bluuebunny/crossref_metadata_2025 huggingface dataset:
Population dynamics with spatial structure and an Allee effect
Authors: Surendran Anudeep , Plank Michael , Simpson Matthew
Published: June 2020

Allee effects describe populations in which long-term survival is only possible if the population density is above some threshold level. A simple mathematical model of an Allee effect is one where initial densities below the threshold lead to population extinction, whereas initial densities above the threshold eventually asymptote to some positive carrying capacity density. Mean field models of population dynamics neglect spatial structure that can arise through short-range interactions, such as short-range competition and dispersal. The influence of such non mean-field effects has not been studied in the presence of an Allee effect. To address this we develop an individual-based model (IBM) that incorporates both short-range interactions and an Allee effect. To explore the role of spatial structure we derive a mathematically tractable continuum approximation of the IBM in terms of the dynamics of spatial moments. In the limit of long-range interactions where the mean-field approximation holds, our modelling framework accurately recovers the mean-field Allee threshold. We show that the Allee threshold is sensitive to spatial structure that mean-field models neglect. For example, we show that there are cases where the mean-field model predicts extinction but the population actually survives and vice versa. Through simulations we show that our new spatial moment dynamics model accurately captures the modified Allee threshold in the presence of spatial structure.
Population genomic and historical analysis reveals a global invasion by bridgehead processes inMimulus guttatus
Authors: Vallejo-Marín Mario , Friedman Jannice , Twyford Alex D. , Lepais Olivier , Ickert-Bond Stefanie M. , Streisfeld Matthew A. , Yant Levi , van Kleunen Mark , Rotter Michael C. , Puzey Joshua R.
Published: June 2020

Humans are transforming species ranges worldwide. While artificial translocations trigger biological invasions with negative effects on biodiversity, invasions provide exceptional opportunities to generate ecological and evolutionary hypotheses. Unfortunately, imperfect historical records and exceedingly complex demographic histories present challenges for the reconstruction of invasion histories. Here we combine historical records, extensive worldwide and genome-wide sampling, and demographic analyses to investigate the global invasion of yellow monkeyflowers (Mimulus guttatus) from North America to Europe and the Southwest Pacific. By sampling 521 plants from 158 native and introduced populations genotyped at >44,000 loci, we determined that invasive North AmericanM. guttatuswas first likely introduced to the British Isles from the Aleutian Islands (Alaska), followed by rapid admixture from multiple parts of the native range. Populations in the British Isles then appear to have served as a bridgehead for vanguard invasions worldwide into the rest of Europe, New Zealand and eastern North America. Our results emphasise the highly admixed nature of introducedM. guttatusand demonstrate the potential of introduced populations to serve as sources of secondary admixture, producing novel hybrids. Unravelling the history of biological invasions provides a starting point to understand how invasive populations adapt to novel environments.
Different effects of phytohormones on Fusarium head blight and Fusarium root rot resistance inBrachypodium distachyon
Authors: Haidoulis J F. , Nicholson P.
Published: June 2020

Fusarium graminearumis a devastating pathogen of small grain cereals causing both Fusarium head blight (FHB) and Fusarium root rot (FRR). Exogenous application of phytohormones has been shown to affect FHB resistance. In contrast to FHB, FRR remains poorly characterised and it is unknown whether phytohormones play similar roles in FHB and FRR. In this present study,B. distachyonfloral tissues at mid-anthesis and root tissues from seedlings were exogenously treated with several phytohormones before inoculation withF. graminearum. The canonical defence-associated phytohormones had differing effects on FHB and FRR. Salicylic acid (SA) significantly increased susceptibility to FRR but not to FHB while jasmonic acid (JA) and ethylene increased resistance to FRR but increased susceptibility to FHB. Additionally, the growth-associated phytohormones auxin and cytokinin significantly increased resistance and susceptibility, respectively, to both diseases. This study is the first to compare phytohormone effects between FHB and FRR in the same host.

Highlight

The tissue-dependent effects of defence phytohormones and tissue-independent effects of development phytohormones onF. graminearum-induced Fusarium head blight and Fusarium root rot diseases in the model cerealBrachypodium distachyon.
BBB pathophysiology independent delivery of siRNA in traumatic brain injury
Authors: Li Wen , Qiu Jianhua , Li Xiang-Ling , Aday Sezin , Zhang Jingdong , Conley Grace , Xu Jun , Langer Robert , Mannix Rebekah , Karp Jeffrey M. , Joshi Nitin
Published: June 2020

