bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of mesenchymal stem cells on metastasis development in mice in vivo
Authors: Meleshina Aleksandra V , Cherkasova Elena I , Shirmanova Marina V , Klementieva Natalia V , Kiseleva Ekaterina V , Snopova Ludmila В , Prodanets Natalia N , Zagaynova Elena V
Published: February 2015

Introduction

In recent years, mesenchymal stem cells (MSCs) have been demonstrated to play an important role in carcinogenesis. However, the effect of MSCs on tumor and metastasis development and the mechanisms underlying the interaction of cancer and stem cells are not completely understood. This study investigated the effect of MSCs on breast cancer metastasis formation by using the methods of in vivo fluorescence and luminescence imaging.

Methods

MSCs were isolated from bone marrow of normal donors, characterized, and genetically labeled with luciferase (luc2). The effects of MSCs on MDA-MB-231 cancer cell proliferation were evaluated in conditioned medium from MSCs. To generate lung metastases, MDA-MB-231 cells stably expressing red fluorescent protein Turbo FP650 were injected intravenously into nude mice. On day 10 after the cancer cell injection, mice were injected via the tail vein with MSCs-luc2 cells (the MET + MSCs group). Animals that received the injection of MDA-MB-231-Turbo FP650 alone (the MET group) and no injections (the intact control group) served as controls. Fluorescence and bioluminescence imaging was performed for monitoring of the metastasis formation and MSC distribution in the recipient’s body.

Results

We found that the proliferative activity of the cancer cells in the presence of MSC conditioned medium was lower than that of the cells grown in conventional culture medium. The metastasis formation in the MET + MSCs group was delayed in time as compared with the MET group. Macroscopic and histological examination of isolated lungs 8 weeks after cancer cell injection showed that the total number of metastases in animals of the MET + MSCs group was significantly lower. Using bioluminescence imaging in vivo, we found that MSCs-luc2 cells survived in the host animal for at least 7 weeks and re-migrated to the lung 6 to 7 weeks after injection. Immunohistochemical analysis revealed the presence of MSCs-luc2 in metastases and lung tissue.

Conclusions

Long-term in vivo bioluminescence imaging of intravenously injected MSCs-luc2 cells showed distribution of MSCs to the lungs and abdominal organs within the first 2 to 3 weeks and re-migration to the lungs in weeks 6 to 7. It was found that MSCs reduced the proliferative activity of cancer cells in vitro and lung metastasis formation in mice.
RETRACTED ARTICLE: Fixed point theorems for solutions of the stationary Schrödinger equation on cones
Authors: Xue Gaixian , Yuzbasi Eve
Published: February 2015

The main aim of this paper is to study and establish some new coincidence point and common fixed point theorems for solutions of the stationary Schrödinger equation on cones. An interesting application is to investigate the existence and uniqueness for solutions of the Dirichlet problem with respect to the Schrödinger operator on cones and the growth property of them.
Dispersion relation as a channel of plasma turbulence evolution
Authors: Comişel Horia , Narita Yasuhito , Motschmann Uwe
Published: February 2015

We present evidence from ion-scale plasma turbulence simulations that normal-mode waves and sideband waves co-exist when a plasma evolves from wave fields into turbulence. Ion-scale fluctuations represent normal-mode fluctuations such as Bernstein and cyclotron modes, accompanied by sideband waves having moderate frequency mismatch with the normal modes. The evolution process is studied using the method of energy partition and frequency broadening. Wave evolution into turbulence exhibits distinct stages: growth phase of normal modes, saturation, and decay. The saturation time is of the order of 1000 ion gyroperiods, which is delayed at higher values of the plasma parameter beta. We conclude that the dispersion relations play the central role in plasma turbulence evolution, serving as the energy flux channel in the spectral domain.
Prostaglandins produced during class A scavenger receptor-mediated macrophage adhesion differentially regulate cytokine production
Authors: Nikolic Dejan M , Vadali Shanthi , He Beixiang , Ware Jerry , Kelly Thomas , Post Steven R
Published: February 2015

Inflammation is associated with modification of the extracellular environment, changes in cytokine expression, and the accumulation of immune cells. Such modifications create ligands that support SR-A-mediated macrophage adhesion and retention. This may be particularly important in settings, such as atherosclerosis and diabetes, as modified lipoproteins and gluc-collagen are ligands for SR-A. SR-A-mediated adhesion requires the PLA2-dependent generation of AA and its metabolism by 12/15 LOX. In contrast, the inhibition of the COX-dependent conversion of AA to PG had no effect on SR-A-mediated adhesion. In this study, macrophages were isolated from SR-A+/+ and SR-A−/− mice and plated on gluc-collagen to test the hypothesis that COX-derived PGs are produced during SR-A-mediated adhesion and regulate macrophage function. SR-A-mediated binding to gluc-collagen induced a rapid but transient increase in PG production, which required the activation of PLA2 and Src kinase but not PI3K. SR-A+/+ macrophages cultured on gluc-collagen for 24 h secreted a similar amount of TNF-α and 2.5-fold more IL-10 than SR-A−/− macrophages. The inhibition of COX substantially increased TNF-α production but reduced IL-10 levels in SR-A+/+ macrophages. These effects of COX inhibition were reversed by exogenous PGE2 and mimicked by specific antagonism of the EP4 receptor. Thus, in addition to the enhancement of macrophage adhesion, SR-A binding to gluc-collagen stimulates PG production, which in turn, differentially regulates the expression of inflammatory cytokines.
mTOR and metabolic regulation of conventional and regulatory T cells
Authors: Liu Chaohong , Chapman Nicole M , Karmaus Peer W F , Zeng Hu , Chi Hongbo
Published: February 2015

mTOR signaling links bioenergetic and biosynthetic metabolism to immune responses. mTOR is activated by diverse upstream stimuli, including immune signals, growth factors, and nutrients. Recent studies highlight crucial roles of mTOR signaling in immune functions mediated by conventional T cells and Tregs. In this review, we discuss the regulation of mTOR signaling in T cells and the functional impacts of mTOR and metabolic pathways on T cell-mediated immune responses, with a particular focus on the differentiation and function of Tregs.
Neutrophils and inflammatory metabolism in antimicrobial functions of the mucosa
Authors: Campbell Eric L , Colgan Sean P
Published: February 2015

