bluuebunny/crossref_metadata_2025 huggingface dataset:
Pneumococcal vaccine uptake and vaccine effectiveness in older adults with invasive pneumococcal disease in Germany
Authors: Perniciaro Stephanie , van der Linden Mark
Published: September 2020

Background

Invasive pneumococcal disease (IPD) in people ≥60 years old is on the rise in Germany. There has been a recommendation for pneumococcal vaccination in this age group since 1998.

Methods

We determined the vaccination status of people ≥60 years old with IPD in Germany. We assessed vaccine effectiveness (VE) of the recommended 23-valent polysaccharide vaccine (PPV23).

Results

The rate of pneumococcal vaccination in older adults with IPD is low, 26%, with only 16% of people receiving a pneumococcal vaccine within the past 5 years. Age- and sex-adjusted vaccine effectiveness (VE) for PPV23 was 37% (95% confidence interval 12% - 55%). For people vaccinated with PPV23 less than 2 years prior to IPD, VE was - 20% (−131% - 34%), between 2-4 years prior to IPD, VE was 56% (20% - 76%), and 47% (17% - 63%) for those vaccinated ≥5 years ago. Excluding serotype 3, overall VE for the remaining serotypes in PPV23 was 63% (49% - 74%). For people receiving PPV23 within the past 2 years, VE against all serotypes except 3 was 49% (12% - 71%); for people vaccinated between 2-4 years prior to IPD 66% (37% - 82%); for those vaccinated ≥5 years ago, 69% (50% - 81%). VE of PPV23 against serotype 3 IPD only was -110% (- 198% - -47%).

Conclusions

To reduce IPD in older adults in Germany, we must increase the rate of pneumococcal vaccine uptake. For 22/23 serotypes, PPV23 was effective. Serotype 3 remains a major problem.
Correlation between serum 25(OH) vitamin D level and sleep quality in elderly patients with type 2 diabetes
Authors: Ma Hongyan , Fan Danni , Li Xiaofei , Qi Ying , Zhao Yang , Zhang Lin
Published: September 2020

Background

Untreated sleep disorders have been linked with type 2 diabetes in previous evidence. This study was to investigate the correlation between serum 25(OH) vitamin D level and sleep quality in elderly patients with type 2 diabetes and reveal the therapeutic potential of 25(OH) vitamin D-based treatments to improve sleeping quality and its effect on diabetes management.

Methods

The sleep quality of 186 elderly patients with type 2 diabetes were assessed by questionaires of Pittsburgh sleep index (PSQI), with a cutoff point of PSQI • 7 defined as poor sleep. The measurement of serum 25(OH) vitamin D, fasting blood glucose, glycosylated hemoglobin, serum creatinine, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and urinary albumin/creatinine ratio were collected. History of diabetic nephropathy, diabetic retinopathy, peripheral neuropathy, blood pressure, height, weight, hypoglycemic drug use, and the duration of diabetes also were recorded. Both univariate and multivariate logistic regression analysis was used to investigate the relationship of serum 25(OH) vitamin D and sleep quality in elderly patients with type 2 diabetes.

Results

The age of elderly patients with type 2 diabetes was 73.6±4.3 years., and duration of diabetes was 8.8 ± 3.0 years. In the study, inadequate quality of sleep was reported in 63% elderly patients with type 2 diabetes. This study revealed that lower level of 25(OH) vitamin D was significantly associated with poor sleep quality in type 2 diabetes patients(P < 0.05). Multivariate logistic regression analysis showed that 25(OH) vitamin D deficiency and the use of insulin were risk factors for of inadequate sleep quality in elderly patients with type 2 diabetes.

Conclusions

Elderly type 2 diabetic patients with 25(OH) vitamin D deficiency showed a high incidence of poor sleep quality, low-level of 25(OH) vitamin D was a risk factor for inadequate quality of sleep in elderly patients with type 2 diabetes.
Kinetics of SARS-CoV-2 infection in the human upper and lower respiratory tracts and their relationship with infectiousness
Authors: Ke Ruian , Zitzmann Carolin , Ribeiro Ruy M. , Perelson Alan S.
Published: September 2020

SARS-CoV-2 is a human pathogen that causes infection in both the upper respiratory tract (URT) and the lower respiratory tract (LRT). The viral kinetics of SARS-CoV-2 infection and how they relate to infectiousness and disease progression are not well understood. Here, we develop data-driven viral dynamic models of SARS-CoV-2 infection in both the URT and LRT. We fit the models to viral load data from patients with likely infection dates known, we estimated that infected individuals with a longer incubation period had lower rates of viral growth, took longer to reach peak viremia in the URT, and had higher chances of presymptomatic transmission. We then developed a model linking viral load to infectiousness. We found that to explain the substantial fraction of transmissions occurring presymptomatically, a person’s infectiousness should depend on a saturating function of the viral load, making the logarithm of the URT viral load a better surrogate of infectiousness than the viral load itself. Comparing the roles of target-cell limitation, the innate immune response, proliferation of target cells and spatial infection in the LRT, we found that spatial dissemination in the lungs is likely to be an important process in sustaining the prolonged high viral loads. Overall, our models provide a quantitative framework for predicting how SARS-CoV-2 within-host dynamics determine infectiousness and represent a step towards quantifying how viral load dynamics and the immune responses determine disease severity.

