bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Production of Carbon Gases and Their Responses to Paleoclimate Conditions: An Example From Xiaolongtan Basin, Southeast Tibetan Plateau
Authors: Wang Gen , Wang Yongli , Wei Zhifu , Sun Zepeng , He Wei , Ma Xueyun
Published: April 2021

Uplift of the Tibetan Plateau plays a significant and lasting role in the variations of climate conditions and global carbon cycle. However, our knowledge is limited due to the lack of long-sequence records revealing rates of CO2 and CH4 production, hampering our understanding of the relationship between paleoclimatic conditions, carbon cycling and greenhouse gas flux. Here, we present a combination of paleoclimate records and low-temperature thermal simulation results from sediments of the Xiaolongtan Basin at the southeastern margin of the Qinghai-Tibetan Plateau, spanning the late Miocene (14.1 ∼ 11.6 Ma). The n-alkane-derived proxies suggested that the sources of organic matter were obviously different: a mixed source including lower organisms and terrestrial higher plants for the Dongshengqiao Formation from 14.1 to 12.6 Ma, and a predominant contribution from terrestrial higher plants for Xiaolongtan Formation between 12.6 and 11.6 Ma. The paleoclimate was generally warm and humid as reflected by the lipid biomarkers, consistent with previous studies. In addition, the carbon gases (including CO2 and hydrocarbon gases) generated by the low-temperature thermal simulation experiments indicated a production rate of CO2 and CH4 were as high as 88,000 ml/kg rock and 4,000 ml/kg rock, respectively, implying there were certain amounts of carbon gases generated and released into the atmosphere during their shallow burial stage. Besides, the calculated production rate of carbon gases and the estimated burial flux of organic carbon varied in response to the variations of paleoclimate conditions. Based on these observations, we propose that the climate conditions predominantly controlled the formation and accumulation of organic matter, which consequently affected the production of carbon gases and burial flux of organic carbon. The results presented here may provide a significant insight into the carbon cycle in the southeast of the Tibetan Plateau.
PPP-BOTDA Distributed Optical Fiber Sensing Technology and Its Application to the Baishuihe Landslide
Authors: Zhao Meng , Yi Xianlong , Zhang Junrong , Lin Chengyuan
Published: April 2021

Serious landslide hazards are prevalent along the Yangtze River in China, particularly in the Three Gorges Reservoir area. Thus, landslide monitoring and forecasting technology research is critical if landslide geological hazards are to be prevented and controlled. Pulse-prepump brillouin optical time domain analysis (PPP-BOTDA) distributed optical fiber sensing technology is a recently developed monitoring method with evident advantages in precision and spatial resolution. Herein, fixed-point immobilization and direct burying methods were adopted to arrange parallel distribution of the strain and temperature-compensated optical fibers along the Baishuihe landslide’s front edge, in order to carry out ground surface deformation monitoring. The strain data acquired from both optical fibers were processed with temperature compensation to obtain the actual optical fiber strain produced by deformation. Butterworth low-pass filter denoising method was employed to determine the filter order (n) and cut-off frequency (Wn). The area differences between the two optical fiber monitoring curves and the fixed horizontal axis were selected as evaluation indexes to obtain the area difference along the optical fiber. This data were then leveraged to determine the positive correlation between the area difference and the optical fiber strain variation degree. Finally, these results were compared with the GPS and field measured data. This study shows that when PPP-BOTDA technology is used for landslide surface deformation monitoring in conjunction with Butterworth filter denoising and strain area difference, the optical fiber strain variation degree analysis results are consistent with the GPS monitoring data and the actual landslide deformation. As such, this methodology is highly relevant for reducing the workload and improving the monitoring precision in landslide monitoring, which in turn will protect lives and property.
Innovative Approaches for the Sedimentological Characterization of Fine Natural and Anthropogenic Sediments in Karst Systems: The Case of the Apuan Alps (Central Italy)
Authors: Nannoni Alessia , Piccini Leonardo , Costagliola Pilario , Batistoni Nicolò , Gabellini Pietro , Cioni Raffaello , Pratesi Gabriele , Bucci Silvia
Published: April 2021

The Apuan Alps (NW Tuscany) is an important area of Central Italy characterized by large karst systems mainly fed via direct and diffuse water infiltration (autogenic recharge). These waters usually transport a clastic sediment load, originated by natural, surface and subsurface rock erosion/weathering which, in part, is deposited underground. In the Apuan Alps, during extreme rain event, huge amounts of carbonate powder, produced as a waste resulting from the quarrying operations of the famous “Carrara” marble, mix up with meteoric waters forming a slurry that is transported through the karst openings into the caves, where the carbonate powder may be deposited along with natural sediments. Depending upon karst hydrology and water fluxes, the slurry may eventually reach karst springs heavily reducing water quality. Mineralogical composition of the sediments collected along karst waterways and springs shows variable proportions of calcite associated with dolomite and silicates particles whereas the marble powder samples from quarry areas are mainly composed by calcite grains. Cave deposits of natural origin have usually a fine-sand grain size whereas spring sediments have a more variable grain-size distribution. Marble powder mainly has a silt grain size and produces a sort of “granulometric and morphometric pollution” which influences the transport mechanism of solid load through the karst systems along both vadose and phreatic waterways.
Short- and Long-Term Effects of Passive and Active Screen Time on Young Children’s Phonological Memory
Authors: Veraksa Nikolay , Veraksa Aleksander , Gavrilova Margarita , Bukhalenkova Daria , Oshchepkova Ekaterina , Chursina Apollinaria
Published: April 2021

