bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor-Immune Partitioning and Clustering (TIPC) algorithm reveals distinct signatures of tumor-immune cell interactions within the tumor microenvironment
Authors: Lau Mai Chan , Borowsky Jennifer , Väyrynen Juha P. , Haruki Koichiro , Zhao Melissa , Costa Andressa Dias , Gu Simeng , Silva Annacarolina da , Arima Kota , Yeong Joe , Felt Kristen D. , Hamada Tsuyoshi , Nishihara Reiko , Lennerz Jochen K. , Fuchs Charles S. , Wu Catherine J. , Ogino Shuji , Nowak Jonathan A.
Published: May 2020

Growing evidence supports the importance of understanding tumor-immune spatial relationship in the tumor microenvironment in order to achieve precision cancer therapy. However, existing methods, based on oversimplistic cell-to-cell proximity, are largely confounded by immune cell density and are ineffective in capturing tumor-immune spatial patterns. Here we developed a novel computational algorithm, termed Tumor-Immune Partitioning and Clustering (TIPC), to offer an effective solution for spatially informed tumor subtyping. Our method could measure the extent of immune cell partitioning between tumor epithelial and stromal areas as well as the degree of immune cell clustering. Using a U.S. nation-wide colorectal cancer database, we showed that TIPC could determine tumor subtypes with unique tumor-immune spatial patterns that were significantly associated with patient survival and key tumor molecular features. We also demonstrated that TIPC was robust to parameter settings and readily applicable to different immune cell types. The capability of TIPC in delineating clinically relevant patient subtypes that encapsulate tumor-immune spatial relationship, immune density, and tumor morphology is expected to shed light on underlying immune mechanisms. Hence, TIPC can be a useful bioinformatics tool for effective characterization of the spatial composition of the tumor-immune microenvironment to inform precision immunotherapy.
Indigenous plants promote insect biodiversity in urban greenspaces
Authors: Mata Luis , Andersen Alan N. , Morán-Ordóñez Alejandra , Hahs Amy K. , Backstrom Anna , Ives Christopher D. , Bickel Daniel , Duncan David , Palma Estibaliz , Thomas Freya , Cranney Kate , Walker Ken , Shears Ian , Semeraro Linda , Malipatil Mallik , Moir Melinda L. , Plein Michaela , Porch Nick , Vesk Peter A. , Smith Tessa R. , Lynch Yvonne
Published: May 2020

The contribution of urban greenspaces to support biodiversity and provide benefits for people is increasingly recognised. However, ongoing management practices still favour (1) vegetation oversimplification, often limiting greenspaces to lawns and tree canopy rather than multi-layered vegetation that includes under and midstorey; and (2) the use of nonnative plant species. These practices likely hinder the potential of greenspaces to sustain indigenous biodiversity, particularly for taxa like insects, that rely on plants for food and habitat. Yet, little is known about which plant species may maximise positive outcomes for taxonomically and functionally diverse insect communities in urban greenspaces. Additionally, while urban environments are expected to experience high rates of introductions, quantitative assessments of the relative occupancy of indigenous vs. introduced insect species in greenspace are rare – hindering understanding of how greenspace management may promote indigenous biodiversity while limiting the establishment of introduced insects. Using a hierarchically replicated study design across 15 public parks, we recorded occurrence data from 552 insect species on 133 plant species – differing in planting design element (lawn, midstorey and tree canopy), midstorey growth form (forbs, lilioids, graminoids and shrubs) and origin (nonnative, native and indigenous) – to assess: (1) the relative contributions of indigenous and introduced insect species and (2) which plant species sustained the highest number of indigenous insects. Our data indicates that the insect community was predominately composed of indigenous rather than introduced species. Our findings further highlight the core role of multi-layered vegetation in sustaining high insect biodiversity in urban areas, with indigenous midstorey and canopy representing key elements to maintain rich and functionally diverse indigenous insect communities. Intriguingly, graminoids supported the highest indigenous insect richness across all studied growth forms by plant origin groups. Taken together, our study emphasise the opportunity posed by indigenous understory and midstorey plants, particularly indigenous graminoids in our study area, to promote indigenous insect biodiversity in urban greenspaces. Our work provides a blueprint and stimulus for built-environment professionals to incorporate into their practice plant species palettes that foster a larger presence of indigenous over regionally native or nonnative plant species, whilst incorporating a broader mixture of midstorey growth forms.
Transcriptome and translatome changes in germinated pollen under heat stress uncover roles of transporter genes involved in pollen tube growth
Authors: Poidevin Laetitia , Forment Javier , Unal Dilek , Ferrando Alejandro
Published: May 2020

