bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific neuronal subpopulations in the rat basolateral amygdala express high levels of nonphosphorylated neurofilaments
Authors: McDonald Alexander Joseph , Mascagni Franco
Published: May 2021

Cortical pyramidal neurons (PNs) containing nonphosphorylated neurofilaments (NNFs) localized with the SMI‐32 monoclonal antibody have been shown to be especially vulnerable to degeneration in Alzheimer's disease (AD). The present investigation is the first to study the expression of SMI‐32+ NNFs in neurons of the basolateral nuclear complex of the amygdala (BNC), which contains cortex‐like PNs and nonpyramidal neurons (NPNs). We observed that PNs in the rat basolateral nucleus (BL), but not in the lateral (LAT) or basomedial (BM) nuclei, have significant levels of SMI‐32‐ir in their somata with antibody diluents that did not contain Triton X‐100, but staining in these cells was greatly attenuated when the antibody diluent contained 0.3% Triton. Using Triton‐containing diluents, we found that all SMI‐32+ neurons in all three of the BNC nuclei were NPNs. Using a dual‐labeling immunoperoxidase technique, we demonstrated that most of these SMI‐32+ NPNs were parvalbumin‐positive (PV+) or somatostatin‐positive NPNs but not vasoactive intestinal peptide‐positive or neuropeptide Y‐positive NPNs. Using a technique that combines retrograde tracing with SMI‐32 immunohistochemistry using intermediate levels of Triton in the diluent, we found that all BNC neurons projecting to the mediodorsal thalamic nucleus (MD) were large NPNs, and most were SMI‐32+. In contrast, BNC neurons projecting to the ventral striatum or cerebral cortex were PNs that expressed low levels of SMI‐32 immunoreactivity (SMI‐32‐ir) in the BL, and no SMI‐32‐ir in the LAT or BM. These data suggest that the main neuronal subpopulations in the BNC that degenerate in AD may be PV+ and MD‐projecting NPNs.
GLPG1205, a GPR84 Modulator: Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Subjects
Authors: Timmis Helen , Van Kaem Tim , Desrivot Julie , Dupont Sonia , Meuleners Luc , Beetens Johan , Helmer Eric , Santermans Eva , Huettner Silke
Published: May 2021

GLPG1205 is a modulator of GPR84, a G‐protein–coupled receptor reported to be associated with several diseases. Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1205 in healthy subjects were evaluated in 2 randomized, double‐blind, placebo‐controlled, single‐site, phase 1 studies. In study 1, 16 (aged 21‐48 years) and 24 (24‐50 years) healthy men received single doses of GLPG1205 10 to 800 mg, and GLPG1205 50, 100, or 200 mg once daily for 14 days, respectively, or placebo. Study 2 evaluated the effect of aging on GLPG1205 pharmacokinetics: 24 healthy men (aged 37–83 years), weight‐matched into 3 age cohorts (65‐74, ≥75, and 18‐50 years), received GLPG1205 50 mg or placebo once daily for 14 days; an open‐label part of this study evaluated a GLPG1205 250‐mg loading dose followed by 50 mg once daily for 13 days in 8 healthy men (aged 68‐74 years). Single (up to 800 mg) and multiple (maximum tolerated dose 100 mg once daily) GLPG1205 doses had favorable safety and tolerability profiles. After single administration of GLPG1205, median time to occurrence of maximum observed plasma concentration and arithmetic mean apparent terminal half‐life ranged from 2.0 to 4.0 and from 30.1 to 140 hours, respectively. Age did not affect GLPG1205 exposure. GPR84 receptor occupancy with GLPG1205 vs placebo confirmed target engagement. These results support further clinical development of GLPG1205.
Performance characterization of video analytics workloads in heterogeneous edge infrastructures
Authors: Rivas Daniel , Guim Francesc , Polo Jordà , Carrera David
Published: May 2021

Powered by deep learning, video analytic applications process millions of camera feeds in real‐time to extract meaningful information from their surroundings. And this number grows by the minute. To avoid saturating the backhaul network and provide lower latencies, a distributed and heterogeneous edge cloud is postulated as a key enabler for widespread video analytics. This article provides a complete characterization of end‐to‐end video analytics across a set of hardware platforms and different neural network architectures. Each platform is selected to fill a different gap in a distributed, shared, and heterogeneous infrastructure. Moreover, we analyze how performance scales on each of these platforms with respect to the amount of resources dedicated to video analytics. Finally, we extract the key conclusions of the characterization to build an experimental model to estimate performance and cost of end‐to‐end video analytics in different edge scenarios. Our experiments show that managing video analytics workloads efficiently requires awareness of both, the platforms in which these are executed, and the full end‐to‐end pipeline. To the best of our knowledge, this is the first work that provides a complete characterization of end‐to‐end video analytics in heterogeneous edge platforms.
Edge intelligence‐enabled supply chain financial model based on Business‐to‐Business e‐business platforms
Authors: Yin Feng , Yang Rongjun , Yu Hongxin , Zhou Wei , Zhao Yuanjun , Zhang Shuai
Published: May 2021

