bluuebunny/crossref_metadata_2025 huggingface dataset:
Triterpenoids and Polysaccharide Fractions ofGanoderma tsugaeExert Different Effects on Antiallergic Activities
Authors: Chen Miaw-Ling , Hsieh Chia-Chien , Chiang Bor-Luen , Lin Bi-Fong
Published: April 2015

This study was to investigate antiallergic effects of triterpenoids (Gt-TRE) and polysaccharide (Gt-PS) extracts fromGanoderma tsugae, using mast cell line RBL-2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells. The results showed that histamine secreted from activated RBL-2H3 mast cells was significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL-) 4 secreted from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS. Further primary CD4+T cells cultures also confirmed that Gt-TRE (5~50 µg/mL) significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect on Th1 cytokines IL-2 and interferon (IFN)-γ. Gt-PS did not affect IL-4 and IL-5 secretions until higher doses (400, 500 µg/mL) and significantly suppressed IFNγsecretions but enhanced IL-2 at these high doses. The reporter gene assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional activity of NF-κB in activated transfected RAW264.7 cells and transfected EL4 cells. IL-4 secreted by this transfected EL-4 cells was also significantly decreased by Gt-TRE but not by Gt-PS, suggesting that these two fractions may exert different effects on NF-κB related cytokines expression. These data suggested that triterpenoids fraction ofGanoderma tsugaemight be the main constituents to alleviate allergic asthma.
Aminoalkylated Merrifield Resins Reticulated by Tris-(2-chloroethyl) Phosphate for Cadmium, Copper, and Iron (II) Extraction
Authors: Dardouri Mokhtar , Ammari Fayçel , Meganem Faouzi
Published: April 2015

We aimed to synthesize novel substituted polymers bearing functional groups to chelate heavy metals during depollution applications. Three polyamine functionalized Merrifield resins were prepared via ethylenediamine (EDA), diethylenetriamine (DETA), and triethylenetetramine (TETA) modifications named, respectively, MR-EDA, MR-DETA, and MR-TETA. The aminoalkylated polymers were subsequently reticulated by tris-(2-chloroethyl) phosphate (TCEP) to obtain new polymeric resins called, respectively, MR-EDA-TCEP, MR-DETA-TCEP, and MR-TETA-TCEP. The obtained resins were characterized via attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), elemental analysis (EA), and thermogravimetric (TGA), thermodynamic (DTA), and differential thermogravimetric (DTG) analysis. The synthesized resins were then assayed to evaluate their efficiency to extract metallic ions such as Cd2+, Cu2+, and Fe2+from aqueous solutions.
TheKampoMedicine Yokukansan Decreases MicroRNA-18 Expression and Recovers Glucocorticoid Receptors Protein Expression in the Hypothalamus of Stressed Mice
Authors: Shimizu Shoko , Tanaka Takashi , Takeda Takashi , Tohyama Masaya , Miyata Shingo
Published: April 2015

It is well known that glucocorticoid receptor (GR) signaling regulates the hypothalamic-pituitary-adrenal (HPA) axis, and GR expression level is associated with HPA axis activity. Recent studies revealed that microRNA- (miR-) 18 and/or 124a are candidate negative regulators of GR in the brain. TheKampomedicine Yokukansan (YKS) can affect psychological symptoms such as depression and anxiety that are associated with stress responses. In this study, we evaluated the effect of YKS on miR-18 and 124a and GR levels in mice exposed to stress. We found that YKS pretreatment normalized elevated plasma corticosterone levels in stress-exposed mice. In addition, GR mRNA levels were downregulated in the brain following stress exposure. While miR-124a expression levels were not altered in the hypothalamus of stress-exposed mice, miR-18 levels decreased in the hypothalamus of YKS-pretreated mice after stress exposure. Finally, GR protein levels in the paraventricular nucleus (PVN) of the hypothalamus after stress exposure recovered in YKS-pretreated mice. Collectively, these data suggest that YKS normalizes GR protein levels by regulating miR-18 expression in the hypothalamus, thus normalizing HPA axis activity following stress exposure.
Decreased IL‐27 Negatively Correlated with Th17 Cells in Non‐Small‐Cell Lung Cancer Patients
Authors: Duan Minchao , Ning Zhengqing , Fu Zhijun , Zhang Jianquan , Liu Guangnan , Wei Qiu , Zheng Xiaoyu
Published: April 2015

The presence of Th17 cells and IL‐27 is observed in a variety of inflammatory associated cancers. However, there are some data on the role of Th17 cells and IL‐27 in the regulation of immune reactions in non‐small‐cell lung cancer (NSCLC). The aim of this study is to assess the variation of Th17 cells and IL‐27 in the peripheral blood (PB) of patients with NSCLC. The proportion of Th17 cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometry. The serum concentrations of IL‐27 and IL‐17 were measured by enzyme‐linked immunosorbent assay (ELISA). The mRNA expression of RORγt and IL‐27 in the peripheral blood was examined by real‐time quantitative polymerase chain reaction (QPCR). Expression of IL‐27 was lower in NSCLC patients compared with normal controls. The frequency of Th17 cells was increased in NSCLC patients, accompanied by the upregulation of IL‐17 and RORγt. IL‐27 negatively correlated with the number of Th17 cells and the RORγt mRNA. Our results indicate that IL‐27 might inhibit Th17 differentiation in NSCLC patients and better understanding of the regulatory effects of IL‐27 on Th17 cells may shed light on potential new targets in cancer prevention and therapy.
Teaching Scientific Computing: A Model-Centered Approach to Pipeline and Parallel Programming with C
Authors: Dolgopolovas Vladimiras , Dagienė Valentina , Minkevičius Saulius , Sakalauskas Leonidas
Published: April 2015

