bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanofibrous cosmetic face mask for transdermal delivery of nano gold: synthesis, characterization, release and zebra fish employed toxicity studies
Authors: Manatunga D. C. , Godakanda V. U. , Herath H. M. L. P. B. , de Silva Rohini M. , Yeh Chen-Yu , Chen Jiann-Yeu , Akshitha de Silva A. A. , Rajapaksha S. , Nilmini Renuka , Nalin de Silva K. M.
Published: September 2020

This study involves the generation of gold nanoparticles (Au NPs) via a novel natural/non-toxic methodology using tea and orange-peel extracts. These were then embedded into a novel blend composed of a polyethylene oxide and gelatin (PEO-Gel) fibre mat. The scanning electron microscopy results indicated that the addition of both collagen (COL) and ascorbic acid (AA) into the PEO-Gel system (PEO-Gel-AA-COL system) enhances the Au NP incorporation into nanofibres leading to a diameter of 164.60 ± 20.95 and 192.43 ± 39.14 nm in contrast to the spraying observed with the Au PEO-Gel system alone. Releasing studies conducted over 30 min indicated that the PEO-Gel-AA-COL-orange peel Au (OpAu) system accounts for a higher content of Au release than the green tea Au (GtAu) NP system where a maximum release could be attained within 10–30 min depending on the amount of Au NPs that have been incorporated. Moreover, the transdermal diffusion studies conducted using Strat membrane indicated that Au NPs from both formulations (PEO-Gel-AA-COL-GtAu nanofibre, PEO-Gel-AA-COL-OpAu nanofibre) have diffused through the stratum corneum and trapped in the dermis and epidermis indicating its transdermal deliverability. Additionally, 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay revealed that nanofibres have similar radical scavenging activity like AA standard. Toxicity evaluation on a zebra fish embryo model confirmed that both GtAu NPs and OpAu NPs do not induce any teratogenic activity and are safe to be used in the range of 1.0–167 µg ml
−1
.
Identification of putative viroplasms within banana cells infected by banana streak MY virus
Authors: Ngo Thu Ha , Webb Richard , Crew Kathleen S. , Vance Megan E. , Thomas John E. , Geering Andrew D. W.
Published: October 2020

The badnavirus replication cycle is poorly understood and most knowledge is based on extrapolations from model viruses such as Cauliflower mosaic virus (CaMV). However, in contrast to CaMV, badnaviruses are thought not to produce viroplasms and therefore it has been a mystery as to where virion assembly occurs. In this study, ultrathin sections of a banana leaf infected with a badnavirus, banana streak MY virus (BSMYV), were examined by transmission electron microscopy. Electron-dense inclusion bodies (EDIBs) were sporadically distributed in parenchymatous tissues of the leaf, most commonly in the palisade and spongy mesophyll cells. These EDIBs had a characteristic structure, comprising an electron-dense core, a single, encircling lacuna and an outer ring of electron-dense material. However, much less frequently, EDIBs with two or three lacunae were observed. In the outer ring, densely packed virions were visible with a shape and size consistent with that expected for badnaviruses. Immunogold labelling was done with primary antibodies that detected the N-terminus of the capsid protein and strong labelling of the outer ring but not the central core or lacuna was observed. It is concluded that the EDIBs that were observed are equivalent in function to the viroplasms of CaMV, although obviously different in composition as there is not a paralogue of the transactivation/viroplasm protein in the badnavirus genome. It is postulated that production of a viroplasm could be a conserved characteristic of all members of the Caulimoviridae.
Inference of malaria transmission dynamics under varying assumptions about the spatial scale of transmission: a modelling study in three elimination settings
Authors: Routledge Isobel , Bhatt Samir
Published: September 2020

Background

Individual-level geographic information about malaria cases, such as the GPS coordinates of residence or health facility, is often collected as part of surveillance in near-elimination settings, but could be more effectively utilised to infer transmission dynamics, in conjunction with additional information such as symptom onset time and genetic distance. However, in the absence of data about the flow of parasites between populations, the spatial scale of malaria transmission is often not clear. As a result, it is important to understand the impact of varying assumptions about the spatial scale of transmission on key metrics of malaria transmission, such as reproduction numbers.

Methods

We developed a method which allows the flexible integration of distance metrics (such as Euclidian distance, genetic distance or accessibility matrices) with temporal information into a single inference framework to infer malaria reproduction numbers. Twelve scenarios were defined, representing different assumptions about the likelihood of transmission occurring over different geographic distances and likelihood of missing infections (as well as high and low amounts of uncertainty in this estimate). These scenarios were applied to four individual level datasets from malaria eliminating contexts to estimate individual reproduction numbers and how they varied over space and time.

Results

Model comparison suggested that including spatial information improved models as measured by ΔAICc, compared to time only results. Across scenarios and across datasets, including spatial information tended to increase the seasonality of temporal patterns in reproduction numbers and reduced noise in the temporal distribution of reproduction numbers. The best performing parameterisations assumed long-range transmission (>200km) was possible.

