bluuebunny/crossref_metadata_2025 huggingface dataset:
Diverse Locations and a Long History: Historical Context for Urban Leopards (Panthera pardus) in the Early Anthropocene From Seoul, Korea
Authors: Powell Joshua , Axmacher Jan C. , Linnell John D. C. , Durant Sarah M.
Published: November 2021

While the urban landscapes of the early Anthropocene may appear hostile to large carnivores, humans and leopards (Panthera pardus) are known to co-inhabit major urban centres like Mumbai (India), Nairobi (Kenya) and Johannesburg (South Africa). We provide evidence that the presence of leopards in urban landscapes is not, however, a new phenomenon and has occurred repeatedly over the early history of the Anthropocene. Using records of Amur leopards (P. p. orientalis) in Seoul, Korea, at the end of the 19th century, a capital city and major urban centre with a high human population density, we explore socio-cultural, political and ecological factors that may have facilitated human-leopard co-occurrence in an urban landscape and the factors that eventually led to the leopards' extirpation. We suggest that, in the absence of unsustainable levels of persecution by humans, leopards are able to persist in urban landscapes which contain small patches of dense vegetation and have sufficient alternative food supplies. In light of the continued expansion of urban landscapes in the 21st century and increasing conservation focus on the presence of large carnivore populations there, this paper provides historical context to human co-existence with leopards in urban landscapes during the Anthropocene–and what we can learn from it for the future.
Case Report: Extrinsic Compression of the Left Main Coronary Artery by a Giant Sinus of Valsalva Aneurysm
Authors: Ning Feifei , Tang Manyun , Wang Mengjie , Muhlestein Joseph B. , Day John D. , Li Guoliang , Yan Yang
Published: November 2021

Sinus of Valsalva aneurysm (SoVA) is an uncommon clinical entity, which is present in roughly 0. 09% of the general population. The cause can either be acquired or congenital. Clinically the SoVA of unruptured status are rarely captured or even diagnosed due to atypical clinical presentations. Here, we present a rare case of exertional angina pectoris and recurrent syncope due to an extrinsically compressed left coronary artery by a giant SoVA in a 50-year-old female patient. This SoVA was successfully repaired by the surgical exclusion and the patient was still doing well after 2 years of follow-up.
Case Report: An Unusual Cause for Recurrent Hemopericardium in a Patient With Dyspnea
Authors: Nguyên Uyên Châu , Vernemmen Astrid I. P. , Segers Patrique , zur Hausen Axel , Driessen Rob G. H. , Pluijmen Maurice J. H. M. , Bekkers Sebastiaan C. A. M.
Published: November 2021

The case concerns a female presenting with dyspnoea resulting from recurrent hemopericardium. Pericardiocentesis, coronary angiography, and extensive laboratory and imaging studies did not reveal the underlying etiology of the hemopericardium. Only after repeat and exploratory surgery, diffuse venous pericardial hemorrhages with localized thrombi typical of angiosarcoma were discovered.
Comparison of the Association Between Arterial Stiffness Indices and Heart Failure in Patients With High Cardiovascular Risk: A Retrospective Study
Authors: Lee Chan Joo , Yoon Minjae , Ha Jaehyung , Oh Jaewon , Park Sungha , Lee Sang-Hak , Kang Seok-Min
Published: November 2021

Objective: Study findings of the relationship of each arterial stiffness index with incident heart failure (HF) are conflicting. We aimed to compare the association between the indices of arterial stiffness and the risk of HF.

Methods: We analysed 3,034 patients from a prospective cohort that enrolled patients with high cardiovascular risk. They underwent brachial-ankle pulse wave velocity (baPWV), brachial pulse pressure (PP), carotid-femoral pulse wave velocity (cfPWV), and central PP measurements.

Results: Over a median follow-up of 4.7 years (interquartile range, 3.4–5.8 years), 65 HF events occurred. The incidence rate of HF was 4.7 per 1,000 person-years [95% confidence interval (CI), 3.7–6.0]. There was no difference in baPWV in those with and without HF events (1,561 ± 401 and 1,520 ± 321 cm/s, respectively, P = 0.415); however, there was a significant difference in brachial PP (63.2 ± 16.9 vs. 52.3 ± 11.5 mmHg, P < 0.001), cfPWV (11.0 ± 3.1 vs. 9.4 ± 2.4 m/s, P < 0.001) and central PP (56.6 ± 19.9 vs. 42.9 ± 13.8 mmHg, P < 0.001). In the multivariable-adjusted model, brachial PP [hazards ratio (HR) per standard deviation unit (SDU), 1.48; 95% CI, 1.19–1.84, P < 0.001], cfPWV (HR per SDU, 1.29; 95% CI, 1.02–1.63, P = 0.032) and central PP (HR per SDU, 1.44; 95% CI, 1.17–1.78; P < 0.001) were associated with incident HF, but baPWV was not (HR per SDU, 0.83; 95% CI, 0.63–1.10; P = 0.198). In the receiver operating characteristic analysis, the area under the curve (AUC) of brachial PP (P < 0.001), cfPWV (P = 0.003) or central PP (P = 0.001) was larger than that of baPWV, and there was no difference in the AUCs of brachial PP, cfPWV and central PP.