The aim of this study is to present an approach to the introduction into pipeline and parallel computing, using a model of the multiphase queueing system. Pipeline computing, including software pipelines, is among the key concepts in modern computing and electronics engineering. The modern computer science and engineering education requires a comprehensive curriculum, so the introduction to pipeline and parallel computing is the essential topic to be included in the curriculum. At the same time, the topic is among the most motivating tasks due to the comprehensive multidisciplinary and technical requirements. To enhance the educational process, the paper proposes a novel model-centered framework and develops the relevant learning objects. It allows implementing an educational platform of constructivist learning process, thus enabling learners’ experimentation with the provided programming models, obtaining learners’ competences of the modern scientific research and computational thinking, and capturing the relevant technical knowledge. It also provides an integral platform that allows a simultaneous and comparative introduction to pipelining and parallel computing. The programming language C for developing programming models and message passing interface (MPI) and OpenMP parallelization tools have been chosen for implementation.
Correlation between the Quality of Attention and Cognitive Competence with Motor Action in Stroke Patients
Authors: Arsic S. , Konstantinovic Lj. , Eminovic F. , Pavlovic D. , Popovic M. B. , Arsic V.
Published: April 2015

It is considered that cognitive function and attention could affect walking, motion control, and proper conduct during the walk. To determine whether there is a difference in the quality of attention and cognitive ability in stroke patients and patients without neurological damage of similar age and education and to determine whether the connection of attention and cognition affects motor skills, the sample consisted of 50 stroke patients tested with hemiparesis, involved in the process of rehabilitation, and 50 persons, randomly chosen, without neurological damage. The survey used the following tests: Trail Making (TMT A B) test for assessing the flexibility of attention; Mini-Mental State Examination (MMSE) for cognitive status; Functional Ambulation Category (FAC) test to assess the functional status and parameters of walk: speed, frequency, and length of stride; STEP test for assessing the precision of movement and balance. With stroke patients, relationship between age and performance on the MMSE test was marginally significant. The ratio of performance to TMT A B test and years does not indicate statistical significance, while statistical significance between the MMSE test performance and education exists. In stroke patients, performance on MMSE test is correlated with the frequency and length of stride walk. The quality of cognitive function and attention is associated with motor skills but differs in stroke patients and people without neurological damage of similar age. The significance of this correlation can supplement research in neurorehabilitation, improve the quality of medical rehabilitation, and contribute to efficient recovery of these patients.
Design of Incremental Conductance Sliding Mode MPPT Control Applied by Integrated Photovoltaic and Proton Exchange Membrane Fuel Cell System under Various Operating Conditions for BLDC Motor
Authors: Hahm Jehun , Kang Hyoseok , Baek Jaeho , Lee Heejin , Park Mignon
Published: April 2015

This paper proposes an integrated photovoltaic (PV) and proton exchange membrane fuel cell (PEMFC) system for continuous energy harvesting under various operating conditions for use with a brushless DC motor. The proposed scheme is based on the incremental conductance (IncCond) algorithm combined with the sliding mode technique. Under changing atmospheric conditions, the energy conversion efficiency of a PV array is very low, leading to significant power losses. Consequently, increasing efficiency by means of maximum power point tracking (MPPT) is particularly important. To manage such a hybrid system, control strategies need to be established to achieve the aim of the distributed system. Firstly, a Matlab/Simulink based model of the PV and PEMFC is developed and validated, as well as the incremental conductance sliding (ICS) MPPT technique; then, different MPPT algorithms are employed to control the PV array under nonuniform temperature and insolation conditions, to study these algorithms effectiveness under various operating conditions. Conventional techniques are easy to implement but produce oscillations at MPP. Compared to these techniques, the proposed technique is more efficient; it produces less oscillation at MPP in the steady state and provides more precise tracking.
Spectral Clustering with Local Projection Distance Measurement
Authors: Diao Chen , Zhang Ai-Hua , Wang Bin
Published: April 2015

Constructing a rational affinity matrix is crucial for spectral clustering. In this paper, a novel spectral clustering via local projection distance measure (LPDM) is proposed. In this method, the Local-Projection-Neighborhood (LPN) is defined, which is a region between a pair of data, and other data in the LPN are projected onto the straight line among the data pairs. Utilizing the Euclidean distance between projective points, the local spatial structure of data can be well detected to measure the similarity of objects. Then the affinity matrix can be obtained by using a new similarity measurement, which can squeeze or widen the projective distance with the different spatial structure of data. Experimental results show that the LPDM algorithm can obtain desirable results with high performance on synthetic datasets, real-world datasets, and images.
Robust Adaptive Principal Component Analysis Based on Intergraph Matrix for Medical Image Registration
Authors: Leng Chengcai , Xiao Jinjun , Li Min , Zhang Haipeng
Published: April 2015

