martins Rubén , Zeitlin Eduardo , Molinolo Alfredo A. , Helguero Luisa A. , Lamb Caroline A. , Gutkind J. Silvio , Lanari Claudia
Published: March 2012

Synthetic progesterone used in contraception drugs (progestins) can promote breast cancer growth, but the mechanisms involved are unknown. Moreover, it remains unclear whether cytoplasmic interactions between the progesterone receptor (PR) and estrogen receptor alpha (ERα) are required for PR activation. In this study, we used a murine progestin-dependent tumor to investigate the role of ERα in progestin-induced tumor cell proliferation. We found that treatment with the progestin medroxyprogesterone acetate (MPA) induced the expression and activation of ERα, as well as rapid nuclear colocalization of activated ERα with PR. Treatment with the pure antiestrogen fulvestrant to block ERα disrupted the interaction of ERα and PR in vitro and induced the regression of MPA-dependent tumor growth in vivo. ERα blockade also prevented an MPA-induced increase in CYCLIN D1 (CCND1) and MYC expression. Chromatin immunoprecipitation studies showed that MPA triggered binding of ERα and PR to the CCND1 and MYC promoters. Interestingly, blockade or RNAi-mediated silencing of ERα inhibited ERα, but not PR binding to both regulatory sequences, indicating that an interaction between ERα and PR at these sites is necessary for MPA-induced gene expression and cell proliferation. We confirmed that nuclear colocalization of both receptors also occurred in human breast cancer samples. Together, our findings argued that ERα–PR association on target gene promoters is essential for progestin-induced cell proliferation. Cancer Res; 72(9); 2416–27. ©2012 AACR.
“OA02” Peptide Facilitates the Precise Targeting of Paclitaxel-Loaded Micellar Nanoparticles to Ovarian Cancer In Vivo
Authors: Xiao Kai , Li Yuanpei , Lee Joyce S. , Gonik Abby M. , Dong Tiffany , Fung Gabriel , Sanchez Eduardo , Xing Li , Cheng Holland R. , Luo Juntao , Lam Kit S.
Published: March 2012

Micellar nanoparticles based on linear polyethylene glycol (PEG) block dendritic cholic acids (CA) copolymers (telodendrimers), for the targeted delivery of chemotherapeutic drugs in the treatment of cancers, are reported. The micellar nanoparticles have been decorated with a high-affinity “OA02” peptide against α-3 integrin receptor to improve the tumor-targeting specificity which is overexpressed on the surface of ovarian cancer cells. “Click chemistry” was used to conjugate alkyne-containing OA02 peptide to the azide group at the distal terminus of the PEG chain in a representative PEG5k-CA8 telodendrimer (micelle-forming unit). The conjugation of OA02 peptide had negligible influence on the physicochemical properties of PEG5k-CA8 nanoparticles and as hypothesized, OA02 peptide dramatically enhanced the uptake efficiency of PEG5k-CA8 nanoparticles (NP) in SKOV-3 and ES-2 ovarian cancer cells via receptor-mediated endocytosis, but not in α-3 integrin-negative K562 leukemia cells. When loaded with paclitaxel, OA02-NPs had significantly higher in vitro cytotoxicity against both SKOV-3 and ES-2 ovarian cancer cells as compared with nontargeted nanoparticles. Furthermore, the in vivo biodistribution study showed OA02 peptide greatly facilitated tumor localization and the intracellular uptake of PEG5k-CA8 nanoparticles into ovarian cancer cells as validated in SKOV3-luc tumor–bearing mice. Finally, paclitaxel (PTX)-loaded OA02-NPs exhibited superior antitumor efficacy and lower systemic toxicity profile in nude mice bearing SKOV-3 tumor xenografts, when compared with equivalent doses of nontargeted PTX-NPs as well as clinical paclitaxel formulation (Taxol). Therefore, OA02-targeted telodendrimers loaded with paclitaxel have great potential as a new therapeutic approach for patients with ovarian cancer. Cancer Res; 72(8); 2100–10. ©2012 AACR.
Risk Prediction Models for Colorectal Cancer: A Review
Authors: Win Aung Ko , MacInnis Robert J. , Hopper John L. , Jenkins Mark A.
Published: March 2012