Conclusion: Among arterial stiffness indices, brachial PWV was less associated with the risk of heart failure, and brachial PP and measures representing central hemodynamics were highly associated with incident HF.
Plume-Induced Subduction Initiation: Revisiting Models and Observations
Authors: Baes Marzieh , Stern Robert J. , Whattam Scott , Gerya Taras V. , Sobolev Stephan V.
Published: November 2021

Subduction initiation induced by a hot and buoyant mantle plume head is unique among proposed subduction initiation mechanisms because it does not require pre-existing weak zones or other forces for lithospheric collapse. Since recognition of the first evidence of subduction nucleation induced by a mantle plume in the Late Cretaceous Caribbean realm, the number of studies focusing on other natural examples has grown. Here, we review numerical and physical modeling and geological-geochemical studies which have been carried out thus far to investigate onset of a new subduction zone caused by impingement of a mantle plume head. As geological-geochemical data suggests that plume-lithosphere interactions have long been important - spanning from the Archean to the present - modeling studies provide valuable information on the spatial and temporal variations in lithospheric deformation induced by these interactions. Numerical and physical modeling studies, ranging from regional to global scales, illustrate the key role of plume buoyancy, lithospheric strength and magmatic weakening above the plume head on plume-lithosphere interactions. Lithospheric/crustal heterogeneities, pre-existing lithospheric weak zones and external compressional/extensional forces may also change the deformation regime caused by plume-lithosphere interaction.
COPUS, PORTAAL, or DART? Classroom Observation Tool Comparison From the Instructor User’s Perspective
Authors: Asgari Mitra , Miles Asha M. , Lisboa Maria Sol , Sarvary Mark A.
Published: November 2021

Classroom observation tools are used to evaluate teaching and learning activities, and to provide constructive feedback to instructors. To help instructors with selecting a suitable tool based on their needs and available resources, in this study, a group of observers assessed lectures of an introductory biology course using three, broadly cited classroom assessment tools in the STEM field: the Classroom Observation Protocol for Undergraduate STEM (COPUS); the Practical Observation Rubric to Assess Active Learning (PORTAAL); and the Decibel Analysis for Research in Teaching (DART). From a user’s perspective, we evaluated 1) the type and extent of information each tool provides, and 2) the time investment and difficulty of working with each tool. The assessment result of each tool was compared, with a list of expected outcomes generated by surveying a group of college instructors and with the result of a self-teaching assessment tool, Teaching Practices Inventory (TPI). Our findings conclude that each tool provided valuable assessment with a broad range of outcomes and time investment: PORTAAL offered the most detailed information on the quality of teaching practices and students’ engagement, but it demanded the greatest time investment. DART provided a basic estimation of active learning proportion with the least effort. The level of assessment outcome and the time investment when using COPUS was found to be less than PORTAAL, and more than DART. The TPI self-assessment outcome was found to be slightly optimistic regarding the proportion of active learning practices used in the studied course. This comparative study can help instructors in selecting a tool that suits their needs and available resources for a better assessment of their classroom teaching and learning.
Research and Application of Cold Productivity Formula of Horizontal Well in the Power-Law Fluid Heavy Oil Reservoir
Authors: Wang Gongchang , Liu Yingxian , Liu Zongbin
Published: November 2021

Considering the rheological properties of fluid, reservoir heterogeneity, and eccentricity factor, the productivity formula of horizontal well for the power-law fluid heavy oil reservoir is derived by transforming the three-dimensional seepage problem into a two-dimensional seepage problem. The heavy oil production calculated by this formula is in good agreement with the actual production in the offshore oil field. Then, the influencing factors of production are analyzed, and the results show that the power-law index has the greatest influence on production. When the power-law index is less than 0.8, the production increases slowly with the power-law index and when it is greater than 0.8, the production increases faster. The power-law index has a greater impact on production for higher production pressure differential and longer horizontal well. Anisotropy has significant influence on the production. When the value of Kh/Kv is less than 10, the production decreases rapidly with the Kh/Kv; after the value of Kh/Kv is greater than 10, the production decreases slower. Eccentricity has trivial impact on the production.
Small Area Estimation of Postfire Tree Density Using Continuous Forest Inventory Data
Authors: Gaines George C. , Affleck David L. R.
Published: November 2021

Wildfire activity in the western United States is expanding and many western forests are struggling to regenerate postfire. Accurate estimates of forest regeneration following wildfire are critical for postfire forest management planning and monitoring forest dynamics. National or regional forest inventory programs can provide vegetation data for direct spatiotemporal domain estimation of postfire tree density, but samples within domains of administrative utility may be small (or empty). Indirect domain expansion estimators, which borrow extra-domain sample data to increase precision of domain estimates, offer a possible alternative. This research evaluates domain sample sizes and direct estimates in domains spanning large geographic extents and ranging from 1 to 10 years in temporal scope. In aggregate, domain sample sizes prove too small and standard errors of direct estimates too high. We subsequently compare two indirect estimators—one generated by averaging over observations that are proximate in space, the other by averaging over observations that are proximate in time—on the basis of estimated standard error. We also present a new estimator of the mean squared error (MSE) of indirect domain estimators which accounts for covariance between direct and indirect domain estimates. Borrowing sample data from within the geographic extents of our domains, but from an expanded set of measurement years, proves to be the superior strategy for augmenting domain sample sizes to reduce domain standard errors in this application. However, MSE estimates prove too frequently negative and highly variable for operational utility in this context, even when averaged over multiple proximate domains.
DNASE1L3 as a Novel Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma Based on Data Mining
Authors: Chen Jianlin , Ding Junping , Huang Wenjie , Sun Lin , Chen Jinping , Liu Yangyang , Zhan Qianmei , Gao Gan , He Xiaoling , Qiu Guowen , Long Peiying , Wei Lishu , Lu Zhenni , Sun Yifan
Published: November 2021