Significance

A quantitative understanding of the kinetics of SARS-CoV-2 infection is key to understanding the development of infectiousness and disease symptoms. To address this need, we developed data-driven within-host models of SARS-CoV-2 infection and showed that lower rates of viral growth lead to longer incubation periods and higher chances of presymptomatic transmission. We found that the logarithm of the URT viral load serves an appropriate surrogate for a person’s infectiousness. We then developed a mechanistic model for infectiousness and showed that a saturation effect in the dependence of transmission on viral load gives rise to this relationship. We also provide evidence of spatial dissemination in the lungs as an important process in sustaining prolonged high viral loads in the LRT.
Deep Immune Profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19
Authors: Vella Laura A. , Giles Josephine R. , Baxter Amy E. , Oldridge Derek A. , Diorio Caroline , Kuri-Cervantes Leticia , Alanio Cécile , Pampena M. Betina , Wu Jennifer E. , Chen Zeyu , Huang Yinghui Jane , Anderson Elizabeth M. , Gouma Sigrid , McNerney Kevin O. , Chase Julie , Burudpakdee Chakkapong , Lee Jessica H. , Apostolidis Sokratis A. , Huang Alexander C. , Mathew Divij , Kuthuru Oliva , Goodwin Eileen C. , Weirick Madison E. , Bolton Marcus J. , Arevalo Claudia P. , Ramos Andre , Jasen Cristina , Giannini Heather M. , D’Andrea Kurt ,   The UPenn COVID Processing Unit, Meyer Nuala J. , Behrens Edward M. , Bassiri Hamid , Hensley Scott E. , Henrickson Sarah E. , Teachey David T. , Betts Michael R. , Wherry E. John
Published: September 2020

Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8 T cells that correlated with use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct and implicate CD8 T cells in clinical presentation and trajectory of MIS-C.

One Sentence Summary

MIS-C is defined by generalized lymphocyte activation that corrects during hospitalization, including elevated plasmablast frequencies and marked activation of vascular patrolling CX3CR1+ CD8 T cells.
Dynamic Modeling of Reported COVID-19 Cases and Deaths with Continuously Varying Case Fatality and Transmission Rate Functions
Authors: Lyu Mingdong , Hall Randolph
Published: September 2020

In this paper, we propose an enhanced SEIRD (Susceptible-Exposed-Infectious-Recovered-Death) model with time varying case fatality and transmission rates for confirmed cases and deaths from COVID-19. We show that when case fatalities and transmission rates are represented by simple Sigmoid functions, historical cases and fatalities can be fit with a relative-root-mean-squared-error accuracy on the order of 2% for most American states over the period from initial cases to July 28 (2020). We find that the model is most accurate for states that so far had not shown signs of multiple waves of the disease (such as New York), and least accurate for states where transmission rates increased after initially declining (such as Hawaii). For such states, we propose an alternate multi-phase model. Both the base model and multi-phase model provide a way to explain historical reported cases and deaths with a small set of parameters, which in the future can enable analyses of uncertainty and variations in disease progression across regions.
Granulosa cell genes that regulate ovarian follicle development beyond the antral stage: the role of estrogen receptor β
Authors: Chakravarthi V. Praveen , Borosha Shaon , Ghosh Subhra , Roby Katherine F. , Wolfe Michael W. , Christenson Lane K. , Karim Rumi M. A.
Published: September 2020

Follicle development beyond the preantral stage is dependent on gonadotropins. FSH signaling is crucial for the advancement of preantral follicles to the antral stage, and LH signaling is essential for further maturation of preovulatory follicles. Estrogen is intricately tied to gonadotropin signaling during the advanced stages of folliculogenesis. We observed thatErβnullovarian follicles fail to develop beyond the antral stage, even after exogenous gonadotropin stimulation. As ERβ is primarily expressed in the granulosa cells (GCs), we explored the gonadotropin-regulated GC genes that induce maturation of antral follicles. Synchronized follicle development was induced by administration of exogenous gonadotropins to wildtype 4-wk-old female rats. The GC transcriptome was analyzed via RNA-sequencing before and after gonadotropin stimulation. AnErβnullmutant model that fails to show follicle maturation was also included in order to identify the ERβ-regulated genes involved at this step. We observed that specific groups of genes were differentially expressed in response to PMSG or hCG administration in wildtype rats. While some of the PMSG or hCG-induced genes showed a similar expression pattern inErβnullGCs, a subset of PMSG- or hCG-induced genes showed a differential expression inErβnullGCs. These latter ERβ-regulated genes included previously known FSH or LH target genes includingLhcgr, Cyp11a1, Cyp19a1, Pgr, Runx2, Egfr, Kiss1, andPtgs2, which are involved in follicle development, oocyte maturation, and ovulation. We also identified novel ERβ-regulated genes includingJaml, Galnt6, Znf750, Dusp9, Wnt16, andMageb16that failed to respond to gonadotropin stimulation inErβnullGCs. Our findings indicate that the gonadotropin-induced spatiotemporal pattern of gene expression is essential for ovarian follicle maturation beyond the antral stage. However, expression of a subset of those gonadotropin-induced genes is dependent on transcriptional regulation by ERβ.
A tale of two transcriptomic responses in agricultural pests via host defenses and viral replication
Authors: Pantha Pramod , Chalivendra Subbaiah , Oh Dong-Ha , Elderd Bret , Dassanayake Maheshi
Published: September 2020

