bluuebunny/crossref_metadata_2025 huggingface dataset:
Discretization, Bifurcation, and Control for a Class of Predator-Prey Interactions
Authors: Tassaddiq Asifa , Shabbir Muhammad Sajjad , Din Qamar , Naaz Humera
Published: January 2022

The present study focuses on the dynamical aspects of a discrete-time Leslie-Gower predator-prey model accompanied by a Holling type III functional response. Discretization is conducted by applying a piecewise constant argument method of differential equations. Moreover, boundedness, existence, uniqueness, and a local stability analysis of biologically feasible equilibria were investigated. By implementing the center manifold theorem and bifurcation theory, our study reveals that the given system undergoes period-doubling and Neimark-Sacker bifurcation around the interior equilibrium point. By contrast, chaotic attractors ensure chaos. To avoid these unpredictable situations, we establish a feedback-control strategy to control the chaos created under the influence of bifurcation. The fractal dimensions of the proposed model are calculated. The maximum Lyapunov exponents and phase portraits are depicted to further confirm the complexity and chaotic behavior. Finally, numerical simulations are presented to confirm the theoretical and analytical findings.
Assessing the Impacts of Crowdshipping Using Public Transport: A Case Study in a Middle-Sized Greek City
Authors: Karakikes Ioannis , Nathanail Eftihia
Published: January 2022

Crowdsourced deliveries or crowdshipping is identified in recent literature as an emerging urban freight transport solution, aiming at reducing delivery costs, congestion, and environmental impacts. By leveraging the pervasive use of mobile technology, crowdshipping is an emerging solution of the sharing economy in the transport domain, as parcels are delivered by commuters rather than corporations. The objective of this research is to evaluate the impacts of crowdshipping through alternative scenarios that consider various levels of demand and adoption by public transport users who act as crowdshippers, based on a case study example in the city of Volos, Greece. This is achieved through the establishment of a tailored evaluation framework and a city-scale urban freight traffic microsimulation model. Results show that crowdshipping has the potential to mitigate last-mile delivery impacts and effectively contribute to improving the system’s performance.
Trends and Composition—A Sedimentological-Chemical-Mineralogical Approach to Constrain the Origin of Quaternary Deposits and Landforms—From a Review to a Manual
Authors: Dill Harald G.
Published: January 2022

In this study, six basic Quaternary landform series (LFS) and their sedimentary deposits (LFS1 aeolian, LFS 2.1 to 2.2 mass wasting, LFS 3 cryogenic-glacial, LFS 4.1 to 4.6 fluvial, LFS 5.1 to 5.2 coastal-marine, LFS 6.1 to 6.3 lacustrine) are subdivided into subtypes and examined with regard to their sedimentological parameters and their mineralogical and chemical compositions. Emphasis is placed on the textural (related to transport and deposition), compositional (sediment load/weight, Eh and pH) and geodynamic maturity of the sedimentary deposits which are influenced by the parent lithology and bedrock tectonic and by the climate during the last 2 Ma. To constrain the development of the LFS and their sediments, composite trend-line diagrams are designed combining sedimentological (x-axis) and chemical/mineralogical dataset (y-axis): (1) sorting vs. heavy mineral content; (2) sphericity of grains vs. silica/carbonate contents; and (3) median vs. Ti/Fe ratios. In addition, the x-y plots showing the log SiO2/Al2O3 vs. log Na2O/K2O are amended by a dataset of the three most common clay minerals, i.e., kaolinite-, mica-, and smectite-group clay minerals. Such joint sedimentological-chemical-mineralogical investigations focused on the depositional environment of unconsolidated clastic sediments of Quaternary age can be used to describe the economic geology and environmental geology of mineral deposits in the pre-Quaternary sedimentary series according to the phrase: “The Present is the key to the Past”. Both trend diagrams and compositional x-y plots can contribute to constraining the development of the full transect of landform series from the fluvial incision and slope retreat to reef islands fringing the coastal zone towards the open sea as far as they are built up of clastic sedimentary deposits enriched in siliceous and/or carbonate minerals. Climate zonation and crustal maturity are the exogenous and endogenous “drivers”, as can be deduced from the compositional (mineralogy and chemistry) and physical (transport and deposition) variations observed in the Quaternary sediments. The current study bridges the gap between a review only based on literature and a hybrid manual generated by practical field studies devoted to applied geosciences in economic and environmental geology (“E & E issue”).
The Active Role of the Internet and Social Media Use in Nonpharmaceutical and Pharmaceutical Preventive Measures against COVID-19
Authors: Xie Tian , Tang Meihui , Zhang Robert Jiqi , Liu James H.
Published: January 2022

