bluuebunny/crossref_metadata_2025 huggingface dataset:
Calibration of the Discrete Element Method and Modeling of Shortening Experiments
Authors: Li Changsheng , Yin Hongwei , Wu Chuang , Zhang Yingchun , Zhang Jiaxing , Wu Zhenyun , Wang Wei , Jia Dong , Guan Shuwei , Ren Rong
Published: May 2021

The discrete element method (DEM) is becoming widely accepted as an effective method for addressing tectonic problems in granular materials. It is capable of reproducing structures observed in the analog model (AM). However, the previous experiments also pointed to variability among DEM models and AMs in the number of fault zones, their dip angle and spacing, and the evolution of the surface slope of a thrust wedge. The accuracy of the DEM depends on the input parameter values, so the calibration of the discrete element method is very important. Microscopic properties of particles and macroscopic properties of loose quartz sand were calibrated through a series of repose angle and biaxial tests. Furthermore, an AM was constructed to simulate the evolution of the thrust wedge to compare with DEM results. DEM and AM results indicate an encouraging overall agreement in model evolution. Based on a new automated wedge quantification method, DEM results were systematically compared with AM results on the number of fault zones, their dip angle and spacing, the evolution of the surface slope of a thrust wedge, and other parameters. Our study provides a necessary comparison between commonly applied modeling approaches, which is important for more confidently applying these methods to understand real fold and thrust belt systems.
Understanding Complex Debris-Covered Glaciers: Concepts, Issues, and Research Directions
Authors: Huo Da , Bishop Michael P. , Bush Andrew B. G.
Published: May 2021

Understanding the climate-glacier dynamics of debris-covered glaciers is notoriously difficult given a multitude of controlling factors and feedback mechanisms involving climate forcing, debris-load properties, supraglacial water bodies, and multi-scale topographic effects. Recent studies have provided insights into controlling factors, and have reported the presence of anomalies that contradict the general consensus of the protective influence of debris loads on ablation dynamics. Nevertheless, numerous processes that regulate glacier dynamics at various spatial and temporal scales have not been adequately accounted for in statistical and numerical modeling studies. Furthermore, important feedbacks involving ablation, topography, irradiance, gravitational debris flux, and supraglacial ponding are often neglected or oversimplified in existing models, which poses a challenge to our understanding of conflicting field observations such as the accelerated mass loss of many Himalayan glaciers, and glacier-subsystem responses (ice-flow, debris flux, surface morphology, and supraglacial water bodies) to climate forcing. This paper provides insights into the complexity of debris-covered glacier systems by addressing concepts and issues associated with forcing factors and glacial processes, and highlights the importance of understanding system couplings and feedbacks. Specifically, we review recent studies on debris-covered glaciers and utilize simulation results based on the Baltoro Glacier in the central Karakoram to discuss important concepts and issues. Our results demonstrate that climate forcing, the properties and transport of debris, topography and supraglacial water bodies are the key controlling factors in a debris-covered glacier system, and that their coupled effects and positive feedbacks may increase the ice loss of a debris-covered glacier. We also recommend new research directions for future studies.
Calculation Model to Predict the Static Armor Layer Size Distribution After the Reconstruction of a Gravel River Bed
Authors: Wang Qiang , Li Like , Li Xinjie , Wang Yuanjian , Nie Ruihua
Published: May 2021

The size distribution of armor layer in mountain rivers is an important factor that affects the stability of the river bed. However, there are relatively few studies on the prediction of armor layer size distribution in the reconstruction process after the previous static armor layer becomes unstable. In response to the above challenges, this study considers the incipient probability of sediment particles as the starting point, and comprehensively considers the coupling relationship between the initial bed materials, bed structure, armor ratio, and flow intensity, using a simple calculation model for predicting the static armor layer size distribution after reconstruction of a gravel-river bed. This paper introduces the concept of critical incipient particle size Dc, and considers that sediment particles smaller than Dc will incipient easily, resulting in a higher probability of being washed out, whereas the incipient probability of sediment particles larger than Dc (this part of the large-particle sediment includes not only the original particles on the bed surface, but also the large sediment particles exposed by the erosion of the bed subsurface) is relatively small. At the same time, this model also uses the armor ratio to reflect the impact of the bed surface structure. This study cites data from five sets of laboratory flume experiments to verify the calculation model, and the experimental results show that the model calculation results are in good agreement with the experimentally measured data, especially in predicting the median diameter D50 of the static armor layer. Our calculation model provides theoretical guidance for the study of mountain riverbed stability, earthquake prevention and disaster reduction.
Hidden Processes During Seasonal Isolation of a High-Altitude Watershed
Authors: Buser-Young Jessica Z. , Lapham Laura L. , Thurber Andrew R. , Williams Kenneth H. , Colwell Frederick S.
Published: May 2021