This paper proposes a novel robust adaptive principal component analysis (RAPCA) method based on intergraph matrix for image registration in order to improve robustness and real-time performance. The contributions can be divided into three parts. Firstly, a novel RAPCA method is developed to capture the common structure patterns based on intergraph matrix of the objects. Secondly, the robust similarity measure is proposed based on adaptive principal component. Finally, the robust registration algorithm is derived based on the RAPCA. The experimental results show that the proposed method is very effective in capturing the common structure patterns for image registration on real-world images.
Downmodulation of Vaccine-Induced Immunity and Protection against the Intracellular BacteriumFrancisella tularensisby the Inhibitory Receptor FcγRIIB
Authors: Franz Brian J. , Li Ying , Bitsaktsis Constantine , Iglesias Bibiana V. , Pham Giang , Sunagar Raju , Kumar Sudeep , Gosselin Edmund J.
Published: April 2015

Fc gamma receptor IIB (FcγRIIB) is the only Fc gamma receptor (FcγR) which negatively regulates the immune response, when engaged by antigen- (Ag-) antibody (Ab) complexes. Thus, the generation of Ag-specific IgG in response to infection or immunization has the potential to downmodulate immune protection against infection. Therefore, we sought to determine the impact of FcγRIIB on immune protection againstFrancisella tularensis(Ft), a Category A biothreat agent. We utilized inactivatedFt(iFt) as an immunogen. Naïve and iFt-immunized FcγRIIB knockout (KO) or wildtype (WT) mice were challenged withFt-live vaccine strain (LVS). While no significant difference in survival between naïve FcγRIIB KO versus WT mice was observed, iFt-immunized FcγRIIB KO mice were significantly better protected than iFt-immunized WT mice.Ft-specific IgA in serum and bronchial alveolar lavage, as well as IFN-γ, IL-10, and TNF-αproduction by splenocytes harvested from iFt-immunized FcγRIIB KO, were also significantly elevated. In addition, iFt-immunized FcγRIIB KO mice exhibited a reduction in proinflammatory cytokine levelsin vivoat 5 days after challenge, which correlates with increased survival followingFt-LVS challenge in published studies. Thus, these studies demonstrate for the first time the ability of FcγRIIB to regulate vaccine-induced IgA production and downmodulate immunity and protection. The immune mechanisms behind the above observations and their potential impact on vaccine development are discussed.
A Novel Operative Procedure for Pelvic Organ Prolapse Utilizing a MRI-Visible Mesh Implant: Safety and Outcome of Modified Laparoscopic Bilateral Sacropexy
Authors: Joukhadar Ralf , Meyberg-Solomayer Gabriele , Hamza Amr , Radosa Julia , Bader Werner , Barski Dimitri , Ismaeel Fakher , Schneider Guenther , Solomayer Erich , Baum Sascha
Published: April 2015

Introduction. Sacropexy is a generally applied treatment of prolapse, yet there are known possible complications of it. An essential need exists for better alloplastic materials.Methods. Between April 2013 and June 2014, we performed a modified laparoscopic bilateral sacropexy (MLBS) in 10 patients using a MRI-visible PVDF mesh implant. Selected patients had prolapse POP-Q stages II-III and concomitant OAB. We studied surgery-related morbidity, anatomical and functional outcome, and mesh-visibility in MRI. Mean follow-up was 7.4 months.Results. Concomitant colporrhaphy was conducted in 1/10 patients. Anatomical success was defined as POP-Q stage 0-I. Apical success rate was 100% and remained stable. A recurrent cystocele was seen in 1/10 patients during follow-up without need for intervention. Out of 6 (6/10) patients with preoperative SUI, 5/6 were healed and 1/6 persisted. De-novo SUI was seen in 1/10 patients. Complications requiring a relaparoscopy were seen in 2/10 patients. 8/10 patients with OAB were relieved postoperatively. The first in-human magnetic resonance visualization of a prolapse mesh implant was performed and showed good quality of visualization.Conclusion. MLBS is a feasible and safe procedure with favorable anatomical and functional outcome and good concomitant healing rates of SUI and OAB. Prospective data and larger samples are required.
Jordan Isomorphisms on Nest Subalgebras
Authors: Yang Aili
Published: April 2015

This paper is devoted to the study of Jordan isomorphisms on nest subalgebras of factor von Neumann algebras. It is shown that every Jordan isomorphismϕbetween the two nest subalgebrasalgMβandalgMγis either an isomorphism or an anti-isomorphism.
Phase Behavior and Physical Parameters of Natural Gas Mixture withCO2
Authors: Hou Dali , Deng Hucheng , Zhang Hao , Li Kai , Sun Lei , Pan Yi
Published: April 2015