During the COVID-19 pandemic, does more internet and social media use lead to taking more- or less-effective preventive measures against the disease? A two-wave longitudinal survey with the general population in mainland China in mid-2020 found that during the COVID-19 pandemic, internet and social media use intensity promoted the adoption of nonpharmaceutical and pharmaceutical antipandemic measures. The first wave of data (n = 1014) showed that the more intensively people used the internet/social media, the more they perceived the threat of the pandemic, and took more nonpharmaceutical preventive measures (e.g., wearing masks, maintaining social distance, and washing hands) as a result. The second wave (n = 220) showed firstly the predicted relationship between internet/social media use intensity and the perceived threat of the pandemic and the adoption of nonpharmaceutical preventive measures by cross-lagged analysis; secondly, the predictive effect of internet/social media use on the adoption of pharmacological measures (i.e., willingness to vaccinate against COVID-19) and the mediating role of perceived pandemic threat were verified. The article concludes with a discussion of the role of the internet and social media use in the fight against COVID-19 in specific macrosocial contexts.
Hygiene Behaviors and SARS-CoV-2-Preventive Behaviors in the Face of the COVID-19 Pandemic: Self-Reported Compliance and Associations with Fear, SARS-CoV-2 Risk, and Mental Health in a General Population vs. a Psychosomatic Patients Sample in Germany
Authors: Lippke Sonia , Keller Franziska M. , Derksen Christina , Kötting Lukas , Dahmen Alina
Published: January 2022

Background: During the COVID-19 pandemic, hygiene behaviors such as keeping distance, avoiding masses, wearing face masks, and complying with hand hygiene recommendations became imperative. The current study aims to determine factors interrelating with hygiene behaviors. Methods: A total of 4049 individuals (1305 male, 2709 female, aged 18–80 years) were recruited from rehabilitation clinics or freely on the internet. They were surveyed via online questionnaires between May 2020 and August 2021. Sociodemographics, hygiene behaviors, and fear of COVID-19 infection were assessed. Results: Overall prevalence for hygiene behaviors was: keeping a distance—88.1%; avoiding mass gatherings—88.0%; wearing face masks—96.9%; and hand hygiene—81.6%, with 70% of the study participants complying with all four researched behaviors. Hygiene behaviors were significantly related to fear in a linear and quadratic fashion. Conclusion: Patients are more compliant according to their self-reported responses than the general population. To improve hygiene behavior, hand hygiene in particular provides options for improvements. A medium level of fear seems to be more functional than too-elevated fear. Behavioral interventions and targeted communication aiming at improving different behaviors in orchestration can help individuals to protect their health and to remain healthy. Accordingly, communication is required to ensure high hygiene standards and patient safety, and to prevent adverse effects.
The Quality of Life of Coronavirus Disease Survivors Living in Rural and Urban Area of Riau Province, Indonesia
Authors: Suyanto Suyanto , Kandel Shashi , Kemal Rahmat Azhari , Arfianti Arfianti
Published: January 2022

This study assesses the status of health-related quality of life (HRQOL) among coronavirus survivors living in rural and urban districts in Riau province, Indonesia. The cross-sectional study was conducted among 468 and 285 Coronavirus disease (COVID-19) survivors living in rural and urban areas, respectively in August 2021. The St. George Respiratory Questionnaire (SGRQ) was used to measure the HRQOL of COVID-19 survivors. A higher total score domain corresponds to worse quality of life status. Quantile regression with the respect to 50th percentile found a significant association for the factors living in rural areas, being female, having comorbidities, and being hospitalized during treatment, with total score of 4.77, 2.43, 7.22, and 21.27 higher than in their contra parts, respectively. Moreover, having received full vaccination had the score 3.96 in total score. The HRQOL of COVID-19 survivors living in rural areas was significantly lower than in urban areas. Factors such as living in rural areas, female sex, having comorbidities, and history of symptomatic COVID-19 infection were identified as significant predictors for lower quality of life. Meanwhile, having full vaccination is a significant predictor for a better quality of life. The results of this study can provide the targeted recommendations for improvement of HRQOL of COVID-19 survivors.
The Impact of Green Credit on the Green Innovation Level of Heavy-Polluting Enterprises—Evidence from China
Authors: Zhang Zhifeng , Duan Hongyan , Shan Shuangshuang , Liu Qingzhi , Geng Wenhui
Published: January 2022

This article uses the “Green Credit Guidelines” promulgated in 2012 as an example to construct a quasi-natural experiment and uses the double difference method to test the impact of the implementation of the “Green Credit Guidelines” on the green innovation activities of heavy-polluting enterprises. The study found that, in comparison to non-heavy polluting enterprises, the implementation of green credit policies inhibited the green innovation of all heavy-polluting enterprises. In the analysis of heterogeneity, this restraint effect did not differ significantly due to the nature of property rights and the company’s size. The mechanism test showed that green credit policy limits the efficiency of business investment and increases the cost of financing business debt. Eliminating corporate credit financing, particularly long-term borrowing, negatively impacts the green innovation behavior of listed companies.
Evaluation of Community Livability Using Gridded Basic Urban Geographical Data—A Case Study of Wuhan
Authors: Luo Qiong , Shu Hong , Zhao Zhongyuan , Qi Rui , Huang Youxin
Published: January 2022