The purpose of this study was to fill this gap by examining the relationship between phonological memory in preschool children and their passive (watching TV) and active screen time with using of Smart Screen Technologies such as tablets and phones with a touch screen interface. Study was conducted in two stages: in Time 1, the association between children’s phonological memory, passive and active screen time and family factors was examined; in Time 2 (1 year later) the impact of passive and active screen time on a child’s individual progress in phonological memory development was evaluated. The study enrolled 122 preschool children aged 5–6 years (M= 5.72, SD = 0.33); boys (54.9%). Information on each child’s average daily passive and active screen time was obtained from a survey with the mother. The survey provided information on how much time each child spent on a typical day with passive (“traditional”) and active (interactive) use of digital devices. For family factors, we included maternal highest educational qualification, family’s financial situation. For children’s characteristics, age, gender and non-verbal fluid intelligence were included. The results indicate that time spent passively with digital devices (watching TV) is negatively related to a child’s ability to process verbal information. In contrast, the interactive time the child spent with Smart Screen Technologies is not significant and does not pose a threat to the development of phonological memory in preschool age. The study also showed that passive and active use of digital devices has no long-term impact on children’s phonological memory development progress over a year. The implications are that use of Smart Screen Technologies, which implies a higher degree of interactivity, is not associated with either short- or long-term negative effects on phonological memory development in preschool age, contrary to passive screen time exposure. The results can be applied in the elaboration of principles and programs on the use of digital devices for the entertainment and education of preschool children.
Clinical and Functional Characterization of Novel INSR Variants in Two Families With Severe Insulin Resistance Syndrome
Authors: Zhou Qiaoli , Yu Jing , Yuan Xuewen , Wang Chunli , Zhu Ziyang , Zhang Aihua , Gu Wei
Published: April 2021

Objective

Defects in the insulin receptor (INSR) gene cause various severe insulin resistance conditions, including Donohue syndrome (DS), Rabson-Mendenhall syndrome (RMS) and type A insulin resistance (type A-IR). This study aimed to investigate the clinical characterization and molecular defects in three Chinese children with INSR-related insulin resistance syndrome.

Methods

We reviewed the clinical data of three Chinese children with INSR-related insulin resistance syndrome from two unrelated kindreds. Genetic analysis was performed using whole-exome sequencing and the effects of the novel variants were further assessed by in vitro functional assays.

Results

The proband with type A-IR presented with acanthosis nigricans, hypertrichosis, and euglycemia with mild insulin resistance in early childhood. His sister presented with features typical of type A-IR and was diagnosed with diabetes mellitus with severe insulin resistance at the age of 9.8 years. The proband with DS showed typical dysmorphic characteristics, severe intrauterine growth retardation, extreme insulin resistance, fasting hypoglycemia and postprandial hyperglycemia from birth. The heterozygote variants c.[3670G>A]; c.[3614C>T] were identified in both siblings with type A-IR; and c.[749_751del]; c.[3355C>T] in the patient with DS. In vitro studies showed that the novel variant c.749_751del [p.(Thr250del)] in the α-subunit, reduced expression of the mature INSR protein and severely impaired INSR function. In contrast, the novel variant c.3670G>A [p.(Val1224Met)] in the β-subunit had no effect on total protein expression and phosphorylation of INSR and Akt, suggesting that the variant p.Val1224Met appeared to be tolerated and was not responsible for the severe insulin resistance.

Conclusion

Our study detailed the clinical features of three patients with type A-IR and DS, and identified two novel variants in the INSR gene. Functional assays indicated the novel variant p.Thr250del was pathogenic. In contrast, the novel variant p.Val1224Met was suggested to be tolerated by our experimental data, even though bioinformatics analyses predicted the variant as deleterious.
A Comparative Study on the Biodegradation of 17β-Estradiol by Candida utilis CU-2 and Lactobacillus casei LC-1
Authors: Ge Huiru , Yang Liansheng , Li Benhang , Feng Yuyan , Wang Shurui , Zheng Yue , Feng Li , Liu Yongze , Du Ziwen , Zhang Liqiu
Published: April 2021

The release and fate of estrogens have attracted more and more public attention. Biodegradation is an important method for estrogen removal from the environment. However, few comparative studies concentrated on the degradation of 17β-estradiol (E2) by fungi and bacteria. In this study, the removal efficiencies of E2 by fungi (Candida utilis CU-2) and bacteria (Lactobacillus casei LC-1) were investigated through influencing factors, kinetics, and biodegradation pathways. The results demonstrated that both C. utilis CU-2 and L. casei LC-1 have the same degradation efficiency, and they can effectively degrade E2 (10 μM) with nearly 97% degradation efficiency. However, the biodegradation efficiency of the two strains only reached 20% when E2 was used as a sole carbon source, while it increased to 97% with 1.2 g/L sucrose, glucose, or sodium acetate supply, indicating the occurrence of co-metabolism. In addition, the results indicated that 35°C and 0.6 g/L sucrose favored the degradation. However, the addition of excessive carbon sucrose (10 g/L) significantly inhibited the biodegradation of E2. Besides, the degradation of E2 with ~0–10 g/L sucrose as co-substrate followed the first-order kinetics well. Through intermediate products analysis, 12 degradation products were identified, and they were mainly produced via hydroxylation and methylation, among others, among which C14H22O4 (m/z:[M + H]+ = 255) was detected as the product with the smallest amount of carbon in this study. Based on the detected products and previous studies, five biodegradation pathways were proposed. To our knowledge, there are few reports about the comparisons of E2 removal between fungi and bacteria. Moreover, the results confirmed that the strain CU-2 and the strain LC-1 may have similar degradation characteristics and metabolic mechanisms in the degradation of E2. This study may provide a promising bio-treatment method with low energy consumption for E2 removal from aqueous environments and help in understanding their biodegradation mechanisms.
The Ethical Matrix as a Tool for Decision-Making Process in Conservation
Authors: Biasetti Pierfrancesco , de Mori Barbara
Published: April 2021

