bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex streamflow responses to climate warming in five river basins in South Yakutia, Russia
Authors: Wang Ping , Shpakova Raisa N.
Published: October 2022

The climate is warming much faster than the global average at the northern mid–high latitudes, leading to intensified hydrological cycles. However, it is unclear whether the response of streamflow to climate change is uniform across river basins with areas of 104–105 km2. In this study, monthly streamflow data from five river basins (Bol’shoy Patom, Chara, Olekma, Timpton, and Uchur) and gridded monthly temperature and precipitation data from the Russian South Yakutia at 53.5–61.5°N were analysed to investigate changes in their annual streamflow from 1934 to 2019 and their responses to climate warming. The results showed significant increasing trends in air temperature for all five basins at rates of 0.20°C–0.22°C/decade (p < 0.001), with faster warming after the 1980s. Apart from the Uchur River Basin, increasing trends in annual precipitation were observed in the other four river basins at rates of 9.3–15.7 mm/decade (p < 0.01). However, temporal changes in streamflow were much more complex than those in air temperature and precipitation among the five basins. Only two of the five basins showed significant increasing trends in annual streamflow with change rates of 17.1 mm/decade (p < 0.001) for the Chara River and 7.7 mm/decade (p < 0.05) for the Olekma River. Although the other three basins showed slightly increasing trends in annual streamflow (1.8–4.0 mm/decade), these trends did not pass significance tests (p > 0.05). By analysing the temperature-precipitation-streamflow relationships, we determined that the annual streamflow positively responds to precipitation, while winter streamflow is most sensitive to temperature. With climate warming, the streamflow during the winter period (October-April) increased significantly in four of the five river basins at rates of 1.4–3.1 mm/decade (p < 0.001), suggesting that warming-induced permafrost thawing increases baseflow. Although the streamflow response of large Siberian rivers to climate change is consistent, our results suggest that the streamflow response to climate change in relatively small river basins (104–105 km2) is much more complex.
Temporal dynamics in zooplankton δ13C and δ15N isoscapes for the North Atlantic Ocean: Decadal cycles, seasonality, and implications for predator ecology
Authors: Espinasse Boris , Sturbois Anthony , Basedow Sünnje L. , Hélaouët Pierre , Johns David G. , Newton Jason , Trueman Clive N.
Published: October 2022

The limited amount of ecological data covering offshore parts of the ocean impedes our ability to understand and anticipate the impact of anthropogenic stressors on pelagic marine ecosystems. Isoscapes, i.e., spatial models of the distribution of stable isotope ratios, have been employed in the recent years to investigate spatio-temporal patterns in biogeochemical process and ecological responses. Development of isoscapes on the scale of ocean basins is hampered by access to suitable reference samples. Here we draw on archived material from long-running plankton survey initiatives, to build temporally explicit isoscape models for the North Atlantic Ocean (> 40°N). A total of 570 zooplankton samples were retrieved from Continuous Plankton Recorder archives and analysed for δ13C and δ15N values. Bayesian generalised additive models were developed to (1) model the relations between isotopic values and a set of predictors and (2) predict isotopic values for the whole of the study area. We produced yearly and seasonal isoscape models for the period 1998–2020. These are the first observation-based time-resolved C and N isoscapes developed at the scale of the North Atlantic Ocean. Drawing on the Stable Isotope Trajectory Analysis framework, we identify five isotopically distinct regions. We discuss the hydro-biogeochemical processes that likely explain theses modes, the differences in temporal dynamics (stability and cycles) and compare our results with previous bioregionalization efforts. Finally, we lay down the basis for using the isoscapes as a tool to define predator distributions and their interactions with the trophic environment. The isoscapes developed in this study have the potential to update our knowledge of marine predator ecology and therefore our capacity to improve their conservation in the future.
A novel lipid metabolism-related lncRNA signature predictive of clinical prognosis in cervical cancer
Authors: Lu Yanzhen , He Xiujun , Fang Xia , Chai Ningxia , Xu Fangfang
Published: October 2022

Background: Cervical cancer (CC) is a serious threat to women populations worldwide. Lipid metabolism is believed to have modulating functions in cancer. Long non-coding RNAs (lncRNAs) are potential biomarkers for the different tumor prognosis. Our work aims at investigating the prognostic value of lipid metabolism-related lncRNAs in CC.

Methods: LncRNA expression profiling was conducted in 291 patients from The Cancer Genome Atlas (TCGA). Patient samples were randomly assigned to the training or testing set in a 3:2 ratio. A novel lipid metabolism-related five-lncRNA signature with prognostic value for CC was built through the univariate Cox regression, least absolute contraction and selection operator (LASSO) regression and multivariate Cox regression analyses, and was further evaluated by the Kaplan-Meier methods. Relevant analyses were also applied to identify the independent clinicopathological factors. GO and KEGG analyses were conducted to investigate the biological functions and molecular pathways. Immune infiltration analysis was included to probe the relationship between lncRNA signature and cancer cell microenvironment.

Results: The novel lipid metabolism-related five-lncRNA signature was confirmed to be predictive of overall survival (OS) in CC patients. Risk score, cancer stage, pregnancy, and BMI were validated as independent factors with prognostic value. GO and KEGG indicated that lipid metabolism participated in several tumor associated functions and pathways. Moreover, our results suggested that the five-lncRNA expression has potential link with tumor immune microenvironment.

