bluuebunny/crossref_metadata_2025 huggingface dataset:
Functions of Oxysterol-Binding Proteins at Membrane Contact Sites and Their Control by Phosphoinositide Metabolism
Authors: Nakatsu Fubito , Kawasaki Asami
Published: June 2021

Lipids must be correctly transported within the cell to the right place at the right time in order to be fully functional. Non-vesicular lipid transport is mediated by so-called lipid transfer proteins (LTPs), which contain a hydrophobic cavity that sequesters lipid molecules. Oxysterol-binding protein (OSBP)-related proteins (ORPs) are a family of LTPs known to harbor lipid ligands, such as cholesterol and phospholipids. ORPs act as a sensor or transporter of those lipid ligands at membrane contact sites (MCSs) where two different cellular membranes are closely apposed. In particular, a characteristic functional property of ORPs is their role as a lipid exchanger. ORPs mediate counter-directional transport of two different lipid ligands at MCSs. Several, but not all, ORPs transport their lipid ligand from the endoplasmic reticulum (ER) in exchange for phosphatidylinositol 4-phosphate (PI4P), the other ligand, on apposed membranes. This ORP-mediated lipid “countertransport” is driven by the concentration gradient of PI4P between membranes, which is generated by its kinases and phosphatases. In this review, we will discuss how ORP function is tightly coupled to metabolism of phosphoinositides such as PI4P. Recent progress on the role of ORP-mediated lipid transport/countertransport at multiple MCSs in cellular functions will be also discussed.
Involvement of TRP Channels in Adipocyte Thermogenesis: An Update
Authors: Sun Wuping , Luo Yixuan , Zhang Fei , Tang Shuo , Zhu Tao
Published: June 2021

Obesity prevalence became a severe global health problem and it is caused by an imbalance between energy intake and expenditure. Brown adipose tissue (BAT) is a major site of mammalian non-shivering thermogenesis or energy dissipation. Thus, modulation of BAT thermogenesis might be a promising application for body weight control and obesity prevention. TRP channels are non-selective calcium-permeable cation channels mainly located on the plasma membrane. As a research focus, TRP channels have been reported to be involved in the thermogenesis of adipose tissue, energy metabolism and body weight regulation. In this review, we will summarize and update the recent progress of the pathological/physiological involvement of TRP channels in adipocyte thermogenesis. Moreover, we will discuss the potential of TRP channels as future therapeutic targets for preventing and combating human obesity and related-metabolic disorders.
Nasal Septum Deviation as the Consequence of BMP-Controlled Changes to Cartilage Properties
Authors: Baddam Pranidhi , Young Daniel , Dunsmore Garett , Nie Chunpeng , Eaton Farah , Elahi Shokrollah , Jovel Juan , Adesida Adetola B. , Dufour Antoine , Graf Daniel
Published: June 2021

The nasal septum cartilage is a specialized hyaline cartilage important for normal midfacial growth. Abnormal midfacial growth is associated with midfacial hypoplasia and nasal septum deviation (NSD). However, the underlying genetics and associated functional consequences of these two anomalies are poorly understood. We have previously shown that loss of Bone Morphogenetic Protein 7 (BMP7) from neural crest (BMP7ncko) leads to midfacial hypoplasia and subsequent septum deviation. In this study we elucidate the cellular and molecular abnormalities underlying NSD using comparative gene expression, quantitative proteomics, and immunofluorescence analysis. We show that reduced cartilage growth and septum deviation are associated with acquisition of elastic cartilage markers and share similarities with osteoarthritis (OA) of the knee. The genetic reduction of BMP2 in BMP7ncko mice was sufficient to rescue NSD and suppress elastic cartilage markers. To our knowledge this investigation provides the first genetic example of an in vivo cartilage fate switch showing that this is controlled by the relative balance of BMP2 and BMP7. Cellular and molecular changes similar between NSD and knee OA suggest a related etiology underlying these cartilage abnormalities.
Enhanced Catalysis of P-doped SnO2 for the V2+/V3+ Redox Reaction in Vanadium Redox Flow Battery
Authors: Feng Xiaojian , Zhang Zixuan , Zhang Tongxue , Xue Jing , Han Chao , Dai Lei , Wang Ling , He Zhangxing
Published: June 2021

In this work, nanosized P-doped SnO2 (SnO2-P) was prepared by a sol–gel method as a catalyst for the V3+/V2+ redox reaction in vanadium redox flow battery. Compared with SnO2, the electrochemical performance of SnO2-P is significantly improved. This is because P doping provides more active sites and shows greatly improved electrical conductivity, thereby increasing the electron transfer rate. As a result, SnO2-P shows better catalytic performance than SnO2. The SnO2-P modified cell is designed, and it exhibits an increase of 47.2 mA h in discharge capacity and 8.7% in energy efficiency compared with the pristine cell at 150 mA cm−2. These increases indicate that the modified cell has a higher electrolyte utilization rate. This study shows that SnO2-P is a new and efficient catalyst for vanadium redox flow battery.
Photocatalytic Oxidation Reactions Mediated by Covalent Organic Frameworks and Related Extended Organic Materials
Authors: Alemán José , Mas-Ballesté Rubén
Published: June 2021

