scholarly journals An Effective Model of Endogenous Clocks and External Stimuli Determining Ciradian Rhythms

2021 ◽  
Author(s):  
Tim Breitenbach ◽  
Charlotte Helfrich-Förster ◽  
Thomas Dandekar
Keyword(s):  
Research Field ◽  
Feedback Loops ◽  
Effective Model ◽  
High Dose ◽  
Mathematical Framework ◽  
Biological Processes ◽  
Similar Idea ◽  
Eukaryotic Organisms ◽  
External Stimuli ◽  
The Impact

Abstract Circadian endogenous clocks of eukaryotic organisms are an established and rapidly developing research field. To investigate and simulate in an effective model the effect of external stimuli on such clocks and their components we developed a software framework for download and simulation. The application is useful to understand the different involved effects in a mathematical simple and effective model. This concerns the effects of Zeitgebers, feedback loops and further modifying components. We start from a known mathematical oscillator model, which is based on experimental molecular findings. This is extended with an effective framework that includes the impact of external stimuli on the circadian oscillations including high dose pharmacological treatment. The external stimuli framework defines a systematic procedure by input-output-interfaces to couple different oscillators. With a similar idea the issue of singularity points of circadian clocks is modeled and related to different model approaches. Tables explain modifications for specific organisms and by different modules. The mathematical framework and formalism is generic and allows to study in general the effect of external stimuli on oscillators and other biological processes. For an easy replication of each numerical experiment presented in this work and an easy implementation of the framework the corresponding Mathematica files are fully made available. They can be downloaded at the following link: https://www.biozentrum.uni-wuerzburg.de/bioinfo/computing/circadian/.

scholarly journals An effective model of endogenous clocks and external stimuli determining circadian rhythms

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tim Breitenbach ◽  
Charlotte Helfrich-Förster ◽  
Thomas Dandekar
Keyword(s):  
Biological Effects ◽  
Research Field ◽  
Effective Model ◽  
High Dose ◽  
Mathematical Framework ◽  
Biological Processes ◽  
Response Curves ◽  
Eukaryotic Organisms ◽  
External Stimuli ◽  
The Impact

AbstractCircadian endogenous clocks of eukaryotic organisms are an established and rapidly developing research field. To investigate and simulate in an effective model the effect of external stimuli on such clocks and their components we developed a software framework for download and simulation. The application is useful to understand the different involved effects in a mathematical simple and effective model. This concerns the effects of Zeitgebers, feedback loops and further modifying components. We start from a known mathematical oscillator model, which is based on experimental molecular findings. This is extended with an effective framework that includes the impact of external stimuli on the circadian oscillations including high dose pharmacological treatment. In particular, the external stimuli framework defines a systematic procedure by input-output-interfaces to couple different oscillators. The framework is validated by providing phase response curves and ranges of entrainment. Furthermore, Aschoffs rule is computationally investigated. It is shown how the external stimuli framework can be used to study biological effects like points of singularity or oscillators integrating different signals at once. The mathematical framework and formalism is generic and allows to study in general the effect of external stimuli on oscillators and other biological processes. For an easy replication of each numerical experiment presented in this work and an easy implementation of the framework the corresponding Mathematica files are fully made available. They can be downloaded at the following link: https://www.biozentrum.uni-wuerzburg.de/bioinfo/computing/circadian/.

scholarly journals Regulation of mRNA cap methylation

2009 ◽  
Vol 425 (2) ◽  
pp. 295-302 ◽  
Author(s):  
Victoria H. Cowling
Keyword(s):  
Gene Expression ◽  
Cell Viability ◽  
Nuclear Export ◽  
Present Review ◽  
Biological Processes ◽  
Experimental Systems ◽  
Efficient Gene ◽  
Cellular Mrnas ◽  
Eukaryotic Organisms ◽  
The Impact

The 7-methylguanosine cap added to the 5′ end of mRNA is essential for efficient gene expression and cell viability. Methylation of the guanosine cap is necessary for the translation of most cellular mRNAs in all eukaryotic organisms in which it has been investigated. In some experimental systems, cap methylation has also been demonstrated to promote transcription, splicing, polyadenylation and nuclear export of mRNA. The present review discusses how the 7-methylguanosine cap is synthesized by cellular enzymes, the impact that the 7-methylguanosine cap has on biological processes, and how the mRNA cap methylation reaction is regulated.