Small interfering RNA (siRNA) represents a powerful strategy to mitigate the long-term sequelae of traumatic brain injury (TBI). However, poor permeability of siRNA across the blood brain barrier (BBB) poses a major hurdle. One approach to overcome this challenge involves treatment administration while the BBB is physically breached post-injury. However, this approach is only applicable to a subset of injuries with substantial BBB breach and can lead to variable therapeutic response due to the heterogeneity of physical breaching of BBB in TBI. Moreover, since physical breaching of BBB is transient, this approach offers a limited window for therapeutic intervention, which is not ideal as repeated dosing beyond the transient window of physically breached BBB might be required. Herein, we report a nanoparticle platform for BBB pathophysiology-independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density, which maximized the active transport of nanoparticles across BBB. Intravenous injection of engineered nanoparticles, within or outside the window of physically breached BBB in TBI mice resulted in 3-fold higher brain accumulation compared to conventional PEGylated nanoparticles and demonstrated up to 50% gene silencing. To our knowledge, this is the first reported example of BBB pathophysiology-independent drug delivery in TBI, and the first time combined modulation of surface chemistry and coating density has been shown to tune BBB penetration of nanoparticles. Taken together, our approach offers a clinically relevant approach to develop siRNA therapeutics for preventing long-term effects of TBI and deserves further exploration.
Monoterpenes alter TAR1-driven physiology inDrosophilaspecies
Authors: Finetti Luca , Tiedemann Lasse , Zhang Xiaoying , Civolani Stefano , Bernacchia Giovanni , Roeder Thomas
Published: June 2020

Monoterpenes are molecules with insecticide properties whose mechanism of action is however not completely elucidated. Furthermore, they seem to be able to modulate the monoaminergic system and several behavioural aspects in insects. In particular, tyramine (TA) and octopamine (OA) and their associated receptors orchestrate physiological processes such as feeding, locomotion and metabolism. Here we show that monoterpenes not only act as biopesticides inDrosophilaspecies but can cause complex behavioural alterations that require a functional type 1 tyramine receptors (TAR1s). Variations in metabolic traits as well as locomotory activity were evaluated in bothDrosophila suzukiiandDrosophila melanogasterafter treatment with three monoterpenes. A TAR1−/−D. melanogasterstrain was used to better understand the relationships between the receptor and monoterpenes-related behavioural changes. Immunohistochemistry analysis revealed that, in theD. melanogasterbrain, TAR1 appeared to be expressed in areas controlling metabolism. In comparison to theD. melanogasterwild type, the TAR−/−flies showed a phenotype characterized by higher triglyceride levels and food intake as well as lower locomotory activity. The monoterpenes, tested at sublethal concentrations, were able to induce a downregulation of the TAR1 coding gene in bothDrosophilaspecies. Furthermore, monoterpenes also altered the behaviour inD. suzukiiandD. melanogasterwild types 24 h after a continuous monoterpene exposure. Interestingly, they were ineffective in modifying the physiological performances of TAR1−/−flies. In conclusion, it appears that monoterpenes not only act as biopesticides forDrosophilabut they can also interfere with its behaviour and metabolism in a TAR1-dependent fashion.
G9a/GLP-Sensitivity of H3K9me2 Demarcates Two Types of Genomic Compartments
Authors: Yan Zixiang , Ji Luzhang , Huo Xiangru , Wang Qianfeng , Zhang Yuwen , Wen Bo
Published: June 2020

In the nucleus, chromatin is folded into hierarchical architecture that is tightly linked to various nuclear functions. However, the underlying molecular mechanisms that confer these architectures remain incompletely understood. Here, we investigated the functional roles of H3 lysine 9 dimethylation (H3K9me2), one of the abundant histone modifications, in three-dimensional (3D) genome organization. Unlike mouse embryonic stem cells (mESCs), inhibition of methyltransferases G9a and GLP in differentiated cells eliminated H3K9me2 predominantly at A-type (active) genomic compartments, and the level of residual H3K9me2 modification was strongly associated with genomic compartments in differentiated cells. Furthermore, chemical inhibition of G9a/GLP in mouse hepatocytes led to the decreased chromatin-nuclear lamina interactions mainly at G9a/GLP sensitive regions (GSRs), the increased degree of genomic compartmentalization, and the up-regulation of hundreds of genes that were associated with alterations of the 3D chromatin. Collectively, our data demonstrated essential roles of H3K9me2 in 3D genome organization.
Nrl is dispensable for specification of rod photoreceptors in adult zebrafish contrasting a deeply conserved requirement earlier in ontogeny
Authors: Oel A. Phillip , Neil Gavin J. , Dong Emily M. , Balay Spencer D. , Collett Keon , Allison W. Ted
Published: June 2020

The transcription factor NRL (Neural Retinal Leucine-zipper) has been canonized, appropriately enough, as the master regulator of photoreceptor cell fate in the retina. NRL is necessary and sufficient to specify rod cell fate and to preclude cone cell fate in mice. By engineering zebrafish we tested if NRL function has conserved roles beyond mammals or beyond nocturnal species, i.e. in a vertebrate possessing a greater and more typical diversity of cone sub-types. Here, transgenic expression of a Nrl homolog from zebrafish or mouse was sufficient to convert developing zebrafish cones into rod photoreceptors. Zebrafishnrl-/-mutants lacked rods (and had excess UV-sensitive cones) as young larvae, thus the conservation of Nrl function between mice and zebrafish appears sound. These data inform hypotheses of photoreceptor evolution through the Nocturnal Bottleneck, suggesting that a capacity to favor nocturnal vision is a property ofNRLthat predates the emergence of early mammals. Strikingly, however, rods were abundant in adultnrl-/-null mutant zebrafish. Rods developed in adults despite Nrl protein being undetectable. Therefore a yet-to-be-revealed non-canonical pathway independent ofnrlis able to specify the fate of some rod photoreceptors.