Covalent Organic Frameworks (COFs) and related extended organic materials have been widely used as photocatalysts in the last few years. Such interest arises from the wide range of covalent linkages employed in their construction, which offer many possibilities to design extended frameworks and to link photoactive building blocks. Thus, the potential utility of predesigned organic photoactive fragments can be synergistically added to the inherent advantages of heterogeneous catalysis, such as recyclability and easy separation of catalyst. In this overview, the current state of the art on the design of organic materials for photocatalytic oxidation reactions will be presented. The designing process of these materials is usually conditioned by the generally accepted concept that crystallinity and porosity defines the quality of the heterogeneous catalysts obtained. The care for the structural integrity of materials obtained is understandable because many properties and applications are intimately related to these features. However, the catalytic activity does not always directly depends on these characteristics. A critical compilation of the available literature is performed in order to offer a general perspective of the use of COFs and Covalent Triazine Frameworks (CTFs) in photocatalytic oxidation processes, including water oxidation, which constitute an important outcome relevant to artificial photosynthesis.
NtrBC Selectively Regulates Host-Pathogen Interactions, Virulence, and Ciprofloxacin Susceptibility of Pseudomonas aeruginosa
Authors: Alford Morgan A. , Baquir Beverlie , An Andy , Choi Ka-Yee G. , Hancock Robert E. W.
Published: June 2021

Pseudomonas aeruginosa is a metabolically versatile opportunistic pathogen capable of infecting distinct niches of the human body, including skin wounds and the lungs of cystic fibrosis patients. Eradication of P. aeruginosa infection is becoming increasingly difficult due to the numerous resistance mechanisms it employs. Adaptive resistance is characterized by a transient state of decreased susceptibility to antibiotic therapy that is distinct from acquired or intrinsic resistance, can be triggered by various environmental stimuli and reverted by removal of the stimulus. Further, adaptive resistance is intrinsically linked to lifestyles such as swarming motility and biofilm formation, both of which are important in infections and lead to multi-drug adaptive resistance. Here, we demonstrated that NtrBC, the master of nitrogen control, had a selective role in host colonization and a substantial role in determining intrinsic resistance to ciprofloxacin. P. aeruginosa mutant strains (ΔntrB, ΔntrC and ΔntrBC) colonized the skin but not the respiratory tract of mice as well as WT and, unlike WT, could be reduced or eradicated from the skin by ciprofloxacin. We hypothesized that nutrient availability contributed to these phenomena and found that susceptibility to ciprofloxacin was impacted by nitrogen source in laboratory media. P. aeruginosa ΔntrB, ΔntrC and ΔntrBC also exhibited distinct host interactions, including modestly increased cytotoxicity toward human bronchial epithelial cells, reduced virulence factor production and 10-fold increased uptake by macrophages. These data might explain why NtrBC mutants were less adept at colonizing the upper respiratory tract of mice. Thus, NtrBC represents a link between nitrogen metabolism, adaptation and virulence of the pathogen P. aeruginosa, and could represent a target for eradication of recalcitrant infections in situ.
Methylenetetrahydrofolate Reductase Gene C677T Polymorphism–Dietary Pattern Interaction on Hyperhomocysteinemia in a Chinese Population: A Cross-Sectional Study
Authors: Leng Song , Zhao Ai , Zhang Jian , Wu Wei , Wang Qian , Wu Shan , Chen Li , Zeng Qiang
Published: June 2021

Background and aim:Hyperhomocysteinemia (Hhcy) has been recognized as a risk factor of several chronic diseases. There is accumulating evidence that both genetic and dietary factors had a notable impact on the risk of Hhcy. The present study aims to investigate the interaction effect on Hhcy between methylenetetrahydrofolate reductase (MTHFR) geneC677Tpolymorphism and dietary intake.

Methods:Data were collected in a cross-sectional survey conducted in China; 3,966 participants with complete information on sociodemographic characteristics, anthropometric measurements, and dietary intake were included in the analyses. Dietary patterns were identified by factor analysis combined with cluster analysis. Blood samples were collected andMTHFR C677Tgenotypes were tested. Both the multiplicative statistical model and the additive model were conducted to investigate the interactive effects.

Results:Proportions ofMTHFR C677Tgenotypes among participants were 29.2% forTT, 47.4% forCT, and 23.4% forCC. Three dietary patterns were identified, namely, the balanced pattern, the snack pattern, and the high-meat pattern. Compared with the balanced pattern, the other two patterns were associated with an elevated risk of Hhcy [the snack pattern: odds ratio (OR) 1.2, 95% confidence interval (CI) 1.0–1.5; the high-meat pattern: OR 1.3, 95% CI 1.1–1.6] after adjustment for age group, gender, residential region, andMTHFR C677Tgenotypes. A multiplicative interaction between the high-meat pattern andMTHFR 677TTgenotype was observed, and synergistic effects between both the snack pattern and the high-meat pattern withMTHFR 677TTwere identified.

Conclusion:Our results indicated thatMTHFR C677Tpolymorphism and dietary patterns had interactive effects on Hhcy among the Chinese population. Subsequent targeted and appropriate dietary guidelines should be recommended for high-risk populations or patients of Hhcy carrying specific genotypes.
Interactive Web-Based Visualization of Multidimensional Physical and Astronomical Data
Authors: Diblen Faruk , Hendriks Luc , Stienen Bob , Caron Sascha , Bakhshi Rena , Attema Jisk
Published: June 2021

In this article, we propose expanding the use of scientific repositories such as Zenodo and HEP data, in particular, to better study multiparametric solutions of physical models. The implementation of interactive web-based visualizations enables quick and convenient reanalysis and comparisons of phenomenological data. To illustrate our point of view, we present some examples and demos for dark matter models, supersymmetry exclusions, and LHC simulations.
Clinical Guidelines for Dentistry in China During the Coronavirus Disease 2019 Pandemic
Authors: Luo Wen , Wang Jing , Tang Maoxue , Peng Jiaming , Ma Wenmin , Wu Yingying
Published: June 2021