Conclusions

Our approach is flexible and provides the potential to incorporate other sources of information which can be converted into distance or adjacency matrices such as travel times or molecular markers.
Inhibition of SHP2 ameliorates psoriasis by decreasing TLR7 endosome localization
Authors: Zhu Yuyu , Shao Fenli , Yan Wei , Chen Zhen Bouman , Ke Bowen , Jiang Xian , Cheng Haibo , Sun Dongdong , Song Chenglin , Kong Lingdong , Guo Wenjie , Lai Yuping , Feng Gen-Sheng , Xu Qiang , Sun Yang
Published: October 2020

Psoriasis is a complex chronic inflammatory skin disease with unclear molecular mechanisms. Here, we identify Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) as a novel accelerator of psoriasis development. Both genetic ablation of SHP2 in macrophages and pharmacological inhibition of SHP2 prevents the development of psoriasis-like skin inflammation in an imiquimod-induced murine model of psoriasis. Mechanistically, SHP2 promotes the trafficking of Toll-like receptor 7 (TLR7) from Golgi to endosome through its interaction with and dephosphorylation of TLR7 at Tyr1024, which promotes the ubiquitination of TLR7 and psoriasis-like skin inflammation. Importantly, SHP2 allosteric inhibitor SHP099 reduces the expression of pro-inflammatory cytokines in peripheral blood mononuclear cells from human patients with psoriasis. Collectively, our findings identify SHP2 as a novel regulator of psoriasis and suggest that SHP2 inhibition may be a promising therapeutic approach for psoriatic patients.
Impact of visual impairment on balance and visual processing functions in students with special educational needs
Authors: Choi KY , Wong HY , Cheung HN , Tseng JK , Chen CC , Wu CL , Eng H , Woo GC , Cheong AMY
Published: October 2020

Introduction

Vision is a critical factor for children’s development. However, prevalence of visual impairment (VI) is high in students with special educational needs (SEN). Other than vision disability, this group of students is prone to having functional deficits. It is unclear whether visual problems relate to these compromised functional deficits. This study aimed to assess the impact of vision on visual processing functions and balance performance in SEN students through a community service in special schools.

Methods

A total of 104 (chronological age 14.3 ± 4.3 years, 43 females) SEN students in Taiwan were assessed and classified as having normal vision (NV) or vision impairment (VI). Visual acuity (distance and near) and contrast sensitivity (CS) were measured as the visual outcomes. Visual processing function assessment included facial expression recognition by Heidi expression test, in terms of card matching (FEC), and examiner’s facial expression matching (FEE), and visual orientation recognition (by mailbox game, VO). Dynamic balance was assessed with Timed Up and Go (TUG) test, while static standing balance was assessed using a force plate to measure the postural sway in double-legged feet-together and tandem stance with eyes open and closed conditions. Static balance was presented in terms of the change in the centre of pressure in maximal medial-lateral (ML) and antero-posterior (AP) sways, sway variability (V), and sway path length (L).

Results

Although visual acuity was significantly worse in VI than NV (p < 0.001), CS was similar in the two groups (p = 0.08). VO, FEC, and FEE also did not differ significantly between groups (p > 0.05). NV performed better in the TUG than VI (p = 0.03). There was a significant interaction between eye condition and the vision group (p < 0.05) for static balance. Pairwise comparisons showed that NV swayed significantly less in ML than VI under tandem stance-open eye condition (p = 0.04), but significantly more in closed eye condition (p = 0.03). Conversely, VI had less V and shorter L than NV under tandem stance-closed eye condition (p = 0.03).

Conclusion

This study is the first to our knowledge to examine the effect of vision on visual processing functions and balance performance in SEN students. Vision did not appear to be the major reason for impairment in visual processing. However, vision plays an important role in maintaining dynamic and static balance in SEN students.
The potential contribution of face coverings to the control of SARS-CoV-2 transmission in schools and broader society in the UK: a modelling study
Authors: Panovska-Griffiths J. , Kerr C.C. , Waites W. , Stuart R.M. , Mistry D. , Foster D. , Klein D.J. , Viner R.M. , Bonell C.
Published: September 2020

Recent findings suggest that an adequate test-trace-isolate (TTI) strategy is needed to prevent a secondary COVID-19 wave with the reopening of society in the UK. Here we assess the potential importance of mandatory masks in the parts of community and in secondary schools. We show that, assuming current TTI levels, adoption of masks in secondary schools in addition to community settings can reduce the size of a second wave, but will not prevent it; more testing of symptomatic people, tracing and isolating of their contacts is also needed. To avoid a second wave, with masks mandatory in secondary schools and in certain community settings, under current tracing levels, 68% or 46% of those with symptomatic infection would need to be tested if masks’ effective coverage were 15% or 30% respectively, compared to 76% and 57% if masks are mandated in community settings but not secondary schools.
Conditional Generative Adversarial Networks for Individualized Treatment Effect Estimation and Treatment Selection
Authors: Ge Qiyang , Huang Xuelin , Fang Shenying , Guo Shicheng , Liu Yuanyuan , Lin Wei , Xiong Momiao
Published: September 2020

