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2022 ◽  
Author(s):  
Emily N Copeland ◽  
Kennedy C Whitley ◽  
Colton JF Watson ◽  
Bradley J Baranowski ◽  
Nigel Kurgan ◽  
...  

Regular exercise can direct muscle kynurenine (KYN) metabolism toward the neuroprotective branch of the kynurenine pathway thereby limiting the accumulation of neurotoxic metabolites in the brain and contributing to mental resilience. While the effect of regular exercise has been studied, the effect of muscle disease on KYN metabolism has not yet been investigated. Previous work has highlighted anxiety-like behaviors in approximately 25% of patients with DMD, possibly due to altered KYN metabolism. Here, we characterized KYN metabolism in mdx mouse models of Duchenne muscular dystrophy (DMD). Young (8-10 week old) DBA/2J (D2) mdx mice, but not age-matched C57BL/10 (C57) mdx mice, had lower levels of circulating KYNA and KYNA:KYN ratio compared with their respective wild-type (WT) controls. Moreover, only D2 mdx mice displayed signs of anxiety-like behaviour, spending more time in the corners of their cages during a novel object recognition test when compared with WT. Along with this, we found that muscles from D2 mdx mice had less peroxisome proliferator-activated receptor-gamma coactivator 1-alpha and kynurenine amino transferase-1 enzyme content as well as elevated expression of inflammatory cytokines compared with WT muscles. Thus, our pilot work shows that KYN metabolism is altered in D2 mdx mice, with a potential contribution from altered muscle health.


2022 ◽  
Author(s):  
Caitlin R Francis ◽  
Hayle Kincross ◽  
Erich J Kushner

In early blood vessel development, trafficking programs, such as those using Rab GTPases, are tasked with delivering vesicular cargo with high spatiotemporal accuracy. However, the function of many Rab trafficking proteins remain ill-defined in endothelial tissue; therefore, their relevance to blood vessel development is unknown. Rab35 has been shown to play an enigmatic role in cellular behaviors which differs greatly between tissue-type and organism. Importantly, Rab35 has never been characterized for its potential contribution in sprouting angiogenesis; thus, our goal was to map Rab35s primary function in angiogenesis. Our results demonstrate that Rab35 is critical for sprout formation; in its absence apicobasal polarity is entirely lost in vitro and in vivo. To determine mechanism, we systematically explored established Rab35 effectors and show that none are operative in endothelial cells. However, we find that Rab35 partners with DENNd1c, an evolutionarily divergent guanine exchange factor, to localize to actin. Here, Rab35 regulates actin polymerization, which is required to setup proper apicobasal polarity during sprout formation. Our findings establish that Rab35 is a potent regulator of actin architecture during blood vessel development.


Energies ◽  
2022 ◽  
Vol 15 (2) ◽  
pp. 584
Author(s):  
Chiara Magni ◽  
Sylvain Quoilin ◽  
Alessia Arteconi

Flexibility is crucial to enable the penetration of high shares of renewables in the power system while ensuring the security and affordability of the electricity dispatch. In this regard, heat–electricity sector coupling technologies are considered a promising solution for the integration of flexible devices such as thermal storage units and heat pumps. The deployment of these devices would also enable the decarbonization of the heating sector, responsible for around half of the energy consumption in the EU, of which 75% is currently supplied by fossil fuels. This paper investigates in which measure the diffusion of district heating (DH) coupled with thermal energy storage (TES) units can contribute to the overall system flexibility and to the provision of operating reserves for energy systems with high renewable penetration. The deployment of two different DH supply technologies, namely combined heat and power units (CHP) and large-scale heat pumps (P2HT), is modeled and compared in terms of performance. The case study analyzed is the future Italian energy system, which is simulated through the unit commitment and optimal dispatch model Dispa-SET. Results show that DH coupled with heat pumps and CHP units could enable both costs and emissions related to the heat–electricity sector to be reduced by up to 50%. DH systems also proved to be a promising solution to grant the flexibility and resilience of power systems with high shares of renewables by significantly reducing the curtailment of renewables and cost-optimally providing up to 15% of the total upward reserve requirements.


2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Caio Andreeta Figueiredo ◽  
Johannes Steffen ◽  
Lorena Morton ◽  
Sushmitha Arumugam ◽  
Oliver Liesenfeld ◽  
...  