Preventing the spread of Coronavirus Disease 2019 (COVID-19) has become the focus of epidemiologists as the highly infectious respiratory disease spreads primarily by close, person-to-person contact via droplets or the skin. Aerosol dissemination may occur in a closed, high-aerosol environment. The aerosols generated in dental procedures can pollute surrounding air and device surfaces. In this paper, we summarize prevention and control measures relating to dentistry. We focus on the relationship between COVID-19 and dental disease prevention and control in dental treatment procedures and imaging examinations, oral health education and perspectives, and guidance for the practice of dentistry during the COVID-19 pandemic to provide a consistent and broadly endorsed standard for dental hospital and clinics.
Hg Isotopes and Enhanced Hg Concentration in the Meishan and Guryul Ravine Successions: Proxies for Volcanism Across the Permian-Triassic Boundary
Authors: Sial Alcides Nóbrega , Chen Jiubin , Korte Christoph , Pandit Manoj Kumar , Spangenberg Jorge E. , Silva-Tamayo Juan Carlos , Lacerda Luiz Drude de , Ferreira Valderez Pinto , Barbosa José Antônio , Gaucher Claudio , Pereira Natan Silva , Riedel Paulo Ricardo
Published: June 2021

High-resolution organic carbon isotope (δ13C), Hg concentration and Hg isotopes curves are presented for the Permian-Triassic boundary (PTB) sections at Guryul Ravine (India) and Meishan D (China). The total organic carbon (TOC)-normalized Hg concentrations reveal more intense environmental changes at the Latest Permian Mass Extinction (LPME) and the earliest Triassic Mass Extinction (ETME) horizons coinciding with majorδ13C shifts. To highlight palaeoredox conditions we used redox-sensitive elements and Rare Earth Element distribution. At Meishan, three Hg/TOC spikes (I, II, and III) are observed. Spike I remains after normalization by total aluminum (Al), but disappears when normalized by total sulfur (TS). Spike III, at the base of Bed 26, corresponds with excursions in the Hg/TS and Hg/Al curves, indicating a change in paleoredox conditions from anoxic/euxinic in the framboidal pyrite-bearing sediments (Bed 26) to oxygenated sediments (Bed 27). At Guryul Ravine, four Hg/TOC spikes were observed: a clear spike I in Bed 46, spike II at the base of the framboidal pyrite-rich Bed 49, spike III at the PTB, and spike IV at the LPME horizon. Some of these Hg/TOC spikes disappear when TS or Al normalization is applied. The spike I remains in the Hg/TS and Hg/Al curves (oxic conditions), spike II only in the Hg/TS curve (anoxic/euxinic), and spikes III and IV only in Hg/Al curves (oxic). In both sections, Hg deposition was organic-matter bound, the role of sulfides being minor and locally restricted to framboidal pyrite-bearing horizons. Positive mass-independent fractionation (MIF) for Hg odd isotopes (odd-MIF) was observed in pre-LPME samples, negative values in the LPME–PTB interval, and positive values above the ETME horizon. Most Hg-isotope patterns are probably controlled by the bathymetry of atmospheric Hg-bearing deposits. The source of Hg can be attributed to the Siberian Traps Large Igneous Province (STLIP). In the LPME-PTB interval, a complex of STLIP sills (Stage 2) intruded coal-bearing sediments. The negativeδ202Hg, the mercury odd-MIF Δ201Hg patterns, and the Δ199Hg–Hg plot in both sections are compatible with volcanic mercury deposition. Our study shows the strength of Hg/TOC ratios as paleoenvironmental proxy and as a tool for stratigraphic correlation.
Centimeter-Scale Lithology and Facies Prediction in Cored Wells Using Machine Learning
Authors: Martin Thomas , Meyer Ross , Jobe Zane
Published: June 2021

Machine-learning algorithms have been used by geoscientists to infer geologic and physical properties from hydrocarbon exploration and development wells for more than 40 years. These techniques historically utilize digital well-log information, which, like any remotely sensed measurement, have resolution limitations. Core is the only subsurface data that is true to geologic scale and heterogeneity. However, core description and analysis are time-intensive, and therefore most core data are not utilized to their full potential. Quadrant 204 on the United Kingdom Continental Shelf has publicly available open-source core and well log data. This study utilizes this dataset and machine-learning models to predict lithology and facies at the centimeter scale. We selected 12 wells from the Q204 region with well-log and core data from the Schiehallion, Foinaven, Loyal, and Alligin hydrocarbon fields. We interpreted training data from 659 m of core at the sub-centimeter scale, utilizing a lithology-based labeling scheme (five classes) and a depositional-process-based facies labeling scheme (six classes). Utilizing a “color-channel-log” (CCL) that summarizes the core image at each depth interval, our best performing trained model predicts the correct lithology with 69% accuracy (i.e., the predicted lithology output from the model is the same as the interpreted lithology) and predicts individual lithology classes of sandstone and mudstone with over 80% accuracy. The CCL data require less compute power than core image data and generate more accurate results. While the process-based facies labels better characterize turbidites and hybrid-event-bed stratigraphy, the machine-learning based predictions were not as accurate as compared to lithology. In all cases, the standard well-log data cannot accurately predict lithology or facies at the centimeter level. The machine-learning workflow developed for this study can unlock warehouses full of high-resolution data in a multitude of geological settings. The workflow can be applied to other geographic areas and deposit types where large quantities of photographed core material are available. This research establishes an open-source, python-based machine-learning workflow to analyze open-source core image data in a scalable, reproducible way. We anticipate that this study will serve as a baseline for future research and analysis of borehole and core data.
Campi Flegrei, Vesuvius and Ischia Seismicity in the Context of the Neapolitan Volcanic Area
Authors: Giudicepietro Flora , Ricciolino Patrizia , Bianco Francesca , Caliro Stefano , Cubellis Elena , D’Auria Luca , De Cesare Walter , De Martino Prospero , Esposito Antonietta M. , Galluzzo Danilo , Macedonio Giovanni , Lo Bascio Domenico , Orazi Massimo , Pappalardo Lucia , Peluso Rosario , Scarpato Giovanni , Tramelli Anna , Chiodini Giovanni
Published: June 2021