Previous researches have highlighted that low-expressing deoxyribonuclease1-like 3 (DNASE1L3) may play a role as a potential prognostic biomarker in several cancers. However, the diagnosis and prognosis roles of DNASE1L3 gene in lung adenocarcinoma (LUAD) remain largely unknown. This research aimed to explore the diagnosis value, prognostic value, and potential oncogenic roles of DNASE1L3 in LUAD. We performed bioinformatics analysis on LUAD datasets downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analyzed with various online databases. We found that both the mRNA and protein levels of DNASE1L3 in patients with LUAD were noticeably lower than that in normal tissues. Low DNASE1L3 expression was significantly associated with higher pathological stages, T stages, and poor prognosis in LUAD cohorts. Multivariate analysis revealed that DNASE1L3 was an independent factor affecting overall survival (HR = 0.680,p= 0.027). Moreover, decreased DNASE1L3 showed strong diagnostic efficiency for LUAD. Results indicated that the mRNA level of DNASE1L3 was positively correlated with the infiltration of various immune cells, immune checkpoints in LUAD, especially with some m6A methylation regulators. In addition, enrichment function analysis revealed that the co-expressed genes may participate in the process of intercellular signal transduction and transmission. GSEA indicated that DNASE1L3 was positively related to G protein-coupled receptor ligand biding (NES = 1.738; P adjust = 0.044; FDR = 0.033) and G alpha (i) signaling events (NES = 1.635; P adjust = 0.044; FDR = 0.033). Our results demonstrated that decreased DNASE1L3 may serve as a novel diagnostic and prognostic biomarker associating with immune infiltrates in lung adenocarcinoma.
Identification of Immune-Related Key Genes in Ovarian Cancer Based on WGCNA
Authors: Quan Qingli , Xiong Xinxin , Wu Shanyun , Yu Meixing
Published: November 2021

Background: Ovarian cancer (OV) is a fatal gynecologic malignancy and has poor survival rate in women over the age of forty. In our study, we aimed to identify genes related to immune microenvironment regulations and explore genes associated with OV prognosis.

Methods: The RNA-seq data of GDC TCGA Ovarian Cancer cohort of 376 patients was retrieved from website. Weighted gene co-expression network analysis (WGCNA) and ESTIMATE algorithm were applied to identify the key genes associated with the immune scores. The correlation between key genes and 22 immune cell types were estimated by using CIBERSORT algorithms.

Results: WGCNA showed that the pink module was most correlated with the immune score. Seven of 14 key genes (FCRL3, IFNG, KCNA3, LY9, PLA2G2D, THEMIS, and TRAT1) were significantly associated with the OS of OV patients. Correlation analysis showed our key genes positively related to M1 macrophages, CD8 T cells, plasma cells, regulatory T (Treg) cells and activated memory CD4 T cells, and negatively related to naive CD4 T cells, M0 macrophages, activated dendritic cells (DCs) and memory B cells. Kaplan-Meier survival analysis showed that lower abundances of neutrophils and higher abundances of M1 macrophages, plasma cells, T cells gamma delta (γδT) cells and follicular helper T (Tfh) cells predicted better OV prognosis.

Conclusion: Forteen key genes related to the immune infiltrating of OV were identified, and seven of them were significantly related to prognosis. These key genes have potential roles in tumor infiltrating immune cells differentiation and proliferation. This study provided potential prognostic markers and immunotherapy targets for OV.
Growth and Labelling of Cell Wall Components of the Brown Alga Ectocarpus in Microfluidic Chips
Authors: Charrier Bénédicte , Boscq Samuel , Nelson Bradley J. , Läubli Nino F.
Published: November 2021

Polydimethylsiloxane (PDMS) chips have proven to be suitable environments for the growth of several filamentous organisms. However, depending on the specimen, the number of investigations concerning their growth and cell differentiation is limited. In this work, we monitored the developmental pattern of the brown alga Ectocarpus inside PDMS lab-on-chips. Two main methods of inoculation of the lab-on-chip were tested, i.e., via the direct injection of spores into the chamber as well as through the insertion of sporophyte filaments. The resulting growth rate, growth trajectory, cell differentiation, and cell branching were monitored and quantified for 20 days inside 25 or 40 μm parallel channels under standard light and temperature conditions. With growth rates of 2.8 μm⋅h–1, normal growth trajectories and cell differentiation, as well as branching occurring inside the microfluidic environment, the main development steps were shown to be similar to those observed in non-constrained in vitro conditions. Additionally, the labelling of Ectocarpus cell wall polysaccharides using calcofluor for cellulose detection and immunolocalisation with monoclonal antibodies for alginates showed the expected patterns when compared to open space growth evaluated with either epifluorescence or confocal microscopy. Overall, this article describes the experimental conditions for observing and studying the basic unaltered processes of brown algal growth using microfluidic technology which provides the basis for future biochemical and biological researches.
Characterizing the Long-Term, Wide-Band and Deep-Water Soundscape Off Hawai’i
Authors: Merkens Karlina , Baumann-Pickering Simone , Ziegenhorn Morgan A. , Trickey Jennifer S. , Allen Ann N. , Oleson Erin M.
Published: November 2021

