bluuebunny/crossref_metadata_2025 huggingface dataset:
The unfolded protein response in relation to mitochondrial biogenesis in skeletal muscle cells
Authors: Mesbah Moosavi Zahra S. , Hood David A.
Published: March 2017

Mitochondria comprise both nuclear and mitochondrially encoded proteins requiring precise stoichiometry for their integration into functional complexes. The augmented protein synthesis associated with mitochondrial biogenesis results in the accumulation of unfolded proteins, thus triggering cellular stress. As such, the unfolded protein responses emanating from the endoplasmic reticulum (UPRER) or the mitochondrion (UPRMT) are triggered to ensure correct protein handling. Whether this response is necessary for mitochondrial adaptations is unknown. Two models of mitochondrial biogenesis were used: muscle differentiation and chronic contractile activity (CCA) in murine muscle cells. After 4 days of differentiation, our findings depict selective activation of the UPRMT in which chaperones decreased; however, Sirt3 and UPRER markers were elevated. To delineate the role of ER stress in mitochondrial adaptations, the ER stress inhibitor TUDCA was administered. Surprisingly, mitochondrial markers COX-I, COX-IV, and PGC-1α protein levels were augmented up to 1.5-fold above that of vehicle-treated cells. Similar results were obtained in myotubes undergoing CCA, in which biogenesis was enhanced by ~2–3-fold, along with elevated UPRMT markers Sirt3 and CPN10. To verify whether the findings were attributable to the terminal UPRER branch directed by the transcription factor CHOP, cells were transfected with CHOP siRNA. Basally, COX-I levels increased (~20%) and COX-IV decreased (~30%), suggesting that CHOP influences mitochondrial composition. This effect was fully restored by CCA. Therefore, our results suggest that mitochondrial biogenesis is independent of the terminal UPRER. Under basal conditions, CHOP is required for the maintenance of mitochondrial composition, but not for differentiation- or CCA-induced mitochondrial biogenesis.
Membrane lipid rafts are disturbed in the response of rat skeletal muscle to short-term disuse
Authors: Petrov Alexey M. , Kravtsova Violetta V. , Matchkov Vladimir V. , Vasiliev Alexander N. , Zefirov Andrey L. , Chibalin Alexander V. , Heiny Judith A. , Krivoi Igor I.
Published: March 2017

Marked loss of skeletal muscle mass occurs under various conditions of disuse, but the molecular and cellular mechanisms leading to atrophy are not completely understood. We investigate early molecular events that might play a role in skeletal muscle remodeling during mechanical unloading (disuse). The effects of acute (6–12 h) hindlimb suspension on the soleus muscles from adult rats were examined. The integrity of plasma membrane lipid rafts was tested utilizing cholera toxin B subunit or fluorescent sterols. In addition, resting intracellular Ca2+ level was analyzed. Acute disuse disturbed the plasma membrane lipid-ordered phase throughout the sarcolemma and was more pronounced in junctional membrane regions. Ouabain (1 µM), which specifically inhibits the Na-K-ATPase α2 isozyme in rodent skeletal muscles, produced similar lipid raft changes in control muscles but was ineffective in suspended muscles, which showed an initial loss of α2 Na-K-ATPase activity. Lipid rafts were able to recover with cholesterol supplementation, suggesting that disturbance results from cholesterol loss. Repetitive nerve stimulation also restores lipid rafts, specifically in the junctional sarcolemma region. Disuse locally lowered the resting intracellular Ca2+ concentration only near the neuromuscular junction of muscle fibers. Our results provide evidence to suggest that the ordering of lipid rafts strongly depends on motor nerve input and may involve interactions with the α2 Na-K-ATPase. Lipid raft disturbance, accompanied by intracellular Ca2+ dysregulation, is among the earliest remodeling events induced by skeletal muscle disuse.
MicroRNA-29a mediates the impairment of intestinal epithelial integrity induced by intrauterine growth restriction in pig
Authors: Zhu Yuhua , Wang Wei , Yuan Taolin , Fu Liangliang , Zhou Lian , Lin Gang , Zhao Shuhong , Zhou Huaijun , Wu Guoyao , Wang Junjun
Published: March 2017

An important characteristic of intrauterine growth restricted (IUGR) neonate is the impaired intestinal barrier function. With the use of a pig model, this study was conducted to identify the responsible microRNA (miRNA) for the intestinal damage in IUGR neonates through comparing the miRNA profile of IUGR and normal porcine neonates and to investigate the regulation mechanism. Compared with the normal ones, we identified 83 upregulated and 76 downregulated miRNAs in the jejunum of IUGR pigs. Notably, IUGR is associated with profoundly increasesd miR-29 family and decreased expression of extracellular matrix (ECM) and tight junction (TJ) proteins in the jejunum. Furthermore, in vitro study using theporcine intestinal epithelial cell line (IPEC-1) showed that inhibition of miR-29a expression could improve the monolayer integrity by increasing cell proliferation and transepithelial resistance. Also, overexpression/inhibition of miR-29a in IPEC-1 cells can suppress/increase the expression of integrin-β1, collagen I, collagen IV, fibronectin, and claudin 1, both at transcriptional and translational levels. Subsequent luciferase reporter assay confirmed a direct interaction between miR-29a and the 3′-untranslated regions of these genes. In conclusion, this study reveals that IUGR-impaired intestinal barrier function is associated with downregulated ECM and TJ protein expression mediated by the upregulation of miR-29a.

