bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycosaminoglycans and glycoproteins influence the elastic response of synovial fluid nanofilms on model oxide surfaces
Authors: Mann Amar S. , Smith Ariell M. , Saltzherr Joyce O. , Gopinath Arvind , Andresen Eguiluz Roberto C.
Published: November 2021

Synovial fluid (SF) is the natural lubricant found in articulated joints, providing unique cartilage surface protecting films under confinement and relative motion. While it is known that the synergistic interactions of the macromolecular constituents provide its unique load-bearing and tribological performance, it is not fully understood how two of the main constituents, glycosaminoglycans (GAGs) and glycoproteins, regulate the formation and mechanics of robust load-bearing films. Here, we present evidence that the load-bearing capabilities, rather than the tribological performance, of the formed SF films depend strongly on its components’ integrity. For this purpose, we used a combination of enzymatic treatments, quartz crystal microbalance with dissipation (QCM-D) and the surface forces apparatus (SFA) to characterize the formation and load-bearing capabilities of SF films on model oxide (i.e., silicates) surfaces. We find that, upon cleavage of proteins, the elasticity of the films is reduced and that cleaving GAGs results in irreversible (plastic) molecular re-arrangements of the film constituents when subjected to confinement. Understanding thin film mechanics of SF can provide insight into the progression of diseases, such as arthritis, but may also be applicable to the development of new implant surface treatments or new biomimetic lubricants.
Recent Urban Development Reduces Bee Abundance and Diversity
Authors: Pfeiffer Vera , Crowder David W. , Silbernagel Janet
Published: November 2021

Wild bee communities persist in cities despite major disruption of nesting and food resources by urban development. Bee diversity and abundance is key for urban agriculture and maintenance of plant diversity, and assessing what aspects of cities enhance bee populations will promote our capacity to retain and provision bee habitat. Here, we assessed how variation in land cover and neighborhood development history affected bee communities in the midwestern US urban landscape of Madison, Wisconsin. We sampled bee communities across 38 sites with relatively high (> 55%) or low (< 30%) levels of impervious surface, and assessed effects of land use and neighborhood development history on bee abundance and species richness. We show abundance and richness of bees was lower in recently developed neighborhoods, with particularly strong negative effects on soil nesting bees. Soil nesting bees and bee community richness decreased as cover of impervious surface increased, but above ground nesting bees were minimally impacted. Bee community similarity varied spatially and based on dissimilar local land cover, only for soil nesting bees, and the overall bee community. Impervious surface limited bee abundance and diversity, but new neighborhoods were associated with greater negative effects. We suggest that enhancing the structural diversity of new neighborhoods in urban ecosystems may imitate the structural benefits of older neighborhoods for bee populations.
A large scale, multiple genome comparison of acidophilic Archaea (pH ≤ 5.0) extends our understanding of oxidative stress responses in polyextreme environments
Authors: Neira Gonzalo , Vergara Eva , Cortez Diego , Holmes David S.
Published: November 2021

Acidophilic Archaea thrive in anaerobic and aerobic low pH environments (<pH 5) rich in dissolved heavy metals that exacerbate stress caused by the production of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), hydroxyl radical (•OH) and superoxide (O2•−). ROS react with lipids, proteins and nucleic acids causing oxidative stress and damage that can lead to cell death. Herein, genes and mechanisms potentially involved in ROS mitigation are predicted in over 200 genomes of acidophilic Archaea with sequenced genomes. These organisms can be subjected to simultaneous multiple stresses such as high temperature, high salinity, low pH and high heavy metal loads. Some of the topics addressed include: (1) the phylogenomic distribution of these genes and what can this tell us about the evolution of these mechanisms in acidophilic Archaea; (2) key differences in genes and mechanisms used by acidophilic versus non-acidophilic Archaea and between acidophilic Archaea and acidophilic Bacteria and (3) how comparative genomic analysis predicts novel genes or pathways involved in oxidative stress responses in Archaea and possible Horizontal Gene Transfer (HGT) events.
T cell-intrinsic vitamin A metabolism and its signaling are targets for memory T cell-based cancer immunotherapy
Authors: Fujiki Fumihiro , Morimoto Soyoko , Katsuhara Akiko , Okuda Akane , Ogawa Saeka , Ueda Eriko , Miyazaki Maki , Isotani Ayako , Ikawa Masahito , Nishida Sumiyuki , Nakajima Hiroko , Tsuboi Akihiro , Oka Yoshihiro , Nakata Jun , Hosen Naoki , Kumanogoh Atsushi , Oji Yusuke , Sugiyama Haruo
Published: November 2021