In this mini-review, we will discuss recent findings that implicate neutrophil infiltration and function in establishing a metabolic environment to facilitate efficient pathogen clearance. For decades, neutrophils have been regarded as short lived, nonspecific granulocytes, equipped with toxic antimicrobial factors and a respiratory burst generating ROS. Recent findings demonstrate the importance of HIF signaling in leukocytes and surrounding tissues during inflammation. Here, we will review the potential mechanisms and outcomes of HIF stabilization within the intestinal mucosa.
Functional analysis of NK cell subsets activated by 721.221 and K562 HLA-null cells
Authors: Lisovsky Irene , Isitman Gamze , Bruneau Julie , Bernard Nicole F
Published: February 2015

HLA-null cell lines [721.221 (henceforth, 721) and K562] are often used to study NK cell activation. NK cells are innate immune lymphocytes that express a variety of stochastically expressed inhibitory and activating receptors. Although it is known that 721 and K562 have divergent origins, they have been used interchangeably to stimulate NK cells in many studies. We hypothesized that the differences between 721 and K562 cells may result in differential NK cell-activation patterns. In this report, we assessed all possible combinations of CD107a expression and IFN-γ and CCL4 secretion in total NK and 3DL1+/− NK cell populations induced by these 2 cell lines. 721 activates a significantly higher frequency of NK cells and 3DL1+ NK cells than K562. The NK cell functional subsets that are stimulated to a higher degree by 721 than K562 include those secreting IFN-γ and/or CCL4. On the other hand, the functional subsets that include CD107 expression contribute to a higher proportion of the total NK cell response following stimulation with K562 than 721. These results have implications for the selection of HLA-null cell lines to use as NK cell stimuli in investigations of their role in infectious diseases, cancer, and transplantation.
Neutrophils in host defense: new insights from zebrafish
Authors: Harvie Elizabeth A , Huttenlocher Anna
Published: February 2015

Neutrophils are highly motile phagocytic cells that play a critical role in the immune response to infection. Zebrafish (Danio rerio) are increasingly used to study neutrophil function and host-pathogen interactions. The generation of transgenic zebrafish lines with fluorescently labeled leukocytes has made it possible to visualize the neutrophil response to infection in real time by use of optically transparent zebrafish larvae. In addition, the genetic tractability of zebrafish has allowed for the generation of models of inherited neutrophil disorders. In this review, we discuss several zebrafish models of infectious disease, both in the context of immunocompetent, as well as neutrophil-deficient hosts and how these models have shed light on neutrophil behavior during infection.
Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells
Authors: Joshi Anagha , Pooley Christopher , Freeman Tom C , Lennartsson Andreas , Babina Magda , Schmidl Christian , Geijtenbeek Teunis , Michoel Tom , Severin Jessica , Itoh Masayoshi , Lassmann Timo , Kawaji Hideya , Hayashizaki Yoshihide , Carninci Piero , Forrest Alistair R R , Rehli Michael , Hume David A
Published: February 2015

The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91 human cell types of myeloid origin by use of CAGE profiling. The CAGE sequencing of these samples has allowed us to investigate diverse aspects of transcription control during myelopoiesis, such as identification of novel transcription factors, miRNAs, and noncoding RNAs specific to the myeloid lineage. We further reconstructed a transcription regulatory network by clustering coexpressed transcripts and associating them with enriched cis-regulatory motifs. With the use of the bidirectional expression as a proxy for enhancers, we predicted over 2000 novel enhancers, including an enhancer 38 kb downstream of IRF8 and an intronic enhancer in the KIT gene locus. Finally, we highlighted relevance of these data to dissect transcription dynamics during progressive maturation of granulocyte precursors. A multifaceted analysis of the myeloid transcriptome is made available (http://www.myeloidome.roslin.ed.ac.uk). This high-quality dataset provides a powerful resource to study transcriptional regulation during myelopoiesis and to infer the likely functions of unannotated genes in human innate immunity.
Five-Year Survival Rates for Treatment-Naive Patients With Advanced Melanoma Who Received Ipilimumab Plus Dacarbazine in a Phase III Trial
Authors: Maio Michele , Grob Jean-Jacques , Aamdal Steinar , Bondarenko Igor , Robert Caroline , Thomas Luc , Garbe Claus , Chiarion-Sileni Vanna , Testori Alessandro , Chen Tai-Tsang , Tschaika Marina , Wolchok Jedd D.
Published: February 2015

Purpose

There is evidence from nonrandomized studies that a proportion of ipilimumab-treated patients with advanced melanoma experience long-term survival. To demonstrate a long-term survival benefit with ipilimumab, we evaluated the 5-year survival rates of patients treated in a randomized, controlled phase III trial.

Patients and Methods

A milestone survival analysis was conducted to capture the 5-year survival rate of treatment-naive patients with advanced melanoma who received ipilimumab in a phase III trial. Patients were randomly assigned 1:1 to receive ipilimumab at 10 mg/kg plus dacarbazine (n = 250) or placebo plus dacarbazine (n = 252) at weeks 1, 4, 7, and 10 followed by dacarbazine alone every 3 weeks through week 22. Eligible patients could receive maintenance ipilimumab or placebo every 12 weeks beginning at week 24. A safety analysis was conducted on patients who survived at least 5 years and continued to receive ipilimumab as maintenance therapy.