NEW & NOTEWORTHY Intrauterine growth restricted (IUGR) remains a major problem for both human health and animal production due to its association with high rates of preweaning morbidity and mortality. We have identified the abnormal expression of microRNA-29a (miR-29a) in the small intestine of IUGR neonates, as well as its targets and mechanisms. These results provide new information about biological characteristics of IUGR-affected intestinal dysfunction and can lead to the development of potentially solution for preventing and treating IUGR in the future.
Emerging tools to study enteric neuromuscular function
Authors: Gulbransen Brian D.
Published: March 2017

Investigating enteric neuromuscular function poses specific challenges that are not encountered in other systems. The gut has a complex cellular composition, and methods to study diverse multicellular interactions during physiological gut functions have been limited. However, new technologies are emerging in optics, genetics, and bioengineering that greatly expand the capabilities to study integrative functions in the gut. In this mini-review, I discuss several areas where the application of these technologies could benefit ongoing efforts to understand enteric neuromuscular function. I specifically focus on technologies that can be applied to study specific cellular networks and the mechanisms that link activity to function.
Hydrogen sulfide improves intestinal recovery following ischemia by endothelial nitric oxide-dependent mechanisms
Authors: Jensen Amanda R. , Drucker Natalie A. , Khaneki Sina , Ferkowicz Michael J. , Markel Troy A.
Published: March 2017

Hydrogen sulfide (H2S) is an endogenous gasotransmitter that has vasodilatory properties. It may be a novel therapy for intestinal ischemia-reperfusion (I/R) injury. We hypothesized that 1) H2S would improve postischemic survival, mesenteric perfusion, mucosal injury, and inflammation compared with vehicle and 2) the benefits of H2S would be mediated through endothelial nitric oxide. C57BL/6J wild-type and endothelial nitric oxide synthase knockout (eNOS KO) mice were anesthetized, and a midline laparotomy was performed. Intestines were eviscerated, the small bowel mesenteric root identified, and baseline intestinal perfusion was determined using laser Doppler. Intestinal ischemia was established by temporarily occluding the superior mesenteric artery. Following ischemia, the clamp was removed, and the intestines were allowed to recover. Either sodium hydrosulfide (2 nmol/kg or 2 µmol/kg NaHS) in PBS vehicle or vehicle only was injected into the peritoneum. Animals were allowed to recover and were assessed for mesenteric perfusion, mucosal injury, and intestinal cytokines. P values < 0.05 were significant. H2S improved mesenteric perfusion and mucosal injury scores following I/R injury. However, in the setting of eNOS ablation, there was no improvement in these parameters with H2S therapy. Application of H2S also resulted in lower levels of intestinal cytokine production following I/R. Intraperitoneal H2S therapy can improve mesenteric perfusion, intestinal mucosal injury, and intestinal inflammation following I/R. The benefits of H2S appear to be mediated through endothelial nitric oxide-dependent pathways.

NEW & NOTEWORTHY H2S is a gaseous mediator that acts as an anti-inflammatory agent contributing to gastrointestinal mucosal defense. It promotes vascular dilation, mucosal repair, and resolution of inflammation following intestinal ischemia and may be exploited as a novel therapeutic agent. It is unclear whether H2S works through nitric oxide-dependent pathways in the intestine. We appreciate that H2S was able to improve postischemic recovery of mesenteric perfusion, mucosal integrity, and inflammation. The beneficial effects of H2S appear to be mediated through endothelial nitric oxide-dependent pathways.
Brain-Machine Interfaces: From Basic Science to Neuroprostheses and Neurorehabilitation
Authors: Lebedev Mikhail A. , Nicolelis Miguel A. L.
Published: March 2017

Brain-machine interfaces (BMIs) combine methods, approaches, and concepts derived from neurophysiology, computer science, and engineering in an effort to establish real-time bidirectional links between living brains and artificial actuators. Although theoretical propositions and some proof of concept experiments on directly linking the brains with machines date back to the early 1960s, BMI research only took off in earnest at the end of the 1990s, when this approach became intimately linked to new neurophysiological methods for sampling large-scale brain activity. The classic goals of BMIs are 1) to unveil and utilize principles of operation and plastic properties of the distributed and dynamic circuits of the brain and 2) to create new therapies to restore mobility and sensations to severely disabled patients. Over the past decade, a wide range of BMI applications have emerged, which considerably expanded these original goals. BMI studies have shown neural control over the movements of robotic and virtual actuators that enact both upper and lower limb functions. Furthermore, BMIs have also incorporated ways to deliver sensory feedback, generated from external actuators, back to the brain. BMI research has been at the forefront of many neurophysiological discoveries, including the demonstration that, through continuous use, artificial tools can be assimilated by the primate brain's body schema. Work on BMIs has also led to the introduction of novel neurorehabilitation strategies. As a result of these efforts, long-term continuous BMI use has been recently implicated with the induction of partial neurological recovery in spinal cord injury patients.
Electrochemical Deposition of Zinc Oxide on the Surface of Composite Membrane Polysulfone-Graphene-Polystyrene in the Presence of Water Soluble Polymers
Authors: Mocanu Alexandra , Rusen Edina , Diacon Aurel , Damian Celina , Dinescu Adrian , Suchea Mirela
Published: March 2017

