bluuebunny/crossref_metadata_2025 huggingface dataset:
The Viscosity of the Top Third of the Lower Mantle Estimated Using GPS, GRACE, and Relative Sea Level Measurements of Glacial Isostatic Adjustment
Authors: Argus Donald F. , Peltier W. Richard , Blewitt Geoffrey , Kreemer Corné
Published: March 2021

We distinguish between two models of solid Earth's viscoelastic response to unloading of the Laurentide ice sheet over the past 26,000 years. The upper mantle viscosity in both models is 0.5 × 1021 Pa s. The viscosity of the top 500 km of the lower mantle (670–1,170 km) in model L17 is 13 × 1021 Pa s, eight times larger than the value of 1.6 × 1021 Pa s in ICE‐6G_D (VM5a). In ICE‐6G_D (VM5a), viscous relaxation of solid Earth was rapid 8,000 years ago and is slow today, with present‐day uplift at the Laurentide ice center being 12 mm/yr. In L17, solid Earth relaxed more slowly 8,000 years ago but is faster today, with present uplift of the ice center occurring at 20 mm/yr. The significant difference is not due to different ice histories given that total ice loss in L17 is just 12% less than in ICE‐6G_D. We determine a comprehensive set of GPS uplift rates for North America that is more accurate than in prior studies due to (1) more sites and a longer data time history, (2) removal of elastic loading produced by increase in Great Lakes water, and (3) technical advances in GPS positioning that have significantly reduced the dispersion in position estimates. We find uplift at the ice center to be about 12 mm/yr, supporting the low value of the viscosity of the top 500 km of the lower mantle in ICE‐6G_D (VM5a), but ruling out the high value in L17.
Dynamics of Eddy Generation in the Southeast Tropical Indian Ocean
Authors: Wang Xuan , Cheng Xuhua , Liu Xiaohui , Chen Dake
Published: March 2021

Satellite observations indicate that the southeast tropical Indian Ocean (SETIO) is a region full of eddies, which are generated near 120°E and propagate westward/southwestward. The vertical structure of eddies shows that eddy‐induced temperature anomalies are mainly confined within the upper 200 m. The maximum anomaly is located at ∼100 m depth, near the depth of the thermocline, indicating that eddy generation is related to vertical motions of the thermocline. To further investigate the generation mechanisms of mesoscale eddies, we obtain a suite of solutions of the 1½‐layer reduced gravity model, which can capture the first baroclinic process quite well. The solutions suggest that wind forcing from the tropical Pacific Ocean and nonlinearity play important roles in eddy generation in the SETIO.
Assessment of Atmospheric Oxidizing Capacity Over the Beijing‐Tianjin‐Hebei (BTH) Area, China
Authors: Feng Tian , Zhao Shuyu , Hu Bo , Bei Naifang , Zhang Xiu , Wu Jiarui , Li Xia , Liu Lang , Wang Ruonan , Tie Xuexi , Li Guohui
Published: March 2021

The atmospheric oxidizing capacity (AOC) plays a key role in atmospheric chemistry, determining the removal of most reduced gases in the atmosphere. In this study, we assess the summertime AOC from 7 to 22 June 2014 associated with a field campaign conducted at Wangdu in the Beijing‐Tianjin‐Hebei region (BTH), China using the WRF‐Chem model. The model reasonably well reproduces the incident solar radiation, ambient O3 and fine particulate matter (PM2.5) concentrations, the photolysis rates of O3 and NO2, and radical concentrations against measurements in the BTH. The model results show high daytime AOC levels in urban areas and relatively low AOC in remote areas of the BTH. The diurnal cycle of the AOC exhibits a unimodal pattern with peaks at noon. OH radical contributes about 68% of the daily average AOC in Beijing, followed by O3 (27%) and NO3 (5%). At Wangdu, the production rate of OH radical reaches around 13 ppb h−1 at noon, which is mainly resulted from the reaction of HO2 with NO. The OH radical loss is primarily contributed by reactions with volatile organic compounds, followed by CO and NO2. Statistically, the population hourly or afternoon average O3 and Ox (=O3 + NO2) concentrations are significantly correlated with the AOC in Beijing, constituting potential simplified tracers to indicate the AOC level.
Representing Human Water Management in a Land Surface Model Using a Supply/Demand Approach
Authors: Zhou Xudong , Polcher Jan , Dumas Patrice
Published: March 2021

The impact of human water management on river discharge is increasingly viewed as a missing process in Earth system modeling. Models which have attempted to include it are generally at coarse resolution and uncoupled to the atmosphere. We propose to describe human water management at high spatial resolution using ORganizing Carbon and Hydrology In Dynamic EcosystEms concept of hydrological‐transfer‐units in the routing parametrization. Irrigated areas are linked to river abstraction points using a minimization process. The directed graphs of river flows and adduction network for irrigation is transposed to propagate water demands upstream. Reservoirs and dams are placed along the graph to balance supply and demands in the four chosen water value classes. Dam regulation is assumed to maximize demand satisfaction and dampen floods while respecting the properties of the infrastructure. The developed human water management module is applied to the Yellow River where irrigation and dam regulation are known to have a strong impact. Results show that the impact of human water management is strongly heterogeneous over space. It propagates along the river channels and can be mitigated by the confluence of tributaries. Moreover, the human impact has a strong seasonality due to time varying irrigation demands and the response of dam regulation. A number of uncertainties still remain and affect the simulated river discharge. Nevertheless, the representation of human water management improves the model's behavior in terms of magnitude and intra‐annual variations of river discharge, and offers the opportunity to implement anthropogenic processes in the water cycle of Earth System Models.
Use of an Efficient Proxy Solution for the Hillslope‐Storage Boussinesq Problem in Upscaling of Subsurface Stormflow
Authors: Ranjram Mark , Craig James R.
Published: March 2021