Memory T cells play an essential role in infectious and tumor immunity. Vitamin A metabolites such as retinoic acid are immune modulators, but the role of vitamin A metabolism in memory T- cell differentiation is unclear. In this study, we identified retinol dehydrogenase 10 (Rdh10), which metabolizes vitamin A to retinal (RAL), as a key molecule for regulating T cell differentiation. T cell-specific Rdh10 deficiency enhanced memory T-cell formation through blocking RAL production in infection model. Epigenetic profiling revealed that retinoic acid receptor (RAR) signaling activated by vitamin A metabolites induced comprehensive epigenetic repression of memory T cell-associated genes, including TCF7, thereby promoting effector T-cell differentiation. Importantly, memory T cells generated by Rdh10 deficiency and blocking RAR signaling elicited potent anti-tumor responses in adoptive T-cell transfer setting. Thus, T cell differentiation is regulated by vitamin A metabolism and its signaling, which should be novel targets for memory T cell-based cancer immunotherapy.
Photostimulation of VTA-IC dopaminergic inputs enhances the salience to consolidate aversive taste recognition memory via D1 receptors
Authors: Gil-Lievana E. , Ramírez-Mejía G. , Urrego-Morales O. , Luis-Islas J. , Gutierrez Ranier. , Bermúdez-Rattoni F.
Published: November 2021

Taste memory involves storing information through plasticity changes in the neural network of taste, including the insular cortex (IC) and ventral tegmental area (VTA), a critical provider of dopamine. Although a VTA-IC dopaminergic pathway has been demonstrated, its role to consolidate taste recognition memory remains poorly understood. We found that photostimulation of dopaminergic neurons in the VTA or VTA-IC dopaminergic terminals of TH-Cre mice increases the salience of a novel taste stimulus regardless of its hedonic value, without altering their taste palatability. Importantly, the inhibition of the D1-like receptor into the IC impairs the salience to facilitate consolidation of an aversive taste recognition memory. Finally, our results showed that VTA photostimulation improves the salience to consolidate a conditioned taste aversion memory through the D1-like receptor into the IC. It is concluded that the dopamine activity from the VTA into IC is required to increase the salience enabling the consolidation of a taste recognition memory. Notably, the D1-like receptor activity into the IC is required to consolidate both innate and learned aversive taste memories but not appetitive taste memory.
The global spread and invasion capacities of alien ants
Authors: Wong Mark K. L. , Economo Evan P. , Guénard Benoit
Published: November 2021

The ecological and economic impacts of biological invasions are usually highly conspicuous, but these are the outcome of a global, multistage process that is obscured from view. For most taxa, we lack a large-scale picture of the movements of alien species, the biases and barriers that promote or inhibit their spread at each stage, and blind spots in our ability to detect species during their spread. For instance, countries rely heavily on customs interceptions to prevent new species introductions, but their efficacy for detecting invaders remains unclear. To address these gaps, we synthesize and provide data at unprecedented geographic resolution on the global diversity and distribution of alien ants, a pervasive group strongly impacting humans and ecosystems. From >145,000 records spanning 602 regions, we identify 522 ant species exhibiting human-mediated spread, doubling recent estimates of their diversity. We show that movements of alien ant species across regions globally are non-random and, moreover, that these flows differ by the extents to which species invade—ranging from arrival to indoor establishment, naturalization, and harmful status. Importantly, we find that almost two-thirds of the 309 species that naturalize globally—most of which are ground- and litter-dwelling—are absent from customs interceptions, which record disproportionately high numbers of arboreal species. Our results illustrate the vast, yet uneven extent of ant invasions globally, and suggest that most alien species bypass biosecurity controls while spreading successfully worldwide. This raises doubts on the efficacy of current customs interceptions procedures and highlights a need for radically new approaches.

Significance statement

Biological invasions impact humans and ecosystems tremendously. Invasions are difficult to address because little is known about large-scale patterns of spread, species’ capacities to invade ecosystems, and the efficacy of existing biosecurity measures. This paper tackles these issues for alien ants, one of the most damaging groups of invasive animals. An unprecedented dataset reveals that 522 ant species exhibit human-mediated spread, 270 more than previously known. Species are grouped under four levels of invasion capacity corresponding to different invasion barriers. Geographic sources and sinks for the groups differ globally. Two-thirds of species with naturalization capacity have never been recorded at customs interceptions, which fail to detect many litter-dwelling species. Novel detection and control strategies for inconspicuous alien organisms are needed.
Factors affecting virus prevalence in honey bees in the Pacific-Northwest, USA
Authors: Pfeiffer Vera W , Crowder David W
Published: November 2021

Global efforts to assess honey bee health show viruses are major stressors that undermine colony performance. Identifying factors that affect virus incidence, such as management practices and landscape context, could aid in slowing virus transmission. Here we surveyed viruses in honey bees from 86 sites in the Pacific Northwest, USA, and tested effects of regional bee density, movement associated with commercial pollination, julian date, and hive management on virus prevalence. We also explored patterns of virus co-occurrence and spatial autocorrelation to identify whether local transmission was a primary driver of pathogen distribution. Our surveys found widespread prevalence of Deformed wing virus (DWV), Sacbrood virus (SBV), and Black queen cell virus (BQCV). BQCV and SBV were most prolific in commercial apiaries, while Chronic bee paralysis virus (CPBV) was more common in hobbyist apiaries than commercial apiaries. DWV was most common in urban landscapes and was best predicted by mite prevalence and julian date, while the incidence of both SBV and BQCV were best predicted by regional apiary density. We did not find evidence of additional spatial autocorrelation for any viruses, although high co-occurrence suggests parallel transmission patterns. Our results support the importance of mite management in slowing virus spread and suggest that greater bee density increases transmission. Our study provides support that viruses are widespread in honey bees and connects known mechanisms of virus transmission to the distribution of pathogens observed across the Pacific Northwest.

