bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthropometric Measures and Incident Diabetic Nephropathy in Participants With Type 2 Diabetes Mellitus
Authors: Hukportie Daniel Nyarko , Li Fu-Rong , Zhou Rui , Zheng Jia-Zhen , Wu Xiao-Xiang , Wu Xian-Bo
Published: August 2021

Background

The prevalence of diabetes is on the rise globally coupled with its associated complications, such as diabetic nephropathy (DN). Obesity has been identified as a risk factor for the development of DN but it is still unclear which obesity index is the best predictor of incident DN.

Methods

Data from the participants with type 2 diabetes mellitus (T2DM) in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study were used to examine the sex-specific association between waist circumference (WC), waist-to-height ratio (WHtR), and body mass index (BMI) with incident DN risk.

Results

Among the 8,887 participants with T2DM (5,489 men and 3,398 women), 5,296 participants (3,345 men and 1,951 women) developed the DN composite outcome during a follow-up period of 24302 person-years. Among men, null associations were observed between all anthropometric measures with incident DN in the multivariate analysis although the 3rd quartile of WHtR showed marginally significant results (P = 0.052). However, among women, both central and general obesity measures were associated with increased risks of incident DN. Compared with participants in the WC <88 cm category, the fully adjusted HR and 95% CI for those in the ≥88 cm of WC was 1.35 (95% CI 1.15-1.57). Compared with the lowest quartile, the fully adjusted HRs and 95% CIs for the 2nd to the 4th quartile of WHtR were 1.09 (95% CI 0.96-1.25), 1.12 (95% CI 0.98-1.28), and 1.14 (95% CI 1.00-1.30) respectively; also, compared with the normal BMI category, the fully adjusted HRs and 95% CIs for class I – class III obese were 1.36 (95% CI 1.10 – 1.67), 1.43 (95% CI 1.16 – 1.78) and 1.32 (95% CI 1.05 – 1.66) respectively.

Conclusions

Among participants with T2DM, higher levels of both central and general obesity indexes were associated with DN risk among women but not in men. Women with T2DM should maintain a healthy weight targeted at reducing both central and general obesity to enhance nephroprotection. Trial registration: ClinicalTrials.gov., no. NCT00000620.
Causal Effect of Blood Pressure on Bone Mineral Density and Fracture: A Mendelian Randomization Study
Authors: He Bin , Yin Lifeng , Zhang Muzi , Lyu Qiong , Quan Zhengxue , Ou Yunsheng
Published: August 2021

Background

Hypertension may have some association with osteoporosis. This Mendelian randomization (MR) study aimed to explore the causal effect of blood pressure (BP) on bone mineral density (BMD), fall, and fracture.

Methods

We used the genome-wide association study (GWAS) summary data among 330,956 European-descent individuals to identify 107 single-nucleotide polymorphisms (SNPs) as the instrumental variables of BP. MR analyses of these instruments were performed on 53,236 European individuals for the association with forearm BMD (FA-BMD), femoral neck BMD (FN-BMD), and lumbar spine BMD (LS-BMD); 451,179 European individuals for fall susceptibility; and up to 1.2 million individuals from European descent for fracture. Conventional inverse variance weighted (IVW) method was adopted to obtain the causal estimates of BP on different outcomes, while weighted median, MR-egger, and MR pleiotropy residual sum and outlier (MR-PRESSO) test were used for sensitivity analyses.

Results

Genetically high pulse pressure (PP) could significantly improve FA-BMD (beta-estimate: 0.038, 95% confidence interval [CI]: 0.013 to 0.063, SE:0.013, P-value=0.003<Bonferroni correction P) in the IVW analysis, indicating that 1-SD increase in PP was associated with the improvement in FA-BMD levels by 0.038 g/cm2 (95% CI: 0.013 to 0.063). This positive finding was also confirmed by weighted-median analysis (beta-estimate: 0.034, 95% CI: 0.000 to 0.067, SE:0.017, P-value=0.046) and MR-Egger analysis (beta-estimate: 0.117, 95% CI: 0.026 to 0.208, SE:0.046, P-value=0.011). However, there was no remarkable MR association between BP and other outcomes (i.e., FN-BMD, LS-BMD, fall, and fracture).

Conclusions

Our findings reveal a potentially causal relationship between high PP and improved FA-BMD, which may provide new sights for the treatment of osteoporosis.
Research on Improved Fault Current Analysis Method for Flexible Direct Current Power Grid Considering Alternating Current Feed
Authors: Sun Yinfeng , Xiong Xin , Wang Zhenhao , Li Guoqing , Wu Xueguang , Wang Weiru
Published: August 2021

Flexible direct current (DC) grid can realize large-scale renewable energy, wide-area coordinated complementation, and reliable power transmission. It is an important development that can be used to support high-voltage and large-capacity flexible DC transmission in the future. The short-circuit current of the DC line is one of the important bases for the selection of key main equipment parameters such as converter valves, DC circuit breakers, and reactors in the flexible DC grid. In this paper, a flexible DC grid equivalent circuit network model with alternating current (AC) feed-in is established. Aiming at the monopolar ground fault of the flexible DC grid grounded through the metal loop, an optimized traditional matrix calculation method is proposed to obtain the accurate line fault current value. On this basis, with an actual engineering background, the equivalent circuit model of the four-terminal bipolar flexible DC power grid is established, and the influence of grounding position, grounding parameters, and current-limiting reactor on the fault current of the DC line is analyzed. Finally, simulation using the PSCAD software verifies the effectiveness and accuracy of the proposed method. The method proposed in this paper can provide the necessary bases and references for the selection of flexible DC grid equipment.
Lightning Strike Location Identification Based on 3D Weather Radar Data
Authors: Lu Mingyue , Zhang Yadong , Ma Zaiyang , Yu Manzhu , Chen Min , Zheng Jianqin , Wang Menglong
Published: August 2021