The hillslope‐storage Boussinesq (hsB) equation is a modification of the one‐dimensional Boussinesq representation of saturated subsurface flow that accommodates the impact of converging and diverging flows resulting from a hillslope with nonconstant width. Here, a surrogate model, the hsB Proxy, is developed which closely emulates the results of high‐quality numerical solutions of the hsB to reproduce the drainage response of a wide range of wedge‐shaped hillslopes in response to a recharge time series at a fraction of the computational cost of a numerical solution and with minimal loss of fidelity. The efficacy of the Proxy in emulating the hsB response of a single hillslope and the aggregate response of a network of hillslopes is demonstrated. The Proxy applies to wedge‐shaped hillslopes with homogenous hydraulic conductivity under uniform recharge, with the expectation that these hillslopes may inform future investigations into the upscaling behavior that results in the known power‐law relationship between subsurface storage and outflow in a basin. The utility of the hsB as a tool for evaluating upscaling problems is demonstrated in two applications. First, the Proxy response is compared to the known basin‐scale recession behavior in the Panola Mountain Research Watershed, under both transient and steady‐state conditions. Second, the Proxy is applied to derive the single best effective hillslope in a basin. The Proxy is expected to be a useful tool for rapid simulation of subsurface flow from hillslopes for use in hydrological models and land surface schemes.
Facilitating electrocatalytic hydrogen evolution via multifunctional tungsten@tungsten disulfide core–shell nanospheres
Authors: Ji Liang , Cao Hongyu , Xing Wensi , Liu Shuaicheng , Deng Qian , Shen Shengping
Published: March 2021

Multifunctional W@WS2 core–shell nanospheres with abundant catalytic sites, enhanced electrical conductivity, and enlarged electrochemical surface area for hydrogen evolution reaction.
SCENTinel 1.0: Development of a Rapid Test to Screen for Smell Loss
Authors: Parma Valentina , Hannum Mackenzie E , O’Leary Maureen , Pellegrino Robert , Rawson Nancy E , Reed Danielle R , Dalton Pamela H
Published: March 2021

Commercially available smell tests are primarily used in research or in-depth clinical evaluations and are too costly and time-consuming for population surveillance in health emergencies like COVID-19. To address this need, we developed the SCENTinel 1.0 test, which rapidly evaluates 3 olfactory functions: detection, intensity, and identification. We tested whether self-administering the SCENTinel 1.0 test discriminates between individuals with self-reported smell loss and those with average smell ability (normosmic individuals) and provides performance comparable to the validated and standardized NIH Toolbox Odor Identification Test in normosmic individuals. Using Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1.0 performance of a group of self-reported anosmic individuals (N = 111, 47 ± 13 years old, F = 71%) and normosmic individuals (N = 154, 47 ± 14 years old, F = 74%) as well as individuals reporting other smell disorders (such as hyposmia or parosmia; N = 42, 55 ± 10 years old, F = 67%). Ninety-four percent of normosmic individuals met our SCENTinel 1.0 accuracy criteria compared with only 10% of anosmic individuals and 64% of individuals with other smell disorders. Overall performance on SCENTinel 1.0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC = 0.95, specificity = 0.94). Odor intensity provided the best single-feature predictor to classify normosmic individuals. Among normosmic individuals, 92% met the accuracy criteria at both SCENTinel 1.0 and the NIH Toolbox Odor Identification Test. SCENTinel 1.0 is a practical test able to discriminate individuals with smell loss and will likely be useful in many clinical situations, including COVID-19 symptom screening.
Simulation for cybersecurity: state of the art and future directions
Authors: Kavak Hamdi , Padilla Jose J , Vernon-Bido Daniele , Diallo Saikou Y , Gore Ross , Shetty Sachin
Published: March 2021

In this article, we provide an introduction to simulation for cybersecurity and focus on three themes: (1) an overview of the cybersecurity domain; (2) a summary of notable simulation research efforts for cybersecurity; and (3) a proposed way forward on how simulations could broaden cybersecurity efforts. The overview of cybersecurity provides readers with a foundational perspective of cybersecurity in the light of targets, threats, and preventive measures. The simulation research section details the current role that simulation plays in cybersecurity, which mainly falls on representative environment building; test, evaluate, and explore; training and exercises; risk analysis and assessment; and humans in cybersecurity research. The proposed way forward section posits that the advancement of collecting and accessing sociotechnological data to inform models, the creation of new theoretical constructs, and the integration and improvement of behavioral models are needed to advance cybersecurity efforts.
Emerging evidence for a mechanistic link between low-frequency oscillation of ventricular repolarization measured from the electrocardiogram T-wave vector and arrhythmia
Authors: Taggart Peter , Pueyo Esther , Duijvenboden Stefan van , Porter Bradley , Bishop Martin , Sampedro-Puente David A , Orini M , Hanson B , Rinaldi Christopher A , Gill Jaswinder S , Lambiase Pier
Published: March 2021