The two-flash experiment, constant composition expansion experiment, saturation pressure measurement experiment, and phase transition observation experiment from well bottom hole to well head of four high CO2content natural gas samples were carried out by using the JEFRI-PVT apparatus made from DBR Company of Canada. The experimental results show that in the four high CO2content gas samples no phase transitions will take place at temperatures greater than 35°C. In the gas-liquid two-phase region, saturation pressures, critical pressure, critical temperature, and an integratedP-Tphase diagram of different CO2content natural gases are calculated by using the modified PR equation of state and modified (T) equation proposed by Saffari. The deviations between the saturation pressure calculated by using the model proposed in this study and experimental measured saturation pressure are very small; the average relative error is only 2.86%. Thus, the model can be used to predict the phase equilibrium parameters of high CO2content natural gas.
Monopoly Profit Maximization: Success and Economic Principles
Authors: von Blanckenburg Korbinian , Neubert Milena
Published: April 2015

This paper presents a classroom experiment on pricing strategies available to monopolists. Each student makes production decisions as a monopolist during the experiment, learning from his/her own experiences what it means to be a price searcher. Full information is provided on cost conditions, while the demand function remains unknown to the participants. Given a sufficient number of periods, students will in principle be able to maximise their profits by applying a simple trial and error strategy. However, one of the objectives of the experiment is to demonstrate to students that search strategies based on economic principles are more efficient.
MicroRNAs in Pancreatic Cancer: Involvement in Carcinogenesis and Potential Use for Diagnosis and Prognosis
Authors: Halkova Tereza , Cuperkova Romana , Minarik Marek , Benesova Lucie
Published: April 2015

Pancreatic cancer is one of the most fatal malignancies with increasing incidence and high mortality. Possibilities for early diagnosis are limited and there is currently no efficient therapy. Molecular markers that have been introduced into diagnosis and treatment of other solid tumors remain unreciprocated in this disease. Recent discoveries have shown that certain microRNAs (miRNAs) take part in fundamental molecular processes associated with pancreatic cancer initiation and progression including cell cycle, DNA repair, apoptosis, invasivity, and metastasis. The mechanism involves both positive and negative regulation of expression of protooncogenes and tumor suppressor genes. Various miRNAs are expressed at different levels among normal pancreatic tissue, chronic pancreatitis, and pancreatic cancer and may therefore serve as a tool to differentiate chronic pancreatitis from early stages of cancer. Other miRNAs can indicate the probable course of the disease or determine the survival prognosis. In addition, there is a growing interest directed at the understanding of miRNA-induced molecular mechanisms. The possibility of intervention in the molecular mechanisms of miRNAs regulation could begin a new generation of pancreatic cancer therapies. This review summarizes the recent reports describing functions of miRNAs in cellular processes underlying pancreatic cancerogenesis and their utility in diagnosis, survival prognosis, and therapy.
Vitamin D and Pain: Vitamin D and Its Role in the Aetiology and Maintenance of Chronic Pain States and Associated Comorbidities
Authors: Shipton Edward A. , Shipton Elspeth E.
Published: April 2015

The emergence of new data suggests that the benefits of Vitamin D extend beyond healthy bones. This paper looks at Vitamin D and its role in the aetiology and maintenance of chronic pain states and associated comorbidities. The interfaces between pain and Vitamin D and the mechanisms of action of Vitamin D on pain processes are explored. Finally the association between Vitamin D and pain comorbidities such as sleep and depression is investigated. The paper shows that Vitamin D exerts anatomic, hormonal, neurological, and immunological influences on pain manifestation, thereby playing a role in the aetiology and maintenance of chronic pain states and associated comorbidities. More research is necessary to determine whether Vitamin D is useful in the treatment of various pain conditions and whether or not the effect is limited to patients who are deficient in Vitamin D.
A Practical and Scalable Tool to Find Overlaps between Sequences
Authors: Haj Rachid Maan , Malluhi Qutaibah
Published: April 2015

The evolution of the next generation sequencing technology increases the demand for efficient solutions, in terms of space and time, for several bioinformatics problems. This paper presents a practical and easy-to-implement solution for one of these problems, namely, the all-pairs suffix-prefix problem, using a compact prefix tree. The paper demonstrates an efficient construction of this time-efficient and space-economical tree data structure. The paper presents techniques for parallel implementations of the proposed solution. Experimental evaluation indicates superior results in terms of space and time over existing solutions. Results also show that the proposed technique is highly scalable in a parallel execution environment.
Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis
Authors: Branis Natalia M. , Wittlin Steven D.
Published: April 2015

Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA) after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45), bicarbonate 16 mmol/L (22–29 mmol/L), and anion gap 19 mmol/L (8–16 mmol/L). Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA) availability. It promotesβ-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.
Lifetime Optimization of a Multiple Sink Wireless Sensor Network through Energy Balancing
Authors: Jain Tapan Kumar , Saini Davinder Singh , Bhooshan Sunil Vidya
Published: April 2015