Fluorescent potentiometric dyes for membrane-potential imaging

1994 ◽  
Vol 52 ◽  
pp. 166-167
Author(s):  
Leslie M. Loew
Keyword(s):  
Membrane Potential ◽  
Single Cells ◽  
Quantitative Imaging ◽  
Optical Recording ◽  
Biological Processes ◽  
Major Focus ◽  
The Past ◽  
Excitable Systems ◽  
Major Application ◽  
The Impact

A major application of potentiometric dyes has been the multisite optical recording of electrical activity in excitable systems. After being championed by L.B. Cohen and his colleagues for the past 20 years, the impact of this technology is rapidly being felt and is spreading to an increasing number of neuroscience laboratories. A second class of experiments involves using dyes to image membrane potential distributions in single cells by digital imaging microscopy - a major focus of this lab. These studies usually do not require the temporal resolution of multisite optical recording, being primarily focussed on slow cell biological processes, and therefore can achieve much higher spatial resolution. We have developed 2 methods for quantitative imaging of membrane potential. One method uses dual wavelength imaging of membrane-staining dyes and the other uses quantitative 3D imaging of a fluorescent lipophilic cation; the dyes used in each case were synthesized for this purpose in this laboratory.

scholarly journals Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2945
Author(s):  
Mélanie Mercier ◽  
Corentin Orvain ◽  
Laurianne Drieu La Rochelle ◽  
Tony Marchand ◽  
Christopher Nunes Gomes ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Skeletal Involvement ◽  
Large B Cell Lymphoma ◽  
Dose Methotrexate ◽  
The Impact ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p <0.001 and 83 vs. 58%, p < 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials.

The underrepresentation of female participants in studies assessing the impact of high-dose exercise on cardiovascular outcomes: a scoping review

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
S Pallikadavath ◽  
R Patel ◽  
CL Kemp ◽  
M Hafejee ◽  
N Peckham ◽  
...  
Keyword(s):  
Scoping Review ◽  
High Volume ◽  
Cardiovascular Outcomes ◽  
High Dose ◽  
Funding Sources ◽  
Review Protocol ◽  
The Mean ◽  
The Impact ◽  
Over Time ◽  
Funding Acknowledgements

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiovascular adaptations as a result of exercise conducted at high-intensity and high-volume are often termed the ‘Athlete’s heart’. Studies have shown that these cardiovascular adaptations vary between sexes. It is important that both sexes are well represented in this literature. However, many studies assessing the impact of high-dose exercise on cardiovascular outcomes under-recruit female participants. Purpose This scoping review aimed to evaluate the representation of females in studies assessing the impact of high-dose exercise on cardiovascular outcomes and demonstrate how this has changed over time. Methods The scoping review protocol as outlined by Arksey and O’Malley was used. OVID and EMBASE databases were searched and studies independently reviewed by two reviewers. Studies must have investigated the effects of high-dose exercise on cardiovascular outcomes. To assess how the recruitment of females has changed over time, two methods were used. One, the median study date was used to categorise studies into two groups. Two, studies were divided into deciles to form ten equal groups over the study period. Mean percentage of female recruitment and percentage of studies that failed to include females were calculated. Results Overall, 250 studies were included. Over half the studies (50.8%, n = 127) did not include female participants. Only 3.2% (n = 8) did not include male participants. Overall, mean percentage recruitment was 18.2%. The mean percentage of recruitment was 14.5% before 2011 and 21.8% after 2011. The most recent decile of studies demonstrated the highest mean percentage of female recruitment (29.3%) and lowest number of studies that did not include female participants (26.9%). Conclusion Female participants are significantly underrepresented in studies assessing cardiovascular outcomes caused by high-dose exercise. The most recent studies show that female recruitment may be improving, however, this still falls significantly short for equal representation. Risk factors, progression and management of cardiovascular diseases vary between sexes, hence, translating findings from male dominated data is not appropriate. Future investigators should aim to establish barriers and strategies to optimise fair recruitment. Mean percentage females recruited per study (%) Percentage studies that do not include women (%) Overall (n = 250) 18.2 50.8 (n = 127) Studies before 2011 (n = 121) 14.5 59.5 (n = 72) Studies after 2011 (n = 129) 21.8 42.6 (n = 55) Table 1: Female recruitment characteristics. The year 2011 (median study year) was chosen as this divides all included studies into two equal groups.