Plant reproduction is one key biological process very sensitive to heat stress and, as a consequence, enhanced global warming poses serious threats to food security worldwide. In this work we have used a high-resolution ribosome profiling technology to study how heat affects both the transcriptome and the translatome ofArabidopsis thalianapollen germinatedin vitro. Overall, a high correlation between transcriptional and translational responses to high temperature was found, but specific regulations at the translational level were also present. We show thatbona fideheat shock genes are induced by high temperature indicating thatin vitrogerminated pollen is a suitable system to understand the molecular basis of heat responses. Concurrently heat induced significant down-regulation of key membrane transporters required for pollen tube growth, thus uncovering heat-sensitive targets. We also found that a large subset of the heat-repressed transporters is specifically up-regulated, in a coordinated manner, with canonical heat-shock genes in pollen tubes grownin vitroandsemi in vivo, based on published transcriptomes fromArabidopsis thaliana. Ribosome footprints were also detected in gene sequences annotated as non-coding, highlighting the potential for novel translatable genes and translational dynamics.
Physical constraints on early blastomere packings
Authors: Giammona James , Campàs Otger
Published: May 2020

At very early embryonic stages, when embryos are composed of just a few cells, establishing the correct packing arrangements (contacts) between cells is essential for the proper development of the organism. As early as the 4-cell stage, the observed cellular packings in different species are distinct and, in many cases, differ from the equilibrium packings expected for simple adherent and deformable particles. It is unclear what are the specific roles that different physical parameters, such as the forces between blastomeres, their division times, orientation of cell division and embryonic confinement, play in the control of these packing configurations. Here we simulate the non-equilibrium dynamics of cells in early embryos and systematically study how these different parameters affect embryonic packings at the 4-cell stage. In the absence of embryo confinement, we find that cellular packings are not robust, with multiple packing configurations simultaneously possible and very sensitive to parameter changes. Our results indicate that the geometry of the embryo confinement determines the packing configurations at the 4-cell stage, removing degeneracy in the possible packing configurations and overriding division rules in most cases. Overall, these results indicate that physical confinement of the embryo is essential to robustly specify proper cellular arrangements at very early developmental stages.

Author summary

At the initial stages of embryogenesis, the precise arrangement of cells in the embryo is critical to ensure that each cell gets the right chemical and physical signals to guide the formation of the organism. Even when the embryo is made of only four cells, different species feature varying cellular arrangements: cells in mouse embryos arrange as a tetrahedron, in the nematode wormC. eleganscells make a diamond and in sea urchins cells arrange in a square configuration. How do cells in embryos of different species control their arrangements? Using computer simulations, we studied how cell divisions, physical contacts between cells and the confinement of the embryo by an eggshell affect the arrangements of cells when the embryos have only 4 cells. We find that the shape of the confining eggshell plays a key role in controlling the cell arrangements, removing unwanted arrangements and robustly specifying the proper contacts between cells. Our results highlight the important roles of embryonic confinement in establishing the proper cell-cell contacts as the embryo starts to develop.
Total mercury concentrations in invasive lionfish (Pterois volitans/miles) from the Atlantic coast of Florida
Authors: Johnson Eric G. , Dichiera Angelina , Goldberg Danielle , Swenarton MaryKate , Gelsleichter James
Published: May 2020