Biogeochemical processes capable of altering global carbon systems occur frequently in Earth’s Critical Zone–the area spanning from vegetation canopy to saturated bedrock–yet many of these phenomena are difficult to detect. Observation of these processes is limited by the seasonal inaccessibility of remote ecosystems, such as those in mountainous, snow- and ice-dominated areas. This isolation leads to a distinct gap in biogeochemical knowledge that ultimately affects the accuracy and confidence with which these ecosystems can be computationally modeled for the purpose of projecting change under different climate scenarios. To examine a high-altitude, headwater ecosystem’s role in methanogenesis, sulfate reduction, and groundwater-surface water exchange, water samples were continuously collected from the river and hyporheic zones (HZ) during winter isolation in the East River (ER), CO watershed. Measurements of continuously collected ER surface water revealed up to 50 μM levels of dissolved methane in July through September, while samples from 12 cm deep in the hyporheic zone at the same location showed a spring to early summer peak in methane with a strong biogenic signature (<65 μM, δ13C-CH4, −60.76‰) before declining. Continuously collected δ18O-H2O and δ2H-H2O isotopes from the water column exhibited similar patterns to discrete measurements, while samples 12 cm deep in the hyporheic zone experienced distinct fluctuations in δ18O-H2O, alluding to significant groundwater interactions. Continuously collected microbial communities in the river in the late fall and early winter revealed diverse populations that reflect the taxonomic composition of ecologically similar river systems, including taxa indicative of methane cycling in this system. These measurements captured several biogeochemical components of the high-altitude watershed in response to seasonality, strengthening our understanding of these systems during the winter months.
Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion
Authors: Casasnovas Jose , Damron Christopher Luke , Jarrell James , Orr Kara S. , Bone Robert N. , Archer-Hartmann Stephanie , Azadi Parastoo , Kua Kok Lim
Published: May 2021

Offspring of obese mothers suffer higher risks of type 2 diabetes due to increased adiposity and decreased β cell function. To date, the sex-differences in offspring islet insulin secretion during early life has not been evaluated extensively, particularly prior to weaning at postnatal day 21 (P21). To determine the role of maternal obesity on offspring islet insulin secretion, C57BL/6J female dams were fed chow or western diet from 4 weeks prior to mating to induce maternal obesity. First, offspring of chow-fed and obese dams were evaluated on postnatal day 21 (P21) prior to weaning for body composition, glucose and insulin tolerance, and islet phasic insulin-secretion. Compared to same-sex controls, both male and female P21 offspring born to obese dams (MatOb) had higher body adiposity and exhibited sex-specific differences in glucose tolerance and insulin secretion. The male MatOb offspring developed the highest extent of glucose intolerance and lowest glucose-induced insulin secretion. In contrast, P21 female offspring of obese dams had unimpaired insulin secretion. Using SAX-HPLC, we found that male MatOb had a decrease in pancreatic heparan sulfate glycosaminoglycan, which is a macromolecule critical for islet health. Notably, 8-weeks-old offspring of obese dams continued to exhibit a similar pattern of sex-differences in glucose intolerance and decreased islet insulin secretion. Overall, our study suggests that maternal obesity induces sex-specific changes to pancreatic HSG in offspring and a lasting effect on offspring insulin secretion, leading to the sex-differences in glucose intolerance.
Epigenomics in Hurthle Cell Neoplasms: Filling in the Gaps Towards Clinical Application
Authors: Canberk Sule , Lima Ana Rita , Pinto Mafalda , Soares Paula , Máximo Valdemar
Published: May 2021

It has been widely described that cancer genomes have frequent alterations to the epigenome, including epigenetic silencing of various tumor suppressor genes with functions in almost all cancer-relevant signalling pathways, such as apoptosis, cell proliferation, cell migration and DNA repair. Epigenetic alterations comprise DNA methylation, histone modification, and microRNAs dysregulated expression and they play a significant role in the differentiation and proliferation properties of TC. In this review, our group assessed the published evidence on the tumorigenic role of epigenomics in Hurthle cell neoplasms (HCN), highlighting the yet limited, heteregeneous and non-validated data preventing its current use in clinical practice, despite the well developed assessment techniques available. The identified evidence gaps call for a joint endeavour by the medical community towards a deeper and more systematic study of HCN, aiming at defining epigenetic markers in early diagnose, allowing for accurate stratification of maligancy and disease risk and for effective systemic treatment.
Tolvaptan in the Management of Acute Euvolemic Hyponatremia After Transsphenoidal Surgery: A Retrospective Single-Center Analysis
Authors: Indirli Rita , Ferreira de Carvalho Júlia , Cremaschi Arianna , Mantovani Beatrice , Sala Elisa , Serban Andreea Liliana , Locatelli Marco , Bertani Giulio , Carosi Giulia , Fiore Giorgio , Tariciotti Leonardo , Arosio Maura , Mantovani Giovanna , Ferrante Emanuele
Published: May 2021

Introduction

Syndrome of inappropriate antidiuresis (SIAD) can be a complication of hypothalamus-pituitary surgery. The use of tolvaptan in this setting is not well established, hence the primary aim of this study was to assess the sodium correction rates attained with tolvaptan compared with standard treatments (fluid restriction and/or hypertonic saline). Furthermore, we compared the length of hospital stay in the two treatment groups and investigated the occurrence of overcorrection and side effects including osmotic demyelination syndrome.