The evaluation of community livability quantifies the demands of human settlement at the micro scale, supporting urban governance decision-making at the macro scale. Big data generated by the urban management of government agencies can provide an accurate, real-time, and rich data set for livability evaluation. However, these data are intertwined by overlapping geographical management boundaries of different government agencies. It causes the difficulty of data integration and utilization when evaluating community livability. To address this problem, this paper proposes a scheme of partitioning basic geographical space into grids by optimally integrating various geographical management boundaries relevant to enterprise-level big data. Furthermore, the system of indexes on community livability is created, and the evaluation model of community livability is constructed. Taking Wuhan as an example, the effectiveness of the model is verified. After the evaluation, the experimental results show that the livability evaluation with reference to our basic geographic grids can effectively make use of governmental big data to spatially identify the multi-dimensional characteristics of a community, including management, environment, facility services, safety, and health. Our technical solution to evaluate community livability using gridded basic urban geographical data is of large potential in producing thematic data of community, constructing a 15-min community living circle of Wuhan, and enhancing the ability of the community to resist risks.
Relevance of a Novel Circuit-Level Model of Episodic Memories to Alzheimer’s Disease
Authors: Kovács Krisztián A.
Published: January 2022

The medial temporal lobe memory system has long been identified as the brain region showing the first histopathological changes in early Alzheimer’s disease (AD), and the functional decline observed in patients also points to a loss of function in this brain area. Nonetheless, the exact identity of the neurons and networks that undergo deterioration has not been determined so far. A recent study has identified the entorhinal and hippocampal neural circuits responsible for encoding new episodic memories. Using this novel model we describe the elements of the episodic memory network that are especially vulnerable in early AD. We provide a hypothesis of how reduced reelin signaling within such a network can promote AD-related changes. Establishing novel associations and creating a temporal structure for new episodic memories are both affected in AD. Here, we furnish a reasonable explanation for both of these previous observations.
Genome-Wide Identification and Expression Profile of OSCA Gene Family Members in Triticum aestivum L.
Authors: Tong Kai , Wu Xinyang , He Long , Qiu Shiyou , Liu Shuang , Cai Linna , Rao Shaofei , Chen Jianping
Published: January 2022

Hyperosmolality and various other stimuli can trigger an increase in cytoplasmic-free calcium concentration ([Ca2+]cyt). Members of the Arabidopsis thaliana (L.) reduced hyperosmolality-gated calcium-permeable channels (OSCA) gene family are reported to be involved in sensing extracellular changes to trigger hyperosmolality-induced [Ca2+]cyt increases and controlling stomatal closure during immune signaling. Wheat (Triticum aestivum L.) is a very important food crop, but there are few studies of its OSCA gene family members. In this study, 42 OSCA members were identified in the wheat genome, and phylogenetic analysis can divide them into four clades. The members of each clade have similar gene structures, conserved motifs, and domains. TaOSCA genes were predicted to be regulated by cis-acting elements such as STRE, MBS, DRE1, ABRE, etc. Quantitative PCR results showed that they have different expression patterns in different tissues. The expression profiles of 15 selected TaOSCAs were examined after PEG (polyethylene glycol), NaCl, and ABA (abscisic acid) treatment. All 15 TaOSCA members responded to PEG treatment, while TaOSCA12/-39 responded simultaneously to PEG and ABA. This study informs research into the biological function and evolution of TaOSCA and lays the foundation for the breeding and genetic improvement of wheat.
The Role of the Gut Microbiota in the Pathogenesis of Diabetes
Authors: Bielka Weronika , Przezak Agnieszka , Pawlik Andrzej
Published: January 2022

Diabetes mellitus is a significant clinical and therapeutic problem because it can lead to serious long-term complications. Its pathogenesis is not fully understood, but there are indications that dysbiosis can play a role in the development of diabetes, or that it appears during the course of the disease. Changes in microbiota composition are observed in both type 1 diabetes (T1D) and type 2 diabetes (T2D) patients. These modifications are associated with pro-inflammation, increased intestinal permeability, endotoxemia, impaired β-cell function and development of insulin resistance. This review summarizes the role of the gut microbiota in healthy individuals and the changes in bacterial composition that can be associated with T1D or T2D. It also presents new developments in diabetes therapy based on influencing the gut microbiota as a promising method to alter the course of diabetes. Moreover, it highlights the lacking data and suggests future directions needed to prove the causal relationship between dysbiosis and diabetes, both T1D and T2D.
Is the Mitochondrial Membrane Potential (∆Ψ) Correctly Assessed? Intracellular and Intramitochondrial Modifications of the ∆Ψ Probe, Rhodamine 123
Authors: Zorova Ljubava D. , Demchenko Evgeniya A. , Korshunova Galina A. , Tashlitsky Vadim N. , Zorov Savva D. , Andrianova Nadezda V. , Popkov Vasily A. , Babenko Valentina A. , Pevzner Irina B. , Silachev Denis N. , Plotnikov Egor Y. , Zorov Dmitry B.
Published: January 2022