Background

Autographa californicaMultiple Nucleopolyhedrovirus (AcMNPV) is a baculovirus with a high potential for its use as a biopesticide against arthropod pests. The budded form of the virus causes a systemic infection when it escapes the midgut to enter the hemolymph of susceptible hosts. Yet, the specific molecular processes underlying the biocidal activity of AcMNPV on its insect hosts are largely unknown.

Results

In this study, we describe the transcriptional responses in two major pests,Spodoptera frugiperdaandTrichoplusia ni, to determine the host-pathogen responses during AcMNPV infection, concurrently with the viral response to the host. We assembled species-specificde novoreference transcriptomes of the hemolymph to identify key transcripts that respond during pathogenesis in these arthropod models where genomic resources are sparse. We found that the suppression of transcriptional processes related to chitin, a metabolite critical for basement membrane stability and tracheal development are central in establishing a systemic infection. Synergistic transcriptional support was observed to suggest suppression of immune responses and induction of oxidative stress indicating disease progression in the host. The entire AcMNPV core genome was expressed in the host hemolymph and viral genes predominantly associated with the budded virus replication, structure, and movement were more abundant than those associated with the occlusion-derived virus. Genes known to directly arrest host cell cycle and development were among the most abundant AcMNPV transcripts in infected hosts. Interestingly, several of the host genes (e.g.Chitin synthase) that were targeted by the pathogen as revealed by our study are also targets of several chemical insecticides currently used commercially to control arthropod pests.

Conclusions

Our results reveal an extensive overlap between biological processes represented by genes differently expressed in both hosts, as well as convergence on highly abundant viral genes expressed in the two hosts, providing an overview of the host-pathogen transcriptomic landscape during systemic infection. Given the diversity of AcMNPV strains that infect a wide range of insect hosts, our study provides a framework where pathogen strains could be selected to target specific host genes that facilitates modulation of the infection strength and specificity of the susceptible hosts.
Species-specific assembly of root-associated bacterial microbiota mediated by a combination of plant specialized metabolites
Authors: Shimasaki Tomohisa , Masuda Sachiko , Garrido-Oter Ruben , Kawasaki Takashi , Aoki Yuichi , Shibata Arisa , Suda Wataru , Shirasu Ken , Yazaki Kazufumi , Nakano Ryohei Thomas , Sugiyama Akifumi
Published: September 2020

Plant specialized metabolites (PSMs) influence the taxonomic compositions of the root-associated microbiota; however, the underlying molecular mechanisms and evolutionary trajectories remain elusive. Here, we show that the bacterial genusArthrobacteris predominant in the tobacco endosphere, and that its enrichment is mediated by a combination of two tobacco-specific PSMs, santhopine and nicotine The isolation and whole genome sequencing of a representative set ofArthrobacterstrains identified independent genomic features, including but not limited to genes for santhopine and nicotine catabolism, which are associated with the colonization competence of tobacco roots. Taken together, these data suggest that plant species-specific root microbiota assembly is mediated by bacterial catabolism of a cocktail of PSMs synthesized by the host plant.
Diet, psychosocial stress, and Alzheimer’s disease-related neuroanatomy in female nonhuman primates
Authors: Frye Brett M. , Craft Suzanne , Register Thomas C. , Andrews Rachel N. , Appt Susan E. , Vitolins Mara Z. , Uberseder Beth , Silverstein-Metzler Marnie G. , Chen Haiying , Whitlow Christopher T. , Kim Jeongchul , Barcus Richard A. , Lockhart Samuel N. , Hoscheidt Siobhan , Say Brandon M. , Corbitt Sarah E. , Shively Carol A.
Published: September 2020

INTRODUCTION

Associations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer’s disease (AD), have been reported, but causal relationships are difficult to determine in human studies.

METHODS

We used structural magnetic resonance imaging in a well-validated nonhuman primate model of AD-like neuropathology to examine the longitudinal effects of diet (Mediterranean versus Western) and social subordination stress on brain anatomy, including global volumes, cortical thicknesses and volumes, and twenty individual regions of interest (ROIs).

RESULTS

Western diet resulted in greater cortical thicknesses, total brain volumes and gray matter, and diminished cerebrospinal fluid and white matter volumes. Socially stressed subordinates had smaller whole brain volumes but larger ROIs relevant to AD than dominants.

DISCUSSION

The observation of increased size of AD-related brain areas is consistent with similar reports of mid-life volume increases predicting increased AD risk later in life. While the biological mechanisms underlying the findings require future investigation, these observations suggest that Western diet and psychosocial stress instigate pathologic changes that increase risk of AD-associated neuropathologies, whereas Mediterranean diet may protect the brain.