Abstract Background Toxoplasma gondii (T. gondii) is a highly successful parasite being able to cross all biological barriers of the body, finally reaching the central nervous system (CNS). Previous studies have highlighted the critical involvement of the blood–brain barrier (BBB) during T. gondii invasion and development of subsequent neuroinflammation. Still, the potential contribution of the choroid plexus (CP), the main structure forming the blood–cerebrospinal fluid (CSF) barrier (BCSFB) have not been addressed. Methods To investigate T. gondii invasion at the onset of neuroinflammation, the CP and brain microvessels (BMV) were isolated and analyzed for parasite burden. Additionally, immuno-stained brain sections and three-dimensional whole mount preparations were evaluated for parasite localization and morphological alterations. Activation of choroidal and brain endothelial cells were characterized by flow cytometry. To evaluate the impact of early immune responses on CP and BMV, expression levels of inflammatory mediators, tight junctions (TJ) and matrix metalloproteinases (MMPs) were quantified. Additionally, FITC-dextran was applied to determine infection-related changes in BCSFB permeability. Finally, the response of primary CP epithelial cells to T. gondii parasites was tested in vitro. Results Here we revealed that endothelial cells in the CP are initially infected by T. gondii, and become activated prior to BBB endothelial cells indicated by MHCII upregulation. Additionally, CP elicited early local immune response with upregulation of IFN-γ, TNF, IL-6, host-defence factors as well as swift expression of CXCL9 chemokine, when compared to the BMV. Consequently, we uncovered distinct TJ disturbances of claudins, associated with upregulation of MMP-8 and MMP-13 expression in infected CP in vivo, which was confirmed by in vitro infection of primary CP epithelial cells. Notably, we detected early barrier damage and functional loss by increased BCSFB permeability to FITC-dextran in vivo, which was extended over the infection course. Conclusions Altogether, our data reveal a close interaction between T. gondii infection at the CP and the impairment of the BCSFB function indicating that infection-related neuroinflammation is initiated in the CP.


2022 ◽  
Vol 14 (2) ◽  
pp. 807
Author(s):  
Ezutah Udoncy Olugu ◽  
Kuan Yew Wong ◽  
Jonathan Yong Chung Ee ◽  
Yslam D. Mammedov

The existence of external two-fold pressure regarding competitiveness and sustainable development in a capital-intensive industry supports the need for sustainable performance. However, endeavors to create a sustainable framework to measure the performance of the oil and gas (O&G) industry are mostly devoted to the production and supply chain of petrochemical products and rarely focus on a maintenance perspective. Motivated by such scarcity, the goal of this research was to discuss and articulate the performance assessment framework by integrating concepts of maintenance and sustainability in the O&G industry. This study proposed the use of a range of performance measures for assessing sustainability on offshore production and drilling platforms. The conceptual framework consists of four aspects of sustainability categorized into technical, environmental, social, and economic dimensions. Each measure was assigned according to its relevance at the strategic, tactical, and functional levels of maintenance decision making. The conceptual framework resulted in hierarchical clusters of twelve strategic indicators. These indicators consist of conventional measures as well as new ones relating to the safety and reliability on offshore platforms. The potential contribution of the present study is found in its intention to empower a better understanding of sustainable maintenance and encourage those making decisions about practical implementation within the O&G industry. This paper culminates with directions for future studies.


2022 ◽  
Author(s):  
Kristina Seftigen ◽  
Marina V. Fonti ◽  
Brian Luckman ◽  
Miloš Rydval ◽  
Petter Stridbeck ◽  
...  

Abstract. The continuous development of new proxies as well as a refinement of existing tools are key to advances in paleoclimate research and improvements in the accuracy of existing climate reconstructions. Herein, we build on recent methodological progress in dendroanatomy – the analyses of wood anatomical parameters in dated tree rings – and introduce the longest (1585–2014 CE) dendroanatomical dataset currently developed for North America. We explore the potential of dendroanatomy of high-elevation Engelmann spruce (Picea engelmannii) as a proxy of past temperatures by measuring anatomical cell dimensions of 15 living trees from the Columbia Icefield area. There, X-ray maximum latewood density (MXD) and its blue intensity counterpart (MXBI) have previously been measured, which allows comparing the different parameters. Our findings highlight anatomical MXD and maximum radial cell wall thickness as the two most promising wood anatomical proxy parameters for past temperatures, each explaining 46 % and 49 %, respectively, of instrumental, high-pass filtered, July–August maximum temperatures over the 1901–1994 period. While both parameters display comparable climatic imprinting at higher frequencies to X-ray derived MXD, the anatomical dataset distinguishes itself from its predecessors by providing the most temporally stable warm-season temperature signal. For the long-term secular trends, discrepancies between anatomical MXD and maximum radial cell wall thickness chronologies were observed, where the former more closely follow the long-term variations of the X-ray based MXD. Further studies, including samples from more diverse age cohorts and the adaptation of RCS-based standardizations, are needed to disentangle the ontogenetic and climatic components of long-term signals stored in the wood anatomical traits and to more comprehensively evaluate the potential contribution of this new dataset to paleoclimate research.