Methods

We retrospectively reviewed 308 transsphenoidal surgical procedures performed between 2011 and 2019 at our hospital. We selected adult patients who developed post-operative SIAD and recorded sodium monitoring, treatment modalities and outcomes. Correction rates were adjusted based on pre-treatment sodium levels.

Results

Twenty-nine patients (9.4%) developed post-operative SIAD. Tolvaptan was administered to 14 patients (median dose 15 mg). Standard treatments were employed in 14 subjects (fluid restriction n=11, hypertonic saline n=1, fluid restriction and hypertonic saline n=2). Tolvaptan yielded higher adjusted sodium correction rates (12.0 mmolL-1/24h and 13.4 mmolL-1/48h) than standard treatments (1.8 mmolL-1/24h, p<0.001, and 4.5 mmolL-1/48h, p=0.004, vs. tolvaptan). The correction rate exceeded 10 mmolL-1/24h or 18 mmolL-1/48h in 9/14 and 2/14 patients treated with tolvaptan, respectively, and in no patient who received standard treatments. No side effects including osmotic demyelination occurred. Tolvaptan was associated with a shorter hospital stay (11vs.15 days, p=0.01).

Conclusions

Tolvaptan is more effective than fluid restriction (with or without hypertonic saline) and allows for a shortened hospital stay in patients with SIAD after transsphenoidal surgery. However, its dose and duration should be carefully tailored, and close monitoring is recommended to allow prompt detection of overcorrection.
The Lifestyle-Dependent Microbial Interactions Vary Between Upstream and Downstream of the Three Gorges Dam
Authors: Wang Shang , Hou Weiguo , Jiang Hongchen , Dong Hailiang , Huang Liuqin , Chen Shu , Wang Bin , Chen Yongcan , Lin Binliang , Deng Ye
Published: May 2021

Dams represent the most significant anthropogenic disturbance to global rivers. Previous studies have shown that free-living and particle-attached microbes exhibited differentially in river and reservoir ecosystems. However, little is known about the dam’s effect on their co-occurrence patterns. Here, a random matrix theory (RMT)-based network approach was used to construct microbial ecological networks for free-living and particle-attached communities in the immediate vicinity of the Three Gorges Dam (TGD), based on a high-throughput sequencing of 16S rRNA gene. Microbial distribution pattern showed that differences caused by lifestyle (free-living vs. particle-attached) were greater than those caused by geographic position (upstream vs. downstream of the TGD). Network analysis revealed higher connectivity and a lower number of modules in the overall downstream networks. Furthermore, considering the lifestyle, the network structures and properties for free-living and particle-attached microbes were different between upstream and downstream of the dam. Specifically, free-living communities located upstream of the dam exhibited a more complex co-occurrence pattern than the particle-attached communities, whereas the opposite was true for those located downstream of the dam. This variation indicated a strong impact of the dam on microbial interactions for microbes with similar lifestyle in the vicinity of the dam. We identified 112 persistent operational taxonomic unit (OTU)-level species that stably coexisted regardless of lifestyle and geographic positions. These persistent species occupied 21.33–25.57% of the total nodes in each network, and together with their first neighbors, they contributed more than 50% of the nodes and edges belonging to each network. Furthermore, we found that taxonomic affiliations for central nodes (with high degree) varied in these persistent species sub-networks. Collectively, our findings expand the current understanding of the dam’s effect on species interaction variation patterns for free-living and particle-attached communities in the vicinity of the dam, which are more complex than traditional alpha and beta microbial diversity.
Admixed Populations Improve Power for Variant Discovery and Portability in Genome-Wide Association Studies
Authors: Lin Meng , Park Danny S. , Zaitlen Noah A. , Henn Brenna M. , Gignoux Christopher R.
Published: May 2021

Genome-wide association studies (GWAS) are primarily conducted in single-ancestry settings. The low transferability of results has limited our understanding of human genetic architecture across a range of complex traits. In contrast to homogeneous populations, admixed populations provide an opportunity to capture genetic architecture contributed from multiple source populations and thus improve statistical power. Here, we provide a mechanistic simulation framework to investigate the statistical power and transferability of GWAS under directional polygenic selection or varying divergence. We focus on a two-way admixed population and show that GWAS in admixed populations can be enriched for power in discovery by up to 2-fold compared to the ancestral populations under similar sample size. Moreover, higher accuracy of cross-population polygenic score estimates is also observed if variants and weights are trained in the admixed group rather than in the ancestral groups. Common variant associations are also more likely to replicate if first discovered in the admixed group and then transferred to an ancestral population, than the other way around (across 50 iterations with 1,000 causal SNPs, training on 10,000 individuals, testing on 1,000 in each population, p = 3.78e-6, 6.19e-101, ∼0 for FST = 0.2, 0.5, 0.8, respectively). While some of these FST values may appear extreme, we demonstrate that they are found across the entire phenome in the GWAS catalog. This framework demonstrates that investigation of admixed populations harbors significant advantages over GWAS in single-ancestry cohorts for uncovering the genetic architecture of traits and will improve downstream applications such as personalized medicine across diverse populations.
Intrinsic Resistance of Chronic Lymphocytic Leukemia Cells to NK Cell-Mediated Lysis Can Be Overcome In Vitro by Pharmacological Inhibition of Cdc42-Induced Actin Cytoskeleton Remodeling
Authors: Wurzer Hannah , Filali Liza , Hoffmann Céline , Krecke Max , Biolato Andrea Michela , Mastio Jérôme , De Wilde Sigrid , François Jean Hugues , Largeot Anne , Berchem Guy , Paggetti Jérôme , Moussay Etienne , Thomas Clément
Published: May 2021