Highlights

- Nrl is conserved and sufficient to specify rod photoreceptors in zebrafish retina

- Nrl is necessary for rod photoreceptors in early ontogeny of zebrafish larvae

- Zebrafish Nrl is functionally conserved with mouse and human NRL

- Remarkably, Nrl is dispensable for rod specification in adult zebrafish
Vascular smooth muscle-derived TRPV1-expressing progenitors are a new source of cold-induced thermogenic adipocytes
Authors: Shamsi Farnaz , Lynes Matthew D. , Piper Mary , Ho Li-Lun , Huang Tian Lian , Tseng Yu-Hua
Published: June 2020

Brown adipose tissue (BAT) functions in energy expenditure in part due its role in thermoregulation. The prominent capacity of BAT to enhance fuel utilization and energy expenditure makes it an attractive target for treating obesity and metabolic disorders. Prolonged cold exposure inducesde novorecruitment of brown adipocytes and activates their thermogenic activity. However, the exact source of cold-induced brown adipocytes is not completely understood. In this study, we sought to investigate the cellular origin of cold-induced brown adipocytes using single-cell RNA sequencing. We identified two distinct types of adipocyte progenitors that contribute tode novorecruitment of brown adipocytes in response to cold challenge. One is the previously known Pdgfra-expressing mesenchymal progenitors and the other is a vascular smooth muscle-derived adipocyte progenitor (VSM-APC) population, which expresses the temperature-sensitive ion channel transient receptor potential cation channel subfamily V member 1 (Trpv1). Using flow cytometry and lineage tracing, we demonstrated that the Trpv1posVSM-APCs were indeed distinct from the Pdgfraposprogenitors and could contribute to brown adipocytes with greater thermogenic potential. Together, these findings illustrate a landscape of thermogenic adipose niche at the single cell resolution and identify a new cellular origin for the development of brown adipocytes.
Fast 3D imaging of giant unilamellar vesicles using reflected light-sheet microscopy with single molecule sensitivity
Authors: Szilagyi Sven A. , Burmeister Moritz , Davis Q. Tyrell , Hermsdorf Gero L. , De Suman , Schäffer Erik , Jannasch Anita
Published: June 2020

Observation of highly dynamic processes inside living cells at the single molecule level is key for a quantitative understanding of biological systems. However, imaging of single molecules in living cells usually is limited by the spatial and temporal resolution, photobleaching and the signal-to-background ratio. To overcome these limitations, light-sheet microscopes with thin selective plane illumination have recently been developed. For example, a reflected light-sheet design combines the illumination by a thin light-sheet with a high numerical aperture objective for single-molecule detection. Here, we developed a reflected light-sheet microscope with active optics for fast, high contrast, two-color acquisition ofz-stacks. We demonstrate fast volume scanning by imaging a two-color giant unilamellar vesicle (GUV) hemisphere. In addition, the high signal-to-noise ratio enabled the imaging and tracking of single lipids in the cap of a GUV. In the long term, the enhanced reflected scanning light sheet microscope enables fast 3D scanning of artificial membrane systems and cells with single-molecule sensitivity and thereby will provide quantitative and molecular insight into the operation of cells.
Family-wide evaluation of RALF peptides inArabidopsis thaliana
Authors: Abarca Alicia , Franck Christina M. , Zipfel Cyril
Published: June 2020

Plant peptide hormones are important players controlling various aspects of plants’ lives. RAPID ALKALINIZATION FACTOR (RALF) peptides have recently emerged as important players in multiple physiological processes. Numerous studies on RALF peptides focused on broad phylogenetic analysis including multiple species. Thus, progress has been made in understanding the evolutionary processes that shaped this family. Nevertheless, to date, there is no comprehensive, family-wide functional study on RALF peptides. Here, we analysed the phylogeny and function of the proposed multigenic RALF peptide family in the model plantArabidopsis thaliana, ecotype Col-0. Our phylogenetic analysis reveals that two of the previously proposed RALF peptides are not genuine RALF peptides, which leads us to propose a new consensusAtRALF peptide family annotation. Moreover, we show that the majority ofAtRALF peptides are able to induce seedling or root growth inhibition inA. thalianaseedlings when applied exogenously as synthetic peptides. Additionally, we show that most of these responses are dependent on theCatharanthus roseusRLK1-LIKE receptor kinase FERONIA, suggesting a pivotal role in the perception of multiple RALF peptides.