Based on the analysis of the existing traditional supply chain financial model, this article proposes an edge intelligence‐enabled supply chain financial model based on Business‐to‐Business (B2B) platforms, combines the operation mechanism of the model and the quantitative analysis thinking of the traditional supply chain financing. This article uses the model to construct and evaluates the cost–benefit model of dealers, manufacturers, and B2B e‐business platforms in the perspective of the supply chain finance for B2B platforms. In order to further explore the operation strategy of supply chain member enterprises, this article also explores the selection of financing objects of B2B platforms, the optimization of financing cost rate formulated by the loan amount of financing enterprises, and the optimization of product order quantity. Numerical analysis shows that the proposed model can directly reflect the changing trend of the relevant parameters of B2B platforms' supply chain financial model and provide suggestions for the cooperation mechanism between supply chain and commercial banks.
Discovery of Nonracemic Amisulpride to Maximize Benefit/Risk of 5‐HT7 and D2 Receptor Antagonism for the Treatment of Mood Disorders
Authors: Hopkins Seth C. , Wilkinson Scott , Corriveau Taryn J. , Nishikawa Hiroyuki , Nakamichi Keiko , Loebel Antony , Koblan Kenneth S.
Published: May 2021

In contrast to the dose‐occupancy relationship in the treatment of schizophrenia, the minimal effective level of dopamine receptor 2 (D2R) blockade for antipsychotics in the treatment of bipolar depression is unknown. Lower doses aimed at reducing extrapyramidal side effects must be balanced against the need to retain the therapeutic benefit of D2R blockade on emergent cycling, mixed, manic, anxiety, and/or psychotic symptoms. Dose‐reductions intended to lower D2R blockade, however, could also decrease concomitant serotonin receptor antagonism and its potential benefit on depressive symptoms. Here, we uncoupled the potential antidepressant activity in amisulpride, driven by 5‐HT7 receptor (5‐HT7R) antagonism, from the D2R‐mediated antipsychotic activity by discovering that each enantiomer favors a different receptor. Aramisulpride was more potent at 5‐HT7R relative to esamisulpride (Ki 47 vs. 1,900 nM, respectively), whereas esamisulpride was more potent at D2R (4.0 vs. 140 nM). We hypothesized that a nonracemic ratio might achieve greater 5‐HT7R‐mediated antidepressant effects at a lower level of D2R blockade. The dose‐occupancy relationship of esamisulpride at D2R was determined by positron emission tomography (PET) imaging in human volunteers. Separately the dose‐relationship of aramisulpride was established in humans using suppression of rapid eye movement (REM) sleep as a marker of 5‐HT7R antagonism. These results led to the discovery of an 85:15 ratio of aramisulpride to esamisulpride (SEP‐4199) that maximizes the potential for antidepressant benefit of aramisulpride via 5‐HT7R and reduces esamisulpride to minimize D2R‐related extrapyramidal side effects while still retaining D2R‐mediated effects predicted to provide benefit in bipolar depression. The antidepressant efficacy of SEP‐4199 was recently confirmed in a proof‐of‐concept trial for the treatment of bipolar depression (NCT03543410).
Learned Embeddings from Deep Learning to Visualize and Predict Protein Sets
Authors: Dallago Christian , Schütze Konstantin , Heinzinger Michael , Olenyi Tobias , Littmann Maria , Lu Amy X. , Yang Kevin K. , Min Seonwoo , Yoon Sungroh , Morton James T. , Rost Burkhard
Published: May 2021

Models from machine learning (ML) or artificial intelligence (AI) increasingly assist in guiding experimental design and decision making in molecular biology and medicine. Recently, Language Models (LMs) have been adapted from Natural Language Processing (NLP) to encode the implicit language written in protein sequences. Protein LMs show enormous potential in generating descriptive representations (embeddings) for proteins from just their sequences, in a fraction of the time with respect to previous approaches, yet with comparable or improved predictive ability. Researchers have trained a variety of protein LMs that are likely to illuminate different angles of the protein language. By leveraging the bio_embeddings pipeline and modules, simple and reproducible workflows can be laid out to generate protein embeddings and rich visualizations. Embeddings can then be leveraged as input features through machine learning libraries to develop methods predicting particular aspects of protein function and structure. Beyond the workflows included here, embeddings have been leveraged as proxies to traditional homology‐based inference and even to align similar protein sequences. A wealth of possibilities remain for researchers to harness through the tools provided in the following protocols. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC.

The following protocols are included in this manuscript:

Basic Protocol 1: Generic use of the bio_embeddings pipeline to plot protein sequences and annotations

Basic Protocol 2: Generate embeddings from protein sequences using the bio_embeddings pipeline

Basic Protocol 3: Overlay sequence annotations onto a protein space visualization

Basic Protocol 4: Train a machine learning classifier on protein embeddings

Alternate Protocol 1: Generate 3D instead of 2D visualizations

Alternate Protocol 2: Visualize protein solubility instead of protein subcellular localization

Support Protocol: Join embedding generation and sequence space visualization in a pipeline
Association of masseter muscles thickness and facial morphology with facial expressions in children
Authors: Guédat Christophe , Stergiopulos Ourania , Kiliaridis Stavros , Antonarakis Gregory S.
Published: May 2021

Objective

To evaluate the potential influence of muscular capacity and facial morphology on facial expressions in children.

Materials and methods

A cross‐sectional study was carried out on 40 healthy children (ages 9–13), without previous orthodontic treatment. Masseter muscle thickness and anthropometric facial proportions were measured using ultrasound and digital calipers respectively. A three‐dimensional infrared face‐tracking system was used to register facial expressions. The maximal amplitude of smile and lip pucker (representing maximal lateral and medial commissure movement) were used for analysis. Stepwise regression was used to investigate whether muscle thickness or anthropometric facial proportions were associated with the quantity of commissure movement.