Conclusion: In conclusion, we built an innovative prognostic risk signature based upon lipid metabolism-related lncRNAs. The five-lncRNA signature may be beneficial to provide novel potential therapeutic targets and improve personalized treatment strategies for CC patients in future clinical treatments.
Identification of potential regulatory long non-coding RNA-associated competing endogenous RNA axes in periplaque regions in multiple sclerosis
Authors: Sabaie Hani , Khorami Rouz Sharareh , Kouchakali Ghazal , Heydarzadeh Samaneh , Asadi Mohammad Reza , Sharifi-Bonab Mirmohsen , Hussen Bashdar Mahmud , Taheri Mohammad , Ayatollahi Seyed Abdulmajid , Rezazadeh Maryam
Published: October 2022

Slow-burning inflammation at the lesion rim is connected to the expansion of chronic multiple sclerosis (MS) lesions. However, the underlying processes causing expansion are not clearly realized. In this context, the current study used a bioinformatics approach to identify the expression profiles and related lncRNA-associated ceRNA regulatory axes in the periplaque region in MS patients. Expression data (GSE52139) from periplaque regions in the secondary progressive MS spinal cord and controls were downloaded from the Gene Expression Omnibus database (GEO), which has details on mRNAs and lncRNAs. Using the R software’s limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also found using the DIANA-LncBase, miRTarBase, and HMDD databases. The Pearson correlation coefficient was used to determine whether there were any positive correlations between DEmRNAs and DElncRNAs in the ceRNA network. Finally, lncRNA-associated ceRNA axes were created based on co-expression and connections between DElncRNA, miRNA, and DEmRNA. We used the Enrichr tool to enrich the biological process, molecular function, and pathways for DEmRNAs and DElncRNAs. A network of DEmRNAs’ protein-protein interactions was developed, and the top five hub genes were found using Cytoscape and STRING. The current study indicates that 15 DEmRNAs, including FOS, GJA1, NTRK2, CTNND1, and SP3, are connected to the MS ceRNA network. Additionally, four DElncRNAs (such as TUG1, ASB16-AS1, and LINC01094) that regulated the aforementioned mRNAs by sponging 14 MS-related miRNAs (e.g., hsa-miR-145-5p, hsa-miR-200a-3p, hsa-miR-20a-5p, hsa-miR-22-3p, hsa-miR-23a-3p, hsa-miR-27a-3p, hsa-miR-29b-3p, hsa-miR-29c-3p, hsa-miR-34a-5p) were found. In addition, the analysis of pathway enrichment revealed that DEmRNAs were enriched in the pathways for the “MAPK signaling pathway”, “Kaposi sarcoma-associated herpesvirus infection”, “Human immunodeficiency virus one infection”, “Lipid and atherosclerosis”, and “Amphetamine addiction”. Even though the function of these ceRNA axes needs to be investigated further, this study provides research targets for studying ceRNA-mediated molecular mechanisms related to periplaque demyelination in MS.
CNNArginineMe: A CNN structure for training models for predicting arginine methylation sites based on the One-Hot encoding of peptide sequence
Authors: Zhao Jiaojiao , Jiang Haoqiang , Zou Guoyang , Lin Qian , Wang Qiang , Liu Jia , Ma Leina
Published: October 2022

Protein arginine methylation (PRme), as one post-translational modification, plays a critical role in numerous cellular processes and regulates critical cellular functions. Though several in silico models for predicting PRme sites have been reported, new models may be required to develop due to the significant increase of identified PRme sites. In this study, we constructed multiple machine-learning and deep-learning models. The deep-learning model CNN combined with the One-Hot coding showed the best performance, dubbed CNNArginineMe. CNNArginineMe performed best in AUC scoring metrics in comparisons with several reported predictors. Additionally, we employed CNNArginineMe to predict arginine methylation proteome and performed functional analysis. The arginine methylated proteome is significantly enriched in the amyotrophic lateral sclerosis (ALS) pathway. CNNArginineMe is freely available at https://github.com/guoyangzou/CNNArginineMe.
Identification of genes modified by N6-methyladenosine in patients with colorectal cancer recurrence
Authors: Zhu Qianru , Huang Xingxing , Yu Shuxian , Shou Lan , Zhang Ruonan , Xie Han , Liang Zimao , Sun Xueni , Feng Jiao , Duan Ting , Zhang Mingming , Xiang Yu , Sui Xinbing , Jin Weiwei , Yu Lili , Wu Qibiao
Published: October 2022

Background: Recent studies demonstrate that N6-methyladenosine (m6A) methylation plays a crucial role in colorectal cancer (CRC). Therefore, we conducted a comprehensive analysis to assess the m6A modification patterns and identify m6A-modified genes in patients with CRC recurrence.

Methods: The m6A modification patterns were comprehensively evaluated by the NMF algorithm based on the levels of 27 m6A regulators, and tumor microenvironment (TME) cell-infiltrating characteristics of these modification patterns were systematically assessed by ssGSEA and CIBERSORT algorithms. The principal component analysis algorithm based on the m6A scoring scheme was used to explore the m6A modification patterns of individual tumors with immune responses. The weighted correlation network analysis and univariable and multivariable Cox regression analyses were applied to identify m6A-modified gene signatures. The single-cell expression dataset of CRC samples was used to explore the tumor microenvironment affected by these signatures.

Results: Three distinct m6A modification patterns with significant recurrence-free survival (RFS) were identified in 804 CRC patients. The TME characterization revealed that the m6A modification pattern with longer RFS exhibited robust immune responses. CRC patients were divided into high- and low-score subgroups according to the m6A score individually, which was obtained from the m6A-related signature genes. The patients with low m6A scores had both longer RFS and overall survival (OS) with altered immune cell infiltration. Notably, m6A-modified genes showed significant differences related to the prognosis of CRC patients in the meta-GEO cohort and TCGA cohort. Single-cell expression indicated that ALVRL1 was centrally distributed in endothelial tip cells and stromal cells.