The aim of this study consisted in the development of an alternative synthesis procedure for hybrid ultrafiltration membranes for water purification. The membranes were obtained by wet-phase inversion method based on aliquots of polysulfone (PSF) and graphene nanoplatelets modified with poly(styrene) (G-PST). The hybrid materials were modified by electrochemical deposition of zinc oxide (ZnO) on one side of the membranes in the presence of water soluble polymers. Raman, XPS, and TGA analyses were used to characterize the chemical and thermal characteristics of the PST-G. SEM analysis showed the formation of asymmetric porous configuration in all cases and the generation of ZnO with different shapes/structures on the bottom surface of the membrane or inside the porous channels. EDS analysis confirmed the formation of ZnO.
QoI-Aware DODAG Construction in RPL-Based Event Detection Wireless Sensor Networks
Authors: Tian Hongliang , Qian Zhihong , Wang Xue , Liang Xiao
Published: March 2017

LLNs are gradually attracting people’s attention for the feature of low energy consumption. RPL is specifically designed for LLNs to construct a high energy efficiency network topology. In the noisy environment, the packet loss rate of RPL-based WSN increases during data transmission. The DODAG constructed by RPL-based WSN increases in depth when communication is affected by noise. In this situation the data transmission in the network will consume more energy. In event detection WSNs, the appropriate network topology enables root to use less sensor data to fuse enough information to determine whether or not an event has occurred. In this paper, we will improve RPL in two ways to optimize topology and reduce energy consumption.(1)The neighbor list and the information of DIO sender’s parent of a node are used to construct a better DODAG in the noisy environment.(2)SPRT and the quality of information of the data are used in the event detecting process for saving energy consumption. Simulation results show that, compared with the original RPL, QoI-aware RPL can reduce the energy consumption by collecting the same quality of information with less data transmission.
Synthesis of Analcime Crystals and Simultaneous Potassium Extraction from Natrolite Syenite
Authors: Chen Jian , Ma Hongwen , Liu Changjiang , Yuan Jiangyan
Published: March 2017

Analcime single crystals were successfully synthesized from natrolite syenite powder (K2O 10.89%) and 92.6% of potassium was extracted simultaneously by means of soda roasting followed by alkali-hydrothermal method. Effects of NaOH concentration, reaction temperature, and holding period on the analcime formation and potassium extraction were investigated systemically. The results indicated that NaOH concentration plays an important role in determining the chemical composition of zeolites and size distribution; by turning the NaOH concentrations, three different pure zeolites (i.e., the phillipsite-Na, the analcime, and the sodalite) were prepared. Besides, a higher temperature could accelerate the dissolution of K+ions and enhance the crystallinity degree of zeolite. The reactions involved in the analcime synthesis can be summarized as follows: sodium aluminum silicate dissolution→precipitation and dissolution of metastable zeolite-P→analcime nucleation→analcime growth. The extraction ratio of K+is associated with the types of synthesized zeolites, among which analcime is the most effective to promote potassium leaching out from zeolite lattice position. The optimal condition for analcime crystallization and K+leaching is found to be as follows: 175°C for 4 h in 0.5 mol/L NaOH solution.
Optimal Zn-Modified Ca–Si-Based Ceramic Nanocoating with Zn Ion Release for Osteoblast Promotion and Osteoclast Inhibition in Bone Tissue Engineering
Authors: Yu Jiangming , Xu Lizhang , Xie Ning , Li Kai , Xi Yanhai , Liu Xiling , Zheng Xuebin , Chen Xiongsheng , Ye Xiaojian , Wei Daixu
Published: March 2017

We investigated the slow release of Zn ion (Zn2+) from nanocoatings and compared the in vitro response of osteoblasts (MC3T3-E1) and proosteoclasts (RAW 264.7) cultured on Ca2ZnSi2O7 nanocoated with different Zn/Ca molar ratios on a Ti-6Al-4V (i.e., Ti) substrate to optimize cell behaviors and molecule levels. Significant morphology differences were observed among samples. By comparing with pure Ti and CaSiO3 nanocoating, the morphology of Ca2ZnSi2O7 ceramic nanocoatings was rough and contained small nanoparticles or aggregations. Slow Zn2+ release from nanocoatings was observed and Zn2+ concentration was regulated by varying the Zn/Ca ratios. The cell-response results showed Ca2ZnSi2O7 nanocoating at different Zn/Ca molar ratios for osteoblasts and osteoclasts. Compared to other nanocoatings and Ti, sample Zn/Ca (0.3) showed the highest cell viability and upregulated expression of the osteogenic differentiation genes ALP, COL-1, and OCN. Additionally, sample Zn/Ca (0.3) showed the greatest inhibition of RAW 264.7 cell growth and decreased the mRNA levels of osteoclast-related genes OAR, TRAP, and HYA1. Therefore, the optimal Zn-Ca ratio of 0.3 in Ca2ZnSi2O7 ceramic nanocoating on Ti had a dual osteoblast-promoting and osteoclast-inhibiting effect to dynamically balance osteoblasts/osteoclasts. These optimal Zn-Ca ratios are valuable for Ca2ZnSi2O7 ceramic nanocoating on Ti-coated implants for potential applications in bone tissue regeneration.
The Correlation of CD206, CD209, and Disease Severity in Behçet’s Disease with Arthritis
Authors: Choi Bunsoon , Suh Chang-Hee , Kim Hyoun-Ah , Sayeed Hasan M. , Sohn Seonghyang
Published: March 2017

