scholarly journals Pathological circadian rhythm states driven by CK2 and noise

2019 ◽  
Author(s):  
Z. Malik ◽  
Y. Fatima ◽  
J. Alam ◽  
R. Singh

AbstractCircadian rhythm maintains sleep–wake cycle in living systems. Disruption of this rhythm may cause diseases. We propose an extended Drosophila circadian rhythm model incorporating cross-talk of CK2 with Per protein. We studied the model using stochastic simulation algorithm, and the behavior of the amplitude, time period and permutation entropy us identify three distinct circadian states namely, active, weak activity, active, weak activity and rhythmic death all driven by CK2. These states may correspond to distinct pathological cellular states of the living system. Noise, an important factor, has ability to switch normal circadian rhythm to any of the three aforementioned circadian states. Fluctuations in system’s size, can help us in deterning the extent of noise present. We also highlighted that disruption in circadian rhythm may lead to various diseases including cancer. We present various cellular pathways driven by per mutant genes and their pathological states.Statement of significanceCircadian rhythm, which is one of the most important biological rhythm, regulates and intervenes various cellular processes. Significant changes in the rhythmic dynamics may lead to pathological states which may trigger various diseases. In this work, the impact of CK2 via per gene mutants on rhythmic dynamics is investigated, and found three distinct states, namely, active, weak activity and rhythmic death driven by CK2 which may correspond to various cellular states. Noise due to intrinsic random molecular events and cellular size variability is found to have the capability of regulating and controlling rhythmic properties, and can trigger to the three rhythmic states. We then listed various possible pathways which are regulated by per gene mutants and corresponding various possible pathological states.

Author(s):  
Daniela Correia da Silva ◽  
Patricia Valentao ◽  
Paula Andrade ◽  
David Pereira

The endoplasmic reticulum (ER) comprises a network of tubules and vesicles that constitutes the largest organelle of the eukaryotic cell. Being the location where most proteins are synthesized and folded, it is crucial for the upkeep of cellular homeostasis. In addition, it is the largest ionic calcium reservoir in cells, tightly regulating the levels of this second messenger according to cellular necessities. Disturbed ER homeostasis triggers the activation of an intricate and conserved molecular machinery, termed the unfolded protein response (UPR). Given the impact of this signaling network upon an extensive list of cellular processes, ER stress is involved in the onset and progression of multiple diseases, including cancer and neurodegenerative disorders. There is, for this reason, an increasing number of publications focused on characterizing and/or modulating ER stress, which have resulted in a wide array of techniques employed to study ER-related molecular events. This review aims to sum up the tools available design a study of this nature.


2020 ◽  
Vol 16 (2) ◽  
pp. 86-92
Author(s):  
Rafael Penadés ◽  
Bárbara Arias ◽  
Mar Fatjó-Vilas ◽  
Laura González-Vallespí ◽  
Clemente García-Rizo ◽  
...  

Background: Epigenetic modifications appear to be dynamic and they might be affected by environmental factors. The possibility of influencing these processes through psychotherapy has been suggested. Objective: To analyse the impact of psychotherapy on epigenetics when applied to mental disorders. The main hypothesis is that psychological treatments will produce epigenetic modifications related to the improvement of treated symptoms. Methods: A computerised and systematic search was completed throughout the time period from 1990 to 2019 on the PubMed, ScienceDirect and Scopus databases. Results: In total, 11 studies were selected. The studies were evaluated for the theoretical framework, genes involved, type of psychotherapy and clinical challenges and perspectives. All studies showed detectable changes at the epigenetic level, like DNA methylation changes, associated with symptom improvement after psychotherapy. Conclusion: Methylation profiles could be moderating treatment effects of psychotherapy. Beyond the detected epigenetic changes after psychotherapy, the epigenetic status before the implementation could act as an effective predictor of response.


2021 ◽  
Vol 13 (1) ◽  
pp. 413
Author(s):  
Maximilian Kardung ◽  
Kutay Cingiz ◽  
Ortwin Costenoble ◽  
Roel Delahaye ◽  
Wim Heijman ◽  
...  