Risk prediction models are important to identify individuals at high risk of developing the disease who can then be offered individually tailored clinical management, targeted screening and interventions to reduce the burden of disease. They are also useful for research purposes when attempting to identify new risk factors for the disease. In this article, we review the risk prediction models that have been developed for colorectal cancer and appraise their applicability, strengths, and weaknesses. We also discuss the factors to be considered for future development and improvement of models for colorectal cancer risk prediction. We conclude that there is no model that sufficiently covers the known risk factors for colorectal cancer that is suitable for assessment of people from across the full range of risk and that a new comprehensive model is needed. Cancer Epidemiol Biomarkers Prev; 21(3); 398–410. ©2011 AACR.
Common Variation in Nemo-Like Kinase Is Associated with Risk of Ovarian Cancer
Authors: Stevens Kristen N. , Kelemen Linda E. , Wang Xianshu , Fridley Brooke L. , Vierkant Robert A. , Fredericksen Zachary , Armasu Sebastian M. , Tsai Ya-Yu , Berchuck Andrew , Narod Steven A. , Phelan Catherine M. , Sutphen Rebecca , Birrer Michael J. , Schildkraut Joellen M. , Sellers Thomas A. , Goode Ellen L. , Couch Fergus J.
Published: March 2012

Background: Overexpression of mitotic kinases has been associated with prognosis, histologic grade, and clinical stage in ovarian cancer, but the relationship between inherited variation in these genes and ovarian cancer risk has not been well defined.

Methods: We measured associations between 397 single nucleotide polymorphisms (SNPs) from 67 mitotic kinases and invasive epithelial ovarian cancer risk in two case–control studies (n = 671 cases; n = 939 controls). Thirty-six candidate SNPs (P < 0.05) were assessed in a replication analysis consisting of three additional studies (n = 1,094 cases; n = 829 controls).

Results: In initial analysis, thirty-six SNPs were suggestive of association with risk of serous ovarian cancer, all subtypes of ovarian cancer, or both (P < 0.05). Replication analyses suggested an association between rs2125846 in the Nemo-like kinase (NLK) gene and ovarian cancer (serous OR = 1.36, 95% CI: 1.11–1.67, P = 1.77 × 10−3; all subtypes OR = 1.30, 95% CI: 1.08–1.56, P = 2.97 × 10−3). Furthermore, rs2125846 was associated with risk in the combined discovery and replication sets (serous OR = 1.33, 95% CI: 1.15–1.54; all subtypes OR = 1.27, 95% CI: 1.12–1.45).

Conclusions: Variation in NLK may be associated with risk of invasive epithelial ovarian cancer. Further studies are needed to confirm and understand the biologic relationship between this mitotic kinase and ovarian cancer risk.

Impact: An association between SNPs in NLK and ovarian cancer may provide biologic insight into the development of this disease. Cancer Epidemiol Biomarkers Prev; 21(3); 523–8. ©2012 AACR.
Prospective Studies of Body Mass Index with Head and Neck Cancer Incidence and Mortality
Authors: Gaudet Mia M. , Patel Alpa V. , Sun Juzhong , Hildebrand Janet S. , McCullough Marjorie L. , Chen Amy Y. , Gapstur Susan M.
Published: March 2012

Background: Results of a pooled analysis of case–control studies show a higher risk of head and neck cancer (HNC) associated with a low body mass index (BMI) and a lower risk associated with being overweight or obese compared with being normal weight. However, these results are prone to bias due to residual confounding by smoking, a strong risk factor, and possible weight loss prior to diagnosis. Using prospectively collected data from the Cancer Prevention Study-II cohort and the Nutrition cohort, we examined the association of BMI with HNC mortality and incidence, overall and by smoking status.

Methods: Mortality analyses included 1,383 cases among 1,059,153 participants; incidence analyses included 340 cases among 150,262 participants. Multivariable Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CI) for the association of BMI with HNC incidence and mortality.

Results: Overall, compared with the category of BMI 22.5–24.9 kg/m2, the categories of BMI 25.0–29.9 kg/m2 and ≥30.0 kg/m2 were associated with a lower risk of HNC mortality but not incidence. In never smokers, there were no associations of BMI with HNC incidence or mortality. In smokers, BMI < 22.5 kg/m2 was associated with a higher risk of HNC mortality (HR = 1.42, 95% CI, 1.20–1.67).

Conclusions: In this prospective cohort, there was no association between BMI and HNC incidence, although BMI was inversely associated with HNC mortality in smokers.

Impact: These suggest that there is no etiologic relationship between BMI and HNC. Cancer Epidemiol Biomarkers Prev; 21(3); 497–503. ©2012 AACR.
Long-Term Psychosocial Outcomes of BRCA1/BRCA2 Testing: Differences across Affected Status and Risk-Reducing Surgery Choice
Authors: Graves Kristi D. , Vegella Patti , Poggi Elizabeth A. , Peshkin Beth N. , Tong Angie , Isaacs Claudine , Finch Clinton , Kelly Scott , Taylor Kathryn L. , Luta George , Schwartz Marc D.
Published: March 2012

Background: Numerous studies have documented the short-term impact of BRCA1/BRCA2 (BRCA1/2) testing; however, little research has examined the long-term impact of testing. We conducted the first long-term prospective study of psychosocial outcomes in a U.S. sample of women who had BRCA1/2 testing.