Results

The 5-year survival rate was 18.2% (95% CI, 13.6% to 23.4%) for patients treated with ipilimumab plus dacarbazine versus 8.8% (95% CI, 5.7% to 12.8%) for patients treated with placebo plus dacarbazine (P = .002). A plateau in the survival curve began at approximately 3 years. In patients who survived at least 5 years and continued to receive ipilimumab, grade 3 or 4 immune-related adverse events were observed exclusively in the skin.

Conclusion

The additional survival benefit of ipilimumab plus dacarbazine is maintained with twice as many patients alive at 5 years compared with those who initially received placebo plus dacarbazine. These results demonstrate a durable survival benefit with ipilimumab in advanced melanoma.
Psychosocial Telephone Counseling for Survivors of Cervical Cancer: Results of a Randomized Biobehavioral Trial
Authors: Wenzel Lari , Osann Kathryn , Hsieh Susie , Tucker Jo A. , Monk Bradley J. , Nelson Edward L.
Published: February 2015

Purpose

Survivors of cervical cancer experience quality-of-life (QOL) disruptions that persist years after treatment. This study examines the effect of a psychosocial telephone counseling (PTC) intervention on QOL domains and associations with biomarkers.

Patients and Methods

We conducted a randomized clinical trial in survivors of cervical cancer, who were ≥ 9 and less than 30 months from diagnosis (n = 204), to compare PTC to usual care (UC). PTC included five weekly sessions and a 1-month booster. Patient-reported outcomes (PROs) and biospecimens were collected at baseline and 4 and 9 months after enrollment. Changes in PROs over time and associations with longitudinal change in cytokines as categorical variables were analyzed using multivariable analysis of variance for repeated measures.

Results

Participant mean age was 43 years; 40% of women were Hispanic, and 51% were non-Hispanic white. Adjusting for age and baseline scores, participants receiving PTC had significantly improved depression and improved gynecologic and cancer-specific concerns at 4 months compared with UC participants (all P < .05); significant differences in gynecologic and cancer-specific concerns (P < .05) were sustained at 9 months. Longitudinal change in overall QOL and anxiety did not reach statistical significance. Participants with decreasing interleukin (IL) -4, IL-5, IL-10, and IL-13 had significantly greater improvement in QOL than those with increasing cytokine levels.

Conclusion

This trial confirms that PTC benefits mood and QOL cancer-specific and gynecologic concerns for a multiethnic underserved population of survivors of cancer. The improvement in PROs with decreases in T-helper type 2 and counter-regulatory cytokines supports a potential biobehavioral pathway relevant to cancer survivorship.
Prognostic Significance of NPM1 Mutations in the Absence of FLT3–Internal Tandem Duplication in Older Patients With Acute Myeloid Leukemia: A SWOG and UK National Cancer Research Institute/Medical Research Council Report
Authors: Ostronoff Fabiana , Othus Megan , Lazenby Michelle , Estey Elihu , Appelbaum Frederick R. , Evans Anna , Godwin John , Gilkes Amanda , Kopecky Kenneth J. , Burnett Alan , List Alan F. , Fang Min , Oehler Vivian G. , Petersdorf Stephen H. , Pogosova-Agadjanyan Era L. , Radich Jerald P. , Willman Cheryl L. , Meshinchi Soheil , Stirewalt Derek L.
Published: February 2015

Purpose

Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3–internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD–negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older patients with AML with this genotype. Therefore, we examined the impact of age on the prognostic significance of NPM1-positive/FLT3-ITD–negative status in older patients with AML.

Patients and Methods

Patients with AML age ≥ 55 years treated with intensive chemotherapy as part of Southwest Oncology Gorup (SWOG) and UK National Cancer Research Institute/Medical Research Council (NCRI/MRC) trials were evaluated. A comprehensive analysis first examined 156 patients treated in SWOG trials. Validation analyses then examined 1,258 patients treated in MRC/NCRI trials. Univariable and multivariable analyses were used to determine the impact of age on the prognostic significance of NPM1 mutations, FLT3-ITDs, and the NPM1-positive/FLT3-ITD–negative genotype.

Results

Patients with AML age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype treated in SWOG trials had a significantly improved 2-year overall survival (OS) as compared with those without this genotype (70% v 32%; P < .001). Moreover, patients age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype had a significantly improved 2-year OS as compared with those age > 65 years with this genotype (70% v 27%; P < .001); any potential survival benefit of this genotype in patients age > 65 years was marginal (27% v 16%; P = .33). In multivariable analysis, NPM1-positive/FLT3-ITD–negative genotype remained independently associated with an improved OS in patients age 55 to 65 years (P = .002) but not in those age > 65 years (P = .82). These results were confirmed in validation analyses examining the NCRI/MRC patients.

Conclusion

NPM1-positive/FLT3-ITD–negative genotype remains a relatively favorable prognostic factor for patients with AML age 55 to 65 years but not in those age > 65 years.
Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo)Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2–Positive Early-Stage Breast Cancer
Authors: Krop Ian E. , Suter Thomas M. , Dang Chau T. , Dirix Luc , Romieu Gilles , Zamagni Claudio , Citron Marc L. , Campone Mario , Xu Na , Smitt Melanie , Gianni Luca
Published: February 2015

Purpose

Trastuzumab emtansine (T-DM1), an antibody–drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC).

Patients and Methods

Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) ≥ 55% received (neo)adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without trastuzumab. T-DM1 was then resumed with optional radiotherapy (sequential or concurrent) for 1 year (planned) of HER2-directed therapy. The coprimary end points were rate of prespecified cardiac events and safety.