Many animals use sound for communication, navigation, and foraging, particularly in deep water or at night when light is limited, so describing the soundscape is essential for understanding, protecting, and managing these species and their environments. The nearshore deep-water acoustic environment off the coast of Kona, Hawai’i, is not well documented but is expected to be strongly influenced by anthropogenic activities such as fishing, tourism, and other vessel activity. To characterize the deep-water soundscape in this area we used High-frequency Acoustic Recording Packages (HARPs) to record acoustic data year-round at a 200 or 320 kHz sampling rate. We analyzed data spanning more than 10 years (2007-2018) by producing measurements of frequency-specific energy and using a suite of detectors and classifiers for general and specific sound sources. This provided a time series for sounds coming from biological, anthropogenic and physical sources. The soundscape in this location is dominated by signals generated by humans and odontocete cetaceans (mostly delphinids), generally alternating on a diel cycle. During daylight hours the dominant sound sources are vessels and echosounders, with strong signals ranging from 10 Hz to 80 kHz and above, while during the night the clicks from odontocetes dominate the soundscape in mid-to-high frequencies, generally between 10 and 90 kHz. Winter-resident humpback whales are present seasonally and produce calls in lower frequencies (200-2,000 Hz). Overall, seasonal variability is relatively subtle, which is unsurprising given the tropical latitude and deep-water environment. These results, and particularly the inclusion of sounds from frequencies above 2 kHz, represent the first long-term analysis of a marine soundscape in the North Pacific, and the first assessment of the intense, daily presence of manmade noise at this site. The decadal time series allows us to characterize the dynamic nature of this location, and to begin to identify changes in the soundscape over time. This type of analysis facilitates protection of natural resources and effective management of human activities in an ecologically important area.
Experimental Investigation on Strength and Failure Characteristics of Cemented Paste Backfill
Authors: Zhang Zhihong , Li Jiacheng
Published: November 2021

The strength characteristics of cemented paste backfill (CPB) in mining areas are key control factors for the safety assessment of overlying strata. A series of experiments about uniaxial compression and triaxial compression were carried out to study the influence of cement content of filling slurry, curing age, and curing temperature on strength behavior of CPB specimens. The failure mechanism and damage feature of CPB have been investigated. The results show the following: (1) The uniaxial compressive strength of CPB specimens exhibits an upward trend with the increase of cement content and curing age. When the cement content is high, the uniaxial compressive strength increases sharply with increasing curing age. (2) The cohesion of CPB specimens increases with the increase of cement content of filling slurry, curing age, and curing temperature. The cohesion of CPB specimens with curing age 7 days and 14 days increases linearly with increasing cement content. At the later stage of curing age, the strength growth of high cement content backfill is significantly greater than that of low cement content. The internal friction angle of the filling increases slightly with increasing filling cement content, curing age, and curing temperature. (3) The shear strength of CPB specimens at curing age 7 days exhibits an upward trend with the increase of confining pressure, while the shear strength at 14 days and 28 days curing age decreases slightly as the confining pressure increases. (4) With the increase of cement content in backfill, the brittleness increases significantly when the backfill is damaged. The failure mode of CPB specimens changes from monoclinic section shear failure to X-type failure with increasing curing age, and the failure process is divided into four stages: pore compaction, linear elastic deformation, plastic deformation, and post-peak failure.
Incidence and Mortality of Acute Respiratory Distress Syndrome in Patients With Burns: A Systematic Review and Meta-Analysis
Authors: Wang Baoli , Chenru Wei , Jiang Yong , Hu Lunyang , Fang He , Zhu Feng , Yu Qing , Zhu Banghui , Wu Guosheng , Sun Yu , Xia Zhaofan
Published: November 2021

Objective: We conducted a systematic review and meta-analysis to comprehensively estimate the incidence and mortality of acute respiratory distress syndrome (ARDS) in overall and subgroups of patients with burns.

Data sources: Pubmed, Embase, the Cochrane Library, CINAHL databases, and China National Knowledge Infrastructure database were searched until September 1, 2021.

Study selection: Articles that report study data on incidence or mortality of ARDS in patients with burns were selected.

Data extraction: Two researchers independently screened the literature, extracted data, and assessed the quality. We performed a meta-analysis of the incidence and mortality of ARDS in patients with burns using a random effects model, which made subgroup analysis according to the study type, inclusion (mechanical ventilation, minimal burn surface), definitions of ARDS, geographic location, mean age, burn severity, and inhalation injury. Primary outcomes were the incidence and mortality of burns patients with ARDS, and secondary outcomes were incidence for different subgroups.