The purpose of this study was to clarify the role of pattern recognition receptors in Behçet’s disease (BD). The frequencies of several pattern recognition receptors (CD11b, CD11c, CD32, CD206, CD209, and dectin-1) were analyzed in patients with BD by flow cytometry, and cytokine levels, interleukin- (IL-) 18, IL-23, and IL-17A, were compared in plasma. The analysis was performed in active (n=13) and inactive (n=13) stages of BD patients. Rheumatoid arthritis patients (n=19), as a disease control, and healthy control (HC) (n=19) were enrolled. The frequencies of CD11b+ and CD32+ cells were significantly increased in active BD patients compared to HC. Disease severity score was correlated to CD11c+, CD206+, and CD209+ in whole leukocytes and CD11b+, CD11c+, CD206+, CD209+, and Dectin-1+ in granulocytes. The plasma levels of IL-17A were significantly different between HC and active BD. IL-18 showed significant difference between active and inactive BD patients. From this study, we concluded the expressions of several pattern recognition receptors were correlated to the joint symptoms of BD.
Dynamic Interferometry Lithography on a TiO2Photoresist Sol-Gel for Diffracting Deflector Module
Authors: Gâté V. , Berthod L. , Langlet M. , Vocanson F. , Verrier I. , Veillas C. , Kaminski A. , Parriaux O. , Jourlin Y.
Published: March 2017

Solar electricity is one of the most promising renewable energy resources. However, the ratio module’s cost/energy produced remains a major issue for classical photovoltaic energy. Many technologies have been developed to solve this problem, by using micro- or nanostructuring on the solar cell or on the module. These kinds of structuring are often used as antireflection and light-trapping tools. In the meantime, other solar technologies are considered, such as concentration photovoltaic modules. This article presents a module combining both approaches, that is, nanostructures and concentration, in order to increase the module’s profitability. Sol-gel derived TiO2diffraction gratings, made by dynamic interferometric lithography, are added on the top of the glass cover to deflect unused light onto the solar cell, increasing the module efficiency.
Investigation of the Effects of Anisotropic Flow of Pore Water and Multilayered Soils on Three-Dimensional Consolidation Characteristics
Authors: Laskar Arpan , Pal Sujit Kumar
Published: March 2017

Many practical engineering problems are seriously different from the assumptions which are considered for one-dimensional consolidation test and need to concentrate on three-dimensional consolidation of soil under different boundary conditions. In this study three-dimensional consolidation tests are performed with four different anisotropic flow conditions of pore water and fifteen different combinations of horizontal layered soils. Twelve different three-dimensional consolidation tests are also performed with different soils, surrounded by anisotropic vertical soil layers on two opposite sides. From these studies, it is observed that the anisotropic flow of pore water does not have any effect on initial and final surface settlement of soil but has a significant effect during the consolidation process. The anisotropic flow of pore water during the consolidation process has an immense effect on the coefficient of consolidation. Horizontal layered soil has a great effect on both surface settlement and the rate of settlement. Vertical soil layers on two opposite sides of consolidative soil have an immense effect on the horizontal movements of consolidating soil, finally affecting the resultant vertical settlement of soil. Vertical anisotropic surrounding soil layers also have an effect on the rate of consolidation settlement.
Effect of a 12-Week Summer Break on School Day Physical Activity and Health-Related Fitness in Low-Income Children from CSPAP Schools
Authors: Fu You , Brusseau Timothy A. , Hannon James C. , Burns Ryan D.
Published: March 2017

Background. The purpose of this study was to examine the effect of a 12-week summer break on school day physical activity and health-related fitness (HRF) in children from schools receiving a Comprehensive School Physical Activity Program (CSPAP). Methods. Participants were school-aged children (N=1,232; 624 girls and 608 boys; mean age=9.5±1.8 years) recruited from three low-income schools receiving a CSPAP. Physical activity and HRF levels were collected during the end of spring semester 2015 and again during the beginning of fall semester 2015. Physical activity was assessed using the Yamax DigiWalker CW600 pedometer. HRF measures consisted of body mass index (BMI) and the Progressive Aerobic Cardiovascular Endurance Run (PACER). Results. Results from a doubly MANCOVA analysis indicated that pedometer step counts decreased from 4,929 steps in the spring to 4,445 steps in the fall (mean difference = 484 steps; P<0.001; Cohen’s d = 0.30) and PACER laps decreased from 31.2 laps in the spring to 25.8 laps in the fall (mean difference = 5.4 laps; P<0.001; Cohen’s d = 0.33). Conclusions. Children from schools receiving a CSPAP intervention had lower levels of school day physical activity and cardiorespiratory endurance following a 12-week summer break.
Clinical Trial Characteristics and Barriers to Participant Accrual: The MD Anderson Cancer Center Experience over 30 years, a Historical Foundation for Trial Improvement
Authors: Tang Chad , Sherman Steven I. , Price Mellanie , Weng Jun , Davis Suzanne E. , Hong David S. , Yao James C. , Buzdar Aman , Wilding George , Lee J. Jack
Published: March 2017

Purpose: Slow-accruing clinical trials delay the translation of basic biomedical research, contribute to increasing health care costs, and may prohibit trials from reaching their original goals.

Experimental Design: We analyzed a prospectively maintained institutional database that tracks all clinical studies at the MD Anderson Cancer Center (Houston, TX). Inclusion criteria were activated phase I–III trials, maximum projected accrual ≥10 participants, and activation prior to March 25, 2011. The primary outcome was slow accrual, defined as <2 participants per year. Correlations of trial characteristics with slow accrual were assessed with logistic regression.