Results

When performing maximal smile, children with thicker masseter muscles were found to have more limited displacement of the commissures (R = 0.39; p = 0.036). When performing lip pucker, children with thicker masseter muscles were found to have greater commissure movement (R = 0.40; p = 0.030). No significant associations were found between anthropometric facial proportions and facial expressions.

Conclusion

Masseter muscle thickness seems to be associated with facial expressions in children. Those with thicker muscles show more limited commissure movement when smiling, but greater movement with lip pucker. This indicates that masticatory muscles may serve as a surrogate for mimic muscle activity. Facial morphology of the subjects does not seem to be associated with facial expression.
Influence of childhood asthma on dental caries: A longitudinal study
Authors: Samec Tomi , Amaechi Bennett Tochukwu , Jan Janja
Published: May 2021

Objectives

The study investigated the influence of childhood asthma on dental caries development and caries risk factors among children with asthma in Slovenia.

Material and methods

The study population consisted of 2–17 years old children (n = 138), who had used anti‐asthmatic medicines for at least 1 year. Controls were their non‐asthmatic siblings (n = 140). International Caries Detection and Assessment System‐II was used to assess caries status. After 3 years, 106 baseline participants (53 asthmatic and 53 siblings) were reexamined. Questionnaires completed by parents and data from the patients' medical records provided information on demographics, child's medical history, medication usage, and oral health behaviors. Additional 308 asthmatic children were examined to assess caries risk factors among children with asthma.

Results

Asthmatic children had significantly higher mean d12fs and D12MFS (p ≤ 0.05), and fewer caries‐free individuals (p ≤ 0.01). In asthmatic children, 3 years mean increment in D12MFS was significantly higher (p ≤ 0.05). Furthermore, progression over 3 years from sound tooth surfaces to decayed cavitated and filled lesions in primary and permanent teeth were present in significantly higher (p ≤ 0.05) percentage, and likewise transition from decayed cavitated lesions to missing tooth surfaces because of caries in primary teeth, and from filled to filled non‐cavitated and cavitated lesions in permanent teeth. Lower caries experience in asthmatic children was associated with lower doses of inhaled glucocorticoid use, leucotriene antagonist use, and daily milk and cheese consumption.

Conclusions

Asthmatic children who had used anti‐asthmatic medicines had higher caries experience and higher caries progression over 3 years in both primary and permanent dentitions. Besides anti‐asthmatic medicines, other factors were associated with higher caries experience in asthmatic children.
Distribution of lip‐seal strength and its relation to oral motor functions
Authors: Kugimiya Yoshihiro , Oki Takeshi , Ohta Midori , Ryu Masahiro , Kobayashi Kenichiro , Sakurai Kaoru , Ueda Takayuki
Published: May 2021

Objectives

Lip‐seal strength, which represents the muscle strength of the lips, appears to chiefly contribute to mastication and pronunciation. However, the functional characteristics of lip‐seal strength in adults are still undefined. The present study aimed to understand not only the distribution of lip‐seal strength in adult men and women but also the effect of age on this strength and identify oral motor functions correlated with lip‐seal strength.

Materials and methods

The subjects included 339 participants (men: 170, age 39.2 ± 18.2 years; women: 169, age 43.1 ± 19.7 years). Oral motor function was evaluated for lip‐seal strength, oral diadochokinesis (ODK), tongue pressure, occlusal force, and masticatory performance. Statistical analyses included the Shapiro–Wilk, Mann–Whitney U, and Jonckheere–Terpstra tests, in addition to the Spearman's correlation analysis and curvilinear regression analysis.

Results

Lip‐seal strength did not have a normal distribution (p < 0.001). The mean ± standard deviation and median (first quartile, third quartile) of lip‐seal strength were 11.2 ± 3.4 and 10.9 (8.7, 13.2)N for the whole sample, 12.3 ± 3.4 and 11.9 (9.4, 14.4)N for men, and 10.2 ± 3.0 and 9.9 (8.0, 12.0)N for women. A significant difference was observed in lip‐seal strength between men and women (p < 0.001). Oral motor functions showed a marked correlation with lip‐seal strength, including tongue pressure, occlusal force, and masticatory performance and ODK (/pa/ and /ta/), tongue pressure, and masticatory ability in men and women, respectively. In women, lip‐seal strength declined with increase in age.

Conclusions

Lip‐seal strength was non‐normally distributed in both men and women, and lip‐seal strength was affected by age only in women. Lip‐seal strength and multiple oral motor functions were significantly correlated. Because the indicators of perioral muscle strength and performance were correlated with lip‐seal strength, lip‐seal strength may also partially reflect the condition of the perioral muscles.
The cold resistance of cottonseed during germination is related to the content of unsaturated fatty acids
Authors: Chen Ying , Tian Liwen , Wan Lu , Xia Jun , Liu Feng , Zhao Ruihai , Wang Tangang , Han Chunli
Published: May 2021