The wireless sensor network consists of small limited energy sensors which are connected to one or more sinks. The maximum energy consumption takes place in communicating the data from the nodes to the sink. Multiple sink WSN has an edge over the single sink WSN where very less energy is utilized in sending the data to the sink, as the number of hops is reduced. If the energy consumed by a node is balanced between the other nodes, the lifetime of the network is considerably increased. The network lifetime optimization is achieved by restructuring the network by modifying the neighbor nodes of a sink. Only those nodes are connected to a sink which makes the total energy of the sink less than the threshold. This energy balancing through network restructuring optimizes the network lifetime. This paper depicts this fact through simulations done in MATLAB.
Detection of Tropical Fungi in Formalin-Fixed, Paraffin-Embedded Tissue: Still an Indication for Microscopy in Times of Sequence-Based Diagnosis?
Authors: Frickmann Hagen , Loderstaedt Ulrike , Racz Paul , Tenner-Racz Klara , Eggert Petra , Haeupler Alexandra , Bialek Ralf , Hagen Ralf Matthias
Published: April 2015

Introduction. The aim of the study was the evaluation of panfungal PCR protocols with subsequent sequence analysis for the diagnostic identification of invasive mycoses in formalin-fixed, paraffin-embedded tissue samples with rare tropical mycoses.Materials and Methods. Five different previously described panfungal PCR/sequencing protocols targeting 18S and 28S ribosomal RNA gene fragments as well as internal transcribed spacer 1 and 2 fragments were evaluated with a collection of 17 formalin-fixed, paraffin-embedded tissue samples of patients with rare and/or tropical invasive mycoses, comprising chromoblastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis, mycetoma/maduromycosis, and rhinosporidiosis, in a proof-of-principle analysis.Results. The primers of the panfungal PCRs readily and predominantly reacted with contaminating environmental fungi that had deposited on the paraffin blocks. Altogether three sequence results of histoplasmosis and mycetoma samples that matched the histological assessment were associated with sample age <10 years and virtually without PCR inhibition.Conclusions. The high risk of amplifying environmental contaminants severely reduces the usefulness of the assessed panfungal PCR/sequencing protocols for the identification of rare and/or tropical mycoses in stored formalin-fixed, paraffin-embedded tissues. Histological assessment remains valuable for such indications if cultural differentiation is impossible from inactivated sample material.
Fertility and Symptom Relief following Robot-Assisted Laparoscopic Myomectomy
Authors: Pitter Michael C. , Srouji Serene S. , Gargiulo Antonio R. , Kardos Leslie , Seshadri-Kreaden Usha , Hubert Helen B. , Weitzman Glenn A.
Published: April 2015

Objective. To examine success of robot-assisted laparoscopic myomectomy (RALM) measured by sustained symptom relief and fertility.Methods. This is a retrospective survey of 426 women who underwent RALM for fibroids, symptom relief, or infertility at three practice sites across the US. We examined rates of symptom recurrence and pregnancy and factors associated with these outcomes.Results. Overall, 70% of women reported being symptom-free, with 62.9% free of symptoms after three years. At >3 years, 66.7% of women who underwent surgery to treat infertility and 80% who were also symptom-free reported achieving pregnancy. Factors independently associated with symptom recurrence included greater time after surgery, preoperative dyspareunia, multiple fibroid surgeries, smoking after surgery, and preexisting diabetes. Factors positively correlated with achieving pregnancy included desiring pregnancy, prior pregnancy, greater time since surgery, and Caucasian race. Factors negatively correlated with pregnancy were advanced age and symptom recurrence.Conclusions. This paper, the first to examine symptom recurrence after RALM, demonstrates both short- and long-term effectiveness in providing symptom relief. Furthermore, RALM may have the potential to improve the chance of conception, even in a population at high risk of subfertility, with greater benefits among those who remain symptom-free. These findings require prospective validation.
Changes in Typhoon Activities and Regional Precipitation Variability over the Korean Peninsula according to Different Phases of El Niño
Authors: Kim Jong-Suk , Yoon Sun-Kwon , Oh Sang Myeong , Moon Young-Il
Published: April 2015

We analyzed typhoon activities such as tropical cyclone (TC) genesis position, movement routes and central pressure of typhoons, and changes in local patterns of rainfall stemming from TCs passing through the Korean domain. The results showed a remarkable difference in changes in typhoons that affect the Korean Peninsula (KP) during cold tongue (CT) and warm pool (WP) El Niño years. In particular, TCs that move through the ocean off Korea and the Kuroshio during WP El Niño years are relatively stronger than TCs formed during CT El Niño years. Furthermore, analysis of large-scale atmosphere-ocean dynamics showed better conditions for TC development and strengthening during WP El Niño years. TC-induced summer rainfall over major Korean river basins decreased from normal years during CT El Niño years (−3.94%) and increased over normal years during WP El Niño years (+33.92%). The results of this diagnostic study rely on short-term observations and relatively little data, but they suggest that CT/WP El Niño cycles influence TC activities and rainfall across the KP. The findings are important for reducing TC damage and ensuring a proper response to climate change in coupled human-environmental systems.
Increased Frequency of CD4+ CD25+ FoxP3+ T Regulatory Cells in Pulmonary Tuberculosis Patients Undergoing Specific Treatment and Its Relationship with Their Immune-Endocrine Profile
Authors: Díaz Ariana , Santucci Natalia , Bongiovanni Bettina , D’Attilio Luciano , Massoni Claudia , Lioi Susana , Radcliffe Stella , Dídoli Griselda , Bottasso Oscar , Bay María Luisa
Published: April 2015