Results: A total of 4,269 clinical trials met inclusion criteria. Trials were activated between January 5, 1981, and March 25, 2011, with a total of 145,214 participants enrolled. Median total enrolment was 16 [interquartile range (IQR), 5–34], with an average enrolment rate of 8.7 participants per year (IQR, 3.3–17.7). There were 755 (18%) trials classified as slow accruing. On multivariable analysis, slow accrual exhibited robust associations with national cooperative group trials (OR = 4.16, P < 0.0001 vs. industry sponsored), time from trial activation to first enrolment (OR = 1.13 per month, P < 0.0001), and maximum targeted accrual (OR = 0.16 per log10 increase, P < 0.0001). Recursive partitioning analysis identified trials requiring more than 70 days (2.3 months) between activation and first participant enrolment as having higher odds of slow accrual (23% vs. 5%, OR = 5.56, P < 0.0001).

Conclusions: We identified factors associated with slow trial accrual. Given the lack of data on clinical trials at the institutional level, these data will help build a foundation from which targeted initiatives may be developed to improve the clinical trial enterprise. Clin Cancer Res; 23(6); 1414–21. ©2017 AACR.
Calcium Sensor, NCS-1, Promotes Tumor Aggressiveness and Predicts Patient Survival
Authors: Moore Lauren M. , England Allison , Ehrlich Barbara E. , Rimm David L.
Published: March 2017

Neuronal Calcium Sensor 1 (NCS-1) is a multi-functional Ca2+-binding protein that affects a range of cellular processes beyond those related to neurons. Functional characterization of NCS-1 in neuronal model systems suggests that NCS-1 may influence oncogenic processes. To this end, the biological role of NCS-1 was investigated by altering its endogenous expression in MCF-7 and MB-231 breast cancer cells. Overexpression of NCS-1 resulted in a more aggressive tumor phenotype demonstrated by a marked increase in invasion and motility, and a decrease in cell-matrix adhesion to collagen IV. Overexpression of NCS-1 was also shown to increase the efficacy of paclitaxel-induced cell death in a manner that was independent of cellular proliferation. To determine the association between NCS-1 and clinical outcome, NCS-1 expression was measured in two independent breast cancer cohorts by the Automated Quantitative Analysis method of quantitative immunofluorescence. Elevated levels of NCS-1 were significantly correlated with shorter survival rates. Furthermore, multivariate analysis demonstrated that NCS-1 status was prognostic, independent of estrogen receptor, progesterone receptor, HER2, and lymph node status. These findings indicate that NCS-1 plays a role in the aggressive behavior of a subset of breast cancers and has therapeutic or biomarker potential.

Implications: NCS-1, a calcium-binding protein, is associated with clinicopathologic features of aggressiveness in breast cancer cells and worse outcome in two breast cancer patient cohorts. Mol Cancer Res; 15(7); 942–52. ©2017 AACR.
Crown-like Structures in Breast Adipose Tissue from Normal Weight Women: Important Impact
Authors: Berger Nathan A.
Published: March 2017

Crown-like structures (CLS), composed of macrophages surrounding dead or dying adipocytes, are a histologic hallmark of the proinflammatory process by which adipose tissue contributes to the increased risk and worse prognosis of breast cancer in obese, postmenopausal patients. In this issue of Cancer Prevention Research, Iyengar and colleagues report the intriguing finding that CLS can be identified in a significant proportion of normal-BMI women undergoing mastectomy for breast cancer risk reduction or therapy. This surprising observation suggests that some normal weight women may have similar mechanisms driving initiation and/or progression of breast cancer as those contributing to the increased incidence and worse prognosis of breast cancer in obese postmenopausal women. The possibility of a common mechanism in both lean and obese women provides added impetus to more fully define this process and evaluate its important implications for prevention and screening strategies as well as therapeutic interventions. Cancer Prev Res; 10(4); 223–5. ©2017 AACR.

See related article by Iyengar et al., p. 235–43.
Standardization of an in vitro Model for Evaluating the Bioavailability of Topically Applied Compounds on Damaged Skin: Application to Sunscreen Analysis
Authors: Jacques-Jamin Carine , Jeanjean-Miquel Corinne , Domergue Anaïs , Bessou-Touya Sandrine , Duplan Hélène
Published: March 2017

Background: Information is lacking on the dermal penetration of topically applied formulations on in vitro skin models, under conditions where the stratum corneum (SC) is damaged. Therefore, we have developed a standardized in vitro barrier-disrupted skin model using tape stripping. Methods: Different tape stripping conditions were evaluated using histology, transepidermal water loss, infrared densitometry, and caffeine absorption. Results: The effects of tape stripping were comparable using pig and human skin. Optimized conditions were used to test the effect of SC damage and UV irradiation on the absorption of an UV filter combination present in a sunscreen. The bioavailability of the filters was extremely low regardless of the extent of skin damage, suggesting bioavailability would not be increased if the consumer applied the sunscreen to sun-damaged skin. Conclusion: This standardized in vitro methodology using pig or human skin for damaged skin will add valuable information for the safety assessment of topically applied products.
Accuracy of Middle Cerebral Artery Doppler Assessment between 34 and 37 Weeks in Fetuses with Red Cell Alloimmunization
Authors: Maisonneuve Emeline , Jayot Aude , Friszer Stéphanie , Castaigne Vanina , Cynober Evelyne , Pernot Françoise , Mailloux Agnès , Jouannic Jean-Marie , Cortey Anne , Carbonne Bruno
Published: March 2017