Strong recent clinical evidence links the presence of prominent oscillations of ventricular repolarization in the low-frequency range (0.04–0.15 Hz) to the incidence of ventricular arrhythmia and sudden death in post-MI patients and patients with ischaemic and non-ischaemic cardiomyopathy. It has been proposed that these oscillations reflect oscillations of ventricular action potential duration at the sympathetic nerve frequency. Here we review emerging evidence to support that contention and provide insight into possible underlying mechanisms for this association.
Evidence of gene nucleotide composition favoring replication and growth in a fastidious plant pathogen
Authors: Castillo Andreina I , Almeida Rodrigo P P
Published: March 2021

Nucleotide composition (GC content) varies across bacteria species, genome regions, and specific genes. In Xylella fastidiosa, a vector-borne fastidious plant pathogen infecting multiple crops, GC content ranges between ∼51-52%; however, these values were gathered using limited genomic data. We evaluated GC content variations across X. fastidiosa subspecies fastidiosa (N = 194), subsp. pauca (N = 107), and subsp. multiplex (N = 39). Genomes were classified based on plant host and geographic origin; individual genes within each genome were classified based on gene function, strand, length, ortholog group, core vs accessory, and recombinant vs non-recombinant. GC content was calculated for each gene within each evaluated genome. The effects of genome and gene-level variables were evaluated with a mixed effect ANOVA, and the marginal-GC content was calculated for each gene. Also, the correlation between gene-specific GC content vs natural selection (dN/dS) and recombination/mutation (r/m) was estimated. Our analyses show that intra-genomic changes in nucleotide composition in X. fastidiosa are small and influenced by multiple variables. Higher AT-richness is observed in genes involved in replication and translation, and genes in the leading strand. In addition, we observed a negative correlation between high-AT and dN/dS in subsp. pauca. The relationship between recombination and GC content varied between core and accessory genes. We hypothesize that distinct evolutionary forces and energetic constraints both drive and limit these small variations in nucleotide composition.
A novel hybrid liquefied natural gas process with absorption refrigeration integrated with molten carbonate fuel cell
Authors: Mehrpooya Mehdi , Bahramian Parimah , Pourfayaz Fathollah , Katooli Hadi , Delpisheh Mostafa
Published: March 2021

The production of liquefied natural gas (LNG) is a high energy-consuming process. The study of ways to reduce energy consumption and consequently to reduce operational costs is imperative. Toward this purpose, this study proposes a hybrid system adopting a mixed refrigerant for the liquefaction of natural gas that is precooled with an ammonia/water absorption refrigeration (AR) cycle utilizing the exhaust heat of a molten carbonate fuel cell, 700°C and 2.74 bar, coupled with a gas turbine and a bottoming Brayton super-critical carbon dioxide cycle. The inauguration of the ammonia/water AR cycle to the LNG process increases the cooling load of the cycle by 10%, providing a 28.3-MW cooling load duty while having a 0.45 coefficient of performance. Employing the hybrid system reduces energy consumption, attaining 85% overall thermal efficiency, 53% electrical efficiency and 35% fuel cell efficiency. The hybrid system produces 6300 kg.mol.h−1 of LNG and 146.55 MW of electrical power. Thereafter, exergy and sensitivity analyses are implemented and, accordingly, the fuel cell had an 83% share of the exergy destruction and the whole system obtained a 95% exergy efficiency.
Phenotypic and genotypic antimicrobial resistance in clinical anaerobic isolates from India
Authors: Sood Anshul , Ray Pallab , Angrup Archana
Published: March 2021

Background

Antimicrobial resistance (AMR) in anaerobes remains a neglected field. The laborious procedures, non-compliance with the standard methodology and differences in interpretive breakpoints add variation in resistance data.

Objectives

To assess the phenotypic and genotypic resistance among clinically important anaerobes to six antibiotics frequently used as empirical therapy for anaerobic infections.

Methods

A total of 150 anaerobic isolates were recovered from clinical specimens. The antimicrobial susceptibility was determined by the breakpoint agar dilution method as per CLSI guidelines. The presence of genes encoding resistance to metronidazole (nim gene), imipenem (cfiA gene) and mobilizable insertion sequence (IS) elements was detected to comprehend their association with phenotypic resistance.

Results

This is a first study of its kind from the Indian subcontinent looking at the AMR and associated genes in anaerobes. Resistance to metronidazole, clindamycin, imipenem, piperacillin/tazobactam and cefoxitin was 32.6%, 42.6%, 0.6%, 38% and 35.3%, respectively. No resistance was observed to chloramphenicol. The nim gene was detected in 24.6% of isolates, of which 70.2% were resistant by phenotype. On sequencing, the PCR products of six random nim genes showed a close similarity to nimE of Bacteroides fragilis with 99% nucleotide and 100% amino acid sequence similarity. The cfiA gene, associated with imipenem resistance, was detected in 16% of isolates.