Studying seismicity in a volcanic environment provides important information on the state of activity of volcanoes. The seismicity of the Neapolitan volcanoes, Campi Flegrei, Vesuvius, and Ischia, shows distinctive characteristics for each volcano, covering a wide range of patterns and types. In this study we relocated some significant volcano-tectonic earthquake swarms that occurred in Campi Flegrei and Vesuvius. Moreover, we compared the earthquake occurrence evolution, the magnitude and the seismic energy release of the three volcanoes. Also, we considered the results of seismic analysis in the light of geochemical and ground deformation data that contribute to defining the state of activity of volcanoes. In Campi Flegrei, which is experiencing a long term unrest, we identified a seismogenic structure at shallow depth in Pisciarelli zone that has been activated repeatedly. The increasing seismicity accompanies an escalation of the hydrothermal activity and a ground uplift phase. At Vesuvius a very shallow seismicity is recorded, which in recent years has shown an increase in terms of the number of events per year. Earthquakes are usually located right beneath the crater axis. They are concentrated in a volume affected by the hydrothermal system. Finally, Ischia generally shows a low level of seismicity, however, in Casamicciola area events with a moderate magnitude can occur and these are potentially capable of causing severe damage to the town and population, due to their small hypocentral depth (typically < 2.5 km). After the seismic crisis of August 21, 2017 (mainshock magnitude M = 4), the seismicity returned to a low level in terms of occurrence rate and magnitude of earthquakes. The seismicity of these three different volcanic areas shows some common aspects that highlight a relevant role of hydrothermal processes in the seismogenesis of volcanic areas. However, while the main swarms in Campi Flegrei and most of the Vesuvian earthquakes are distributed along conduit-like structures, the seismicity of Ischia is mainly located along faults. Furthermore, the temporal evolution of seismicity in Neapolitan volcanic area suggests a concomitant increase in the occurrence of earthquakes both in Campi Flegrei and Vesuvius in recent years.
Comparative Assessment and Future Prediction Using CMIP6 and CMIP5 for Annual Precipitation and Extreme Precipitation Simulation
Authors: Li Jingjing , Huo Ran , Chen Hua , Zhao Ying , Zhao Tianhui
Published: June 2021

This study assesses the improvement of the latest Coupled Model Intercomparison Project Phase 6 (CMIP6) over Coupled Model Intercomparison Project Phase 5 (CMIP5) for precipitation simulation. Precipitation simulations under different future climate scenarios are also compared in this work. The results show that: 1) CMIP6 has no overall advantage over CMIP5 in simulating total precipitation (PRCPTOT) and maximum consecutive dry days (CDD). The performance of CMIP6 increases or decreases regionally in PRCPTOT and consecutive dry days. But it is slightly worse than CMIP5 in simulating very wet days (R95pTOT). 2) Comparing the trend test results of CMIP5 and CMIP6 in the future, there are more areas with significant trend based on Mann–Kendall test in CMIP6 compared with that of CMIP5. The differences in PRCPTOT are mainly found in Amazon Basin and Western Africa. The differences between the R95pTOT trends mainly noticeable in South America and Western Africa, and the differences in CDD are mainly reflected in Central Asia, Sahara Desert and central South America. 3) In Southern South America and Western North America, the PRCPTOT changing rate of CMIP6 in the future under various scenarios is always greater than that of CMIP5; in Alaska, Western Africa, Southern Africa, the PRCPTOT changing rate of CMIP6 in the future under various scenarios is always less than that of CMIP5. In Southern South America, the R95pTOT changing rate of CMIP6 in the future under various scenarios is always greater than that of CMIP5; in Alaska, East Asia, North Asia, the R95pTOT changing rate of CMIP6 in the future under various scenarios is always less than that of CMIP5. In almost half of the regions, the CDD changing rate of CMIP6 is less than that of CMIP5 under all scenarios, namely Australia, Amazon Basin, Southern South America, Central America, Western North America, Central North America, Eastern North America, Central Asia, Tibet.
Follicle-Stimulating Hormone-Secreting Pituitary Adenoma Inducing Spontaneous Ovarian Hyperstimulation Syndrome, Treatment Using In Vitro Fertilization and Embryo Transfer: A Case Report
Authors: Du Xiaofang , Zhang Wen , Wang Xingling , Yu Xiaona , Li Zhen , Guan Yichun
Published: June 2021

Objective

To describe the management of a patient with a pituitary adenoma secreting follicle-stimulating hormone (FSH) associated with spontaneous ovarian hyperstimulation syndrome (sOHSS) who was treated with in vitro fertilization and embryo transfer (IVF-ET).