The mitochondrial membrane potential (∆Ψ) is the driving force providing the electrical component of the total transmembrane potential of hydrogen ions generated by proton pumps, which is utilized by the ATP synthase. The role of ∆Ψ is not limited to its role in bioenergetics since it takes part in other important intracellular processes, which leads to the mandatory requirement of the homeostasis of ∆Ψ. Conventionally, ∆Ψ in living cells is estimated by the fluorescence of probes such as rhodamine 123, tetramethylrodamine, etc. However, when assessing the fluorescence, the possibility of the intracellular/intramitochondrial modification of the rhodamine molecule is not taken into account. Such changes were revealed in this work, in which a comparison of normal (astrocytic) and tumor (glioma) cells was conducted. Fluorescent microscopy, flow cytometry, and mass spectrometry revealed significant modifications of rhodamine molecules developing over time, which were prevented by amiodarone apparently due to blocking the release of xenobiotics from the cell and their transformation with the participation of cytochrome P450. Obviously, an important role in these processes is played by the increased retention of rhodamines in tumor cells. Our data require careful evaluation of mitochondrial ∆Ψ potential based on the assessment of the fluorescence of the mitochondrial probe.
Gut Microbiota as a Source of Uremic Toxins
Authors: Popkov Vasily A. , Zharikova Anastasia A. , Demchenko Evgenia A. , Andrianova Nadezda V. , Zorov Dmitry B. , Plotnikov Egor Y.
Published: January 2022

Uremic retention solutes are the compounds that accumulate in the blood when kidney excretory function is impaired. Some of these compounds are toxic at high concentrations and are usually known as “uremic toxins”. The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually mortality during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes increase during uremia; however, the exact origin for most of them is still debatable. There are three main sources for such compounds: exogenous ones are consumed with food, whereas endogenous ones are produced by the host metabolism or by symbiotic microbiota metabolism. In this article, we identify uremic retention solutes presumably of gut microbiota origin. We used database analysis to obtain data on the enzymatic reactions in bacteria and human organisms that potentially yield uremic retention solutes and hence to determine what toxins could be synthesized in bacteria residing in the human gut. We selected biochemical pathways resulting in uremic retention solutes synthesis related to specific bacterial strains and revealed links between toxin concentration in uremia and the proportion of different bacteria species which can synthesize the toxin. The detected bacterial species essential for the synthesis of uremic retention solutes were then verified using the Human Microbiome Project database. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of the synthesis of a particular toxin by the human metabolism. Our study presents a novel bioinformatics approach for the elucidation of the origin of both uremic retention solutes and uremic toxins and for searching for the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.
The Endometrial Microbiome and Its Impact on Human Conception
Authors: Toson Bruno , Simon Carlos , Moreno Inmaculada
Published: January 2022

Changes in the female genital tract microbiome are consistently correlated to gynecological and obstetrical pathologies, and tract dysbiosis can impact reproductive outcomes during fertility treatment. Nonetheless, a consensus regarding the physiological microbiome core inside the uterine cavity has not been reached due to a myriad of study limitations, such as sample size and experimental design variations, and the influence of endometrial bacterial communities on human reproduction remains debated. Understanding the healthy endometrial microbiota and how changes in its composition affect fertility would potentially allow personalized treatment through microbiome management during assisted reproductive therapies, ultimately leading to improvement of clinical outcomes. Here, we review current knowledge regarding the uterine microbiota and how it relates to human conception.
ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors
Authors: Ueno Sayaka , Sudo Tamotsu , Hirasawa Akira
Published: January 2022

Ataxia–telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.
Multiple Antimicrobial Effects of Hybrid Peptides Synthesized Based on the Sequence of Ribosomal S1 Protein from Staphylococcus aureus
Authors: Kravchenko Sergey V. , Domnin Pavel A. , Grishin Sergei Y. , Panfilov Alexander V. , Azev Viacheslav N. , Mustaeva Leila G. , Gorbunova Elena Y. , Kobyakova Margarita I. , Surin Alexey K. , Glyakina Anna V. , Fadeev Roman S. , Ermolaeva Svetlana A. , Galzitskaya Oxana V.
Published: January 2022

The need to develop new antimicrobial peptides is due to the high resistance of pathogenic bacteria to traditional antibiotics now and in the future. The creation of synthetic peptide constructs is a common and successful approach to the development of new antimicrobial peptides. In this work, we use a simple, flexible, and scalable technique to create hybrid antimicrobial peptides containing amyloidogenic regions of the ribosomal S1 protein from Staphylococcus aureus. While the cell-penetrating peptide allows the peptide to enter the bacterial cell, the amyloidogenic site provides an antimicrobial effect by coaggregating with functional bacterial proteins. We have demonstrated the antimicrobial effects of the R23F, R23DI, and R23EI hybrid peptides against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, and Bacillus cereus. R23F, R23DI, and R23EI can be used as antimicrobial peptides against Gram-positive and Gram-negative bacteria resistant to traditional antibiotics.
The Mycobacterium tuberculosis PE_PGRS Protein Family Acts as an Immunological Decoy to Subvert Host Immune Response
Authors: Sharma Tarina , Alam Anwar , Ehtram Aquib , Rani Anshu , Grover Sonam , Ehtesham Nasreen Z. , Hasnain Seyed E.
Published: January 2022