Treatment response is heterogeneous. However the classical methods treat the treatment response as homogeneous and estimate the average treatment effects. The traditional methods are difficult to apply to precision oncology. The artificial intelligence (AI) is a powerful tool for precision oncology. It can accurately estimate the individualized treatment effects and learn optimal treatment choices. Therefore, the AI approach can substantially improve progress and treatment outcomes of patients. As one of AI approach, conditional generative adversarial nets for inference of individualized treatment effects (GANITE) have been developed. However, the GANITE can only deal with binary treatment and does not provide a tool for optimal treatment selection. To overcome these limitations, we modify conditional generative adversarial networks (MCGANs) to allow estimation of individualized effects of any types of treatments including binary, categorical and continuous treatments. We propose to use sparse techniques for selection of biomarkers that predict the best treatment for each patient. Simulations show that the CGANs outperform seven other state-of-the-art methods: linear regression (LR), Bayesian linear ridge regression (BLR), KNN, random forest classification (RF (C)), random forest regression (RF (R)), logistic regression (LogR) and support vector machine (SVM). To illustrate their applications, the proposed CGANs were applied to 256 patients with newly diagnosed acute myeloid leukemia (AML) who were treated with high dose ara-C (HDAC), Idarubicin (IDA) and both of these two treatments (HDAC+IDA) at M. D. Anderson Cancer Center. Our results showed that the MCGAN can more accurately and robustly estimate the individualized treatment effects than other state-of-the art methods. Several biomarkers such as GSK3, BILIRUBIN, SMAC are identified and a total of 30 biomarkers can explain 36.8% of treatment effect variation.
Parameters for assessment of talar neck geometry: a protocol for scoping literature review
Authors: Sharma Siddhartha , Jindal Karan , Patel Sandeep , Prabhakar Sharad , Dhillon Mandeep S.
Published: September 2020

Background

Understanding the three-dimensional anatomy of the talar neck is essential in assessing reduction of talar neck fractures, as well as in planning surgical correction for talar malunions. However, the geometrical parameters that describe this anatomy are sparsely reported in the literature.

Objectives

This review aims to identify from the existing literature, those geometrical parameters that describe the three-dimensional anatomy of the talar neck.

Methods

A scoping literature review will be conducted in accordance with the PRISMA-ScR guidelines. The primary searches will be conducted on the PubMed, EMBASE and Scopus databases, using a pre-defined search strategy. Any original research study (whether clinical or cadaveric, prospective or retrospective, comparative or noncomparative), looking at the human talus neck geometry or morphology will be included. Studies that do not describe the talar neck geometry, animal studies, review articles, conference abstracts and case reports will be excluded. Geometrical parameters (including techniques to measure these) that describe the three-dimensional anatomy of the talar neck will be identified. Qualitative analysis will be done by means of appropriate tables and diagrams. If feasible, quantitative analysis to determine pooled estimated of geometrical parameters identified in the review will be conducted by a random-effects meta-analysis model. No formal risk-of-bias assessment has been planned, as this is a scoping literature review.
Comparative transcriptomics and host-specific parasite gene expression profiles inform on drivers of proliferative kidney disease
Authors: Faber Marc , Yoon Sohye , Shaw Sophie , de Paiva Alves Eduardo , Wang Bei , Qi Zhitao , Okamura Beth , Hartikainen Hanna , Secombes Christopher J. , Holland Jason W.
Published: September 2020

The myxozoan parasite,Tetracapsuloides bryosalmonaehas a two-host life cycle alternating between freshwater bryozoans and salmonid fish. Infected fish can develop Proliferative Kidney Disease (PKD), characterised by a gross lymphoid-driven kidney pathology in wild and farmed salmonids. To facilitate an in-depth understanding ofT. bryosalmonae-host interactions, we have adopted a two-host parasite transcriptome sequencing approach to minimize host contamination in the absence of a completeT. bryosalmonaegenome. Parasite contigs common to both infected hosts (the intersect transcriptome; 7,362 contigs) were typically AT-rich (60-75% AT). 5,432 contigs within the intersect were annotated with 1,930 unannotatde contigs encoding for unknown transcripts. We have focused on transcripts encoding proteins involved in; nutrient acquisition, host-parasite interactions, development, and cell-to-cell communication or proteins of unknown function, establishing their potential importance in each host by RT-qPCR. Host-specific expression profiles were evident, particularly in transcripts encoding proteases and proteins involved in lipid metabolism, cell adhesion, and development. We confirm for the first time the presence of homeobox proteins and a frizzled homologue in myxozoan parasites.

The novel insights into myxozoan biology that this study reveals will help to focus research in developing future disease control strategies.
Temporal emergence of age-associated changes in cognitive and physical function in vervets (Chlorocebus aethiops sabaeus)
Authors: Frye Brett M. , Valure Payton M. , Craft Suzanne , Baxter Mark G. , Scott Christie , Wise-Walden Shanna , Bissinger David , Register Hannah M. , Copeland Carson , Jorgensen Matthew J. , Justice Jamie N. , Kritchevsky Stephen B. , Register Thomas C. , Shively Carol A.
Published: September 2020

