bluuebunny/crossref_metadata_2025 huggingface dataset:
Greenland Ice Sheet Surface Runoff Projections to 2200 Using Degree-Day Methods
Authors: Yue Chao , Zhao Liyun , Wolovick Michael , Moore John C.
Published: November 2021

Surface runoff from the Greenland ice sheet (GrIS) has dominated recent ice mass loss and is having significant impacts on sea-level rise under global warming. Here, we used two modified degree-day (DD) methods to estimate the runoff of the GrIS during 1950–2200 under the extensions of historical, RCP 4.5, and RCP 8.5 scenarios. Near-surface air temperature and snowfall were obtained from five Earth System Models. We applied new degree-day factors to best match the results of the surface energy and mass balance model, SEMIC, over the whole GrIS in a 21st century simulation. The relative misfits between tuned DD methods and SEMIC during 2050–2089 were 3% (RCP4.5) and 12% (RCP8.5), much smaller than the 30% difference between untuned DD methods and SEMIC. Equilibrium line altitude evolution, runoff-elevation feedback, and ice mask evolution were considered in the future simulations to 2200. The ensemble mean cumulative runoff increasing over the GrIS was equivalent to sea-level rises of 6 ± 2 cm (RCP4.5) and 9 ± 3 cm (RCP8.5) by 2100 relative to the period 1950–2005, and 13 ± 4 cm (RCP4.5) and 40 ± 5 cm (RCP8.5) by 2200. Runoff-elevation feedback produced runoff increases of 5 ± 2% (RCP4.5) and 6 ± 2% (RCP8.5) by 2100, and 12 ± 4% (RCP4.5) and 15 ± 5% (RCP8.5) by 2200. Two sensitivity experiments showed that increases of 150% or 200%, relative to the annual mean amount of snowfall in 2080–2100, in the post-2100 period would lead to 10% or 20% more runoff under RCP4.5 and 5% or 10% under RCP8.5 because faster ice margin retreat and ice sheet loss under RCP8.5 dominate snowfall increases and ice elevation feedbacks.
One Atmosphere: Integrating Air Pollution and Climate Policy and Governance
Authors: Zusman Eric , Unger Charlotte , Borgford-Parnell Nathan , Mar Kathleen A.
Published: November 2021

Few challenges pose a greater threat to a healthy planet and people than air pollution and climate change. Over the past three decades, research has demonstrated that integrated solutions to air pollution and climate change can yield co-benefits that support cost-effective, coherent policies. However, research on co-benefits has yet to generate policy responses consistent with this promise. This paper argues that realizing this potential requires more rigorous research on how governance affects the opportunities and incentives to align the interests of government agencies, scientists, and other stakeholders at multiple levels. The article proposes a “One Atmosphere approach” consisting of three building blocks to strengthen that alignment: (1) continually incorporating and strategically timing the introduction of integrated visions; (2) reforming governance arrangements to encourage interagency collaboration and multi-stakeholder cooperation; and (3) supporting integrated visions and institutional cooperation with standardized metrics and assessment methods. This article is also the introduction to the Special Issue ‘One Atmosphere: Integrating Air Pollution and Climate Policy and Governance’, aimed at fostering the multidisciplinary dialogue needed for more integrated air pollution and climate change policies.
Projected Elevated [CO2] and Warming Result in Overestimation of SPAD-Based Rice Leaf Nitrogen Status for Nitrogen Management
Authors: Tao Ye , Zhang Jishuang , Song Lian , Cai Chuang , Wang Dongming , Wei Wei , Gu Xinyue , Yang Xiong , Zhu Chunwu
Published: November 2021

Nitrogen (N) has a unique place in agricultural systems with large requirements. To achieve optimal nitrogen management that meets the needs of agricultural systems without causing potential environmental risks, it is of great significance to increase N use efficiency (NUE) in agricultural systems. A chlorophyll meter, for example, the SPAD-502, can provide a simple, nondestructive, and quick method for monitoring leaf N status and NUE. However, the SPAD-based crop leaf’s N status varies greatly due to environmental factors such as CO2 concentration ([CO2]) or temperature variations. In this study, we conducted [CO2] (ambient and enriched up to 500 μmol moL1) and temperature (ambient and increased by 1.5~2.0 °C) controlled experiments from 2015 to 2017 and in 2020 in two Free-Air CO2 Enrichment (FACE) sites. Leaf characters (SPAD readings, chlorophyll a + b, N content, etc.) of seven rice cultivars were measured in this four year experiment. Here, we provide evidence that SPAD readings are significantly linearly correlated with rice leaf chlorophyll a + b content (chl a + b) and N content, while the relationships are profoundly affected by elevated [CO2] and warming. Under elevated [CO2] treatment (E), the relationship between chl a + b content and N content remains unchanged, but SPAD readings and chl a + b content show a significant difference to those under ambient (A) treatment, which distorts the SPAD-based N monitoring. Under warming (T), and combined elevated [CO2] and warming (ET) treatments, both of the relationships between SPAD and leaf a + b content and between leaf a + b content and N content show a significant difference to those under A treatment. To deal with this issue under the background of global climate change dominated by warming and elevated [CO2] in the future, we need to increase the SPAD reading’s threshold value by at least 5% to adjust for applying N fertilizer within the rice cropping system by mid-century.
Rare and Extreme Wildland Fire in Sakha in 2021
Authors: Hayasaka Hiroshi
Published: November 2021