Conclusion: The m6A modification plays an indispensable role in the formation of TME diversity and complexity. Importantly, the signatures (TOP2A, LRRC58, HAUS6, SMC4, ACVRL1, and KPNB1) were identified as m6A-modified genes associated with CRC recurrence, thereby serving as a promising predictive biomarker or therapeutic target for patients with CRC recurrence.
The paternal genetic legacy of Hungarian-speaking Rétköz (Hungary) and Váh valley (Slovakia) populations
Authors: Pamjav Horolma , Fóthi Ábel , Dudás Dániel , Tapasztó Attila , Krizsik Virág , Fóthi Erzsébet
Published: October 2022

One hundred and six Rétköz and 48 Váh valley samples were collected from the contact zones of Hungarian-Slovakian territories and were genotyped for Y-chromosomal haplotypes and haplogroups. The results were compared with contemporary and archaic data from published sources. The genetic composition of the Rétköz population from Hungary and the Váh valley population from Slovakia indicates different histories. In the Rétköz population, the paternal lineages that were also found in the Hungarian Conquerors, such as R1a-Z93, N-M46, Q-M242, and R1b-L23, were better preserved. These haplogroups occurred in 10% of the population. The population of the Váh valley, however, is characterized by the complete absence of these haplogroups. Our study did not detect a genetic link between the Váh valley population and the Hungarian Conquerors; the genetic composition of the Váh valley population is similar to that of the surrounding Indo-European populations. The Hungarian Rétköz males shared common haplotypes with ancient Xiongnu, ancient Avar, Caucasian Avar, Abkhazian, Balkarian, and Circassian males within haplogroups R1a-Z93, N1c-M46, and R1b-L23, indicating a common genetic footprint. Another difference between the two studied Hungarian populations can be concluded from the Fst-based MDS plot. The Váh valley, in the western part of the Hungarian-Slovakian contact zone, is genetically closer to the Western Europeans. In contrast, Rétköz is in the eastern part of that zone and therefore closer to the Eastern Europeans.
Galectin-9 protects humanized-ACE2 immunocompetent mice from SARS-CoV-2 infection
Authors: Yeung Stephen T. , Premeaux Thomas A. , Du Li , Niki Toshiro , Pillai Satish K. , Khanna Kamal M. , Ndhlovu Lishomwa C.
Published: October 2022

SARS-CoV-2 remains a global health crisis even with effective vaccines and the availability of FDA approved therapies. Efforts to understand the complex disease pathology and develop effective strategies to limit mortality and morbidity are needed. Recent studies reveal circulating Galectin-9 (gal-9), a soluble beta-galactoside binding lectin with immunoregulatory properties, are elevated in SARS-CoV-2 infected individuals with moderate to severe disease. Moreover, in silico studies demonstrate gal-9 can potentially competitively bind the ACE2 receptor on susceptible host cells. Here, we determined whether early introduction of exogenous gal-9 following SARS-CoV-2 infection in humanized ACE2 transgenic mice (K18-hACE2) may reduce disease severity. Mice were infected and treated with a single dose of a human recombinant form of gal-9 (rh-gal-9) and monitored for morbidity. Subgroups of mice were humanely euthanized at 2- and 5- days post infection (dpi) for viral levels by plaque assay, immune changes measures by flow cytometry, and soluble mediators by protein analysis from lung tissue and bronchoalveolar Lavage fluid (BALF). Mice treated with rh-gal-9 during acute infection had improved survival compared to PBS treated controls. At 5 dpi, rh-gal-9 treated mice had enhanced viral clearance in the BALF, but not in the lung parenchyma. Increased T and dendritic cells and decreased neutrophil frequencies in the lung at 5 dpi were observed, whereas BALF had elevated levels of type-I interferons and proinflammatory cytokines. These results suggest a role for rh-gal-9 in limiting acute COVID-19. Further studies are required to determine the optimal design of gal-9 treatment to effectively ameliorate COVID-19 disease.
HLA-C dysregulation as a possible mechanism of immune evasion in SARS-CoV-2 and other RNA-virus infections
Authors: Loi Eleonora , Moi Loredana , Cabras Paola , Arduino Giulia , Costanzo Giulia , Del Giacco Stefano , Erlich Henry A. , Firinu Davide , Caddori Aldo , Zavattari Patrizia
Published: October 2022

One of the mechanisms by which viruses can evade the host’s immune system is to modify the host’s DNA methylation pattern. This work aims to investigate the DNA methylation and gene expression profile of COVID-19 patients, divided into symptomatic and asymptomatic, and healthy controls, focusing on genes involved in the immune response. In this study, changes in the methylome of COVID-19 patients’ upper airways cells, the first barrier against respiratory infections and the first cells presenting viral antigens, are shown for the first time. Our results showed alterations in the methylation pattern of genes encoding proteins implicated in the response against pathogens, in particular the HLA-C gene, also important for the T-cell mediated memory response. HLA-C expression significantly decreases in COVID-19 patients, especially in those with a more severe prognosis and without other possibly confounding co-morbidities. Moreover, our bionformatic analysis revealed that the identified methylation alteration overlaps with enhancers regulating HLA-C expression, suggesting an additional mechanism exploited by SARS-CoV-2 to inhibit this fundamental player in the host’s immune response. HLA-C could therefore represent both a prognostic marker and an excellent therapeutic target, also suggesting a preventive intervention that conjugate a virus-specific antigenic stimulation with an adjuvant increasing the T-cell mediated memory response.
Role of epigenetic modification in interferon treatment of hepatitis B virus infection
Authors: Yang Zhijing , Sun Baozhen , Xiang Jingcheng , Wu Han , Kan Shaoning , Hao Ming , Chang Lu , Liu Huimin , Wang Dongxu , Liu Weiwei
Published: October 2022