Dual declines in gait speed and cognitive performance are associated with increased risk of developing dementia. Characterizing the patterns of such impairments therefore is paramount to distinguishing healthy from pathological aging. Nonhuman primates such as vervet/African green monkeys (Chlorocebus aethiops sabaeus) are important models of human neurocognitive aging, yet the trajectory of dual decline has not been characterized. We therefore 1) assessed whether cognitive and physical performance (i.e., gait speed) are lower in older aged animals; 2) explored the relationship between performance in a novel task of executive function (Wake Forest Maze Task – WFMT) and a well-established assessment of working memory (Delayed Response Task – DR Task); and 3) examined the association between baseline gait speed with executive function and working memory at one-year follow-up. We found 1) physical and cognitive declines with age; 2) strong agreement between performance in the novel WFMT and DR task; and 3) that slow gait predicted poor cognitive performance in both domains. Our results suggest that older-aged vervets exhibit a coordinated suite of traits consistent with human aging and that slow gait may be a risk factor for cognitive decline. This integrative approach provides evidence that gait speed and cognitive function differ across the lifespan in female vervet monkeys, which advances them as a model that could be used to evaluate the trajectory of dual decline over time.
On-site eDNA detection of species using ultra-rapid mobile PCR
Authors: Doi Hideyuki , Watanabe Takeshi , Nishizawa Naofumi , Saito Tatsuya , Nagata Hisao , Kameda Yuichi , Maki Nobutaka , Ikeda Kousuke , Fukuzawa Takashi
Published: September 2020

Molecular methods, including environmental DNA (eDNA) methods, provide essential information for biological and conservation sciences. Molecular measurements are often performed in the laboratory, which limits their scope, especially for rapid on-site analysis. eDNA methods for species detection provide essential information for the management and conservation of species and communities in various environments. We developed an innovative novel method for on-site eDNA measurements using an ultra-rapid mobile PCR platform. We tested the ability of our method to detect the distribution of silver carp, Hypophthalmichthys molitrix, an invasive fish in Japanese rivers and lakes. Our method reduced the measurement time to 30 min and provided high detectability of aquatic organisms compared to the national observation surveys using multiple fishing nets and laboratory extraction/detection using a benchtop qPCR platform. Our on-site eDNA method can be immediately applied to various taxa and environments.
Making sense of the linear genome, gene function and TADs
Authors: Long Helen S , Greenaway Simon , Powell George , Mallon Ann-Marie , Lindgren Cecilia M , Simon Michelle M
Published: October 2020

Background

Topologically associating domains (TADs) are thought to act as functional units in the genome. TADs co-localise genes and their regulatory elements as well as forming the unit of genome switching between active and inactive compartments. This has led to the speculation that genes which are required for similar processes may fall within the same TADs, allowing them to share regulatory programs and efficiently switch between chromatin compartments. However, evidence to link genes within TADs to the same regulatory program is limited.

Results

We investigated the functional similarity of genes which fall within the same TAD. To do this we developed a TAD randomisation algorithm to generate sets of “random TADs” to act as null distributions. We found that while pairs of paralogous genes are enriched in TADs overall, they are depleted in TADs with CCCTC-binding factor (CTCF) ChIP-seq peaks at both boundaries. By assessing gene constraint as a proxy for functional importance we found that genes which singly occupy a TAD have greater functional importance than genes which share a TAD, and these genes are enriched for developmental processes. We found little evidence that pairs of genes in CTCF bound TADs are more likely to be co-expressed or share functional annotations than can be explained by their linear proximity alone.

Conclusions

These results suggest that algorithmically defined TADs consist of two functionally different groups, those which are bound by CTCF and those which are not. We detected no association between genes sharing the same CTCF TADs and increased co- expression or functional similarity, other than that explained by linear genome proximity. We do however find that functionally important genes are more likely to fall within a TAD on their own suggesting that TADs play an important role in the insulation of these genes.
Dincta: Data Integration and Cell Type Annotation of Single Cell Transcriptomes
Authors: Shi Songting
Published: October 2020

Abstract

We proposed a method for data integration and cell type annotation (Dincta) of single cell transcriptomes in a unify framework. The Dincta can handle three cases. In the first case, the data has been annotated the cell type for all cells, Dincta can integrate the the data into a common low dimension embedding space such that cells with different cell types separate while cells from the different batches but in the same cell type cluster together. In the second case, the data was only annotated for part of cells, such as one sample, Dincta can integrate the data into a common low dimension embedding space such that cells with different cell types separate while cells from the different batches but in the same cell type cluster together. Moreover, it can infer the known or novel cell type of the cells with unknown cell type initially. In the third case, there are no cell type information of cells, we can run Dincta in an unsupervised way. It can infer the number of new cell types and annotate the cells into its correspond cell type, and do data integration keeping cells from different cell type separate while removing the batch effects to mix cells in the same cell type. Dincta is simple, accurate and efficient to integrate data, which keeps the cell type information preserved while removes the batch effects, and infers the known or novel cell types of cells.
Fibrous caps in atherosclerosis form by Notch-dependent mechanisms common to arterial media development
Authors: Martos Carlos J. , Albarrán-Juárez Julián , Morales-Cano Daniel , Caballero Ainoa , MacGrogan Donal , de la Pompa José Luis , Carramolino Laura , Bentzon Jacob F.
Published: September 2020

Rationale

The rupture of the fibrous cap in atherosclerotic lesions is the underlying cause of most thrombi leading to heart attack and a frequent cause of stroke. Caps are produced by smooth muscle cells (SMCs) that are recruited to the subendothelial space. We hypothesized that the recruitment mechanisms are likely common to embryonic artery development, which relies prominently on Notch signaling to form the subendothelial layers of medial SMCs.