Tuberculosis (TB) is a major health problem requiring an appropriate cell immune response (IR) to be controlled. Since regulatory T cells (Tregs) are relevant in IR regulation, we analyzed Tregs variations throughout the course of TB treatment and its relationship with changes in immune-endocrine mediators dealing with disease immunopathology. The cohort was composed of 41 adult patients, 20 of them completing treatment and follow-up. Patients were bled at diagnosis (T0) and at 2 (T2), 4 (T4), 6 (T6), and 9 months following treatment initiation. Twenty-four age- and sex-matched healthy controls (HCo) were also included. Tregs (flow cytometry) from TB patients were increased at T0 (versus HCoP<0.05), showing even higher values at T2 (versus T0P<0.01) and T4 (versus T0P<0.001). While IL-6, IFN-γ, TGF-β(ELISA), and Cortisol (electrochemiluminescence, EQ) were augmented, DHEA-S (EQ) levels were diminished at T0 with respect to HCo, with cytokines and Cortisol returning to normal values at T9. Tregs correlated positively with IFN-γ(R=0.868,P<0.05) at T2 and negatively at T4 (R=-0.795,P<0.05). Lowered levels of proinflammatory cytokines together with an increased frequency of Tregs of patients undergoing specific treatment might reflect a downmodulatory effect of these cells on the accompanying inflammation.
Myostatin Neutralization Results in Preservation of Muscle Mass and Strength in Preclinical Models of Tumor-Induced Muscle Wasting
Authors: Smith Rosamund C. , Cramer Martin S. , Mitchell Pamela J. , Capen Andrew , Huber Lysiane , Wang Rong , Myers Laura , Jones Bryan E. , Eastwood Brian J. , Ballard Darryl , Hanson Jeff , Credille Kelly M. , Wroblewski Victor J. , Lin Boris K. , Heuer Josef G.
Published: April 2015

Skeletal muscle wasting occurs in a great majority of cancer patients with advanced disease and is associated with a poor prognosis and decreased survival. Myostatin functions as a negative regulator of skeletal muscle mass and has recently become a therapeutic target for reducing the loss of skeletal muscle and strength associated with clinical myopathies. We generated neutralizing antibodies to myostatin to test their potential use as therapeutic agents to attenuate the skeletal muscle wasting due to cancer. We show that our neutralizing antimyostatin antibodies significantly increase body weight, skeletal muscle mass, and strength in non–tumor-bearing mice with a concomitant increase in mean myofiber area. The administration of these neutralizing antibodies in two preclinical models of cancer-induced muscle wasting (C26 colon adenocarcinoma and PC3 prostate carcinoma) resulted in a significant attenuation of the loss of muscle mass and strength with no effect on tumor growth. We also show that the skeletal muscle mass– and strength-preserving effect of the antibodies is not affected by the coadministration of gemcitabine, a common chemotherapeutic agent, in both non–tumor-bearing mice and mice bearing C26 tumors. In addition, we show that myostatin neutralization with these antibodies results in the preservation of skeletal muscle mass following reduced caloric intake, a common comorbidity associated with advanced cancer. Our findings support the use of neutralizing antimyostatin antibodies as potential therapeutics for cancer-induced muscle wasting. Mol Cancer Ther; 14(7); 1661–70. ©2015 AACR.
Altered MicroRNA Expression Profiles in Activated Mast Cells Following IgE-FcεRI Cross-Linking with Antigen
Authors: Teng Yaoshu , Zhang Ruxin , Yu Hongzhi , Wang Hong , Hong Zhicong , Zhuang Wenjie , Huang Yu
Published: April 2015

Background/Aims: MicroRNAs (miRNAs) are critical regulators of immune responses and immunologic disorders. However, little is known about miRNA expression and function during mast cell differentiation, proliferation and activation. This study aimed to determine the miRNA expression profiles in mast cells stimulated by immunoglobulin E (IgE) and antigen and to analyze the potential functions of specific miRNAs. Methods: Bone marrow-derived mast cells (BMMCs) generated from differentiated mouse bone marrow cells were untreated (Unstimu) or stimulated with IgE-antigen complexes for 1 h or 6 h (Stimu). The miRNA profiles were evaluated by miRNA microarray. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. Results: Seven significantly up-regulated and 10 down-regulated miRNAs were identified in the 1 h Stimu group relative to the Unstimu group (fold change>2; P<0.05). Of 8 miRNAs randomly selected from the 17 identified, the expression levels of 6 were confirmed by quantitative real-time PCR (qRT-PCR). The potential target genes of several candidate miRNAs were enriched in FcεRI signaling, response to stimulus and cellular exocytosis. Conclusion: The expression of many miRNAs changes following IgE-FcεRI cross-linking in activated mast cells, and these miRNAs probably play key regulatory roles in core signaling pathways and biological behaviors. Evaluating the functions of these characteristic miRNAs will further our understanding of IgE-associated allergic disease pathogenesis and the development of therapeutic strategies.
Augmented Rac1 Expression and Activity are Associated with Oxidative Stress and Decline of β Cell Function in Obesity
Authors: Zhou Shutong , Yu Dongni , Ning Shangyong , Zhang Heli , Jiang Lei , He Lei , Li Miao , Sun Mingxiao
Published: April 2015