Data synthesis: Pooled weighted estimate of the incidence and mortality of ARDS in patients with burns was 0.24 [95% confidence interval (CI)0.2–0.28] and 0.31 [95% CI 0.18−0.44]. Incidences of ARDS were obviously higher in patients on mechanical ventilation (incidence = 0.37), diagnosed by Berlin definition (incidence = 0.35), and with over 50% inhalation injury proportion (incidence = 0.41) than in overall patients with burns. Patients with burns who came from western countries and with inhalation injury have a significantly higher incidence of ARDS compared with those who came from Asian/African countries (0.28 vs. 0.25) and without inhalation injury (0.41 vs. 0.24).

Conclusion: This systematic review and meta-analysis revealed that the incidence of ARDS in patients with burns is 24% and that mortality is as high as 31%. The incidence rates are related to mechanical ventilation, location, and inhalation injury. The patients with burns from western countries and with inhalation injury have a significantly higher incidence than patients from Asian/African countries and without inhalation injury.

Systematic Review Registration: identifier: CRD42021144888.
TatD DNases Contribute to Biofilm Formation and Virulence in Trueperella pyogenes
Authors: Zhang Zehui , Liang Yinfeng , Yu Lihui , Chen Menghan , Guo Yuru , Kang Zhiruo , Qu Chenghu , Tian Chunlian , Zhang Dexian , Liu Mingchun
Published: November 2021

TatD DNases are conserved proteins in a variety of organisms and are considered potential virulence factors in Plasmodium falciparum and Streptococcus pneumoniae. However, the function of TatD DNases has not yet been determined in Trueperella pyogenes, which causes various infections in animals and leads to economic losses. In this study, we describe the roles of TatD DNases in T. pyogenes (TpTatDs). A bioinformatics analysis was performed to investigate the sequence characteristics of TpTatDs, and then the ability of recombinant TatD proteins to hydrolyze DNA was determined in the presence of divalent cations. Moreover, we constructed tatD-deficient mutants. The biofilms formed by the wild-type and mutant strains were observed under a microscope. The mortality and bacterial load in the spleen of mice infected with the wild-type strain and tatD-deficient mutants were determined to obtain insights into the role of TatDs in the virulence of T. pyogenes. Two TatD DNases were identified in T. pyogenes. They were Mg2+-dependent DNases and exhibited DNA endonuclease activity. Compared with those formed by the parental strain, biofilms formed by mutants showed a significantly reduced thickness and biomass. Moreover, mutants produced a lower bacterial load in the spleen of mice and compromised virulence. Our data indicated that TatD DNases in T. pyogenes are involved in biofilm formation and required for virulence during infections.
PmtA Regulates Pyocyanin Expression and Biofilm Formation in Pseudomonas aeruginosa
Authors: Thees Amy V. , Pietrosimone Kathryn M. , Melchiorre Clare K. , Marden Jeremiah N. , Graf Joerg , Lynes Michael A. , Maltz-Matyschsyk Michele
Published: November 2021

The opportunistic pathogen Pseudomonas aeruginosa expresses a small molecular weight, cysteine-rich protein (PmtA), identified as a metallothionein (MT) protein family member. The MT family proteins have been well-characterized in eukaryotes as essential for zinc and copper homeostasis, protection against oxidative stress, and the ability to modify a variety of immune activities. Bacterial MTs share sequence homology, antioxidant chemistry, and heavy metal-binding capacity with eukaryotic MTs, however, the impact of bacterial MTs on virulence and infection have not been well-studied. In the present study, we investigated the role of PmtA in P. aeruginosa PAO1 using a PmtA-deficient strain (ΔpmtA). Here we demonstrated the virulence factor, pyocyanin, relies on the expression of PmtA. We showed that PmtA may be protective against oxidative stress, as an alternative antioxidant, glutathione, can rescue pyocyanin expression. Furthermore, the expression of phzM, which encodes a pyocyanin precursor enzyme, was decreased in the ΔpmtA mutant during early stationary phase. Upregulated pmtA expression was previously detected in confluent biofilms, which are essential for chronic infection, and we observed that the ΔpmtA mutant was disrupted for biofilm formation. As biofilms also modulate antibiotic susceptibility, we examined the ΔpmtA mutant susceptibility to antibiotics and found that the ΔpmtA mutant is more susceptible to cefepime and ciprofloxacin than the wild-type strain. Finally, we observed that the deletion of pmtA results in decreased virulence in a waxworm model. Taken together, our results support the conclusion that PmtA is necessary for the full virulence of P. aeruginosa and may represent a potential target for therapeutic intervention.
An Unbound Proline-Rich Signaling Peptide Frequently Samples Cis Conformations in Gaussian Accelerated Molecular Dynamics Simulations
Authors: Alcantara Juan , Stix Robyn , Huang Katherine , Connor Acadia , East Ray , Jaramillo-Martinez Valeria , Stollar Elliott J. , Ball K. Aurelia
Published: November 2021