One sentence summary

The majority ofA. thalianaRALF peptides inhibit growth in a FERONIA-dependent manner
Genetic Variability affects the Skeletal Response to Unloading
Authors: Friedman Michael A. , Abood Abdullah , Senwar Bhavya , Zhang Yue , Maroni Camilla Reina , Ferguson Virginia L. , Farber Charles R. , Donahue Henry J.
Published: June 2020

Mechanical unloading decreases bone volume and strength. In humans and mice, bone mineral density is highly heritable, and in mice the response to changes in loading varies with genetic background. Thus, genetic variability may affect the response of bone to unloading. As a first step to identify genes involved in bone response to unloading, we evaluated the effects of unloading in eight inbred mouse strains: C57BL/6J, PWK/PhJ, WSB/EiJ, A/J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HlLtJ, and CAST/EiJ. C57BL/6J and NOD/ShiLtJ mice had the greatest unloading induced loss of diaphyseal cortical bone volume and strength. NZO/HlLtJ mice had the greatest metaphyseal trabecular bone loss, and C57BL/6J, WSB/EiJ, NOD/ShiLtJ, and CAST/EiJ mice had the greatest epiphyseal trabecular loss. Bone loss in the epiphyses displayed the highest heritability. With immobilization, mineral:matrix was reduced, and carbonate:phosphate and crystallinity were increased. A/J mice displayed the greatest unloading induced loss of mineral:matrix. Changes in gene expression in response to unloading were greatest in NOD/ShiLtJ and CAST/EiJ mice. The most upregulated genes in response to unloading were associated with increased collagen synthesis and extracellular matrix formation. Our results demonstrate a strong differential response to unloading as a function of strain. Diversity outbred (DO) mice are a high-resolution mapping population derived from these eight inbred founder strains. These results suggest DO mice will be highly suited for examining the genetic basis of the skeletal response to unloading.
When killers become thieves: trogocytosed PD-1 inhibits NK cells in cancer
Authors: Hasim Mohammed S. , Marotel Marie , Hodgins Jonathan J. , Vulpis Elisabetta , Shih Han-Yun , Scheer Amit , MacMillan Olivia , Alonso Fernando G. , Burke Kelly P. , Cook David P. , Petrucci Maria Teresa , Santoni Angela , Fallon Padraic G. , Sharpe Arlene H. , Sciumè Giuseppe , Veillette Andre , Zingoni Alessandra , McCurdy Arleigh , Ardolino Michele
Published: June 2020

Leucocytes often perform trogocytosis, the process by which cells acquire parts of the plasma membrane from interacting cells. Accumulating evidence indicates that trogocytosis modulates immune responses, but the underlying molecular mechanisms are unclear. Here, using two mouse models of leukemia, we found that cytotoxic lymphocytes perform trogocytosis at high rates with tumor cells. While performing trogocytosis, both Natural Killer and CD8+T cells acquire the checkpoint receptor PD-1 from leukemia cells. In vitro and in vivo investigation revealed that PD-1 protein found on the surface of Natural Killer cells, rather than being endogenously expressed, was derived entirely from leukemia cells. Mechanistically, SLAM receptors were essential for PD-1 trogocytosis. PD-1 acquired via trogocytosis actively suppressed anti-tumor immunity, as revealed by the positive outcome of PD-1 blockade in PD-1-deficient mice. PD-1 trogocytosis was corroborated in patients with clonal plasma cell disorders, where Natural Killer cells that stained for PD-1 also stained for tumor cell markers. Our results, in addition to shedding light on a previously unappreciated mechanism underlying the presence of PD-1 on Natural Killer and cytotoxic T cells, reveal the immune-regulatory effect of membrane transfer occurring when immune cells contact tumor cells.

Once sentence summary

Natural Killer cells are inhibited by PD-1 acquired from the surface of tumor cells via trogocytosis.
A survey of pairwise epistasis supports an outside-in hierarchy of clade-specifying and function-defining residues in PSD95 PDZ3
Authors: Nedrud David , Coyote-Maestas Willow , Schmidt Daniel
Published: June 2020

Deep mutational scanning enables data-driven models of protein structure and function. Here, we adapted Saturated Programmable Insertion Engineering as an economical and programmable deep mutational scanning technique. We validate this approach with an existing single mutant dataset in the PSD95 PDZ3 domain, and further characterize most pairwise double mutants to study how a mutation’s phenotype depends on mutations at other sites, a phenomenon called epistasis. We observe wide-spread proximal negative epistasis, which we attribute to mutations affecting thermodynamic stability, and strong long-range positive epistasis, which is enriched in an evolutionarily conserved and function-defining network of ‘sector’ and clade-specifying residues. Conditional neutrality of mutations in clade-specifying residues compensates for deleterious mutations in sector positions. This suggests an outside-in hierarchy of interactions through which positive epistasis between clade-specifying residues and the PDZ sector facilitated the evolutionary expansion and specialization of PDZ domains.
BERTology Meets Biology: Interpreting Attention in Protein Language Models
Authors: Vig Jesse , Madani Ali , Varshney Lav R. , Xiong Caiming , Socher Richard , Rajani Nazneen Fatema
Published: June 2020

Transformer architectures have proven to learn useful representations for protein classification and generation tasks. However, these representations present challenges in interpretability. Through the lens of attention, we analyze the inner workings of the Transformer and explore how the model discerns structural and functional properties of proteins. We show that attention (1) captures the folding structure of proteins, connecting amino acids that are far apart in the underlying sequence, but spatially close in the three-dimensional structure, (2) targets binding sites, a key functional component of proteins, and (3) focuses on progressively more complex biophysical properties with increasing layer depth. We also present a three-dimensional visualization of the interaction between attention and protein structure. Our findings align with known biological processes and provide a tool to aid discovery in protein engineering and synthetic biology. The code for visualization and analysis is available athttps://github.com/salesforce/provis.
Integration of Machine Learning Improves the Prediction Accuracy of Molecular Modelling for M. jannaschii Tyrosyl-tRNA Synthetase Substrate Specificity
Authors: Duan Bingya , Sun Yingfei
Published: June 2020