Mycobacterium tuberculosis (M.tb) is a successful pathogen that can reside within the alveolar macrophages of the host and can survive in a latent stage. The pathogen has evolved and developed multiple strategies to resist the host immune responses. M.tb escapes from host macrophage through evasion or subversion of immune effector functions. M.tb genome codes for PE/PPE/PE_PGRS proteins, which are intrinsically disordered, redundant and antigenic in nature. These proteins perform multiple functions that intensify the virulence competence of M.tb majorly by modulating immune responses, thereby affecting immune mediated clearance of the pathogen. The highly repetitive, redundant and antigenic nature of PE/PPE/PE_PGRS proteins provide a critical edge over other M.tb proteins in terms of imparting a higher level of virulence and also as a decoy molecule that masks the effect of effector molecules, thereby modulating immuno-surveillance. An understanding of how these proteins subvert the host immunological machinery may add to the current knowledge about M.tb virulence and pathogenesis. This can help in redirecting our strategies for tackling M.tb infections.
AGC1 Deficiency: Pathology and Molecular and Cellular Mechanisms of the Disease
Authors: Pardo Beatriz , Herrada-Soler Eduardo , Satrústegui Jorgina , Contreras Laura , del Arco Araceli
Published: January 2022

AGC1/Aralar/Slc25a12 is the mitochondrial carrier of aspartate-glutamate, the regulatory component of the NADH malate-aspartate shuttle (MAS) that transfers cytosolic redox power to neuronal mitochondria. The deficiency in AGC1/Aralar leads to the human rare disease named “early infantile epileptic encephalopathy 39” (EIEE 39, OMIM # 612949) characterized by epilepsy, hypotonia, arrested psychomotor neurodevelopment, hypo myelination and a drastic drop in brain aspartate (Asp) and N-acetylaspartate (NAA). Current evidence suggest that neurons are the main brain cell type expressing Aralar. However, paradoxically, glial functions such as myelin and Glutamine (Gln) synthesis are markedly impaired in AGC1 deficiency. Herein, we discuss the role of the AGC1/Aralar-MAS pathway in neuronal functions such as Asp and NAA synthesis, lactate use, respiration on glucose, glutamate (Glu) oxidation and other neurometabolic aspects. The possible mechanism triggering the pathophysiological findings in AGC1 deficiency, such as epilepsy and postnatal hypomyelination observed in humans and mice, are also included. Many of these mechanisms arise from findings in the aralar-KO mice model that extensively recapitulate the human disease including the astroglial failure to synthesize Gln and the dopamine (DA) mishandling in the nigrostriatal system. Epilepsy and DA mishandling are a direct consequence of the metabolic defect in neurons due to AGC1/Aralar deficiency. However, the deficits in myelin and Gln synthesis may be a consequence of neuronal affectation or a direct effect of AGC1/Aralar deficiency in glial cells. Further research is needed to clarify this question and delineate the transcellular metabolic fluxes that control brain functions. Finally, we discuss therapeutic approaches successfully used in AGC1-deficient patients and mice.
Cholesterol in the Cell Membrane—An Emerging Player in Atherogenesis
Authors: Paukner Karel , Králová Lesná Ivana , Poledne Rudolf
Published: January 2022

Membrane cholesterol is essential for cell membrane properties, just as serum cholesterol is important for the transport of molecules between organs. This review focuses on cholesterol transport between lipoproteins and lipid rafts on the surface of macrophages. Recent studies exploring this mechanism and recognition of the central dogma—the key role of macrophages in cardiovascular disease—have led to the notion that this transport mechanism plays a major role in the pathogenesis of atherosclerosis. The exact molecular mechanism of this transport remains unclear. Future research will improve our understanding of the molecular and cellular bases of lipid raft-associated cholesterol transport.
Treatment with Mesenchymal Stromal Cells Overexpressing Fas-Ligand Ameliorates Acute Graft-versus-Host Disease in Mice
Authors: Vacaru Andrei Mircea , Mazilu Ana-Maria , Dumitrescu Madalina , Fenyo Ioana Madalina , Gafencu Anca Violeta , Vacaru Ana-Maria
Published: January 2022

Allogeneic hematopoietic cell transplantation (allo-HCT) has the potential to cure malignant and non-malignant hematological disorders, but because of the serious side effects of this intervention its applications are limited to a restricted number of diseases. Graft-versus-host disease (GvHD) is the most frequent complication and the leading cause of mortality and morbidity following allo-HCT. It results from the attack of the transplanted T cells from the graft against the cells of the recipient. There is no clear treatment for this severe complication. Due to their immunomodulatory properties, mesenchymal stromal cells (MSC) have been proposed to treat GvHD, but the results did not meet expectations. We have previously showed that the immunomodulatory effect of the MSC was significantly enhanced through adenoviral-mediated overexpression of FasL. In this study, we have tested the properties of FasL-overexpressing MSC in vivo, in a mouse model for acute GvHD. We found that treatment with FasL-overexpressing MSC delayed the onset of the disease and increased survival of the mice.
LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear Palsy
Authors: Abu Bakar Zulzikry Hafiz , Bellier Jean-Pierre , Yanagisawa Daijiro , Kato Tomoko , Mukaisho Ken-ichi , Tooyama Ikuo
Published: January 2022

Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein associated with neurodegenerative diseases. In patients with progressive supranuclear palsy (PSP), FtMt was shown to accumulate in nigral neurons. Here, we investigated FtMt and LC3 in the post-mortem midbrain of PSP patients to reveal novel aspects of the pathology. Immunohistochemistry was used to assess the distribution and abnormal changes in FtMt and LC3 immunoreactivities. Colocalization analysis using double immunofluorescence was performed, and subcellular patterns were examined using 3D imaging and modeling. In the substantia nigra pars compacta (SNc), strong FtMt-IR and LC3-IR were observed in the neurons of PSP patients. In other midbrain regions, such as the superior colliculus, the FtMt-IR and LC3-IR remained unchanged. In the SNc, nigral neurons were categorized into four patterns based on subcellular LC3/FtMt immunofluorescence intensities, degree of colocalization, and subcellular overlapping. This categorization suggested that concomitant accumulation of LC3/FtMt is related to mitophagy processes. Using the LC3-IR to stage neuronal damage, we retraced LC3/FtMt patterns and revealed the progression of FtMt accumulation in nigral neurons. Informed by these findings, we proposed a hypothesis to explain the function of FtMt during PSP progression.
3D Bioprinting of Gelatin–Xanthan Gum Composite Hydrogels for Growth of Human Skin Cells
Authors: Piola Beatrice , Sabbatini Maurizio , Gino Sarah , Invernizzi Marco , Renò Filippo
Published: January 2022

In recent years, bioprinting has attracted much attention as a potential tool for generating complex 3D biological constructs capable of mimicking the native tissue microenvironment and promoting physiologically relevant cell–cell and cell–matrix interactions. The aim of the present study was to develop a crosslinked 3D printable hydrogel based on biocompatible natural polymers, gelatin and xanthan gum at different percentages to be used both as a scaffold for cell growth and as a wound dressing. The CellInk Inkredible 3D printer was used for the 3D printing of hydrogels, and a glutaraldehyde solution was tested for the crosslinking process. We were able to obtain two kinds of printable hydrogels with different porosity, swelling and degradation time. Subsequently, the printed hydrogels were characterized from the point of view of biocompatibility. Our results showed that gelatin/xanthan-gum bioprinted hydrogels were biocompatible materials, as they allowed both human keratinocyte and fibroblast in vitro growth for 14 days. These two bioprintable hydrogels could be also used as a helpful dressing material.
The Beneficial Effects of Combining Anti-Aβ Antibody NP106 and Curcumin Analog TML-6 on the Treatment of Alzheimer’s Disease in APP/PS1 Mice
Authors: Su Ih-Jen , Hsu Chia-Yu , Shen Santai , Chao Po-Kuan , Hsu John Tsu-An , Hsueh Jung-Tsung , Liang Jia-Jun , Hsu Ying-Ting , Shie Feng-Shiun
Published: January 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a multifactorial etiology. A multitarget treatment that modulates multifaceted biological functions might be more effective than a single-target approach. Here, the therapeutic efficacy of combination treatment using anti-Aβ antibody NP106 and curcumin analog TML-6 versus monotherapy was investigated in an APP/PS1 mouse model of AD. Our data demonstrate that both combination treatment and monotherapy attenuated brain Aβ and improved the nesting behavioral deficit to varying degrees. Importantly, the combination treatment group had the lowest Aβ levels, and insoluble forms of Aβ were reduced most effectively. The nesting performance of APP/PS1 mice receiving combination treatment was better than that of other APP/PS1 groups. Further findings indicate that enhanced microglial Aβ phagocytosis and lower levels of proinflammatory cytokines were concurrent with the aforementioned effects of NP106 in combination with TML-6. Intriguingly, combination treatment also normalized the gut microbiota of APP/PS1 mice to levels resembling the wild-type control. Taken together, combination treatment outperformed NP106 or TML-6 monotherapy in ameliorating Aβ pathology and the nesting behavioral deficit in APP/PS1 mice. The superior effect might result from a more potent modulation of microglial function, cerebral inflammation, and the gut microbiota. This innovative treatment paradigm confers a new avenue to develop more efficacious AD treatments.
Bidirectional lncRNA Transfer between Cuscuta Parasites and Their Host Plant
Authors: Wu Yuguo , Luo Dong , Fang Longfa , Zhou Qiang , Liu Wenxian , Liu Zhipeng
Published: January 2022

Dodder species (Cuscuta spp.) are holoparasites that have extensive material exchange with their host plants through vascular connections. Recent studies on cross-species transfer have provided breakthrough insights, but little is known about the interaction mechanisms of the inter-plant mobile substances in parasitic systems. We sequenced the transcriptomes of dodder growing on soybean hosts to characterize the long non-coding RNA (lncRNA) transfer between the two species, and found that lncRNAs can move in high numbers (365 dodder lncRNAs and 14 soybean lncRNAs) in a bidirectional manner. Reverse transcription-polymerase chain reaction further confirmed that individual lncRNAs were trafficked in the dodder–soybean parasitic system. To reveal the potential functions of mobile transcripts, the Gene Ontology terms of mobile lncRNA target genes were predicted, and mobile dodder target genes were found to be mainly enriched in “metabolic process”, “catalytic activity”, “signaling”, and “response to stimulus” categories, whereas mobile soybean target genes were enriched in organelle-related categories, indicating that specific mobile lncRNAs may be important in regulating dodder parasitism. Our findings reveal that lncRNAs are transferred between dodder and its host soybean plants, which may act as critical regulators to coordinate the host–dodder interaction at the whole parasitic level.
Metabolic Rewiring by Human Placenta-Derived Mesenchymal Stem Cell Therapy Promotes Rejuvenation in Aged Female Rats
Authors: Kim Kyeoung-Hwa , Lee Kyung-Ah
Published: January 2022