Objective

To analyze the causal roles of the Notch signaling pathway in SMCs for atherogenesis and cap formation.

Methods and Results

Notch elements involved in arterial media development were found expressed in regions of fibrous cap in mouse plaques. To assess the causal role of Notch signaling in cap formation, we studied atherosclerosis in mice in which the Notch pathway was inactivated specifically in SMCs by conditional knockout of the essential effector transcription factor RBPJ. No major effects were observed on plaque size, but the presence of cap SMCs was significantly reduced. Lineage tracing revealed that the accumulation of SMC-derived plaque cells in the cap region was unaltered but that Notch-defective cells failed to re-acquire the SMC phenotype in the cap. To analyze whether the accumulation of SMC-derived cells in atherogenesis requires down-regulation of Notch signaling, we studied atherosclerosis in mice with constitutive Notch signaling in SMCs achieved by conditional expression of the Notch intracellular domain. Forced Notch signaling inhibited the ability of medial SMCs to contribute to plaque cells, including both cap SMCs and osteochondrogenic cells, and significantly reduced atherosclerosis development.

Conclusions

Sequential loss and gain of Notch signaling is needed to build the cap SMC population. The shared mechanisms with embryonic arterial media assembly suggest that the fibrous cap forms as aneo-mediathat restores the connection between endothelium and stabilizing SMCs, which is transiently disrupted by atherogenesis.
Brain Connectivity and Behavioral Changes in a Spaceflight Analog Environment with Elevated CO2
Authors: McGregor Heather R. , Lee Jessica K. , Mulder Edwin R. , De Dios Yiri E. , Beltran Nichole E. , Kofman Igor S. , Bloomberg Jacob J. , Mulavara Ajitkumar P. , Seidler Rachael D.
Published: October 2020

Astronauts are exposed to microgravity and elevated CO2levels onboard the International Space Station. Little is known about how microgravity and elevated CO2combine to affect the brain and sensorimotor performance during and after spaceflight. Here we examined changes in resting-state functional connectivity (FC) and sensorimotor behavior associated with a spaceflight analog environment. Participants underwent 30 days of strict 6°head-down tilt bed rest with elevated ambient CO2(HDBR+CO2). Resting-state functional magnetic resonance imaging and sensorimotor assessments were collected 13 and 7 days prior to bed rest, on days 7 and 29 of bed rest, and 0, 5, 12, and 13 days following bed rest. We assessed the time course of FC changes from before, during, to after HDBR+CO2. We then compared the observed connectivity changes with those of a HDBR control group, which underwent HDBR in standard ambient air. Moreover, we assessed associations between post-HDBR+CO2FC changes and alterations in sensorimotor performance. HDBR+CO2was associated with significant changes in functional connectivity between vestibular, visual, somatosensory and motor brain areas. Several of these sensory and motor regions showed post-HDBR+CO2FC changes that were significantly associated with alterations in sensorimotor performance. We propose that these FC changes reflect multisensory reweighting associated with adaptation to the HDBR+CO2microgravity analog environment. This knowledge will further improve HDBR as a model of microgravity exposure and contribute to our knowledge of brain and performance changes during and after spaceflight.
Understanding the genetic diversity of the guayabillo (Psidium galapageium), an endemic plant of the Galapagos Islands
Authors: Urquia Diego , Pozo Gabriela , Gutierrez Bernardo , Rowntree Jennifer K. , de Lourdes Torres Maria
Published: September 2020

Oceanic archipelagos are known to host a variety of endemic plant species. The genetic diversity and structure of these species is an important indicator of their evolutionary history and can inform appropriate conservation strategies that mitigate the risks to which they’re exposed, including invasive species and environmental disturbances. A comprehensive consideration of the role of their natural history, as well as the landscape features and the geological history of the islands themselves is required to adequately understand any emerging patterns. Such is the case for the guayabillo (Psidium galapageium), an understudied endemic plant from the Galapagos Islands with important ecological and economic roles. In this study we designed and evaluated 13 informative SSR markers and used them to investigate the genetic diversity, population structure and connectivity of the guayabillo populations from San Cristobal, Isabela and Santa Cruz islands. A total of 208 guayabillo individuals were analyzed, revealing a strong population structure between islands and two distinct genetic lineages for the Santa Cruz population. Overall, the guayabillo genetic diversity is relatively high, an unusual pattern for an insular endemic species which is possibly explained by its polyploidy and the geographical features of the islands. These include their broad altitudinal ranges and habitat heterogeneity. For populations displaying a lower genetic diversity such as San Cristobal, the history of human disturbance could be an important factor explaining these observations. Some similarities between individuals in Santa Cruz and the San Cristobal population could be explained by population differentiation or distinct natural histories of separate lineages. Our findings highlight the complex population dynamics that shape the genetic diversity of species like the guayabillo and emphasize the need to explore the currently unresolved questions about this Galapagos endemic plant.
Maximum Parsimony Inference of Phylogenetic Networks in the Presence of Polyploid Complexes
Authors: Yan Zhi , Cao Zhen , Liu Yushu , Nakhleh Luay
Published: September 2020