Design of enzyme binding pocket to accommodate substrates with different chemical structure is a great challenge. Traditionally, thousands even millions of mutants have to be screened in wet-lab experiment to find a ligand-specific mutant and large amount of time and resources is consumed. To accelerate the screening process, here we propose a novel workflow through integration of molecular modeling and data-driven machine learning method to generate mutant libraries with high enrichment ratio for recognition of specific substrate. M. jannaschii tyrosyl-tRNA synthetase (Mj. TyrRS) is used as an example system to give a proof of concept since the sequence and structure of many unnatural amino acid specific Mj. TyrRS mutants have been reported. Based on the crystal structures of different Mj. TyrRS mutants and Rosetta modeling result, we find D158G/P is the critical residue which influences the backbone disruption of helix with residue 158-163. Our results show that compared with random mutation, Rosetta modeling and score function calculation can elevate the enrichment ratio of desired mutants by 2-fold in a test library having 687 mutants, while after calibration by machine learning model trained using known data of Mj. TyrRS mutants and ligand, the enrichment ratio can be elevated by 11-fold. This molecular modeling and machine learning-integrated workflow is anticipated to significantly benefit to the Mj. tyrRS mutant screening and substantially reduce the time and cost of web-lab experiment. Besides, this novel process will have broad application in the field of computational protein design.

CCS Concepts

• Applied computing • Life and medical sciences • Computational biology • Molecular structural biology
Host immunity alters successional ecology and stability of the microbiome in a C. elegans model
Authors: Taylor Megan , Vega NM
Published: June 2020

A growing body of data suggests that the microbiome of a species can vary considerably from individual to individual, but the reasons for this variation - and the consequences for the ecology of these communities – remain only partially explained. In mammals, the emerging picture is that the metabolic state and immune system status of the host affects the composition of the microbiome, but quantitative ecological microbiome studies are challenging to perform in higher organisms. Here we show that these phenomena can be quantitatively analyzed in the tractable nematode hostCaenorhabditis elegans. Mutants in innate immunity, in particular the DAF-2/Insulin Growth Factor (IGF) pathway, are shown to contain a microbiome that differs from that of wild type nematodes. We analyze the underlying basis of these differences from the perspective of community ecology by comparing experimental observations to the predictions of a neutral sampling model and conclude that fundamental differences in microbiome ecology underlie the observed differences in microbiome composition. We test this hypothesis by introducing a minor perturbation to the colonization conditions, allowing us to assess stability of communities in different host strains. Our results show that altering host immunity changes the importance of inter-species interactions within the microbiome, resulting in differences in community composition and stability that emerge from these differences in host-microbe ecology.

Importance

Here we use aCaenorhabditis elegansmicrobiome model to demonstrate how genetic differences in innate immunity alter microbiome composition, diversity, and stability by changing the ecological processes that shape these communities. These results provide insight into the role of host genetics in controlling the ecology of host-associated microbiota, resulting in differences in community composition, successional trajectories, and response to perturbation.
Pectin induced colony expansion of soil-derived Flavobacterium strains
Authors: Kraut-Cohen Judith , Shapiro Orr H. , Dror Barak , Cytryn Eddie
Published: June 2020

The genusFlavobacteriumis characterized by the capacity to metabolize complex organic compounds and a unique gliding motility mechanism. They are often abundant in root microbiomes of various plants, but the factors contributing to this high abundance are currently unknown. In this study, we evaluated the effect of various plant-associated poly- and mono-saccharides on colony expansion of twoFlavobacteriumstrains. Both strains were able to spread on pectin and other polysaccharides such as microcrystalline cellulose. However, only pectin (but not pectin monomers), a component of plant cell walls, enhanced colony expansion on solid surfaces in a dose- and substrate-dependent manner. On pectin, flavobacteria exhibited bi-phasic motility, with an initial phase of rapid expansion, followed by growth within the colonized area. Proteomic and gene expression analyses revealed significant induction of carbohydrate metabolism related proteins when flavobacteria were grown on pectin, including selected SusC/D, TonB-dependent glycan transport operons. Our results show a positive correlation between colony expansion and the upregulation of proteins involved in sugar uptake, suggesting an unknown linkage between specific operons encoding for glycan uptake and metabolism and flavobacterial expansion. Furthermore, within the context of flavobacterial-plant interactions, they suggest that pectin may facilitate flavobacterial expansion on plant surfaces in addition to serving as an essential carbon source.

Contribution to the field statement

Members of theFlavobacteriumgenus are frequently rhizosphere competent,i.e.abundant and generally enriched on root surfaces relative to surrounding bulk soil, and previous studies suggest that they may play a role in plant health and ecosystem functioning. However, little is known about genetic and physiological factors that facilitate flavobacterial colonization and proliferation in this highly competitive environment.