Decision making-process in conservation can be very complex, having to deal with various value dimensions and potential conflicts. In fact, conflicts and competing interests between stakeholders are among the most quoted reasons for failure of projects. Ethical analysis can be helpful in this regard. In this paper we present a revision of the Ethical Matrix specifically tailored to decision-making processes in conservation. The Ethical Matrix is a conceptual tool devised to help decision-makers by supplying them with a framework of the ethically relevant aspects involved in decision-making process. It was originally developed for the ethical assessment of agri-food biotechnologies and later has been applied to other fields. The revised version we propose here has been designed for the ethical analysis of conservation priority-setting and impact. As conservation can raise many ethical relevant controversies, conceptual tools like the one presented here can be of help for conservationists, providing a map of the value demands involved. This map can be used to question the reasonableness of the value judgments, estimate the impact of different courses of actions, anticipate conflicts, and rank their severeness.
The Composition of Intestinal Microbiota From Collichthys lucidus and Its Interaction With Microbiota From Waters Along the Pearl River Estuary in China
Authors: Wu Peng , Liu Yong , Li Chunhou , Xiao Yayuan , Wang Teng , Lin Lin , Xie Yufang
Published: April 2021

By their nature and geographical location, estuaries shape different marine habitats via freshwater and seawater interactions. Thus, fish intestinal microbiota, as mediated by estuary habitat fluctuations, are fundamentally important but rarely studied. Similarly, it is unclear how, and to what extent, water microbiota influences fish intestinal microbiota in different estuary habitats. In this study, the euryhaline fish species, Collichthys lucidus from three different habitats in the Pearl River estuary (PRE) was investigated to determine the influence of habitat fluctuation on intestinal microbiota. The three water environments selected for sample collection were very different, particularly for chlorophyll-a, suspended solid, and nutrient constituents. Using high-throughput sequencing of 16S rRNA gene amplicons, we observed that dominant microbial genera in surrounding estuary waters or fish intestines were seldom shared. The most dominant genera in water samples were Candidatus Actinomarina and HIMB11, while Bifidobacterium, Stenotrophomonas, Escherichia-Shigella and Rhodopseudomonas were more abundant in fish intestines. Fish hosts can shape fish intestinal microbiota. However, microbial exchange was also found between fish intestines and water samples. The frequency of microbial exchange between fish intestines and water samples was increased from upstream to downstream estuary points, and was influenced by changes in seawater salinity in the estuary. Finally, core intestinal microbiota from C. lucidus was analyzed, and showed that Bifidobacterium, Rhodopseudomonas, Escherichia-Shigella, Acinetobacter, and Stenotrophomonas were highly abundant. These microbiota were theoretically implicated in immune responses, nutrient metabolism, probiotics, and potential pathogen behaviors. Overall, these data highlighted the composition of C. lucidus intestinal microbiota in different habitats across the PRE.
Evaluating Social Policy Scenarios for Tourism Development of Barú Island (Colombia) Using Structural Qualitative Modeling
Authors: Ramos-Jiliberto Rodrigo , Jiliberto Herrera Rodrigo
Published: April 2021

Social policies are commonly defined from scattered knowledge. It is hard to find examples of social policy design based on a systemic perspective, and even harder with formal modeling support. To advance in filling this gap, we studied the case of the tourism development on Barú Island. In this place, tourism is a critical economic activity based on local ecosystem services, but it is being developed without planning and outside of a sustainability focus. We build a qualitative model of the social structure of tourism development that is taking place in the locality. Model building was based on experiences and opinions of local stakeholders, gathered through participatory procedures. Using our model, we projected the future states of the system, assuming several hypothetical public policy scenarios. More specifically, we evaluated the system responses to: (a) a multivariate business–as–usual (BAU) scenario, and (b) two multivariate aprioristic scenarios, pointed to improve expected outcomes. These scenarios were based on the opinions of both stakeholders and experts. We also tested: (c) simple (univariate) aposterioristic scenarios, built from the structural analysis of the system using the sensitivity matrix. Finally, we included: (d) a trivial (and unattainable) scenario, in which every model variable was increased or decreased at convenience. The outcomes of our scenario analysis were evaluated using four different weight sets applied to the projected states of system variables, representing different strategic priorities: social-economic, environmental, mixed, and plain. Our results show that the projected outcomes differ among the tested scenarios and the strategic priority to be adopted. However, in all cases the BAU scenario was markedly the worst. For every strategic priority, some simple aposterioristic scenarios performed slightly better, as compared to the more complex aprioristic ones, and even better than the trivial scenario. This result was more noticeable under the plain strategy. We conclude that aposterioristic scenarios derived from the sensitivity matrix of the qualitative model, particularly decreasing migration risk and increasing governance strength, are the best candidates for tourism policy-making in Barú among the evaluated alternatives. These results should be put in its context and adapted before they can be transferred to other study-cases. Our findings suggest that social policy-making can benefit from structural qualitative modeling. In particular, this approach may give analytical support to the selection of intervention measures from a structural perspective, based on defined strategic priorities. For this purpose, however, the model itself and the outcomes obtained from its analysis should be updated steadily.
Evapotranspiration Intensification Over Unchanged Temperate Vegetation in the Baltic Countries Is Being Driven by Climate Shifts
Authors: Montibeller Bruno , Jaagus Jaak , Mander Ülo , Uuemaa Evelyn
Published: April 2021