Natural killer (NK) cells are innate effector lymphocytes with strong antitumor effects against hematologic malignancies such as chronic lymphocytic leukemia (CLL). However, NK cells fail to control CLL progression on the long term. For effective lysis of their targets, NK cells use a specific cell-cell interface, known as the immunological synapse (IS), whose assembly and effector function critically rely on dynamic cytoskeletal changes in NK cells. Here we explored the role of CLL cell actin cytoskeleton during NK cell attack. We found that CLL cells can undergo fast actin cytoskeleton remodeling which is characterized by a NK cell contact-induced accumulation of actin filaments at the IS. Such polarization of the actin cytoskeleton was strongly associated with resistance against NK cell-mediated cytotoxicity and reduced amounts of the cell-death inducing molecule granzyme B in target CLL cells. Selective pharmacological targeting of the key actin regulator Cdc42 abrogated the capacity of CLL cells to reorganize their actin cytoskeleton during NK cell attack, increased levels of transferred granzyme B and restored CLL cell susceptibility to NK cell cytotoxicity. This resistance mechanism was confirmed in primary CLL cells from patients. In addition, pharmacological inhibition of actin dynamics in combination with blocking antibodies increased conjugation frequency and improved CLL cell elimination by NK cells. Together our results highlight the critical role of CLL cell actin cytoskeleton in driving resistance against NK cell cytotoxicity and provide new potential therapeutic point of intervention to target CLL immune escape.
Regulation of Th1 T Cell Differentiation by Iron via Upregulation of T Cell Immunoglobulin and Mucin Containing Protein-3 (TIM-3)
Authors: Pfeifhofer-Obermair Christa , Tymoszuk Piotr , Nairz Manfred , Schroll Andrea , Klais Gloria , Demetz Egon , Engl Sabine , Brigo Natascha , Weiss Günter
Published: May 2021

Iron plays an important role in host–pathogen interactions, in being an essential element for both pathogen and host metabolism, but also by impacting immune cell differentiation and anti-microbial effector pathways. Iron has been implicated to affect the differentiation of T lymphocytes during inflammation, however, so far the underlying mechanism remained elusive. In order to study the role of iron in T cell differentiation we here investigated how dietary iron supplementation affects T cell function and outcome in a model of chronic infection with the intracellular bacterium Salmonella enterica serovar typhimurium (S. Typhimurium). Iron loading prior to infection fostered bacterial burden and, unexpectedly, reduced differentiation of CD4+ T helper cells type 1 (Th1) and expression of interferon-gamma (IFNγ), a key cytokine to control infections with intracellular pathogens. This effect could be traced back to iron-mediated induction of the negative immune checkpoint regulator T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), expressed on the surface of this T cell subset. In vitro experiments demonstrated that iron supplementation specifically upregulated mRNA and protein expression of TIM-3 in naïve Th cells in a dose-depdendent manner and hindered priming of those T cells towards Th1 differentiation. Importantly, administration of TIM-3 blocking antibodies to iron-loaded mice infected with S. Typhimurium virtually restored Th1 cell differentiation and significantly improved bacterial control. Our data uncover a novel mechanism by which iron modulates CD4+ cell differentiation and functionality and hence impacts infection control with intracellular pathogens. Specifically, iron inhibits the differentiation of naive CD4+ T cells to protective IFNγ producing Th1 lymphocytes via stimulation of TIM-3 expression. Finally, TIM-3 may serve as a novel drug target for the treatment of chronic infections with intracellular pathogens, specifically in iron loading diseases.
Development of Lentiviral Vectors Pseudotyped With Influenza B Hemagglutinins: Application in Vaccine Immunogenicity, mAb Potency, and Sero-Surveillance Studies
Authors: Ferrara Francesca , Del Rosario Joanne Marie M. , da Costa Kelly A. S. , Kinsley Rebecca , Scott Simon , Fereidouni Sasan , Thompson Craig , Kellam Paul , Gilbert Sarah , Carnell George , Temperton Nigel
Published: May 2021