Lightning is an instantaneous, intense, and convective weather phenomenon that can produce great destructive power and easily cause serious economic losses and casualties. It always occurs in convective storms with small spatial scales and short life cycles. Weather radar is one of the best operational instruments that can monitor the detailed 3D structures of convective storms at high spatial and temporal resolutions. Thus, extracting the features related to lightning automatically from 3D weather radar data to identify lightning strike locations would significantly benefit future lightning predictions. This article makes a bold attempt to apply three-dimensional radar data to identify lightning strike locations, thereby laying the foundation for the subsequent accurate and real-time prediction of lightning locations. First, that issue is transformed into a binary classification problem. Then, a suitable dataset for the recognition of lightning strike locations based on 3D radar data is constructed for system training and evaluation purposes. Furthermore, the machine learning methods of a convolutional neural network, logistic regression, a random forest, and k-nearest neighbors are employed to carry out experiments. The results show that the convolutional neural network has the best performance in identifying lightning strike locations. This technique is followed by the random forest and k-nearest neighbors, and the logistic regression produces the worst manifestation.
Global Connectivity of Southern Ocean Ecosystems
Authors: Murphy Eugene J. , Johnston Nadine M. , Hofmann Eileen E. , Phillips Richard A. , Jackson Jennifer A. , Constable Andrew J. , Henley Sian F. , Melbourne-Thomas Jessica , Trebilco Rowan , Cavanagh Rachel D. , Tarling Geraint A. , Saunders Ryan A. , Barnes David K. A. , Costa Daniel P. , Corney Stuart P. , Fraser Ceridwen I. , Höfer Juan , Hughes Kevin A. , Sands Chester J. , Thorpe Sally E. , Trathan Philip N. , Xavier José C.
Published: August 2021

Southern Ocean ecosystems are globally important. Processes in the Antarctic atmosphere, cryosphere, and the Southern Ocean directly influence global atmospheric and oceanic systems. Southern Ocean biogeochemistry has also been shown to have global importance. In contrast, ocean ecological processes are often seen as largely separate from the rest of the global system. In this paper, we consider the degree of ecological connectivity at different trophic levels, linking Southern Ocean ecosystems with the global ocean, and their importance not only for the regional ecosystem but also the wider Earth system. We also consider the human system connections, including the role of Southern Ocean ecosystems in supporting society, culture, and economy in many nations, influencing public and political views and hence policy. Rather than Southern Ocean ecosystems being defined by barriers at particular oceanic fronts, ecological changes are gradual due to cross-front exchanges involving oceanographic processes and organism movement. Millions of seabirds and hundreds of thousands of cetaceans move north out of polar waters in the austral autumn interacting in food webs across the Southern Hemisphere, and a few species cross the equator. A number of species migrate into the east and west ocean-basin boundary current and continental shelf regions of the major southern continents. Human travel in and out of the Southern Ocean region includes fisheries, tourism, and scientific vessels in all ocean sectors. These operations arise from many nations, particularly in the Northern Hemisphere, and are important in local communities as well as national economic, scientific, and political activities. As a result of the extensive connectivity, future changes in Southern Ocean ecosystems will have consequences throughout the Earth system, affecting ecosystem services with socio-economic impacts throughout the world. The high level of connectivity also means that changes and policy decisions in marine ecosystems outside the Southern Ocean have consequences for ecosystems south of the Antarctic Polar Front. Knowledge of Southern Ocean ecosystems and their global connectivity is critical for interpreting current change, projecting future change impacts, and identifying integrated strategies for conserving and managing both the Southern Ocean and the broader Earth system.
Phylogenetic Diversity of Urban Floras in the Central Urals
Authors: Tretyakova Alyona S. , Yakimov Basil N. , Kondratkov Pavel V. , Grudanov Nickolay Yu. , Cadotte Marc W.
Published: August 2021

Modern cities harbor a high diversity of plants, and urban floras are significantly different from non-urban floras especially when considering the proportion of alien species found in cities. However, it is not clear whether urban areas disproportionately select for species from relatively few evolutionary lineages or provide opportunities for species across the full spectrum of plant lineages. Here, we examined the taxonomic and phylogenetic diversity of the floras in four cities (Yekaterinburg, Kamensk-Uralsky, Krasnoufimsk, and Turinsk) in the understudied region of Central Urals (Russian Federation). We classified native species into indigenous and apophytic species, namely, those that are sensitive to anthropogenic disturbance and those that have expanded their range with human activity, respectively. Alien species were classified into archaeophytes and neophytes according to when they were introduced (i.e., before or after than 1800). Phylogenetic diversity was quantified using Faith’s index to reflect total evolutionary history in urban areas and mean phylogenetic distance (MPD) to reflect species dissimilarity. Phylogenetic diversity of native species was higher than that for alien species, and the standardized effect size (SES) of MPD for natives was positive, reflecting their general dissimilarity from one another, while it was very negative for aliens, showing that they were phylogenetically clustered. However, among natives, apophytes were significantly clustered, while indigenous species were overdispersed. For the aliens, MPD was higher for archaeophytes compared to neophytes, though both groups were significantly clustered. These results show that urbanization leads to a non-random selection of plants. Apophytes and alien plants were composed of closely related species, reflecting similar ecological traits and are likely to be pre-adapted to the environmentally altered and highly disturbed urban environment.
Low Diversity and Strong Genetic Structure Between Feeding and Nesting Areas in Brazil for the Critically Endangered Hawksbill Sea Turtle
Authors: Simões Thyara Noely , Santos Ednilza Maranhão dos , Santos Alesandro Souza , Gaiotto Fernanda Amato , Costa Marco Antônio , Assis Elza Thaynara Cardoso de Menezes , Neves Vivian Chimendes da Silva , Magalhães Werlanne Mendes de Santana , Mascarenhas Rita , Bonfim Waltyane Alves Gomes , Neves Juliede Nonato , Solé Mirco
Published: August 2021