A large-scale wildland fire occurred in Sakha in 2021. The results of fire analysis showed that the total number of hotspots in 2021 exceeded 267,000. This is about 5.8 times the average number of fires over the last 19 years since 2002. The largest daily number of hotspots in 2021 was 16,226, detected on 2 August. On 7 August, about half of the daily hotspots (52.6% = 8175/15,537 × 100) were detected in a highest fire density area (HFA, 62.5–65° N, 125–130° E) near Yakutsk under strong southeasterly wind (wind velocity about 12 m/s (43 km/h)). The results of weather analysis using various weather maps are as follows: The large meandering westerlies due to stagnant low-pressure systems in the Barents Sea brought high-pressure systems and warm air masses from the south to high latitudes, creating warm, dry conditions that are favorable conditions for fire. In addition to these, strong southeasterly winds at lower air levels blew which were related to the development of high-pressure systems in the Arctic Ocean. The HFA was located in the strong wind region (>8 m/s) of the v-wind map. The record-breaking Sakha fire season of 2021 is an example of extreme phenomena wrought by rapid climate change.
Bioaerosol Emission from Biofilters: Impact of Bed Material Type and Waste Gas Origin
Authors: Affek Katarzyna , Tabernacka Agnieszka , Załęska-Radziwiłł Monika , Doskocz Nina , Muszyński Adam
Published: November 2021

Three semi-technical scale biofilters were applied to treat waste gases at different industrial sites in Poland: a mechanical–biological treatment plant of municipal solid waste, a wastewater treatment plant and a food industry plant. Two types of materials were used as beds in the biofilters: stumpwood chips and pine bark, and stumpwood chips, pine bark and compost from green waste. Both bed materials supported the microbial growth and high numbers (106–108 cfu/g dry mass (DM)) of culturable bacteria, and fungi in beds were observed. There was no correlation between the number of microorganisms (cfu/g DM) and the respiratory activity in the biofilter beds. However, microbial respiration activity corresponded with microbial abundance expressed as microbial equivalents (ME), which was calculated based on adenosine triphosphate (ATP) determination. The biofilters either reduced or increased bioaerosol emissions from industrial plants, depending on the microbial content in the waste gases. A high microbial content in the waste gases made the effect of microbial emission from the biofilter bed negligible. The type of biofilter bed and number of microorganisms in the bed also influenced the final bioaerosol emission, but these factors were relevant for biofilters that treated waste gases with low microbial concentrations.
Ensemble Forecasting Experiments Using the Breeding of Growing Modes with Perturbed Land Variables
Authors: Zeng Xin-Min , Liang Yong-Jing , Wang Yang , Zheng Yi-Qun
Published: November 2021

Although land surface influences atmospheric processes significantly, insufficient studies have been conducted on the ensemble forecasts using the breeding of growing modes (BGM) with perturbed land surface variables. To investigate the practicability of perturbed land variables for ensemble forecasting, we used the ARWv3 mesoscale model to generate ensembles for an event of 24 h heavy rainfall with perturbed atmospheric and land variables by the BGM method. Results show that both atmospheric and land variables can generate initial perturbations with BGM, except that they differ in time and saturation characteristics, e.g., saturation is generally achieved in approximately 30 h with a growth rate of ~1.30 for atmospheric variables versus 102 h and growth rate of 1.02 for land variables. With the increase in precipitation, the importance of the perturbations of land variables also increases as compared to those of atmospheric variables. Moreover, the influence of the perturbations of land variables on simulated precipitation is still relatively large, although smaller than that of atmospheric variables, e.g., the spreads of perturbed atmospheric and land subsets were 7.3 and 3.8 mm, respectively. The benefits of perturbed initialisation can also be observed in terms of probability forecast. All findings indicate that the BGM method with perturbed land variables has the potential to ensemble forecasts for precipitation.
Modifications to Snow-Melting and Flooding Processes in the Hydrological Model—A Case Study in Issyk-Kul, Kyrgyzstan
Authors: Uwamahoro Solange , Liu Tie , Nzabarinda Vincent , Habumugisha Jules Maurice , Habumugisha Theogene , Harerimana Barthelemy , Bao Anming
Published: November 2021

Streamflow impacts water supply and flood protection. Snowmelt floods occur frequently, especially in mountainous areas, and they pose serious threats to natural and socioeconomic systems. The current forecasting method relies on basic snowmelt accumulation and has geographic limitations that restrict the accuracy and timeliness of flood simulation and prediction. In this study, we clarified the precipitation types in two selected catchments by verifying accumulated and maximum temperatures’ influences on snow melting using a separation algorithm of rain and snow that incorporates with the temperatures. The new snow-melting process utilizing the algorithm in the soil and water assessment tool model (SWAT) was also developed by considering the temperatures. The SWAT model was used to simulate flooding and snowmelt in the catchments. We found that the contributions of snowmelt to the river flow were approximately 6% and 7% higher, according to our model compared to the original model, for catchments A and B, respectively. After the model improvement, the flood peaks increased by 49.42% and 43.87% in A and B, respectively. The contributions of snowmelt to stream flow increased by 24.26% and 31% for A and B, respectively. Generally, the modifications improved the model accuracy, the accuracy of snowmelt’s contributions to runoff, the accuracy of predicting flood peaks, the time precision, and the flood frequency simulations.
Impact of Vehicle Fleet Modernization on the Traffic-Originated Air Pollution in an Urban Area—A Case Study
Authors: Holnicki Piotr , Nahorski Zbigniew , Kałuszko Andrzej
Published: November 2021

