bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Purification Treatment Relieves the Damage of Hyperlipidemia to PBMCs
Authors: Zhang Xiao Meng , Gu Yan Hong , Deng Hao , Xu Zheng Quan , Zhong Ze Yuan , Lyu Xia Jie , Jin Hui Min , Yang Xiu Hong
Published: July 2021

Background: Hyperlipidemia {hypercholesterolemia [cholesterol >5.18 mmol/L) or hypertriglyceridemia [triglycerides >2.3 mmol/L], mixed hyperlipidemia [cholesterol >5.18 mmol/L and triglycerides >2.3 mmol/L], and high low-density lipoproteinemia [low-density lipoprotein (LDL) >3.4 mmol/L]} is a strong risk factor for arteriosclerosis and cardiovascular disease (CVD). Therapy with lipid-lowering drugs often results in many side effects. Our study aimed to investigate the potential effects of non-drug therapy with double-filtration plasmapheresis (DFPP) on lipid metabolism-, endoplasmic reticulum (ER) stress-, and apoptosis-related proteins in peripheral blood mononuclear cells (PBMCs) before and after lipid clearance in patients with hyperlipidemia.

Methods: Thirty-five hyperlipidemia patients were selected. Proteins related to lipid metabolism [CD36, proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL receptor], ER stress [glucose-regulated protein 78 (Grp78), C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), and eukaryotic initiation factor 2α (EIF2α)], and apoptosis [B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (BAX), and cysteinyl aspartate specific proteinase-3 (Caspase-3)] were assayed by Western blot, reactive oxygen species (ROS) were measured by flow cytometry (FCM), and ELISA detected serum inflammatory [interleukin (IL)-1β, IL-6, and tumor necrosis factor α (TNF-α)] factors.

Results: Compared with their pre-DFPP values, the values of most lipid metabolic parameters, such as cholesterol, triglycerides, LDL, lipoprotein a [Lp(a)], and small dense LDL (sdLDL) cholesterol, were reduced after DFPP. DFPP was associated with the downregulation of proteins related to lipid metabolism, ER stress, and apoptosis, resulting in decreased ROS and serum inflammatory factor release.

Conclusion: DFPP has lipid-lowering activity and can also regulate lipid metabolism-, ER stress-, and apoptosis-related proteins in PBMCs and reduce the levels of inflammatory factors in patients with hyperlipidemia (ClinicalTrials.gov number: NCT03491956).
The β2-Subunit of Voltage-Gated Calcium Channels Regulates Cardiomyocyte Hypertrophy
Authors: Pickel Simone , Cruz-Garcia Yiliam , Bandleon Sandra , Barkovits Katalin , Heindl Cornelia , Völker Katharina , Abeßer Marco , Pfeiffer Kathy , Schaaf Alice , Marcus Katrin , Eder-Negrin Petra , Kuhn Michaela , Miranda-Laferte Erick
Published: July 2021

L-type voltage-gated calcium channels (LTCCs) regulate crucial physiological processes in the heart. They are composed of the Cavα1 pore-forming subunit and the accessory subunits Cavβ, Cavα2δ, and Cavγ. Cavβ is a cytosolic protein that regulates channel trafficking and activity, but it also exerts other LTCC-independent functions. Cardiac hypertrophy, a relevant risk factor for the development of congestive heart failure, depends on the activation of calcium-dependent pro-hypertrophic signaling cascades. Here, by using shRNA-mediated Cavβ silencing, we demonstrate that Cavβ2 downregulation enhances α1-adrenergic receptor agonist-induced cardiomyocyte hypertrophy. We report that a pool of Cavβ2 is targeted to the nucleus in cardiomyocytes and that the expression of this nuclear fraction decreases during in vitro and in vivo induction of cardiac hypertrophy. Moreover, the overexpression of nucleus-targeted Cavβ2 in cardiomyocytes inhibits in vitro-induced hypertrophy. Quantitative proteomic analyses showed that Cavβ2 knockdown leads to changes in the expression of diverse myocyte proteins, including reduction of calpastatin, an endogenous inhibitor of the calcium-dependent protease calpain. Accordingly, Cavβ2-downregulated cardiomyocytes had a 2-fold increase in calpain activity as compared to control cells. Furthermore, inhibition of calpain activity in Cavβ2-downregulated cells abolished the enhanced α1-adrenergic receptor agonist-induced hypertrophy observed in these cells. Our findings indicate that in cardiomyocytes, a nuclear pool of Cavβ2 participates in cellular functions that are independent of LTCC activity. They also indicate that a downregulation of nuclear Cavβ2 during cardiomyocyte hypertrophy promotes the activation of calpain-dependent hypertrophic pathways.
Effect of Dosage Reduction of Hypoglycemic Multidrug Regimens on the Incidences of Acute Glycemic Complications in People With Type 2 Diabetes Who Fast During Ramaḍān: A Randomized Controlled Trial
Authors: Zaghlol Louay Y. , Beirat Amir F. , Amarin Justin Z. , Hassoun Al Najar Amro M. , Hasan Yazan Y. , Qtaishat Abdallah , Tierney Michael E. , Zaghlol Raja Y. , Zayed Ayman A.
Published: July 2021

Objective

We aimed to investigate the effect of dosage reduction of four hypoglycemic multidrug regimens on the incidences of acute glycemic complications in people with type 2 diabetes who fast during Ramaḍān.