Physiology ◽  
2022 ◽  
Author(s):  
Jessica L. Bradshaw ◽  
Spencer C Cushen ◽  
Nicole R Phillips ◽  
Styliani Goulopoulou

Circulating cell-free mitochondrial DNA (ccf-mtDNA) released upon cell injury or death stimulates diverse pattern recognition receptors to activate innate immune responses and initiate systemic inflammation. In this review, we discuss the temporal changes of ccf-mtDNA during pregnancy and its potential contribution to adverse pregnancy outcomes in pregnancy complications.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 330
Author(s):  
Ioannis Gkouveris ◽  
Akrivoula Soundia ◽  
Panagiotis Gouveris ◽  
Dionysia Zouki ◽  
Danny Hadaya ◽  
...  

Antiresorptive agents such as bisphosphonates (BP) and denosumab are commonly prescribed for the management of primary bone malignancy, bone metastasis, osteoporosis, Paget disease, or other bone disorders. Medication-related osteonecrosis of the Jaws (MRONJ) is a rare but significant complication of antiresorptive medications. Duration, dose, and antiresorptive potency as well as concomitant diseases, additional medications, and local factors affect MRONJ incidence and severity. MRONJ pathophysiology is still poorly understood. Nevertheless, decreased bone resorption due to osteoclastic inhibition along with trauma, infection/inflammation, or blood supply inhibition are considered synergistic factors for disease development. In addition, previous data research examined the effects of antiresorptive medication on immune system components and introduced potential alterations on immune response as novel elements in MRONJ pathogenesis. Considering that macrophages are the first cells in the nonspecific immune response, it is not surprising that these multifaceted players attracted increased attention in MRONJ research recently. This current review attempted to elucidate the effects of antiresorptive medications on several aspects of macrophage activity in relation to the complex inflammatory microenvironment of MRONJ. Collectively, unravelling the mode of action and extent of macrophages’ potential contribution in MRONJ occurrence will provide novel insight in disease pathogenesis and potentially identify intrinsic therapeutic targets.


Author(s):  
Gan Zhu ◽  
Ping Song ◽  
Jing Wu ◽  
Minglan Luo ◽  
Zhipeng Chen ◽  
...  

Nucleic acids underlie the storage and retrieval of genetic information literally in all living organisms, and also provide us excellent materials for making artificial nanostructures and scaffolds for constructing multi-enzyme systems with outstanding performance in catalyzing various cascade reactions, due to their highly diverse and yet controllable structures, which are well determined by their sequences. The introduction of unnatural moieties into nucleic acids dramatically increased the diversity of sequences, structures, and properties of the nucleic acids, which undoubtedly expanded the toolbox for making nanomaterials and scaffolds of multi-enzyme systems. In this article, we first introduce the molecular structures and properties of nucleic acids and their unnatural derivatives. Then we summarized representative artificial nanomaterials made of nucleic acids, as well as their properties, functions, and application. We next review recent progress on constructing multi-enzyme systems with nucleic acid structures as scaffolds for cascade biocatalyst. Finally, we discuss the future direction of applying nucleic acid frameworks in the construction of nanomaterials and multi-enzyme molecular machines, with the potential contribution that unnatural nucleic acids may make to this field highlighted.


Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 115
Author(s):  
Maria Chomova

Diabetes mellitus (DM) has been associated with cognitive complications in the brain resulting from acute and chronic metabolic disturbances happening peripherally and centrally. Numerous studies have reported on the morphological, electrophysiological, biochemical, and cognitive changes in the brains of diabetic individuals. The detailed pathophysiological mechanisms implicated in the development of the diabetic cognitive phenotype remain unclear due to intricate molecular changes evolving over time and space. This review provides an insight into recent advances in understanding molecular events in the diabetic brain, focusing on cerebral glucose and insulin uptake, insulin action in the brain, and the role of the brain in the regulation of glucose homeostasis. Fully competent mitochondria are essential for energy metabolism and proper brain function; hence, the potential contribution of mitochondria to the DM-induced impairment of the brain is also discussed.


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