Marine turtle nesting areas are characterized by receiving several females every year. The species Eretmochelys imbricata, known as hawksbill turtle is listed as Critically Endangered by the IUCN, and has been the target of studies on genetic structure and population diversity in nesting areas. Therefore, this study aimed to analyze the genetic diversity and haplotype composition of populations sampled in nesting areas from the coast of northeastern Brazil based on the mtDNA D-loop region. We used genetic information and compared it with data from feeding areas available in public databases. We recorded a total of six exclusive haplotypes in the nesting areas and 27 exclusive haplotypes for the feeding areas. The H_1 haplotype was shared in all nesting areas. The turtles of these regions had a low diversity and a genetic structure composed of five divergent groups separating the reproductive areas from the ones of feeding areas. Positive and significant geographical distance relationships were also recorded with FST values (r = 0.2302, p = 0.007). Our results revealed that hawksbill turtles from reproductive areas comprise a single population that needs management strategies to protect the threatened species, in addition to providing information that contributes to future actions for the species conservation.
Foraging and Drifting Patterns of the Highly Eusocial Neotropical Stingless Bee Melipona fasciculata Assessed by Radio-Frequency Identification Tags
Authors: Oliveira Ricardo Caliari , Contrera Felipe Andrés León , Arruda Helder , Jaffé Rodolfo , Costa Luciano , Pessin Gustavo , Venturieri Giorgio Cristino , de Souza Paulo , Imperatriz-Fonseca Vera Lúcia
Published: August 2021

Bees play a key role in ecosystem services as the main pollinators of numerous flowering plants. Studying factors influencing their foraging behavior is relevant not only to understand their biology, but also how populations might respond to changes in their habitat and to the climate. Here, we used radio-frequency identification tags to monitor the foraging behavior of the neotropical stingless beeMelipona fasciculatawith special interest in drifting patterns i.e., when a forager drifts into a foreign nest. In addition, we collected meteorological data to study how abiotic factors affect bees’ activity and behavior. Our results show that only 35% of bees never drifted to another hive nearby, and that factors such as temperature, humidity and solar irradiation affected the bees drifting rates and/or foraging activity. Moreover, we tested whether drifting levels would decrease after marking the nest entrances with different patterns. However, contrary to our predictions, there was an increase in the proportion of drifting, which could indicate factors other than orientation mistakes playing a role in this behavior. Overall, our results demonstrate how managed bee populations are affected by both nearby hives and climate factors, offering insights on their biology and potential commercial application as crop pollinators.
A Multi-Criteria Decision Support System for Strategic Planning at the Swiss Forest Enterprise Level: Coping With Climate Change and Shifting Demands in Ecosystem Service Provisioning
Authors: Thrippleton Timothy , Blattert Clemens , Bont Leo Gallus , Mey Reinhard , Zell Jürgen , Thürig Esther , Schweier Janine
Published: August 2021

Sustainable forest management plays a key role for forest biodiversity and the provisioning of ecosystem services (BES), including the important service of carbon sequestration for climate change mitigation. Forest managers, however, find themselves in the increasingly complex planning situation to balance the often conflicting demands in BES. To cope with this situation, a prototype of a decision support system (DSS) for strategic (long-term) planning at the forest enterprise level was developed in the present project. The DSS was applied at three case study enterprises (CSEs) in Northern Switzerland, two lowland and one higher-elevation enterprise, for a 50-year time horizon (2010 to 2060) under present climate and three climate change scenarios (‘wet’, ‘medium’, ‘dry’). BES provisioning (for biodiversity, timber production, recreation, protection against gravitational hazards and carbon sequestration) was evaluated for four management scenarios (no management, current (BAU), lower and higher management intensity) using a utility-based multi-criteria decision analysis. Additionally, four alternative preference scenarios for BES provisioning were investigated to evaluate the robustness of the results to shifting BES preferences. At all CSEs, synergies between carbon sequestration, biodiversity and protection function as well as trade-offs between carbon sequestration and timber production occurred. The BAU management resulted in the highest overall utility in 2060 for different climate and BES preference scenarios, with the exception of one lowland CSE under current BES preference, where a lower intensity management performed best. Although climate change had a relatively small effect on overall utility, individual BES indicators showed a negative climate change impact for the lowland CSEs and a positive effect for the higher elevation CSE. The patterns of overall utility were relatively stable to shifts in BES preferences, with exception of a shift toward a preference for carbon sequestration. Overall, the study demonstrates the potential of the DSS to investigate the development of multiple BES as well as their synergies and trade-offs for a set of lowland and mountainous forest enterprises. The new system incorporates a wide set of BES indicators, a strong empirical foundation and a flexible multi-criteria decision analysis, enabling stakeholders to take scientifically well-founded decisions under changing climatic conditions and political goals.
Beyond Tropical Storms: Understanding Disturbance and Forest Dynamics
Authors: Heartsill-Scalley Tamara , López-Marrero Tania
Published: August 2021