Background: The Doppler measurement of middle cerebral artery peak systolic velocity (MCA-PSV) is considered the gold standard for the noninvasive detection of moderate to severe anemia. However, the accuracy of this test has not been evaluated so far, specifically beyond 34 weeks. Objectives: To assess the accuracy of MCA-PSV to detect moderate to severe fetal anemia and to identify risk factors associated with false-positive and false-negative MCA-PSV values after 34 weeks. Study Design: We studied a retrospective cohort of 150 pregnant women with severe alloimmunization who delivered between 2010 and 2014 and correlated MCA-PSV and fetal or neonatal hemoglobin levels. Results: Sensitivity to predict severe anemia was 69%, with a false-negative rate of 3.6%. When MCA Doppler assessment was normal, the identification of serosal effusions increased the detection rate of severe fetal anemia to 94%, with a false-negative rate of 0.8%. False-positive MCA-PSV measurements were more frequent in fetuses with 1 previous intrauterine transfusion (p = 0.0002), but were not associated with MCA resistance index, intrauterine growth restriction and fetal heart rate. Conclusions: Between 34 and 37 weeks, sensitivity of MCA-PSV Doppler assessment alone is 69% and increases to 94% when also considering signs of hydrops. False-positive MCA-PSV measurements are more frequent in case of former fetal transfusion.
Recurrence and Risk Factors for Relapse in Patients with Non-Small Cell Lung Cancer Treated by Surgery with Curative Intent
Authors: Cruz Cristiana , Afonso Margarida , Oliveiros Bárbara , Pêgo Alice
Published: March 2017

Introduction: Surgery remains the potentially curative treatment for early-stage non-small cell lung cancer (NSCLC). Despite this, tumor recurrence is the most common cause of treatment failure after surgery. Methods: Data were collected retrospectively from clinical files of patients who underwent lung surgery for NSCLC from January 2008 to December 2012 in a University Hospital. Demographic data, tumor characteristics, type of surgery and recurrence were recorded. A comparison of the distribution of variables using adjustment tests was made. Results: The study included 102 patients, 68.6% were male with a mean age of 63.7 ± 9.3 years old. The majority of tumors had a peripheral location (72.5%) and consisted of adenocarcinomas (61.8%). The most frequently performed surgery was lobectomy. Recurrence was noted in 43.1% of cases. Mean disease-free survival was 57.9 ± 3.8 months. Multifactorial analyses showed that stage IIIA, tumor located in other lobes than the right lower lobe and pleural invasion were independent predictors of recurrence. Conclusion: Our recurrence rate was similar to those in the international literature. As in other studies, we found a positive relation between the lymphatic permeation and pleural invasion and the risk of lung cancer recurrence. We consider that some characteristics of the tumor should be assessed to define alternative modalities of treatment and follow-up in order to predict and rapidly recognize the recurrence.
Chromosome Painting in Callicebus nigrifrons Provides Insights into the Genome Evolution of Titi Monkeys and the Ancestral Callicebinae Karyotype
Authors: Pereira Araújo Naiara , Alves do Espírito Santo Alice , do Socorro Pereira Valéria , Stanyon Roscoe , Svartman Marta
Published: March 2017

We studied the chromosomes of Callicebus nigrifrons with conventional and molecular cytogenetic methods. Our chromosome painting analysis in C. nigrifrons together with previous reports allowed us to hypothesize an ancestral Callicebinae karyotype with 2n = 48. The associations of human chromosomes (HSA) 2/22, 7/15, 10/11, and the inverted HSA2/16 would link Callicebus, Cheracebus, and Plecturocebus and would thus be present in the ancestral Callicebinae karyotype. Four fusions (HSA1b/1c, 3c/8b, 13/20, and 14/15/3/21) and 1 fission (HSA2/22) are synapomorphies of Callicebus. The associations HSA3/15 and HSA3/9 are chromosome features linking Callicebus and Cheracebus, whereas the association HSA13/17 would represent a link between Callicebus and the moloch group (Plecturocebus). Only 6 of the 33 recognized titi monkey species have now been painted with human chromosome-specific probes. Further analyses are needed to clarify the phylogenomic relationships in this species-rich group.
Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator
Authors: Shi Chongjun , Zhang Nini , Feng Yang , Cao Jiewei , Chen Xuyi , Liu Bin
Published: March 2017

Background/Aims: Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Methods: Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB) kinase-β (IKK-β) phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation. Results: We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9) and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1) activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB) activation, inhibitor of κB (IκB)-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK)- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells. Conclusion: The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of metastatic prostate cancer.
Autocrine VEGF and IL-8 Promote Migration via Src/Vav2/Rac1/PAK1 Signaling in Human Umbilical Vein Endothelial Cells
Authors: Ju Li , Zhou Zhiwen , Jiang Bo , Lou Yue , Guo Xirong
Published: March 2017