Influenza B viruses (IBV) cause respiratory disease epidemics in humans and are therefore components of seasonal influenza vaccines. Serological methods are employed to evaluate vaccine immunogenicity prior to licensure. However, classical methods to assess influenza vaccine immunogenicity such as the hemagglutination inhibition assay (HI) and the serial radial hemolysis assay (SRH), have been proven to have many limitations. As such, there is a need to develop innovative methods that can improve on these traditional assays and provide advantages such as ease of production and access, safety, reproducibility, and specificity. It has been previously demonstrated that the use of replication-defective viruses, such as lentiviral vectors pseudotyped with influenza A hemagglutinins in microneutralization assays (pMN) is a safe and sensitive alternative to study antibody responses elicited by natural influenza infection or vaccination. Consequently, we have produced Influenza B hemagglutinin-pseudotypes (IBV PV) using plasmid-directed transfection. To activate influenza B hemagglutinin, we have explored the use of proteases in increasing PV titers via their co-transfection during pseudotype virus production. When tested for their ability to transduce target cells, the influenza B pseudotypes produced exhibit tropism for different cell lines. The pseudotypes were evaluated as alternatives to live virus in microneutralization assays using reference sera standards, mouse and human sera collected during vaccine immunogenicity studies, surveillance sera from seals, and monoclonal antibodies (mAbs) against IBV. The influenza B pseudotype pMN was found to effectively detect neutralizing and cross-reactive responses in all assays and shows promise as an effective and versatile tool in influenza research.
TLR7 Signaling Drives the Development of Sjögren’s Syndrome
Authors: Wang Yawen , Roussel-Queval Annie , Chasson Lionel , Hanna Kazazian Noël , Marcadet Laetitia , Nezos Andrianos , Sieweke Michael H. , Mavragani Clio , Alexopoulou Lena
Published: May 2021

Sjögren’s syndrome (SS) is a chronic systemic autoimmune disease that affects predominately salivary and lacrimal glands. SS can occur alone or in combination with another autoimmune disease like systemic lupus erythematosus (SLE). Here we report that TLR7 signaling drives the development of SS since TLR8-deficient (TLR8ko) mice that develop lupus due to increased TLR7 signaling by dendritic cells, also develop an age-dependent secondary pathology similar to associated SS. The SS phenotype in TLR8ko mice is manifested by sialadenitis, increased anti-SSA and anti-SSB autoantibody production, immune complex deposition and increased cytokine production in salivary glands, as well as lung inflammation. Moreover, ectopic lymphoid structures characterized by B/T aggregates, formation of high endothelial venules and the presence of dendritic cells are formed in the salivary glands of TLR8ko mice. Interestingly, all these phenotypes are abrogated in double TLR7/8-deficient mice, suggesting that the SS phenotype in TLR8-deficient mice is TLR7-dependent. In addition, evaluation of TLR7 and inflammatory markers in the salivary glands of primary SS patients revealed significantly increased TLR7 expression levels compared to healthy individuals, that were positively correlated to TNF, LT-α, CXCL13 and CXCR5 expression. These findings establish an important role of TLR7 signaling for local and systemic SS disease manifestations, and inhibition of such will likely have therapeutic value.
Human Milk Oligosaccharides: Their Effects on the Host and Their Potential as Therapeutic Agents
Authors: Rousseaux Anaïs , Brosseau Carole , Le Gall Sophie , Piloquet Hugues , Barbarot Sébastien , Bodinier Marie
Published: May 2021

Breastmilk is known to be very important for infants because it provides nutrients and immunological compounds. Among these compounds, human milk oligosaccharides (HMOs) represent the third most important component of breastmilk after lipids and lactose. Several experiments demonstrated the beneficial effects of these components on the microbiota, the immune system and epithelial barriers, which are three major biological systems. Indeed, HMOs induce bacterial colonization in the intestinal tract, which is beneficial for health. The gut bacteria can act directly and indirectly on the immune system by stimulating innate immunity and controlling inflammatory reactions and by inducing an adaptive immune response and a tolerogenic environment. In parallel, HMOs directly strengthen the intestinal epithelial barrier, protecting the host against pathogens. Here, we review the molecular mechanisms of HMOs in these different compartments and highlight their potential use as new therapeutic agents, especially in allergy prevention.
Which Method for Which Purpose? A Comparison of Line Intercept Transect and Underwater Photogrammetry Methods for Coral Reef Surveys
Authors: Urbina-Barreto Isabel , Garnier Rémi , Elise Simon , Pinel Romain , Dumas Pascal , Mahamadaly Vincent , Facon Mathilde , Bureau Sophie , Peignon Christophe , Quod Jean-Pascal , Dutrieux Eric , Penin Lucie , Adjeroud Mehdi
Published: May 2021

The choice of ecological monitoring methods and descriptors determines the effectiveness of a program designed to assess the state of coral reef ecosystems. Here, we comparer the relative performance of the traditional Line Intercept Transect (LIT) method with three methods derived from underwater photogrammetry: LIT on orthomosaics, photoquadrats from orthomosaics, and surface analyses on orthomosaics. The data were acquired at Reunion Island on five outer reef slopes and two coral communities on underwater lava-flows. Coral cover was estimated in situ using the LIT method and with LITs and photoquadrats digitized on orthomosaic. Surface analyses were done on the same orthomosaics. Structural complexity of the surveyed sites was calculated from digital elevation models using three physical descriptors (fractal dimension, slope, surface complexity), and used to explore their possible influence in coral cover estimates. We also compared the methods in terms of scientific outputs, the human expertise and time required. Coral cover estimates obtained with in situ LITs were higher than those obtained with digitized LITs and photoquadrats. Surfaces analyses on orthomosaics yielded the lowest but most the precise cover estimates (i.e., lowest sample dispersion). Sites with the highest coral cover also had the highest structural complexity. Finally, when we added scientific outputs, and requirements for human expertise and time to our comparisons between methods, we found that surface analysis on the orthomosaics was the most efficient method. Photoquadrats were more time-consuming than both in situ and digitized LITs, even though they provided coral cover estimates similar to those of digitized LITs and yielded more than one descriptor. The LIT in situ method remains the least time-consuming and most effective for species-level taxonomic identifications but is the most limited method in terms of data outputs and representativeness of the ecosystem.
Environmental Factors Causing Stress in Avicennia marina Mangrove in Rabigh Lagoon Along the Red Sea: Based on a Multi-Approach Study
Authors: Aljahdali Mohammed O. , Alhassan Abdullahi B. , Zhang Zhaohui
Published: May 2021