Methods

We report a clinical case of a woman of reproductive age with menstrual irregularity, infertility and ovarian hyperstimulation due to recurrent pituitary adenoma secreting FSH, which persisted after transsphenoidal surgery.She underwent the diagnosis by magnetic resonance imaging (MRI) and laboratory tests,and finally she was treated with IVF-ET.

Result(s)

The patient was plagued by a recurrent pituitary adenoma for many years and tried various treatments. After complete transsphenoidal surgery, sOHSS decreased, as shown by a reduction in oestradiol levels and an improvement in the ultrasonography parameters; however, secondary amenorrhea occurred. Finally, pregnancy was achieved through IVF-ET and the symptoms of ovarian hyperstimulation were relieved.

Conclusion(s)

IVF-ET was found to be effective for the treatment of recurrent pituitary adenoma, thus representing a therapeutic option that should be taken into consideration in such cases.
Update of Radiofrequency Ablation for Treating Benign and Malignant Thyroid Nodules. The Future Is Now
Authors: Tufano Ralph P. , Pace-Asciak Pia , Russell Jonathon O. , Suárez Carlos , Randolph Gregory W. , López Fernando , Shaha Ashok R. , Mäkitie Antti , Rodrigo Juan P. , Kowalski Luiz Paulo , Zafereo Mark , Angelos Peter , Ferlito Alfio
Published: June 2021

Thermal and chemical ablation are minimally invasive procedures that avoid removal of the thyroid gland and target symptomatic nodules directly. Internationally, Radiofrequency ablation (RFA) is among one of the most widely used thermal ablative techniques, and is gaining traction in North America. Surgery remains the standard of care for most thyroid cancer, and in the right clinical setting, Active Surveillance (AS) can be a reasonable option for low risk disease. Minimally invasive techniques have emerged as an alternative option for patients deemed high risk for surgery, or for those patients who wish to receive a more active treatment approach compared to AS. Herein, we review the literature on the safety and efficacy of RFA for treating benign non-functioning thyroid nodules, autonomously functioning thyroid nodules, primary small low risk thyroid cancer (namely papillary thyroid cancer) as well as recurrent thyroid cancer.
How Smart is the Grid?
Authors: Lo Cascio Ermanno , Girardin Luc , Ma Zhenjun , Maréchal François
Published: June 2021

Ancient Romans called urbs the set of buildings and infrastructures, and civitas the Roman citizens. Today instead, while the society is surfing the digital tsunami, urbs and civitas tend to become much closer, almost merging, that we might attempt to condensate these into a single concept: smart grid. Internet of things, artificial intelligence, blockchain, and quantum cryptography are only a few of the technologies that are likely to contribute to determining the final portrait of the future smart grid. However, to understand the effective sustainability of complex grids, specific tools are required. To this end, in this article, a new taxonomic framework has been developed starting from a general analysis of the emerging solutions, identifying intersectoral synergies and limitations with respect to the ‘smart grid’ concept. Finally, from the scenario portrayed, a set of issues involving engineering, regulation, security, and social frameworks have been derived in a theoretical fashion. The findings are likely to suggest the urgent need for multidisciplinary cooperation to address engineering and ontological challenges gravitating around the smart grid concept.
Effects of Sex and Breeding Status on Skull Morphology in Cooperatively Breeding Ansell’s Mole-Rats and an Appraisal of Sexual Dimorphism in the Bathyergidae
Authors: Caspar Kai R. , Müller Jacqueline , Begall Sabine
Published: June 2021

African mole-rats of the genus Fukomys (Northern common mole-rats) combine a monogamous mating system and pronounced sexual size dimorphism; a pattern highly untypical for mammals. At the same time, they live in cooperatively breeding groups composed of reproductive and non-reproductive members of both sexes. How and to which degree sex and breeding status influence morphofunctional characters in eusocial mole-rats is not well characterized but essential to come to a comprehensive understanding of their peculiar social system. Here, we explore patterns of morphological differentiation in skulls of Ansell’s mole-rats (Fukomys anselli) by means of multivariate analysis of linear skull measurements combined with a 2D shape analysis of cranium and mandible. Compared to females, males display larger skulls relative to body size and show an expansion of the facial portion of the cranium, while reproductive status did not have an effect on any of the traits studied. We also show that species of Fukomys mole-rats display a scaling of relative sexual body size dimorphism in compliance to Rensch’s rule, which is deemed indicative of intense male intrasexual competition. For the bathyergid family as a whole, results of scaling analyses were more ambiguous, but also indicative of Rensch’s rule conformity. In line with genetic field data, our results point to a greater role of male-male conflicts in Fukomys than is traditionally assumed and support the notion that reproductive status does not correlate with morphofunctional segregation in these unusual rodents.
Phylogenetic Endemism Hotspots of North American Birds Are Associated With Warm Temperatures and Long- and Short-Term Climate Stability
Authors: Acevedo Sebastian , Sandel Brody
Published: June 2021