Phylogenetic networks provide a powerful framework for modeling and analyzing reticulate evolutionary histories. While polyploidy has been shown to be prevalent not only in plants but also in other groups of eukaryotic species, most work done thus far on phylogenetic network inference assumes diploid hybridization. These inference methods have been applied, with varying degrees of success, to data sets with polyploid species, even though polyploidy violates the mathematical assumptions underlying these methods. Statistical methods were developed recently for handling specific types of polyploids and so were parsimony methods that could handle polyploidy more generally yet while excluding processes such as incomplete lineage sorting. In this paper, we introduce a new method for inferring most parsimonious phylogenetic networks on data that include polyploid species. Taking gene trees as input, the method seeks a phylogenetic network that minimizes deep coalescences while accounting for polyploidy. The method could also infer trees, thus potentially distinguishing between auto- and allo-polyploidy. We demonstrate the performance of the method on both simulated and biological data. The inference method as well as a method for evaluating given phylogenetic networks are implemented and publicly available in the PhyloNet software package.
SARS-CoV-2 D614G Variant Exhibits Enhanced Replicationex vivoand Earlier Transmissionin vivo
Authors: Hou Yixuan J. , Chiba Shiho , Halfmann Peter , Ehre Camille , Kuroda Makoto , Dinnon Kenneth H , Leist Sarah R. , Schäfer Alexandra , Nakajima Noriko , Takahashi Kenta , Lee Rhianna E. , Mascenik Teresa M. , Edwards Caitlin E. , Tse Longping V. , Boucher Richard C. , Randell Scott H. , Suzuki Tadaki , Gralinski Lisa E. , Kawaoka Yoshihiro , Baric Ralph S.
Published: September 2020

The D614G substitution in the S protein is most prevalent SARS-CoV-2 strain circulating globally, but its effects in viral pathogenesis and transmission remain unclear. We engineered SARS-CoV-2 variants harboring the D614G substitution with or without nanoluciferase. The D614G variant replicates more efficiency in primary human proximal airway epithelial cells and is more fit than wildtype (WT) virus in competition studies. With similar morphology to the WT virion, the D614G virus is also more sensitive to SARS-CoV-2 neutralizing antibodies. Infection of human ACE2 transgenic mice and Syrian hamsters with the WT or D614G viruses produced similar titers in respiratory tissue and pulmonary disease. However, the D614G variant exhibited significantly faster droplet transmission between hamsters than the WT virus, early after infection. Our study demonstrated the SARS-CoV2 D614G substitution enhances infectivity, replication fitness, and early transmission.
A synthetic small molecule stalls pre-mRNA splicing by promoting an early-stage U2AF2–RNA complex
Authors: Chatrikhi Rakesh , Feeney Callen F. , Pulvino Mary J. , Alachouzos Georgios , MacRae Andrew J. , Falls Zackary , Rai Sumit , Brennessel William W. , Jenkins Jermaine L. , Walter Matthew J. , Graubert Timothy A. , Samudrala Ram , Jurica Melissa S. , Frontier Alison J. , Kielkopf Clara L.
Published: September 2020

Dysregulated pre-mRNA splicing is an emerging Achilles heel of cancers and myelodysplasias. To expand the currently limited portfolio of small molecule drug leads, we screened for chemical modulators of the U2AF complex, which nucleates spliceosome assembly and is mutated in myelodysplasias. A hit compound specifically enhances RNA binding by a U2AF2 subunit. Remarkably, the compound inhibits splicing of representative substrates in cells and stalls spliceosome assembly at the stage of U2AF function. Computational docking, together with structure-guided mutagenesis, indicates that the compound bridges an active conformation of the U2AF2 RNA recognition motifsviahydrophobic and electrostatic moieties. Altogether, our results highlight the potential of trapping early spliceosome assembly as an effective pharmacological means to manipulate pre-mRNA splicing. By extension, we suggest that stabilizing inactive checkpoints may offer a breakthrough approach for small molecule inhibition of multi-stage macromolecular assemblies.
Global Analysis of the Mammalian MHC class I Immunopeptidome at the Organism-Wide Scale
Authors: Kubiniok Peter , Marcu Ana , Bichmann Leon , Kuchenbecker Leon , Schuster Heiko , Hamelin David , Despault Jérome , Kovalchik Kevin , Wessling Laura , Kohlbacher Oliver , Stevanovic Stefan , Rammensee Hans-Georg , Neidert Marian C. , Sirois Isabelle , Caron Etienne
Published: September 2020