Methods

We conducted an open-label, parallel-group, randomized controlled trial at a tertiary care center in Amman, Jordan. We recruited adults with type 2 diabetes who expressed an intention to fast during Ramaḍān and were adherent to one of four regimens—namely: metformin and glimepiride; metformin and vildagliptin; metformin and insulin glargine U100; or, metformin, insulin glargine U100, and human regular insulin. We randomly assigned participants in a 2:1 ratio to low- or regular-dosage therapy. The primary outcomes were the incidences of hypoglycemia and hyperglycemia during the 29 days of Ramaḍān 2017, and the secondary outcomes were the incidences of diabetic ketoacidosis and hyperosmolar hyperglycemic state during the same period.

Results

We randomly assigned 687 participants to low-dosage therapy (n = 458) or regular-dosage therapy (n = 229) and included 678 (452 and 226, respectively) in the final analysis. The incidence of hypoglycemia was lower in the low-dosage group compared with the regular-dosage group (19 [4.2%] vs. 52 [23.0%], respectively; OR, 0.15 [95% CI, 0.08–0.26]; P < 0.001). The incidence of hyperglycemia did not differ between the low- and regular-dosage groups (319 [70.6%] vs. 154 [68.1%], respectively; OR, 1.12 [95% CI, 0.79–1.58]; P = 0.5). No participants experienced diabetic ketoacidosis or hyperosmolar hyperglycemic state. Each 1% decrease in the baseline HbA1c concentration was associated with a 19.9-fold (95% CI, 9.6–41.5; P < 0.001) increase in the odds of hypoglycemia, and each 1% increase in the baseline HbA1c concentration was associated with a 15.7-fold (95% CI, 10.0–24.6; P < 0.001) increase in the odds of hyperglycemia.

Conclusion

Dosage reduction decreases the incidence of hypoglycemia without a concomitant increase in the incidences of hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic state in people with type 2 diabetes who fast during Ramaḍān.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier NCT04237493.
Cannabinoid Receptor 1 Inhibition in Chronic Kidney Disease: A New Therapeutic Toolbox
Authors: Dao Myriam , François Helene
Published: July 2021

Chronic kidney disease (CKD) concerns millions of individuals worldwide, with few therapeutic strategies available to date. Recent evidence suggests that the endocannabinoid system (ECS) could be a new therapeutic target to prevent CKD. ECS combines receptors, cannabinoid receptor type 1 (CB1R) and type 2 (CB2R), and ligands. The most prominent receptor within the kidney is CB1R, its endogenous local ligands being anandamide and 2-arachidonoylglycerol. Therefore, the present review focuses on the therapeutic potential of CB1R and not CB2R. In the normal kidney, CB1R is expressed in many cell types, especially in the vasculature where it contributes to the regulation of renal hemodynamics. CB1R could also participate to water and sodium balance and to blood pressure regulation but its precise role remains to decipher. CB1R promotes renal fibrosis in both metabolic and non-metabolic nephropathies. In metabolic syndrome, obesity and diabetes, CB1R inhibition not only improves metabolic parameters, but also exerts a direct role in preventing renal fibrosis. In non-metabolic nephropathies, its inhibition reduces the development of renal fibrosis. There is a growing interest of the industry to develop new CB1R antagonists without central nervous side-effects. Experimental data on renal fibrosis are encouraging and some molecules are currently under early-stage clinical phases (phases I and IIa studies). In the present review, we will first describe the role of the endocannabinoid receptors, especially CB1R, in renal physiology. We will next explore the role of endocannabinoid receptors in both metabolic and non-metabolic CKD and renal fibrosis. Finally, we will discuss the therapeutic potential of CB1R inhibition using the new pharmacological approaches. Overall, the new pharmacological blockers of CB1R could provide an additional therapeutic toolbox in the management of CKD and renal fibrosis from both metabolic and non-metabolic origin.
The Combination of Lime and Plant Species Effects on Trace Metals (Copper and Cadmium) in Soil Exchangeable Fractions and Runoff in the Red Soil Region of China
Authors: Xu Lei , Xing Xiangyu , Cui Hongbiao , Zhou Jing , Zhou Jun , Peng Jianbiao , Bai Jingfeng , Zheng Xuebo , Ji Mingfei
Published: July 2021

The water-soluble heavy metal ions in contaminated soil may enter aquatic ecosystem through runoff, thus causing negative impact on the water environment. In this study, a two-year in situ experiment was carried out to explore an effective way to reduce the runoff erosion and water-soluble copper (Cu) and cadmium (Cd) in a contaminated soil (Cu: 1,148 mg kg−1, Cd: 1.31 mg kg−1) near a large Cu smelter. We evaluated the ability to influence soil properties by four Cu-tolerance plant species (Pennisetum sp., Elsholtzia splendens, Vetiveria zizanioides, Setaria pumila) grown in a contaminated acidic soil amended with lime. The results show that the addition of lime can significantly reduce the exchangeable fraction (EXC) of Cu and Cd in soil (81.1–85.6% and 46.3–55.9%, respectively). Plant species cannot change the fraction distributions of Cu and Cd in the lime-amended soils, but they can reduce the runoff generation by 8.39–77.0%. Although water-soluble Cu concentrations in the runoff were not significantly differed and water-soluble Cd cannot be detected among the four plant species, the combined remediation can significantly reduce 35.9–63.4% of Cu erosion to aquatic ecosystem, following the order: Pennisetum sp. > Elsholtzia splendens > Vetiveria zizanioides > Setaria pumila. The implication of this study would provide valuable insights for contaminated soil management and risk reduction in the Cu and Cd contaminated regions.
Impact of the “Low-Carbon City Pilot” Policy on Energy Intensity Based on the Empirical Evidence of Chinese Cities
Authors: Hong Min , Chen Shuanglian , Zhang Kexian
Published: July 2021