Human activities have dramatically altered the distribution and abundance of species, and our impacts are likely to increase in the near future. Conservation efforts are typically faced with scarce resources, forcing us to prioritize areas based in part on estimates of their conservation value. Two major factors in conservation value are a species uniqueness and its extinction risk. Though these ideas are multidimensional, one important component of uniqueness is evolutionary distinctness, while risk is strongly related to geographic range size. These components are combined in an assemblage-level measure called phylogenetic endemism (PE), which measures the degree to which the species in an assemblage are small-ranged and phylogenetically distinct. Broad-scale patterns and correlates of PE are becoming better known for a variety of groups, and have been shown to depend on current climate, geographic isolation and long-term climate stability. Human impacts (e.g., land cover changes), are likely to shape PE as well, though the coarse resolution of most previous studies may make this difficult to detect. Overall, PE patterns at fine spatial and temporal resolutions are not well understood. Here, we fill this gap using data from the North American Breeding Bird Survey. These data comprise a long-term annual record with fine spatial resolution and a near-continental extent. We assess geographic patterns and trends in PE, and relate these to a range of putative predictor variables including measures of current climate, land cover, long-term and recent climate change. Bird PE is concentrated in three main hotspots: the west coast, the southeast and south-central Canada east of the Rockies. High PE values tended to occur in regions with high temperatures and stability in temperature, both in the long (21,000 year) and short (35 year) time scales. PE patterns are driven more strongly by patterns of range size than phylogenetic distinctiveness, and are trending gradually upward, driven by increasingly frequent sightings of small-ranged species. These results indicate the importance of climate stability on multiple time scales in influencing endemism patterns and suggest a surprisingly minor influence of direct human land use. The increase in PE through time may reflect successful conservation efforts that have led to population recoveries of some small-ranged species.
Relating the Strength of Density Dependence and the Spatial Distribution of Individuals
Authors: Brush Micah , Harte John
Published: June 2021

Spatial patterns in ecology contain useful information about underlying mechanisms and processes. Although there are many summary statistics used to quantify these spatial patterns, there are far fewer models that directly link explicit ecological mechanisms to observed patterns easily derived from available data. We present a model of intraspecific spatial aggregation that quantitatively relates static spatial patterning to negative density dependence. Individuals are placed according to the colonization rule consistent with the Maximum Entropy Theory of Ecology (METE), and die with probability proportional to their abundance raised to a power α, a parameter indicating the degree of density dependence. This model can therefore be interpreted as a hybridization of MaxEnt and mechanism. Our model shows quantitatively and generally that increasing density dependence randomizes spatial patterning. α = 1 recovers the strongly aggregated METE distribution that is consistent with many ecosystems empirically, and as α → 2 our prediction approaches the binomial distribution consistent with random placement. For 1 < α < 2, our model predicts more aggregation than random placement but less than METE. We additionally relate our mechanistic parameter α to the statistical aggregation parameter k in the negative binomial distribution, giving it an ecological interpretation in the context of density dependence. We use our model to analyze two contrasting datasets, a 50 ha tropical forest and a 64 m2 serpentine grassland plot. For each dataset, we infer α for individual species as well as a community α parameter. We find that α is generally larger in the tightly packed forest than the sparse grassland, and the degree of density dependence increases at smaller scales. These results are consistent with current understanding in both ecosystems, and we infer this underlying density dependence using only empirical spatial patterns. Our model can easily be applied to other datasets where spatially explicit data are available.
Oral Tolerance Induced by Heat Shock Protein 65-Producing Lactococcus lactis Mitigates Inflammation in Leishmania braziliensis Infection
Authors: Guerra Priscila Valera , Andrade Camila Mattos , Nunes Ivanéia Valeriano , Gama Brena Cardoso , Tibúrcio Rafael , Santos Washington Luis Conrado , Azevedo Vasco Ariston , Tavares Natalia Machado , Rebouças Juliana de Souza , Maiolii Tatiani Uceli , Faria Ana Maria Caetano , Brodskyn Cláudia Ida
Published: June 2021

Cutaneous leishmaniasis caused byL. braziliensisinduces a pronounced Th1 inflammatory response characterized by IFN-γ production. Even in the absence of parasites, lesions result from a severe inflammatory response in which inflammatory cytokines play an important role. Different approaches have been used to evaluate the therapeutic potential of orally administrated heat shock proteins (Hsp). These proteins are evolutionarily preserved from bacteria to humans, highly expressed under inflammatory conditions and described as immunodominant antigens. Tolerance induced by the oral administration of Hsp65 is capable of suppressing inflammation and inducing differentiation in regulatory cells, and has been successfully demonstrated in several experimental models of autoimmune and inflammatory diseases. We initially administered recombinantLactococcus lactis(L. lactis) prior to infection as a proof of concept, in order to verify its immunomodulatory potential in the inflammatory response arising fromL. braziliensis. Using this experimental approach, we demonstrated that the oral administration of a recombinantL. lactisstrain, which produces and secretes Hsp65 fromMycobacterium lepraedirectly into the gut, mitigated the effects of inflammation caused byL. braziliensisinfection in association or not with PAM 3CSK4 (N-α-Palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-L-cysteine, a TLR2 agonist). This was evidenced by the production of anti-inflammatory cytokines and the expansion of regulatory T cells in the draining lymph nodes of BALB/c mice. Ourin vitroexperimental results suggest that IL-10, TLR-2 and LAP are important immunomodulators inL. braziliensisinfection. In addition, recombinantL. lactisadministered 4 weeks after infection was observed to decrease lesion size, as well as the number of parasites, and produced a higher IL-10 production and decrease IFN-γ secretion. Together, these results indicate that Hsp65-producingL. lactiscan be considered as an alternative candidate for treatment in both autoimmune diseases, as well as in chronic infections that cause inflammatory disease.
Acute Kidney Injury Induced Lupus Exacerbation Through the Enhanced Neutrophil Extracellular Traps (and Apoptosis) in Fcgr2b Deficient Lupus Mice With Renal Ischemia Reperfusion Injury
Authors: Saisorn Wilasinee , Saithong Supichcha , Phuengmaung Pornpimol , Udompornpitak Kanyarat , Bhunyakarnjanarat Thansita , Visitchanakun Peerapat , Chareonsappakit Awirut , Pisitkun Prapaporn , Chiewchengchol Direkrit , Leelahavanichkul Asada
Published: June 2021