Methods: Participants were 464 women who underwent genetic testing for BRCA1/2 mutations. Prior to testing, we measured sociodemographics, clinical variables, and cancer specific and general distress. At long-term follow-up (Median = 5.0 years; Range = 3.4–9.1 years), we assessed cancer-specific and genetic testing distress, perceived stress, and perceived cancer risk. We evaluated the impact of BRCA1/2 test result and risk-reducing surgery on long-term psychosocial outcomes.

Results: Among participants who had been affected with breast or ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β = 0.41, P < 0.0001), uncertainty (β = 0.18, P < 0.0001), and perceived stress (β = 0.17, P = 0.005) compared with women who received negative (i.e., uninformative) results. Among women unaffected with breast/ovarian cancer, BRCA1/2 carriers reported higher genetic testing distress (β = 0.39, P < 0.0001) and lower positive testing experiences (β = 0.25, P = 0.008) than women with negative results. Receipt of risk-reducing surgery was associated with lower perceived cancer risk (P < 0.0001).

Conclusions: In this first prospective long-term study in a U.S. sample, we found modestly increased distress in BRCA1/2 carriers compared with women who received uninformative or negative test results. Despite this modest increase in distress, we found no evidence of clinically significant dysfunction.

Impact: Although a positive BRCA1/2 result remains salient among carriers years after testing, testing does not seem to impact long-term psychologic dysfunction. Cancer Epidemiol Biomarkers Prev; 21(3); 445–55. ©2012 AACR.
Use of Statin Medications and Risk of Esophageal Adenocarcinoma in Persons with Barrett's Esophagus
Authors: Kantor Elizabeth D. , Onstad Lynn , Blount Patricia L. , Reid Brian J. , Vaughan Thomas L.
Published: March 2012

Background: Persons with Barrett's esophagus experience increased incidence of esophageal adenocarcinoma and may benefit from use of preventives. Studies suggest that statin medications may have chemopreventive properties; we therefore assessed the association between statin use and progression to esophageal adenocarcinoma.

Methods: In a prospective cohort of 411 persons with Barrett's, Cox regression was used to calculate HRs for nonsteroidal anti-inflammatory drug (NSAID) and statin use accounting for variation in use during follow-up and adjusting for age, sex, and smoking.

Results: The HRs for statin use among all participants were 0.59 [95% confidence interval (CI), 0.26–1.33] and 0.68 (95% CI, 0.30–1.54) before and after further adjustment for NSAID use, respectively. Among persons with high-grade dysplasia, the HRs for statin use were 0.31 (95% CI, 0.11–0.86) and 0.41 (95% CI, 0.13–1.26) before and after adding NSAIDs to the model, respectively.

Conclusions: While the reduced risk of esophageal adenocarcinoma observed among statin users may be explained by chance, the point estimates are similar in magnitude to those previously reported for NSAID use in this cohort and are unlikely to be confounded by known risk factors.

Impact: Further study in larger cohorts and meta-analyses of the potential for statins to reduce risk of esophageal adenocarcinoma is warranted. Cancer Epidemiol Biomarkers Prev; 21(3); 456–61. ©2012 AACR.
Common Genetic Variants in Prostate Cancer Risk Prediction—Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)
Authors: Lindström Sara , Schumacher Fredrick R. , Cox David , Travis Ruth C. , Albanes Demetrius , Allen Naomi E. , Andriole Gerald , Berndt Sonja I. , Boeing Heiner , Bueno-de-Mesquita H. Bas , Crawford E. David , Diver W. Ryan , Gaziano J. Michael , Giles Graham G. , Giovannucci Edward , Gonzalez Carlos A. , Henderson Brian , Hunter David J. , Johansson Mattias , Kolonel Laurence N. , Ma Jing , Le Marchand Loïc , Pala Valeria , Stampfer Meir , Stram Daniel O. , Thun Michael J. , Tjonneland Anne , Trichopoulos Dimitrios , Virtamo Jarmo , Weinstein Stephanie J. , Willett Walter C. , Yeager Meredith , Hayes Richard B. , Severi Gianluca , Haiman Christopher A. , Chanock Stephen J. , Kraft Peter
Published: March 2012

Background: One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent single-nucleotide polymorphism markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer, and age.

Methods: We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data.

Results: The best risk model (C-statistic = 0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P = 0.009), with highest accuracy in men younger than 60 years (C-statistic = 0.679). The absolute ten-year risk for 50-year-old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile).

Conclusions: Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from prostate-specific antigen screening.

Impact: Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited. Cancer Epidemiol Biomarkers Prev; 21(3); 437–44. ©2012 AACR.