Reducing energy intensity is conducive to the sustainable use of non-renewable fossil energy, and is also one of the main strategies to deal with climate change and environmental degradation. The effect of national macro-level factors on energy intensity has been basically confirmed, but the effect of regional low-carbon policy remains to be investigated. Based on this, our analysis exploits China’s “low-carbon city pilot” policy as a quasi-natural experiment and conducts the difference-in-difference resign. We collect the panel data of 271 cities in China from 2006 to 2016. The empirical results show that: first, the low-carbon city pilot policy can effectively reduce the energy intensity. Second, there exist heterogeneous effects on energy intensity among different cities, and the inhibition effects in eastern cities, high economic development cites, and non-old industrial-base cities are more significant. Third, the policy mainly affects regional energy intensity through technological innovation rather than industrial structure optimization mechanism.
Effects of Climate Change vs. Grazing Exclusion on Species Diversity Over 18 Years Along an Elevation Gradient in the European Alps
Authors: Kaufmann Rüdiger , Mayer Roland , Schallhart Nikolaus , Erschbamer Brigitta
Published: July 2021

Climate change was already shown to increase species numbers in high elevations. In contrast, grazing might interfere with climate change effects. To disentangle both the effects remains a major challenge of alpine ecology. The present study investigated both the effects on species diversity along an elevation gradient in the Austrian Central Alps. We aimed to answer the following questions: How do species diversity and frequency of subalpine–alpine–subnival plant communities change in grazed sites with time? Do competitive plant species increase in the communities? How does grazing exclusion affect species diversity, functional groups, and strategy types? Are environmental changes (temperature, sunshine duration, precipitation) responsible for diversity changes or does grazing override climate effects? The study was carried out for 18 years along an elevation gradient from 1,958 to 2,778 m a.s.l. at Obergurgl (Tyrol, Austria), including six different plant communities. A total of 11 grazing exclusions were established. At each community, the frequency of the species was counted in 1 m2 plots yearly or at least every 3–4 years. Environmental data were obtained from the weather station Obergurgl. Changes of the community parameters and the species composition were analyzed by partial redundancy analyses and mixed-effect models. Species diversity increased with time at all grazed sites, but this increase was suppressed under grazing exclusion. Grazing exclusion effects became pronounced after 5 years. The most consistent result was the increase of bryophytes throughout. At the subalpine grassland, tall-growing species expanded in the exclosures; at the upper alpine Carex curvula grassland, snow bed species decreased with grazing exclusion. Among the environmental factors, sunshine duration of the previous year’s autumn quartal was found to be the essential variable for the changes. We concluded that diversity increases in grazed communities of the Austrian Central Alps can be attributed to climate change. An indication of slightly reduced and altered weather effects under grazing exclusion was found.
Characterization and Phylogenetic Analysis of a Novel GH43 β-Xylosidase From Neocallimastix californiae
Authors: Stabel Marcus , Hagemeister Julia , Heck Zacharias , Aliyu Habibu , Ochsenreither Katrin
Published: July 2021

Degradation of lignocellulosic materials to release fermentable mono- and disaccharides is a decisive step toward a sustainable bio-based economy, thereby increasing the demand of robust and highly active lignocellulolytic enzymes. Anaerobic fungi of the phylum Neocallimastigomycota are potent biomass degraders harboring a huge variety of such enzymes. Compared to cellulose, hemicellulose degradation has received much less attention; therefore, the focus of this study has been the enzymatic xylan degradation of anaerobic fungi as these organisms produce some of the most effective known hydrolytic enzymes. We report the heterologous expression of a GH43 xylosidase, Xyl43Nc, and a GH11 endoxylanase, X11Nc, from the anaerobic fungus Neocallimastix californiae in Escherichia coli. The enzymes were identified by screening of the putative proteome. Xyl43Nc was highly active against 4-Nitrophenol-xylopyranosides with a Km of 0.72 mM, a kcat of 29.28 s−1, a temperature optimum of 32°C and a pH optimum of 6. When combined, Xyl43Nc and X11Nc released xylose from beechwood xylan and arabinoxylan from wheat. Phylogenetic analysis revealed that Xyl43Nc shares common ancestry with enzymes from Spirochaetes and groups separately from Ascomycete sequences in our phylogeny, highlighting the importance of horizontal gene transfer in the evolution of the anaerobic fungi.
A Web Screening on Educational Initiatives to Increase Citizens’ Literacy on Genomics and Genetics
Authors: Sassano Michele , Calabrò Giovanna Elisa , Boccia Stefania
Published: July 2021

Introduction

Population awareness and empowerment in omics sciences represent a fundamental driver to increase the adoption of evidence-based approaches in personalized medicine. In this context, a pivotal role is played by citizens’ literacy, and educational initiatives carried out in this context are key assets to drive future effective interventions. With the present study, we summarized the educational initiatives conducted worldwide aimed at increasing citizens’ literacy in omics sciences.

Materials and Methods

We conducted a web search of the educational initiatives aimed at improving citizens’ literacy in omics sciences undertaken worldwide, by using three search engines (Google, Bing, and Yahoo Search), in English and in Italian languages.