Lagoons along the Red Sea are socio-economically important but most vulnerable ecosystems. Strong evaporation, strengthened due to global warming, leads to high salinity and high temperature in surface water, which exacerbate physiological stress in mangroves. Rabigh Lagoon is characterized by unusually large spatial differences in nutrient dynamics and physicochemical parameters. We conducted a multi-approach study to demonstrate how environmental factors cause growth retardation and stress in mangroves. There were significant variations (P < 0.05) in water salinities and temperatures, nitrogen and phosphorus abundance in sediments, and antioxidants in mangroves among 8 sites across the lagoon. Salinity and water temperature rapidly increased from the northern where Red Sea seawater enters to the southern end, but dissolved oxygen declined. High salinity (44.9), high surface water temperature (28.8°C) and relatively high nutrients at the southern end of the lagoon (S8) corresponded to high concentrations of antioxidants. High δ13C (−12.4‰) and δ15N (4.9‰) in the sediments at S8 also reveal relatively high nutrient level due to stagnant water, camel grazing, and runoff bringing in fertilizer from agriculture activities in the catchments during seasonal flooding events. Principal component analyses showed that N and P limitation at the lagoon entrance is the leading cause for mangrove stress, while high salinity, temperature, and low dissolved oxygen are the predominant factors for high antioxidants concentrations at the southern end of the lagoon.
Drift Indices Confirm That Rapid Larval Displacement Is Essential for Recruitment Success in High-Latitude Oceans
Authors: Tiedemann Maik , Slotte Aril , Nash Richard D. M. , Stenevik Erling K. , Kjesbu Olav S.
Published: May 2021

Larval drift is a key process for successful fish recruitment. We used Norwegian spring-spawning herring (Clupea harengus) as model species to investigate the relationship between larval drift and recruitment. Larval drift indices were derived from simulations based on survey observations between 1993 and 2016. We show that forward simulated larval drift indices have an important positive relation to recruitment success. The relationship demonstrates elevated recruitment when larvae relocate rapidly northwards toward the Barents Sea. Negative or low larval drift indices coincide with only weak recruitment emphasizing limited survival in years with enhanced larval retention. Hence, with this work we combine drift model outcomes refined with survey data indicating that more extensive larval drift is an important component in population dynamics for high-latitude small pelagic fishes. However, larval displacement alone represents only one among many controlling factors but may offer possible predictions of the probability of higher or lower recruitment in the short term. The applicability of the drift indices is adaptable in all world oceans and all marine organisms that occupy planktonic life stages exposed to dynamic ocean currents. The study demonstrates how larval drift indices help to identify larval transport or retention to be crucial for population replenishment.
On the Nanomechanical and Viscoelastic Properties of Coatings Made of Recombinant Sea Star Adhesive Proteins
Authors: Lefevre Mathilde , Tran Thi Quynh , De Muijlder Thomas , Pittenger Bede , Flammang Patrick , Hennebert Elise , Leclère Philippe
Published: May 2021

To attach to surfaces in the sea, sea stars produce proteinaceous adhesive secretions. Sfp1 is a major constituent of this adhesive, where it is present in the form of four subunits (named Sfp1α to δ) displaying specific protein-, carbohydrate- and metal-binding domains. Recently, two recombinant proteins inspired from Sfp1 have been produced: one corresponding to the C-terminal part of Sfp1β and the other to the full-length Sfp1δ. Adsorption ability tests showed that both recombinant proteins were able to adsorb and to form coatings on different surfaces in artificial seawater as well as in Tris buffer supplemented with NaCl or CaCl2. In this study, we used Atomic Force Microscopy (AFM) to characterize the nanomechanical properties of these coatings with an emphasis on functional characteristics such as adhesive properties and modulus of elasticity. We used AFM techniques which are the most appropriate to characterize the coating microstructure combined with the mapping of its nanomechanical properties.
High Infection Fatality Rate Among Elderly and Risk Factors Associated With Infection Fatality Rate and Asymptomatic Infections of COVID-19 Cases in Hong Kong
Authors: Tao Jun , Zhang Xiaoyu , Musa Salihu S. , Yang Lin , He Daihai
Published: May 2021

Background: Since the emergence in December 2019, the COVID-19 pandemic has become one of the greatest global public health threats in history. However, asymptomatic infections have increased the challenges of providing accurate estimates for the infection fatality rate (IFR) of COVID-19.