In this study we found that pectin stimulates flavobacterial colonies in a bi-phasic manner, initially characterized by rapid expansion on agar followed by increased biomass production. This appears to be linked to pectin-stimulated induction of specific TonB-associated proteins evidentially involved in the binding and uptake of complex sugars. Given the fact that pectin and other glycans are a primary component of plant cell walls, we hypothesize that these mechanisms are at least partially responsible for the rhizosphere competence of flavobacteria.
Prevalence of SARS-CoV-2 among workers returning to Bihar gives snapshot of COVID across India
Authors: Malani Anup , Mohanan Manoj , Kumar Chanchal , Kramer Jake , Tandel Vaidehi
Published: June 2020

India has reported the fourth highest number of confirmed SARS-CoV-2 cases worldwide. Because there is little community testing for COVID, this case count is likely an underestimate. When India partially exited from lockdown on May 4, 2020, millions of daily laborers left cities for their rural family homes. RNA testing on a near-random sample of laborers returning to the state of Bihar is used to estimate positive testing rate for COVID across India for a 6-week period immediately following the initial lifting of India’s lockdown. Positive testing rates among returning laborers are only moderately correlated with, and 21% higher than, Indian states’ official reports, which are not based on random sampling. Higher prevalence among returning laborers may also reflect greater COVID spread in crowded poor communities such as slums.
Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population
Authors: Klein Sabra L. , Pekosz Andrew , Park Han-Sol , Ursin Rebecca L. , Shapiro Janna R. , Benner Sarah E. , Littlefield Kirsten , Kumar Swetha , Naik Harnish Mukesh , Betenbaugh Michael J. , Shrestha Ruchee , Wu Annie A. , Hughes Robert M. , Burgess Imani , Caturegli Patricio , Laeyendecker Oliver , Quinn Thomas C. , Sullivan David , Shoham Shmuel , Redd Andrew D. , Bloch Evan M. , Casadevall Arturo , Tobian Aaron A.R.
Published: June 2020

Convalescent plasma is currently one of the leading treatments for COVID-19, but there is a paucity of data identifying therapeutic efficacy. A comprehensive analysis of the antibody responses in potential plasma donors and an understanding of the clinical and demographic factors that drive variant antibody responses is needed. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to Spike (S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain (S-RBD), and an IgG avidity assay. Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics. IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing titers. Using neutralization titer as the reference, the sensitivity of the IgG ELISAs ranged between 95-98%, but specificity was only 20-32%. Male sex, older age, and hospitalization with COVID-19 were all consistently associated with increased antibody responses across the serological assays. Neutralizing antibody titers were reduced over time in contrast to overall antibody responses. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody levels.

One Sentence Summary

There is substantial heterogeneity in the antibody response to SARS-CoV-2 infection, with greater antibody responses being associated with male sex, advancing age, and hospitalization with COVID-19.
Secondary pneumonia in critically ill ventilated patients with COVID-19
Authors: Maes Mailis , Higginson Ellen , Pereira-Dias Joana , Curran Martin , Parmar Surendra , Khokhar Fahad , Cuchet-Lourenço Delphine , Lux Janine , Sharma-Hajela Sapna , Ravenhill Benjamin , Mahroof Razeen , Solderholm Amelia , Forrest Sally , Sridhar Sushmita , Brown Nicholas , Baker Stephen , Navapurkar Vilas , Dougan Gordon , Scott Josefin Bartholdson , Conway Morris Andrew
Published: June 2020

Background

Pandemic COVID-19 caused by the coronavirus SARS-CoV-2 has a high incidence of patients with severe acute respiratory syndrome (SARS). Many of these patients require admission to an intensive care unit (ICU) for invasive artificial ventilation and are at significant risk of developing a secondary, ventilator-associated pneumonia (VAP).

Objectives

To study the incidence of VAP, as well as differences in secondary infections, and bacterial lung microbiome composition of ventilated COVID-19 and non-COVID-19 patients.

Methods

In this prospective observational study, we compared the incidence of VAP and secondary infections using a combination of a TaqMan multi-pathogen array and microbial culture. In addition, we determined the lung microbime composition using 16S RNA analyisis. The study involved eighteen COVID-19 and seven non-COVID-19 patients receiving invasive ventilation in three ICUs located in a single University teaching hospital between April 13th2020 and May 7th2020.

Results

We observed a higher percentage of confirmed VAP in COVID-19 patients. However, there was no statistical difference in the detected organisms or pulmonary microbiome when compared to non-COVID-19 patients.