Human hepatitis B virus (HBV) is a small, enveloped DNA virus that causes acute and chronic hepatitis. Chronic hepatitis B (CHB) is associated with hepatocellular carcinoma pathogenesis. Interferons (IFNs) have been used for the treatment of CHB for a long time, with advantages including less treatment duration and sustained virological response. Presently, various evidence suggests that epigenetic modification of the viral covalently closed circular DNA (cccDNA) and the host genome is crucial for the regulation of viral activity. This modification includes histone acetylation, DNA methylation, N6-methyladenosine, and non-coding RNA modification. IFN treatment for CHB can stimulate multiple IFN-stimulated genes for inhibiting virus replication. IFNs can also affect the HBV life cycle through epigenetic modulation. In this review, we summarized the different mechanisms through which IFN-α inhibits HBV replication, including epigenetic regulation. Moreover, the mechanisms underlying IFN activity are discussed, which indicated its potential as a novel treatment for CHB. It is proposed that epigenetic changes such as histone acetylation, DNA methylation, m6A methylation could be the targets of IFN, which may offer a novel approach to HBV treatment.
Mechanotransduction in skin wound healing and scar formation: Potential therapeutic targets for controlling hypertrophic scarring
Authors: Yin Jiayi , Zhang Shiming , Yang Chao , Wang Yan , Shi Bing , Zheng Qian , Zeng Ni , Huang Hanyao
Published: October 2022

Hypertrophic scarring (HTS) is a major source of morbidity after cutaneous injury. Recent studies indicate that mechanical force significantly impacts wound healing and skin regeneration which opens up a new direction to combat scarring. Hence, a thorough understanding of the underlying mechanisms is essential in the development of efficacious scar therapeutics. This review provides an overview of the current understanding of the mechanotransduction signaling pathways in scar formation and some strategies that offload mechanical forces in the wounded region for scar prevention and treatment.
Anti-SARS-CoV-2 vaccination in people with multiple sclerosis: Lessons learnt a year in
Authors: Pugliatti Maura , Hartung Hans-Peter , Oreja-Guevara Celia , Pozzilli Carlo , Airas Laura , Alkhawajah Mona , Grigoriadis Nikolaos , Magyari Melinda , Van Wijmeersch Bart , Zakaria Magd , Linker Ralf , Chan Andrew , Vermersch Patrick , Berger Thomas
Published: October 2022

It has been over a year since people with multiple sclerosis (pwMS) have been receiving vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a negligible number of cases in which vaccination led to a relapse or new onset MS, experts around the world agree that the potential consequences of COVID-19 in pwMS by far outweigh the risks of vaccination. This article reviews the currently available types of anti-SARS-CoV-2 vaccines and the immune responses they elicit in pwMS treated with different DMTs. Findings to date highlight the importance of vaccine timing in relation to DMT dosing to maximize protection, and of encouraging pwMS to get booster doses when offered.
TCR repertoire profiling revealed antigen-driven CD8+ T cell clonal groups shared in synovial fluid of patients with spondyloarthritis
Authors: Komech Ekaterina A. , Koltakova Anastasia D. , Barinova Anna A. , Minervina Anastasia A. , Salnikova Maria A. , Shmidt Evgeniya I. , Korotaeva Tatiana V. , Loginova Elena Y. , Erdes Shandor F. , Bogdanova Ekaterina A. , Shugay Mikhail , Lukyanov Sergey , Lebedev Yury B. , Zvyagin Ivan V.
Published: October 2022

Spondyloarthritis (SpA) comprises a number of inflammatory rheumatic diseases with overlapping clinical manifestations. Strong association with several HLA-I alleles and T cell infiltration into an inflamed joint suggest involvement of T cells in SpA pathogenesis. In this study, we performed high-throughput T cell repertoire profiling of synovial fluid (SF) and peripheral blood (PB) samples collected from a large cohort of SpA patients. We showed that synovial fluid is enriched with expanded T cell clones that are shared between patients with similar HLA genotypes and persist during recurrent synovitis. Using an algorithm for identification of TCRs involved in immune response we discovered several antigen-driven CD8+ clonal groups associated with risk HLA-B*27 or HLA-B*38 alleles. We further show that these clonal groups were enriched in SF and had higher frequency in PB of SpA patients vs healthy donors, implying their relevance to SpA pathogenesis. Several of the groups were shared among patients with different SpAs that suggests a common immunopathological mechanism of the diseases. In summary, our results provide evidence for the role of specific CD8+ T cell clones in pathogenesis of SpA.
Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironment
Authors: Chen Zihang , Zhu Qiqi , Deng Xueqin , Yao Wenqing , Zhang Wenyan , Liu Weiping , Tang Yuan , Zhao Sha
Published: October 2022

Background

Angioimmunoblastic T-cell lymphoma (AITL) has a rich tumor microenvironment (TME) that typically harbors plenty of CD4+tumor infiltrating lymphocytes, (TIL)-T-cells (so called common AITL). Nonetheless, AITL with large numbers of CD8+TIL-Ts that outnumber CD4+cells have been observed (CD8-predominant AITL). However, detailed comparison of CD8-predominant AITL and common AITL are still lacking.