Background/Aims: Pro-angiogenic factors VEGF and IL-8 play a major role in modulating the migratory potential of endothelial cells. The goal of this study was to investigate the effect of autocrine VEGF and IL-8 in the form of self-conditioned medium (CM) on human umbilical vein endothelial cells (HUVECs). Methods: Enzyme-linked immunosorbent assay (ELISA) examined the automatic secretion of VEGF and IL-8 protein by HUVECs. Western blot, small interfering RNA (siRNA), pulldown and Transwell assays were used to explore the role and the mechanism of autocrine VEGF and IL-8 in migration of HUVECs. Results: Neutralizing VEGF and IL-8 in CM significantly abrogated CM-induced migration of HUVECs. Autocrine VEGF and IL-8 increased Src phosphorylation, Rac1 activity and PAK1 phosphorylation in a time dependent manner. Additionally, blocking Rac1 activity with Rac1 siRNA largely abolished autocrine VEGF and IL-8-induced cell migration. Vav2 siRNA suppressed autocrine VEGF and IL-8-induced Rac1 activation and cell migration. Furthermore, blocking Src signaling with PP2, a specific inhibitor for Src, markedly prevented autocrine VEGF and IL-8-induced Vav2 and Rac1 activation as well as consequently cell migration. PAK1 siRNA also significantly abolished autocrine VEGF and IL-8-induced cell migration. Conclusions: We demonstrated for the first time that autocrine VEGF and IL-8 promoted endothelial cell migration via the Src/Vav2/Rac1/PAK1 signaling pathway. This finding reveals the molecular mechanism in the increase of endothelial cell migration induced by autocrine growth factors and cytokines, which is expected to provide a novel therapeutic target in vascular diseases.
Patient values and preferences for antithrombotic therapy in atrial fibrillation
Authors: Loewen Peter S. , Ji Angela Tianshu , Kapanen Anita , McClean Alison
Published: March 2017

Guidelines recommend that patients’ values and preferences should be considered when selecting stroke prevention therapy for atrial fibrillation (SPAF). However, doing so is difficult, and tools to assist clinicians are sparse. We performed a narrative systematic review to provide clinicians with insights into the values and preferences of AF patients for SPAF antithrombotic therapy. Narrative systematic review of published literature from database inception. Research questions: 1) What are patients’ AF and SPAF therapy values and preferences? 2) How are SPAF therapy values and preferences affected by patient factors? 3) How does conveying risk information affect SPAF therapy preferences? and 4) What is known about patient values and preferences regarding novel oral anticoagulants (NOACs) for SPAF? Twenty-five studies were included. Overall study quality was moderate. Severe stroke was associated with the greatest disutility among AF outcomes and most patients value the stroke prevention efficacy of therapy more than other attributes. Utilities, values, and preferences about other outcomes and attributes of therapy are heterogeneous and unpredictable. Patients’ therapy preferences usually align with their values when individualised risk information is presented, although divergence from this is common. Patients value the attributes of NOACs but frequently do not prefer NOACs over warfarin when all therapy-related attributes are considered. In conclusion, patients’ values and preferences for SPAF antithrombotic therapy are heterogeneous and there is no substitute for directly clarifying patients’ individual values and preferences. Research using choice modelling and tools to help clinicians and patients clarify their SPAF therapy values and preferences are needed.

Supplementary Material to this article is available online at www.thrombosis-online.com.
External validation of the VTE-BLEED score for predicting major bleeding in stable anticoagulated patients with venous thromboembolism
Authors: Klok Frederikus A. , Barco Stefano , Konstantinides Stavros V.
Published: March 2017

One of the main determinants of establishing the optimal treatment duration of patients with venous thromboembolism (VTE) is the risk of major bleeding during long-term anticoagulant therapy. The 6-variable VTE-BLEED score was recently developed to enable estimation of this bleeding risk. This study aimed at externally validating VTE-BLEED. This was a post-hoc study of the randomised, double-blind, double-dummy, Hokusai-VTE study that compared edoxaban versus warfarin for treatment of VTE. VTE-BLEED was calculated in all 8,240 study patients. The numbers of adjudicated major bleeding events during ‘stable anticoagulation’, i. e. occurring after day 30, in patients with low (total score <2 points) and high risk of bleeding (total score ≥2 points) were compared for the overall study population, patients randomised to edoxaban or warfarin, and for important patient subcategories. During ‘stable’ anticoagulation, major bleeding occurred in 1.02% (40/3,903) and 0.82% (32/3,899) of patients treated with warfarin and edoxaban, respectively. For the overall study population, the risks of bleeding in the low and high risk groups were 0.51% and 2.03%, respectively, for an odds ratio (OR) of 4.04 (95% confidence interval [CI]: 2.51–6.48). ORs were 5.04 (95%CI: 2.62–9.69) and 3.09 (95%CI: 1.54–6.22) for warfarin and edoxaban, respectively. VTE-BLEED was consistently able to identify patients at a 2.5- to 11-fold higher bleeding risk across all the predefined subcategories, as well as for the treatment period between day 30 to day 180, and beyond day 180. In conclusion, patients identified as high risk by VTE-BLEED had a four-fold increased risk of bleeding during the chronic phase of treatment.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Predictors of active cancer thromboembolic outcomes
Authors: Tafur Alfonso J. , Caprini Joseph A. , Cote Lauren , Trujillo-Santos Javier , Del Toro Jorge , Garcia-Bragado Fernando , Tolosa Carles , Barillari Giovanni , Visona Adriana , Monreal Manuel ,   the RIETE Investigators
Published: March 2017