Most of the knowledge of tropical storm effects on forests is from studies conducted in reserves and protected areas. Effects on other settings such as urban forests, coastal forests, and in landscapes with mixed land uses and covers are, comparatively, less studied. Yet research from a range of forest types and landscape compositions is needed to inform actions associated with management, mitigation, or restoration efforts before and after storms. Studies of forests comprising various conditions, along with long-term observations, would offer unique insights into the varied and cumulative effects of tropical storms on forest ecosystems. The Caribbean island of Puerto Rico is one of the sites where most tropical storm-forest studies are conducted, yet studies come from a limited set of sites. Using Puerto Rico as a case study, we emphasize the need for broader research approaches that represent the wider range of forests that are exposed to tropical storms. Such an approach will provide valuable knowledge and understanding needed to inform and take actions across landscape settings, forest context, and socio-environmental conditions.
A Call for a Better Understanding of Aquatic Chytrid Biology
Authors: Laundon Davis , Cunliffe Michael
Published: August 2021

The phylum Chytridiomycota (the “chytrids”) is an early-diverging, mostly unicellular, lineage of fungi that consists of significant aquatic saprotrophs, parasites, and pathogens, and is of evolutionary interest because its members retain biological traits considered ancestral in the fungal kingdom. While the existence of aquatic chytrids has long been known, their fundamental biology has received relatively little attention. We are beginning to establish a detailed understanding of aquatic chytrid diversity and insights into their ecological functions and prominence. However, the underpinning biology governing their aquatic ecological activities and associated core processes remain largely understudied and therefore unresolved. Many biological questions are outstanding for aquatic chytrids. What are the mechanisms that control their development and life cycle? Which core processes underpin their aquatic influence? What can their biology tell us about the evolution of fungi and the wider eukaryotic tree of life? We propose that the field of aquatic chytrid ecology could be further advanced through the improved understanding of chytrid biology, including the development of model aquatic chytrids and targeted studies using culture-independent approaches.
Bioinformatics Analysis Identifies Molecular Markers Regulating Development and Progression of Endometriosis and Potential Therapeutic Drugs
Authors: Peng Ying , Peng Cheng , Fang Zheng , Chen Gang
Published: August 2021

Endometriosis, a common disease that presents as polymorphism, invasiveness, and extensiveness, with clinical manifestations including dysmenorrhea, infertility, and menstrual abnormalities, seriously affects quality of life in women. To date, its underlying etiological mechanism of action and the associated regulatory genes remain unclear. This study aimed to identify molecular markers and elucidate mechanisms underlying the development and progression of endometriosis. Specifically, we downloaded five microarray expression datasets, namely, GSE11691, GSE23339, GSE25628, GSE7305, and GSE105764, from the Gene Expression Omnibus (GEO) database. These datasets, obtained from endometriosis tissues, alongside normal controls, were subjected to in-depth bioinformatics analysis for identification of differentially expressed genes (DEGs), followed by analysis of their function and pathways via gene ontology (GO) and KEGG pathway enrichment analyses. Moreover, we constructed a protein–protein interaction (PPI) network to explore the hub genes and modules, and then applied machine learning algorithms support vector machine-recursive feature elimination and least absolute shrinkage and selection operator (LASSO) analysis to identify key genes. Furthermore, we adopted the CIBERSORTx algorithm to estimate levels of immune cell infiltration while the connective map (CMAP) database was used to identify potential therapeutic drugs in endometriosis. As a result, a total of 423 DEGs, namely, 233 and 190 upregulated and downregulated, were identified. On the other hand, a total of 1,733 PPIs were obtained from the PPI network. The DEGs were mainly enriched in immune-related mechanisms. Furthermore, machine learning and LASSO algorithms identified three key genes, namely, apelin receptor (APLNR), C–C motif chemokine ligand 21 (CCL21), and Fc fragment of IgG receptor IIa (FCGR2A). Furthermore, 16 small molecular compounds associated with endometriosis treatment were identified, and their mechanism of action was also revealed. Taken together, the findings of this study provide new insights into the molecular factors regulating occurrence and progression of endometriosis and its underlying mechanism of action. The identified therapeutic drugs and molecular markers may have clinical significance in early diagnosis of endometriosis.
Systematic Analysis Identifies a Specific RNA-Binding Protein-Related Gene Model for Prognostication and Risk-Adjustment in HBV-Related Hepatocellular Carcinoma
Authors: Li Maoshi , Liu Zhongwei , Wang Jing , Liu Huimin , Gong Hongmei , Li Shilian , Jia Ming , Mao Qing
Published: August 2021

Objective

Increasing evidence shows that dysregulated RNA binding proteins (RBPs) modulate the progression of several malignancies. Nevertheless, their clinical implications of RBPs in HBV-related hepatocellular carcinoma (HCC) remain largely undefined. Here, this study systematically analyzed the associations of RBPs with HBV-related HCC prognosis.