The agricultural industry is severely affected by low temperature due to its wide range of adverse effects. This work aimed to elucidate the changes in fatty acid composition during cotton (Gossypium L.) seed germination and the relationship of that change and germination characteristics. Three temperatures, 15/12 (T12), 21/18 (T18), and 25/25 °C day/night (T25), were set to treat Xinluzao 65 (L65) and Xinhai 35 (H35). Under T12, the germination rate, germination index, and water absorption rate of the cotton seeds decreased, and the mean time of germination increased compared to T25. The germination rate, germination index and water absorption rate of H35 were 6.67, 5.15, and 17% higher, respectively, than those of L65 under the T2 treatment. The total lipids, saturated fatty acid/unsaturated fatty acid (SFA/UFA) ratio, and monounsaturated fatty acid/polyunsaturated fatty acid (MUFA/PUFA) ratio were 3.75, 0.30, and 4.98% higher, respectively, in H35 than in L65 under the T25 treatment. The water absorption rate of L65 was significantly positively correlated with C18:2 and significantly negatively correlated with C24:0 and C18:1. The water absorption rate and germination rate of H35 were significantly positively correlated with C14:0 and C16:1, and C18:2 was significantly negatively correlated with the germination rate and the water absorption rate. Therefore, low‐temperature stress in cotton results in an increase in the water absorption rate and consequent decreases in the concentrations of SFAs C20:0, C22:0, and C24:0, as well as an increase in the concentration of UFA C16:1. These changes enhance the ability of cotton seeds to resist cold damage.
Formic Acid as a Potential On‐Board Hydrogen Storage Method: Development of Homogeneous Noble Metal Catalysts for Dehydrogenation Reactions
Authors: Guo Jian , Yin Chengkai K. , Zhong Dulin L. , Wang Yilin L. , Qi Tiangui , Liu Guihua H. , Shen Leiting T. , Zhou Qiusheng S. , Peng Zhihong H. , Yao Hong , Li Xiaobin B.
Published: May 2021

Hydrogen can be used as an energy carrier for renewable energy to overcome the deficiency of its intrinsically intermittent supply. One of the most promising application of hydrogen energy is on‐board hydrogen fuel cells. However, the lack of a safe, efficient, convenient, and low‐cost storage and transportation method for hydrogen limits their application. The feasibility of mainstream hydrogen storage techniques for application in vehicles is briefly discussed in this Review. Formic acid (FA), which can reversibly be converted into hydrogen and carbon dioxide through catalysis, has significant potential for practical application. Historic developments and recent examples of homogeneous noble metal catalysts for FA dehydrogenation are covered, and the catalysts are classified based on their ligand types. The Review primarily focuses on the structure−function relationship between the ligands and their reactivity and aims to provide suggestions for designing new and efficient catalysts for H2 generation from FA.
Regulating Utilization Efficiency of the Photogenerated Charge Carriers by Constructing Donor–π–Acceptor Polymers for Upgrading Photocatalytic CO2Reduction
Authors: Chen Jinqing , Zhong Hong , Lv Haowei , Liu Ruixia , Wang Ruihu
Published: May 2021

Photocatalytic CO2reduction offers a promising approach for managing global carbon balance. The smooth delivery of the photoexcited electrons to the active sites without the extra photosensitizers is still challenging. Herein, a series of donor–π–acceptor conjugated organic polymers (COPs) were produced using anthracene, cobalt‐coordinated bipyridyl, and benzene as donor, acceptor, and π linker units, respectively. The introduction of phenyl linker significantly improved the activities of photocatalytic CO2reduction upon visible light illumination. Structure–performance relationship examinations uncovered that donor–π–acceptor structure promotes mobility of charge carriers and utilization efficiency on the catalytically active sites, resulting in high photocatalytic activity and durability for CO2photoreduction. The in‐depth insights into the electron transport processes open new perspectives for further optimization and rational design of photoactive polymers with high efficiency for solar‐energy conversion.
DebarcodeR increases fluorescent cell barcoding capacity and accuracy
Authors: Reisman Benjamin J. , Barone Sierra M. , Bachmann Brian O. , Irish Jonathan M.
Published: May 2021

Fluorescent cell barcoding (FCB) enables efficient collection of tens to hundreds of flow cytometry samples by covalently marking cells with varying concentration of spectrally distinct dyes. A key consideration in FCB is to balance the density of dye barcodes, the complexity of cells in the sample, and the desired accuracy of the debarcoding. Unfortunately, barcoding bench and computational methods have not benefited from the high dimensional revolution in cytometry due to a lack of automated computational tools that effectively balance these common cytometry needs. DebarcodeR addresses these unmet needs by providing a framework for computational debarcoding augmented by improvements to experimental methods. Adaptive regression modeling accounted for differential dye uptake between different cell types and Gaussian mixture modeling provided a robust method to probabilistically assign cells to samples. Assignment tolerance parameters are available to allow users to balance high cell recovery with accurate assignments. Improvements to experimental methods include: (1) inclusion of an “external standard” control where a pool of all cells was stained a single level of each barcoding dyes and (2) an “internal standard” where each cell is stained with a single level of a separate dye. DebarcodeR significantly improved speed, accuracy, and reproducibility of FCB while avoiding selective loss of unusual cell subsets when debarcoding microtiter plates of cell lines and heterogenous mixtures of primary cells. DebarcodeR is available on Github as an R package that works with flowCore and Cytoverse packages at github.com/cytolab/DebarcodeR.
Which hand knows the “right” word? What hand selection reveals about vocabulary in pre‐and school‐aged children
Authors: van Rootselaar Nicole A. , Grandmont Dana , Gibb Robbin , Li Fangfang , Gonzalez Claudia L. R.
Published: May 2021