Conclusions

The possibility of isolates carrying AMR genes to become resistant to antibiotics by acquisition of IS elements mandates attention to periodically monitor the resistance patterns and geographic distribution of these genes and IS elements to understand the trends of AMR in anaerobes.
Temporal kinetics of bovine mammary IgG secretion into colostrum and transition milk
Authors: Schalich Kasey M , Reiff Olivia M , Nguyen Blake T , Lamb Cassandra L , Mondoza Cecilia R , Selvaraj Vimal
Published: March 2021

Neonatal calf survival and health is predominantly dependent on sufficient consumption of immunoglobulin G (IgG) and the resulting transfer of passive immunity (TPI). In this study, we investigate the potential for continued IgG secretion and temporal kinetics of mammary IgG output in sequential milkings performed at 0, 4, 16, 28, 40, and 52 hr postcalving in Holstein dairy cows. For colostrum (0 hr), we also scrutinize the relationships between IgG concentration, volume, refractometer readings (˚Bx values, Brix) and concentration of sugars (lactose and glucose). Mammary transcripts postpartum (0 hr) indicated that active IgG secretion continues beyond the first milking (colostrum; n = 4 to 5). IgG measurements at the different timepoints indicated that colostrum represents only 25.1% of the total IgG produced across the 6 sequential milking timepoints, with a substantial 48.9% being secreted into transition milk over the next 3 timepoints (4-, 6-, and 28-hr) combined. The differences on the basis of IgG concentrations across 0-, 4-, and 16-hr milking timepoints were not statistically significant (P = 0.1522; n = 9). For colostrum, volume remained highly variable, even with induced let-down prior to milking (n = 27). Nonetheless, colostrum IgG secretion was significantly co-regulated with volume (R2 = 0.915; P < 0.001; n = 18), an association that was stronger than that measured for lactose (R2 = 0.803; P < 0.001; n = 18) and glucose (R2 = 0.467; P = 0.002; n = 17). Comparing colostrum ˚Bx values to absolute IgG concentrations showed no correlation (R2 = 0.127; P = 0.07; n = 27); biochemical separation of colostrum components indicated that both proteins and nonprotein solutes could affect ˚Bx values (P < 0.0001 for both; n = 5). This suggests that ˚Bx values do not reasonably indicate IgG concentration to serve as a measure of “colostrum quality.” Additionally, our finding that early transition milk (4-, 6-, and 28-hr) can contribute substantially more IgG than colostrum forces a rethink of existing feeding paradigms and means to maximize TPI in calves. Collectively, our results reveal the remarkable value of early transition milk and caveats to colostrum assessments that could advance application in enhancing neonatal calf health.
Projecting the Global Potential Distribution of Cydia pomonella (Lepidoptera: Tortricidae) Under Historical and RCP4.5 Climate Scenarios
Authors: Guo Siwei , Ge Xuezhen , Zou Ya , Zhou Yuting , Wang Tao , Zong Shixiang
Published: March 2021

The codling moth Cydia pomonella (L.) (Lepidoptera: Tortricidae) is a destructive pest of apple (Malus domestica (Rosales: Rosaceae)), pear (Pyrus spp. (Rosales: Rosaceae)), and other pome tree fruits; outbreaks cause significant ecological and economic losses. In this study, we used CLIMEX model to predict and evaluate the global risk of C. pomonella based on historical climate data (1989–2018) and simulated future climate data (2071–2100) under the RCP4.5 scenarios. Cydia pomonella exhibited a wide distribution under both historical and future climate conditions. Climate change is predicted to expand the northern boundary of the potential distribution from approximately 60°N to 75°N. Temperature was the most dominant factor in climatic suitability for the pest. Combinations of multiple meteorological factors (relative humidity and precipitation) associated with a failure to break diapause in certain regions also affect suitability, particularly in northern South America and central Africa. Irrigation only had a slight impact on species favorability in some areas. The projections established in our study present insight into the global potential suitability of C. pomonella under climate change scenarios by the end of the 21st century. Farmers should be aware of the risk associated with the pest based on the results, which would provide guidance for quarantine agencies and trade negotiators worldwide.
Cavitary Coccidioidomycosis: Impact of azole antifungal therapy
Authors: Panicker Renni R , Bartels Helen C , Gotway Michael B , Ampel Neil M , Buras Matthew R , Lim Elisabeth S , Blair Janis E
Published: March 2021

Approximately 5 to 15% of patients with pulmonary coccidioidomycosis subsequently develop pulmonary cavities. These cavities may resolve spontaneously over a number of years; however, some cavities never close, and a small proportion causes complications such as hemorrhage, pneumothorax or empyema. The impact of azole antifungal treatment on coccidioidal cavities has not been studied. Because azoles are a common treatment for symptomatic pulmonary coccidioidomycosis, we aimed to assess the impact of azole therapy on cavity closure. From January 1, 2004, through December 31, 2014, we retrospectively identified 313 patients with cavitary coccidioidomycosis and excluded 42 who had the cavity removed surgically, leaving 271 data sets available for study. Of the 271 patients, 221 (81.5%) received azole therapy during 5-year follow-up; 50 patients did not receive antifungal treatment. Among the 271 patients, cavities closed in 38 (14.0%). Statistical modeling showed that cavities were more likely to close in patients in the treated group than in the nontreated group (hazard ratio, 2.14 [95% CI: 1.45–5.66]). Cavities were less likely to close in active smokers than nonsmokers (11/41 [26.8%] vs 97/182 [53.3%]; P = 0.002) or in persons with than without diabetes (27/74 [36.5%] vs 81/149 [54.4%]; P = 0.01).We did not find an association between cavity size and closure. Our findings provide rationale for further study of treatment protocols in this subset of patients with coccidioidomycosis.