Results

Median follow-up was 24.6 months. No prespecified cardiac events or symptomatic congestive heart failures were reported. Four patients (2.7%) had asymptomatic LVEF declines (≥ 10 percentage points from baseline to LVEF < 50%), leading to T-DM1 discontinuation in one patient. Of 148 patients who received ≥ one cycle of T-DM1, 82.4% completed the planned 1-year duration of HER2-directed therapy. During T-DM1 treatment, 38.5% and 2.7% of patients experienced grade 3 and 4 adverse events, respectively. Approximately 95% of patients receiving T-DM1 plus radiotherapy completed ≥ 95% of the planned radiation dose with delay ≤ 5 days.

Conclusion

Use of T-DM1 for approximately 1 year after anthracycline-based chemotherapy was feasible and generally well tolerated by patients with HER2-positive EBC, providing support for phase III trials of T-DM1 in this setting.
Improving Wait Times for Elective Chemotherapy Through Pre-Preparation: A Quality-Improvement Project at the National University Cancer Institute of Singapore
Authors: Soh Thomas I Peng , Tan Yi Siew , Hairom Zarinah , Ibrahim Mariana , Yao Yao , Wong Yuet Peng , Lim Siew Woon , Lim Siew Eng , Goh Boon Cher , Tan Chee Seng
Published: February 2015

Pre-preparation of chemotherapy, together with effective telephone triaging, is an effective way to reduce chemotherapy wait times.
Models of Cancer Survivorship Care: Overview and Summary of Current Evidence
Authors: Halpern Michael T. , Viswanathan Meera , Evans Tammeka S. , Birken Sarah A. , Basch Ethan , Mayer Deborah K.
Published: February 2015

There is substantial variation in survivorship care models. The authors conclude that the optimal nature, timing, intensity, format, and outcomes of survivorship care models are uncertain and require further research.
Risk and Consequences of Chemotherapy-Induced Febrile Neutropenia in Patients With Metastatic Solid Tumors
Authors: Weycker Derek , Li Xiaoyan , Edelsberg John , Barron Rich , Kartashov Alex , Xu Hairong , Lyman Gary H.
Published: February 2015

Among patients receiving myelosuppressive chemotherapy for metastatic cancer in US clinical practice, febrile neutropenia is a frequent complication associated with morbidity, mortality, and economic costs.
Implementing Lung Cancer Screening Using Low-Dose Computed Tomography: Recommendations From an Expert Panel
Authors: Ramsey Scott D. , Malin Jennifer L. , Goulart Bernardo , Ambrose Laurie F. , Kanne Jeffrey P. , McKee Andrea B. , Reed Shelby D. , Schwartz J. Sanford , Sullivan Sean D.
Published: February 2015

Implementation of effective and efficient population-based CT lung cancer screening will require involvement and coordination of stakeholders across the health care system.
Assessing Interprofessional Teamwork in Inpatient Medical Oncology Units
Authors: Weaver A. Charlotta , Callaghan Mary , Cooper Abby L. , Brandman James , O'Leary Kevin J.
Published: February 2015

The authors conclude that in inpatient oncology units, discrepancies exist between nurses' and physicians' ratings of teamwork and collaboration. Oncologists seem to be unaware that teamwork is suboptimal in this setting.
Plk4-dependent phosphorylation of STIL is required for centriole duplication
Authors: Kratz Anne-Sophie , Bärenz Felix , Richter Kai T. , Hoffmann Ingrid
Published: February 2015

Duplication of centrioles, namely the formation of a procentriole next to the parental centriole, is regulated by the polo-like kinase Plk4. Only a few other proteins, including STIL (SCL/TAL1 interrupting locus, SIL) and Sas-6, are required for the early step of centriole biogenesis. Following Plk4 activation, STIL and Sas-6 accumulate at the cartwheel structure at the initial stage of the centriole assembly process. Here, we show that STIL interacts with Plk4 in vivo. A STIL fragment harboring both the coiled-coil domain and the STAN motif shows the strongest binding affinity to Plk4. Furthermore, we find that STIL is phosphorylated by Plk4. We identified Plk4-specific phosphorylation sites within the C-terminal domain of STIL and show that phosphorylation of STIL by Plk4 is required to trigger centriole duplication.
Nuclear p120-catenin contributes to anoikis resistance of Lobular Breast Cancer through Kaiso-dependent Wnt11 expression
Authors: van de Ven Robert A. H. , Tenhagen Milou , Meuleman Wouter , van Riel Jeske J. G. , Schackmann Ron C. J. , Derksen Patrick W. B.
Published: February 2015

E-cadherin inactivation underpins the progression of invasive lobular breast carcinoma (ILC). In ILC, p120-catenin (p120) translocates to the cytosol where it controls anchorage independence through the Rho-Rock signaling pathway, a key mechanism driving tumor growth and metastasis. We now demonstrate that anchorage-independent ILC cells show an increase in nuclear p120, which results in relief of transcriptional repression by Kaiso. To identify the Kaiso target genes that control anchorage independence we performed genome-wide mRNA profiling on anoikis resistant mouse ILC cells, and identified 29 candidate target genes including the established Kaiso target Wnt11. Our data indicate that anchorage-independent upregulation of Wnt11 in ILC cells is controlled by nuclear p120 through inhibition of Kaiso-mediated transcriptional repression. Finally, we show that Wnt11 promotes activation of RhoA, which causes ILC anoikis resistance. Our findings thereby establish a mechanistic link between E-cadherin loss and subsequent control of Rho-driven anoikis resistance through p120/Kaiso-dependent expression of Wnt11.
Treatment of cardiac arrhythmias in Rett Syndrome with sodium channel blocking antiepileptic drugs
Authors: Herrera José A. , Ward Christopher S. , Pitcher Meagan R. , Percy Alan K. , Skinner Steven , Kaufmann Walter E. , Glaze Daniel G. , Wehrens Xander H. T. , Neul Jeffrey L.
Published: February 2015