The main subject of this paper is an analysis of the influence of changes in the air pollution caused by road traffic, due to its modernization, on the air quality in Warsaw conurbation, Poland. Using the Calpuff model, simulations of the yearly averaged concentrations of NOx, CO, PM10, and PM2.5 were performed, together with an assessment of the population exposure to individual pollutions. Source apportionment analysis indicates that traffic is the main source of NOx and CO concentrations in the city atmosphere. Utilizing the Euro norms emission standards, a scenario of vehicle emission abatement is formulated based on the assumed general vehicle fleet modernization and transition to Euro 6 emission standards. Computer simulations show a reduction in NOx concentrations attributed to emission mitigation of passenger cars, trucks and vans, and public transport buses, respectively. On the other hand, improving air quality in terms of CO concentrations depends almost exclusively on gasoline vehicle modernization. The implementation of the considered scenario causes an adequate reduction in the population exposure and related health effects. In particular, implementation of the scenario discussed results in a 47% reduction (compared with the baseline value) in the attributable yearly deaths related to NOx pollution. In spite of a substantial contribution of vehicle traffic to the overall PM pollution, modernization of the fuel combustion causes only minor final effects because the dominant share of PM pollution in Warsaw originates from the municipal sector and the transboundary inflow.
Victor A. McKusick, the “Father of Medical Genetics”
Authors: Martini Alessandro , Cassina Matteo
Published: November 2021

The Special Issue “Genetics of hearing loss” is dedicated to Victor A [...]
A Simple Frequency Formulation for the Tangent Oscillator
Authors: He Ji-Huan , Yang Qian , He Chun-Hui , Khan Yasir
Published: November 2021

The frequency of a nonlinear vibration system is nonlinearly related to its amplitude, and this relationship is critical in the design of a packaging system and a microelectromechanical system (MEMS). This paper proposes a straightforward frequency prediction method for nonlinear oscillators with arbitrary initial conditions. The tangent oscillator, the hyperbolic tangent oscillator, a singular oscillator, and a MEMS oscillator are chosen to elucidate the simple solving process. The results, when compared with those obtained by the homotopy perturbation method, exhibit a good agreement. This paper introduces a very convenient procedure for attaining quick and accurate insight into the vibration property of a nonlinear vibration system.
Roots of Elliptic Scator Numbers
Authors: Fernandez-Guasti Manuel
Published: November 2021

The Victoria equation, a generalization of De Moivre’s formula in 1+n dimensional scator algebra, is inverted to obtain the roots of a scator. For the qth root in S1+n of a real or a scator number, there are qn possible roots. For n=1, the usual q complex roots are obtained with their concomitant cyclotomic geometric interpretation. For n≥2, in addition to the previous roots, new families arise. These roots are grouped according to two criteria: sets satisfying Abelian group properties under multiplication and sets catalogued according to director conjugation. The geometric interpretation is illustrated with the roots of unity in S1+2.
High Glucose Concentrations Impair the Processing and Presentation of Mycobacterium tuberculosis Antigens In Vitro
Authors: Monroy-Mérida Guadalupe , Guzmán-Beltrán Silvia , Hernández Fernando , Santos-Mendoza Teresa , Bobadilla Karen
Published: November 2021

Type 2 diabetes is an established risk factor for tuberculosis, but the underlying mechanisms are largely unknown. We established an in vitro model to analyze the effect of high glucose concentrations in antigen processing and presentation in antigen-presenting cells. Human monocyte-derived macrophages (MDMs) were exposed to high (11 mM and 30 mM) and low (5.5 mM) glucose concentrations and infected with Mycobacterium tuberculosis (Mtb). Flow cytometry was used to analyze the effect of high glucose concentrations in histocompatibility complex (MHC) class II molecules (HLA-DR) and co-stimulatory molecules (CD80 and CD86), indispensable for an adequate antigenic presentation and CD4+ T cell activation. HLA-DR and CD86 were significantly decreased by high glucose concentrations compared with low glucose concentrations. Confocal microscopy was used to detect Rab 5 and Lamp-1, proteins involved in the kinetics of antigen processing as early markers, and Rab 7 and cathepsin D as late markers. We observed a delay in the dynamics of the acquisition of Rab 7 and cathepsin D in high glucose concentrations. Moreover, the kinetics of the formation M. tuberculosis peptide–MHC II complexes in MDMs was decreased under high glucose concentrations, reducing their capacity for T cell activation. These findings suggest that high glucose concentrations directly affect antigenic processing, and therefore antigenic presentation.
Combined Anti-Adipogenic Effects of Hispidulin and p-Synephrine on 3T3-L1 Adipocytes
Authors: Lee Dahae , Kwak Hee Jae , Kim Byoung Ha , Kim Seung Hyun , Kim Dong-Wook , Kang Ki Sung
Published: November 2021

Hispidulin is abundant in Arrabidaea chica, Crossostephium chinense, and Grindelia argentina, among others. p-Synephrine is the main phytochemical constituent of Citrus aurantium. It has been used in combination with various other phytochemicals to determine synergistic effects in studies involving human participants. However, there have been no reports comparing the anti-adipogenic effects of the combination of hispidulin and p-synephrine. The current study explores the anti-adipogenic effects of hispidulin alone and in combination with p-synephrine in a murine preadipocyte cell line, 3T3-L1. Co-treatment resulted in a greater inhibition of the formation of red-labeled lipid droplets than the hispidulin or p-synephrine-alone treatments. Co-treatment with hispidulin and p-synephrine also significantly inhibited adipogenic marker proteins, including Akt, mitogen-activated protein kinases, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, glucocorticoid receptor, and CCAAT/enhancer-binding protein β. Although further studies are required to assess the effects of each drug on pharmacokinetic parameters, a combination treatment with hispidulin and p-synephrine may be a potential alternative strategy for developing novel anti-obesity drugs.
Cholecystokinin-B Receptor-Targeted Nanoparticle for Imaging and Detection of Precancerous Lesions in the Pancreas
Authors: Smith Jill P. , Cao Hong , Edmondson Elijah F. , Dasa Siva Sai Krishna , Stern Stephan T.
Published: November 2021