Methods

We compared clinicopathological features, TIL subsets, TME T cell receptor-β (TRB), and immunoglobulin heavy chain (IGH) repertoires, and gene expression profiles in six CD8-predominant and 12 common AITLs using case-control matching (2014 to 2019).

Results

Comparing with common AITLs, CD8-predominant AITLs showed more frequent edema (P = 0.011), effusion (P = 0.026), high elevated plasma EBV-DNA (P = 0.008), and shorter survival (P = 0.034). Moreover, they had more pronounced eosinophil increase (P = 0.004) and a higher Ki67 index (P = 0.041). Flow cytometry revealed an inverted CD4/CD8 ratio in TIL-Ts and lower TIL-B proportions (P = 0.041). TRB repertoire metrics deteriorated, including lower productive clones (P = 0.014) and higher clonality score (P = 0.019). The IGH repertoire was also narrowed, showing a higher proportion of the top 10 clones (P = 0.002) and lower entropy (P = 0.027). Gene expression analysis showed significant enrichment for upregulated negative regulation of immune system processes and downregulated T-cell activation and immune cell differentiation.

Conclusion

Our findings demonstrated that CD8-predominant AITL is a distinct immune pattern of AITL characterized by anti-tumor immunity impairment and an immunosuppressive microenvironment. These characteristics can interpret its severe clinical manifestations and poor outcomes.
Abscisic acid activates desiccation tolerance responses in intertidal seaweed Neoporphyra haitanensis
Authors: Zhang Caixia , Chen Juanjuan , Yang Rui , Luo Qijun , Wang Tiegan , Zhang Peng , Chen Haimin
Published: October 2022

Intertidal macroalgae have adapted to deal with environmental stresses, in particular desiccation. The phytohormone abscisic acid (ABA) plays an important role in the regulation of a suite of critical responses in plants, including desiccation tolerance. The red alga Neoporphyra haitanensis contains a high level of ABA, but its mechanism of action in N. haitanensis is unknown. In this study, the effect of ABA treatment on the relative water content of thalli during the dehydration-rehydration cycle was evaluated and it was identified that ABA treatment resulted in decreased thalli water loss and an accelerated rehydration process. The effects of addition of ABA upon the activation of antioxidant responses, photosynthetic parameters and gene transcription profiles of N. haitanensis were also evaluated. The results revealed that exogenous ABA regulated the activation of the antioxidant system, including by increasing the activity of antioxidant enzymes, increasing the concentrations of ascorbic acid (AsA) and glutathione (GSH), as well as upregulating the expression of genes encoding antioxidant enzymes and enzymes that synthesize AsA and GSH. ABA treatment also inhibited photosynthesis by reducing light capture and down-regulating the Calvin cycle to save energy; ABA supplementation further simultaneously activated repair mechanisms to avoid excessive DNA and protein damage. The results presented herein demonstrate that ABA plays a crucial role in the regulation of stress tolerance in seaweeds, which may be of great importance when examining the adaptation of this organism to the intertidal environment.
Long-term response of an estuarine ecosystem to drastic nutrients changes in the Changjiang River during the last 59 years: A modeling perspective
Authors: Shi Shenyang , Xu Yi , Li Weiqi , Ge Jianzhong
Published: October 2022

The riverine nutrient inputs to the ocean reflects land-use changes and can affect the health of coastal environments over time, especially for a highly-anthropogenically influenced river-estuary-shelf system. To investigate the impact of riverine inputs on the Changjiang Estuary ecosystem at a multi-decadal time scale where long-term observations are limited, we built a three-dimensional physics-biogeochemistry-coupled model system based on the Finite-Volume Community Ocean Model (FVCOM) and the European Regional Shelf Ecosystem Model (ERSEM). Our model successfully simulated the temporal and spatial nutrient variabilities in the river-estuary-shelf con7tinuum from 1960 to 2018. The results showed increasing trends of nitrate and phosphate and fluctuating silicate variability, thereby leading to rising nitrogen (N) to phosphorus (P) ratios and decreasing silicon (Si) to N and P ratios. Such changes in the stoichiometric relationship of nutrient species also alter the community structure of the primary producers in estuaries. Our model showed a general increase of diatoms over the 59 years, corresponding to decreased proportions of micro-phytoplankton and pico- phytoplankton. With different backgrounds of light and nutrient limitations in the river and inner shelf, our model suggests that the trend of the diatom proportion in the light-limited river mouth is more associated with silicate variability, with decreased diatom proportions occurring in the 2000s. Our model relates the hydroclimate, nutrient load, and biogeochemical cycling, reproducing estuarine ecosystem variability and clarifying issues such as the causality of the ecosystem interactions.
Utilization of riverine organic matter by macrobenthic communities in a temperate prodelta
Authors: Szczepanek Marta , Silberberger Marc J. , Koziorowska-Makuch Katarzyna , Kędra Monika
Published: October 2022