Highlights

Three viruses were widespread in honey bee populations across the Pacific Northwest, USA

Black queen cell and Sacbrood viruses were most common in high density hives

Deformed wing virus was most common in hives that had high mite loads

The presence of many viruses in bees suggests parallel or synergistic transmission
Heterogeneous run-and-tumble motion accounts for transient non-Gaussian super-diffusion in haematopoietic multi-potent progenitor cells
Authors: Partridge Benjamin , Anton Sara Gonzalez , Khorshed Reema , Adams George , Pospori Constandina , Celso Cristina Lo , Lee Chiu Fan
Published: November 2021

Multi-potent progenitor (MPP) cells act as a key intermediary step between haematopoietic stem cells and the entirety of the mature blood cell system. Their eventual fate determination is thought to be achieved through migration in and out of spatially distinct niches. Here we first analyze statistically MPP cell trajectory data obtained from a series of long time-course 3D in-vivo imaging experiments on irradiated mouse calvaria, and report that MPPs display transient super-diffusion with apparent non-Gaussian displacement distributions. Second, we explain these experimental findings using a run-and-tumble model of cell motion which incorporates the observed dynamical heterogeneity of the MPPs. Third, we use our model to extrapolate the dynamics to time-periods currently inaccessible experimentally, which enables us to quantitatively estimate the time and length scales at which super-diffusion transitions to Fickian diffusion. Our work sheds light on the potential importance of motility in early haematopoietic progenitor function.
Disorder in Ca2+ Release Unit Locations Confers Robustness but Cuts Flexibility of Heart Pacemaking
Authors: Maltsev Anna V. , Maltsev Victor A.
Published: November 2021

Excitation-contraction coupling kinetics are dictated by the rate and rhythm of the excitations generated by sinoatrial-nodal cells. These cells generate local Ca releases (LCRs) that activate Na/Ca exchanger current, which accelerates diastolic depolarization and determines the rate and rhythm of the excitations. The LCRs are generated by clusters of ryanodine receptors, Ca release units (CRUs), residing in the sarcoplasmic reticulum. While the spatial CRU distribution in pacemaker cells exhibits substantial heterogeneity, it remains unknown if it has any functional importance. Using numerical modeling, here we showed that with a square lattice distribution of CRUs, Ca-induced-Ca-release propagation during diastolic depolarization is insufficient for pacemaking within a broad lower range of realistic ICaL densities. Allowing each CRU to deviate from its original lattice position fundamentally changes the model behavior: during diastolic depolarization sparks propagate, forming LCRs observed experimentally. As disorder in the CRU positions increases, the CRU distribution exhibits larger empty spaces but simultaneously CRU clusters, as in Poisson clumping. Propagating within the clusters, Ca release becomes synchronized, increasing AP firing rate and reviving pacemaker function within lower ICaL densities at which cells with lattice CRU distribution were dormant/non-firing. However, cells with fully disordered CRU positions cannot reach low firing rates and their β-adrenergic receptor stimulation effect was substantially decreased. Thus, order/disorder in CRU locations regulates Ca release propagation and could be harnessed by pacemaker cells to regulate their function. Excessive disorder is expected to limit heart rate range that may contribute to heart rate range decline with age and in disease.

The present numerical modeling study shows that disorder in locations of Ca release units in cardiac pacemaker cells has substantial functional impact by creating release clusters, similar to Poisson clumping, and opportunity of Ca release to propagate within the clusters.
Genetic mapping of genotype-by-ploidy effects in Arabidopsis thaliana
Authors: Wijnen Cris L. , Becker Frank F.M. , Okkersen Andries A. , de Snoo C. Bastiaan , Boer Martin P. , van Eeuwijk Fred A. , Wijnker Erik , Keurentjes Joost J.B.
Published: November 2021

Plants can express different phenotypic responses following polyploidization, but ploidy-dependent phenotypic variation has so far not been assigned to specific genetic factors. To map such effects, segregating populations at different ploidy levels are required. The availability of an efficient haploid-inducer line in Arabidopsis thaliana allows for the rapid development of large populations of segregating haploid offspring. Because Arabidopsis haploids can be self-fertilised to give rise to homozygous doubled haploids, the same genotypes can be phenotyped at both the haploid and diploid ploidy level. Here, we compared the phenotypes of recombinant haploid and diploid offspring derived from a cross between two late flowering accessions to map genotype x ploidy (GxP) interactions. Ploidy-specific quantitative trait loci (QTLs) were detected at both ploidy levels. This implies that mapping power will increase when phenotypic measurements of monoploids are included in QTL analyses. A multi-trait analysis further revealed pleiotropic effects for a number of the ploidy specific QTLs as well as opposite effects at different ploidy levels for general QTLs. Taken together, we provide evidence of genetic variation between different Arabidopsis accessions being causal for dissimilarities in phenotypic responses to altered ploidy levels, revealing a GxP effect. Additionally, by investigating a population derived from late flowering accessions we revealed a major vernalisation specific QTL for variation in flowering time, countering the historical bias of research in early flowering accessions.
Mosaic loss of chromosome Y in aged human microglia
Authors: Vermeulen Michael C. , Pearse Richard , Young-Pearse Tracy , Mostafavi Sara
Published: November 2021