Even though the Khorana risk score (KRS) has been validated to predict against the development of VTE among patients with cancer, it has a low positive predictive value. It is also unknown whether the score predicts outcomes in patients with cancer with established VTE. We selected a cohort of patients with active cancer from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the prognostic value of the KRS at inception in predicting the likelihood of VTE recurrences, major bleeding and mortality during the course of anticoagulant therapy. We analysed 7948 consecutive patients with cancer-associated VTE. Of these, 2253 (28 %) scored 0 points, 4550 (57 %) 1–2 points and 1145 (14 %) scored ≥3 points. During the course of anticoagulation, amongst patient with low, moderate and high risk KRS, the rate of VTE recurrences was of 6.21 (95 %CI: 4.99–7.63), 11.2 (95 %CI: 9.91–12.7) and 19.4 (95 %CI: 15.4–24.1) events per 100 patient-years; the rate of major bleeding of 5.24 (95 %CI: 4.13–6.56), 10.3 (95 %CI: 9.02–11.7) and 19.4 (95 %CI: 15.4–24.1) bleeds per 100 patient-years and the mortality rate of 25.3 (95 %CI: 22.8–28.0), 58.5 (95 %CI: 55.5–61.7) and 120 (95 %CI: 110–131) deaths per 100 patient-years, respectively. The C-statistic was 0.53 (0.50–0.56) for recurrent VTE, 0.56 (95 %CI: 0.54–0.59) for major bleeding and 0.54 (95 %CI: 0.52–0.56) for death. In conclusion, most VTEs occur in patients with low or moderate risk scores. The KRS did not accurately predict VTE recurrence, major bleeding, or mortality among patients with cancer-associated thrombosis.
On Kentrodoris and Jorunna (Gastropoda Opisthobranchia)
Authors: Marcus Eveline D. B.-R.
Published: March 2017

As 15 espécies anteriormente descritas como Kentrodoris ou Jorunna são revistas. O resultado é que 6 espécies são válidas, 3 já tinham sido removidas para outros gêneros, uma é sinônimo, e 5 não podem com certeza ser colocadas no presente grupo. Por outro lado, descrições pormenorizadas de 3 materiais, identificados com outras espécies, revelam tratar-se de 3 espécies novas, Jorunna alisonae, J. malcolmi e /. zania. Além disso, 2 espécies novas são descritas, J. luisae e J. lemchei. Awuka spazzola revelou-se como Jorunna. A distinção entre Kentrodoris e Jorunna no Tratado de Grassé (Odhner, 1968: 871) baseia-se ainda nas diagnoses de Bergh (1876). Bergh tinha, nas suas espécies, confundido a papila penial inerme e o estilete da glândula vestibular, e descrito o gênero Kentrodoris com estilete penial e glândula vestibular inerme. Em Doris johnstoni (= tomentosa) Alder Hancock (1845) haviam acertadamente reconhecido a papila penial inerme e o estilete da glândula vestibular. Para esta espécie Bergh criou o gênero Jorunna (1876). O meu estudo de 9 espécies, como também boas descrições de 2 espécies ulteriores, mostram que todas as 10 espécies suficientemente conhecidas têm estilete na glândula vestibular e a papila penial inerme. A única espécie com duto masculino cuticularizado é Kendrodoris rubescens. Todas as outras espécies pertencem a Jorunna.
Aspectos do comportamento alimentar dos morcegos hematófago, Desmodus rotundus
Authors: Sazima Ivan
Published: March 2017

O comportamento alimentar do morcego hematófago, Desmodus rotundus, junto ao gado bovino e equino, foi observado em condições naturais, na região de Campinas, São Paulo. Grande parte dos resultados concorda com as informações disponíveis sobre os hábitos deste morcego em outras localidades neotropicais. O início da sua atividade alimentar esteve relacionado com a ausência de luar. Esta espécie utilizou abrigos noturnos temporários, próximos ao gado, antes e depois das investidas alimentares. Nestes abrigos, foi observado o comportamento de manutenção da distância individual entre os morcegos (emissão de guinchos, empurrões e investidas). O ataque ao gado confinado em estábulos foi precedido pelo pouso, nas paredes internas, por um certo período (“investigação do local”). Três posturas básicas, adotadas pelos morcegos, permitem apoiar-se, durante a alimentação, no chão ou na vítima. No chão, apenas a postura quadrúpede foi observada; na vítima, as posturas agachada e pendurada foram adotadas. Aparentemente, a “preferência” dos morcegos por um certo local no corpo das vítimas poderia ser atribuída, em parte, à “acessibilidade” do local, qualidade que depende tanto das possíveis posturas adotadas pelos morcegos, como do comportamento da vítima. As interações observadas entre os morcegos, nos locais de alimentação, incluíram indivíduos alimentando-se juntos, outros alimentando-se sucessivamente numa mesma mordedura e, ainda, uma disputa entre dois morcegos numa mesma mordedura. Um possível “grito de alarme” foi observado numa ocasião. O número de mordeduras observadas por noite não correspondeu ao número de morcegos que se alimentaram no gado e, raramente, a mesma mordedura foi refeita na noite seguinte.
Functional anatomy of Donax hanleyanus Philippi 1847 (Donacidae - Bivalvia)
Authors: Narchi Walter
Published: March 2017

Este artigo não contém resumo.
The atlantic species of Onchidella (gastropoda Pulmonata ): part 2
Authors: Marcus Eveline Du Bois-Reymond
Published: March 2017

Os caracteres apücáveis à classificação são discutidos e uma chave para as oito espécies do Atlântico central e oriental é dada. Das 18 espécies de Onchidella mencionadas do Atlântico, duas, pachyderma (Plate, 1893) e pulchella Watson, 1925, não são reconhecíveis. O mesmo refere-se à Onchidella celtica (Seurat, 1932). O. remanei Marcus, 1956, foi reconhecida como sinônimo de celtica(Cuvier, 1817). As cinco espécies do Atlântico oriental das quais material pôde ser estudado, celtica, incisa, capensis, accrensis e a nova espécie phttippei, são descritas. Algumas observações sobre O. floridana são acrescentadas. O. maculata, O. monodi e O. souriei são discutidas. Onchidella é o único gênero dos Onchidiacea que ocorre no Atlântico. A distribuição das espécies é indicada no mapa (Fig. 56).