Macrobenthos is an important component of organic carbon storage and energy flow in marine systems, including these impacted by riverine discharge and high share of allochthonous organic matter (OM). Changing environmental conditions, such as lower precipitation and snow cover duration, may affect patterns of riverine input, therefore it is crucial to know how benthic communities utilize different OM sources in areas affected by rivers. Using Bayesian stable isotope mixing models, we assessed the diet composition of common macroinvertebrates forming benthic communities in the transition zone of one of the largest river outlets in the Baltic Sea region, the Vistula River prodelta. Furthermore, we analyzed the spatial and temporal variability in the biomass-weighted resource utilization by those communities. Contribution of riverine OM to the particulate OM in Vistula prodelta decreased with increasing depth. Despite similar distances to the river mouth, the relative contribution of riverine OM to the diet of all studied taxa also decreased with increasing depth, which corresponded to organic matter composition in prodelta waters. Nevertheless, due to synchronous structural changes in benthic communities, and changes in the feeding modes of dominant species, particularly Macoma balthica and Hediste diversicolor, the riverine organic carbon share in the biomass of benthic communities often remained the highest in the deepest prodelta parts. Our study corroborates that benthic primary consumers act as a gateway for riverine organic matter into the marine food web and illustrates that sediment properties and resource partitioning affects spatial structure of benthic communities and their abilities to utilize allochthonous OM.
Role of cross-diagonal reinforcements in lieu of seismic confining stirrups in the performance enhancement of square RC columns carrying axial load subjected to close-range explosive loading
Authors: Anas S. M. , Alam Mehtab , Isleem Haytham F. , Najm Hadee Mohammed , Sabri Sabri Mohanad Muayad
Published: October 2022

Exposure of building infrastructures to accidental or intentional blasts is an extreme load condition that may cause irreparable damage leading to the collapse of buildings. Columns being principal elements are the most important for the stability and safety of the buildings under accidental explosions and subversive blast events and therefore attract the attention of structural engineers and researchers. Some recent examples are the Beirut seaport explosion (August 2020), the explosion at an ammunition warehouse in Ryazan City of Russia (October 2020), the gas explosion in China’s Hubei Province (June 2021), a blast at a chemical factory on the outskirts of Bangkok (July 2021), and the explosion on a container ship docked at Dubai’s Jebel Ali Port (July 2021). In the crises like ongoing conflict between Russia and Ukraine, the enhanced response of the principal components of a structure may save the life of the building users by limiting severe damage to the structure. In this study, three experimentally tested 3000-mm-long normal strength concrete columns, 300mm x 300mm, provided with (i) conventional reinforcement, (ii) seismic reinforcements over top and bottom confining regions (600 mm), and (iii) seismic reinforcement over confining and mid-height regions, carrying an axial working load of 950 kN available in the literature, are modeled in the ABAQUS 2020 code and are subjected to 82 kg TNT close-range explosive load at a scaled distance 1.0 m/kg1/3using the software’s explicit module. In addition to this, one column with seismic reinforcement over its entire length has been considered and modeled. The concrete damage plasticity model is explored for nonlinear elastic and inelastic behaviors, degradation of stiffness, and loading rate effect on concrete. Following the validation of the numerical models, the seismic reinforcements of the columns have been replaced by the cross-diagonal reinforcements between the conventional stirrups with the same axial load. Blast performance of the columns with the seismic reinforcements and with replaced diagonal reinforcements is critically examined and discussed. The results show that the application of cross-diagonal reinforcements as a replacement for the seismic reinforcements enhances the blast resistance of the reinforced concrete column significantly by reducing the damage and displacement.
The role of telepathology in improving cancer diagnostic and research capacity in sub-Saharan Africa
Authors: Razzano Dana , Puranam Kaushik , Tomoka Tamiwe , Fedoriw Yuri
Published: October 2022

Non-communicable disease (NCD), including cancer, disproportionately affect Low- and Middle-Income Countries (LMICs). This inequity is in part due to limitations of pathology services, both human and infrastructural. While significant improvements have been made to address these gaps, creative approaches that are mindful of regional priorities, cultural differences, and unique local challenges are needed. In this perspective, we will describe the implementation of telepathology services in sub-Saharan Africa (SSA) that serve as cornerstones for direct patient care, multi-disciplinary care coordination, research programs, and building human capacity through training. Models and challenges of system implementation, sustainability, and pathologist engagement will be discussed. Using disease and site-specific examples, we will suggest metrics for quality control and improvement initiatives that are critical for providing high-quality cancer registry data and necessary for future implementation of therapeutic and interventional clinical trials.
18 kDa translocator protein positron emission tomography facilitates early and robust tumor detection in the immunocompetent SB28 glioblastoma mouse model
Authors: Bartos Laura M. , Kirchleitner Sabrina V. , Blobner Jens , Wind Karin , Kunze Lea H. , Holzgreve Adrien , Gold Lukas , Zatcepin Artem , Kolabas Zeynep Ilgin , Ulukaya Selin , Weidner Lorraine , Quach Stefanie , Messerer Denise , Bartenstein Peter , Tonn Joerg C. , Riemenschneider Markus J. , Ziegler Sibylle , von Baumgarten Louisa , Albert Nathalie L. , Brendel Matthias
Published: October 2022

Introduction

The 18 kDa translocator protein (TSPO) receives growing interest as a biomarker in glioblastoma. Mouse models can serve as an important tool for the investigation of biomarkers in glioblastoma, but several glioblastoma models indicated only low TSPO-PET signals in contrast to high TSPO-PET signals of human glioblastoma. Thus, we aimed to investigate TSPO-PET imaging in the syngeneic immunocompetent SB28 mouse model, which is thought to closely represent the tumor microenvironment (TME) of human glioblastoma.