Mosaic loss of chromosome Y (LOY) is a particularly common acquired structural mutation in the leukocytes of aging men and it has been shown to correlate with several age-related diseases including Alzheimer’s disease (AD). To derive the molecular basis of LOY in brain cells, we create an integrated resource by aggregating data from 21 single-cell and single-nuclei RNA brain studies, yielding 763,410 cells to investigate the presence and cell-type specific burden of LOY. We created robust quantification metrics for assessing LOY, which were validated using a multi-modal dataset. Using this new resource and LOY-quantification approach, we found that LOY frequencies differed widely between CNS cell-types and individual donors. Among five common neural cell types, microglia were most affected by LOY (7.79%, n=41,949), while LOY in neurons was rare (0.48%, n=220,010). Differential gene expression analysis in microglia found 188 autosomal genes, 6 X-linked genes, and 11 pseudoautosomal genes, pointing to broad dysregulation in lipoprotein metabolism, inflammatory response, and antigen processing that coincides with loss of Y. To our knowledge, we provide the first evidence of LOY in the microglia, and highlight its potential roles in aging and the pathogenesis of neurodegenerative disorders such as AD.
Monocarboxylate Transporter 1 (MCT1) mediates succinate export in the retina
Authors: Bisbach Celia M. , Hass Daniel T. , Hurley James B.
Published: November 2021

Purpose

Succinate is exported by the retina and imported by eyecup tissue. The transporter(s) mediating this process have not yet been identified. Recent studies showed that Monocarboxylate Transporter 1 (MCT1) can transport succinate across plasma membranes in cardiac and skeletal muscle. Retina and retinal pigment epithelium (RPE) both express multiple MCT isoforms including MCT1. We tested the hypothesis that MCTs facilitate retinal succinate export and RPE succinate import.

Methods

We assessed retinal succinate export and eyecup succinate import in short term ex vivo culture using gas chromatography-mass spectrometry. We test the dependence of succinate export and import on pH, proton ionophores, conventional MCT substrates, and the MCT inhibitors AZD3965, AR-C155858, and diclofenac.

Results

Succinate exits retinal tissue through MCT1 but does not enter RPE through MCT1 or any other MCT. Intracellular succinate levels are a contributing factor that determines if an MCT1-expressing tissue will export succinate.

Conclusions

MCT1 facilitates export of succinate from retinas. An unidentified, non-MCT transporter facilitates import of succinate into RPE.
Microbiota-instructed regulatory T cell differentiation is mediated by a distinct RORγt+ antigen presenting cell subset
Authors: Kedmi Ranit , Najar Tariq , Mesa Kailin R. , Grayson Allyssa , Kroehling Lina , Hao Yuhan , Hao Stephanie , Pokrovskii Maria , Xu Mo , Talbot Jhimmy , Wang Jiaxi , Germino Joe , Lareau Caleb A. , Satpathy Ansuman T. , Anderson Mark S. , Laufer Terri M. , Aifantis Iannis , Bartleson Juliet M. , Allen Paul M. , Paidassi Helena , Gardner James M. , Stoeckius Marlon , Littman Dan R.
Published: November 2021

The mutualistic relationship of gut-resident microbiota and cells of the host immune system promotes homeostasis that ensures maintenance of the microbial community and of a poised, but largely non-aggressive, immune cell compartment1, 2. Consequences of disturbing this balance, by environmental or genetic factors, include proximal inflammatory conditions, like Crohn’s disease, and systemic illnesses, both metabolic and autoimmune. One of the means by which this equilibrium is achieved is through induction of both effector and suppressor or regulatory arms of the adaptive immune system. In mice, Helicobacter species induce regulatory (iTreg) and follicular helper (Tfh) T cells in the colon-draining mesenteric lymph nodes under homeostatic conditions, but can instead induce inflammatory Th17 cells when iTreg cells are compromised3, 4. How Helicobacter hepaticus and other gut bacteria direct T cells to adopt distinct functions remains poorly understood. Here, we investigated which cells and molecular components are required to convey the microbial instruction for the iTreg differentiation program. We found that antigen presentation by cells expressing RORγt, rather than by classical dendritic cells, was both required and sufficient for iTreg induction. These RORγt+ cells, likely to be type 3 innate lymphoid cells (ILC3) and/or a recently-described population of Aire+ cells termed Janus cells5, require the MHC class II antigen presentation machinery, the chemokine receptor CCR7, and αv integrin, which activates TGF-β, for iTreg cell differentiation. In the absence of any of these, instead of iTreg cells there was expansion of microbiota-specific pathogenic Th17 cells, which were induced by other antigen presenting cells (APCs) that did not require CCR7. Thus, intestinal commensal microbes and their products target multiple APCs with pre-determined features suited to directing appropriate T cell differentiation programs, rather than a common APC that they endow with appropriate functions. Our results illustrate the ability of microbiota to exploit specialized functions of distinct innate immune system cells, targeting them to achieve the desired composition of equipoised T cells, thus maintaining tolerance.
Pre-implantation mouse embryo movement under hormonally altered conditions
Authors: Lufkin Hannah , Flores Diana , Raider Zachary , Madhavan Manoj , Dawson Madeline , Coronel Anna , Sharma Dhruv , Arora Ripla
Published: November 2021