RESEARCH IN CONTEXT

Systematic review: The authors reviewed the literature with PubMed and Google Scholar and found a number of publications which are cited that suggest that AD pathogenesis begins well before the onset of symptoms.

Interpretation: Our findings support the hypothesis that Western diet and psychosocial stress may instigate neuroinflammatory responses that increase risk of later developing AD-like neuropathologies, whereas the structural stasis in the Mediterranean diet group may represent a resilient phenotype.

Future directions: The manuscript serves as a critical first step in describing risk and resilient phenotypes during middle age in a nonhuman primate model of AD-like neuropathology. This report lays the groundwork for ongoing efforts to determine whether neuroinflammatory profiles differed across diet and stress groups. Future studies should aim to understand the temporal emergence of functional disparities associated with the changes in brain structure observed here.

HIGHLIGHTS

Global brain volumes changed in response to Western, but not Mediterranean, diet.

Western diet increased cortical thickness in multiple regions relevant to AD.

Mediterranean diet did not alter cortical thicknesses relevant to AD.

Brain regions associated with AD risk differed between low and high stress monkeys.

Psychosocial stress may modulate the effects of diet on the brain.
Pair bonding slows epigenetic aging and alters methylation in brains of prairie voles
Authors: Sailer Lindsay L. , Haghani Amin , Zoller Joseph A. , Li Caesar Z. , Ophir Alexander G. , Horvath Steve
Published: September 2020

The quality of romantic relationships can be predictive of health consequences related to aging. DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how pair bonding impacts aging. Prairie voles (Microtus ochrogaster) have emerged as a model to study social attachment among adult pairs. Here we describe DNA methylation-based estimators of age for prairie voles based on novel DNA methylation data generated on highly conserved mammalian CpGs measured with a custom array. The multi-tissue epigenetic clock for voles was trained on 3 tissue sources (ear, liver, and samples of brain tissue from within the pair bonding circuit). A novel dual species human-vole clock accurately measured relative age defined as the ratio of chronological age to maximum age. According to the human-vole clock of relative age, sexually inexperienced voles exhibit accelerated epigenetic aging in brain tissue (p= 0.02) when compared to pair bonded animals of the same chronological age. Epigenome wide association studies identified CpGs in four genes that were strongly associated with pair bonding across the three tissue types (brain, ear, and liver):Hnrnph1, Fancl, Fam13b, andFzd1. Further, four CpGs (near theBmp4exon,Eif4g23 prime UTR,Robo1exon, andNfat5intron) exhibited a convergent methylation change between pair bonding and aging. This study describes highly accurate DNA methylation-based estimators of age in prairie voles and provides evidence that pair bonding status modulates the methylome.
Glioma stem cells invasive phenotype at optimal stiffness is driven by MGAT5 dependent mechanosensing
Authors: Marhuenda Emilie , Fabre Christine , Zhang Cunjie , Martin-Fernandez Martà , Iskratsch Thomas , Saleh Ali , Bauchet Luc , Cambedouzou Julien , Hugnot Jean-Philippe , Duffau Hugues , Dennis James W. , Cornu David , Bakalara Norbert
Published: September 2020

Glioblastomas stem-like cells (GSCs) by invading the brain parenchyma escape resection and radiotherapy. GSC invasion is associated with altered N-glycosylation pattern of integrins and other transmembrane proteins resulting in changed mechanosensing but details are elusive. Because the tumour microenvironment has an increased stiffness we studied the interaction between matrix stiffness, N-glycosylation and GSC migration. To mimic the fibrillar microenvironments, we designed 3D-ex-polyacrylonitrile nanofibers scaffolds (NFS) with adjustable stiffnesses by loading multiwall carbon nanotubes (MWCNT). We found that migration of GSCs was maximum at 166 kPa. Migration rate was correlated with cell shape, expression of focal adhesion (FA), Epithelial to Mesenchymal Transition (EMT) proteins and (β1,6) branched N-glycan binding, galectin-3. Mutation of MGAT5 in GSC inhibited N-glycans (β1–6) branching, suppressed the stiffness dependence of FA and EMT protein expression as well as migration on 166kPa NFS; underpinning the role of multibranched N-glycans as a critical regulator of mechanotransduction by GSC.

Significance Statement

During pathological processes in which cell migration is involved, cells undergo important functional changes in protein glycosylation and are responsive to environmental mechanical modifications. We addressed the question of the glycosylation role in mechanotransduction regulation of glioma stem cells. We created a bio-inspired 3D nanofiber scaffold (NFS) loaded with multiwall carbon nanotubes to obtain NFS of adjustable stiffness in physiological and pathological ranges. We highlighted and described a mechanism of fine mechanotransduction leading to a nonlinear migration response regarding to 3D microenvironment stiffness values. We show the importance to develop mechano-pharmacology as new therapeutic target by demonstrating the relationship existing between environmental stiffness and multibranched N-glycans catalysed by the MGAT5 enzyme to optimize directed migration.
Aneuploidy-driven genome instability triggers resistance to chemotherapy
Authors: Ippolito Marica Rosaria , Martis Valentino , Hong Christy , Wardenaar René , Zerbib Johanna , Spierings Diana C.J. , Ben-David Uri , Foijer Floris , Santaguida Stefano
Published: September 2020

Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage, together with mutational burden, might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven genome instability and chemoresistance and might explain why some chemotherapies fail to succeed.
Prenatal Methadone Exposure Disrupts Behavioral Development and Alters Motor Neuron Intrinsic Properties and Local Circuitry
Authors: Grecco Gregory G. , Mork Briana , Huang Jui Yen , Metzger Corinne E. , Haggerty David L. , Reeves Kaitlin C. , Gao Yong , Hoffman Hunter , Katner Simon N. , Masters Andrea R. , Morris Cameron W. , Newell Erin A. , Engleman Eric A. , Baucum Anthony J. , Kim Jieun , Yamamoto Bryan K. , Allen Matthew R. , Wu Yu-Chien , Lu Hui-Chen , Sheets Patrick L. , Atwood Brady K.
Published: September 2020

Despite the rising prevalence of methadone treatment in pregnant women with opioid use disorder, the effects of methadone on neurobehavioral development remain unclear. We developed a translational mouse model of prenatal methadone exposure (PME) that resembles the typical pattern of opioid use by pregnant women who first use oxycodone then switch to methadone maintenance pharmacotherapy, and subsequently become pregnant while maintained on methadone. We investigated the effects of PME on physical development, sensorimotor behavior, and motor neuron properties using a multidisciplinary approach of physical, biochemical, and behavioral assessments along with brain slice electrophysiology and in vivo magnetic resonance imaging. PME produced substantial impairments in offspring physical growth, activity in an open field, and sensorimotor milestone acquisition which were associated with alterations in motor neuron functioning and connectivity. The present study adds to the limited work examining PME by providing a comprehensive, translationally relevant characterization of how PME disrupts offspring development.
Evolution of the canonical sex chromosomes of the guppy and its relatives
Authors: Kirkpatrick M. , Sardell J.M. , Pinto B. J. , Dixon G. , Peichel C. L. , Schartl M.
Published: September 2020

The sex chromosomes of the guppy,Poecilia reticulata, and its close relatives are of particular interest: they are much younger than the highly degenerate sex chromosomes of model systems such as mammals andDrosophila melanogaster, and they carry many of the genes responsible for the males’ dramatic coloration. Over the last decade, several studies have analyzed these sex chromosomes using a variety of approaches including sequencing genomes and transcriptomes, cytology, and linkage mapping. Conflicting conclusions have emerged, in particular concerning the history of the sex chromosomes and the evolution of suppressed recombination between the X and Y. Here we address these controversies by reviewing the evidence and reanalyzing data. We find no support for a nonrecombining sex determining region (SDR) or evolutionary strata inP. reticulata. Further, we find that the evidence most strongly support the hypothesis that the SDRs ofP. pictaandP. wingeievolved independently after those lineages diverged. We identify possible causes of conflicting results in previous studies and suggest best practices going forward.
The role of pregnancy-specific glycoproteins on trophoblast motility in three-dimensional gelatin hydrogels
Authors: Zambuto Samantha G. , Rattila Shemona , Dveksler Gabriela , Harley Brendan A.C.
Published: September 2020

Trophoblast invasion is a complex biological process necessary for establishment of pregnancy; however, much remains unknown regarding what signaling factors coordinate the extent of invasion. Pregnancy-specific glycoproteins (PSGs) are some of the most abundant circulating trophoblastic proteins in maternal blood during human pregnancy, with maternal serum concentrations rising to as high as 200-400 μg/mL at term. Here, we employ three-dimensional (3D) trophoblast motility assays consisting of trophoblast spheroids encapsulated in 3D gelatin hydrogels to quantify trophoblast outgrowth area, viability, and cytotoxicity in the presence of PSG1 and PSG9 as well as epidermal growth factor and Nodal. We show PSG9 reduces trophoblast motility whereas PSG1 increases motility. Further, we assess bulk nascent protein production by encapsulated spheroids to highlight the potential of this approach to assess trophoblast response (motility, remodeling) to soluble factors and extracellular matrix cues. Such models provide an important platform to develop a deeper understanding of early pregnancy.

Graphical Abstract
Effects of species traits and ecosystem characteristics on species detection by eDNA metabarcoding in lake fish communities
Authors: Doi Hideyuki , Matsuoka Shunsuke , Matsuzaki Shin-ichiro S. , Nagano Mariko , Sato Hirotoshi , Yamanaka Hiroki , Matsuhashi Saeko , Yamamoto Satoshi , Minamoto Toshifumi , Araki Hitoshi , Ikeda Kousuke , Kato Atsuko , Kumei Kouichi , Maki Nobutaka , Mitsuzuka Takashi , Takahara Teruhiko , Toki Kimihito , Ueda Natsuki , Watanabe Takeshi , Yamazoe Kanji , Miya Masaki
Published: September 2020