Background: The aim of this study was to clarify the relationship among Rac1 expression and activation, oxidative stress and β cell dysfunction in obesity. Methods: In vivo, serum levels of glucose, insulin, oxidative stress markers and Rac1 expression were compared between ob/ob mice and C57BL/6J controls. Then, these variables were rechecked after the administration of the specific Rac1 inhibitor-NSC23766 in ob/ob mice. In vitro, NIT-1 β cells were cultured in a hyperglycemic and/or hyperlipidemic state with or without NSC23766, and the differences of Rac1 expression and translocation, NADPH oxidase(Nox) enzyme activity, reactive oxygen species (ROS) and insulin mRNA were observed. Results: ob/ob mice displayed abnormal glycometabolism, oxidative stress and excessive expression of Rac1 in the pancreas. NSC23766 injection inhibited the expression of Rac1 in the pancreas, along with amelioration of oxidative stress and glycometabolism in obese mice. Under hyperglycemic and/or hyperlipidemic conditions, Rac1 translocated to the cellular membrane, induced activation of the NADPH oxidase enzyme and oxidative stress, and simultaneously reduced the insulin mRNA expression in NIT-1 β cells. Inhibiting Rac1 activity could alleviate oxidative stress and meliorate the decline of insulin mRNA in β cells. Conclusions: Rac1 might contribute to oxidative stress systemically and locally in the pancreas in obesity. The excessive activation and expression of Rac1 in obesity were associated with β cell dysfunction through ROS production.
Exendin-4 Promotes Beta Cell Proliferation via PI3k/Akt Signalling Pathway
Authors: Wang Chaoxun , Chen Xiaopan , Ding Xiaoying , He Yanju , Gu Chengying , Zhou Ligang
Published: April 2015

Background/Aims: Prevention of diabetes requires maintenance of a functional beta-cell mass, the postnatal growth of which depends on beta cell proliferation. Past studies have shown evidence of an effect of an incretin analogue, Exendin-4, in promoting beta cell proliferation, whereas the underlying molecular mechanisms are not completely understood. Methods: Here we studied the effects of Exendin-4 on beta cell proliferation in vitro and in vivo through analysing BrdU-incorporated beta cells. We also analysed the effects of Exendin-4 on beta cell mass in vivo, and on beta cell number in vitro. Then, we applied specific inhibitors of different signalling pathways and analysed their effects on Exendin-4-induced beta cell proliferation. Results: Exendin-4 increased beta cell proliferation in vitro and in vivo, resulting in significant increases in beta cell mass and beta cell number, respectively. Inhibition of PI3K/Akt signalling, but not inhibition of either ERK/MAPK pathway, or JNK pathway, significantly abolished the effects of Exendin-4 in promoting beta cell proliferation. Conclusion: Exendin-4 promotes beta cell proliferation via PI3k/Akt signaling pathway.
TIMP-1 Induces α-Smooth Muscle Actin in Fibroblasts to Promote Urethral Scar Formation
Authors: Sa Yinglong , Li Chao , Li Hongbin , Guo Hailin
Published: April 2015

Background/Aims: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been reported to upregulate in urethral scar. However, the underlying molecular mechanisms remain undefined. Methods: Here, we studied levels of TIMP-1 and α-smooth muscle actin (α-SMA) in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Then we either overexpressed TIMP-1, or inhibited TIMP-1 by lentiviruses carrying a transgene or a short hairpin small interfering RNA for TIMP-1 in human fibroblasts. We examined the effects of modulation of TIMP-1 on α-SMA, and on epithelial-mesenchymal transition (EMT)-related genes. We also studied the underlying mechanisms. Results: We detected significantly higher levels of TIMP-1 and α-smooth muscle actin (α-SMA) in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Moreover, the levels of TIMP-1 and α-SMA strongly correlated. Moreover, we found that TIMP-1 significantly increased levels of α-SMA, transforming growth factor β 1 (TGFβ1), Collagen I and some other key factors related to an enhanced EMT, suggesting that TIMP-1 may induce transformation of fibroblasts into myofibroblasts to promote tissue EMT to enhance the formation of urethral scar. Moreover, increases in TIMP-1 also induced an increase in fibroblast cell growth and cell invasion, in an ERK/MAPK-signaling-dependent manner. Conclusion: Our study thus highlights a pivotal role of TIMP-1 in urethral scar formation.
The Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Performance in Treatment-Resistant Depression. A Systematic Review
Authors: Serafini Gianluca , Pompili Maurizio , Belvederi Murri Martino , Respino Matteo , Ghio Lucio , Girardi Paolo , Fitzgerald Paul B. , Amore Mario
Published: April 2015