Research has shown that infants with increased right‐hand selection for their first gestures perform better at an array of language tasks when they are tested later as toddlers. There is a smaller body of literature which focuses on preschoolers and how their right‐handed movements relate to their speech and vocabulary development. Some research has established a connection between right‐hand preference for grasping and speech production ability in preschool children, but the link to gestures is relatively unexplored in this age group. We investigated if lateralized gestures (pointing) are related to measures of language development (vocabulary) in a preschool‐age sample. Specifically, typically developing children (aged 3–6) completed the Peabody Picture Vocabulary Test (PPVT) to assess receptive language. We recorded their hand preference for pointing during the PPVT and the incidence of mistakes (pointing to the wrong picture). Despite the length of the test, children were more likely to select a correct response with their right hand. This result suggests a relationship between lateralized communicative gestures (pointing) and receptive language. This study provides evidence for an intimate relationship between right‐handed manual movement and language development. Implications of this finding include developing simple fine‐motor tasks to detect and/or ameliorate delayed language development.
Processes that drive the population structuring of Jenynsia lineata (Cyprinidontiformes, Anablepidae) in the La Plata Basin
Authors: Briñoccoli Yanina F. , Jardim de Queiroz Luiz , Bogan Sergio , Paracampo Ariel , Posadas Paula E. , Somoza Gustavo M. , Montoya‐Burgos Juan I. , Cardoso Yamila P.
Published: May 2021

The distribution of genetic diversity across a species distribution range is rarely homogeneous, as the genetic structure among populations is related to the degree of isolation among them, such as isolation by distance, isolation by barrier, and isolation by environment.

Jenynsia lineata is a small viviparous fish that inhabits a wide range of habitats in South America. To decipher the isolation processes that drive population structuring in J. lineata, we analyzed 221 sequences of the mitochondrial cytochrome c oxidase I gene (COI), from 19 localities. Then, we examined the influence of the three most common types of isolation in order to explain the genetic variation found in this species.

Our results revealed a marked structuration, with three groups: (a) La Plata/Desaguadero Rivers (sampling sites across Argentina, Uruguay, and Southern Brazil), (b) Central Argentina, and (c) Northern Argentina. A distance‐based redundancy analysis, including the explanatory variables geographical distances, altitude, latitude, and basin, was able to explain up to 65% of the genetic structure. A variance partitioning analysis showed that the two most important variables underlying the structuration in J. lineata were altitude (isolation by environment) and type of basin (isolation by barrier).

Our results show that in this species, the processes of population diversification are complex and are not limited to a single mechanism. The processes that play a prominent role in this study could explain the high rate of diversity that characterizes freshwater fish species. And these processes in turn are the basis for possible speciation events.
New karyotype for Mesomys stimulax (Rodentia, Echimyidae) from the Brazilian Amazon: A case for species complex?
Authors: Malcher Stella Miranda , Pieczarka Julio Cesar , Pereira Adenilson Leão , do Amaral Paulo José Siqueira , Rossi Rogério Vieira , Saldanha Juliane , Nagamachi Cleusa Yoshiko
Published: May 2021

Mesomys Wagner, 1845 (Rodentia, Echimyidae, Eumysopinae) currently has four recognized species, three of which occur in Brazil: Mesomys hispidus (probably a species complex), M. occultus, and M. stimulax. Mesomys leniceps is found in montane forests of northern Peru. Mesomys stimulax, the focus of the present study, has a distribution that is restricted to the central and eastern Amazonia south of the Amazon River, extending from the left bank of the Tapajós River to the right bank of the Tocantins River, and south to the southeast portion of Pará State. The genus presents karyotypes with diploid number 2n = 60 and Fundamental Number (FN) = 116 for M. hispidus and M. stimulax, and 2n = 42, FN = 54 for M. occultus. We studied the karyotype of a female specimen of M. stimulax collected from the Tapirapé‐Aquiri National Forest, Marabá, Pará, Brazil, in the Xingu/Tocantins interfluvium. The obtained karyotype (2n = 60 and FN = 110) differs from that described in the literature for both M. stimulax and M. hispidus by exhibiting more biarmed chromosomes, probably due to pericentric inversions and/or centromeric repositioning, and exhibiting differences in the amount and distribution of constitutive heterochromatin (CH). These results suggest that, similar to what has already been proposed for M. hispidus, M. stimulax may represent a species complex and/or cryptic species. The mechanisms of chromosomal diversification in Mesomys and the biogeographic implications are discussed reinforcing the need for broad systematic review for Mesomys.
Directional seed and pollen dispersal and their separate effects on anisotropy of fine‐scale spatial genetic structure among seedlings in a dioecious, wind‐pollinated, and wind‐dispersed tree species, Cercidiphyllum japonicum
Authors: Nakanishi Atsushi , Goto Susumu , Sumiyoshi Chikako , Isagi Yuji
Published: May 2021