Although environmental DNA (eDNA) metabarcoding is acknowledged to be an exceptionally useful and powerful tool for monitoring surveys, it has limited applicability, particularly for nationwide surveys. To evaluate the performance of eDNA metabarcoding in broad-scale monitoring, we examined the effects of species ecological/biological traits and ecosystem characteristics on species detection rates and the consequences for community analysis. We conducted eDNA metabarcoding on fish communities in 18 Japanese lakes on a country-wide scale. By comparing species records, we found that certain species traits, including body size, body shape, saltwater tolerance, and habitat preferences, influenced eDNA detection. We also found that the proportion of species detected decreased significantly with an increase in lake surface area, owing to an ecosystem-size effect on species detection. We conclude that species traits, including habitat preferences and body size, and ecosystem size should be taken into consideration when assessing the performance of eDNA metabarcoding in broad-scale monitoring.
Controlled Release of Anti-inflammatory and Pro-angiogenic Factors from Macroporous Scaffolds
Authors: Liang Jia-Pu , Accolla Robert P. , Jiang Kaiyuan , Li Ying , Stabler Cherie L.
Published: September 2020

The simultaneous local delivery of anti-inflammatory and pro-angiogenic agents via biomaterial scaffolds presents a promising method for improving the engraftment of tissue-engineered implants while avoiding potentially detrimental systemic delivery. In this study, PDMS microbeads were loaded with either anti-inflammatory dexamethasone (Dex) or pro-angiogenic 17β-estradiol (E2) and subsequently integrated into a single macroporous scaffold to create a controlled, dual drug-delivery platform. Compared to a standard monolithic drug dispersion scaffold, macroporous scaffolds containing drug-loaded microbeads exhibited reduced initial burst release and increased the durability of drug release for both agents. Incubation of scaffolds with LPS-stimulated M1 macrophages found that Dex suppressed the production of pro-inflammatory and pro-angiogenic factors, when compared to drug-free control scaffolds; however, the co-incubation of macrophages with Dex and E2 scaffolds restored their pro-angiogenic features. Following implantation, Dex-loaded microbead scaffolds (Dex-µBS) suppressed host cell infiltration and integration, when compared to controls. In contrast, the co-delivery of dexamethasone with estrogen from the microbead scaffold (Dex/E2-µBS) dampened overall host cell infiltration but restored graft vascularization. These results demonstrate the utility of a microbead scaffold approach for the controlled, tailored, and local release of multiple drugs from an open framework implant. It further highlights the complementary impacts of local Dex and E2 delivery to direct the healthy integration of implants, which has broad applications to the field of tissue engineering and regenerative medicine.
MogR is a ubiquitous transcriptional repressor affecting motility, biofilm formation and virulence inBacillus thuringiensis
Authors: Smith Veronika , Josefsen Malin , Lindbäck Toril , Hegna Ida K. , Finke Sarah , Tourasse Nicolas J. , Nielsen-LeRoux Christina , Økstad Ole Andreas , Fagerlund Annette
Published: September 2020

Flagellar motility is considered an important virulence factor in different pathogenic bacteria. InListeria monocytogenesthe transcriptional repressor MogR regulates motility in a temperature-dependent manner, directly repressing flagellar- and chemotaxis genes. The only other bacteria known to carry amogRhomolog are members of theBacillus cereusgroup, which includes motile species such asB. cereusandBacillus thuringiensisas well as the non-motile speciesBacillus anthracis, Bacillus mycoidesandBacillus pseudomycoides. Furthermore, the main motility locus inB. cereusgroup bacteria, carrying the genes for flagellar synthesis, appears to be more closely related toL. monocytogenesthan toBacillus subtilis,which belongs to a separate phylogenetic group of Bacilli and does not carry amogRortholog. Here, we show that inB. thuringiensis, MogR overexpression results in non-motile cells devoid of flagella. Global gene expression profiling showed that 110 genes were differentially regulated by MogR overexpression, including flagellar motility genes, but also genes associated with virulence, stress response and biofilm lifestyle. Accordingly, phenotypic assays showed that MogR also affects cytotoxicity and biofilm formation inB. thuringiensis. Overexpression of a MogR variant mutated in two amino acids within the putative DNA binding domain restored phenotypes to those of an empty vector control. In accordance, introduction of these mutations resulted in complete loss in MogR binding to its candidate flagellar locus target sitein vitro. In contrast toL. monocytogenes, MogR appears to be regulated in a growth-phase dependent and temperature-independent manner inB. thuringiensis407. Interestingly,mogRwas found to be conserved also in non-motileB. cereusgroup species such asB. mycoidesandB. pseudomycoides, which both carry major gene deletions in the flagellar motility locus and where inB. pseudomycoides mogRis the only gene retained. Furthermore,mogRis expressed in non-motileB. anthracis. Altogether this provides indications of an expanded set of functions for MogR inB. cereusgroup species, beyond motility regulation. In conclusion, MogR constitutes a novelB. thuringiensispleiotropic transcriptional regulator, acting as a repressor of motility genes, and affecting the expression of a variety of additional genes involved in biofilm formation and virulence.
Reconstructing the history and biological consequences of a plant invasion on the Galápagos islands
Authors: Gibson Matthew J.S. , de Lourdes Torres María , Brandvain Yaniv , Moyle Leonie C.
Published: September 2020