Understanding the molecular principles that govern the composition of the mammalian MHC-I immunopeptidome (MHC-Ii) across different primary tissues is fundamentally important to predict how T cell respond in different contextsin vivo. Here, we performed a global analysis of the mammalian MHC-Ii from 29 and 19 primary human and mouse tissues, respectively. First, we observed that different HLA-A, -B and -C allotypes do not contribute evenly to the global composition of the MHC-Ii across multiple human tissues. Second, we found that peptides that are presented in a tissue-dependent and -independent manner share very distinct properties. Third, we discovered that proteins that are evolutionarily hyperconserved represent the primary source of the MHC-Ii at the organism-wide scale. Finally, we uncovered new components of the antigen processing and presentation network that may drive the high level of heterogeneity of the MHC-Ii across different tissues in mammals. This study opens up new avenues toward a system-wide understanding of antigen presentationin vivoand may serve as ground work to understand tissue-dependent T cell responses in autoimmunity, infectious diseases and cancer.
Discovery of genomic loci associated with sleep apnoea risk through multi-trait GWAS analysis with snoring
Authors: Campos Adrian I. , Ingold Nathan , Huang Yunru , Mitchell Brittany L. , Kho Pik-Fang , Han Xikun , García-Marín Luis M. , Ong Jue-Sheng ,   23andMe Research Team, Law Matthew H. , Yokoyama Jennifer S. , Martin Nicholas G. , Dong Xianjun , Cuellar-Partida Gabriel , MacGregor Stuart , Aslibekyan Stella , Rentería Miguel E.
Published: October 2020

Background

Sleep apnoea is characterised by periods of halted breathing during sleep. Despite its association with severe health conditions, the aetiology of sleep apnoea remains understudied, and previous genetic analyses have not identified many robustly associated genetic risk variants.

Methods

We performed a genome-wide association study (GWAS) meta-analysis of sleep apnoea across five cohorts (NTotal=523,366), followed by a multi-trait analysis of GWAS (MTAG) to boost power, leveraging the high genetic correlation between sleep apnoea and snoring. We then adjusted our results for the genetic effects of body mass index (BMI) using multi-trait-based conditional & joint analysis (mtCOJO) and sought replication of lead hits in a large cohort of participants from 23andMe, Inc (NTotal=1,477,352; Ncases=175,522). We also explored genetic correlations with other complex traits and performed a phenome-wide screen for causally associated phenotypes using the latent causal variable method.

Results

Our MTAG analysis uncovered 49 significant independent loci associated with sleep apnoea risk. Twenty-nine variants were replicated in the 23andMe cohort. We observed genetic correlations with several complex traits, including multisite chronic pain, diabetes, eye disorders, high blood pressure, osteoarthritis, chronic obstructive pulmonary disease, and BMI-associated conditions.

Conclusions

Our study uncovered multiple genetic loci associated with sleep apnoea risk, thus increasing our understanding of the aetiology of this condition and its relationship with other complex traits.
Neuroanatomical Considerations for Optimizing Thalamic Deep Brain Stimulation in Tourette Syndrome
Authors: Morishita Takashi , Sakai Yuki , Iida Hitoshi , Yoshimura Saki , Ishii Atsushi , Fujioka Shinsuke , Tanaka Saori C. , Inoue Tooru
Published: October 2020

Background

Deep brain stimulation (DBS) of the centromedian (CM) thalamic nucleus has reportedly been used to treat severe Tourette syndrome (TS) with promising outcomes; however, it remains unclear how DBS electrode position and stimulation parameters modulate the specific area and related networks. We aimed to evaluate the relationships between the anatomical location of stimulation fields and clinical responses including therapeutic and side effects.

Methods

We collected data from eight TS patients treated with DBS. We evaluated the clinical outcomes using Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and Hamilton Depression Rating Scale (HAM-D). The DBS lead location was evaluated in the normalised brain space using a 3-D atlas. The volume of tissue activated (VTA) was determined, and the associated normative connective analyses were performed to link the stimulation field with the therapeutic and side effects.

Results

The mean follow-up period was 10.9 ± 3.9 months. All clinical scale showed significant significant improvement. While the VTA associated with therapeutic effects covers the CM and ventrolateral nuclei and showed association with motor networks, those associated with paraesthesia and dizziness were associated with stimulation of the ventralis caudalis and red nucleus, respectively. Depressed mood was associated with the spread of stimulation current to the mediodorsal nucleus and showed association with limbic networks.

Conclusion

Our study addresses the importance of accurate implantation of DBS electrodes for obtaining standardised clinical outcomes and suggests that meticulous programming with careful monitoring of clinical symptoms may improve outcomes.
Seroprevalence of SARS-CoV-2 IgG antibodies, in Corsica (France), April and June 2020
Authors: Lisandru Capai , Nazli Ayhan , Shirley Masse , Jean Canarelli , Stéphane Priet , Helene Simeoni Marie , Remi Charrel , Xavier de Lamballerie , Alessandra Falchi
Published: October 2020