Prevailing directions of seed and pollen dispersal may induce anisotropy of the fine‐scale spatial genetic structure (FSGS), particularly in wind‐dispersed and wind‐pollinated species. To examine the separate effects of directional seed and pollen dispersal on FSGS, we conducted a population genetics study for a dioecious, wind‐pollinated, and wind‐dispersed tree species, Cercidiphyllum japonicum Sieb. et Zucc, based on genotypes at five microsatellite loci of 281 adults of a population distributed over a ca. 80 ha along a stream and 755 current‐year seedlings. A neighborhood model approach with exponential‐power‐von Mises functions indicated shorter seed dispersal (mean = 69.1 m) and much longer pollen dispersal (mean = 870.6 m), effects of dispersal directions on the frequencies of seed and pollen dispersal, and the directions with most frequent seed and pollen dispersal (prevailing directions). Furthermore, the distance of effective seed dispersal within the population was estimated to depend on the dispersal direction and be longest at the direction near the prevailing direction. Therefore, patterns of seed and pollen dispersal may be affected by effective wind directions during the period of respective dispersals. Isotropic FSGS and spatial sibling structure analyses indicated a significant FSGS among the seedlings generated by the limited seed dispersal, but anisotropic analysis for the seedlings indicated that the strength of the FSGS varied with directions between individuals and was weakest at a direction near the directions of the most frequent and longest seed dispersal but far from the prevailing direction of pollen dispersal. These results suggest that frequent and long‐distance seed dispersal around the prevailing direction weakens the FSGS around the prevailing direction. Therefore, spatially limited but directional seed dispersal would determine the existence and direction of FSGS among the seedlings.
Relating leaf traits to seedling performance in a tropical forest: building a hierarchical functional framework
Authors: Umaña María Natalia , Swenson Nathan G. , Marchand Philippe , Cao Min , Lin Luxiang , Zhang Caicai
Published: May 2021

Trait‐based approaches have been extensively used in community ecology to provide a mechanistic understanding of the drivers of community assembly. However, a foundational assumption of the trait framework, traits relate to performance, has been mainly examined through univariate relationships that simplify the complex phenotypic integration of organisms. We evaluate a conceptual framework in which traits are organized hierarchically combining trait information at the individual‐ and species‐level from biomass allocation and organ‐level traits. We focus on photosynthetic traits and predict that the positive effects of increasing plant leaf mass on growth depend on species‐level leaf traits. We modeled growth data on more than 1,500 seedlings from 97 seedling species from a tropical forest in China. We found that seedling growth increases with allocation to leaves (high leaf area ratio and leaf mass fraction) and this effect is accentuated for species with high specific leaf area and leaf area. Also, we found that light has a significant effect on growth, and this effect is additive with leaf allocation traits. Our work offers an approach to gain further understanding of the effects of traits on the whole plant‐level growth via a hierarchical framework including organ‐level and biomass allocation traits at species and individual levels.
Hide ‘n seq: Direct versus indirect metabarcoding of coral reef cryptic communities
Authors: Nichols Patrick K. , Timmers Molly , Marko Peter B.
Published: May 2021

Ecological patterns in biodiversity are primarily based on conspicuous organisms. Few methods are used to survey the taxonomically rich cryptobiome, which is made up of inhabitants from within microhabitats. One way that cryptic marine biodiversity can be non‐invasively surveyed is by analyzing environmental DNA (eDNA) present in seawater. Using coral reefs as a model system, here we compare estimates of cryptic diversity among community biomass and eDNA metabarcoding sampling methods with a broad eukaryotic marker (COI). First, contributions to eDNA were investigated across cryptobiomes through a comparison of community metabarcoded biomass from standardized autonomous reef monitoring structures (ARMS) to eDNA acquired from seawater in which individual ARMS were soaked. Second, we compared these results to those from eDNA samples taken from within reef crevices and the ambient water column. Metabarcoding of community biomass from ARMS and eDNA from the two types of water samples revealed significantly different communities of cryptic coral reef habitat with little overlap between methods. Taxa that were unique to metabarcoding of ARMS biomass were predominantly from chitinous and calcifying groups (polychaetes, palaemonid shrimp, mollusks, brittle stars, and red algae), which suggests that these taxa are underrepresented in eDNA surveys. Other than the corals themselves, sponges and red algae were significant drivers of reef crevice community differences, while ambient seawater samples detected mostly planktonic organisms and reef fishes. Our data indicate that both eDNA and ARMS provide incomplete accounting of cryptic diversity. Direct sampling of biomass is best suited for building taxonomies and improving databases, whereas eDNA methods offer rapid insights into the composition of cryptobiomes. Because each method likely captures different taxa, multiple targeted assays can be used to provide the greatest estimates of metazoan and macroalgal richness.
Boosting the Activity and Stability with Dual‐Metal‐N Couplings for Li–O2 Battery
Authors: Wu Shan , Wu Di , Zhang Dawei , Liu Wenhong , Luo Hao , He Jianbo , Yang Qingchun , Li Zhiwei , Liu Ruiping
Published: May 2021

Electrocatalysts with high efficiency are crucial for improving the storage capacity and electrochemical stability of lithium–oxygen batteries (LOBs). In this work, through a facile hydrothermal method, cobalt–nitrogen‐doped carbon nanocubes (Co–N/C), the calcination products of zeolitic imidazolate framework (ZIF–67) are encapsulated by ultrathin C–MoS2 nanosheets to obtain Co–N/C@C–MoS2 composites which are used as host materials for the oxygen cathode. The synergistic effect between Co–Nx active sites and Mo–N coupling centers effectively promotes the formation and decomposition of Li2O2 during repeated discharge and charge process. The mesoporous C–MoS2 nanosheets with delicately designed morphology facilitate charge transfer and account for improved reaction kinetics and more importantly, suppressed side reactions between the carbon materials and the electrolyte. The oxygen cathode with the Co–N/C@C–MoS2 host shows a high initial discharge specific capacity of 21 197 mA h g−1 and a long operation life of 332 cycles. Theoretical calculation provides in‐depth explanation for the reaction mechanism and offers insights for the rational design of electrocatalysts for LOBs.
Prevalence of transthyretin amyloidosis in patients with heart failure and no left ventricular hypertrophy
Authors: Devesa Ana , Camblor Blasco Andrea , Pello Lázaro Ana María , Askari Elham , Lapeña Gregoria , Gómez Talavera Sandra , Taibo Urquía Mikel , Rodríguez Olleros Celia , Tuñón José , Ibáñez Borja , Aceña Álvaro
Published: May 2021