Background: Major depressive disorder (MDD) is a disabling illness associated with significant functional and psychosocial impairment. Although many psychopharmacological agents are currently available for its treatment, many MDD patients suffer from treatment-resistant depression (TRD). Methods: A systematic review of the current literature (Pubmed/Medline, Scopus and ScienceDirect search) has been conducted with the primary aim to investigate the role of repetitive transcranial magnetic stimulation (rTMS) in improving neurocognition in patients with TRD. Studies were included according to the following criteria: (a) being an original paper in a peer-reviewed journal and (b) having analyzed the effect of rTMS on neurocognitive functioning in TRD. Results: The combined search strategy yielded a total of 91 articles, of which, after a complete analysis, 22 fulfilled our inclusion criteria. Based on the main findings, most of the selected studies suggested the existence of a trend towards improvements in the neurocognitive profile using rTMS. Negative findings have also been reported. However, most studies were limited by their small sample size or included mixed samples, or the adopted single-blind designs potentially biased the blinding of the study design. Conclusion: rTMS is a noninvasive brain stimulation that may be considered a valuable and promising technique for cognitive enhancement in TRD.
Does BDNF Val66Met Polymorphism Confer Risk for Posttraumatic Stress Disorder?
Authors: Wang Tengfei
Published: April 2015

Background: Evidence has indicated that BDNF (brain-derived neurotrophic factor) Val66Met genetic variant could be linked to the development of posttraumatic stress disorder (PTSD). However, clinical observations studying the BDNF polymorphism and the risk of PTSD yielded contradictory results. In this meta-analysis we evaluated the association between BDNF Val66Met and PTSD risk. Method: Systematic searches in online databases retrieved 6 relevant publications. Different inherited models were utilized to perform the pooled analysis. Subgroup analyses and sensitive analyses based on Hardy-Weinberg equilibrium (HWE) test results were also carried out. Results: Our study did not found a significant overall effect of BDNF Val66Met on the susceptibility to PTSD under various genetic models. In contrast, subgroup analyses suggested that the stress status of the control group, but not ethnicity, may influence the relationship of BDNF Val66Met with PTSD risk. After the exclusion of a study that was not in HWE, our conclusions remained unchanged during the influence analyses. Conclusions: This meta-analysis suggested no genetic association of BDNF Val66Met with vulnerability to PTSD. Further research studies are warranted to clarify the impact of BDNF variants on the occurrence of PTSD.
Optical Imaging Innovations for Atherosclerosis Research
Authors: Megens Remco T.A. , Bianchini Mariaelvy , Schmitt Martin M.N. , Weber Christian
Published: April 2015

Cardiovascular disease is the leading cause of death and morbidity worldwide. Improving vascular prevention and therapy based on a refined mechanistic pervasion of atherosclerosis as the underlying pathology could limit the effect of vascular disease in aging societies. During the past decades, microscopy has contributed greatly to a better understanding of vascular physiology and pathology by allowing imaging of living specimen with subcellular resolution and high specificity. An important advance has been accomplished through the application of multiphoton microscopy in the vascular domain, a technological development that enabled multidimensional and dynamic imaging deep into the cellular architecture of intact tissue under physiological conditions. To identify and validate new targets for treating atherosclerosis, novel imaging strategies with nanoscale resolution will be essential to visualize molecular processes in intracellular and extracellular compartments. This review will discuss the current use of 2-photon microscopy and will provide an overview and outlook on options for introducing nanoscopic optical imaging modalities in atherosclerosis research.
Small Conductance Calcium-Activated Potassium Current Is Important in Transmural Repolarization of Failing Human Ventricles
Authors: Yu Chih-Chieh , Corr Christopher , Shen Changyu , Shelton Richard , Yadava Mrinal , Rhea Isaac B. , Straka Susan , Fishbein Michael C. , Chen Zhenhui , Lin Shien-Fong , Lopshire John C. , Chen Peng-Sheng
Published: April 2015

Background—

The transmural distribution of apamin-sensitive small conductance Ca
2+
-activated K
+
(SK) current (
I
KAS
) in failing human ventricles remains unclear.

Methods and Results—

We optically mapped left ventricular wedge preparations from 12 failing native hearts and 2 rejected cardiac allografts explanted during transplant surgery. We determined transmural action potential duration (APD) before and after 100 nmol/L apamin administration in all wedges and after sequential administration of apamin, chromanol, and E4031 in 4 wedges. Apamin prolonged APD from 363 ms (95% confidence interval [CI], 341–385) to 409 (95% CI, 385–434;
P
<0.001) in all hearts, and reduced the transmural conduction velocity from 36 cm/s (95% CI, 30–42) to 32 cm/s (95% CI, 27–37;
P
=0.001) in 12 native failing hearts at 1000 ms pacing cycle length (PCL). The percent APD prolongation is negatively correlated with baseline APD and positively correlated with PCL. Only 1 wedge had M-cell islands. The percentages of APD prolongation in the last 4 hearts at 2000 ms PCL after apamin, chromanol, and E4031 were 9.1% (95% CI, 3.9–14.2), 17.3% (95% CI, 3.1–31.5), and 35.9% (95% CI, 15.7–56.1), respectively. Immunohistochemical staining of subtype 2 of SK protein showed increased expression in intercalated discs of myocytes.

Conclusions—

SK current is important in the transmural repolarization in failing human ventricles. The magnitude of
I
KAS
is positively correlated with the PCL, but negatively correlated with APD when PCL is fixed. There is abundant subtype 2 of SK protein in the intercalated discs of myocytes.