Lay Summary

Coccidioidomycosis, known as valley fever, is a fungal infection that infrequently causes cavities to form in the lungs, which potentially results in long-term lung symptoms. We learned that cavities closed more often in persons who received antifungal drugs, but most cavities never closed completely.
Norovirus in Cancer Patients: A Review
Authors: Kondapi Divya Samantha , Ramani Sasirekha , Estes Mary K , Atmar Robert L , Okhuysen Pablo C
Published: March 2021

Norovirus (NoV) is the leading cause of viral-related diarrhea in cancer patients, in whom it can be chronic, contributing to decreased quality of life, interruption of cancer care, malnutrition, and altered mucosal barrier function. Immunosuppressed cancer patients shed NoV for longer periods of time than immunocompetent hosts, favoring quasispecies development and emergence of novel NoV variants. While nucleic acid amplification tests (NAATs) for NoV diagnosis have revolutionized our understanding of NoV burden of disease, not all NAATs provide information on viral load or infecting genotype. There is currently no effective antiviral or vaccine for chronic NoV infections. Screening for inhibitors of NoV replication in intestinal organoid culture models and creation of NoV-specific adoptive T cells are promising new strategies to develop treatments for chronic NoV in immunosuppressed patients. Herein we summarize data on the epidemiology, clinical manifestations, diagnostic challenges, and treatment of NoV infection in patients with cancer.
The microtubule-associated protein WDL4 modulates auxin distribution to promote apical hook opening in Arabidopsis
Authors: Deng Jia , Wang Xiangfeng , Liu Ziqiang , Mao Tonglin
Published: March 2021

The unique apical hook in dicotyledonous plants protects the shoot apical meristem and cotyledons when seedlings emerge through the soil. Its formation involves differential cell growth under the coordinated control of plant hormones, especially ethylene and auxin. Microtubules are essential players in plant cell growth that are regulated by multiple microtubule-associated proteins (MAPs). However, the role and underlying mechanisms of MAP-microtubule modules in differential cell growth are poorly understood. In this study, we found that the previously uncharacterized Arabidopsis MAP WAVE-DAMPENED2-LIKE4 (WDL4) protein plays a positive role in apical hook opening. WDL4 exhibits a temporal expression pattern during hook development in dark-grown seedlings that is directly regulated by ethylene signaling. WDL4 mutants showed a delayed hook opening phenotype while overexpression of WDL4 resulted in enhanced hook opening. In particular, wdl4-1 mutants exhibited stronger auxin accumulation in the concave side of the apical hook. Furthermore, the regulation of the auxin maxima and trafficking of the auxin efflux carriers PIN-FORMED1 (PIN1) and PIN7 in the hook region is critical for WDL4-mediated hook opening. Together, our study demonstrates that WDL4 positively regulates apical hook opening by modulating auxin distribution, thus unraveling a mechanism for MAP-mediated differential plant cell growth.
Across the great divide: revision of the genusEupetaurus(Sciuridae: Pteromyini), the woolly flying squirrels of the Himalayan region, with the description of two new species
Authors: Jackson Stephen M , Li Quan , Wan Tao , Li Xue-You , Yu Fa-Hong , Gao Ge , He Li-Kun , Helgen Kristofer M , Jiang Xue-Long
Published: March 2021

The woolly flying squirrel, Eupetaurus cinereus, is among the rarest and least studied mammals in the world. For much of the 20th century it was thought to be extinct, until it was rediscovered in 1994 in northern Pakistan. This study outlines the first taxonomic and biogeographical review of the genus Eupetaurus, which until now has contained only a single species. Careful review of museum specimens and published records of Eupetaurus demonstrates that the genus occurs in three widely disjunct areas situated on the western (northern Pakistan and north-western India), north-central (south-central Tibet, northern Sikkim and western Bhutan) and south-eastern margins (north-western Yunnan, China) of the Himalayas. Taxonomic differentiation between these apparently allopatric populations of Eupetaurus was assessed with an integrative approach involving both morphological examinations and molecular phylogenetic analyses. Phylogenetic reconstruction was implemented using sequences of three mitochondrial [cytochrome b (Cytb), mitochondrially encoded 12S and 16S ribosomal RNA (12S, 16S)] and one nuclear [interphotoreceptor retinoid-binding protein (IRBP)] gene fragment. Morphological assessments involved qualitative examinations of features preserved on museum skins and skulls, supplemented with principal components analysis of craniometric data. Based on genetic and morphological comparisons, we suggest that the three widely disjunct populations of Eupetaurus are each sufficiently differentiated genetically and morphologically to be recognized as distinct species, two of which are described here as new.
Persistent Fetal Kidney Lobulation: Anatomy and Pathology
Authors: Ritz Brianna , Nestor Nicholas , Ruiz Kristina , Aldawood Ali , Zdilla Matthew , Klinkhachorn Penprapa
Published: March 2021

Persistent fetal lobulation of the kidneys is an uncommon condition that causes the surface of the kidney to appear as several lobules instead of smooth, flat and continuous. Persistent fetal lobulation may lead to unnecessary testing and subsequent clinical complications by masquerading as other lesions (e.g., cysts and tumors) in diagnostic imaging. Therefore, this report details the gross anatomy as well as histology of a series of lobulated kidneys. Further, this report provides gross anatomical and histological comparison with other kidney pathologies that may appear similar in diagnostic imaging.