Methods: We calculated the asymptomatic case ratios based on the reported COVID-19 cases in Hong Kong where intensive testing has been conducted in close contacts and high-risk populations. We estimated the IFR using both symptomatic and asymptomatic cases as denominator. The boosted regression tree (BRT) and multivariable logistic regression models were used to identify relative contribution and effect size of the risk factors associated with the asymptomatic cases and IFRs.

Results: The ratio of the asymptomatic patients in Hong Kong was higher than many other regions over the world. Imported cases had a higher asymptomatic proportion than local cases. Older age and male were associated with a higher IFR than younger age and females.

Conclusion: Policymakers should consider the potential risk factors for the asymptomatic infections and IFRs by the Hong Kong surveillance data to mitigate the diseases and reduce the case mortality of COVID-19.
Kidney Biopsy in Patients With Monoclonal Gammopathy: A Multicenter Retrospective Cohort Study
Authors: Nie Sheng , Wang Mengyi , Wan Qijun , Kong Yaozhong , Ou Jun , Jia Nan , Zhang Xiaodong , Luo Fan , Liu Xiaoting , Wang Lin , Cao Yue , Chen Ruixuan , Zhao Mingpeng , Chan David Yiu Leung , Wang Guobao
Published: May 2021

Objectives: To analyze the clinical characteristics and renal pathological manifestations of patients with monoclonal gammopathy (MG) and kidney injury.

Methods: This was a multicenter retrospective cohort study conducted at four tertiary hospitals in China. The study population comprised patients with MG admitted from January 1 2013 to December 31 2020. Hospitalization records, laboratory data, and kidney biopsy reports of all patients were collected from the electronic hospital information systems. The study outcomes included kidney disease progression and major hemorrhagic complications after kidney biopsy.

Results: We identified 1,164 patients with MG, 782 (67.2%) of whom had underlying kidney injury. Of 101 patients who underwent kidney biopsy, 16 had malignant neoplasms. Amyloid nephropathy was the most common finding (n = 34, 33.7%), followed by membranous nephropathy (n = 18, 17.8%) and membranoproliferative nephritis (n = 8, 7.9%). Among 85 patients with non-malignant hematologic conditions who underwent kidney biopsy, 43 had MG of renal significance (MGRS) related lesions and 42 had MG-unrelated lesions. The risk of kidney disease progression was higher in patients with kidney injury than in patients without kidney injury.

Conclusion: Among patients with MG and kidney injury, only 12.9% underwent kidney biopsy and more than 40% of these patients had MG-unrelated lesions. A kidney biopsy is safe and essential to maximize the possibility of correct diagnosis for patients with clinically suspected MG of renal significance (MGRS).
Diazotrophs for Lowering Nitrogen Pollution Crises: Looking Deep Into the Roots
Authors: Imran Asma , Hakim Sughra , Tariq Mohsin , Nawaz Muhammad Shoib , Laraib Iqra , Gulzar Umaira , Hanif Muhammad Kashif , Siddique Muhammad Jawad , Hayat Mahnoor , Fraz Ahmad , Ahmad Muhammad
Published: May 2021

During and after the green revolution in the last century, agrochemicals especially nitrogen (N) were extensively used. However, it resulted in a remarkable increase in crop yield but drastically reduced soil fertility; increased the production cost, food prices, and carbon footprints; and depleted the fossil reserves with huge penalties to the environment and ecological sustainability. The groundwater, rivers, and oceans are loaded with N excess which is an environmental catastrophe. Nitrogen emissions (e.g., ammonia, nitrogen oxide, nitrous oxide) play an important role in global climate change and contribute to particulate matter and acid rain causing respiratory problems, cancers, and damage to forests and buildings. Therefore, the nitrogen-polluted planet Earth needs concerted global efforts to avoid the disaster. Improved agricultural N management focuses on the synchronization of crop N demand and N supply along with improving the N-use efficiency of the crops. However, there is very little focus on the natural sources of N available for plants in the form of diazotrophic bacteria present inside or on the root surface and the rhizosphere. These diazotrophs are the mini-nitrogen factories that convert available (78%) atmospheric N2 to ammonia through a process known as “biological nitrogen fixation” which is then taken up by the plants for its metabolic functioning. Diazotrophs also stimulate root architecture by producing plant hormones and hence improve the plant’s overall ability to uptake nutrients and water. In recent years, nanotechnology has revolutionized the whole agri-industry by introducing nano-fertilizers and coated/slow-releasing fertilizers. With this in mind, we tried to explore the following questions: To what extent can the crop N requirements be met by diazotroph inoculation? Can N input to agriculture be managed in a way leading to environmental benefits and farmers saving money? Can nanotechnology help in technological advancement of diazotroph application? The review suggests that an integrated technology based on slow-releasing nano-fertilizer combined with diazotrophs should be adopted to decrease nitrogen inputs to the agricultural system. This integrated technology would minimize N pollution and N losses to much extent.
Induction and Repression of Hydrolase Genes in Aspergillus oryzae
Authors: Tanaka Mizuki , Gomi Katsuya
Published: May 2021