Survival from pancreatic cancer remains extremely poor, in part because this malignancy is not diagnosed in the early stages, and precancerous pancreatic intraepithelial neoplasia (PanIN) lesions are not seen on routine radiographic imaging. Since the cholecystokinin-B receptor (CCK-BR) becomes over-expressed in PanIN lesions, it may serve as a target for early detection. We developed a biodegradable fluorescent polyplex nanoparticle (NP) that selectively targets the CCK-BR. The NP was complexed to a fluorescent oligonucleotide with Alexa Fluor 647 for far-red imaging and to an oligonucleotide conjugated to Alexa Fluor 488 for localization by immunohistochemistry. Fluorescence was detected over the pancreas of five- to ten-month-old LSL-KrasG12D/+; P48-Cre (KC) mice only after the injection of the receptor target-specific NP and not after injection of untargeted NP. Ex vivo tissue imaging and selective immunohistochemistry confirmed particle localization only to PanIN lesions in the pancreas and not in other organs, supporting the tissue specificity. A human pancreas tissue microarray demonstrated immunoreactivity for the CCK-BR only in the PanIN lesions and not in normal pancreas tissue. The long-term goal would be to develop this imaging tool for screening human subjects at high risk for pancreatic cancer to enable early cancer detection.
Subcellular Localization of Seed-Expressed LEA_4 Proteins Reveals Liquid-Liquid Phase Separation for LEA9 and for LEA48 Homo- and LEA42-LEA48 Heterodimers
Authors: Ginsawaeng Orarat , Heise Carolin , Sangwan Rohit , Karcher Daniel , Hernández-Sánchez Itzell Euridice , Sampathkumar Arun , Zuther Ellen
Published: November 2021

LEA proteins are involved in plant stress tolerance. In Arabidopsis, the LEA_4 Pfam group is the biggest group with the majority of its members being expressed in dry seeds. To assess subcellular localization in vivo, we investigated 11 seed-expressed LEA_4 proteins in embryos dissected from dry seeds expressing LEA_4 fusion proteins under its native promoters with the Venus fluorescent protein (proLEA_4::LEA_4:Venus). LEA_4 proteins were shown to be localized in the endoplasmic reticulum, nucleus, mitochondria, and plastids. LEA9, in addition to the nucleus, was also found in cytoplasmic condensates in dry seeds dependent on cellular hydration level. Most investigated LEA_4 proteins were detected in 4-d-old seedlings. In addition, we assessed bioinformatic tools for predicting subcellular localization and promoter motifs of 11 seed-expressed LEA_4 proteins. Ratiometric bimolecular fluorescence complementation assays showed that LEA7, LEA29, and LEA48 form homodimers while heterodimers were formed between LEA7-LEA29 and LEA42-LEA48 in tobacco leaves. Interestingly, LEA48 homodimers and LEA42-LEA48 heterodimers formed droplets structures with liquid-like behavior. These structures, along with LEA9 cytoplasmic condensates, may have been formed through liquid-liquid phase separation. These findings suggest possible important roles of LLPS for LEA protein functions.
The ANXA2/S100A10 Complex—Regulation of the Oncogenic Plasminogen Receptor
Authors: Bharadwaj Alamelu G. , Kempster Emma , Waisman David M.
Published: November 2021

The generation of the serine protease plasmin is initiated by the binding of its zymogenic precursor, plasminogen, to cell surface receptors. The proteolytic activity of plasmin, generated at the cell surface, plays a crucial role in several physiological processes, including fibrinolysis, angiogenesis, wound healing, and the invasion of cells through both the basement membrane and extracellular matrix. The seminal observation by Albert Fischer that cancer cells, but not normal cells in culture, produce large amounts of plasmin formed the basis of current-day observations that plasmin generation can be hijacked by cancer cells to allow tumor development, progression, and metastasis. Thus, the cell surface plasminogen-binding receptor proteins are critical to generating plasmin proteolytic activity at the cell surface. This review focuses on one of the twelve well-described plasminogen receptors, S100A10, which, when in complex with its regulatory partner, annexin A2 (ANXA2), forms the ANXA2/S100A10 heterotetrameric complex referred to as AIIt. We present the theme that AIIt is the quintessential cellular plasminogen receptor since it regulates the formation and the destruction of plasmin. We also introduce the term oncogenic plasminogen receptor to define those plasminogen receptors directly activated during cancer progression. We then discuss the research establishing AIIt as an oncogenic plasminogen receptor-regulated during EMT and activated by oncogenes such as SRC, RAS, HIF1α, and PML-RAR and epigenetically by DNA methylation. We further discuss the evidence derived from animal models supporting the role of S100A10 in tumor progression and oncogenesis. Lastly, we describe the potential of S100A10 as a biomarker for cancer diagnosis and prognosis.
Microglial Potassium Channels: From Homeostasis to Neurodegeneration
Authors: Cocozza Germana , Garofalo Stefano , Capitani Riccardo , D’Alessandro Giuseppina , Limatola Cristina
Published: November 2021