Aims

As evidenced by scintigraphy imaging, the prevalence of transthyretin (TTR) cardiac amyloidosis in heart failure patients with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH) ranges between 13% and 19%. The natural evolution of cardiac amyloidosis begins with the deposition of amyloid material in the myocardium, with LVH ensuing at later stages. With current imaging modalities, it is possible to detect TTR cardiac amyloidosis before the hypertrophic stage. The aim of this study was to determine the prevalence of TTR cardiac amyloidosis in HFpEF patients without LVH.

Methods and results

The study prospectively enrolled patients admitted for HF with LV ejection fraction (LVEF) ≥ 50% and LV wall thickness <12 mm. TTR cardiac amyloidosis was diagnosed according to accepted criteria, which include positive cardiac 99‐Tc‐DPD scintigraphy in the absence of monoclonal protein expansion in blood. Transthyretin gene sequencing was performed in positive patients. From July 2017 to January 2020, 329 patients with HFpEF and LV thickness <12 mm were identified. After exclusions, 58 patients completed the study with cardiac scintigraphy (79 years, 54% men; median LVEF 60% and LV wall thickness 10.5 mm). Three patients (5.2%) were positive for TTR cardiac amyloidosis; genetic analysis excluded the presence of hereditary TTR amyloidosis. Positive patients baseline characteristics (84 years, 67% men, LVEF 60%, and LV wall thickness 11 mm) were similar to patients without TTR, except for troponin levels (0.05 vs. 0.02 ng/mL, P = 0.03) and glomerular filtration rate (82 vs. 60 mL/min, P = 0.032), which were higher in TTR patients.

Conclusions

In a cohort of patients with HFpEF without LVH, the prevalence of TTR cardiac amyloidosis was 5%. Early diagnosis of cardiac involvement in TTR amyloidosis (before manifest LVH) would seem recommendable because newly approved specific treatments can prevent additional deposition of amyloid material.
Association of preoperative infections, nasal Staphylococcus aureus colonization and gut microbiota with left ventricular assist device outcomes
Authors: Yuzefpolskaya Melana , Lumish Heidi S. , Javaid Azka , Cagliostro Barbara , Mondellini Giulio M. , Bohn Bruno , Sweat Austin , Onat Duygu , Braghieri Lorenzo , Takeda Koji , Naka Yoshifumi , Sayer Gabriel T. , Uriel Nir , Aaron Justin G. , Montassier Emmanuel , Demmer Ryan T. , Colombo Paolo C.
Published: May 2021

Aims

Infections are common following left ventricular assist device (LVAD) implantation and predict adverse events. Infections are frequent prior to LVAD implantation although their impact on postoperative outcomes remains unknown. Gut and nasal microbial imbalance may predispose to mucosal colonization with pathogens. Herein, we investigated the predictive role of pre‐LVAD infections, and explored the association of nasal Staphylococcus aureus (SA) colonization and gut microbiota, on postoperative outcomes.

Methods and results

Overall, 254 LVAD patients were retrospectively categorized based on pre‐LVAD infection status: Group 1, bacterial/fungal bloodstream infection (BSI); Group 2, other bacterial/fungal; Group 3, viral; and Group 4, no infection. In a subset of patients, nasal SA colonization (n = 140) and pre‐LVAD stool (n = 25) were analysed using 16S rRNA sequencing. A total of 75 (29%) patients had a pre‐LVAD infection [Group 1: 22 (29%); Group 2: 41 (55%); Group 3: 12 (16%)]. Pre‐LVAD BSIs were independent predictors of 1‐year postoperative mortality and infections [Group 1 vs. 4: hazard ratio (HR) 2.70, P = 0.036 vs. HR 1.8, P = 0.046]. In an unadjusted analysis, pre‐LVAD infections other than BSIs, INTERMACS profile ≤2, higher serum creatinine, lower serum albumin and nasal SA colonization were also significantly associated with postoperative infections. Patients with early post‐LVAD infections exhibited decreased microbial diversity (P < 0.05).

Conclusions

Pre‐LVAD infections are common. BSIs independently predict postoperative mortality and infections. Additional studies are needed to confirm our findings that pre‐LVAD SA nasal colonization and gut microbial composition can help stratify patients' risk for infectious complications after LVAD implantation.
Regulatory T cells and transplantation tolerance: Emerging from the darkness?
Authors: Waldmann Herman
Published: May 2021

The field of tissue transplantation has revolutionized the treatment of patients with failing organs. Its success, thus far, has depended on combinations of immunosuppressive drugs that damp host immunity, while also imposing numerous unwanted side‐effects. There is a longstanding recognition that better treatment outcomes, will come from replacing these drugs, fully or in part, by taking advantage of tractable physiological mechanisms of self‐tolerance. The past 50 years have seen many advances in the field of self‐tolerance, but perhaps, the most tractable of these has been the more recent discovery of a subset T‐cells (Treg) whose role is to regulate or damp immunity.