The filamentous fungus Aspergillus oryzae, also known as yellow koji mold, produces high levels of hydrolases such as amylolytic and proteolytic enzymes. This property of producing large amounts of hydrolases is one of the reasons why A. oryzae has been used in the production of traditional Japanese fermented foods and beverages. A wide variety of hydrolases produced by A. oryzae have been used in the food industry. The expression of hydrolase genes is induced by the presence of certain substrates, and various transcription factors that regulate such expression have been identified. In contrast, in the presence of glucose, the expression of the glycosyl hydrolase gene is generally repressed by carbon catabolite repression (CCR), which is mediated by the transcription factor CreA and ubiquitination/deubiquitination factors. In this review, we present the current knowledge on the regulation of hydrolase gene expression, including CCR, in A. oryzae.
Glycosylation at Asn254 Is Required for the Activation of the PDGF-C Protein
Authors: Hu Wenjie , Zhang Ruting , Chen Wei , Lin Dongyue , Wei Kun , Li Jiahui , Zhang Bo , Li Xuri , Tang Zhongshu
Published: May 2021

Platelet-derived growth factor C (PDGF-C) is a member of the PDGF/VEGF (vascular endothelial growth factor) family, which includes proteins that are well known for their mitogenic effects on multiple cell types. Glycosylation is one of the most important forms of posttranslational modification that has a significant impact on secreted and membrane proteins. Glycosylation has many well-characterized roles in facilitating protein processing and contributes to appropriate folding, conformation, distribution, and stability of proteins that are synthesized intracellularly in the endoplasmic reticulum (ER) and Golgi apparatus. Although the general process and functions of glycosylation are well documented, there are most likely others yet to be discovered, as the glycosylation of many potential substrates has not been characterized. In this study, we report that the PDGF-C protein is glycosylated at three sites, including Asn25, Asn55, and Asn254. However, we found that mutations at any of these sites do not affect the protein expression or secretion. Similarly, disruption of PDGF-C glycosylation had no impact on its progression through the ER and Golgi apparatus. However, the introduction of a mutation at Asn254 (N254 A) prevents the activation of full-length PDGF-C and its capacity for signaling via the PDGF receptor. Our findings reveal that glycosylation affects PDGF-C activation rather than the protein synthesis or processing. This study characterizes a crucial modification of the PDGF-C protein, and may shed new light on the process and function of glycosylation.
The Therapeutic Potential of Galectin-3 in the Treatment of Intrahepatic Cholangiocarcinoma Patients and Those Compromised With COVID-19
Authors: Li Hao , Li Jianmin , Xiao Wei , Zhang Yujing , Lv Yuan , Yu Xing , Zheng Jiao
Published: May 2021

The novel coronavirus pneumonia COVID-19 is characterized by all age susceptibility, which imposes a dramatic threat to the human species all over the world. According to current available data, the cytokine storm appears to be the most life-threatening symptom of severe COVID-19 cases accompanied with lung fibrosis. Galectin-3 (Gal-3), a member of soluble β-galactoside-binding lectin families, has been implicated as a key regulator in various inflammation conditions in addition to its well-documented roles in cancer. The pro-inflammatory activity of Gal-3 in the inflammatory response and lung fibrosis of COVID-19 has been proposed by emerging studies, which suggested that inhibition of Gal-3 may represent a novel treatment approach for COVID-19 patients. Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor prognosis. ICC accounts for 10–25% of primary liver cancers with limited therapeutic options, which has higher incidence in Asian countries, particularly in China. Cancer patients, including ICC patients, are highly vulnerable to COVID-19 due to their impaired immune system. It is thus undoubtedly a challenge for our oncology department to establish effective treatment strategies under the influence of the COVID-19 crisis. According to our management procedures in the COVID-19 era, emergency treatment will be applied to ICC patients who are under life-threatening conditions, despite the COVID-19 infection. To the best of our knowledge, the modulatory function of Gal-3 in ICC is still barely explored to date. In order to evaluate the therapeutic potential of Gal-3 for ICC patients or those comprised with COVID-19, we herein report our preliminary investigation into roles of Gal-3 in ICC. Our results exhibited that the expression of Gal-3 was significantly up-regulated in ICC tissues, and a significant correlation was observed between its overexpression and malignant progression of ICC cells. We further discussed the activity and possible molecular mechanisms of Gal-3 in ICC, which may pave the ways for further exploring the possibility of Gal-3 as a potential therapeutic target for treating ICC patients or those with COVID-19-related conditions.
Lymph Node Immune Profiles as Predictive Biomarkers for Immune Checkpoint Inhibitor Response
Authors: Goode Emily F. , Roussos Torres Evanthia T. , Irshad Sheeba
Published: May 2021

The need for predictive biomarkers that can accurately predict patients who will respond to immune checkpoint inhibitor (ICI) immunotherapies remains a clinically unmet need. The majority of research efforts have focused on expression of immune-related markers on the tumour and its associated tumour microenvironment (TME). However, immune response to tumour neoantigens starts at the regional lymph nodes, where antigen presentation takes place and is regulated by multiple cell types and mechanisms. Knowledge of the immunological responses in bystander lymphoid organs following ICI therapies and their association with changes in the TME, could prove to be a valuable component in understanding the treatment response to these agents. Here, we review the emerging data on assessment of immunological responses within regional lymph nodes as predictive biomarkers for immunotherapies.