The growing interest in the role of microglia in the progression of many neurodegenerative diseases is developing in an ever-expedited manner, in part thanks to emergent new tools for studying the morphological and functional features of the CNS. The discovery of specific biomarkers of the microglia phenotype could find application in a wide range of human diseases, and creates opportunities for the discovery and development of tailored therapeutic interventions. Among these, recent studies highlight the pivotal role of the potassium channels in regulating microglial functions in physiological and pathological conditions such as Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis. In this review, we summarize the current knowledge of the involvement of the microglial potassium channels in several neurodegenerative diseases and their role as modulators of microglial homeostasis and dysfunction in CNS disorders.
Therapeutic Approaches in Lysosomal Storage Diseases
Authors: Fernández-Pereira Carlos , San Millán-Tejado Beatriz , Gallardo-Gómez María , Pérez-Márquez Tania , Alves-Villar Marta , Melcón-Crespo Cristina , Fernández-Martín Julián , Ortolano Saida
Published: November 2021

Lysosomal Storage Diseases are multisystemic disorders determined by genetic variants, which affect the proteins involved in lysosomal function and cellular metabolism. Different therapeutic approaches, which are based on the physiologic mechanisms that regulate lysosomal function, have been proposed for these diseases. Currently, enzyme replacement therapy, gene therapy, or small molecules have been approved or are under clinical development to treat lysosomal storage disorders. The present article reviews the main therapeutic strategies that have been proposed so far, highlighting possible limitations and future perspectives.
The Potential of Traditional Norwegian KVEIK Yeast for Brewing Novel Beer on the Example of Foreign Extra Stout
Authors: Kawa-Rygielska Joanna , Adamenko Kinga , Pietrzak Witold , Paszkot Justyna , Głowacki Adam , Gasiński Alan , Leszczyński Przemysław
Published: November 2021

The development of craft brewing has spurred huge interest in unusual and traditional technologies and ingredients allowing the production of beers that would fulfil consumers’ growing demands. In this study, we evaluated the brewing performance of traditional Norwegian KVEIK yeast during the production of Foreign Extra Stout beer. The content of alcohol of the KVEIK-fermented beer was 5.11–5.58% v/v, the extract content was 5.05–6.66% w/w, and the pH value was 4.53–4.83. The KVEIK yeast was able to completely consume maltose and maltotriose. The mean concentration of glycerol in KVEIK-fermented beers was higher than in the control sample (1.51 g/L vs. 1.12 g/L, respectively). The use of KVEIK-type yeast can offer a viable method for increasing the concentration of phenolic compounds in beer and for boosting its antioxidative potential. The beers produced with KVEIK-type yeast had a total phenol content of 446.9–598.7 mg GAE/L, exhibited antioxidative potential of 0.63–1.08 mM TE/L in the DPPH• assay and 3.85–5.16 mM TE/L in the ABTS•+ assay, and showed a ferric ion reducing capacity (FRAP) of 3.54–4.14 mM TE/L. The KVEIK-fermented bears contained various levels of volatile compounds (lower or higher depending on the yeast strain) and especially of higher alcohols, such as 3-metylobutanol, 2-metylobutanol, and 1-propanol, or ethyl esters, such as ethyl acetate or decanoate, compared to the control beers. In addition, they featured a richer fruity aroma (apricot, dried fruit, apples) than the control beers fermented with a commercial US-05 strain.
The Imbalance of Mitochondrial Fusion/Fission Drives High-Glucose-Induced Vascular Injury
Authors: Zheng Yunsi , Luo Anqi , Liu Xiaoquan
Published: November 2021

Emerging evidence shows that mitochondria fusion/fission imbalance is related to the occurrence of hyperglycemia-induced vascular injury. To study the temporal dynamics of mitochondrial fusion and fission, we observed the alteration of mitochondrial fusion/fission proteins in a set of different high-glucose exposure durations, especially in the early stage of hyperglycemia. The in vitro results show that persistent cellular apoptosis and endothelial dysfunction can be induced rapidly within 12 hours’ high-glucose pre-incubation. Our results show that mitochondria maintain normal morphology and function within 4 hours’ high-glucose pre-incubation; with the extended high-glucose exposure, there is a transition to progressive fragmentation; once severe mitochondria fusion/fission imbalance occurs, persistent cellular apoptosis will develop. In vitro and in vivo results consistently suggest that mitochondrial fusion/fission homeostasis alterations trigger high-glucose-induced vascular injury. As the guardian of mitochondria, AMPK is suppressed in response to hyperglycemia, resulting in imbalanced mitochondrial fusion/fission, which can be reversed by AMPK stimulation. Our results suggest that mitochondrial fusion/fission’s staged homeostasis may be a predictive factor of diabetic cardiovascular complications.
Cellular Senescence: Mechanisms and Therapeutic Potential
Authors: Liao Zehuan , Yeo Han Lin , Wong Siaw Wen , Zhao Yan
Published: November 2021