Methods

Based on differentially expressed RBPs between HBV-related HCC and control specimens, prognosis-related RBPs were screened by univariate analyses. A LASSO model was then created. Kaplan-Meier curves, ROCs, multivariate analyses, subgroup analyses and external verification were separately applied to assess the efficacy of this model in predicting prognosis and recurrence of patients. A nomogram was created by incorporating the model and clinical indicators, which was verified by ROCs, calibration curves and decision curve analyses. By CIBERSORT algorithm, the association between the risk score and immune cell infiltrations was evaluated.

Results

Totally, 54 RBPs were distinctly correlated to prognosis of HBV-related HCC. An 11-RBP model was created, containing POLR2L, MRPS12, DYNLL1, ZFP36, PPIH, RARS, SRP14, DDX41, EIF2B4, and NOL12. This risk score sensitively and accurately predicted one-, three- and five-year overall survival, disease-free survival, and progression-free interval. Compared to other clinical parameters, this risk score had the best predictive efficacy. Also, the clinical generalizability of the model was externally verified in the GSE14520 dataset. The nomogram may predict patients’ survival probabilities. Also, the risk score was related to the components in the immune microenvironment.

Conclusion

Collectively, RBPs may act as critical elements in the malignant progression of HBV-related HCC and possess potential implications on prognostication and therapy decision.
Predictive Value of the TP53/PIK3CA/ATM Mutation Classifier for Patients With Bladder Cancer Responding to Immune Checkpoint Inhibitor Therapy
Authors: Pan Yi-Hui , Zhang Jia-Xing , Chen Xu , Liu Fei , Cao Jia-Zheng , Chen Yu , Chen Wei , Luo Jun-Hang
Published: August 2021

Background

Only a proportion of patients with bladder cancer may benefit from durable response to immune checkpoint inhibitor (ICI) therapy. More precise indicators of response to immunotherapy are warranted. Our study aimed to construct a more precise classifier for predicting the benefit of immune checkpoint inhibitor therapy.

Methods

This multi-cohort study examined the top 20 frequently mutated genes in five cohorts of patients with bladder cancer and developed the TP53/PIK3CA/ATM mutation classifier based on the MSKCC ICI cohort. The classifier was then validated in a validation set consisting of IMvigor210 cohort and Broad/Dana-Farber cohort. The molecular profile and immune infiltration characteristics in each subgroup as defined by this classifier were explored.

Results

Among all 881 patients with bladder cancer, the mutation frequency of TP53, PIK3CA, and ATM ranked in the top 20 mutated genes. The TP53/PIK3CA/ATM mutation classifier was constructed based on the Memorial Sloan Kettering Cancer Center (MSKCC) ICI cohort and only showed predictive value for patients with bladder cancer who received ICI therapy (median overall survival: low-risk group, not reached; moderate-risk group, 13.0 months; high-risk group, 8.0 months; P<0.0001). Similar results were found in subgroups of MSKCC ICI cohort defined by tumor mutation burden. Multivariate Cox analysis revealed that the risk group defined by the classifier served as an independent prognostic factor for overall survival in patients with bladder cancer. Efficacy of the classifier was verified in a validation set consisting of IMvigor210 cohort and Broad/Dana-Farber cohort. Lower expression of PD-1/PD-L1 and less tumor immune infiltration were observed in the high-risk group than the other two groups of the TCGA cohort and the IMvigor210 cohort.

Conclusion

Our study constructed a TP53/PIK3CA/ATM mutation classifier to predict the benefit of immune checkpoint inhibitor therapy for patients with bladder cancer. This classifier can potentially complement the tumor mutation burden and guide clinical ICI treatment decisions according to distinct risk levels.
Visceral Adipose Tissue: A New Target Organ in Virus-Induced Type 1 Diabetes
Authors: Zipris Danny
Published: August 2021

Type 1 diabetes (T1D) is a proinflammatory pathology that leads to the specific destruction of insulin producing β-cells and hyperglycaemia. Much of the knowledge about type 1 diabetes (T1D) has focused on mechanisms of disease progression such as adaptive immune cells and the cytokines that control their function, whereas mechanisms linked with the initiation of the disease remain unknown. It has been hypothesized that in addition to genetics, environmental factors play a pivotal role in triggering β-cell autoimmunity. The BioBreeding Diabetes Resistant (BBDR) and LEW1.WR1 rats have been used to decipher the mechanisms that lead to virus-induced T1D. Both animals develop β-cell inflammation and hyperglycemia upon infection with the parvovirus Kilham Rat Virus (KRV). Our earlier in vitro and in vivo studies indicated that KRV-induced innate immune upregulation early in the disease course plays a causal role in triggering β-cell inflammation and destruction. Furthermore, we recently found for the first time that infection with KRV induces inflammation in visceral adipose tissue (VAT) detectable as early as day 1 post-infection prior to insulitis and hyperglycemia. The proinflammatory response in VAT is associated with macrophage recruitment, proinflammatory cytokine and chemokine upregulation, endoplasmic reticulum (ER) and oxidative stress responses, apoptosis, and downregulation of adipokines and molecules that mediate insulin signaling. Downregulation of inflammation suppresses VAT inflammation and T1D development. These observations are strikingly reminiscent of data from obesity and type 2 diabetes (T2D) in which VAT inflammation is believed to play a causal role in disease mechanisms. We propose that VAT inflammation and dysfunction may be linked with the mechanism of T1D progression.
Intestinal Regulatory T Cells as Specialized Tissue-Restricted Immune Cells in Intestinal Immune Homeostasis and Disease
Authors: Jacobse Justin , Li Jing , Rings Edmond H. H. M. , Samsom Janneke N. , Goettel Jeremy A.
Published: August 2021