This article is intended to first provide the reader with some historical background to explain why we have been slow to identify these cells, despite numerous clues to their existence, and also to indicate how little we know about how they achieve their regulatory function in averting transplant rejection. However, as is often the case in immunology, the therapeutic needs often dictate that our advances move to translation even before detailed explanations of the science are available. The final part of the article will briefly summarize how Treg are being harnessed as agents to interface with or perhaps, replace current drug combinations.
Differential Interleukin‐8 thresholds for chemotaxis and netosis in human neutrophils
Authors: Teijeira Alvaro , Garasa Saray , Ochoa Maria del Carmen , Cirella Assunta , Olivera Irene , Glez‐Vaz Javier , Andueza Maria Pilar , Migueliz Itziar , Alvarez Maite , Rodríguez‐Ruiz Maria Esperanza , Rouzaut Ana , Berraondo Pedro , Sanmamed Miguel F. , Perez Gracia Jose L. , Melero Ignacio
Published: May 2021

In humans, IL‐8 (CXCL8) is a key chemokine for chemotaxis of polymorphonuclear leukocytes and monocytes/macrophages when acting on CXCR1 and CXCR2. CXCL8 activity on neutrophils includes chemotaxis and eliciting the extrusion of neutrophil extracellular traps (NETs). In this study, we show that concentrations of IL‐8 that induce NETosis surpass in at least one order of magnitude those required to elicit chemoattraction in human neutrophils. IL‐8‐induced NETosis was less dependent on G‐proteins than migration, while extracellular Ca+2 chelation similarly inhibited both processes. Reactive oxygen species (ROS) were more important for NETosis than for chemotaxis as evidenced by neutralization with N‐acetyl ‐cysteine. Interestingly, selective blockade with anti‐CXCR1 mAb inhibited NETosis much more readily than chemotaxis, while pharmacological inhibition of both CXCR1 and CXCR2, or selective inhibition for CXCR2 alone, similarly inhibited both functions. Together, these results propose a model according to which low concentrations of IL‐8 in a gradient attract neutrophils to the inflammatory foci, while high receptor‐saturating concentrations of IL‐8 give rise to NETosis once leukocytes reach the core of the inflammatory insult.
The Chemistry of β‐Hydroxy Hydroperoxides
Authors: Louvel Dan , De Dios Miguel Thomas , Duc Vu Nam , Duguet Nicolas
Published: May 2021

β‐Hydroxy hydroperoxides (β‐hydroperoxy alcohols) are interesting chemical platforms, notably for the preparation of 1,2,4‐trioxanes, that are key features of numerous bioactive products such as artemisinin. In this review, the main synthetic methods to prepare β‐hydroxy hydroperoxides are presented, such as the photooxidation of allylic alcohols with singlet oxygen and the ring‐opening of epoxides with H2O2. The main applications of β‐hydroxy hydroperoxides are also detailed, including their peracetalization to 1,2,4‐trioxanes, their use as epoxidating agents and their fragmentation to carbonyl compounds. A final section is dedicated to the general characteristics and practical aspects of β‐hydroxy hydroperoxides, including their stability, safety and characterization through spectroscopic means.
Is Europe also facing an opioid crisis?—A survey of European Pain Federation chapters
Authors: Häuser Winfried , Buchser Eric , Finn David P. , Dom Geerd , Fors Egil , Heiskanen Tarja , Jarlbaek Lene , Knaggs Roger D. , Kosek Eva , Krcevski‐Škvarč Nevenka , Pakkonen Kaire , Perrot Serge , Trouvin Anne‐Priscille , Morlion Bart
Published: May 2021

Background

There is considerable public interest in whether Europe is facing an opioid crisis comparable to the one in the United States and the contribution of opioid prescriptions for pain to a potential opioid crisis.

Methods

A task force of the European Pain Federation (EFIC) conducted a survey with its national chapter representatives on trends of opioid prescriptions and of drug‐related emergency departments and substance use disorder treatment admissions and of deaths as proxies of opioid‐related harms over the last 20 years.

Results

Data from 25 European countries were received. In most European countries opioid prescriptions increased from 2004 to 2016. The levels of opioid consumption and their increase differed between countries. Some Eastern European countries still have a low opioid consumption. Opioids are mainly prescribed for acute pain and chronic noncancer pain in some Western and Northern European countries. There was a parallel increase in opioid prescriptions and some proxies of opioid‐related harms in France, Finland and the Netherlands, but not in Germany, Spain and Norway. In United Kingdom, opioid overdose deaths, but not opioid prescriptions increased between 2016 and 2018. There are no robust data available on whether prescribed opioids for pain patients contributed to opioid‐related harms.

Conclusions

There are marked differences between European countries in trends of opioid prescribing and of proxies for opioid‐related harms. Europe as a whole is not facing an opioid crisis. Discussions on the potential harms of opioids should not obstruct their prescription for cancer pain and palliative care.

Significance

Europe as a whole is not facing an opioid crisis. Some Eastern European countries have limited access to opioid medicines. Discussions on the potential harms of opioid medicines for noncancer pain should not obstruct opioid therapy for cancer therapy and palliative care.