Cellular senescence is a complex and multistep biological process which cells can undergo in response to different stresses. Referring to a highly stable cell cycle arrest, cellular senescence can influence a multitude of biological processes—both physiologically and pathologically. While phenotypically diverse, characteristics of senescence include the expression of the senescence-associated secretory phenotype, cell cycle arrest factors, senescence-associated β-galactosidase, morphogenesis, and chromatin remodelling. Persistent senescence is associated with pathologies such as aging, while transient senescence is associated with beneficial programmes, such as limb patterning. With these implications, senescence-based translational studies, namely senotherapy and pro-senescence therapy, are well underway to find the cure to complicated diseases such as cancer and atherosclerosis. Being a subject of major interest only in the recent decades, much remains to be studied, such as regarding the identification of unique biomarkers of senescent cells. This review attempts to provide a comprehensive understanding of the diverse literature on senescence, and discuss the knowledge we have on senescence thus far.
Using Deep Convolutional Neural Networks for Enhanced Ultrasonographic Image Diagnosis of Differentiated Thyroid Cancer
Authors: Chan Wai-Kin , Sun Jui-Hung , Liou Miaw-Jene , Li Yan-Rong , Chou Wei-Yu , Liu Feng-Hsuan , Chen Szu-Tah , Peng Syu-Jyun
Published: November 2021

Differentiated thyroid cancer (DTC) from follicular epithelial cells is the most common form of thyroid cancer. Beyond the common papillary thyroid carcinoma (PTC), there are a number of rare but difficult-to-diagnose pathological classifications, such as follicular thyroid carcinoma (FTC). We employed deep convolutional neural networks (CNNs) to facilitate the clinical diagnosis of differentiated thyroid cancers. An image dataset with thyroid ultrasound images of 421 DTCs and 391 benign patients was collected. Three CNNs (InceptionV3, ResNet101, and VGG19) were retrained and tested after undergoing transfer learning to classify malignant and benign thyroid tumors. The enrolled cases were classified as PTC, FTC, follicular variant of PTC (FVPTC), Hürthle cell carcinoma (HCC), or benign. The accuracy of the CNNs was as follows: InceptionV3 (76.5%), ResNet101 (77.6%), and VGG19 (76.1%). The sensitivity was as follows: InceptionV3 (83.7%), ResNet101 (72.5%), and VGG19 (66.2%). The specificity was as follows: InceptionV3 (83.7%), ResNet101 (81.4%), and VGG19 (76.9%). The area under the curve was as follows: Incep-tionV3 (0.82), ResNet101 (0.83), and VGG19 (0.83). A comparison between performance of physicians and CNNs was assessed and showed significantly better outcomes in the latter. Our results demonstrate that retrained deep CNNs can enhance diagnostic accuracy in most DTCs, including follicular cancers.
Natural Compounds as Target Biomolecules in Cellular Adhesion and Migration: From Biomolecular Stimulation to Label-Free Discovery and Bioactivity-Based Isolation
Authors: Péter Beatrix , Boldizsár Imre , Kovács Gábor M. , Erdei Anna , Bajtay Zsuzsa , Vörös Alexandra , Ramsden Jeremy J. , Szabó Ildikó , Bősze Szilvia , Horvath Robert
Published: November 2021

Plants and fungi can be used for medical applications because of their accumulation of special bioactive metabolites. These substances might be beneficial to human health, exerting also anti-inflammatory and anticancer (antiproliferative) effects. We propose that they are mediated by influencing cellular adhesion and migration via various signaling pathways and by directly inactivating key cell adhesion surface receptor sites. The evidence for this proposition is reviewed (by summarizing the natural metabolites and their effects influencing cellular adhesion and migration), along with the classical measuring techniques used to gain such evidence. We systematize existing knowledge concerning the mechanisms of how natural metabolites affect adhesion and movement, and their role in gene expression as well. We conclude by highlighting the possibilities to screen natural compounds faster and more easily by applying new label-free methods, which also enable a far greater degree of quantification than the conventional methods used hitherto. We have systematically classified recent studies regarding the effects of natural compounds on cellular adhesion and movement, characterizing the active substances according to their organismal origin (plants, animals or fungi). Finally, we also summarize the results of recent studies and experiments on SARS-CoV-2 treatments by natural extracts affecting mainly the adhesion and entry of the virus.
Generation of a Novel High-Affinity Antibody Binding to PCSK9 Catalytic Domain with Slow Dissociation Rate by CDR-Grafting, Alanine Scanning and Saturated Site-Directed Mutagenesis for Favorably Treating Hypercholesterolemia
Authors: Bai Zhengli , Xu Menglong , Mei Ying , Hu Tuo , Zhang Panpan , Chen Manman , Lv Wenxiu , Lu Chenchen , Tan Shuhua
Published: November 2021

Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has become an attractive therapeutic strategy for lowering low-density lipoprotein cholesterol (LDL-C). In this study, a novel high affinity humanized IgG1 mAb (named h5E12-L230G) targeting the catalytic domain of human PCSK9 (hPCSK9) was generated by using CDR-grafting, alanine-scanning mutagenesis, and saturated site-directed mutagenesis. The heavy-chain constant region of h5E12-L230G was modified to eliminate the cytotoxic effector functions and mitigate the heterogeneity. The biolayer interferometry (BLI) binding assay and molecular docking study revealed that h5E12-L230G binds to the catalytic domain of hPCSK9 with nanomolar affinity (KD = 1.72 nM) and an extremely slow dissociation rate (koff, 4.84 × 10−5 s−1), which interprets its quite low binding energy (−54.97 kcal/mol) with hPCSK9. Additionally, h5E12-L230G elevated the levels of LDLR and enhanced the LDL-C uptake in HepG2 cells, as well as reducing the serum LDL-C and total cholesterol (TC) levels in hyperlipidemic mouse model with high potency comparable to the positive control alirocumab. Our data indicate that h5E12-L230G is a high-affinity anti-PCSK9 antibody candidate with an extremely slow dissociation rate for favorably treating hypercholesterolemia and relevant cardiovascular diseases.
MoS2 QDs/8-Armed Poly(Ethylene Glycol) Fluorescence Sensor for Three Nitrotoluenes (TNT) Detection
Authors: Zhang Xiaoyuan , Su Zhiqiang
Published: November 2021