Results

We identified five initiatives in Europe, 22 in non-European countries, and 13 in Italy. Overall, the majority (69%) were web-based initiatives, while 31% required in-person attendance. The online initiatives included web pages for reading, online lessons/courses, web portals, videos/short movies, animations, and apps for mobile devices. The residential initiatives, on the other hand, included exhibitions, seminars, courses, symposia, information stands in public places, guided visits to research laboratories, and interactive laboratories. All the initiatives were highly heterogeneous in terms of methodologies and the topics addressed.

Discussion and Conclusion

Overall, we identified a variety of initiatives aimed at improving citizens’ literacy in omics sciences, with the largest majority carried out in the United States and being web-based. Our results showed heterogeneity among the initiatives as to the dealt topics and the adopted methods. Further research is needed, however, to quantitatively assess the effectiveness of educational initiatives to improve citizens’ literacy in omics sciences.
The Expression Profiles of mRNAs and lncRNAs in Buffalo Muscle Stem Cells Driving Myogenic Differentiation
Authors: Zhang Ruimen , Wang Jinling , Xiao Zhengzhong , Zou Chaoxia , An Qiang , Li Hui , Zhou Xiaoqing , Wu Zhuyue , Shi Deshun , Deng Yanfei , Yang Sufang , Wei Yingming
Published: July 2021

Buffalo breeding has become an important branch of the beef cattle industry. Hence, it is of great significance to study buffalo meat production and meat quality. However, the expression profiles of mRNA and long non-coding RNAs (lncRNA) molecules in muscle stem cells (MuSCs) development in buffalo have not been explored fully. We, therefore, performed mRNA and lncRNA expression profiling analysis during the proliferation and differentiation phases of MuSCs in buffalo. The results showed that there were 4,820 differentially expressed genes as well as 12,227 mRNAs and 1,352 lncRNAs. These genes were shown to be enriched in essential biological processes such as cell cycle, p53 signaling pathway, RNA transport and calcium signaling pathway. We also identified a number of functionally important genes, such as MCMC4, SERDINE1, ISLR, LOC102394806, and LOC102403551, and found that interference with MYLPF expression significantly inhibited the differentiation of MuSCs. In conclusion, our research revealed the characteristics of mRNA and lncRNA expression during the differentiation of buffalo MuSCs. This study can be used as an important reference for the study of RNA regulation during muscle development in buffalo.
ROS/RNS Balancing, Aerobic Fermentation Regulation and Cell Cycle Control – a Complex Early Trait (‘CoV-MAC-TED’) for Combating SARS-CoV-2-Induced Cell Reprogramming
Authors: Costa José Hélio , Mohanapriya Gunasekaran , Bharadwaj Revuru , Noceda Carlos , Thiers Karine Leitão Lima , Aziz Shahid , Srivastava Shivani , Oliveira Manuela , Gupta Kapuganti Jagadis , Kumari Aprajita , Sircar Debabrata , Kumar Sarma Rajeev , Achra Arvind , Sathishkumar Ramalingam , Adholeya Alok , Arnholdt-Schmitt Birgit
Published: July 2021

In a perspective entitled ‘From plant survival under severe stress to anti-viral human defense’ we raised and justified the hypothesis that transcript level profiles of justified target genes established from in vitro somatic embryogenesis (SE) induction in plants as a reference compared to virus-induced profiles can identify differential virus signatures that link to harmful reprogramming. A standard profile of selected genes named ‘ReprogVirus’ was proposed for in vitro-scanning of early virus-induced reprogramming in critical primary infected cells/tissues as target trait. For data collection, the ‘ReprogVirus platform’ was initiated. This initiative aims to identify in a common effort across scientific boundaries critical virus footprints from diverse virus origins and variants as a basis for anti-viral strategy design. This approach is open for validation and extension. In the present study, we initiated validation by experimental transcriptome data available in public domain combined with advancing plant wet lab research. We compared plant-adapted transcriptomes according to ‘RegroVirus’ complemented by alternative oxidase (AOX) genes during de novo programming under SE-inducing conditions with in vitro corona virus-induced transcriptome profiles. This approach enabled identifying a major complex trait for early de novo programming during SARS-CoV-2 infection, called ‘CoV-MAC-TED’. It consists of unbalanced ROS/RNS levels, which are connected to increased aerobic fermentation that links to alpha-tubulin-based cell restructuration and progression of cell cycle. We conclude that anti-viral/anti-SARS-CoV-2 strategies need to rigorously target ‘CoV-MAC-TED’ in primary infected nose and mouth cells through prophylactic and very early therapeutic strategies. We also discuss potential strategies in the view of the beneficial role of AOX for resilient behavior in plants. Furthermore, following the general observation that ROS/RNS equilibration/redox homeostasis is of utmost importance at the very beginning of viral infection, we highlight that ‘de-stressing’ disease and social handling should be seen as essential part of anti-viral/anti-SARS-CoV-2 strategies.
The Effect of Immunosuppressive Adjuvant Kynurenine on Type 1 Diabetes Vaccine
Authors: Sun Jing , Shi Jiandong , Li Jianfang , Wu Meini , Li Yanhan , Jia Sengquan , Ma Chunli , Wang Xinyi , Li Zhiyuan , Hu Ningzhu , Hu Yunzhang
Published: July 2021