Precise regulation of embryo movement is crucial to successful implantation, but the role of ovarian hormones in this process is not understood. We ascertain the effects of altered hormonal environment on embryo movement using two delayed implantation models: Natural lactational Diapause (ND), a naturally occurring alternate model of pregnancy, and Artificially induced Diapause (AD), a laboratory version of ND. Our previous work suggests that embryos in a natural pregnancy (NP) first display unidirectional clustered embryo movement, followed by bidirectional scattering and spacing movement. In contrast, in the ND model, embryos are present as clusters near the oviductal-uterine junction for ~24-hours longer than NP, followed by locations consistent with a unidirectional scattering and spacing movement. Intriguingly, the AD model closely resembles embryo location in NP and not ND. Further, unlike the popular paradigm of reduced estrogen (E2) levels in diapause E2 levels are comparable across NP, ND, and AD, while progesterone (P4) levels are reduced in ND and highly increased in AD when compared to NP. Exogenous administration of E2 or P4 modifies the unidirectional clustered embryo movement, while E2 treatment causes a reduction in P4 and affects the bidirectional phase of embryo movement. Taken together, our data suggest embryo movement can be modulated by both P4 and E2. Understanding natural hormonal adaptation in diapause provides an opportunity to determine key players regulating embryo movement and implantation success. This knowledge can be leveraged to understand pregnancy survival and implantation success in hormonally altered conditions in the clinic.
A marine fungus efficiently degrades polyethylene
Authors: Gao Rongrong , Liu Rui , Sun Chaomin
Published: November 2021

Plastics pollution has been a global concern. Huge quantities of polyethylene (PE), the most abundant and refractory plastic in the world, have been accumulating in the environment causing serious ecological problems. However, the paucity of microorganisms and enzymes that efficiently degrading PE seriously impedes the development of bio-products to eliminate this environmental pollution. Here, by screening hundreds of plastic waste-associated samples, we isolated a fungus (named Alternaria sp. FB1) that possessing a prominent capability of colonizing, degrading and utilizing PE. Strikingly, the molecular weight of PE film decreased 95% after the fungal treatment. Using GC-MS, we further clarified that a four-carbon product (named Diglycolamine) accounted for 93.28% of all degradation products after the treatment by strain FB1. We defined potential enzymes that involved in the degradation of PE through a transcriptomic method. The degradation capabilities of two representative enzymes including a laccase and a peroxidase were verified. Lastly, a complete biodegradation process of PE is proposed. Our study provides a compelling candidate for further investigation of degradation mechanisms and development of biodegradation products of PE.
TAILS identifies candidate substrates and biomarkers of ADAMTS7, a therapeutic protease target in coronary artery disease
Authors: MacDonald Bryan T , Keshishian Hasmik , Mundorff Charles C , Arduini Alessandro , Lai Daniel , Bendinelli Kayla , Popp Nicholas R , Bhandary Bidur , Clauser Karl R , Specht Harrison , Elowe Nadine H , Laprise Dylan , Xing Yi , Kaushik Virendar K , Carr Steven A , Ellinor Patrick T
Published: November 2021

Loss-of-function mutations in the secreted enzyme ADAMTS7 (a disintegrin and metalloproteinase with thrombospondin motifs 7) are associated with protection for coronary artery disease (CAD). ADAMTS7 catalytic inhibition has been proposed as a therapeutic strategy for treating CAD; however, the lack of an endogenous substrate has hindered the development of activity-based biomarkers. To identify ADAMTS7 extracellular substrates and their cleavage sites relevant to vascular disease, we used TAILS (terminal amine isotopic labeling of substrates), a method for identifying protease-generated neo-N termini. We compared the secreted proteome of vascular smooth muscle and endothelial cells expressing either full-length mouse ADAMTS7 WT, catalytic mutant ADAMTS7 E373Q or a control luciferase adenovirus. Significantly enriched N-terminal cleavage sites in ADAMTS7 WT samples were compared to the negative control conditions and filtered for stringency, resulting in catalogs of high confidence candidate ADAMTS7 cleavage sites from our three independent TAILS experiments. Within the overlap of these discovery sets, we identified 24 unique cleavage sites from 16 protein substrates, including cleavage sites in EFEMP1 (EGF-containing fibulin-like extracellular matrix protein 1/Fibulin-3). The ADAMTS7 TAILS preference for EMEMP1 cleavage at the amino acids 123.124 over the adjacent 124.125 site was validated using both endogenous EFEMP1 and purified EFEMP1 in a binary in vitro cleavage assay. Collectively our TAILS discovery experiments have uncovered hundreds of potential substrates and cleavage sites to explore disease related biological substrates and facilitate activity-based ADAMTS7 biomarker development.
Insights into the trafficking of human leukocytes to colostrum evidences a modulation of the B lymphocyte compartment in obesity
Authors: Piñeiro-Salvador Raúl , Vazquez-Garza Eduardo , Cruz-Cardenas José Antonio , Licona-Cassani Cuauhtémoc , de Jesús García-Rivas Gerardo , Moreno-Vásquez Jorge , Alcorta-García Mario René , Lara-Diaz Victor Javier , Brunck Marion E. G.
Published: November 2021