Aging is a degenerative process involving cell function deterioration, leading to altered metabolic pathways, increased metabolite diversity, and dysregulated metabolism. Previously, we reported that human placenta-derived mesenchymal stem cells (hPD-MSCs) have therapeutic effects on ovarian aging. This study aimed to identify hPD-MSC therapy-induced responses at the metabolite and protein levels and serum biomarker(s) of aging and/or rejuvenation. We observed weight loss after hPD-MSC therapy. Importantly, insulin-like growth factor-I (IGF-I), known prolongs healthy life spans, were markedly elevated in serum. Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS) analysis identified 176 metabolites, among which the levels of 3-hydroxybutyric acid, glycocholic acid, and taurine, which are associated with health and longevity, were enhanced after hPD-MSC stimulation. Furthermore, after hPD-MSC therapy, the levels of vitamin B6 and its metabolite pyridoxal 5′-phosphate were markedly increased in the serum and liver, respectively. Interestingly, hPD-MSC therapy promoted serotonin production due to increased vitamin B6 metabolism rates. Increased liver serotonin levels after multiple-injection therapy altered the expression of mRNAs and proteins associated with hepatocyte proliferation and mitochondrial biogenesis. Changes in metabolites in circulation after hPD-MSC therapy can be used to identify biomarker(s) of aging and/or rejuvenation. In addition, serotonin is a valuable therapeutic target for reversing aging-associated liver degeneration.
Tracking of Endothelial Cell Migration and Stiffness Measurements Reveal the Role of Cytoskeletal Dynamics
Authors: Romano Dominick J. , Gomez-Salinero Jesus M. , Šunić Zoran , Checco Antonio , Rabbany Sina Y.
Published: January 2022

Cell migration is a complex, tightly regulated multistep process in which cytoskeletal reorganization and focal adhesion redistribution play a central role. Core to both individual and collective migration is the persistent random walk, which is characterized by random force generation and resistance to directional change. We first discuss a model that describes the stochastic movement of ECs and characterizes EC persistence in wound healing. To that end, we pharmacologically disrupted cytoskeletal dynamics, cytochalasin D for actin and nocodazole for tubulin, to understand its contributions to cell morphology, stiffness, and motility. As such, the use of Atomic Force Microscopy (AFM) enabled us to probe the topography and stiffness of ECs, while time lapse microscopy provided observations in wound healing models. Our results suggest that actin and tubulin dynamics contribute to EC shape, compressive moduli, and directional organization in collective migration. Insights from the model and time lapse experiment suggest that EC speed and persistence are directionally organized in wound healing. Pharmacological disruptions suggest that actin and tubulin dynamics play a role in collective migration. Current insights from both the model and experiment represent an important step in understanding the biomechanics of EC migration as a therapeutic target.
Interleukin-4 Aggravates LPS-Induced Striatal Neurodegeneration In Vivo via Oxidative Stress and Polarization of Microglia/Macrophages
Authors: Jang Jaegeun , Hong Ahreum , Chung Youngcheul , Jin Byungkwan
Published: January 2022

The present study investigated the effects of interleukin (IL)-4 on striatal neurons in lipopolysaccharide (LPS)-injected rat striatum in vivo. Either LPS or PBS as a control was unilaterally injected into the striatum, and brain tissues were processed for immunohistochemical and Nissl staining or for hydroethidine histochemistry at the indicated time points after LPS injection. Analysis by NeuN and Nissl immunohistochemical staining showed a significant loss of striatal neurons at 1, 3, and 7 days post LPS. In parallel, IL-4 immunoreactivity was upregulated as early as 1 day, reached a peak at 3 days, and was sustained up to 7 days post LPS. Increased levels of IL-4 immunoreactivity were exclusively detected in microglia/macrophages, but not in neurons nor astrocytes. The neutralizing antibody (NA) for IL-4 significantly protects striatal neurons against LPS-induced neurotoxicity in vivo. Accompanying neuroprotection, IL-4NA inhibited activation of microglia/macrophages, production of reactive oxygen species (ROS), ROS-derived oxidative damage and nitrosative stress, and produced polarization of microglia/macrophages shifted from M1 to M2. These results suggest that endogenous IL-4 expressed in LPS-activated microglia/macrophages contributes to striatal neurodegeneration in which oxidative/nitrosative stress and M1/M2 polarization are implicated.
Targeting Cancer with CRISPR/Cas9-Based Therapy
Authors: Balon Katarzyna , Sheriff Adam , Jacków Joanna , Łaczmański Łukasz
Published: January 2022