Inducing antigen-specific tolerance is a promising treatment for preventing or reversing Type 1 diabetes (T1D). In contrast to a vaccine that induces immune responses against pathogens, a tolerogenic vaccine can suppress immunity against antigens causing diseases by administrating a mixture of self-antigens with an adjuvant that decreases the strength of antigen-specific response. Kynurenine (Kyn) is an endogenous substance that can inhibit the natural killer cell and T cell proliferation and promote the differentiation of naïve T cells into regulatory T cells (Tregs). In this study, we evaluated the efficacy of Kyn as a novel suppressive adjuvant. Kyn was co-immunized with GAD65 phage vaccine to induce Tregcells and tolerogenic responses for the prevention of T1D in NOD mouse model. Mice were subcutaneously immunized two times with 1011Pfu (100μL,1012Pfu/ml) GAD65 phage vaccine doses mixed with 200 μg of Kyn. Serum antibodies and cytokines were detected by ELISA and electrochemiluminescence, respectively. Flow cytometry assay was used to analyze DC and Treg. MTS was used for the analysis of spleen lymphocyte proliferation. RNA sequencing was used to investigate mRNA and miRNA expression profiles in spleen lymphocytes. Compared to GAD65 phage vaccine alone, co-immunization of Kyn and GAD65 phage vaccine resulted in the prevention of hyperglycemia in 60% of mice for at least one month. Further, Kyn enhances GAD65-specific Th2-mediated immune responses; regulates the Th1/Th2 imbalance and increases the secretion of Th2 cytokines and the number of CD4+CD25+Foxp3+T cells; suppresses DC maturation and GAD65-specific T lymphocyte proliferation. Moreover, we integrated Kyn related miRNA and mRNA expression profiles obtained from the spleen lymphocyte RNA-sequencing which was stimulated by Kynin vitro. These data provide an important basis for understanding the mechanisms underlying Kyn as an immunosuppressive adjuvant which regulated the immune response. These findings suggest that Kyn can serve as an effective suppressive adjuvant candidate for Type 1 diabetes vaccines.
Germinal Centre Shutdown
Authors: Arulraj Theinmozhi , Binder Sebastian C. , Robert Philippe A. , Meyer-Hermann Michael
Published: July 2021

Germinal Centres (GCs) are transient structures in secondary lymphoid organs, where affinity maturation of B cells takes place following an infection. While GCs are responsible for protective antibody responses, dysregulated GC reactions are associated with autoimmune disease and B cell lymphoma. Typically, ‘normal’ GCs persist for a limited period of time and eventually undergo shutdown. In this review, we focus on an important but unanswered question – what causes the natural termination of the GC reaction? In murine experiments, lack of antigen, absence or constitutive T cell help leads to premature termination of the GC reaction. Consequently, our present understanding is limited to the idea that GCs are terminated due to a decrease in antigen access or changes in the nature of T cell help. However, there is no direct evidence on which biological signals are primarily responsible for natural termination of GCs and a mechanistic understanding is clearly lacking. We discuss the present understanding of the GC shutdown, from factors impacting GC dynamics to changes in cellular interactions/dynamics during the GC lifetime. We also address potential missing links and remaining questions in GC biology, to facilitate further studies to promote a better understanding of GC shutdown in infection and immune dysregulation.
Toward Improved Model Capacities for Assessment of Climate Impacts on Coastal Bentho-Pelagic Food Webs and Ecosystem Services
Authors: Horn Sabine , Meunier Cédric L. , Fofonova Vera , Wiltshire Karen H. , Sarker Subrata , Pogoda Bernadette , Asmus Harald
Published: July 2021

Global climate change is a key driver of change in coastal waters with clear effects on biological communities and marine ecosystems. Human activities in combination with climate change exert a tremendous pressure on marine ecosystems and threaten their integrity, structure, and functioning. The protection of these ecosystems is a major target of the 14th United Nations sustainable development goal “Conserve and sustainably use the oceans, seas and marine resources for sustainable development.” However, due to the complexity of processes and interactions of stressors, the status assessment of ecosystems remains a challenge. Holistic food web models, including biological and environmental data, could provide a suitable basis to assess ecosystem health. Here, we review climate change impacts on different trophic levels of coastal ecosystems ranging from plankton to ecologically and economically important fish and shellfish species. Furthermore, we show different food web model approaches, their advantages and limitations. To effectively manage coastal ecosystems, we need both a detailed knowledge base of each trophic level and a holistic modeling approach for assessment and prediction of future scenarios on food web-scales. A new model approach with a seamless coupling of physical ocean models and food web models could provide a future tool for guiding ecosystem-based management.
Ranking 67 Florida Reefs for Survival of Acropora cervicornis Outplants
Authors: Banister Raymond B. , van Woesik Robert
Published: July 2021

Over the past three decades, coral populations have declined across the tropical and subtropical oceans because of thermal stress, coral diseases, and pollution. Restoration programs are currently attempting to re-establish depauperate coral populations along the Florida reef tract. We took an integrated Bayesian approach to determine which Florida reefs ranked highest based on the survival of outplanted colonies ofAcropora cervicornisfrom 2012 to 2018. Survival ofA. cervicornisoutplants was highly variable in the upper Florida Keys with some reefs showing the highest likelihood of survival (e.g., North Dry Rocks, Carysfort, Key Largo Dry Rocks, and Conch Reef), whereas some adjacent reefs showed the lowest likelihood of survival (e.g., an Unnamed Reef, Pickles Reef, and U47 Patch Reef). Similarly, survival was highly variable in the middle and lower Florida Keys and in the Broward-Miami subregions. Survival was high and less variable in Biscayne Bay and low and less variable in the Marquesas subregions. The reefs that ranked lowest for outplant survival were exposed to high wave energy. Partitioning out the spatial effects of reefs and subregions from the model, we detected spatial latent effects of low survival that were most evident in the middle and the upper Florida Keys, particularly between 2015 and 2017. The overall high spatial and temporal variability in survival among adjacent reefs highlights a need to outplant nursery-reared colonies strategically, in order to optimize coral-population recovery efforts in Florida.
Practical Method to Screen Contaminated Holograms of Flocs Using Light Intensity
Authors: Choi Sun Min , Seo Jun Young , Lee Guan-hong , Shen Xiaoteng , Ha Ho Kyung
Published: July 2021