Breastmilk is a dynamic fluid which initial goal is to provide the most adapted nutrition to the neonate. Additional functions have been recently attributed to breastmilk, with the evidence of a specific microbiota and the presence of a variety of components of the immune system, such as cytokines and leukocytes. The composition of breastmilk varies through time, according to the health status of mother and child, and altogether contributes to future health of the infant. Obesity is a rising condition worldwide, that creates a state of systemic, chronic inflammation including leukocytosis. Here, we asked whether colostrum, the milk produced within the first 48 h post-partum, would contain a distinct leukocyte composition depending on the body mass index (BMI) of the mother. We applied a panel of 6 antibodies plus viability marker to the peripheral blood and colostrum obtained from obese (BMI > 30) and lean (BMI < 25) mothers to characterize 10 major leukocyte subpopulations using flow cytometry. While lymphoid cells were otherwise unaffected by their tissue of origin, the phenotypes of granulocyte and monocyte populations significantly contrasted between blood and colostrum, including variations in morphology and surface expression of CD45 and CD16. These differences recapitulated across groups, which suggests a generalized cell-specific phenotype alteration caused by trafficking to colostrum. The B lymphocyte compartment was significantly reduced in obese colostrum and these cells did not exhibit enhanced CD16 shedding in this tissue, unlike B lymphocytes from lean mothers’ colostrum. This is the first exhaustive characterization of major leukocyte subsets in obese mothers’ colostrum, and the first report of leukocyte subpopulations from Latin-American women’s colostrum. This pioneering study is a steppingstone to further investigate active immunity in human breastmilk.
Nonenzymatic loop-closing ligation generates RNA hairpins and is a template-free way to assemble functional RNAs
Authors: Wu L.-F. , Liu Z. , Roberts S. J. , Su M. , Szostak J. W. , Sutherland J. D.
Published: November 2021

RNA hairpin loops are the predominant element of secondary structure in functional RNAs. The emergence of primordial functional RNAs, such as ribozymes that fold into complex structures that contain multiple hairpin loops, is generally thought to have been supported by template-directed ligation. However, template inhibition and RNA misfolding problems impede the emergence of function. Here we demonstrate that RNA hairpin loops can be synthesized directly from short RNA duplexes with single-stranded overhangs by nonenzymatic loop-closing ligation chemistry. We show that loop-closing ligation allows full-length functional ribozymes containing a hairpin loop to be assembled free of inhibitory template strands. This approach to the assembly of structurally complex RNAs suggests a plausible pathway for the emergence of functional RNAs before a full-length RNA copying process became available.
What is the best fitness measure in wild populations? A case study on the power of short-term fitness proxies to predict reproductive value
Authors: Alif Vita Živa , Dunning Jamie , Chik Heung Ying Janet , Burke Terry , Schroeder Julia
Published: November 2021

Fitness is at the core of evolutionary theory, but it is difficult to measure accurately. One way to measure long-term fitness is by calculating the individual’s reproductive value, which represents the expected number of allele copies an individual passes on to distant future generations. However, this metric of fitness is scarcely used because the estimation of individual’s reproductive value requires long-term pedigree data, which is rarely available in wild populations where following individuals from birth to death is often impossible. Wild study systems therefore use short-term fitness metrics as proxies, such as the number of offspring produced. This study obtained three frequently used short-term proxies for fitness obtained at different offspring life stages (eggs, hatchlings, fledglings and recruits), and compared their ability to predict reproductive values derived from the genetic pedigree of a wild passerine bird population. We used twenty years of precise field observations and a near-complete genetic pedigree to calculate reproductive success, individual growth rate and de-lifed fitness as lifetime fitness measures, and as annual de-lifed fitness. We compared the power of these metrics to predict reproductive values and lineage survival to the end of the study period. The three short-term fitness proxies predict the reproductive values and lineage survival only when measured at the recruit stage. There were no significant differences between the different fitness proxies at the same offspring stages in predicting the reproductive values and lineage survival. Annual fitness at one year old predicted reproductive values equally well as lifetime de-lifed fitness. However, none of the short-term fitness proxies was strongly associated with the reproductive values. In summary, the commonly short-term fitness proxies capture long-term fitness with intermediate accuracy at best, if measured at recruitment stage. As lifetime fitness measured at recruit stage and annual fitness in the first year of life were the best proxies of long-term fitness, we encourage their future use.
Sequence characterization of eccDNA content in glyphosate sensitive and resistant Palmer amaranth from geographically distant populations
Authors: Spier Camposano Hailey , Molin William T. , Saski Christopher A.
Published: November 2021