Invasive lionfish (Pterois volitans/miles) pose a serious threat to marine ecosystems throughout the western Atlantic Ocean and Caribbean Sea. The development of a fishery for lionfish has been proposed as a strategy for controlling populations; however, there is concern about consumption of this species by humans due to its high trophic position and potential for bioaccumulation of mercury. We analyzed total mercury (THg) in tissues of lionfish from two locations on the east coast of Florida. THg in lionfish increased with size and differed by location and sex. THg was highest in muscle tissue and was strongly positively correlated among tissues. THg in lionfish was lower than other commonly consumed marine fishes, and falls into Florida’s least restrictive advisory level. Consumption of lionfish poses a low risk and concerns over mercury bioaccumulation should not present a significant barrier to lionfish harvest.
Method for Zero-Waste Circular Economy using worms for plastic agriculture: Augmenting polystyrene consumption and plant growth
Authors: Gan Samuel Ken-En , Phua Ser-Xian , Yeo Joshua Yi , Heng Zealyn Shi-Lin , Xing Zhenxiang
Published: May 2020

Polystyrene (PS) is one of the major plastics contributing to environmental pollution with its durability and resistance to natural biodegradation. Recent research showed that meal-worms (Tenebrio molitor) and superworms (Zophobas morio) are naturally able to consume PS as a carbon food source and degrade them without observable toxic effects. In this study, we explored the effects of possible food waste contamination and use of worm frass as potential plant fertilizers. We found that small amounts of sucrose and bran increased PS consumption and that the worm frass alone could support dragon fruit cacti (Hylocereus undatus) growth, with superworm frass in particular, supporting better growth and rooting than mealworm frass and control media over a fortnight. As known fish and poultry feed, these finding present worms as a natural solution to simultaneously tackle both the global plastic problem and urban farming issue in a zero-waste sustainable bioremediation cycle.
Non-canonical glutamate-cysteine ligase activity protects against ferroptosis
Authors: Kang Yun Pyo , Mockabee-Macias Andrea , Jiang Chang , Harris Isaac S. , DeNicola Gina M.
Published: May 2020

Cysteine is required for maintaining cellular redox homeostasis in both normal and transformed cells. Deprivation of cysteine induces the iron-dependent form of cell death known as ferroptosis; however, the metabolic consequences of cysteine starvation beyond impairment of glutathione synthesis are uncharacterized. Here, we find that cystine starvation promotes ferroptosis not only through the inhibition of glutathione (GSH) synthesis, but also through the accumulation of glutamate. Surprisingly, we find that glutamate-cysteine ligase catalytic subunit (GCLC) prevents glutamate accumulation through the generation of alternative γ-glutamyl peptides. Further, inhibition of GCLC accelerates ferroptosis under cystine starvation in a GSH-independent manner. These results indicate that GCLC has an additional, non-canonical role in the protection against ferroptosis to maintain glutamate homeostasis under cystine starvation.
Tim29 is required for stem cell activity during regeneration in the flatwormMacrostomum lignano
Authors: Mouton Stijn , Ustyantsev Kirill , Beltman Frank , Glazenburg Lisa , Berezikov Eugene
Published: May 2020

Domain of Unknown Function (DUF) genes are broadly conserved in metazoa but have an unknown biological function. Previously, we established transcriptional profiles of the germline and stem cells of the flatwormMacrostomum lignano(Grudniewska et al., 2016). Here, we used this information to probe the function of DUF genes inM. lignano. Recently, Kang et al. (2016) found that DUF2366 is a mitochondrial inner membrane protein that interacts with the protein import complex TIM22. DUF2366 was renamed TIM29, and shown to stabilize the TIM22 complex, but its biological role remained largely unknown. We now demonstrate that DUF2366/TIM29 is dispensable in the homeostatic condition inM. lignano, but is essential to adapt to a highly proliferative state required for regeneration. Our results show that ‘de-DUFing’ the function of DUF genes might require special biological conditions, such as regeneration, and establishesM. lignanoas an informative platform to study DUF genes.
A target enrichment probe set for resolving the flagellate plant tree of life
Authors: Breinholt Jesse W. , Carey Sarah B. , Tiley George P. , Davis E. Christine , Endara Lorena , McDaniel Stuart F. , Neves Leandro G. , Sessa Emily B. , von Konrat Matt , Chantanaorrapint Sahut , Fawcett Susan , Ickert-Bond Stefanie M. , Labiak Paulo H. , Larraín Juan , Lehnert Marcus , Lewis Lily R. , Nagalingum Nathalie S. , Patel Nikisha , Rensing Stefan A. , Testo Weston , Vasco Alejandra , Villarreal Juan Carlos , Williams Evelyn Webb , Burleigh J. Gordon
Published: May 2020

Premise of the study

New sequencing technologies enable the possibility of generating large-scale molecular datasets for constructing the plant tree of life. We describe a new probe set for target enrichment sequencing to generate nuclear sequence data to build phylogenetic trees with any flagellate plants, comprising hornworts, liverworts, mosses, lycophytes, ferns, and gymnosperms.