Submergible digital holographic camera can measure the in situ size and shape of suspended particles, such as complex flocs and biological organisms, without disturbance. As the number of particles in the water column increases, overlapping concentric rings (interference patterns) can contaminate the holographic images. Using light intensity (LI), this study proposes a practical method to assess the degree of contamination and screen out contaminated images. The outcomes from image processing support that LI normalized on a gray scale of 0 (black) to 255 (white) can be a reliable criterion for defining the contamination boundary. Results found that as LI increased, the shape of the particle size distribution shifted from a positively skewed to a normal distribution. When LI was lower than approximately 80, owing to the distortion of particle properties, the settling velocities derived from the contaminated holograms with mosaic patterns were underestimated compared to those from the uncontaminated holograms. The proposed method can contribute to a more accurate estimation of the transport and behavior of cohesive sediments in shallow estuarine environments.
Nanoparticle-Assisted Diagnosis and Treatment for Abdominal Aortic Aneurysm
Authors: Yin Li , Zhang Kaijie , Sun Yuting , Liu Zhenjie
Published: July 2021

An abdominal aortic aneurysm (AAA) is a localized dilatation of the aorta related to the regional weakening of the wall structure, resulting in substantial morbidity and mortality with the aortic ruptures as complications. Ruptured AAA is a dramatic catastrophe, and aortic emergencies constitute one of the leading causes of acute death in older adults. AAA management has been centered on surgical repair of larger aneurysms to mitigate the risks of rupture, and curative early diagnosis and effective pharmacological treatments for this condition are still lacking. Nanoscience provided a possibility of more targeted imaging and drug delivery system. Multifunctional nanoparticles (NPs) may be modified with ligands or biomembranes to target agents' delivery to the lesion site, thus reducing systemic toxicity. Furthermore, NPs can improve drug solubility, circulation time, bioavailability, and efficacy after systemic administration. The varied judiciously engineered nano-biomaterials can exist stably in the blood vessels for a long time without being taken up by cells. Here, in this review, we focused on the NP application in the imaging and treatment of AAA. We hope to make an overview of NP-assisted diagnoses and therapy in AAA and discussed the potential of NP-assisted treatment.
Effect of Immune Cell Infiltration on Occurrence of Pulmonary Hypertension in Pulmonary Fibrosis Patients Based on Gene Expression Profiles
Authors: Zhu Feng , Zuo Lili , Hu Rui , Wang Jin , Yang Zhihua , Qi Xin , Feng Limin
Published: July 2021

Pulmonary hypertension (PH) is a frequent complication in patients with pulmonary fibrosis (PF), whereas the mechanism was not well-understood. This study aimed to explore the influence of immune cell infiltration on PH status based on the genomic expression profiles. Microarray data of GSE24988 were downloaded from the GEO database, including 116 lung tissue samples derived from PF patients with various PH status. Proportion of infiltrated immune cells was evaluated using CIBERSORT, a gene expression-based de-convolution algorithm. A random forest classifier was constructed and out of bag (OOB) cross-validation was carried out for PH prediction. The proportions of immune infiltration cells varied differently in PH samples except T regulatory cells (p-value = 0). Compared with non-PH samples, increased number of naive B cells and plasma cells were identified in PH samples, whereas activated dendritic cells and M2 macrophages were relatively lower (p < 0.05). In the random forest model, these four types of immune cells obtained a higher variable importance score than other cells, including mean decreased accuracy and mean decreased gini evaluation. We ran the OOB cross-validation in each sample of datasets (training set and testing set) and obtained 79 and 69% accuracy, respectively. Abnormal proportions of four types of immune cells were identified in PH samples compared with non-PH samples, suggesting their involvement in PH development. In summary, the immune cell infiltration in PF patients is associated with the PH status of patients, which deserves further investigation in the future.
Vagus Nerve Stimulation Promotes Epithelial Proliferation and Controls Colon Monocyte Infiltration During DSS-Induced Colitis
Authors: Meroni Elisa , Stakenborg Nathalie , Gomez-Pinilla Pedro J. , Stakenborg Michelle , Aguilera-Lizarraga Javier , Florens Morgane , Delfini Marcello , de Simone Veronica , De Hertogh Gert , Goverse Gera , Matteoli Gianluca , Boeckxstaens Guy E.
Published: July 2021

Background: We previously showed increased susceptibility to dextran sulfate sodium (DSS)-induced colitis in vagotomized mice. Here, we evaluated whether vagus nerve stimulation (VNS) is able to reduce the severity of DSS colitis and aimed to unravel the mechanism involved.

Methods: Colitis was induced in wild type mice by 2.5% DSS administration in drinking water for 5 days. VNS (5 Hz, 1 ms, 1 mA) was applied 1 day prior to and after 4 days of DSS administration to evaluate changes in epithelial integrity and inflammatory response, respectively. Epithelial integrity was assessed using TUNEL and Ki67 staining. Monocytes, immature and mature macrophages were sorted from colonic samples and gene expression levels of pro-inflammatory cytokines were studied.