Conclusion

COVID-19 makes people more susceptible to developing VAP, partly but not entirely due to the increased duration of ventilation. The pulmonary dysbiosis caused by COVID-19, and the array of secondary infections observed are similar to that seen in critically ill patients ventilated for other reasons.
Nowcasting the COVID–19 pandemic in Bavaria
Authors: Günther Felix , Bender Andreas , Katz Katharina , Küchenhoff Helmut , Höhle Michael
Published: June 2020

To assess the current dynamic of an epidemic it is central to collect information on the daily number of newly diseased cases. This is especially important in real-time surveillance, where the aim is to gain situational awareness, e.g., if cases are currently increasing or decreasing. Reporting delays between disease onset and case reporting hamper our ability to understand the dynamic of an epidemic close to now when looking at the number of daily reported cases only. Nowcasting can be used to adjust daily case counts for occurred-but-not-yet-reported events. Here, we present a novel application of nowcasting to data on the current COVID–19 pandemic in Bavaria. It is based on a hierarchical Bayesian model that considers changes in the reporting delay distribution over time and associated with the weekday of reporting. Furthermore, we present a way to estimate the effective time-dependent case reproduction number Re(t) based on predictions of the nowcast. The approaches are based on previously published work, that we considerably extended and adapted to the current task of nowcasting COVID–19 cases. We provide methodological details of the developed approach, illustrate results based on data of the current epidemic, and evaluate the model based on synthetic and retrospective data on COVID–19 in Bavaria. Results of our nowcasting are reported to the Bavarian health authority and published on a webpage on a daily basis (https://corona.stat.uni-muenchen.de/). Code and synthetic data for the analysis is available from https://github.com/FelixGuenther/nc_covid19_bavaria and can be used for adaptions of our approach to different data.
Time in treatment: Examining mental illness trajectories across inpatient psychiatric treatment
Authors: Oh Hyuntaek , Lee Jaehoon , Kim Seungman , Rufino Katrina A. , Fonagy Peter , Oldham John M. , Schanzer Bella , Patriquin Michelle A.
Published: June 2020

Early discharge or reduced length of stay for inpatient psychiatric patients is related to increased readmission rates and worse clinical outcomes including increased risk for suicide. Trajectories of mental illness outcomes have been identified as an important method for predicting the optimal length of stay but the distinguishing factors that separate trajectories remain unclear. We sought to identify the distinct classes of patients who demonstrated similar trajectories of mental illness over the course of inpatient treatment, and we explore the patient characteristics associated with these mental illness trajectories. We used data (N= 3,406) from an inpatient psychiatric hospital with intermediate lengths of stay. Using growth mixture modeling, latent mental illness scores were derived from six mental illness indicators: psychological flexibility, emotion regulation problems, anxiety, depression, suicidal ideation, and disability. The patients were grouped into three distinct trajectory classes: (1) High-Risk, Rapid Improvement (HR-RI); (2) Low-Risk, Gradual Improvement (LR-GI); and (3) High-Risk, Gradual Improvement (HR-GI). The HR-GI was significantly younger than the other two classes. The HR-GI had significantly more female patients than males, while the LR-GI had more male patients than females. Our findings indicated that younger females had more severe mental illness at admission and only gradual improvement during the inpatient treatment period, and they remained in treatment for longer lengths of stay, than older males.
The impact of SARS-CoV-2 transmission fear and COVID-19 pandemic on the mental health of patients with primary immunodeficiency disorders, severe asthma, and other high-risk groups
Authors: Çölkesen Fatih , Kılınçel Oğuzhan , Sözen Mehmet , Yıldız Eray , Beyaz Şengül , Çölkesen Fatma , Aytekin Gökhan , Koçak Mehmet Zahid , Alsancak Yakup , Araz Murat , Arslan Şevket
Published: June 2020

Background

The adverse effects of COVID-19 pandemic on the mental health of high-risk group patients for morbidity and mortality and its impact on public health in the long term have not been clearly determined.

Objective

To determine the level of COVID-19 related transmission fear and anxiety in healthcare workers and patients with primary immunodeficiency disorder (PID), severe asthma, and the ones with other comorbidities.

Methods

The healthcare workers and patients with PID, severe asthma (all patients receiving biological agent treatment), malignancy, cardiovascular disease, hypertension (90% of patients receiving ACEI or ARB therapy), diabetes mellitus (42 % of patients receiving DPP-4 inhibitor therapy) were included in the study. A total of 560 participants, 80 individuals in each group, were provided. The hospital anxiety and depression scale (HADS) and Fear of illness and virus evaluation (FIVE) scales were applied to the groups with face to face interview methods.

Results

The mean age was 49.30 ± 13.74 years and 306 (55 %) were female. The FIVE Scale and HADS-A scale scores of health care workers were significantly higher than other groups scores (p = 0.001 and 0.006). The second-highest scores belonged to patients with PID. There was no significant difference between the groups for the HADS-D score (p=0.07). The lowest score in all scales was observed in patients with hypertension.

Conclusions

This study demonstrated that in the pandemic process, patients with primary immunodeficiency, asthma patients, and other comorbid patients, especially healthcare workers, should be referred to the centers for the detection and treatment of mental health conditions.
The impact of the COVID-19 pandemic on quality of life, physical and psychosocial wellbeing in breast cancer patients and survivors – a prospective, multicenter cohort study
Authors: Bargon CA Claudia A , Batenburg Marilot CT , van Stam Lilianne E , van der Molen Dieuwke R Mink , van Dam Iris E , van der Leij Femke , Baas Inge O , Ernst Miranda F , Maarse Wiesje , Vermulst Nieke , Schoenmaeckers Ernst JP , van Dalen Thijs , Bijlsma Rhodé M , Young-Afat Danny A , Doeksen Annemiek , Verkooijen Helena M ,   UMBRELLA study group
Published: June 2020

Purpose

The COVID-19 pandemic and the resulting social distancing and lockdown measures are having a substantial impact on daily life and medical management of people with breast cancer. We evaluated to what extent these changes have affected quality of life and physical, and psychosocial wellbeing of people (being) treated for breast cancer.