Disordered proline-rich motifs are common across the proteomes of many species and are often involved in protein-protein interactions. Proline is a unique amino acid due to the covalent bond between the backbone nitrogen and the proline side chain. The resulting five-membered ring allows proline to sample the cis state about its peptide bond, which other residues cannot do as readily. Because proline-rich disordered sequences exist as ensembles that likely include structures with the proline peptide bond in cis, a robust methodology to accurately account for these conformations in the overall ensemble is crucial. Observing the cis conformations of proline in a disordered sequence is challenging both experimentally and computationally. Nitrogen-hydrogen NMR spectroscopy cannot directly observe proline residues, which lack an amide bond, and computational methods struggle to overcome the large kinetic barrier between the cis and trans states, since isomerization usually occurs on the order of seconds. In the current work, Gaussian accelerated molecular dynamics was used to overcome this free energy barrier and simulate proline isomerization in a tetrapeptide (KPTP) and in the 12-residue proline-rich SH3 binding peptide, ArkA. We found that Gaussian accelerated molecular dynamics, when combined with a lowered peptide bond dihedral angle potential energy barrier (15 kcal/mol), allowed sufficient sampling of the proline cis and trans states on a microsecond timescale. All ArkA prolines spend a significant fraction of time in cis, leading to a more compact ensemble with less polyproline II helix structure than an ArkA ensemble with all peptide bonds in trans. The ensemble containing cis prolines also matches more closely to in vitro circular dichroism data than the all-trans ensemble. The ability of the ArkA prolines to isomerize likely affects the peptide’s ability to bind its partner SH3 domain, and should be studied further. This is the first molecular dynamics simulation study of proline isomerization in a biologically relevant proline-rich sequence that we know of, and a similar protocol could be applied to study multi-proline isomerization in other proline-containing proteins to improve conformational diversity and agreement with in vitro data.
Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma
Authors: Dai Zili , Liu Taisheng , Liu Guihong , Deng Zhen , Yu Peng , Wang Baiyao , Cen Bohong , Guo Liyi , Zhang Jian
Published: November 2021

Background: Lung cancer is the leading cause of cancer-related death globally. Hypoxia can suppress the activation of the tumor microenvironment (TME), which contributes to distant metastasis. However, the role of hypoxia-mediated TME in predicting the diagnosis and prognosis of lung adenocarcinoma (LUAD) patients remains unclear.

Methods: Both RNA and clinical data from the LUAD cohort were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Both univariate and multivariate Cox regression analyses were used to further screen prognosis-related hypoxia gene clusters. Time-dependent receiver operation characteristic (ROC) curves were established to evaluate the predictive sensitivity and specificity of the hypoxia-related risk signature. The characterization of gene set enrichment analysis (GSEA) and TME immune cell infiltration were further explored to identify hypoxia-related immune infiltration.

Results: Eight hypoxia-related genes (LDHA, DCN, PGK1, PFKP, FBP1, LOX, ENO3, and CXCR4) were identified and established to construct a hypoxia-related risk signature. The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p < 0.0001). The AUCs for 1-, 3-, and 5-year overall survival were 0.736 vs. 0.741, 0.656 vs. 0.737, and 0.628 vs. 0.649, respectively. The high-risk group was associated with immunosuppression in the TME.

Conclusion: The hypoxia-related risk signature may represent an independent biomarker that can differentiate the characteristics of TME immune cell infiltration and predict the prognosis of LUAD.
Processing of RNA Containing 8-Oxo-7,8-Dihydroguanosine (8-oxoG) by the Exoribonuclease Xrn-1
Authors: Phillips Cheyenne N. , Schowe Shawn , Langeberg Conner J. , Siddique Namoos , Chapman Erich G. , Resendiz Marino J. E.
Published: November 2021

Understanding how oxidatively damaged RNA is handled intracellularly is of relevance due to the link between oxidized RNA and the progression/development of some diseases as well as aging. Among the ribonucleases responsible for the decay of modified (chemically or naturally) RNA is the exonuclease Xrn-1, a processive enzyme that catalyzes the hydrolysis of 5′-phosphorylated RNA in a 5′→3′ direction. We set out to explore the reactivity of this exonuclease towards oligonucleotides (ONs, 20-nt to 30-nt long) of RNA containing 8-oxo-7,8-dihydroguanosine (8-oxoG), obtained via solid-phase synthesis. The results show that Xrn-1 stalled at sites containing 8-oxoG, evidenced by the presence of a slower moving band (via electrophoretic analyses) than that observed for the canonical analogue. The observed fragment(s) were characterized via PAGE and MALDI-TOF to confirm that the oligonucleotide fragment(s) contained a 5′-phosphorylated 8-oxoG. Furthermore, the yields for this stalling varied from app. 5–30% with 8-oxoG located at different positions and in different sequences. To gain a better understanding of the decreased nuclease efficiency, we probed: 1) H-bonding and spatial constraints; 2) anti-syn conformational changes; 3) concentration of divalent cation; and 4) secondary structure. This was carried out by introducing methylated or brominated purines (m1G, m6,6A, or 8-BrG), probing varying [Mg2+], and using circular dichroism (CD) to explore the formation of structured RNA. It was determined that spatial constraints imposed by conformational changes around the glycosidic bond may be partially responsible for stalling, however, the results do not fully explain some of the observed higher stalling yields. We hypothesize that altered π-π stacking along with induced H-bonding interactions between 8-oxoG and residues within the binding site may also play a role in the decreased Xrn-1 efficiency. Overall, these observations suggest that other factors, yet to be discovered/established, are likely to contribute to the decay of oxidized RNA. In addition, Xrn-1 degraded RNA containing m1G, and stalled mildly at sites where it encountered m6,6A, or 8-BrG, which is of particular interest given that the former two are naturally occurring modifications.
Efficient and Accurate Synapse Detection With Selective Structured Illumination Microscopy on the Putative Regions of Interest of Ultrathin Serial Sections
Authors: Kim Gyeong Tae , Bahn Sangkyu , Kim Nari , Choi Joon Ho , Kim Jinseop S. , Rah Jong-Cheol
Published: November 2021