Results: VNS applied prior to DSS administration (i.e., prophylactic VNS) reduced disease activity index (VNS 0.8 ± 0.6 vs. sham 2.8 ± 0.7, p < 0.001, n = 5) and tended to improve histology score. Prophylactic VNS significantly increased epithelial cell proliferation and diminished apoptosis compared to sham stimulation. VNS applied at day 4 during DSS administration (i.e., therapeutic VNS) decreased the influx of monocytes, monocyte-derived macrophages and neutrophils, and significantly reduced pro-inflammatory cytokine expression (i.e., Tnfα and Cxcl1) in immature macrophages compared to sham stimulation.

Conclusions: A single period of VNS applied prior to DSS exposure reduced DSS-induced colitis by an improvement in epithelial integrity. On the other hand, VNS applied during the inflammatory phase of DSS colitis reduced cytokine expression in immature macrophages. Our data further underscores the potential of VNS as novel therapeutic approach for inflammatory bowel diseases.
Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex Modulates Electroencephalographic Functional Connectivity in Alzheimer’s Disease
Authors: Guo Yi , Dang Ge , Hordacre Brenton , Su Xiaolin , Yan Nan , Chen Siyan , Ren Huixia , Shi Xue , Cai Min , Zhang Sirui , Lan Xiaoyong
Published: July 2021

Background: Increasing evidence demonstrates that repetitive transcranial magnetic stimulation (rTMS) treatment of the dorsolateral prefrontal cortex is beneficial for improving cognitive function in patients with Alzheimer’s disease (AD); however, the underlying mechanism of its therapeutic effect remains unclear.

Objectives/Hypothesis: The aim of this study was to investigate the impact of rTMS to the dorsolateral prefrontal cortex on functional connectivity along with treatment response in AD patients with different severity of cognitive impairment.

Methods: We conducted a 2-week treatment course of 10-Hz rTMS over the left dorsolateral prefrontal cortex in 23 patients with AD who were split into the mild or moderate cognitive impairment subgroup. Resting state electroencephalography and general cognition was assessed before and after rTMS. Power envelope connectivity was used to calculate functional connectivity at the source level. The functional connectivity of AD patients and 11 cognitively normal individuals was compared.

Results: Power envelope connectivity was higher in the delta and theta bands but lower in the beta band in the moderate cognitive impairment group, compared to the cognitively normal controls, at baseline (p < 0.05). The mild cognitive impairment group had no significant abnormities. Montreal Cognitive Assessment scores improved after rTMS in the moderate and mild cognitive impairment groups. Power envelope connectivity in the beta band post-rTMS was increased in the moderate group (p < 0.05) but not in the mild group. No significant changes in the delta and theta band were found after rTMS in both the moderate and mild group.

Conclusion: High-frequency rTMS to the dorsolateral prefrontal cortex modulates electroencephalographic functional connectivity while improving cognitive function in patients with AD. Increased beta connectivity may have an important mechanistic role in rTMS therapeutic effects.
Lack of the Transient Receptor Potential Vanilloid 1 Shifts Cannabinoid-Dependent Excitatory Synaptic Plasticity in the Dentate Gyrus of the Mouse Brain Hippocampus
Authors: Egaña-Huguet Jon , Saumell-Esnaola Miquel , Achicallende Svein , Soria-Gomez Edgar , Bonilla-Del Río Itziar , García del Caño Gontzal , Barrondo Sergio , Sallés Joan , Gerrikagoitia Inmaculada , Puente Nagore , Elezgarai Izaskun , Grandes Pedro
Published: July 2021

The transient receptor potential vanilloid 1 (TRPV1) participates in synaptic functions in the brain. In the dentate gyrus, post-synaptic TRPV1 in the granule cell (GC) dendritic spines mediates a type of long-term depression (LTD) of the excitatory medial perforant path (MPP) synapses independent of pre-synaptic cannabinoid CB1 receptors. As CB1 receptors also mediate LTD at these synapses, both CB1 and TRPV1 might be influencing the activity of each other acting from opposite synaptic sites. We tested this hypothesis in the MPP–GC synapses of mice lacking TRPV1 (TRPV1-/-). Unlike wild-type (WT) mice, low-frequency stimulation (10 min at 10 Hz) of TRPV1-/- MPP fibers elicited a form of long-term potentiation (LTP) that was dependent on (1) CB1 receptors, (2) the endocannabinoid 2-arachidonoylglycerol (2-AG), (3) rearrangement of actin filaments, and (4) nitric oxide signaling. These functional changes were associated with an increase in the maximum binding efficacy of guanosine-5′-O-(3-[35S]thiotriphosphate) ([35S]GTPγS) stimulated by the CB1 receptor agonist CP 55,940, and a significant decrease in receptor basal activation in the TRPV1-/- hippocampus. Finally, TRPV1-/- hippocampal synaptosomes showed an augmented level of the guanine nucleotide-binding (G) Gαi1, Gαi2, and Gαi3 protein alpha subunits. Altogether, the lack of TRPV1 modifies CB1 receptor signaling in the dentate gyrus and causes the shift from CB1 receptor-mediated LTD to LTP at the MPP–GC synapses.
Microbial Infections Are a Risk Factor for Neurodegenerative Diseases
Authors: Lotz Sarah K. , Blackhurst Britanie M. , Reagin Katie L. , Funk Kristen E.
Published: July 2021

Neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, comprise a family of disorders characterized by progressive loss of nervous system function. Neuroinflammation is increasingly recognized to be associated with many neurodegenerative diseases but whether it is a cause or consequence of the disease process is unclear. Of growing interest is the role of microbial infections in inciting degenerative neuroinflammatory responses and genetic factors that may regulate those responses. Microbial infections cause inflammation within the central nervous system through activation of brain-resident immune cells and infiltration of peripheral immune cells. These responses are necessary to protect the brain from lethal infections but may also induce neuropathological changes that lead to neurodegeneration. This review discusses the molecular and cellular mechanisms through which microbial infections may increase susceptibility to neurodegenerative diseases. Elucidating these mechanisms is critical for developing targeted therapeutic approaches that prevent the onset and slow the progression of neurodegenerative diseases.
Caregiving for Patients With Frontotemporal Dementia in Latin America
Authors: Piña-Escudero Stefanie Danielle , Aguirre Gloria Annette , Javandel Shireen , Longoria-Ibarrola Erika Mariana
Published: July 2021

Latin America is a vast heterogeneous territory where chronic diseases such as mild cognitive impairment or dementia are becoming higher. Frontotemporal dementia (FTD) prevalence in this region is estimated to be around 12–18 cases per thousand persons. However, this prevalence is underestimated given the lack of awareness of FTD even among healthcare professionals. Family members are responsible for the care of patients with FTD at home. These caregivers deliver care despite being ill-equipped and living in the context of austerity policies and social inequities. They often face unsurmountable financial and social burdens that are specific to the region. The most important step to support caregivers in Latin America is to increase awareness of the disease at all levels. Healthcare diplomacy is fundamental to create joint efforts that push policies forward to protect caregivers of FTD patients.
Exploring the Interaction Between Handedness and Body Parts Ownership by Means of the Implicit Association Test
Authors: Crivelli Damiano , Peviani Valeria , Salvato Gerardo , Bottini Gabriella
Published: July 2021

The experience of owning a body is built upon the integration of exteroceptive, interoceptive, and proprioceptive signals. Recently, it has been suggested that motor signals could be particularly important in producing the feeling of body part ownership. One thus may hypothesize that the strength of this feeling may not be spatially uniform; rather, it could vary as a function of the degree by which different body parts are involved in motor behavior. Given that our dominant hand plays a leading role in our motor behavior, we hypothesized that it could be more strongly associated with one’s self compared to its non-dominant counterpart. To explore whether this possible asymmetry manifests as a stronger implicit association of the right hand (vs left hand) with the self, we administered the Implicit Association Test to a group of 70 healthy individuals. To control whether this asymmetric association is human-body specific, we further tested whether a similar asymmetry characterizes the association between a right (vs left) animal body part with the concept of self, in an independent sample of subjects (N= 70, 140 subjects total). Our results revealed a linear relationship between the magnitude of the implicit association between the right hand with the self and the subject’s handedness. In detail, the strength of this association increased as a function of hand preference. Critically, the handedness score did not predict the association of the right-animal body part with the self. These findings suggest that, in healthy individuals, the dominant and non-dominant hands are differently perceived at an implicit level as belonging to the self. We argue that such asymmetry may stem from the different roles that the two hands play in our adaptive motor behavior.
Rhythmic Neural Patterns During Empathy to Vicarious Pain: Beyond the Affective-Cognitive Empathy Dichotomy
Authors: Zebarjadi Niloufar , Adler Eliyahu , Kluge Annika , Jääskeläinen Iiro P. , Sams Mikko , Levy Jonathan
Published: July 2021

Empathy is often split into an affective facet for embodied simulation or sometimes sensorial processing, and a cognitive facet for mentalizing and perspective-taking. However, a recent neurophenomenological framework proposes a graded view on empathy (i.e., “Graded Empathy”) that extends this dichotomy and considers multiple levels while integrating complex neural patterns and representations of subjective experience. In the current magnetoencephalography study, we conducted a multidimensional investigation of neural oscillatory modulations and their cortical sources in 44 subjects while observing stimuli that convey vicarious pain (vs no-pain) in a broad time window and frequency range to explore rich neural representations of pain empathy. Furthermore, we collected participants’ subjective-experience of sensitivity to vicarious pain, as well as their self-reported trait levels of affective and cognitive empathy to examine the possible associations between neural mechanisms and subjective experiences and reports. While extending previous electrophysiological studies that mainly focused on alpha suppression, we found here four significant power modulation patterns corresponding to multiple facets of empathy: an early central (peaking in the paracentral sulcus) alpha (6–11 Hz) suppression pattern plausibly reflecting sensory processing, two early beta (15–23 Hz) suppression patterns in the mid-cingulate cortex (plausibly reflecting the affective component) and in the precuneus (plausibly reflecting the cognitive component), and a late anterior (peaking in the orbitofrontal cortex) alpha-beta (11–19 Hz) enhancement pattern (plausibly reflecting cognitive-control inhibitory response). Interestingly, the latter measure was negatively correlated with the subjective sensitivity to vicarious pain, thereby possibly revealing a novel inhibitory neural mechanism determining the subjective sensitivity to vicarious pain. Altogether, these multilevel findings cannot be accommodated by the dichotomous model of empathy (i.e., affective-cognitive), and provide empirical support to theGraded Empathyneurophenomenological framework. Furthermore, this work emphasizes the importance of examining multiple neural rhythms, their cortical generators, and reports of subjective-experience in the aim of elucidating the complex nature of empathy.