The introduction of non-native species into new habitats is one of the foremost risks to global biodiversity. Here, we evaluate a recent invasion of wild tomato (Solanum pimpinellifolium) onto the Galápagos islands from a population genomic perspective, using a large panel of novel collections from the archipelago as well as historical accessions from mainland Ecuador and Peru. We infer a recent invasion ofS. pimpinellifoliumon the islands, largely the result of a single event from central Ecuador which, despite its recency, has rapidly spread onto several islands in the Galápagos. By reconstructing patterns of local ancestry throughout the genomes of invasive plants, we uncover evidence for recent hybridization and introgression betweenS. pimpinellifoliumand the closely related endemic speciesSolanum cheesmaniae. Two large introgressed regions overlap with known fruit color loci involved in carotenoid biosynthesis. Instead of red fruits, admixed individuals with endemic haplotypes at these loci have orange fruit colors that are typically characteristic of the endemic species. We therefore infer that introgression explains the observed trait convergence. Moreover, we infer roles for two independent loci in driving this pattern, and a likely history of selection favoring the repeated phenotypic transition from red to orange fruits. Together, our data reconstruct a complex history of invasion, expansion, and gene flow among wild tomatoes on the Galápagos islands. These findings provide critical data on the evolutionary importance of hybridization during colonization and its role in influencing conservation outcomes.

Significance Statement

The isolation and unique diversity of the Galápagos Islands provide numerous natural experiments that have enriched our understanding of evolutionary biology. Here we use population genomic sequencing to reconstruct the timing, path, and consequences of a biological invasion by wild tomato onto the Galápagos. We infer that invasive populations originated from a recent human-mediated migration event from central Ecuador. Our data also indicate that invasive populations are hybridizing with endemic populations, and that this has led to some invasive individuals adopting both fruit color genes and the fruit color characteristic of the endemic island species. Our results demonstrate how hybridization can shape patterns of trait evolution over very short time scales, and characterize genetic factors underlying invasive success.
Regulation of retinal neurogenesis by somatostatin signaling
Authors: Weir Kurt , Kim Dong Won , Blackshaw Seth
Published: September 2020

Neuropeptides have been reported to regulate progenitor proliferation and neurogenesis in the central nervous system. However, these studies have typically been conducted using pharmacological agents inex vivopreparations, andin vivoevidence for their developmental function is generally lacking. Recent scRNA-Seq studies have identified multiple neuropeptides and their receptors as being selectively expressed in neurogenic progenitors of the embryonic mouse and human retina. This includes Sstr2, whose ligand somatostatin is transiently expressed by immature retinal ganglion cells. By analyzing retinal explants treated with selective ligands that target these receptors, we found that Sstr2-dependent somatostatin signaling induces a dose-dependent inhibition of photoreceptor generation while increasing the relative fraction of primary progenitor cells. These effects were confirmed by scRNA-Seq analysis of retinal explants and abolished inSstr2-deficient retinas. Although no changes in the relative fraction of primary progenitors or photoreceptor precursors were observed inSstr2-deficient retinasin vivo, scRNA-Seq analysis demonstrated accelerated differentiation of neurogenic progenitors. We conclude that Sstr2 signaling may act to negatively regulate retinal neurogenesis in combination with other retinal ganglion cell-derived secreted factors such as Shh, althoughin vivoSstr2 is dispensable for normal retinal development.
Temporal patterns inIxodes ricinusmicrobial communities: an insight into tick-borne microbe interactions
Authors: Lejal E , Chiquet J , Aubert J , Robin S , Estrada-Peña A , Rue O , Midoux C , Mariadassou M , Bailly X , Cougoul A , Gasqui P , Cosson JF , Chalvet-Monfray K , Vayssier-Taussat M , Pollet T
Published: September 2020

Background

Ticks transmit pathogens of medical and veterinary importance, and represent an increasing threat for human and animal health. Important steps in assessing disease risk and developing possible new future control strategies involve identifying tick-borne microbes, their temporal dynamics and interactions.

Methods

Using high throughput sequencing, we studied the microbiota dynamics ofIxodes ricinusfrom 371 nymphs collected monthly over three consecutive years in a peri-urban forest. After adjusting a Poisson Log Normal model to our data set, the implementation of a principal component analysis as well as sparse network reconstruction and differential analysis allowed us to assess inter-annual, seasonal and monthly variability ofI. ricinusmicrobial communities as well as their interactions.

Results

Around 75% of the detected sequences belonged to five genera known to be maternally inherited bacteria in arthropods and potentially circulating in ticks: CandidatusMidichloria, Rickettsia, Spiroplasma, ArsenophonusandWolbachia. The structure of theI. ricinusmicrobiota was temporally variable with interannual recurrence and seemed to be mainly driven by OTUs belonging to environmental genera. The total network analysis revealed a majority of positive (partial) correlations. We identified strong relationships between OTUs belonging toWolbachiaandArsenophonus, betraying the presence of the parasitoid waspIxodiphagus hookeriin ticks, and the well known arthropod symbiontSpiroplasma, previously documented to be involved in the defense against parasitoid wasp inDrosophila melanogaster. Other associations were observed between the tick symbiont CandidatusMidichloriaand pathogens belonging toRickettsia, probablyRickettsia helvetica. More specific network analysis finally suggested that the presence of pathogens belonging to generaBorrelia, AnaplasmaandRickettsiamight disrupt microbial interactions inI. ricinus.