Methods

Dynamic TSPO-PET/CT imaging was performed for 60 min after injection of 13.6 ± 4.2 MBq [18F]GE-180. Contrast enhanced CT (ceCT) was acquired prior to PET and served for assessment of tumor volumes and attenuation correction. SB28 and sham mice were imaged at an early (week-1; n = 6 SB28, n = 6 sham) and a late time-point (week-3; n = 8 SB28, n = 9 sham) after inoculation. Standard of truth ex vivo tumor volumes were obtained for SB28 mice at the late time-point. Tracer kinetics were analyzed for the lesion site and the carotid arteries to establish an image derived input function (IDIF). TSPO-PET and ceCT lesion volumes were compared with ex vivo volumes by calculation of root-mean-square-errors (RMSE). Volumes of distribution (VTmax/mean) in the lesion were calculated using carotid IDIF and standardized uptake values (SUVmax/mean) were obtained for a 40–60 min time frame.

Results

Higher uptake rate constants (K1) were observed for week-1 SB28 tumor lesions when compared to week-3 SB28 tumor lesions. Highest agreement between TSPO-PET lesion volumes and ex vivo tumor volumes was achieved with a 50% maximum threshold (RMSE-VT: 39.7%; RMSE-SUV: 34.4%), similar to the agreement of ceCT tumor volumes (RMSE: 30.1%). Lesions of SB28 mice had higher PET signal when compared to sham mice at week-1 (VTmax 6.6 ± 2.9 vs. 3.9 ± 0.8, p = 0.035; SUVmax 2.3 ± 0.5 vs. 1.2 ± 0.1, p < 0.001) and PET signals remained at a similar level at week-3 (VTmax 5.0 ± 1.6 vs. 2.7 ± 0.8, p = 0.029; SUVmax 1.9 ± 0.5 vs. 1.2 ± 0.2, p = 0.0012). VTmax correlated with SUVmax (R2 = 0.532, p < 0.001).

Conclusion

TSPO-PET imaging of immunocompetent SB28 mice facilitates early detection of tumor signals over sham lesions. SB28 tumors mirror high TSPO-PET signals of human glioblastoma and could serve as a valuable translational model to study TSPO as an imaging biomarker.
Comparative research of intestinal microbiota diversity and body mass regulation in Eothenomys miletus from different areas of Hengduan mountain regions
Authors: Yan Bowen , Jia Ting , Wang Zhengkun , Zhu Wanlong
Published: October 2022

In order to investigate the effects of different areas on intestinal bacterial diversity and body mass regulation in Eothenomys miletus from Hengduan mountain regions, and to explore the community structure and diversity of intestinal microflora and their role in body mass regulation. E. miletus was collected from five areas including Deqin (DQ), Xianggelila (XGLL), Lijiang (LJ), Jianchuan (JC), and Dali (DL), we used 16S rRNA sequencing technology combined with physiological and morphological methods to study the intestinal microbiota diversity, abundance and community structure of the intestinal bacteria in winter, and to explore the influence of geographical factors, physiological indicators including food intake, resting metabolic rate (RMR), non-shivering thermogenesis (NST), neuropeptide Y (NPY), Agouti-Related Protein (AgRP), proopiomelanocortin (POMC), cocaine and amphetamine regulated transcription peptide (CART), and morphological indicators including body mass, body length and other nine indicators on the intestinal microflora diversity in E. miletus. The results showed that there were significant differences in metabolic indexes such as RMR, NST, NPY, AgRP, and morphological indexes such as body length, tail length and ear length among the five regions. Bacterial community in intestinal tract of E. miletus mainly includes three phyla, of which Firmicutes is the dominant phyla, followed by Bacteroidetes and Tenericutes. At the genus level, the dominant bacterial genera were S24-7(UG), Clostridiales (UG), and Lachnospiraceae (UG), etc. α diversity of intestinal microorganisms in DL and JC were significantly different from that in the other three regions. Genera of intestinal microorganisms in DL and JC were also the most. Moreover, Bacteroides, Ruminococcus, and Treponema could affect energy metabolism in E. miletus, which were closely related to the environment in which they lived. All of these results indicated that different areas in Hengduan Mountain had certain effects on the structure of intestinal microbial community in E. miletus, which were responded positively to changes in food abundance and other environmental factors. Furthermore, Firmicutes and Bacteroidetes play an important role in the body mass regulation in E. miletus.
Effect of poplar ecological retreat project on soil bacterial community structure in Dongting Lake wetland
Authors: Wu Haipeng , Xiao Sha , Dai Juan , Xiong Ying , Cao Jiao , Qu Xinyu , Wang Guiqiao , Yang Ruiqing
Published: October 2022

As an important environmental protection measure, the Poplar Ecological Retreat (PER) project aims to restore the ecology of the Dongting Lake (DL, China’s second largest freshwater lake) wetland. And its ecological impact is yet to be revealed. This study selected soil bacterial community structure (BCS) as an indicator of ecological restoration to explore the ecological impact of PER project on DL wetland. Soil samples were collected from reed area (RA, where poplar had never been planted, as the end point of ecological restoration for comparison in this study), poplar planting area (PA), poplar retreat for 1-year area (PR1A) and poplar retreat for 2 years area (PR2A), then their soil properties and BCS were measured. The results showed that the PER project caused significant changes in soil properties, such as the soil organic matter (SOM) and moisture, and an increase in the diversity and richness index of soil BCS. The Shannon-wiener index of RA, PA, PR1A and PR2A were 3.3, 2.63, 2.75 and 2.87, respectively. The number of operational taxonomic units (OTUs) changed similarly to the Shannon-wiener index. The Pearson correlation analysis and redundancy analysis (RDA) showed that the poplar retreat time, SOM and moisture content were the main factors leading to the increase of BCS diversity. All of these indicated that after the implementation of the PER project, the ecology of the lake area showed a trend of gradual recovery.
1,25-D3 attenuates cerebral ischemia injury by regulating mitochondrial metabolism via the AMPK/AKT/GSK3β pathway
Authors: Li Yutian , Li Xiangling , Xu Shuangli , Zhao Yingzhe , Pang Meng , Zhang Xiaojun , Wang Xuejian , Wang Yanqiang
Published: October 2022