Shifts in climate driven by anthropogenic land use and land cover change are expected to alter various land–atmosphere interactions. Evapotranspiration (ET) is one of these processes and plays a fundamental role in the hydrologic cycle. Using gridded reanalysis and remote sensing data, we investigated the spatiotemporal trends of precipitation, temperature, and ET for areas in the Baltic countries Lithuania, Latvia and Estonia where the land cover type had not changed from 2000 to 2018. We focused on ET but investigated the spatiotemporal trends for the three variables at monthly, seasonal, and annual time scales during this period to quantify trade-offs among months and seasons. We used the Mann-Kendall test and Sen’s slope to calculate the trends and rate of change for the three variables. Although precipitation showed fewer statistically significant increasing and decreasing trends due to its high variability, temperature showed only increasing trends. The trends were concentrated in late spring (May, +0.14°C annually), summer (June and August, +0.10°C), and early autumn (September, +0.13°C). For unchanged forest and cropland areas, we found no statistically significant ET trends. However, Sen’s slope indicated increasing ET in April, May, June, and September for forest areas and in May and June for cropland. Our results indicate that during the study period, the temperature changes may have lengthened the growing season, which affected the ET patterns of forest and cropland areas. The results also provide important insights into the regional water balance and complement the findings of other studies.
Genome-Wide Detection of Runs of Homozygosity in Laiwu Pigs Revealed by Sequencing Data
Authors: Fang Yifei , Hao Xinyu , Xu Zhong , Sun Hao , Zhao Qingbo , Cao Rui , Zhang Zhe , Ma Peipei , Sun Yanxiao , Qi Zengmin , Wei Qingkui , Wang Qishan , Pan Yuchun
Published: April 2021

Laiwu pigs, distinguished by their high intramuscular fat of 7–9%, is an indigenous pig breed of China, and recent studies also found that Laiwu pigs showed high resistance to Porcine circovirus type 2. However, with the introduction of commercial varieties, the population of Laiwu pigs has declined, and some lineages have disappeared, which could result in inbreeding. Runs of homozygosity (ROH) can be used as a good measure of individual inbreeding status and is also normally used to detect selection signatures so as to map the candidate genes associated with economically important traits. In this study, we used data from Genotyping by Genome Reducing and Sequencing to investigate the number, length, coverage, and distribution patterns of ROH in 93 Chinese Laiwu pigs and identified genomic regions with a high ROH frequency. The average inbreeding coefficient calculated by pedigree was 0.021, whereas that estimated by all detected ROH segments was 0.133. Covering 13.4% of the whole genome, a total of 7,508 ROH segments longer than 1 Mb were detected, whose average length was 3.76 Mb, and short segments (1–5 Mb) dominated. For individuals, the coverage was in the range between 0.56 and 36.86%. For chromosomes, SSC6 had the largest number (n = 688), and the number of ROH in SSC12 was the lowest (n = 215). Thirteen ROH islands were detected in our study, and 86 genes were found within those regions. Some of these genes were correlated with economically important traits, such as meat quality (ECI1, LRP12, NDUFA4L2, GIL1, and LYZ), immunity capacity (IL23A, STAT2, STAT6, TBK1, IFNG, and ITH2), production (DCSTAMP, RDH16, and GDF11), and reproduction (ODF1 and CDK2). A total of six significant Gene Ontology terms and nine significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, most of which were correlated with disease resistance and biosynthesis processes, and one KEGG pathway was related to lipid metabolism. In addition, we aligned all of the ROH islands to the pig quantitative trait loci (QTL) database and finally found eight QTL related to the intramuscular fat trait. These results may help us understand the characteristics of Laiwu pigs and provide insight for future breeding strategies.
DNA Repair Repertoire of the Enigmatic Hydra
Authors: Barve Apurva , Galande Alisha A. , Ghaskadbi Saroj S. , Ghaskadbi Surendra
Published: April 2021