Support or Funding Information

West Virginia University, West Liberty University, NASA West Virginia Space Grant Consortium, and West Virginia Research Challenge Fund

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Novel mutations in the Myo5a gene cause a dilute coat color phenotype in mice
Authors: Zhang Hui , Wu Zhongping , Yang Lijuan , Zhang Zhen , Chen Hao , Ren Jun
Published: March 2021

C57BL/6 laboratory mice usually show black coat color. We observed a dilute (gray) coat color phenotype in progenies of two C57BL/6 mice. This phenotype is inherited in an autosomal recessive mode. To uncover the molecular mechanism underlying this naturally occurring phenotypic variation, we performed whole‐genome sequencing (25×) on 10 offspring of the two founder mice. The whole‐genome DNA sequencing and additional RNA‐Seq data reveal that Myo5a is the gene responsible for the coat color dilution in C57BL/6 mice, and novel mutations in the Myo5a gene are likely causal. We further performed reverse transcription‐quantitative PCR, and showed increased expression of truncated Myo5a transcripts encoding dysfunctional proteins and decreased expression of Myo5a full‐length transcripts encoding functional proteins in mutant individuals. The decrease in full‐length messenger RNA abundance was accompanied by reduced Myo5a protein level and deficient melanosome transport, a potential mechanistic link between the Myo5a mutations and the dilute color phenotype. This study not only advances our understanding of the molecular mechanisms of pigmentation in mice, but also provides a typical case of deciphering the molecular basis of phenotypic variation in mice by genomic analyses and subsequent functional work.
5,6‐dihydroxy‐8Z,11Z,14Z,17Z‐eicosatetraenoic acid accelerates the healing of colitis by inhibiting transient receptor potential vanilloid 4‐mediated signaling
Authors: Kobayashi Koji , Ashina Kohei , Derouiche Sandra , Hamabata Taiki , Nakamura Tatsuro , Nagata Nanae , Takenouchi Shinya , Tominaga Makoto , Murata Takahisa
Published: March 2021

5,6‐dihydroxy‐8Z,11Z,14Z,17Z‐eicosatetraenoic acid (5,6‐DiHETE) is an eicosapentaenoic acid‐derived lipid metabolite, which we previously detected in inflamed mouse colon. In this study, we investigated the pathophysiological roles of 5,6‐DiHETE in murine colitis and its underlying mechanisms of action, focusing on the effects on transient receptor potential vanilloid (TRPV) channel activity. Oral administration of dextran sodium sulfate (DSS, 2%, for 4 days) caused colon inflammation, which peaked on day 7 and gradually declined by day 18. 5,6‐DiHETE concentration in colon tissue was significantly increased during the healing phase of colitis (days 9 to 18). In vitro study showed that pretreatment with 5,6‐DiHETE (0.1‐1 μM, 30 minutes) significantly inhibited endothelial barrier disruption induced by a TRPV4 agonist (GSK1016790A, 50 nM). Intracellular Ca2+ imaging also showed that pretreatment with 5,6‐DiHETE (1 μM, 10 minutes) reduced GSK1016790A‐induced intracellular Ca2+ increase in HEK293T cells overexpressing TRPV4. In vivo, intraperitoneal administration of 5,6‐DiHETE (50 µg kg−1 day−1) during the healing phase accelerated the recovery from DSS‐induced colitis. Pathological studies showed that the administration of 5,6‐DiHETE inhibited edema formation and leukocyte infiltration in inflamed colon tissue. In conclusion, we identified 5,6‐DiHETE as a novel endogenous TRPV4 antagonist, and we also demonstrated that its administration promotes the healing of colitis by inhibiting inflammatory responses.
The lysosomal membrane protein Sidt2 is a vital regulator of mitochondrial quality control in skeletal muscle
Authors: Wang Lizhuo , Yu Cui , Pei Wenjun , Geng Mengya , Zhang Yao , Li Zihui , Liang Feiteng , Tan Fengbiao , Du Hui , Gao Jialin
Published: March 2021

The role of Sidt2 in the process of glucose and lipid metabolism has been recently reported. However, whether Sidt2 is involved in the metabolic regulation in skeletal muscle remains unknown. In this study, for the first time, using skeletal muscle‐selective Sidt2 knockout mice, we found that Sidt2 was vital for the quality control of mitochondria in mouse skeletal muscle. These mice showed significantly reduced muscle tolerance and structurally abnormal mitochondria. Deletion of the Sidt2 gene resulted in decreased expression of mitochondrial fusion protein 2 (Mfn2) and Dynamin‐related protein 1 (Drp1), as well as peroxisome proliferator‐activated receptor γ coactivator‐1 (PGC1‐α). In addition, the clearance of damaged mitochondria in skeletal muscle was inhibited upon Sidt2 deletion, which was caused by blockade of autophagy flow. Mechanistically, the fusion of autophagosomes and lysosomes was compromised in Sidt2 knockout skeletal muscle cells. In summary, the deletion of the Sidt2 gene not only interfered with the quality control of mitochondria, but also inhibited the clearance of mitochondria and caused the accumulation of a large number of damaged mitochondria, ultimately leading to the abnormal structure and function of skeletal muscle.
Polyfunctionality of the CXCR4/CXCL12 axis in health and disease: Implications for therapeutic interventions in cancer and immune‐mediated diseases
Authors: Britton C. , Poznansky M. C. , Reeves P.
Published: March 2021

Historically the chemokine receptor CXCR4 and its canonical ligand CXCL12 are associated with the bone marrow niche and hematopoiesis. However, CXCL12 exhibits broad tissue expression including brain, thymus, heart, lung, liver, kidney, spleen, and bone marrow. CXCR4 can be considered as a node which is integrating and transducing inputs from a range of ligand‐receptor interactions into a responsive and divergent network of intracellular signaling pathways that impact multiple cellular processes such as proliferation, migration, and stress resistance. Dysregulation of the CXCR4/CXCL12 axis and consequent fundamental cellular processes, are associated with a panoply of disease. This review frames the polyfunctionality of the receptor at a molecular, physiological, and pathophysiological levels. Transitioning our perspective of this axis from a single gene/protein:single function model to a polyfunctional signaling cascade highlights the potential for finer therapeutic intervention and cautions against a reductionist approach.
Satellite cells deficiency and defective regeneration in dynamin 2‐related centronuclear myopathy
Authors: F. Almeida Camila , Bitoun Marc , Vainzof Mariz
Published: March 2021