The EU’s 2018 Bioeconomy Strategy Update and the European Green Deal recently confirmed that the bioeconomy is high on the political agenda in Europe. Here, we propose a conceptual analysis framework for quantifying and analyzing the development of the EU bioeconomy. The bioeconomy has several related concepts (e.g., bio-based economy, green economy, and circular economy) and there are clear synergies between these concepts, especially between the bioeconomy and circular economy concepts. Analyzing the driving factors provides important information for monitoring activities. We first derive the scope of the bioeconomy framework in terms of bioeconomy sectors and products to be involved, the needed geographical coverage and resolution, and time period. Furthermore, we outline a set of indicators linked to the objectives of the EU’s bioeconomy strategy. In our framework, measuring developments will, in particular, focus on the bio-based sectors within the bioeconomy as biomass and food production is already monitored. The selected indicators commit to the EU Bioeconomy Strategy objectives and conform with findings from previous studies and stakeholder consultation. Additionally, several new indicators have been suggested and they are related to measuring the impact of changes in supply, demand drivers, resource availability, and policies on sustainability goals.


Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 286
Author(s):  
Mary Frances Nakamya ◽  
Moses B. Ayoola ◽  
Leslie A. Shack ◽  
Mirghani Mohamed ◽  
Edwin Swiatlo ◽  
...  

Polyamines such as putrescine, cadaverine, and spermidine are small cationic molecules that play significant roles in cellular processes, including bacterial stress responses and host–pathogen interactions. Streptococcus pneumoniae is an opportunistic human pathogen, which causes several diseases that account for significant morbidity and mortality worldwide. As it transits through different host niches, S. pneumoniae is exposed to and must adapt to different types of stress in the host microenvironment. We earlier reported that S. pneumoniae TIGR4, which harbors an isogenic deletion of an arginine decarboxylase (ΔspeA), an enzyme that catalyzes the synthesis of agmatine in the polyamine synthesis pathway, has a reduced capsule. Here, we report the impact of arginine decarboxylase deletion on pneumococcal stress responses. Our results show that ΔspeA is more susceptible to oxidative, nitrosative, and acid stress compared to the wild-type strain. Gene expression analysis by qRT-PCR indicates that thiol peroxidase, a scavenger of reactive oxygen species and aguA from the arginine deiminase system, could be important for peroxide stress responses in a polyamine-dependent manner. Our results also show that speA is essential for endogenous hydrogen peroxide and glutathione production in S. pneumoniae. Taken together, our findings demonstrate the critical role of arginine decarboxylase in pneumococcal stress responses that could impact adaptation and survival in the host.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 806-807
Author(s):  
Philip Buck

Abstract The incidence of vaccine-preventable diseases remains high among older adults in the US, despite longstanding immunization recommendations, and is projected to increase as the population ages. The impact of US population aging on the burden of four vaccine-preventable diseases (influenza, pneumococcal disease, shingles, and pertussis) was modeled over a 30-year time horizon, with cumulative direct and indirect costs increasing from $378 billion over 10 years to $1.28 trillion over 30 years. Compared to current levels of vaccination coverage, increasing coverage was predicted to avert over 33 million cases of disease and greater than $96 billion in disease-associated costs, with a corresponding increase in vaccination costs of approximately $83 billion over the entire 30-year time period. Specific examples of cost-effectiveness analyses that assess the epidemiologic and economic impact of vaccination against shingles and pertussis in older adults will be discussed. Part of a symposium sponsored by the Health Behavior Change Interest Group.


2021 ◽  
Vol 10 (6) ◽  
pp. 1239
Author(s):  
Alexandru Cojocaru ◽  
Emilia Burada ◽  
Adrian-Tudor Bălșeanu ◽  
Alexandru-Florian Deftu ◽  
Bogdan Cătălin ◽  
...  

As the average age and life expectancy increases, the incidence of both acute and chronic central nervous system (CNS) pathologies will increase. Understanding mechanisms underlying neuroinflammation as the common feature of any neurodegenerative pathology, we can exploit the pharmacology of cell specific ion channels to improve the outcome of many CNS diseases. As the main cellular player of neuroinflammation, microglia play a central role in this process. Although microglia are considered non-excitable cells, they express a variety of ion channels under both physiological and pathological conditions that seem to be involved in a plethora of cellular processes. Here, we discuss the impact of modulating microglia voltage-gated, potential transient receptor, chloride and proton channels on microglial proliferation, migration, and phagocytosis in neurodegenerative diseases.