Since its discovery by Abraham Trembley in 1744, hydra has been a popular research organism. Features like spectacular regeneration capacity, peculiar tissue dynamics, continuous pattern formation, unique evolutionary position, and an apparent lack of organismal senescence make hydra an intriguing animal to study. While a large body of work has taken place, particularly in the domain of evolutionary developmental biology of hydra, in recent years, the focus has shifted to molecular mechanisms underlying various phenomena. DNA repair is a fundamental cellular process that helps to maintain integrity of the genome through multiple repair pathways found across taxa, from archaea to higher animals. DNA repair capacity and senescence are known to be closely associated, with mutations in several repair pathways leading to premature ageing phenotypes. Analysis of DNA repair in an animal like hydra could offer clues into several aspects including hydra’s purported lack of organismal ageing, evolution of DNA repair systems in metazoa, and alternative functions of repair proteins. We review here the different DNA repair mechanisms known so far in hydra. Hydra genes from various DNA repair pathways show very high similarity with their vertebrate orthologues, indicating conservation at the level of sequence, structure, and function. Notably, most hydra repair genes are more similar to deuterostome counterparts than to common model invertebrates, hinting at ancient evolutionary origins of repair pathways and further highlighting the relevance of organisms like hydra as model systems. It appears that hydra has the full repertoire of DNA repair pathways, which are employed in stress as well as normal physiological conditions and may have a link with its observed lack of senescence. The close correspondence of hydra repair genes with higher vertebrates further demonstrates the need for deeper studies of various repair components, their interconnections, and functions in this early metazoan.
Remission of Thymoma on Steroid Therapy in a Patient With Atypical Thymoma-Associated Multiorgan Autoimmunity: A Case Report and Literature Review
Authors: Wrona Ewa , Dębska-Szmich Sylwia , Pastuszka Marta , Braun Marcin , Czyżykowski Rafał , Potemski Piotr
Published: April 2021

In up to 34% of cases, thymoma, itself a rare neoplasm, is accompanied by autoimmune disorders, two of which are thymoma-associated multiorgan autoimmunity (TAMA) and paraneoplastic autoimmune multiorgan syndrome (PAMS). Unfortunately, differential diagnosis between these two entities can be challenging since no strict PAMS definition exists and PAMS can overlap with a subgroup of TAMA patients with skin lesions as leading presentation. We present a case of a 68-year-old woman with a diagnosis of thymoma accompanied by myasthenia gravis, hypothyroidism and GvHD-like mucocutaneous lesions that initially could account to both TAMA and PAMS diagnosis. However, following the exclusion of humoral autoimmunity against components of epithelial cells junction, TAMA was finally established. Interestingly, the introduction of corticosteroid therapy for TAMA symptom management resulted in unexpected partial remission of thymoma with no impact on mucocutaneous lesions. Our case study is an example of two extremely rare phenomena accompanying thymomas: unprecedented TAMA presentation with GvHD-like mucositis, which as we postulate should be placed in the spectrum of TAMA, and tumor remission on steroids.
Immune Protection of a Helminth Protein in the DSS-Induced Colitis Model in Mice
Authors: Long Shao Rong , Liu Ruo Dan , Kumar Deepak Vijaya , Wang Zhong Quan , Su Chien-Wen
Published: April 2021

Inflammatory bowel disease (IBD) increases the risk of colorectal cancer, and it has the potential to diminish the quality of life. Recent clinical and experimental evidence demonstrate protective aspects of parasitic helminth infection against IBD. Reports have highlighted the potential use of helminths and their byproducts as potential treatment for IBD. In the current study, we studied the effect of a newborn larvae-specific serine protease from Trichinella spiralis (TsSp) on the host immune and inflammatory responses. A 49-kDa recombinant TsSp (rTsSp) was expressed in Escherichia coli BL21 (DE3) and purified. The cytotoxicity of rTsSp was analyzed. The immune protective effect of rTsSp was studied by using dextran sodium sulfate (DSS)-induced mouse colitis model. The result illustrated that rTsSp has no toxic effects on cells. We further demonstrated that administration of the rTsSp without the additional adjuvant before the induction of DSS-induced colitis reduced the severity of intestinal inflammation and the disease index; it suppressed macrophage infiltration, reduced TNF-α secretion, and induced IL-10 expression. Our findings suggest therapeutic potential of rTsSp on colitis by altering the effect of macrophages. Data also suggest immunotherapy with rTsSp holds promise for use as an additional strategy to positively modulate inflammatory processes involved in IBD.
The Role of Proprotein Convertases in the Regulation of the Function of Immune Cells in the Oncoimmune Response
Authors: Rose Mélanie , Duhamel Marie , Rodet Franck , Salzet Michel
Published: April 2021