Dynamin 2 (DNM2) is a ubiquitously expressed protein involved in many functions related to trafficking and remodeling of membranes and cytoskeleton dynamics. Mutations in the DNM2 gene cause the autosomal dominant centronuclear myopathy (AD‐CNM), characterized mainly by muscle weakness and central nuclei. Several defects have been identified in the KI‐Dnm2R465W/+ mouse model of the disease to explain the muscle phenotype, including reduction of the satellite cell pool in muscle, but the functional consequences of this depletion have not been characterized until now. Satellite cells (SC) are the main source for muscle growth and regeneration of mature tissue. Here, we investigated muscle regeneration in the KI‐Dnm2R465W/+ mouse model for AD‐CNM. We found a reduced number of Pax7‐positive SCs, which were also less activated after induced muscle injury. The muscles of the KI‐Dnm2R465W/+ mouse regenerated more slowly and less efficiently than wild‐type ones, formed fewer new myofibers, and did not recover its normal mass 15 days after injury. Altogether, our data provide evidence that the muscle regeneration is impaired in the KI‐Dnm2R465W/+ mouse and contribute with one more layer to the comprehension of the disease, by identifying a new pathomechanism linked to DNM2 mutations which may be involved in the muscle‐specific impact occurring in AD‐CNM.
Maternal adiponectin prevents visceral adiposity and adipocyte hypertrophy in prenatal androgenized female mice
Authors: Wu Yanling , Chanclón Belén , Micallef Peter , Stener‐Victorin Elisabet , Wernstedt Asterholm Ingrid , Benrick Anna
Published: March 2021

Hyperandrogenism is the main characteristic of polycystic ovary syndrome, which affects placental function and fetal growth, and leads to reproductive and metabolic dysfunction in female offspring. Adiponectin acts on the placenta and may exert endocrine effects on the developing fetus. This study aims to investigate if maternal and/or fetal adiponectin can prevent metabolic and reproductive dysfunction in prenatal androgenized (PNA) female offspring. Adiponectin transgenic (APNtg) and wild‐type dams received dihydrotestosterone/vehicle injections between gestational days 16.5‐18.5 to induce PNA offspring, which were followed for 4 months. Offspring from APNtg dams were smaller than offspring from wild‐type dams, independent of genotype. Insulin sensitivity was higher in wild‐type mice from APNtg dams compared to wild‐types from wild‐type dams, and insulin sensitivity correlated with fat mass and adipocyte size. PNA increased visceral fat% and adipocyte size in wild‐type offspring from wild‐type dams, while wild‐type and APNtg offspring from APNtg dams were protected against this effect. APNtg mice had smaller adipocytes than wild‐types and this morphology was associated with an increased expression of genes regulating adipogenesis (Ppard, Pparg, Cebpa, and Cebpb) and metabolism (Chrebp and Lpl). Anogenital distance was increased in all PNA‐exposed wild‐type offspring, but there was no increase in PNA APNtg offspring, suggesting that adiponectin overexpression protects against this effect. In conclusion, elevated adiponectin levels in utero improve insulin sensitivity, reduce body weight and fat mass gain in the adult offspring and protect against PNA‐induced visceral adiposity. In conclusion, these data suggest that PNA offspring benefit from prenatal adiponectin supplementation.
The microbiota plays a critical role in the reactivity of lung immune components to innate ligands
Authors: Marquant Quentin , Laubreton Daphné , Drajac Carole , Mathieu Elliot , Bouguyon Edwige , Noordine Marie‐Louise , Remot Aude , Riffault Sabine , Thomas Muriel , Descamps Delphyne
Published: March 2021

The gut microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the gut and/or lung microbiota in the education of pulmonary innate immune responses. Here, we tested whether the endogenous microbiota in general can modulate the reactivity of pulmonary tissue to pathogen stimuli by comparing the response of specific‐pathogen‐free (SPF) and germ‐free (GF) mice. Thus, we observed earlier and greater inflammation in the pulmonary compartment of GF mice than that of SPF mice after intranasal instillation to lipopolysaccharide (LPS), a component of Gram‐negative bacteria. Toll‐like receptor 4 (TLR4) was more abundantly expressed in the lungs of GF mice than those of SPF mice at steady state, which could predispose the innate immunity of GF mice to strongly react to the environmental stimuli. Lung explants were stimulated with different TLR agonists or infected with the human airways pathogen, respiratory syncytial virus (RSV), resulting in greater inflammation under almost all conditions for the GF explants. Finally, alveolar macrophages (AM) from GF mice presented a higher innate immune response upon RSV infection than those of SPF mice. Overall, these data suggest that the presence of microbiota in SPF mice induced a process of innate immune tolerance in the lungs by a mechanism which remains to be elucidated. Our study represents a step forward to establishing the link between the microbiota and the immune reactivity of the lungs.
A zebrafish toolbox for biomechanical signaling in cardiovascular development and disease
Authors: Rödel Claudia Jasmin , Abdelilah-Seyfried Salim
Published: March 2021

Purpose of review

The zebrafish embryo has emerged as a powerful model organism to investigate the mechanisms by which biophysical forces regulate vascular and cardiac cell biology during development and disease. A versatile arsenal of methods and tools is available to manipulate and analyze biomechanical signaling. This review aims to provide an overview of the experimental strategies and tools that have been utilized to study biomechanical signaling in cardiovascular developmental processes and different vascular disease models in the zebrafish embryo. Within the scope of this review, we focus on work published during the last two years.