Renal ischemia is the most common cause of acute kidney injury (AKI) that might be exacerbate lupus activity through neutrophil extracellular traps (NETs) and apoptosis. Here, the renal ischemia reperfusion injury (I/R) was performed in Fc gamma receptor 2b deficient (Fcgr2b-/-) lupus mice and the in vitro experiments. At 24 h post-renal I/R injury, NETs in peripheral blood neutrophils and in kidneys were detected using myeloperoxidase (MPO), neutrophil elastase (NE) and citrullinated histone H3 (CitH3), as well as kidney apoptosis (activating caspase-3), which were prominent in Fcgr2b-/- mice more compared to wild-type (WT). After 120 h renal-I/R injury, renal NETs (using MPO and NE) were non-detectable, whereas glomerular immunoglobulin (Ig) deposition and serum anti-dsDNA were increased in Fcgr2b-/- mice. These results imply that renal NETs at 24 h post-renal I/R exacerbated the lupus nephritis at 120 h post-renal I/R injury in Fcgr2b-/- lupus mice. Furthermore, a Syk inhibitor attenuated NETs, that activated by phorbol myristate acetate (PMA; a NETs activator) or lipopolysaccharide (LPS; a potent inflammatory stimulator), more prominently in Fcgr2b-/- neutrophils than the WT cells as determined by dsDNA, PAD4 and MPO. In addition, the inhibitors against Syk and PAD4 attenuated lupus characteristics (serum creatinine, proteinuria, and anti-dsDNA) in Fcgr2b-/- mice at 120 h post-renal I/R injury. In conclusion, renal I/R in Fcgr2b-/- mice induced lupus exacerbation at 120 h post-I/R injury partly because Syk-enhanced renal NETs led to apoptosis-induced anti-dsDNA, which was attenuated by a Syk inhibitor.
Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity
Authors: Westfall Susan , Caracci Francesca , Estill Molly , Frolinger Tal , Shen Li , Pasinetti Giulio M.
Published: June 2021

Chronic stress manifests as depressive- and anxiety-like behavior while recurrent stress elicits disproportionate behavioral impairments linked to stress-induced immunological priming. The gut-brain-microbiota-axis is a promising therapeutic target for stress-induced behavioral impairments as it simultaneously modulates peripheral and brain immunological landscapes. In this study, a combination of probiotics and prebiotics, known as a synbiotic, promoted behavioral resilience to chronic and recurrent stress by normalizing gut microbiota populations and promoting regulatory T cell (Treg) expansion through modulation of ileal innate lymphoid cell (ILC)3 activity, an impact reflecting behavioral responses better than limbic brain region neuroinflammation. Supporting this conclusion, a multivariate machine learning model correlatively predicted a cross-tissue immunological signature of stress-induced behavioral impairment where the ileal Treg/T helper17 cell ratio associated to hippocampal chemotactic chemokine and prefrontal cortex IL-1β production in the context of stress-induced behavioral deficits. In conclusion, stress-induced behavioral impairments depend on the gut-brain-microbiota-axis and through ileal immune regulation, synbiotics attenuate the associated depressive- and anxiety-like behavior.
Circulating Mitochondrial DNA Stimulates Innate Immune Signaling Pathways to Mediate Acute Kidney Injury
Authors: Liu Jiaye , Jia Zhanjun , Gong Wei
Published: June 2021

Mitochondrial dysfunction is increasingly considered as a critical contributor to the occurrence and progression of acute kidney injury (AKI). However, the mechanisms by which damaged mitochondria mediate AKI progression are multifactorial and complicated. Mitochondrial DNA (mtDNA) released from damaged mitochondria could serve as a danger-associated molecular pattern (DAMP) and activate the innate immune system through STING, TLR9, NLRP3, and some other adaptors, and further mediate tubular cell inflammation and apoptosis. Accumulating evidence has demonstrated the important role of circulating mtDNA and its related pathways in the progression of AKI, and regulating the proteins involved in these pathways may be an effective strategy to reduce renal tubular injury and alleviate AKI. Here, we aim to provide a comprehensive overview of recent studies on mtDNA-mediated renal pathological events to provide new insights in the setting of AKI.
In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope
Authors: Larid Guillaume , Pancarte Mikael , Offer Géraldine , Clavel Cyril , Martin Marielle , Pradel Vincent , Auger Isabelle , Lafforgue Pierre , Roudier Jean , Serre Guy , Balandraud Nathalie
Published: June 2021

Objectives

Rheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modification of arginine involved in peptidic bounds (arginyl residue) by PeptidylArginine Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrin(ogen) (hFib) and can be specifically detected by the AhFibA assay. Five citrullinated peptides derived from hFib together represent almost all of the epitopes recognized by patients with ACPA-positive RA, namely: α36–50cit, α171–185cit, α501–515cit, α621–635cit, and β60–74cit. The use of antibody fine specificities as markers of clinical phenotypes has become a major challenge. Our objective was to study whether RA clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against the epitopes borne by the five peptides.

Methods

184 ACPA-positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patient characteristics including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2 antibodies, AhFibA, and antibodies against the five citrullinated hFib (hFib-cit) peptides were analyzed by ELISA.