Critical determinants of synaptic functions include subcellular locations, input sources, and specific molecular characteristics. However, there is not yet a reliable and efficient method that can detect synapses. Electron microscopy is a gold-standard method to detect synapses due to its exceedingly high spatial resolution. However, it requires laborious and time-consuming sample preparation and lengthy imaging time with limited labeling methods. Recent advances in various fluorescence microscopy methods have highlighted fluorescence microscopy as a substitute for electron microscopy in reliable synapse detection in a large volume of neural circuits. In particular, array tomography has been verified as a useful tool for neural circuit reconstruction. To further improve array tomography, we developed a novel imaging method, called “structured illumination microscopy on the putative region of interest on ultrathin sections”, which enables efficient and accurate detection of synapses-of-interest. Briefly, based on low-magnification conventional fluorescence microscopy images, synapse candidacy was determined. Subsequently, the coordinates of the regions with candidate synapses were imaged using super-resolution structured illumination microscopy. Using this system, synapses from the high-order thalamic nucleus, the posterior medial nucleus in the barrel cortex were rapidly and accurately imaged.
Nanocellulose: Resources, Physio-Chemical Properties, Current Uses and Future Applications
Authors: Kaur Prabhpreet , Sharma Neha , Munagala Meghana , Rajkhowa Rangam , Aallardyce Ben , Shastri Yogendra , Agrawal Ruchi
Published: November 2021

The growing environmental concerns due to the excessive use of non-renewable petroleum based products have raised interest for the sustainable synthesis of bio-based value added products and chemicals. Recently, nanocellulose has attracted wide attention because of its unique properties such as high surface area, tunable surface chemistry, excellent mechanical strength, biodegradability and renewable nature. It serves wide range of applications in paper making, biosensor, hydrogel and aerogel synthesis, water purification, biomedical industry and food industry. Variations in selection of source, processing technique and subsequent chemical modifications influence the size, morphology, and other characteristics of nanocellulose and ultimately their area of application. The current review is focused on extraction/synthesis of nanocellulose from different sources such as bacteria and lignocellulosic biomass, by using various production techniques ranging from traditional harsh chemicals to green methods. Further, the challenges in nanocellulose production, physio-chemical properties and applications are discussed with future opportunities. Finally, the sustainability of nanocellulose product as well as processes is reviewed by taking a systems view. The impact of chemicals, energy use, and waste generated can often negate the benefit of a bio-based product. These issues are evaluated and future research needs are identified.
Overtraining Strengthens the Visual Discrimination Memory Trace Outside the Hippocampus in Male Rats
Authors: Lehmann Hugo , Stykel Morgan G. , Glenn Melissa J.
Published: November 2021

The hippocampus (HPC) may compete with other memory systems when establishing a representation, a process termed overshadowing. However, this overshadowing may be mitigated by repeated learning episodes, making a memory resistant to post-training hippocampal damage. In the current study, we examined this overshadowing process for a hippocampal-dependent visual discrimination memory in rats. In Experiment 1, male rats were trained to criterion (80% accuracy on two consecutive days) on a visual discrimination and then given 50 additional trials distributed over 5 days or 10 weeks. Regardless of this additional learning, extensive damage to the HPC caused retrograde amnesia for the visual discrimination, suggesting that the memory remained hippocampal-dependent. In Experiment 2, rats received hippocampal damage before learning and required approximately twice as many trials to acquire the visual discrimination as control rats, suggesting that, when the overshadowing or competition is removed, the non-hippocampal memory systems only slowly acquires the discrimination. In Experiment 3, increasing the additional learning beyond criterion by 230 trials, the amount needed in Experiment 2 to train the non-hippocampal systems in absence of competition, successfully prevented the retrograde amnesic effects of post-training hippocampal damage. Combined, the findings suggest that a visual discrimination memory trace can be strengthened in non-hippocampal systems with overtraining and become independent of the HPC.
The Hair Cell α9α10 Nicotinic Acetylcholine Receptor: Odd Cousin in an Old Family
Authors: Lipovsek Marcela , Marcovich Irina , Elgoyhen Ana Belén
Published: November 2021