One quarter of deaths in Rett Syndrome (RTT), an X-linked neurodevelopmental disorder, are sudden and unexpected. RTT is associated with prolonged QTc interval (LQT), and LQT-associated cardiac arrhythmias are a potential cause of unexpected death. Standard of care for LQT in RTT is treatment with β-adrenergic antagonists; however, recent work indicates that acute treatment of mice with RTT with a β-antagonist, propranolol, did not prevent lethal arrhythmias. In contrast, acute treatment with a sodium channel blocker, phenytoin, prevented arrhythmias. Chronic dosing of propranolol may be required for efficacy; therefore, we tested the efficacy of chronic treatment with either propranolol or phenytoin on RTT mice. Phenytoin completely abolished arrhythmias, whereas propranolol showed no benefit. Surprisingly, phenytoin also normalized weight and activity, but worsened breathing patterns. To explore the role of sodium channel blockers on QT in people with RTT, we performed a retrospective analysis of QT status before and after sodium channel blocker antiepileptic therapies. Individuals with RTT and LQT significantly improved their QT interval status after being started on sodium channel blocker antiepileptic therapies. Thus, sodium channel blockers should be considered for the clinical management of LQT in individuals with RTT.
The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway
Authors: Roboti Peristera , Sato Keisuke , Lowe Martin
Published: February 2015

Golgins are coiled-coil proteins that participate in membrane tethering events at the Golgi apparatus. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210, which is mutated in the rare skeletal disorder achondrogenesis type 1A, have yielded conflicting results regarding its involvement in trafficking. Here, we re-investigated the trafficking role of GMAP-210, and find that it is indeed required for efficient trafficking in the secretory pathway. GMAP-210 acts at both the ERGIC and Golgi apparatus during anterograde trafficking, and is also required for retrograde trafficking to the endoplasmic reticulum. Using co-depletion experiments, we also find that GMAP-210 acts in a partially redundant manner with the golgin GM130 to ensure efficient anterograde cargo delivery to the cis-Golgi. In summary, our results indicate a role for GMAP-210 in several trafficking steps at the ER/Golgi interface, some of which are partially redundant with another golgin, namely GM130.
Ways to be different: foraging adaptations that facilitate higher intake rates in a northerly-wintering shorebird compared to a low-latitude conspecific
Authors: Ruthrauff Daniel R. , Dekinga Anne , Gill Robert E. , van Gils Jan A. , Piersma Theunis
Published: February 2015

At what phenotypic level do closely related subspecies that live in different environments differ with respect to food detection, ingestion, and processing? This question motivated an experimental study on rock sandpipers (Calidris ptilocnemis). The species’ nonbreeding range spans 20 degrees of latitude, the extremes of which are inhabited by two subspecies: Calidris p. ptilocnemis that winters primarily in upper Cook Inlet, Alaska (61°N), and C. p. tschuktschorum that overlaps slightly with C. p. ptilocnemis but whose range extends much farther south (∼40°N). In view of the strongly contrasting energetic demands of their distinct nonbreeding distributions, we conducted experiments to assess the behavioural, physiological, and sensory aspects of foraging, and we used the bivalve Macoma balthica for all trials. Ptilocnemis consumed a wider range of prey sizes, had higher maximum rates of energy intake, processed shell waste at higher maximum rates, and handled prey more quickly. Notably, however, the two subspecies did not differ in their abilities to find buried prey. The subspecies were similar in size and had equally sized gizzards, but the more northern ptilocnemis individuals were 10–14% heavier than their same-sex tschuktschorum counterparts. The higher body mass in ptilocnemis likely resulted from hypertrophy of digestive organs (e.g. intestine, liver) related to digestion and nutrient assimilation. Given the previously established equality of the two subspecies’ metabolic capacities, we propose that the high-latitude nonbreeding range of ptilocnemis rock sandpipers is primarily facilitated by digestive (i.e. physiological) aspects of their foraging ecology rather than behavioural or sensory aspects.
Evolution of voltage-gated ion channels at the emergence of Metazoa
Authors: Moran Yehu , Barzilai Maya Gur , Liebeskind Benjamin J. , Zakon Harold H.
Published: February 2015

Voltage-gated ion channels are large transmembrane proteins that enable the passage of ions through their pore across the cell membrane. These channels belong to one superfamily and carry pivotal roles such as the propagation of neuronal and muscular action potentials and the promotion of neurotransmitter secretion in synapses. In this review, we describe in detail the current state of knowledge regarding the evolution of these channels with a special emphasis on the metazoan lineage. We highlight the contribution of the genomic revolution to the understanding of ion channel evolution and for revealing that these channels appeared long before the appearance of the first animal. We also explain how the elucidation of channel selectivity properties and function in non-bilaterian animals such as cnidarians (sea anemones, corals, jellyfish and hydroids) can contribute to the study of channel evolution. Finally, we point to open questions and future directions in this field of research.
The Activity of Isolated Neurons and the Modulatory State of an Isolated Nervous System Represent a Recent Behavioural State
Authors: Dyakonova V.E. , Hernádi L. , Ito E. , Dyakonova T.L , Chistopolsky I.A. , Zakharov I.S. , Sakharov D.A.
Published: February 2015