scholarly journals The Challenge of Illusory Perception of Animals: The Impact of Methodological Variability in Cross-species Investigation

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1618
Author(s):  
Maria Santacà ◽  
Christian Agrillo ◽  
Maria Elena Miletto Petrazzini
Keyword(s):  
Research Field ◽  
Choice Test ◽  
Training Procedure ◽  
Biologically Relevant ◽  
Selective Pressures ◽  
Extensive Training ◽  
Behavioural Research ◽  
Illusory Perception ◽  
Methodological Approaches ◽  
The Impact

Although we live on the same planet, there are countless different ways of seeing the surroundings that reflect the different individual experiences and selective pressures. In recent decades, visual illusions have been used in behavioural research to compare the perception between different vertebrate species. The studies conducted so far have provided contradictory results, suggesting that the underlying perceptual mechanisms may differ across species. Besides the differentiation of the perceptual mechanisms, another explanation could be taken into account. Indeed, the different studies often used different methodologies that could have potentially introduced confounding factors. In fact, the possibility exists that the illusory perception is influenced by the different methodologies and the test design. Almost every study of this research field has been conducted in laboratories adopting two different methodological approaches: a spontaneous choice test or a training procedure. In the spontaneous choice test, a subject is presented with biologically relevant stimuli in an illusory context, whereas, in the training procedure, a subject has to undergo an extensive training during which neutral stimuli are associated with a biologically relevant reward. Here, we review the literature on this topic, highlighting both the relevance and the potential weaknesses of the different methodological approaches.

scholarly journals Pharmacologic modulation of 5-fluorouracil by folinic acid and high-dose pyridoxine for treatment of patients with digestive tract carcinomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David Machover ◽  
Wathek Almohamad ◽  
Vincent Castagné ◽  
Christophe Desterke ◽  
Léa Gomez ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Digestive Tract ◽  
Vitamin B6 ◽  
Colorectal Adenocarcinoma ◽  
High Dose ◽  
High Concentration ◽  
Carcinoma Of The Esophagus ◽  
Pancreas Adenocarcinoma ◽  
The Impact ◽  
High Dose Vitamin

AbstractSupplementation of cancer cells exposed to 5-fluorouracil (FUra) and folinic acid (FA) with high concentration pyridoxal 5′-phosphate, the cofactor of vitamin B6, potentiates the cytotoxicity of FUra in a synergistic interaction mode. We report a pilot study in 13 patients with previously untreated advanced carcinoma of the digestive tract to assess the impact of high-dose pyridoxine (PN) on the antitumor activity of regimens comprising FUra and FA. Five patients had colorectal adenocarcinoma (CRC); 5 had pancreas adenocarcinoma (PC); and 3 had squamous cell carcinoma of the esophagus (EC). Patients with CRC and with PC received oxaliplatin, irinotecan, FUra and FA, and patients with EC had paclitaxel, carboplatin, FUra and FA. PN iv from 1000 to 3000 mg/day preceded each administration of FA and FUra. Eleven patients responded. Two patients with CRC attained CRs and 3 had PRs with reduction rates ≥ 78%. Two patients with PC attained CRs, and 2 had PRs with reduction rates ≥ 79%. Responders experienced disappearance of most metastases. Of 3 patients with EC, 2 attained CRs. Median time to attain a response was 3 months. Unexpected toxicity did not occur. Results suggest that high-dose vitamin B6 enhances antitumor potency of regimens comprising FUra and FA.