Proprotein convertases (PC) are a family of 9 serine proteases involved in the processing of cellular pro-proteins. They trigger the activation, inactivation or functional changes of many hormones, neuropeptides, growth factors and receptors. Therefore, these enzymes are essential for cellular homeostasis in health and disease. Nine PC subtilisin/kexin genes (PCSK1 to PCSK9) encoding for PC1/3, PC2, furin, PC4, PC5/6, PACE4, PC7, SKI-1/S1P and PCSK9 are known. The expression of PC1/3, PC2, PC5/6, Furin and PC7 in lymphoid organs such as lymph nodes, thymus and spleen has suggested a role for these enzymes in immunity. In fact, knock-out of Furin in T cells was associated with high secretion of pro-inflammatory cytokines and autoantibody production in mice. This suggested a key role for this enzyme in immune tolerance. Moreover, Furin through its proteolytic activity, regulates the suppressive functions of Treg and thus prevents chronic inflammation and autoimmune diseases. In macrophages, Furin is also involved in the regulation of their inflammatory phenotype. Similarly, PC1/3 inhibition combined with TLR4 stimulation triggers the activation of the NF-κB signaling pathway with an increased secretion of pro-inflammatory cytokines. Factors secreted by PC1/3 KD macrophages stimulated with LPS exert a chemoattractive effect on naive auxiliary T lymphocytes (Th0) and anti-tumoral activities. The link between TLR and PCs is thus very important in inflammatory response regulation. Furin regulates TL7 and TLR8 processing and trafficking whereas PC1/3 controls TLR4 and TLR9 trafficking. Since PC1/3 and Furin are key regulators of both the innate and adaptive immune responses their inhibition may play a major role in oncoimmune therapy. The role of PCs in the oncoimmune response and therapeutic strategies based on PCs inhibition are proposed in the present review.
Trans Fatty Acid Intake Induces Intestinal Inflammation and Impaired Glucose Tolerance
Authors: Okamura Takuro , Hashimoto Yoshitaka , Majima Saori , Senmaru Takafumi , Ushigome Emi , Nakanishi Naoko , Asano Mai , Yamazaki Masahiro , Takakuwa Hiroshi , Hamaguchi Masahide , Fukui Michiaki
Published: April 2021

Background and Aims

Many nutritional and epidemiological studies have shown that high consumption of trans fatty acids can cause several adverse effects on human health, including cardiovascular disease, diabetes, and cancer. In the present study, we investigated the effect of trans fatty acids on innate immunity in the gut by observing mice fed with a diet high in trans fatty acids, which have been reported to cause dysbiosis.

Methods

We used C57BL6/J mice and fed them with normal diet (ND) or high-fat, high-sucrose diet (HFHSD) or high-trans fatty acid, high-sucrose diet (HTHSD) for 12 weeks. 16S rRNA gene sequencing was performed on the mice stool samples, in addition to flow cytometry, real-time PCR, and lipidomics analysis of the mice serum and liver samples. RAW264.7 cells were used for the in vitro studies.

Results

Mice fed with HTHSD displayed significantly higher blood glucose levels and advanced fatty liver and intestinal inflammation, as compared to mice fed with HFHSD. Furthermore, compared to mice fed with HFHSD, mice fed with HTHSD displayed a significant elevation in the expression of CD36 in the small intestine, along with a reduction in the expression of IL-22. Furthermore, there was a significant increase in the populations of ILC1s and T-bet-positive ILC3s in the lamina propria in mice fed with HTHSD. Finally, the relative abundance of the family Desulfovibrionaceae, which belongs to the phylum Proteobacteria, was significantly higher in mice fed with HFHSD or HTHSD, than in mice fed with ND; between the HFHSD and HTHSD groups, the abundance was slightly higher in the HTHSD group.

Conclusions

This study revealed that compared to saturated fatty acid intake, trans fatty acid intake significantly exacerbated metabolic diseases such as diabetes and fatty liver.
Dietary Derived Micronutrients Modulate Immune Responses Through Innate Lymphoid Cells
Authors: Shi Zhengzheng , Ohno Hiroshi , Satoh-Takayama Naoko
Published: April 2021

Innate lymphoid cells (ILCs) are a group of innate immune cells that possess overlapping features with T cells, although they lack antigen-specific receptors. ILCs consist of five subsets-ILC1, ILC2, ILC3, lymphoid tissue inducer (LTi-like) cells, and natural killer (NK) cells. They have significant functions in mediating various immune responses, protecting mucosal barrier integrity and maintaining tissue homeostasis in the lung, skin, intestines, and liver. ILCs react immediately to signals from internal and external sources. Emerging evidence has revealed that dietary micronutrients, such as various vitamins and minerals can significantly modulate immune responses through ILCs and subsequently affect human health. It has been demonstrated that micronutrients control the development and proliferation of different types of ILCs. They are also potent immunoregulators in several autoimmune diseases and play vital roles in resolving local inflammation. Here, we summarize the interplay between several essential micronutrients and ILCs to maintain epithelial barrier functions in various mucosal tissues and discuss their limitations and potentials for promoting human health.
Phenotypical Diversification of Early IFNα-Producing Human Plasmacytoid Dendritic Cells Using Droplet-Based Microfluidics
Authors: Van Eyndhoven Laura C. , Chouri Eleni , Subedi Nikita , Tel Jurjen
Published: April 2021

Plasmacytoid dendritic cells (pDCs) are a rare type of highly versatile immune cells that besides their specialized function of massive type I interferon (IFN-I) production are able to exert cytotoxic effector functions. However, diversification upon toll like receptor (TLR)-induced activation leads to highly heterogeneous responses that have not been fully characterized yet. Using droplet-based microfluidics, we showed that upon TLR7/8 and TLR9-induced single-cell activation only 1-3% secretes IFNα, and only small fractions upregulate cytotoxicity markers. Interestingly, this 1-3% of early IFN-producing pDCs, also known as first responders, express high levels of programmed death-ligand 1 (PD-L1) and TNF-related apoptosis-inducing ligand (TRAIL), which makes these hybrid cells similar to earlier described IFN-I producing killer pDCs (IKpDCs). IFN-I priming increases the numbers of IFNα producing cells up to 40%, but does not significantly upregulate the cytotoxicity markers. Besides, these so-called second responders do not show a cytotoxic phenotype as potent as observed for the first responders. Overall, our results indicate that the first responders are the key drivers orchestrating population wide IFN-I responses and possess high cytotoxic potential.
Respiratory Impairment Predicts Response to IL-1 and IL-6 Blockade in COVID-19 Patients With Severe Pneumonia and Hyper-Inflammation
Authors: Della-Torre Emanuel , Lanzillotta Marco , Campochiaro Corrado , Cavalli Giulio , De Luca Giacomo , Tomelleri Alessandro , Boffini Nicola , De Lorenzo Rebecca , Ruggeri Annalisa , Rovere-Querini Patrizia , Castagna Antonella , Landoni Giovanni , Tresoldi Moreno , Ciceri Fabio , Zangrillo Alberto , Dagna Lorenzo
Published: April 2021