Behavioural/motivational state is known to influence nearly all aspects of physiology and behaviour. The cellular basis of behavioural state control is only partially understood. Our investigation, performed on the pond snail Lymnaea stagnalis whose nervous system is useful for work on completely isolated neurons, provided several results related to this problem. First, we demonstrate that the behavioural state can produce long-term changes in individual neurons that persist even after neuron isolation from the nervous system. Specifically, we found that pedal serotonergic neurons that control locomotion show higher activity and lower membrane potential after being isolated from the nervous systems of hungry animals. Second, we show that the modulatory state (the chemical neuroactive microenvironment of the central ganglia) changes in accord with the nutritional state of an animal and produces predicted changes in single isolated locomotor neurons. Third, we report that observed hunger induced effects can be explained by the increased synthesis of serotonin in pedal serotonergic neurons, which impacts the electrical activity of isolated serotonergic neurons and the intensity of extrasynaptic serotonin release from the pedal ganglia.
Electrogenesis in the lower Metazoa and implications for neuronal integration
Authors: Meech Robert W.
Published: February 2015

Electrogenic communication appears to have evolved independently in a variety of animal and plant lineages. Considered here are metazoan cells as disparate as the loose three-dimensional parenchyma of glass sponges, the two-dimensional epithelial sheets of hydrozoan jellyfish and the egg cell membranes of the ctenophore Beroe ovata, all of which are capable of generating electrical impulses. Neuronal electrogenesis may have evolved independently in ctenophores and cnidarians but the dearth of electrophysiological data relating to ctenophore nerves means that our attention is focused on the Cnidaria, whose nervous systems have been the subject of extensive study. The aim here is to show how their active and passive neuronal properties interact to give integrated behaviour. Neuronal electrogenesis, goes beyond simply relaying ‘states of excitement’ and utilizes the equivalent of a set of basic electrical ‘apps’ to integrate incoming sensory information with internally generated pacemaker activity. A small number of membrane-based processes make up these analogue applications. Passive components include the decremental spread of current determined by cellular anatomy; active components include ion channels specified by their selectivity and voltage dependence. A recurring theme is the role of inactivating potassium channels in regulating performance. Although different aspects of cnidarian behaviour are controlled by separate neuronal systems, integrated responses and coordinated movements depend on interactions between them. Integrative interactions discussed here include those between feeding and swimming, between tentacle contraction and swimming and between slow and fast swimming in the hydrozoan jellyfish Aglantha digitale.
Improvement of Toluene Oxidation Catalysis by Cu Doping into Co3O4 in Pt/Co3O4/CeO2–ZrO2–SnO2/γ-Al2O3 Catalysts
Authors: Masui Toshiyuki , Kamata Tomoya , Fukuhara Nashito , Imanaka Nobuhito
Published: February 2015

1 wt % Pt/11 wt % (Co1−xCux)3O4−δ/16 wt % Ce0.62Zr0.20Sn0.18O2.0/γ-Al2O3 catalysts were prepared to realize complete combustion of toluene at lower temperatures than that of a 1 wt % Pt/11 wt % Co3O4/16 wt % Ce0.62Zr0.20Sn0.18O2.0/γ-Al2O3 catalyst previously reported by our group without increasing the amount of platinum. Addition of copper into the Co3O4 lattice was effective to facilitate oxygen release and storage, and thereby, the toluene oxidation activity was enhanced. The highest activity for the combustion of toluene was observed using a 1 wt % Pt/13 wt % (Co0.97Cu0.03)3O4−δ/16 wt % Ce0.62Zr0.20Sn0.18O2.0/γ-Al2O3 catalyst, and despite a smaller platinum loading in the present catalyst, toluene was completely oxidized to carbon dioxide and water vapor at the lower temperature of 140 °C compared to that (160 °C) using 1 wt % Pt/11 wt % Co3O4/16 wt % Ce0.62Zr0.20Sn0.18O2.0/γ-Al2O3.
Use of In Situ Generated Nitrosocarbonyl Compounds in Catalytic Asymmetric α-Hydroxylation and α-Amination Reactions
Authors: Maji Biplab , Yamamoto Hisashi
Published: February 2015

Nitroso compounds are highly fascinating electrophiles as they are able to selectively transfer both the heteroatoms in a variety of oxidation reactions. Bench stable aryl-nitroso compounds are most extensively utilized for this purpose. However, the prominent success of aryl-nitroso chemistry is still immature because of the difficulty in the cleavage of N-aryl bond. Nitrosocarbonyl compounds with easily removable protecting groups (e.g. Boc and Cbz) on the other hand are more attractive reagents. They are highly reactive, easily manipulable, and readily available via the oxidation of N-protected hydroxylamines. However, the transient nature and incompatibility of the catalytic processes with their generation has incarcerated their use mostly in hetero-Diels–Alder and ene reactions. In this account we will summarize our efforts to utilize the nitrosocarbonyl compounds as a source of electrophilic oxygen and nitrogen in a variety of asymmetric carbon–heteroatom bond-forming reactions. The O- vs. N-selectivity can be tuned by switching reaction conditions. Thus, highly functionalized tertiary α-hydroxy and α-amino carboxylic acids, tertiary α-hydroxy phosphonic acid derivatives and β-amino alcohols were synthesized in high yields and high enantioselectivities using nitrosocarbonyl compounds as a source of electrophilic oxygen and nitrogen.
Glass-transition Temperature Determination for Polymers Using Europium Complex as a Fluorescence Probe
Authors: Aoki Mika , Kawaguchi Daisuke , Ganbe Tatsuya , Sekine Nobuyuki , Okamoto Kenji , Tanaka Keiji
Published: February 2015

We showed that a thermally stable europium complex can be used as a fluorescence probe to characterize glass-transition behavior for polymers. This kind of simple but novel work opens many possibilities of measurements for physical properties of polymers at higher temperatures.
Effective Hydrazine Electrochemical Sensors Based on Porous CuO Nanobelts Supported on Cu Substrate
Authors: Wang Shaozhen , Xu Xiaoyue , Zhang Xiaojun
Published: February 2015