New Strategies for the Treatment of Acute Myeloid Leukemia Including Antibodies and Other Novel Agents

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Martin S. Tallman
Keyword(s):  
Older Adults ◽  
Acute Myeloid Leukemia ◽  
Multidrug Resistance ◽  
Myeloid Leukemia ◽  
Cytotoxic Agents ◽  
High Dose ◽  
Farnesyltransferase Inhibitors ◽  
Younger Adults ◽  
The Impact ◽  
Acute Myeloid

Abstract The prognosis for younger adults (≤ 55–60 years) with acute myeloid leukemia (AML) has improved during the last four decades. However, there has been little progress in the treatment of older adults. This disappointing observation is important because the median age of patients with AML is about 70 years. Approximately 60%–80% of younger adults with AML achieve complete remission (CR) with the cytotoxic agents cytarabine and an anthracycline such as daunorubicin or idarubicin or the anthracenedione mitoxantrone. However, only 30%–40% of such patients are alive and disease-free at 5 years. Among older adults, CR is achieved in 40%–55%, but there are very few long-term survivors. Many studies have evaluated the impact of alternative doses and schedules, as well as additional cytotoxic drugs, on the prognosis for this group of patients. The outcome has not improved substantially beyond that achieved with conventional doses of an anthracycline and cytarabine followed by high-dose cytarabine consolidation. Several factors identified at diagnosis can predict outcome. The most important of these is the karyotype of the leukemic cells. Another critical factor is the presence of transmembrane transporter proteins, which confer multidrug resistance and mutations in or overexpression of specific genes such as WT1, C/EBPα, BAX, and BCL-2/BAX ratio, BAALC, EVI1, KIT and FLT3. The development of specific agents directed at gene mutations, signal transduction pathways and unique cell surface antigens provide the foundation for new therapeutic strategies. Such agents include the immunoconjugate gemtuzumab ozogamicin, multidrug resistance inhibitors, farnesyltransferase inhibitors, histone deacetylase and proteosome inhibitors, antiangiogenesis agents, FLT3 inhibitors, apoptosis inhibitors, and nucleoside analogs. All of these agents can potentially address the heterogeneous abnormalities in AML and significantly improve the outcome for patients.

Cholangiocarcinoma: The impact of endobiliary high-dose-rate (HDR) brachytherapy dose response on survival

Brachytherapy ◽  
2006 ◽  
Vol 5 (2) ◽  
pp. 91
Author(s):  
Matthew Biagioli ◽  
B-Chen Wen ◽  
Brandon Patton ◽  
Caroline Hoffman ◽  
Mark Harvey
Keyword(s):  
Dose Rate ◽  
Dose Response ◽  
High Dose Rate ◽  
High Dose ◽  
Hdr Brachytherapy ◽  
The Impact

scholarly journals Editorial from the Editor in Chief: Impact factors and open access publishing

2006 ◽  
Vol 24 (4) ◽  
pp. 467-468
Author(s):  
Dieter H.H. Hoffmann
Keyword(s):  
Impact Factor ◽  
Ultrashort Pulses ◽  
Dense Matter ◽  
High Energy ◽  
Research Field ◽  
High Energy Density ◽  
Open Access Publishing ◽  
Impact Factors ◽  
Particle Beams ◽  
The Impact

The primary goal of Laser and Particle Beams as part of the Cambridge University Press is the dissemination of knowledge in our research field. How effective we are in this respect is not easy to determine. But the impact factor published annually in June by Thomson ISI® 2005 Journal Citation Reports (JCR), gives at least an indication and a method to compare other journals in the field. In this respect, Laser and Particle Beams is a journal with a very high ranking in the field of applied physics, but it also compares very well to journals in other field of physics. The impact factor of a journal gives an account of how often an average paper in the journal is referred to, in a two year time span after publication. The current impact factor of 2.59 is based on an evaluation conducted in 2005 of Laser and Particle Beams publications of 2003 and 2004. During the evaluation period (2005), Laser and Particle Beams publications were cited about 1000 times. The topics that attracted most attention were Fast Ignition (Deutsch, 2004; Mulser & Schneider, 2004a; Hora, 2004; Mulser & Bauer, 2004b), Inertial Fusion Targets (Borisenko et al., 2003), and Ion and Electron Acceleration in laser plasma and Ultrashort Pulses (Shorokhov & Pukhov, 2004; Osman et al., 2004; Malka & Fritzler, 2004; Limpouch et al., 2004; Pegoraro et al., 2004). However, the editorial boards of Laser and Particle Beams strongly encourage authors to submit their results in High Energy Density Physics, the emerging field of Warm Dense Matter, Pulsed Power and Accelerator Physics and Technology.

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