Background

Restraining maladaptive inflammation is considered a rationale strategy to treat severe coronavirus disease-19 (COVID-19) but available studies with selective inhibitors of pro-inflammatory cytokines have not provided unequivocal evidence of survival advantage. Late administration is commonly regarded as a major cause of treatment failure but the optimal timing for anti-cytokine therapy initiation in COVID-19 patients has never been clearly established.

Objectives

To identify a window of therapeutic opportunity for maximizing the efficacy of interleukin (IL)-1 and IL-6 blockade in COVID-19.

Methods

Survival at the longest available follow-up was assessed in severe hyper-inflamed COVID-19 patients treated with anakinra, tocilizumab, sarilumab, or standard of care, stratified according to respiratory impairment at the time of treatment initiation.

Results

107 patients treated with biologics and 103 contemporary patients treated with standard of care were studied. After a median of 106 days of follow-up (range 3-186), treatment with biologics was associated with a significantly higher survival rate compared to standard therapy when initiated in patients with a PaO2/FiO2 ≥ 100 mmHg (p < 0.001). Anakinra reduced mortality also in patients with PaO2/FiO2 < 100 mmHg (p = 0.04).

Conclusions

IL-1 and IL-6 blocking therapies are more likely to provide survival advantage in hyper-inflamed COVID-19 patients when initiated before the establishment of severe respiratory failure.
The cGAS-STING Pathway: Novel Perspectives in Liver Diseases
Authors: Xu Dongwei , Tian Yizhu , Xia Qiang , Ke Bibo
Published: April 2021

Liver diseases represent a major global health burden accounting for approximately 2 million deaths per year worldwide. The liver functions as a primary immune organ that is largely enriched with various innate immune cells, including macrophages, dendritic cells, neutrophils, NK cells, and NKT cells. Activation of these cells orchestrates the innate immune response and initiates liver inflammation in response to the danger signal from pathogens or injured cells and tissues. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a crucial signaling cascade of the innate immune system activated by cytosol DNA. Recognizing DNA as an immune-stimulatory molecule is an evolutionarily preserved mechanism in initiating rapid innate immune responses against microbial pathogens. The cGAS is a cytosolic DNA sensor eliciting robust immunity via the production of cyclic GMP-AMPs that bind and activate STING. Although the cGAS-STING pathway has been previously considered to have essential roles in innate immunity and host defense, recent advances have extended the role of the cGAS-STING pathway to liver diseases. Emerging evidence indicates that overactivation of cGAS-STING may contribute to the development of liver disorders, implying that the cGAS-STING pathway is a promising therapeutic target. Here, we review and discuss the role of the cGAS-STING DNA-sensing signaling pathway in a variety of liver diseases, including viral hepatitis, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), primary hepatocellular cancer (HCC), and hepatic ischemia-reperfusion injury (IRI), with highlights on currently available therapeutic options.
A Novel Framework to Predict Relative Habitat Selection in Aquatic Systems: Applying Machine Learning and Resource Selection Functions to Acoustic Telemetry Data From Multiple Shark Species
Authors: Griffin Lucas P. , Casselberry Grace A. , Hart Kristen M. , Jordaan Adrian , Becker Sarah L. , Novak Ashleigh J. , DeAngelis Bryan M. , Pollock Clayton G. , Lundgren Ian , Hillis-Starr Zandy , Danylchuk Andy J. , Skomal Gregory B.
Published: April 2021

Resource selection functions (RSFs) have been widely applied to animal tracking data to examine relative habitat selection and to help guide management and conservation strategies. While readily used in terrestrial ecology, RSFs have yet to be extensively used within marine systems. As acoustic telemetry continues to be a pervasive approach within marine environments, incorporation of RSFs can provide new insights to help prioritize habitat protection and restoration to meet conservation goals. To overcome statistical hurdles and achieve high prediction accuracy, machine learning algorithms could be paired with RSFs to predict relative habitat selection for a species within and even outside the monitoring range of acoustic receiver arrays, making this a valuable tool for marine ecologists and resource managers. Here, we apply RSFs using machine learning to an acoustic telemetry dataset of four shark species to explore and predict species-specific habitat selection within a marine protected area. In addition, we also apply this RSF-machine learning approach to investigate predator-prey relationships by comparing and averaging tiger shark relative selection values with the relative selection values derived for eight potential prey-species. We provide methodological considerations along with a framework and flexible approach to apply RSFs with machine learning algorithms to acoustic telemetry data and suggest marine ecologists and resource managers consider adopting such tools to help guide both conservation and management strategies.
Heterarchy Reveals Social Organization of a Smooth Stingray (Bathytoshia brevicaudata) Population in a Provisioned Food Context
Authors: Pini-Fitzsimmons Joni , Knott Nathan A. , Brown Culum
Published: April 2021