Nicotinic acetylcholine receptors (nAChRs) are a subfamily of pentameric ligand-gated ion channels with members identified in most eumetazoan clades. In vertebrates, they are divided into three subgroups, according to their main tissue of expression: neuronal, muscle and hair cell nAChRs. Each receptor subtype is composed of different subunits, encoded by paralogous genes. The latest to be identified are the α9 and α10 subunits, expressed in the mechanosensory hair cells of the inner ear and the lateral line, where they mediate efferent modulation. α9α10 nAChRs are the most divergent amongst all nicotinic receptors, showing marked differences in their degree of sequence conservation, their expression pattern, their subunit co-assembly rules and, most importantly, their functional properties. Here, we review recent advances in the understanding of the structure and evolution of nAChRs. We discuss the functional consequences of sequence divergence and conservation, with special emphasis on the hair cell α9α10 receptor, a seemingly distant cousin of neuronal and muscle nicotinic receptors. Finally, we highlight potential links between the evolution of the octavolateral system and the extreme divergence of vertebrate α9α10 receptors.
Incidence, Demographics, and Outcomes of Penetrating Trauma in Sweden During the Past Decade
Authors: Günther Mattias , Dahlberg Martin , Rostami Amir , Azadali Ali , Arborelius Ulf P. , Linder Fredrik , Rostami Elham
Published: November 2021

Trauma injury is the sixth leading cause of death worldwide, and interpersonal violence is one of the major contributors in particular regarding injuries to the head and neck. The incidence, demographics, and outcomes of penetrating trauma reaching hospitals in Sweden are not known. We report the largest, nationwide epidemiological study of penetrating injuries in Sweden, using the Swedish Trauma Registry (SweTrau). A multi-center retrospective descriptive study of 4,776 patients was conducted with penetrating injuries in Sweden, between 2012 and 2018. Due to the increase in coverage of the SweTrau registry during the same period, we chose to analyze the average number of cases for the time intervals 2013–2015 and 2016–2018 and compare those trends to the reports of the Swedish National Council for Crime Prevention (Brå) as well. A total of 663 patients had Injury Severity Score (ISS) ≥ 15 at admission and were included in the study. Three hundred and sixty-eight (55.5%) were stab wounds (SW), 245 (37.0%) gunshot wounds (GSW), and 50 (7.5%) other traumas. A majority of the cases involved injuries to the head, neck, and face. SW increased from 145 during 2013–2015 to 184 during the second period of 2016–2018. The increase was greater for GSW from 92 to 141 during the same respective periods. This trend of increase over time was also seen in head, neck, and face injuries. The 30-day mortality was unaffected (48–47%) in GSW and trended toward lower in SW (24–21%) when comparing 2013–2015 with 2016–2018. Patients with head trauma had 45% mortality compared to 18% for non-head trauma patients. Head trauma also resulted in worse outcomes, only 13% had Glasgow outcome score (GOS) 5 compared to 27% in non-head trauma. The increasing number of cases of both SW and GSW corresponded well with reports from Brå although further studies also are needed to address deaths outside of hospitals and not registered at the SweTrau. The majority of cases had injuries to the head, neck, and face and were associated with higher mortality and poor outcomes. Further studies are needed to understand the contributing factors to these worse outcomes in Sweden and whether more targeted trauma care of these patients can improve outcomes.
Focal Seizures and Posterior Reversible Encephalopathy Syndrome as Presenting Signs of IgA Vasculitis/Henoch-Schoenlein Purpura—An Educative Case and Systematic Review of the Literature
Authors: Funken Dominik , Götz Friedrich , Bültmann Eva , Hennies Imke , Gburek-Augustat Janina , Hempel Julya , Dressler Frank , Baumann Ulrich , Klemann Christian
Published: November 2021

Background:IgA vasculitis/Henoch-Schoenlein purpura (IgAV/HSP) is a systemic small vessel vasculitis of unknown pathogenesis predominantly affecting children. While skin, GI tract, joints, and kidneys are frequently affected and considered, central nervous system (CNS) involvement of this disease is underestimated.

Methods:We provide a case report and systematically review the literature on IgAV, collecting data on the spectrum of neurological manifestations.

Results:We report on a 7-year-old girl with IgAV who presented with diplopia and afebrile focal seizures, which preceded the onset of purpura. Cranial magnetic resonance imaging was consistent with posterior reversible encephalopathy syndrome (PRES), showing typical focal bilateral parietal swelling and cortical and subcortical high signal intensities on T2-fluid attenuated inversion recovery (FLAIR) images predominantly without diffusion restriction. Cerebrospinal fluid analysis and blood tests excluded systemic inflammation or vasculitis. Interestingly, hypertension was not a hallmark of the developing disease in the initial phase of PRES manifestation. Renal disease and other secondary causes for PRES were also excluded. Supportive- and steroid treatment resulted in restitutionad integrum. Reviewing the literature, we identified 28 other cases of IgAV with CNS involvement. Severe CNS involvement includes seizures, cerebral edema, or hemorrhage, as well as PRES. Thirteen patients fulfilled all diagnostic criteria of PRES. The mean age was 11.2 years (median 8.0, range 5-42 years), with no reported bias toward gender or ethnic background. Treatment regimens varied from watchful waiting to oral and intravenously steroids up to plasmapheresis. Three cases showed permanent CNS impairment.

Conclusion:Collectively, our data demonstrate that (I) severe CNS involvement such as PRES is an underappreciated feature of IgAV, (II) CNS symptoms may precede other features of IgAV, (III) PRES can occur in IgAV, and differentiation from CNS vasculitis is challenging, (IV) pathogenesis of PRES in the context of IgAV remains elusive, which hampers treatment decisions. We, therefore, conclude that clinical awareness and the collection of structured data are necessary to elucidate the pathophysiological connection of IgAV and PRES.