The brain injury caused by cerebral ischemia-reperfusion is related to mitochondrial damage. Maintaining the normal function of mitochondria, promoting angiogenesis, protecting neuronal cells, and resisting oxidative stress are the keys to functional recovery after acute ischemic stroke. In this study, we established a middle cerebral artery occlusion (MCAO) model and investigated the effects of 1α,25-dihydroxyvitamin D3 (VitD or 1,25-D3) on mitochondrial function via the adenosine 5'-monophosphate-activated protein kinase (AMPK)/protein kinase B (AKT)/glycogen synthase kinase-3β (GSK-3β) signaling pathway in rats with cerebral ischemia-reperfusion injury. The neurological function and infarct size were measured in each group. Hematoxylin-eosin, neuronal nucleus, and Nissl staining procedures were conducted to observe the morphology and number of the cerebral cortical neurons. Western blotting was then used to analyze p-AMPK, vitamin D receptor (VDR), p-GSK-3β, p-AKT, P53, cytochrome C (CytC), TGF-β, and vascular endothelial growth factor (VEGF) in mitochondria. Immunofluorescence staining was used to observe the expression of CytC and caspase-3. Succinate dehydrogenase, ATPase, reactive oxygen species, and malondialdehyde were detected by kits. RT-qPCR was used to analyze TGF-β, VEGF, P53, and CytC mRNA. The results revealed that the cerebral infarct volume, neurological function score, apoptotic protein P53, CytC, caspase-3, reactive oxygen species, and malondialdehyde were significantly increased in MCAO rats. 1,25-D3 reduced the infarct size and neurological function score, activated VDR, upregulated TGF-β, p-AMPK, p-AKT, p-GSK-3β, VEGF, ATP, and succinate dehydrogenase, and downregulated P53, CytC, caspase-3, reactive oxygen species, and malondialdehyde. As an antagonist of VDRs, pyridoxal-5-phosphate could partially block the neuroprotective effect of 1,25-D3. In conclusion, 1,25-D3 activated AMPK/AKT/GSK-3β signaling and VDRs, inhibited P53, CytC, and caspase-3, increased TGF-β and VEGF, regulated mitochondrial metabolism, reduced neuronal apoptosis, promoted vascular growth, and exerted neuroprotective effects. These findings suggest that this signaling pathway may be an effective target for the treatment of ischemic stroke.
Revealing human sensitivity to a latent temporal structure of changes
Authors: Marković Dimitrije , Reiter Andrea M. F. , Kiebel Stefan J.
Published: October 2022

Precisely timed behavior and accurate time perception plays a critical role in our everyday lives, as our wellbeing and even survival can depend on well-timed decisions. Although the temporal structure of the world around us is essential for human decision making, we know surprisingly little about how representation of temporal structure of our everyday environment impacts decision making. How does the representation of temporal structure affect our ability to generate well-timed decisions? Here we address this question by using a well-established dynamic probabilistic learning task. Using computational modeling, we found that human subjects' beliefs about temporal structure are reflected in their choices to either exploit their current knowledge or to explore novel options. The model-based analysis illustrates a large within-group and within-subject heterogeneity. To explain these results, we propose a normative model for how temporal structure is used in decision making, based on the semi-Markov formalism in the active inference framework. We discuss potential key applications of the presented approach to the fields of cognitive phenotyping and computational psychiatry.
Anatomical labeling of intracranial arteries with deep learning in patients with cerebrovascular disease
Authors: Hilbert Adam , Rieger Jana , Madai Vince I. , Akay Ela M. , Aydin Orhun U. , Behland Jonas , Khalil Ahmed A. , Galinovic Ivana , Sobesky Jan , Fiebach Jochen , Livne Michelle , Frey Dietmar
Published: October 2022

Brain arteries are routinely imaged in the clinical setting by various modalities, e.g., time-of-flight magnetic resonance angiography (TOF-MRA). These imaging techniques have great potential for the diagnosis of cerebrovascular disease, disease progression, and response to treatment. Currently, however, only qualitative assessment is implemented in clinical applications, relying on visual inspection. While manual or semi-automated approaches for quantification exist, such solutions are impractical in the clinical setting as they are time-consuming, involve too many processing steps, and/or neglect image intensity information. In this study, we present a deep learning-based solution for the anatomical labeling of intracranial arteries that utilizes complete information from 3D TOF-MRA images. We adapted and trained a state-of-the-art multi-scale Unet architecture using imaging data of 242 patients with cerebrovascular disease to distinguish 24 arterial segments. The proposed model utilizes vessel-specific information as well as raw image intensity information, and can thus take tissue characteristics into account. Our method yielded a performance of 0.89 macro F1 and 0.90 balanced class accuracy (bAcc) in labeling aggregated segments and 0.80 macro F1 and 0.83 bAcc in labeling detailed arterial segments on average. In particular, a higher F1 score than 0.75 for most arteries of clinical interest for cerebrovascular disease was achieved, with higher than 0.90 F1 scores in the larger, main arteries. Due to minimal pre-processing, simple usability, and fast predictions, our method could be highly applicable in the clinical setting.