Hydrazine sensors, especially hydrazine electrochemical sensors, have been widely studied due to their portability and rapid and high sensitivity. Recently, however, the development of many hydrazine electrochemical sensors has been limited because the modifier on the electrodes tends to fall off easily during surface modification. In the present work, we designed a porous CuO nanobelt on a Cu rod as a composite electrode to detect hydrazine, which exhibited ultrahigh sensitivity of 41.17 mA µM−1 cm−2 and very low detection limit of 0.1 µM, and they especially avoided the possibility of the inconvenient modifying process and falling off. All the results indicated that these composite electrodes have a good potential application in the detection of hydrazine.
In vitro retention of a new thermoplastic titratable mandibular advancement device
Authors: Braem Marc
Published: February 2015

Oral appliance (OA) therapy with a mandibular advancement device (OAm) is a non-invasive, alternative approach to maintaining upper airway patency. The main requirement for an OAm to be effective is the adequate retention on the teeth while the patient is asleep. We evaluated the retentive forces of a new low-cost, customizable, titratable, thermoplastic OAm (BluePro®; BlueSom, France). Dental impressions and casts were made for one patient with complete upper and lower dental arches including the third molars and class II bite proportions. A setup based on Frasaco ANA-4 models was also used. Two protrusive positions of the mandible were investigated: 3 mm and 8 mm, representing respectively 25% and 65% of the maximal protrusion. The forces required to remove the BluePro® device from the carriers were recorded continuously over 730 cycles (=365 days, twice a day) to simulate 1 year of clinical use. At 8 mm protrusion the BluePro® device showed retentive forces of ~27N. There was a slight but non-significant decrease in retentive forces in the tests on the epoxified carriers which was not found on the ANA-4 carriers. There were no significant differences between the carriers as a function of protrusion. The BluePro® device tested in the present study possesses sufficient retention forces to resist initial jaw opening forces and full mouth opening forces estimated to be ~20N. It could therefore broaden the indications for use of thermoplastic OAms. It could provide a temporary OAm while a custom-made OAm is being manufactured or repaired. Patients could be provided with a low-cost try-out device capable of reliable titration, providing an indication of effectiveness and of patient acceptance of an OAm, although the effect of device shape and size on therapeutic outcome is not yet known. Finally it could provide an affordable OAm solution in resource-restricted healthcare settings.
The diagnostic usability of selected narrativity indices in stories about close relationships in the assessment of personality organization
Authors: Soroko Emilia
Published: February 2015

Cel

Celem prezentowanych badań było sprawdzenie użyteczności wybranych wskaźników narracyjności wypowiedzi autobiograficznych na temat ważnych relacji interpersonalnych, w diagnozie poziomu organizacji osobowości neurotycznego (NPO) oraz borderline (BPO).

Metoda

Do predykcji poziomu organizacji osobowości użyto wybranych wskaźników narracyjności, szczegółowych oraz zgeneralizowanych, wywiedzionych z dwóch odrębnych poziomów analizy. Były to wskaźniki 1) leksykalne określane w zautomatyzowany sposób oraz 2) poziomu odbioru wypowiedzi, które dotyczyły koherencji narracji i były oceniane metodą sędziów kompetentnych.

Wyniki

Wskaźnik narracyjności działanie „ja” okazał się dobrym predyktorem zarówno BPO jak i NPO, a czynnik ludzki dobrym predyktorem BPO, jeśli osiągał niskie wartości. Ponadto zgeneralizowany wskaźnik, opisujący narracje nasycone intencjonalnością, konkretnością, działaniem „ja”, ale jednocześnie pozbawione czynnika ludzkiego, okazał się najlepszym predyktorem BPO. Określono też, że jeśli koherencja narracji oraz wymiar koherencji – integracja – wzrastają, to prawdopodobieństwo diagnozy BPO maleje.

Wnioski

Badania wspierają tezę, że powierzchniowe wskaźniki narracyjności mogą być predyktorami głębokiej struktury osobowości. Wyniki są uzasadnione w świetle teorii Kernberga i mają potencjał użyteczności diagnostycznej w praktyce klinicznej jako dodatkowe źródła informacji w procesie diagnostycznym i psychoterapeutycznym.
The Montreal Cognitive Assessment 7.2 – Polish adaptation and research on equivalency
Authors: Gierus Jacek , Mosiołek Anna , Koweszko Tytus , Kozyra Olga , Wnukiewicz Paulina , Łoza Bartosz , Szulc Agata
Published: February 2015

Cel

Montrealska Skala Oceny Funkcji Poznawczych MoCA jest przesiewowym narzędziem do wykrywania łagodnych zaburzeń poznawczych (Mild Cognitive Impairmnent –MCI). Dotąd dostępna była w Polsce jedna wersja tej metody. Aby móc ocenić progresję zaburzeń albo efektywność terapii wymagane są dwie wersje o udokumentowanej równoważności. Przetłumaczono angielską wersję 7.2. metody i zaadaptowano ją kulturowo aby utrzymać odpowiednią rzetelność pomiaru. Następnie zbadano równoważność obu polskich wersji. Niniejszy artykuł ma na celu przedstawienie procesu adaptacji polskiej wersji skali MoCA 7.2. oraz wyników badań nad równoważnością obu dostępnych polskich wersji.

Metoda

66 pacjentów psychiatrycznych (37 mężczyzn, 29 kobiety) z różnego stopnia i różnej etiologii dysfunkcjami poznawczymi, zostało przebadanych za pomocą obu wersji Montrealskiej Skali Oceny Funkcji Poznawczych. Kolejność podawania metod była losowa, nie stosowano pomiędzy nimi żadnych przerw czasowych.