In this work, ammonia cross-linked 8-armed polyethylene glycol hydrogel material was successfully synthesized and used as a template for synthesizing nanoparticles with fluorescent properties. The 8-armed polyethylene glycol hydrogel template was used to prepare molybdenum disulfide quantum dots (MoS2 QDs). The ammonium tetrathiomolybdate functioned as a molybdenum source and hydrazine hydrate functioned as a reducing agent. The fluorescence properties of the as-prepared MoS2 QDs were investigated. The bursting of fluorescence caused by adding different concentrations of explosive TNT was studied. The study indicated that the synthesized MoS2 QDs can be used for trace TNT detection with a detection limit of 6 nmol/L and a detection range of 16–700 nmol/L. Furthermore, it indicated that the fluorescence-bursting mechanism is static bursting.
MoS2 Nanodonuts for High-Sensitivity Surface-Enhanced Raman Spectroscopy
Authors: Ghopry Samar Ali , Sadeghi Seyed M. , Berrie Cindy L. , Wu Judy Z.
Published: November 2021

Nanohybrids of graphene and two-dimensional (2D) layered transition metal dichalcogenides (TMD) nanostructures can provide a promising substrate for extraordinary surface-enhanced Raman spectroscopy (SERS) due to the combined electromagnetic enhancement on TMD nanostructures via localized surface plasmonic resonance (LSPR) and chemical enhancement on graphene. In these nanohybrid SERS substrates, the LSPR on TMD nanostructures is affected by the TMD morphology. Herein, we report the first successful growth of MoS2 nanodonuts (N-donuts) on graphene using a vapor transport process on graphene. Using Rhodamine 6G (R6G) as a probe, SERS spectra were compared on MoS2 N-donuts/graphene nanohybrids substrates. A remarkably high R6G SERS sensitivity up to 2 × 10−12 M has been obtained, which can be attributed to the more robust LSPR effect than in other TMD nanostructures such as nanodiscs as suggested by the finite-difference time-domain simulation. This result demonstrates that non-metallic TMD/graphene nanohybrids substrates can have SERS sensitivity up to one order of magnitude higher than that reported on the plasmonic metal nanostructures/2D materials SERS substrates, providing a promising scheme for high-sensitivity, low-cost applications for biosensing.
Current Challenges and Future Trends of Enzymatic Paper-Based Point-of-Care Testing for Diabetes Mellitus Type 2
Authors: Ortiz-Martínez Margarita , Flores-DelaToba Raquel , González-González Mirna , Rito-Palomares Marco
Published: November 2021

A point-of-care (POC) can be defined as an in vitro diagnostic test that can provide results within minutes. It has gained enormous attention as a promising tool for biomarkers detection and diagnosis, as well as for screening of chronic noncommunicable diseases such as diabetes mellitus. Diabetes mellitus type 2 is one of the metabolic disorders that has grown exponentially in recent years, becoming one of the greatest challenges to health systems. Early detection and accurate diagnosis of this disorder are essential to provide adequate treatments. However, efforts to reduce incidence should remain not only in these stages but in developing continuous monitoring strategies. Diabetes-monitoring tools must be accessible and affordable; thus, POC platforms are attractive, especially paper-based ones. Paper-based POCs are simple and portable, can use different matrixes, do not require highly trained staff, and are less expensive than other platforms. These advantages enhance the viability of its application in low-income countries and hard-to-reach zones. This review aims to present a critical summary of the main components required to create a sensitive and affordable enzymatic paper-based POC, as well as an oriented analysis to highlight the main limitations and challenges of current POC devices for diabetes type 2 monitoring and future research opportunities in the field.
Quantitative, Temperature-Calibrated and Real-Time Glucose Biosensor Based on Symmetrical-Meandering-Type Resistor and Intertwined Capacitor Structure
Authors: Ma Yangchuan , Qiang Tian , Gao Minjia , Liang Junge , Jiang Yanfeng
Published: November 2021

Here, we propose a glucose biosensor with the advantages of quantification, excellent linearity, temperature-calibration function, and real-time detection based on a resistor and capacitor, in which the resistor works as a temperature sensor and the capacitor works as a biosensor. The resistor has a symmetrical meandering type structure that increases the contact area, leading to variations in resistance and effective temperature monitoring of a glucose solution. The capacitor is designed with an intertwined structure that fully contacts the glucose solution, so that capacitance is sensitively varied, and high sensitivity monitoring can be realized. Moreover, a polydimethylsiloxane microfluidic channel is applied to achieve a fixed shape, a fixed point, and quantitative measurements, which can eliminate influences caused by fluidity, shape, and thickness of the glucose sample. The glucose solution in a temperature range of 25–100 °C is measured with variations of 0.2716 Ω/°C and a linearity response of 0.9993, ensuring that the capacitor sensor can have reference temperature information before detecting the glucose concentration, achieving the purpose of temperature calibration. The proposed capacitor-based biosensor demonstrates sensitivities of 0.413 nF/mg·dL−1, 0.048 nF/mg·dL−1, and 0.011 pF/mg·dL−1; linearity responses of 0.96039, 0.91547, and 0.97835; and response times less than 1 second, respectively, at DC, 1 kHz, and 1 MHz for a glucose solution with a concentration range of 25–1000 mg/dL.
Gene–Toxicant Interactions in Gulf War Illness: Differential Effects of the PON1 Genotype
Authors: Vahey Jacqueline , Gifford Elizabeth J. , Sims Kellie J. , Chesnut Blair , Boyle Stephen H. , Stafford Crystal , Upchurch Julie , Stone Annjanette , Pyarajan Saiju , Efird Jimmy T. , Williams Christina D. , Hauser Elizabeth R.
Published: November 2021