Recent findings

Genetic and pharmacological tools for the manipulation of cardiac function allow alterations of hemodynamic flow patterns in the zebrafish embryo and various types of transgenic lines are available to report endothelial cell responses to biophysical forces. These tools have not only revealed the impact of biophysical forces on cardiovascular development but also helped to establish more accurate models for cardiovascular diseases including cerebral cavernous malformations, hereditary hemorrhagic telangiectasias, arteriovenous malformations, and lymphangiopathies.

The zebrafish embryo is a valuable vertebrate model in which in-vivo manipulations of biophysical forces due to cardiac contractility and blood flow can be performed. These analyses give important insights into biomechanical signaling pathways that control endothelial and endocardial cell behaviors. The technical advances using this vertebrate model will advance our understanding of the impact of biophysical forces in cardiovascular pathologies.
Single-cell RNA sequencing to study vascular diversity and function
Authors: Ma Feiyang , Hernandez Gloria E. , Romay Milagros , Iruela-Arispe M. Luisa
Published: March 2021

Purpose of review

Single-cell RNA sequencing (scRNA-seq) can capture the transcriptional profile of thousands of individual cells concurrently from complex tissues and with remarkable resolution. Either with the goal of seeking information about distinct cell subtypes or responses to a stimulus, the approach has provided robust information and promoted impressive advances in cardiovascular research. The goal of this review is to highlight strategies and approaches to leverage this technology and bypass potential caveats related to evaluation of the vascular cells.

Recent findings

As the most recent technological development, details associated with experimental strategies, analysis, and interpretation of scRNA-seq data are still being discussed and scrutinized by investigators across the vascular field. Compilation of this information is valuable for those using the technology but particularly important to those about to start utilizing scRNA-seq to seek transcriptome information of vascular cells.

As our field progresses to catalog transcriptomes from distinct vascular beds, it is undeniable that scRNA-seq technology is here to stay. Sharing approaches to improve the quality of cell dissociation procedures, analysis, and a consensus of best practices is critical as information from this powerful experimental platform continues to emerge.
Viral Pneumonia is Associated with Increased Risk and Earlier Development of Post-Inflammatory Pulmonary Fibrosis
Authors: Shojaee Abbas , Siner Jonathan M. , Zinchuk Andrey , Aryan Yalda , Kaminski Naftali , Dela Cruz Charles S.
Published: March 2021

Severe inflammatory response, acute respiratory distress syndrome, and death are established serious consequences of the acute phase of severe viral pneumonia. However, the long-term respiratory outcomes of severe viral pneumonia, including its association with pulmonary fibrosis, are less known.

Objective

To determine whether viral pneumonia is associated with an increased incidence of post-inflammatory pulmonary fibrosis.

Design

We performed two retrospective observational cohort studies using longitudinal hospitalization records from the States of California (2005-2011) and Florida (2009-2015) for the discovery and validation studies, respectively. Patients who were 85-years-old and younger with at least two hospital encounters but without a prior diagnosis of pulmonary fibrosis were included. International Classification of Diseases-9 (ICD9) codes of primary and secondary diagnoses and procedures were used to identify the exposure: diagnosis of viral pneumonia; the outcome: incidence of post-inflammatory pulmonary fibrosis [PIPF, ICD9: 515]; and the confounders.

Methods

Chronological age was used as the study time scale. Non-parametric Kaplan-Meier (KM) estimator and semiparametric Cox Proportional Hazard modelling were used to assessing the risk of PIPF. P-values < 10−3 were considered significant.

Results

Among 9,802,565 patients from California and 8,741,345 patients in Florida cohorts, the prevalence of PIPF was 0.61% and 0.62% over 7 and 6.75 years, respectively. Patients with incident PIPF were older than those without [68(SD: 11) vs. 40(22) years]; among patients with PIPF, those with viral pneumonia diagnosis were younger than those without [63(12) versus 68(11) years]. Incidence of PIPF was higher for those with viral pneumonia diagnosis versus those without [1.6 (CI:1.51-1.69) vs. 0.91 (CI:0.86-0.96)] cases per 1000 person-years in California and in Florida [1.11 (CI:1.06 −1.16) vs, 0.93 (CI:0.89-0.98)]. Viral pneumonia was associated with increased risk of incident PIPF in both California aHR = 1.49 (1.38, 1.61), and Florida aHR of 1.26 (1.20, 1.33) cohorts (Table). Among patients who developed PIPF, the median time to diagnosis was 7.41 (6.16 −8.66) and 4.80 (4.34 - 5.26) years earlier for patients with viral pneumonia versus without in California and Florida cohorts. The association of viral pneumonia was not found for idiopathic pulmonary fibrosis [ICD9: 516.3]. Our findings suggest that patients hospitalized with viral pneumonia may have long term respiratory sequela that is often overlooked and suggest a need for additional studies focusing on phenotyping susceptible patients. This finding is especially important in light of the current COVID-19 pandemic because viral pneumonia is the most common manifestations of the disease, which could lead to subsequent fibrosis.