FOXP3+regulatory T cells (Treg cells) are a specialized population of CD4+T cells that restrict immune activation and are essential to prevent systemic autoimmunity. In the intestine, the major function of Treg cells is to regulate inflammation as shown by a wide array of mechanistic studies in mice. While Treg cells originating from the thymus can home to the intestine, the majority of Treg cells residing in the intestine are induced from FOXP3negconventional CD4+T cells to elicit tolerogenic responses to microbiota and food antigens. This process largely takes place in the gut draining lymph nodesviainteraction with antigen-presenting cells that convert circulating naïve T cells into Treg cells. Notably, dysregulation of Treg cells leads to a number of chronic inflammatory disorders, including inflammatory bowel disease. Thus, understanding intestinal Treg cell biology in settings of inflammation and homeostasis has the potential to improve therapeutic options for patients with inflammatory bowel disease. Here, the induction, maintenance, trafficking, and function of intestinal Treg cells is reviewed in the context of intestinal inflammation and inflammatory bowel disease. In this review we propose intestinal Treg cells do not compose fixed Treg cell subsets, but rather (like T helper cells), are plastic and can adopt different programs depending on microenvironmental cues.
High Species Richness and Extremely Low Abundance of Cumacean Communities Along the Shelf and Slope of the Gulf of Guinea (West Africa)
Authors: Stȩpień Anna , Pabis Krzysztof , Sobczyk Robert , Serigstad Bjorn
Published: August 2021

The Gulf of Guinea belongs to the most scarcely sampled marine basins in the oceans of the world. We have analyzed diversity and distribution patterns of cumacean communities on the shelf and slope, along the coast of Ghana. The material was collected in October and November of 2012 using a van Veen grab (0.1 m2) on nine transects. Six stations were located at each transect (25, 50, 100, 250, 500, and 1,000 m). Sixty-three species of Cumacea were recorded withLeuconandEocumaas the most speciose genera, with 12 and eight species, respectively. Comparisons of species richness with literature data pointed that the Ghanaian coast hosts very diverse communities. About 95% of species were new to science, and the number of cumacean species known from the West Africa increased by over 100%. Nevertheless, most of the species had extremely low abundance, 13 singletons and 15 doubletons were found. Mean density of cumaceans was estimated at only 1.5 ind./0.1 m2. Species accumulation curve did not reach the asymptotic level, suggesting undersampling, despite the fact that sampling effort was high (250 samples). The highest species richness was recorded in the inner shelf (25–50 m) and on the slope (1,000 m). Cluster analysis separated shallow water communities from deeper regions on the shelf and upper slope. The most unique species composition was found at 1,000 m. Principal component analysis showed the importance of oxygen, sediments, and human-related disturbance for distribution of cumacean communities. In the shallows, oxygen content and presence of gravel were the most important factors structuring communities. In the deeper bottom areas (250–1,000 m), cumacean fauna was affected by local pollution, mainly by higher concentration of barium, other heavy metals, and THC.
The Phospholipid N-Methyltransferase and Phosphatidylcholine Synthase Pathways and the ChoXWV Choline Uptake System Involved in Phosphatidylcholine Synthesis Are Widely Conserved in Most, but Not All Brucella Species
Authors: Aragón-Aranda Beatriz , Palacios-Chaves Leyre , Salvador-Bescós Miriam , de Miguel María Jesús , Muñoz Pilar M. , Vences-Guzmán Miguel Ángel , Zúñiga-Ripa Amaia , Lázaro-Antón Leticia , Sohlenkamp Christian , Moriyón Ignacio , Iriarte Maite , Conde-Álvarez Raquel
Published: August 2021

The brucellae are facultative intracellular bacteria with a cell envelope rich in phosphatidylcholine (PC). PC is abundant in eukaryotes but rare in prokaryotes, and it has been proposed that Brucella uses PC to mimic eukaryotic-like features and avoid innate immune responses in the host. Two PC synthesis pathways are known in prokaryotes: the PmtA-catalyzed trimethylation of phosphatidylethanolamine and the direct linkage of choline to CDP-diacylglycerol catalyzed by the PC synthase Pcs. Previous studies have reported that B. abortus and B. melitensis possess non-functional PmtAs and that PC is synthesized exclusively via Pcs in these strains. A putative choline transporter ChoXWV has also been linked to PC synthesis in B. abortus. Here, we report that Pcs and Pmt pathways are active in B. suis biovar 2 and that a bioinformatics analysis of Brucella genomes suggests that PmtA is only inactivated in B. abortus and B. melitensis strains. We also show that ChoXWV is active in B. suis biovar 2 and conserved in all brucellae except B. canis and B. inopinata. Unexpectedly, the experimentally verified ChoXWV dysfunction in B. canis did not abrogate PC synthesis in a PmtA-deficient mutant, which suggests the presence of an unknown mechanism for obtaining choline for the Pcs pathway in Brucella. We also found that ChoXWV dysfunction did not cause attenuation in B. suis biovar 2. The results of these studies are discussed with respect to the proposed role of PC in Brucella virulence and how differential use of the Pmt and Pcs pathways may influence the interactions of these bacteria with their mammalian hosts.
Cloning, Heterologous Expression, and Characterization of a βκ-Carrageenase From Marine Bacterium Wenyingzhuangia funcanilytica: A Specific Enzyme for the Hybrid Carrageenan–Furcellaran
Authors: Cao Siqi , Zhang Yuying , Chen Guangning , Shen Jingjing , Han Jin , Chang Yaoguang , Xiao Hang , Xue Changhu
Published: August 2021