Results

Anti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 – 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were associated with rheumatoid nodules (OR = 2.71 [1.00 – 7.16], p= 0.044).

Conclusion

Immune complexes containing anti-α501-515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. Apheresis of these epitope-specific antibodies might be a new therapeutic opportunity for patients with rheumatoid nodules.
The Use of Biologic Modifiers as a Bridge to Hematopoietic Cell Transplantation in Primary Immune Regulatory Disorders
Authors: Arnold Danielle E. , Chellapandian Deepak , Leiding Jennifer W.
Published: June 2021

Recently, primary immune regulatory disorders have been described as a subset of inborn errors of immunity that are dominated by immune mediated pathology. As the pathophysiology of disease is elucidated, use of biologic modifiers have been increasingly used successfully to treat disease mediated clinical manifestations. Hematopoietic cell transplant (HCT) has also provided definitive therapy in several PIRDs. Although biologic modifiers have been largely successful at treating disease related manifestations, data are lacking regarding long term efficacy, safety, and their use as a bridge to HCT. This review highlights biologic modifiers in the treatment of several PIRDs and there use as a therapeutic bridge to HCT.
Herbal Plants: The Role of AhR in Mediating Immunomodulation
Authors: Bungsu Izzah , Kifli Nurolaini , Ahmad Siti Rohaiza , Ghani Hazim , Cunningham Anne Catherine
Published: June 2021

The prevalence of chronic inflammatory diseases including inflammatory bowel disease (IBD), autoimmunity and cancer have increased in recent years. Herbal-based compounds such as flavonoids have been demonstrated to contribute to the modulation of these diseases although understanding their mechanism of action remains limited. Flavonoids are able to interact with cellular immune components in a distinct way and influence immune responses at a molecular level. In this mini review, we highlight recent progress in our understanding of the modulation of immune responses by the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor whose activity can be regulated by diverse molecules including flavonoids. We focus on the role of AhR in integrating signals from flavonoids to modulate inflammatory responses using in vitro and experimental animal models. We also summarize the limitations of these studies. Medicinal herbs have been widely used to treat inflammatory disorders and may offer a valuable therapeutic strategy to treat aberrant inflammatory responses by modulation of the AhR pathway.
Cytokine Consistency Between Bone Marrow and Peripheral Blood in Patients With Philadelphia-Negative Myeloproliferative Neoplasms
Authors: Chen Pu , Wu Boting , Ji Lili , Zhan Yanxia , Li Feng , Cheng Luya , Cao Jingjing , Chen Hehui , Ke Yang , Min Zhihui , Sun Lihua , Hua Fanli , Chen Hao , Cheng Yunfeng
Published: June 2021

Background: Inflammation might play a critical role in the pathogenesis and progression of Philadelphia-negative myeloproliferative neoplasms (Ph−MPNs) with elevated inflammatory cytokines in peripheral blood (PB). However, the inflammatory status inside the bone marrow (BM), which is the place of malignancy origin and important microenvironment of neoplasm evolution, has not yet been elucidated.

Methods: Inflammatory cytokine profiles in PB and BM of 24 Ph-MPNs patients were measured by a multiplex quantitative inflammation array. Cytokines that correlated between PB and BM were selected and then validated by ELISA in a separate cohort of 52 MPN patients. Furthermore, a panel of cytokines was identified and examined for potential application as non-invasive markers for the diagnosis and prediction of fibrosis progress of MPN subtypes.

Results: The levels of G-CSF, I-309, IL-1β, IL-1ra, IL-12p40, IL-15, IL-16, M-CSF, MIG, PDGF-BB, and TIMP-1 in BM supernatants were significantly higher than those in PB (all p < 0.05). Linear correlations between BM and PB levels were found in 13 cytokines, including BLC, Eotaxin-2, I-309, sICAM-1, IL-15, M-CSF, MIP-1α, MIP-1δ, RANTES, TIMP-1, TIMP-2, sTNFRI, and sTNFRII (all R > 0.4 and p < 0.05). Levels of BLC, Eotaxin-2, M-CSF, and TIMP-1 in PB were significantly different from those in health controls (all p < 0.05). In PB, levels of TIMP-1 and Eotaxin-2 in essential thrombocythemia (ET) group were significantly lower than those in groups of prefibrotic primary myelofibrosis (pre-PMF) [TIMP-1: 685.2 (322.2–1,229) ng/ml vs. 1,369 (1,175–1,497) ng/ml, p = 0.0221; Eotaxin-2: 531.4 (317.9–756.6) pg/ml vs. 942.4 (699.3–1,474) pg/ml, p = 0.0393] and primary myelofibrosis (PMF) [TIMP-1: 685.2 (322.2–1229) ng/ml vs. 1,365 (1,115–1,681) ng/ml, p = 0.0043; Eotaxin-2: 531.4 (317.9–756.6) pg/ml vs. 1,010 (818–1,556) pg/ml, p = 0.0030]. The level of TIMP-1 in myelofibrosis (MF) >1 group was significantly higher than that in MF ≤ 1 group.

Conclusion: Abnormal inflammatory status is present in MPN, especially in its BM microenvironment. Consistency between PB and BM levels was found in multiple inflammatory cytokines. Circulating cytokine levels of BLC, M-CSF, Eotaxin-2, and TIMP-1 reflected inflammation inside BM niche, suggesting potential diagnostic value for MPN subtypes and prognostic value for fibrosis progression.