The discovery of non-chromosomal circular DNA offers new directions in linking genome structure with function in plant biology. Glyphosate resistance through EPSPS gene copy amplification in Palmer amaranth was due to an autonomously replicating extra-chromosomal circular DNA mechanism (eccDNA). CIDER-Seq analysis of geographically distant glyphosate sensitive (GS) and resistant (GR) Palmer Amaranth (Amaranthus palmeri) revealed the presence of numerous small extra-chromosomal circular DNAs varying in size and with degrees of repetitive content, coding sequence, and motifs associated with autonomous replication. In GS biotypes, only a small portion of these aligned to the 399 kb eccDNA replicon, the vehicle underlying gene amplification and genetic resistance to the herbicide glyphosate. The aligned eccDNAs from GS were separated from one another by large gaps in sequence. In GR biotypes, the eccDNAs were present in both abundance and diversity to assemble into a nearly complete eccDNA replicon. Mean sizes of eccDNAs were similar in both biotypes and were around 5kb with larger eccDNAs near 25kb. Gene content for eccDNAs ranged from 0 to 3 with functions that include ribosomal proteins, transport, metabolism, and general stress response genetic elements. Repeat content among smaller eccDNAs indicate a potential for recombination into larger structures. Genomic hotspots were also identified in the Palmer amaranth genome with a disposition for gene focal amplifications as eccDNA. The presence of eccDNA may serve as a reservoir of genetic heterogeneity in this species and may be functionally important for survival.
Scoping the Line Up: A Comparison of Biomonitoring Methodologies for Surf Zone Fish Communities
Authors: Gold Zachary , Koch McKenzie Q. , Schooler Nicholas K. , Emery Kyle A. , Dugan Jenifer E. , Miller Robert J. , Page Henry M. , Schroeder Donna M. , Hubbard David M. , Madden Jessica R. , Whitaker Stephen G. , Barber Paul H.
Published: November 2021

Surf zones are highly dynamic marine ecosystems that are subject to increasing anthropogenic and climatic pressures, posing multiple challenges for biomonitoring. Traditional methods such as seines and hook and line surveys are often labor intensive, taxonomically biased, and can be physically hazardous. Emerging techniques, such as baited remote underwater video (BRUV) and environmental DNA (eDNA) are promising nondestructive tools for assessing marine biodiversity in surf zones of sandy beaches. Here we compare the relative performance of beach seines, BRUV, and eDNA in characterizing community composition of bony (teleost) and cartilaginous (elasmobranch) fishes of surf zones at 18 open coast sandy beaches in southern California. Seine and BRUV surveys captured overlapping, but distinct fish communities with 50% (18/36) of detected species shared. BRUV surveys more frequently detected larger species (e.g. sharks and rays) while seines more frequently detected one of the most abundant species, barred surfperch (Amphistichus argenteus). In contrast, eDNA metabarcoding captured 83.3% (30/36) of all fishes observed in seine and BRUV surveys plus 59 additional species, including 13 that frequent surf zone habitats. eDNA approaches showed significantly higher sensitivity than seine and BRUV methods and more consistently detected 29 of the 30 (96.7%) jointly observed species across beaches. The six species detected by BRUV/seines, but not eDNA either lacked reference sequences, were only resolved at higher taxonomic ranks (e.g.Embiotocidaesurfperches), or were detected below occupancy thresholds. Low site-species overlap between methods limited comparisons of richness and abundance estimates, highlighting the challenge of comparing biomonitoring approaches. Despite potential for improvement, results overall demonstrate that eDNA can provide a cost-effective tool for long-term surf zone monitoring that complements data from seine and BRUV surveys, allowing more comprehensive surveys of vertebrate diversity in surf zone habitats.
The developmentally-timed decay of an essential microRNA family is seed sequence-dependent
Authors: Donnelly Bridget F. , Yang Bing , Grimme Acadia L. , Vieux Karl-Frédéric , Liu Chen-Yu , Zhou Lecong , McJunkin Katherine
Published: November 2021

MicroRNA (miRNA) abundance is tightly controlled by regulation of biogenesis and decay. Here we show that the mir-35 miRNA family undergoes selective decay at the transition from embryonic to larval development in C. elegans. The seed sequence of the miRNA is necessary and largely sufficient for this regulation. Sequences outside the seed (3’ end) regulate mir-35 abundance in the embryo but are not necessary for sharp decay at the transition to larval development. Enzymatic modifications of the miRNA 3’ end are neither prevalent nor correlated with changes in decay, suggesting that miRNA 3’ end display is not a core feature of this mechanism and further supporting a seed-driven decay model. Our findings demonstrate that seed sequence-specific decay can selectively and coherently regulate all redundant members of a miRNA seed family, a class of mechanism that has great biological and therapeutic potential for dynamic regulation of a miRNA family’s target repertoire.
Microscopic Characterization of the Chloride Permeation Pathway in the Human Excitatory Amino Acid Transporter 1 (EAAT1)
Authors: Pant Shashank , Wu Qianyi , Ryan Renae , Tajkhorshid Emad
Published: November 2021