Carrageenan is a group of important food polysaccharides with high structural heterogeneity. Furcellaran is a typical hybrid carrageenan, which contains the structure consisted of alternative β-carrageenan and κ-carrageenan motifs. Although several furcellaran-hydrolyzing enzymes have been characterized, their specificity for the glycosidic linkage was still unclear. In this study, we cloned, expressed, and characterized a novel GH16_13 furcellaran-hydrolyzing enzyme Cgbk16A_Wf from the marine bacterium Wenyingzhuangia fucanilytica CZ1127. Cgbk16A_Wf exhibited its maximum activity at 50°C and pH 6.0 and showed high thermal stability. The oligosaccharides in enzymatic products were identified by liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. It was confirmed that Cgbk16A_Wf specifically cleaves the β-1,4 linkages between β-carrageenan and κ-carrageenan motifs from non-reducing end to reducing end. Considering the structural heterogeneity of carrageenan and for the unambiguous indication of the specificity, we recommended to name the furcellaran-hydrolyzing activity represented by Cgbk16A as “βκ-carrageenase” instead of “furcellaranase”.
Hanseniaspora vineae and the Concept of Friendly Yeasts to Increase Autochthonous Wine Flavor Diversity
Authors: Carrau Francisco , Henschke Paul A.
Published: August 2021

In this perspective, we will explain the concept of “friendly” yeasts for developing wine starters that do not suppress desirable native microbial flora at the initial steps of fermentation, as what usually happens with Saccharomyces strains. Some non-Saccharomyces strains might allow the development of yeast consortia with the native terroir microflora of grapes and its region. The positive contribution of non-Saccharomyces yeasts was underestimated for decades. Avoiding them as spoilage strains and off-flavor producers was the main objective in winemaking. It is understandable, as in our experience after more than 30 years of wine yeast selection, it was shown that no more than 10% of the isolated native strains were positive contributors of superior flavors. Some species that systematically gave desirable flavors during these screening processes were Hanseniaspora vineae and Metschnikowia fructicola. In contrast to the latter, H. vineae is an active fermentative species, and this fact helped to build an improved juice ecosystem, avoiding contaminations of aerobic bacteria and yeasts. Furthermore, this species has a complementary secondary metabolism with S. cerevisiae, increasing flavor complexity with benzenoid and phenylpropanoid synthetic pathways practically inexistent in conventional yeast starters. How does H. vineae share the fermentation niche with other yeast strains? It might be due to the friendly conditions it creates, such as ideal low temperatures and low nitrogen demand during fermentation, reduced synthesis of medium-chain fatty acids, and a rich acetylation capacity of aromatic higher alcohols, well-known inhibitors of many yeasts. We will discuss here how inoculation of H. vineae strains can give the winemaker an opportunity to develop ideal conditions for flavor expression of the microbial terroir without the risk of undesirable strains that can result from spontaneous yeast fermentations.
Streptomyces tardus sp. nov.: A Slow-Growing Actinobacterium Producing Candicidin, Isolated From Sediments of the Trondheim Fjord
Authors: Králová Stanislava , Sandoval-Powers Megan , Fawwal Dorelle V. , Degnes Kristin F. , Lewin Anna Sofia , Klinkenberg Geir , Nguyen Giang-Son , Liles Mark R. , Wentzel Alexander
Published: August 2021

Marine environments are home to an extensive number of microorganisms, many of which remain unexplored for taxonomic novelty and functional capabilities. In this study, a slow-growing Streptomyces strain expressing unique genomic and phenotypic characteristics, P38-E01T, was described using a polyphasic taxonomic approach. This strain is part of a collection of over 8,000 marine Actinobacteria isolates collected in the Trondheim fjord of Norway by SINTEF Industry (Trondheim, Norway) and the Norwegian University of Science and Technology (NTNU, Trondheim, Norway). Strain P38-E01T was isolated from the sediments of the Trondheim fjord, and phylogenetic analyses affiliated this strain with the genus Streptomyces, but it was not closely affiliated with other described species. The closest related type strains were Streptomyces daliensis YIM 31724T (98.6%), Streptomyces rimosus subsp. rimosus ATCC 10970T (98.4%), and Streptomyces sclerotialus NRRL ISP-5269T (98.3%). Predominant fatty acids were C16:0 iso, C16:0, and Summed Feature 3, and the predominant respiratory quinones were MK-10(H6), MK-10(H4), and MK9(H4). The main polar lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, and phosphoglycolipid. The whole-cell sugars were glucose, ribose, and in minor amounts, mannose. The cell wall peptidoglycan contained LL-diaminopimelic acid. The draft genome has a size of 6.16 Mb, with a %G + C content of 71.4% and is predicted to contain at least 19 biosynthetic gene clusters encoding diverse secondary metabolites. Strain P38-E01T was found to inhibit the growth of the pathogenic yeast Candida albicans ATCC 90028 and a number of Gram-positive bacterial human and plant pathogens. Metabolites extracted from cultures of P38-E01T were analyzed by mass spectrometry, and it was found that the isolate produced the antifungal compound candicidin. Phenotypic and chemotaxonomic signatures, along with phylogenetic analyses, distinguished isolate P38-E01T from its closest neighbors; thus, this isolate represents a novel species of the genus Streptomyces for which the name Streptomyces tardus sp. nov. (P38-E01T = CCM 9049T = DSM 111582T) is proposed.
Dietary Tributyrin Administration Improves Intestinal Morphology and Selected Bacterial and Short-Chain Fatty Acid Profiles in Broilers Under an Isocaloric Feeding Regime
Authors: Hu Qunbing , Yin Fugui , Li Baocheng , Guo Yuming , Yin Yulong
Published: August 2021