Our aim was to assess the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection after the lockdown in a sample of the Corsican population. Between 16th April and 15th June 2020, 2,312 residual sera were collected from patients having carried out a blood analysis in one of the participating laboratories. Residual sera obtained from persons of all ages were tested for the presence of anti-SARS-CoV-2 IgG using the EUROIMMUN enzyme immunoassay kit for semiquantitative detection of IgG antibodies against S1 domain of viral spike protein (ELISA-S). Borderline and positive samples in ELISA-S were also tested with an in-house virus neutralization test (VNT). Prevalence values were adjusted for sex and age. A total of 1,973 residual sera samples were included in the study. The overall seroprevalence based on ELISA-S was 5.27% [95% confidence interval (CI) 4.33-6.35] and 5.46% [4.51-6.57] after adjustment. Gender was not associated with IgG detection. However, significant differences were observed between age groups (p-value = 1 E-5) and particularly for people being younger than 50 years of age (Odd ratio (OR) = 2.86 95% CI [1.80-4.53]; p-value <0.000001*). The prevalence of neutralizing antibody titers ≥40 was of 3% [2.28-3.84]. In conclusion the present study showed that a low seroprevalence for COVID-19 in Corsica in accordance with values reported for other French regions in which the impact of the pandemic was low.
Artificial intelligence to predict the risk of mortality from Covid-19: Insights from a Canadian Application
Authors: Snider Brett , Phillips Paige , MacLean Aryn , McBean Edward , Gadsden S. Andrew , Yawney John
Published: October 2020

The Severe Acute Respiratory Syndrome COVID-19 virus (SARS-CoV-2) has had enormous impacts, indicating need for non-pharmaceutical interventions (NPIs) using Artificial Intelligence (AI) modeling. Investigation of AI models and statistical models provides important insights within the province of Ontario as a case study application using patients’ physiological conditions, symptoms, and demographic information from datasets from Public Health Ontario (PHO) and the Public Health Agency of Canada (PHAC). The findings using XGBoost provide an accuracy of 0.9056 for PHO, and 0.935 for the PHAC datasets. Age is demonstrated to be the most important variable with the next two variables being Hospitalization and Occupation. Further, AI models demonstrate identify the importance of improved medical practice which evolved over the six months in treating COVID-19 virus during the pandemic, and that age is absolutely now the key factor, with much lower importance of other variables that were important to mortality near the beginning of the pandemic.

An XGBoost model is shown to be fairly accurate when the training dataset surpasses 1000 cases, indicating that AI has definite potential to be a useful tool in the fight against COVID-19 even when caseload numbers needed for effective utilization of AI model are not large.
Virus evolution affected early COVID-19 spread
Authors: Corcoran Derek , Urban Mark C. , Wegrzyn Jill , Merow Cory
Published: October 2020

As the SARS-Cov-2 virus spreads around the world afflicting millions of people, it has undergone divergent genetic mutations. Although most of these mutations are expected to be inconsequential, some mutations in the spike protein structure have been hypothesized to affect the critical stage at which the virus invades human cells, which could affect transmission probability and disease expression. If true, then we expect an increased growth rate of reported COVID-19 cases in regions dominated by viruses with these altered proteins. We modeled early global infection dynamics based on clade assignment along with other demographic and meteorological factors previously found to be important. Clade, but not variant D614G which has been associated with increased viral load, enhanced our ability to describe early COVID-19 growth dynamics. Including clade identity in models significantly improved predictions over earlier work based only on weather and demographic variables. In particular, higher proportions of clade 19A and 19B were negatively correlated with COVID-19 growth rate, whereas higher proportions of 20A and 20C were positively correlated with growth rate. A strong interaction between the prevalence of clade 20C and relative humidity suggests that the impact of clade identity might be more important when coupled with certain weather conditions. In particular, 20C an 20A generate the highest growth rates when coupled with low humidity. Projections based on data through April 2020 suggest that, without intervention, COVID-19 has the potential to grow more quickly in regions dominated by the 20A and 20C clades, including most of South and North America.
Tracking private WhatsApp discourse about COVID-19: A longitudinal infodemiology study in Singapore
Authors: Tan Edina YQ , Wee Russell RE , Ern Saw Young , Heng Kylie JQ , Chin Joseph WE , Tong Eddie M.W. , Liu Jean CJ
Published: September 2020

Background

Worldwide, social media traffic increased following the onset of the coronavirus disease (COVID-19) pandemic. Although the spread of COVID-19 content has been described for several social media platforms (e.g., Twitter, Facebook), little is known about how content is spread via private messaging platforms such as WhatsApp.

Objective

In this study, we documented: (i) how WhatsApp is used to transmit COVID-19 content; (ii) the characteristics of WhatsApp users based on their usage patterns; and (iii) how usage patterns link to well-being.

Methods

We used the experience sampling method to track day-to-day WhatsApp usage during the COVID-19 pandemic. For one week, participants reported each day the extent to which they had received, forwarded, or discussed COVID-19 content. The final dataset comprised 924 data points collected from 151 participants.

Results

During the week-long monitoring, most participants (143/151, 95%) reported at least one COVID-19-related use of WhatsApp. When a taxonomy was generated based on usage patterns, 1 in 10 participants (21/151, 14%) were found to have received and shared a high volume of forwarded COVID-19 content – akin to ‘super spreaders’ identified on other social media platforms. Finally, those who engaged with more COVID-19 content in their personal chats were more likely to report having COVID-19 thoughts throughout the day.

Conclusions

These findings provide a rare window into discourse on private messenger platforms. In turn, this can inform risk communication strategies during the pandemic.