Methods and Results

We leveraged existing transcriptome and genome sequence data to design a set of 56,989 probes for target enrichment sequencing of 451 nuclear exons and non-coding flanking regions across flagellate plant lineages. We describe the performance of target enrichment using the probe set across flagellate plants and demonstrate the potential of the data to resolve relationships among both ancient and closely related taxa.

Conclusions

A target enrichment approach using the new probe set provides a relatively low-cost solution to obtain large-scale nuclear sequence data for inferring phylogenetic relationships across flagellate plants.
Privacy-preserving genotype imputation with fully homomorphic encryption
Authors: Gürsoy Gamze , Chielle Eduardo , Brannon Charlotte M. , Maniatakos Michail , Gerstein Mark
Published: May 2020

Genotype imputation is the statistical inference of unknown genotypes using known population haplotype structures observed in large genomic datasets, such as HapMap and 1000 genomes project. Genotype imputation can help further our understanding of the relationships between genotypes and traits, and is extremely useful for analyses such as genome-wide association studies and expression quantitative loci inference. Increasing the number of genotyped genomes will increase the statistical power for inferring genotype-phenotype relationships, but the amount of data required and the compute-intense nature of the genotype imputation problem overwhelms servers. Hence, many institutions are moving towards outsourcing cloud services to scale up research in a cost effective manner. This raises privacy concerns, which we propose to address via homomorphic encryption. Homomorphic encryption is a type of encryption that allows data analysis on cipher texts, and would thereby avoid the decryption of private genotypes in the cloud. Here we develop an efficient, privacy-preserving genotype imputation algorithm, p-Impute, using homomorphic encryption. Our results showed that the performance of p-Impute is equivalent to the state-of-the-art plaintext solutions, achieving up to 99% micro area under curve score, and requiring a scalable amount of memory and computational time.
CryoEM reveals how the small molecule EGCG binds to Alzheimer’s brain-derived tau fibrils and initiates fibril disaggregation
Authors: Seidler PM , Boyer DR , Sawaya MR , Ge P , Shin WS , DeTure MA , Dickson DW , Jiang L , Eisenberg DS
Published: May 2020

EGCG, the most abundant favanol in green tea, is one of the few natural compounds known to inhibit amyloid fibril formation of proteins associated with neurodegeneration, and to disaggregate amyloid fibrils. Little is known of the mechanism of molecular action of EGCG, or how it or other small molecules interact with amyloid fibrils. Here we present a 3.9 Å resolution cryoEM structure that reveals the site of EGCG binding to Alzheimer’s disease (AD) brain-derived tau fibrils. The structure suggests that EGCG disaggregates fibrils of AD-tau by wedging into a cleft that is at the interface of two protofilaments of the paired helical filament, and by causing charge repulsions between tau layers of the fibril. In support of this, we observe separation of the protofilaments that EGCG wedges between, and accompanying displacement of the adjacent β-helix domain. By resolving the site of EGCG binding, our structure defines a pharmacophore-like cleft in the AD-tau fibril that will be of use for the discovery of surrogate compounds with more desirable drug-like properties.
Wnt3 distribution in the zebrafish brain is determined by expression, diffusion and multiple molecular interactions
Authors: Veerapathiran Sapthaswaran , Teh Cathleen , Zhu Shiwen , Kartigayen Indira , Korzh Vladimir , Matsudaira Paul T. , Wohland Thorsten
Published: May 2020