The current study was conducted to investigate the effect of dietary tributyrin (TB) administration on the intestinal and growth performances in Arbor Acres (AA) broilers under an isocaloric feeding regime. A total of 540 day-old healthy AA broilers were randomly assigned to five treatments with 12 replicates (pens) per treatment and nine birds per pen for 42 days. The dietary treatments were basal diet (control) and basal diet with TB at doses of 0.23 g/kg (TB1), 0.46 g/kg (TB2), 0.92 g/kg (TB3), and 1.84 g/kg (TB4). Particularly, to achieve the isocaloric and cost-saving experimental diets, soybean oil was replaced by the TB product (Eucalorie®) with equivalent metabolic energy contents, and the formulas were rebalanced with zeolite to get the sum of all the feed ingredients to 100%. On days 21 and 42, after weighing, the birds (one bird per replicate) whose body weight was close to the replicate average were euthanized to investigate the effect of dietary TB on intestinal morphology, intestinal bacterial population, and short-chain fatty acid contents. The results revealed that dietary TB administration increased the average daily gain, gain/feed ratio, and European broiler index (P < 0.05) and improved the intestinal morphology (P < 0.05) as indicated by higher villus height and the ratios of villus height/crypt depth in broilers. The incremental levels of TB increased the ileal Lactobacillus content (P = 0.05) and cecal Bacillus content (P = 0.02), respectively. Moreover, dietary TB administration also increased the contents of most of the selected short-chain fatty acids in ileal and cecal digesta (P < 0.05). Collectively, dietary TB administration quadratically improved the growth performance, intestinal morphology, beneficial bacterial population, and short-chain fatty acid levels under the isocaloric feeding regime, indicating better profit return potential in practical poultry operation.
Transcriptomic Profile of Mycobacterium smegmatis in Response to an Imidazo[1,2-b][1,2,4,5]tetrazine Reveals Its Possible Impact on Iron Metabolism
Authors: Vatlin Aleksey A. , Shitikov Egor A. , Shahbaaz Mohd , Bespiatykh Dmitry A. , Klimina Ksenia M. , Christoffels Alan , Danilenko Valery N. , Maslov Dmitry A.
Published: August 2021

Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex bacteria, is one of the most pressing health problems. The development of new drugs and new therapeutic regimens effective against the pathogen is one of the greatest challenges in the way of tuberculosis control. Imidazo[1,2-b][1,2,4,5]tetrazines have shown promising activity against M. tuberculosis and M. smegmatis strains. Mutations in MSMEG_1380 lead to mmpS5–mmpL5 operon overexpression, which provides M. smegmatis with efflux-mediated resistance to imidazo[1,2-b][1,2,4,5]tetrazines, but the exact mechanism of action of these compounds remains unknown. To assess the mode of action of imidazo[1,2-b][1,2,4,5]tetrazines, we analyzed the transcriptomic response of M. smegmatis to three different concentrations of 3a compound: 1/8×, 1/4×, and 1/2× MIC. Six groups of genes responsible for siderophore synthesis and transport were upregulated in a dose-dependent manner, while virtual docking revealed proteins involved in siderophore synthesis as possible targets for 3a. Thus, we suggest that imidazo[1,2-b][1,2,4,5]tetrazines may affect mycobacterial iron metabolism.
Distinct Neural Substrates Support Phonological and Orthographic Working Memory: Implications for Theories of Working Memory
Authors: Purcell Jeremy , Rapp Brenda , Martin Randi C.
Published: August 2021

Prior behavioral and neuroimaging evidence supports a separation between working memory capacities in the phonological and orthographic domains. Although these data indicate distinct buffers for orthographic and phonological information, prior neural evidence does indicate that nearby left inferior parietal regions support both of these working memory capacities. Given that no study has directly compared their neural substrates based on data from the same individuals, it is possible that there is a common left inferior parietal region shared by both working memory capacities. In fact, those endorsing an embedded processes account of working memory might suggest that parietal involvement reflects a domain-general attentional system that directs attention to long-term memory representations in the two domains, implying that the same neural region supports the two capacities. Thus, in this work, a multivariate lesion-symptom mapping approach was used to assess the neural basis of phonological and orthographic working memory using behavioral and lesion data from the same set of 37 individuals. The results showed a separation of the neural substrates, with regions in the angular gyrus supporting orthographic working memory and with regions primarily in the supramarginal gyrus supporting phonological working memory. The results thus argue against the parietal involvement as supporting a domain-general attentional mechanism and support a domain-specific buffer account of working memory.