The advent of new technologies and statistical analyses has provided valuable insights into chondrichthyan social behavior. It has become apparent that sharks and rays lead more complex social lives than previously believed. Heterarchy combines hierarchy and social network theory and although it is not a new concept, it is rarely applied to animal social interactions. Here, we applied heterarchy to a case study involving smooth stingrays foraging for fish scraps at boat ramp in Jervis Bay, NSW Australia. We took advantage of their attraction to this site to examine their social behavior during agonistic interactions over the provisioned resource. We observed a stable, relatively linear but shallow dominance hierarchy that was highly transitive dominated by a single individual. Social network analysis revealed a non-random social network centered on the dominant individual. Contrary to previous research, size did not predict dominance, but it was correlated with network centrality. The factors determining dominance of lower ranks were difficult to discern, which is characteristic of despotic societies. This study provides the first heterarchical assessment of stingray sociality, and suggests this species is capable of complex social behavior. Given higher dominance and centrality relate to greater access to the provisioned resource, the observed social structure likely has fitness implications.
Picophytoplankton Niche Partitioning in the Warmest Oligotrophic Sea
Authors: Coello-Camba Alexandra , Agustí Susana
Published: April 2021

Pico-sizedSynechococcus,Prochlorococcus, and eukaryotes are the dominant photosynthetic organisms in the vast warm and oligotrophic regions of the ocean. In this paper, we aim to characterize the realized niches of the picophytoplanktonic community inhabiting the Red Sea, the warmest oligotrophic sea, which is considered to be a model for the future ocean. We quantify population abundances and environmental variables over several oceanographic surveys, and use stepwise regression, principal-component analysis (PCA), and compositional-data analysis to identify the realized niches of the three picophytoplanktonic groups. Water temperature varied from 21.4 to 32.4°C within the upper 200-m water column, with the warmest waters being found in the South, where nutrients increased.Synechococcusdominated the biomass, contributing 47.6% to the total picophytoplankton biomass, followed by picoeukaryotes (26.4%) andProchlorococcus(25.9%), whose proportions contrast significantly with those reported in the subtropical ocean, whereProchlorococcusprevails. There were positive and significant relationships between temperature and the three populations, although these were weak forProchlorococcus(R2= 0.08) and stronger and steeper forSynechococcus(R2= 0.57). The three populations centered their maximum abundances (Lorentzian fits) at similar low nutrient values.Synechococcuswere centered close to the surface at ≈77% of surface photosynthetically active radiation (PAR) and ≈30.6°C. The picoeukaryotes were centered at lower light (≈6.4% surface PAR) and warm waters (≈30°C).Prochlorococcuswas segregated from the surface waters and centered deep at low light (≈3.2% surface PAR). Light and temperature were the most influential factors determining the community composition, withSynechococcusdominating ∼74% of the picophytoplankton biovolume in the warmest (>30°C) waters. In the warm and mesotrophic southern Red Sea, the moderate abundances of picoeukaryotes andSynechococcussuggest increasing competition with nano and microphytoplankton. Our observations agree with predictions of increasing vertical segregation of picophytoplankton communities with future warming and revealSynechococcus’s significant capacity to adapt to warming.
Decreased Sulfate Content and Zeta Potential Distinguish Glycosaminoglycans of the Extracellular Matrix of Osteoarthritis Cartilage
Authors: Nunes Rodolfo de Melo , Girão Virgínia Claudia Carneiro , Cunha Pablyana Leila Rodrigues , Feitosa Judith Pessoa Andrade , Pinto Ana Carolina Matias Dinelly , Rocha Francisco Airton Castro
Published: April 2021

We aimed to determine the characteristics that distinguish glycosaminoglycans (GAGs) from osteoarthritis (OA) and normal cartilage and from men and women. Cartilage samples from 30 patients subjected to total joint arthroplasty secondary to OA or fracture (control) were evaluated, and the GAG content (μg/mg dry cartilage) after proteolysis was determined by densitometry, using agarose-gel electrophoresis. Relative percentages of carbon (C), nitrogen (N), and sulfur (S) in GAGs were determined by elemental microanalysis, as well as the zeta potential. Seventeen samples (56.6%) were from patients >70 years old, with 20 (66.6%) from women, and most [20 (66.6%)] were from the hip. The GAG content was similar regardless of patients being >/≤ 70 years old with 96.5 ± 63.5 and 78.5 ± 38.5 μg/mg (P = 0.1917), respectively. GAG content was higher in women as compared to men, with 89.5 ± 34.3 and 51.8 ± 13.3 μg/mg, respectively (P = 0.0022), as well as in OA than fracture samples, with 98.4 ± 63.5 and 63.6 ± 19.6 μg/mg, respectively (P = 0.0355). The GAG extracted from the cartilage of patients >70 years old had increase in N, and there were no gender differences regarding GAG elemental analysis. GAG from OA had a highly significant (P = 0.0005) decrease in S% (1.79% ± 0.25%), as compared to fracture samples (2.3% ± 0.19%), with an associated and significant (P = 0.0001) reduction of the zeta potential in the OA group. This is the first report of a reduced S content in GAG from OA patients, which is associated with a reduced zeta potential.