Conclusions

Here, we identified theI. ricinusmicrobiota and documented for the first time the existence and recurrence of marked temporal shifts in the tick microbial community dynamics. We statistically showed strong relationships between the presence of some pathogens and the structure of theI. ricinusnon-pathogenic microbes. We interestingly detected close links between some tick symbionts and the potential presence of either pathogenicRickettsiaor a parasitoid in ticks. All these new findings might be very promising for the future development of new control strategies of ticks and tick-borne diseases.
Complex spike firing adapts to saliency of inputs and engages readiness to act
Authors: Bina Lorenzo , Romano Vincenzo , Hoogland Tycho M. , Bosman Laurens W.J. , De Zeeuw Chris I.
Published: September 2020

The cerebellum is involved in cognition next to motor coordination. During complex tasks, climbing fiber input to the cerebellum can deliver seemingly opposite signals, covering both motor and non-motor functions. To elucidate this ambiguity, we hypothesized that climbing fiber activity represents the saliency of inputs leading to action-readiness. We addressed this hypothesis by recording Purkinje cell activity in lateral cerebellum of awake mice learning go/no-go decisions based on entrained saliency of different sensory stimuli. As training progressed, the timing of climbing fiber signals switched in a coordinated fashion with that of Purkinje cell simple spikes towards the moment of occurrence of the salient stimulus that required action. Trial-by-trial analysis indicated that emerging climbing fiber activity is not linked to individual motor responses or rewards per se, but rather reflects the saliency of a particular sensory stimulus that engages a general readiness to act, bridging the non-motor with the motor functions.

In brief

Mice were trained to identify the saliency of different sensory inputs in that they had to learn to ignore a prominent sound cue and respond to a light tactile cue in a Go/No-Go licking task. As the mice learned to discriminate the two inputs and respond to the proper signal, the Purkinje cells in the lateral cerebellum switched their climbing fiber activity (i.e., complex spike activity) towards the moment of occurrence of the salient stimulus that required a response, while concomitantly shifting the phase of their simple spike modulation. Trial-by-trial analysis indicates that the emerging climbing fiber activity is not linked to the occurrence of the motor response or reward per se, but rather reflects the saliency of a particular sensory stimulus engaging a general readiness to act.
Structural asymmetry along protein sequences and co-translational folding
Authors: McBride John M. , Tlusty Tsvi
Published: September 2020

Proteins are translated from the N- to the C-terminal, raising the basic question of how this innate directionality affects their evolution. To explore this question, we analyze 16,200 structures from the protein data bank (PDB). We find remarkable enrichment ofα-helices at the C terminal andβ-sheets at the N terminal. Furthermore, thisα-βasymmetry correlates with sequence length and contact order, both determinants of folding rate, hinting at possible links to co-translational folding (CTF). Hence, we propose the ‘slowest-first’ scheme, whereby protein sequences evolved structural asymmetry to accelerate CTF: the slowest-folding elements (e.g. β-sheets) are positioned near the N terminal so they have more time to fold during translation. Our model predicts that CTF can be accelerated, up to double the rate, when folding time is commensurate with translation time; analysis of the PDB reveals that structural asymmetry is indeed maximal in this regime. This correspondence is greater in prokaryotes, which generally require faster protein production. Altogether, this indicates that accelerating CTF is a substantial evolutionary force whose interplay with stability and functionality is encoded in sequence asymmetry.
GAMYB modulatesbHLH142and is homeostatically regulated by TDR during rice anther tapetal and pollen development
Authors: Ko Swee-Suak , Li Min-Jeng , Ho Yi-Cheng , Yu Chun-Ping , Yang Ting-Ting , Lin Yi-Jyun , Hsing Hung-Chien , Chen Tien-Kuan , Jhong Chung-Min , Li Wen-Hsiung , Ku Maurice Sun-Ben
Published: September 2020

GAMYB, UDT1, TIP2/bHLH142, TDR, and EAT1/DTD are important transcription factors (TFs) that play a crucial role during rice pollen development. This study demonstrates that bHLH142 acts downstream of UDT1 and GAMYB and works as a “hub” in these two pollen pathways. We show that GAMYB modulatesbHLH142expression through specific binding to the MYB motif ofbHLH142promoter during early stage of pollen development; while TDR acts as a transcriptional repressor of the GAMYB modulation ofbHLH142by binding to the E-box close to the MYB motif on the promoter. The up- and down-regulation of TFs highlights the importance that a tight, precise, and coordinated regulation among these TFs is essential for normal pollen development. Most notably, this study illustrates the regulatory pathways of GAMYB and UDT1 that rely onbHLH142in a direct and an indirect manner, respectively, and function in different tissues with distinct biological functions during pollen development. This study advances our understanding of the molecular mechanisms of rice pollen development.

Highlight

GAMYB can directly modulate the transactivation of thebHLH142, but the modulation is repressed by TDR to keep the homeostasis ofbHLH142gene expression to ensure normal pollen development.