Cancer is a devastating condition characterised by the uncontrolled division of cells with many forms remaining resistant to current treatment. A hallmark of cancer is the gradual accumulation of somatic mutations which drive tumorigenesis in cancerous cells, creating a mutation landscape distinctive to a cancer type, an individual patient or even a single tumour lesion. Gene editing with CRISPR/Cas9-based tools now enables the precise and permanent targeting of mutations and offers an opportunity to harness this technology to target oncogenic mutations. However, the development of safe and effective gene editing therapies for cancer relies on careful design to spare normal cells and avoid introducing other mutations. This article aims to describe recent advancements in cancer-selective treatments based on the CRISPR/Cas9 system, especially focusing on strategies for targeted delivery of the CRISPR/Cas9 machinery to affected cells, controlling Cas9 expression in tissues of interest and disrupting cancer-specific genes to result in selective death of malignant cells.
Carbamylated Proteins in Renal Disease: Aggravating Factors or Just Biomarkers?
Authors: Gorisse Laëtitia , Jaisson Stéphane , Piétrement Christine , Gillery Philippe
Published: January 2022

Carbamylation is a nonenzymatic post-translational modification resulting from the reaction between cyanate, a urea by-product, and proteins. In vivo and in vitro studies have demonstrated that carbamylation modifies protein structures and functions, triggering unfavourable molecular and cellular responses. An enhanced formation of carbamylation-derived products (CDPs) is observed in pathological contexts, especially during chronic kidney disease (CKD), because of increased blood urea. Significantly, studies have reported a positive correlation between serum CDPs and the evolutive state of renal failure. Further, serum concentrations of carbamylated proteins are characterized as strong predictors of mortality in end-stage renal disease patients. Over time, it is likely that these modified compounds become aggravating factors and promote long-term complications, including cardiovascular disorders and inflammation or immune system dysfunctions. These poor clinical outcomes have led researchers to consider strategies to prevent or slow down CDP formation. Even if growing evidence suggests the involvement of carbamylation in the pathophysiology of CKD, the real relevance of carbamylation is still unclear: is it a causal phenomenon, a metabolic consequence or just a biological feature? In this review, we discuss how carbamylation, a consequence of renal function decline, may become a causal phenomenon of kidney disease progression and how CDPs may be used as biomarkers.
Nuclear Cytoskeleton in Virus Infection
Authors: Horníková Lenka , Bruštíková Kateřina , Huérfano Sandra , Forstová Jitka
Published: January 2022

The nuclear lamina is the main component of the nuclear cytoskeleton that maintains the integrity of the nucleus. However, it represents a natural barrier for viruses replicating in the cell nucleus. The lamina blocks viruses from being trafficked to the nucleus for replication, but it also impedes the nuclear egress of the progeny of viral particles. Thus, viruses have evolved mechanisms to overcome this obstacle. Large viruses induce the assembly of multiprotein complexes that are anchored to the inner nuclear membrane. Important components of these complexes are the viral and cellular kinases phosphorylating the lamina and promoting its disaggregation, therefore allowing virus egress. Small viruses also use cellular kinases to induce lamina phosphorylation and the subsequent disruption in order to facilitate the import of viral particles during the early stages of infection or during their nuclear egress. Another component of the nuclear cytoskeleton, nuclear actin, is exploited by viruses for the intranuclear movement of their particles from the replication sites to the nuclear periphery. This study focuses on exploitation of the nuclear cytoskeleton by viruses, although this is just the beginning for many viruses, and promises to reveal the mechanisms and dynamic of physiological and pathological processes in the nucleus.
Endoplasmic Reticulum Stress Contributed to Dipyridamole-Induced Impaired Autophagic Flux and Glioma Apoptosis
Authors: Chang Cheng-Yi , Wu Chih-Cheng , Wang Jiaan-Der , Liao Su-Lan , Chen Wen-Ying , Kuan Yu-Hsiang , Wang Wen-Yi , Chen Chun-Jung
Published: January 2022

Elevation of intracellular cAMP levels has been implicated in glioma cell proliferation inhibition, differentiation, and apoptosis. Inhibition of phosphodiesterase is a way to elevate intracellular cAMP levels. The present study aimed to investigate the anti-glioma potential of dipyridamole, an inhibitor of phosphodiesterase. Upon treatment with dipyridamole, human U87 glioma cells decreased cell viability, clonogenic colonization, migration, and invasion, along with Noxa upregulation, Endoplasmic Reticulum (ER) stress, impaired autophagic flux, Yes-associated Protein 1 (YAP1) phosphorylation, and YAP1 reduction. Pharmacological and genetic studies revealed the ability of dipyridamole to initiate Noxa-guided apoptosis through ER stress. Additionally, the current study further identified the biochemical role of YAP1 in communicating with ER stress and autophagy under situations of dipyridamole treatment. YAP1 promoted autophagy and protected glioma cells from dipyridamole-induced apoptotic cell death. Dipyridamole impaired autophagic flux and rendered glioma cells more vulnerable to apoptotic cell death through ER stress-inhibitable YAP1/autophagy axis. The overall cellular changes caused by dipyridamole appeared to ensure a successful completion of apoptosis. Dipyridamole also duplicated the biochemical changes and apoptosis in glioma T98G cells. Since dipyridamole has additional biochemical and pharmacological properties, further research centered on the anti-glioma mechanisms of dipyridamole is still needed.