Wnt3 proteins are lipidated and glycosylated, secreted signaling molecules that play an important role in zebrafish neural patterning and brain development. However, the transport mechanism of lipid-modified Wnts through the hydrophilic extracellular environment for long-range action remains unresolved. Here, we determine how Wnt3 accomplishes long-range distribution in the zebrafish brain. First, we characterize the Wnt3-producing source and Wnt3-receiving target regions. Subsequently, we analyze Wnt3 mobility at different length scales by fluorescence correlation spectroscopy and fluorescence recovery after photo-bleaching. We demonstrate that Wnt3 spreads extracellularly and interacts with heparan sulfate proteoglycans (HSPG). We then determine the binding affinity of Wnt3 to its receptor, Frizzled1 (Fzd1), using fluorescence cross-correlation spectroscopy, and show that the co-receptor, low-density lipoprotein receptor-related protein 5 (Lrp5), is required for Wnt3-Fzd1 interaction. Our results are consistent with the extracellular distribution of Wnt3 by a diffusive mechanism that is modified by tissue morphology, interactions with HSPG and Lrp5-mediated receptor binding, to regulate zebrafish brain development.
The Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR) and routine hematological parameters of COVID-19 Patient : A perspective of the Indian scenario from a frontline pilot study of 32 COVID-19 cases in a Tertiary Care Institute of North India
Authors: Tiwari Neema , Nath Devajit , Madan Jyotsna , Singh Savitri , Bajpai Prashant , Madan Ujjwal
Published: June 2020

Introduction
The coronavirus disease 2019(COVID-19) is caused by the virus SARS-CoV-2 and is declared as a global pandemic by the World Health Organization (WHO). Various hematological parameters alteration has been documented in the Chinese literature in SARS-Cov-2 infection. However, there is a need for research to evaluate the pattern of the hematological parameters of COVID-19 patients in the Indian population.
Aims & Objectives:
The objective of the study is to see the Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), and other hematological parameters alteration of COVID-19 patients along with their clinical course in the Indian scenario.
Methods:
A single-center prospective study of 32 patients with laboratory-confirmed COVID-19 admitted to Super Speciality Pediatric Hospital & Post Graduate Teaching Institute NOIDA, from March to April, were enrolled for the study. The demographic data, the clinical status of the patients during admission and follow up, baseline, and follow up hematological findings were recorded. Statistical analysis of the data was carried out, and relevant findings were presented.
Results:
Demographic characterization shows a mean age of 37.7 years, male (41.9%), female (58.1%)with the majority of patients are mildly symptomatic to asymptomatic(93%). The CBC values and NLR, PLR at baseline between the male and the female patients, are not showing any statistically significant difference as the 95% C.I. A statistically significant increment in the lab parameters is observed in follow-up visits.
Conclusion:
The majority of the patients are younger and have mild clinical presentation with female predominance. Pediatric cases have mild symptomology. Baseline CBC findings show mild neutrophilia, lymphopenia, eosinopenia, and normal to mild thrombocytopenia. An increase in CBC parameters, NLR was noted in follow up cases. Anemia was not noted in baseline CBC and in the follow-up group. A onetime PLR is not indicative of disease progression.

Key words: Corona virus,COVID-19,CBC,NLR,PLR
Whole exome sequencing identifies genes associated with non-obstructive azoospermia
Authors: Zhang Hongguo , Huang Hui , Zhang Xinyue , Li Wei , Jiang Yuting , Li Jia , Li Leilei , Zhao Jing , He Jing , Chen Mucheng , Wang Ruixue , Wu Jing , Peng Zhiyu , Liu Ruizhi
Published: May 2020

Background

Genetic etiology is the main cause of non-obstructive azoospermia, but little is known about the landscape of the disease causative genes.

Objective

To identify the association of non-obstructive azoospermia and the putative causative genetic factors.

Design, setting, and participants

A single-center perspective case-control study of 133 patients, with clinicopathologic non-obstructive azoospermia and 495 fertile men control was performed. Eleven trio families were available and enrolled from the 133 patients’ families.

Outcome measurements and statistical analysis

Whole exome sequencing based rare variant association study between the cases and controls was performed by means of gene burden association testing. Linkage analysis on the trio family was also described to screen the causative genes.