Methods

This study was conducted within the prospective Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation (UMBRELLA). Shortly after the implementation of COVID-19 measures, extra questionnaires were sent to 1595 cohort participants, including standard UMBRELLA quality of life (EORTC) questionnaires. Patient-reported outcomes (PROs) were compared to the most recent PROs collected within UMBRELLA before COVID-19. The impact of COVID-19 on PROs was evaluated using mixed models analysis.

Results

In total, 1051 patients (66%) completed the questionnaires. One third (n = 327, 31%) reported a higher threshold to contact their general practitioner due to COVID-19. A significant deterioration in emotional functioning was observed (82·6 to 77·9, p < 0.001) and 505 (48%, 95% CI 45-51) patients reported moderate to severe loneliness. Small significant improvements were observed in QoL, physical-, social- and role functioning scores. In the subgroup of 51 patients under active treatment, there was a strong deterioration in social functioning (69·8 to 5·0, p = 0·03).

Conclusion

Due to COVID-19, patients (being) treated for breast cancer are less likely to contact physicians, and experience a deterioration in emotional functioning. Patients undergoing active treatment report a strong drop in social functioning. One in two patients reports (severe) loneliness. Online applications facilitating peer contact and e-mental health interventions could support mental health and social interaction times of total lockdown or social distancing.
Early identification of postpartum depression using demographic, clinical, and digital phenotyping
Authors: Hahn Lisa , Eickhoff Simon B. , Habel Ute , Stickeler Elmar , Schnakenberg Patricia , Goecke Tamme W. , Stickel Susanne , Franz Matthias , Dukart Juergen , Chechko Natalia
Published: June 2020

Background

Postpartum depression (PPD) and adjustment disorder (AD) affect up to 25% of women after childbirth. However, there are no accurate screening tools for either disorder to identify at-risk mothers and enable them to benefit from early intervention.

Aims

To evaluate combinations of anamnestic, clinical and remote assessments for an early and accurate identification of PPD and AD.

Method

Two cohorts of mothers giving birth were included in the study (N=308 and N=193). At baseline, participants underwent a detailed anamnestic and clinical interview. Remote assessments were collected over twelve weeks comprising mood and stress levels as well as depression and attachment scores. At twelve weeks postpartum, an experienced clinician assigned the participants to three distinct groups: women with PPD, women with AD, and healthy controls (HC). Combinations of these assessments were assessed for an early an accurate detection of PPD and AD in the first cohort and, after pre-registration, prospectively validated in the second cohort.

Results

Combinations of postnatal depression, attachment (for AD) and mood scores at week 3 achieved balanced accuracies of 93% and 79% for differentiation of PPD and AD from HC in the prospective validation cohort. Differentiation between AD and PPD, with a balanced accuracy of 73 % was possible at week 6 based on mood levels only.

Conclusions

Combinations of in clinic and remote self-assessments allowed for early and accurate detection of PPD and AD as early as three weeks postpartum, enabling early intervention to the benefit of both mothers and children.
Assessing the nationwide impact of COVID-19 mitigation policies on the transmission rate of SARS-CoV-2 in Brazil
Authors: Jorge Daniel C. P. , Rodrigues Moreno S. , Silva Mateus S. , Cardim Luciana L. , da Silva Nívea B. , Silveira Ismael H. , Silva Vivian A. F. , Pereira Felipe A. C. , de Azevedo Arthur R. , Amad Alan A. S. , Pinho Suani T.R. , Andrade Roberto F. S. , Ramos Pablo I. P. , Oliveira Juliane F.
Published: June 2020

COVID-19 is now identified in almost all countries in the world, with poorer regions being particularly more disadvantaged to efficiently mitigate the impacts of the pandemic. In the absence of efficient therapeutics or vaccines, control strategies are currently based on non-pharmaceutical interventions, comprising changes in population behavior and governmental interventions, among which the prohibition of mass gatherings, closure of non-essential establishments, quarantine and movement restrictions. In this work we analyzed the effects of 707 published governmental interventions, and population adherence thereof, on the dynamics of COVID-19 cases across all 27 Brazilian states, with emphasis on state capitals and remaining inland cities. A generalized SEIR (Susceptible, Exposed, Infected and Removed) model with a time-varying transmission rate (TR), that considers transmission by asymptomatic individuals, is presented. We analyze the effect of both the extent of enforced measures across Brazilian states and population movement on the changes in the TR and effective reproduction number. The social mobility reduction index, a measure of population movement, together with the stringency index, adapted to incorporate the degree of restrictions imposed by governmental regulations, were used in conjunction to quantify and compare the effects of varying degrees of policy strictness across Brazilian states. Our results show that population adherence to social distance recommendations plays an important role for the effectiveness of interventions and represents a major challenge to the control of COVID-19 in low- and middle-income countries.