About 25–35% of United States veterans who fought in the 1990–1991 Gulf War report several moderate or severe chronic systemic symptoms, defined as Gulf War illness (GWI). Thirty years later, there is little consensus on the causes or biological underpinnings of GWI. The Gulf War Era Cohort and Biorepository (GWECB) was designed to investigate genetic and environmental associations with GWI and consists of 1343 veterans. We investigate candidate gene–toxicant interactions that may be associated with GWI based on prior associations found in human and animal model studies, focusing on SNPs in or near ACHE, BCHE, and PON1 genes to replicate results from prior studies. SOD1 was also considered as a candidate gene. CDC Severe GWI, the primary outcome, was observed in 26% of the 810 deployed veterans included in this study. The interaction between the candidate SNP rs662 and pyridostigmine bromide (PB) pills was found to be associated with CDC Severe GWI. Interactions between PB pill exposure and rs3917545, rs3917550, and rs2299255, all in high linkage disequilibrium in PON1, were also associated with respiratory symptoms. These SNPs could point toward biological pathways through which GWI may develop, which could lead to biomarkers to detect GWI or to better treatment options for veterans with GWI.
Transient Complete Resolution of Tourette Syndrome Symptoms Following Personalized Depth Electrode Placement
Authors: MacLean Jennifer A. , Ferman Diana , Chu Jason K. , Liker Mark A. , Sanger Terence D.
Published: November 2021

Treatment refractory Tourette syndrome has been shown to be improved with deep brain stimulation, but with multiple possible stimulation locations and variable and incomplete benefit. This study presents a single case of complete amelioration of motor and verbal tics in a patient with Tourette syndrome during placement of 12 stereo-EEG electrodes to identify optimal targets for permanent stimulating electrodes. Subsequently, substantial improvement in motor and verbal tic frequency occurred with placement and programming of permanent electrodes in bilateral globus pallidus internus and nucleus accumbens, but without the complete resolution seen during depth electrode placement. We suggest that simultaneous stimulation at multiple patient-specific targets could provide effective control of Tourette symptomatology, but further study will be needed.
Cognitive and Behavioral Patterns across Psychiatric Conditions
Authors: Admon Roee , Klavir Oded
Published: November 2021

Psychiatric conditions represent a highly heterogeneous group of disorders associated with chronic distress and a sharp decline in quality of life [...]
Modulation of Hippocampal Astroglial Activity by Synaptamide in Rats with Neuropathic Pain
Authors: Manzhulo Igor , Manzhulo Olga , Tyrtyshnaia Anna , Ponomarenko Arina , Konovalova Sophia , Ermolenko Ekaterina , Milkina Elena , Starinets Anna
Published: November 2021

The present study demonstrates that synaptamide (N-docosahexaenoylethanolamine), an endogenous metabolite of docosahexaenoic acid, when administered subcutaneously (4 mg/kg/day, 14 days), exhibits analgesic activity and promotes cognitive recovery in the rat sciatic nerve chronic constriction injury (CCI) model. We analyzed the dynamics of GFAP-positive astroglia and S100β-positive astroglia activity, the expression of nerve growth factor (NGF), and two subunits of the NMDA receptor (NMDAR1 and NMDAR2A) in the hippocampi of the experimental animals. Hippocampal neurogenesis was evaluated by immunohistochemical detection of DCX. Analysis of N-acylethanolamines in plasma and in the brain was performed using the liquid chromatography-mass spectrometry technique. In vitro and in vivo experiments show that synaptamide (1) reduces cold allodynia, (2) improves working memory and locomotor activity, (3) stabilizes neurogenesis and astroglial activity, (4) enhances the expression of NGF and NMDAR1, (5) increases the concentration of Ca2+ in astrocytes, and (6) increases the production of N-acylethanolamines. The results of the present study demonstrate that synaptamide affects the activity of hippocampal astroglia, resulting in faster recovery after CCI.
The Role of the Human Brain Neuron–Glia–Synapse Composition in Forming Resting-State Functional Connectivity Networks
Authors: Kahali Sayan , Raichle Marcus E. , Yablonskiy Dmitriy A.
Published: November 2021

While significant progress has been achieved in studying resting-state functional networks in a healthy human brain and in a wide range of clinical conditions, many questions related to their relationship to the brain’s cellular constituents remain. Here, we use quantitative Gradient-Recalled Echo (qGRE) MRI for mapping the human brain cellular composition and BOLD (blood–oxygen level-dependent) MRI to explore how the brain cellular constituents relate to resting-state functional networks. Results show that the BOLD signal-defined synchrony of connections between cellular circuits in network-defined individual functional units is mainly associated with the regional neuronal density, while the between-functional units’ connectivity strength is also influenced by the glia and synaptic components of brain tissue cellular constituents. These mechanisms lead to a rather broad distribution of resting-state functional network properties. Visual networks with the highest neuronal density (but lowest density of glial cells and synapses) exhibit the strongest coherence of the BOLD signal as well as the strongest intra-network connectivity. The Default Mode Network (DMN) is positioned near the opposite part of the spectrum with relatively low coherence of the BOLD signal but with a remarkably balanced cellular contents, enabling DMN to have a prominent role in the overall organization of the brain and hierarchy of functional networks.