Excitatory amino acid transporters (EAATs) are glutamate transporters that belong to the solute carrier 1A (SLC1A) family. They couple glutamate transport to the co-transport of three sodium (Na+) ions and one proton (H+) and the counter-transport of one potassium (K+) ion. In addition to this coupled transport, binding of substrate and Na+ ions to EAATs activates a thermodynamically uncoupled chloride (Cl−) conductance. Structures of SLC1A family members have revealed that these transporters use a twisting elevator mechanism of transport, where a mobile transport domain carries substrate and coupled ions across the membrane, while a static scaffold domain anchors the transporter in the membrane. We have recently demonstrated that the uncoupled Cl− conductance is activated by the formation of an aqueous pore at the domain interface during the transport cycle in archaeal GltPh. However, a pathway for the uncoupled Cl− conductance has not been reported for the EAATs and it is unclear if such a pathway is conserved. Here, we employ all-atom molecular dynamics (MD) simulations combined with enhanced sampling, free-energy calculations, and experimental mutagenesis to approximate large-scale conformational changes during the transport process and identified a Cl− conducting conformation in human EAAT1. We were able to extensively sample the large-scale structural transitions, allowing us to capture an intermediate conformation formed during the transport cycle with a continuous aqueous pore at the domain interface. The free-energy calculations performed for the conduction of Cl− and Na+ ions through the captured conformation, highlight the presence of two hydrophobic gates which control the selective movement of Cl− through the aqueous pathway. Overall, our findings provide insights into the mechanism by which a human glutamate transporter can support the dual functions of active transport and passive Cl− permeation and confirming the commonality of this mechanism in different members of the SLC1A family.
Assessment of temporal complexity in functional MRI between rest and task conditions
Authors: Omidvarnia Amir , Liégeois Raphaël , Amico Enrico , Preti Maria Giulia , Zalesky Andrew , Van De Ville Dimitri
Published: November 2021

Dynamic models of cortical activity, as measured by functional magnetic resonance imaging (fMRI), have recently brought out important insights into the organization of brain function. In terms of temporal complexity, these hemodynamic signals have been shown to exhibit critical behaviour at the edge between order and disorder. In this study, we aimed to revisit the properties and spatial distribution of temporal complexity in resting state and task fMRI of 100 unrelated subjects from the Human Connectome Project (HCP). First, we compared two common choices of complexity measures (i.e., Hurst exponent versus multiscale entropy) and reported high similarity between them. Second, we investigated the influence of experimental paradigms and found high task-specific complexity. We considered four mental tasks in the HCP database for the analysis: Emotion, Working memory, Social, and Language. Third, we tailored a recently-proposed statistical framework that incorporates the structural connectome, to assess the spatial distribution of complexity measures. These results highlight brain regions including parts of the default mode network and cingulate cortex with significantly stronger complex behaviour than the rest of the brain, irrespective of task. In sum, temporal complexity measures of fMRI are reliable markers of the cognitive status.
Board gender diversity and firms' internationalization speed: the role of female directors' characteristics
Authors: Ren Ge , Zeng Ping
Published: November 2021

Purpose

Drawing on the gender self-schema theory, upper echelons theory and the literature on international business, this study aims to examine the impact of board gender diversity on firms' internationalization speed.

Design/methodology/approach

In this study, secondary data of 886 listed Chinese manufacturing firms from 2009 to 2018 are studied using the ordinary least squares regression model as the baseline method, an instrumental variable method is adopted for endogeneity control and both fixed and random effect models are adopted for the robustness test.

Findings

Board gender diversity reduces firms' internationalization speed, and the negative effect between board gender diversity and internationalization speed is stronger when the average age of female directors is older and weaker when female directors have international experience or financial background.

Practical implications

First, Chinese firms need to increase or decrease board gender diversity to match the board to firms' internationalization strategy. Increasing board gender diversity may be a more appropriate choice for firms that are expanding rapidly internationally, and vice versa. Second, when introducing female directors to international firms, it is essential to address other characteristics of these directors beyond their gender.

Originality/value

First, the authors contribute to the literature on board gender diversity using Chinese manufacturing firms as our research sample, which provides new insights into the economic consequences of increasing the number of female directors. Second, this research contributes to the literature on firms' internationalization speed. Third, the authors capture in more detail the economic consequences of increasing board gender diversity in the context of China.
The impact of emerging technology influences product placement effectiveness: a scoping study from interactive marketing perspective
Authors: Pavlič Jani , Tomažič Tina , Kožuh Ines
Published: November 2021

Purpose

Interactive marketing (IM) has influenced commercial communication, including product placement (PP), which has become an essential form of integrating brands within the mass media. Existing research on PP has exceeded traditional TV and movies, and there is a lack of reviews considering the advanced technological perspectives. This scoping study aims to investigate PP in the context of IM and explore relations between technology-related factors and the effects of placement.

Design/methodology/approach

The scoping study follows a systematic approach with strictly defined inclusion and exclusion criteria, research questions and a search strategy to identify relevant studies and extract the data. A two-stage screening process on 713 publications resulted in 42 studies for the final examination.

Findings

The results complemented existing theory by identifying and synthesizing the essential technology-related factors and their (un)favorable impacts on PP effectiveness, where interactivity was examined the most frequently. The results also outlined the (un)explored concepts of PP according to media technology and related factors, and show a prevailing research interest in in-game advertising and cognitive responses. Accordingly, the study provides implications for marketers and directions for future research.

Originality/value

This review is the first to examine PP studies in the context of IM and technology-related factors influencing the effect of placement.