Hand ◽  
2021 ◽  
pp. 155894472199080
Author(s):  
Danielle A Thornburg ◽  
Nikita Gupta ◽  
Nathan Chow ◽  
Jack Haglin ◽  
Shelley Noland

Background: Medicare reimbursement trends across multiple surgical subspecialties have been analyzed; however, little has been reported regarding the long-term trends in reimbursement of hand surgery procedures. The aim of this study is to analyze trends in Medicare reimbursement for commonly performed hand surgeries. Methods: Using the Centers for Medicare and Medicaid Services Physician and Other Supplier Public Use File, we determined the 20 hand surgery procedure codes most commonly billed to Medicare in 2016. Reimbursement rates were collected and analyzed for each code from The Physician Fee Schedule Look-Up Tool for years 2000 to 2019. We compared the change in reimbursement rate for each procedure to the rate of inflation in US dollars, using the Consumer Price Index (CPI) over the same time period. Results: The reimbursement rate for each procedure increased on average by 13.9% during the study period while the United States CPI increased significantly more by 46.7% ( P < .0001). When all reimbursement data were adjusted for inflation to 2019 dollars, the average reimbursement for all included procedures in this study decreased by 22.6% from 2000 to 2019. The average adjusted reimbursement rate for all procedures decreased by 21.92% from 2000 to 2009 and decreased by 0.86% on average from 2009 to 2019 ( P < .0001). Conclusion: When adjusted for inflation, Medicare reimbursement for hand surgery has steadily decreased over the past 20 years. It will be important to consider the implications of these trends when evaluating healthcare policies and the impact this has on access to hand surgery.


2021 ◽  
pp. 232102222110243
Author(s):  
Mohuya Deb Purkayastha ◽  
Joyeeta Deb ◽  
Ram Pratap Sinha

The present study estimated labour-use efficiency of 48 branches of Assam Gramin Vikash Bank at its branch level, covering three districts of Barak Valley, which falls under Silchar region of the bank for the time period from 2010–2011 to 2017–2018. The study applied data envelopment analysis for estimating labour-use efficiency. In the second stage, the study applied censored Tobit regression for determining the impact of several contextual variables on efficiency. The study reveals that the mean labour-use efficiency score of the selected branches is 76% when averaged for the in-sample branches over the observation period. Results of the Tobit regression identified cluster 2 and total business of the branches as the significant factors for determining efficiency and the number of employees as a significant variable influencing inefficiency. JEL Classifications: G2, G20, G21, J3


Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 767
Author(s):  
He N. Xu ◽  
Joanna Floros ◽  
Lin Z. Li ◽  
Shaili Amatya

Employing the optical redox imaging technique, we previously identified a significant redox shift of nicotinamide adenine dinucleotide (NAD and the reduced form NADH) in freshly isolated alveolar macrophages (AM) from ozone-exposed mice. The goal here was twofold: (a) to determine the NAD(H) redox shift in cryopreserved AM isolated from ozone-exposed mice and (b) to investigate whether there is a difference in the redox status between cryopreserved and freshly isolated AM. We found: (i) AM from ozone-exposed mice were in a more oxidized redox state compared to that from filtered air (FA)-exposed mice, consistent with the results obtained from freshly isolated mouse AM; (ii) under FA exposure, there was no significant NAD(H) redox difference between fresh AM that had been placed on ice for 2.5 h and cryopreserved AM; however, under ozone exposure, fresh AM were more oxidized than cryopreserved AM; (iii) via the use of nutrient starvation and replenishment and H2O2-induced oxidative stress of an AM cell line, we showed that this redox difference between cryopreserved and freshly isolated AM is likely the result of the double “hit”, i.e., the ozone-induced oxidative stress plus nutrient starvation that prevented freshly isolated AM from a full recovery after being on ice for a prolonged time period. The cryopreservation technique we developed eliminates/minimizes the effects of oxidative stress and nutrient starvation on cells. This method can be adopted to preserve lung macrophages from animal models or clinical patients for further investigations.


Author(s):  
Lorenzo Cangiano ◽  
Sabrina Asteriti

AbstractIn the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract salient visual information. The first opportunity for such interaction is offered by electrical coupling of the photoreceptors themselves, which is mediated by gap junctions located at the contact points of specialised cellular processes: synaptic terminals, telodendria and radial fins. Here, we examine the evolutionary pressures for and against interphotoreceptor coupling, which are likely to have shaped how coupling is deployed in different species. The impact of coupling on signal to noise ratio, spatial acuity, contrast sensitivity, absolute and increment threshold, retinal signal flow and colour discrimination is discussed while emphasising available data from a variety of vertebrate models spanning from lampreys to primates. We highlight the many gaps in our knowledge, persisting discrepancies in the literature, as well as some major unanswered questions on the actual extent and physiological role of cone-cone, rod-cone and rod-rod communication. Lastly, we point toward limited but intriguing evidence suggestive of the ancestral form of coupling among ciliary photoreceptors.


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