Wyniki

Nie stwierdzono istotnych różnic (p=0,601) w wynikach ogólnych pierwszej polskiej wersji MoCA oraz wersji równoważnej. Równoważność mierzona współczynnikiem korelacji rho Spearmana (rho=0,926) okazała się bardzo wysoka.

Wnioski

Obie polskie wersje skali MoCA są równoważne i mogą być potencjalnie użyteczne w badaniach z powtarzanym pomiarem, przy ocenie progresji zaburzeń poznawczych oraz w badaniach nad efektywnością leczenia. Możliwość ich kolejnego użycia stwarza warunki do śledzenia możliwości poznawczych pacjentów, bez konieczności podawania tego samego materiału testowego.
The prevalence of common mental disorders in the population of adult Poles by sex and age structure – an EZOP Poland study
Authors: Kiejna Andrzej , Piotrowski Patryk , Adamowski Tomasz , Moskalewicz Jacek , Wciórka Jacek , Stokwiszewski Jakub , Rabczenko Daniel , Kessler Ronald
Published: February 2015

Cel

W artykule zaprezentowano rozpowszechnienie powszechnie występujących zaburzeń psychicznych(CMD) według klasyfikacji DSM-IV, podczas całego życia (LT), na podstawie oceny reprezentatywnej grupy 10081 Polaków w wieku od 18 do 64 lat.

Metoda

Komputerowa wersja narzędzia CIDI 3.0 została zaadoptowana zgodnie z protokołem WMH. Badanie zostało przeprowadzone przez certyfikowanych i nadzorowanych ankieterów.

Wyniki

Wśród 18 CMD najwyższe rozpowszechnienie dotyczyło nadużywania alkoholu, które częściej rozpoznawano u mężczyzn (18,6%) niż u kobiet (3,3%), (p<0,01). Drugie rozpowszechnienie dotyczyło ataków paniki, a różnice pomiędzy wskaźnikami dla kobiet (8,5%) i dla mężczyzn (3,9%) były istotne (p<0,01). Podobnie, depresja blisko dwukrotnie częściej, występowała u kobiet (4,0%) niż u mężczyzn (1,9%), (p<0,01). Wyższe wskaźniki rozpowszechnienia dotyczyły kobiet z diagnozą: uogólnione zaburzenie lękowe, agorafobia, zaburzenie paniczne, fobia specyficzna (p<0,01) oraz dystymia (p<0,05). Wśród mężczyzn częściej stwierdzano nadużywanie alkoholu oraz uzależnienie od alkoholu i substancji (p<0,01) a także występowanie hipomanii (p<0,05). Dla większości z analizowanych zaburzeń wyższe wskaźniki rozpowszechnienia, z różnicami istotnymi statystycznie pomiędzy wartościami odnosiły się do wyższych przedziałów wiekowych. Natomiast w przypadku fobii społecznej i fobii specyficznych, nadużywania substancji wskaźnik rozpowszechnienia był najwyższy wśród mężczyzn z najniższego przedziału wiekowego. Nie stwierdzono różnic istotnych statystycznie hipomanii w poszczególnych przedziałach wiekowych zarówno u mężczyzn jak i u kobiet.

Wnioski

Wskaźniki rozpowszechnienia uzyskane w badaniu EZOP Polska różnią się od wskaźników rozpowszechnienia zaburzeń psychicznych opisywanych wcześniej w innych krajach. Niższe wartości odnosiły się do rozpowszechnienia zaburzeń afektywnych oraz niektórych zaburzeń lękowych. Jedynie nadużywanie alkoholu rozpoznano częściej niż w pozostałych badaniach o zbliżonej metodologii za wyjątkiem Ukrainy, gdzie rozpowszechnienie tego zaburzenia było na zbliżonym poziomie.
Diagnosis of Posttraumatic Stress Disorder (PTSD) by the Structured Clinical Interview SCID-I
Authors: Zawadzki Bogdan , Popiel Agnieszka , Cyniak-Cieciura Maria , Jakubowska Barbara , Pragłowska Ewa
Published: February 2015

Cel

Trafna i rzetelna diagnoza pourazowego zaburzenia stresowego jest ważna w praktyce klinicznej, orzecznictwie i badaniach naukowych. Celem badania było określenie właściwości psychometrycznych polskiej wersji ustrukturalizowanego wywiadu klinicznego SCID-I-PTSD, przeznaczonego do diagnozy pourazowego zaburzenia stresowego w oparciu o kryteria DSM-IV-TR.

Metoda

W badaniu uwzględniono dane od pięciuset dwudziestu sześciu uczestników wypadków drogowych. Podstawę diagnozy klinicznej stanowił wywiad SCID-I-PTSD. Osoby badane wypełniały także zestaw narzędzi samoopisowych służących do oceny objawów PTSD (PDS), depresji (BDI-II), lęku (STAI) i potraumatycznych przekonań (PTCI).

Wyniki

Pomiar za pomocą wywiadu cechuje wysoka rzetelność oraz trafność zbieżna i różnicowa. W porównaniu do narzędzia samoopisowego wywiad SCID-I-PTSD charakteryzuje się wyższą specyficznością. Pozycje wywiadu wykazują dobre własności psychometryczne (za wyjątkiem pozycji C3) oraz brak stronniczości w odniesieniu do płci. Analizy nie pozwoliły na jednoznaczne określenie struktury czynnikowej objawów PTSD.

Wnioski

Otrzymane wyniki pozwalają twierdzić, że ustrukturalizowany wywiad kliniczny SCID-I, część poświęcona badaniu PTSD, wchodząca w skład Modułu F (zaburzenia lękowe) stanowi trafne i rzetelne narzędzie diagnozy pourazowego zaburzenia stresowego.