Results and limitations

Totally 80 genes (p < 0.05) were identified associated with non-obstructive azoospermia (2 of which were previously reported), meanwhile 5 novel genes out of which were also found potentially causative through the linkage analysis on the trio families. The pathway enrichment analysis was also provided to assess the potential interaction between genes identified in this study and previously reported together. The 5 novel identified overlap genes by both above mentioned test with the rare mutations account for an overall 20% (26 /133 patients) incidence, together with the 2 known genes together would account for an overall 20% incidence for non-obstructive azoospermia in this study. The study is limited by the lack of functional biological study.

Conclusions

Five novel genes were identified associated with non-obstructive azoospermia by means of both rare variant association study and linkage analysis through trio families. They could account for about 20% clinical incidence among the patients in our study.

Patient summary

133 infertile patients (11 of them with parents enrolled) with idiopathic non-obstructive azoospermia and 300 fertile male controls were recruited from single clinic center.

All patients underwent semen analyses at least on three different occasions.
Novel Vβ specific germline contacts shape an elite controller T cell response
Authors: Wang Yang , Tsitsiklis Alexandra , Gao Wei , Chu H. Hamlet , Zhang Yan , Li Wei , Wong Wing Ki , Deane Charlotte M. , Neau David , Slansky Jill E. , Thomas Paul G. , Robey Ellen A. , Dai Shaodong
Published: June 2020

Certain CD8 T cell responses are particularly effective at controlling infection, as exemplified by elite control of HIV in individuals harboring HLA-B57. To understand the structural features that contribute to CD8 T cell elite control, we focused on a strongly protective CD8 T cell response directed against a parasite-derived peptide (HF10) presented by an atypical MHC-I molecule, H-2Ld. This response exhibits a focused TCR repertoire dominated by Vβ2, and a representative TCR (TG6) in complex with Ld-HF10 reveals an unusual structure in which both MHC and TCR contribute extensively to peptide specificity, along with a parallel footprint of TCR on its pMHC ligand. The parallel footprint is a common feature of Vβ2-containing TCRs and correlates with an unusual Vα-Vβ interface, CDR loop conformations, and Vβ2-specific germline contacts with peptide. Vβ2 and Ldmay represent “specialist” components for antigen recognition that allow for particularly strong and focused T cell responses.
Enzymatic RNA Biotinylation for Affinity Purification and Identification of RNA-protein Interactions
Authors: Busby Kayla N. , Fulzele Amitkumar , Zhang Dongyang , Bennett Eric J. , Devaraj Neal K.
Published: June 2020

Throughout their cellular lifetime, RNA transcripts are bound to proteins, playing crucial roles in RNA metabolism, trafficking, and function. Despite the importance of these interactions, identifying the proteins that interact with an RNA of interest in mammalian cells represents a major challenge in RNA biology. Leveraging the ability to site-specifically and covalently label an RNA of interest usingE. ColitRNA guanine transglycosylase and an unnatural nucleobase substrate, we establish the identification of RNA-protein interactions and the selective enrichment of cellular RNA in mammalian systems. We demonstrate the utility of this approach through the identification of known binding partners of 7SK snRNA via mass spectrometry. Through a minimal 4-nucleotide mutation of the long noncoding RNA HOTAIR, enzymatic biotinylation enables identification putative HOTAIR binding partners in MCF7 breast cancer cells that suggest new potential pathways for oncogenic function. Furthermore, using RNA sequencing and qPCR, we establish that an engineered enzyme variant achieves high levels of labeling selectivity against the human transcriptome allowing for 145-fold enrichment of cellular RNA directly from mammalian cell lysates. The flexibility and breadth of this approach suggests that this system could be routinely applied to the functional characterization of RNA, greatly expanding the toolbox available for studying mammalian RNA biology.
Serratia marcescenssecretes proteases and chitinases with larvicidal activity againstAnopheles dirus
Authors: Jupatanakul Natapong , Pengon Jutharat , Selisana Shiela Marie Gines , Choksawangkarn Waeowalee , Jaito Nongluck , Saeung Atiporn , Bunyong Ratchanu , Posayapisit Navaporn , Thammatinna Khrongkhwan , Kalpongnukul Nuttiya , Aupalee Kittipat , Pisitkun Trairak , Kamchonwongpaisan Sumalee
Published: June 2020

Vector control, the most efficient tool to reduce mosquito-borne disease transmission, has been compromised by the rise of insecticide resistance. Recent studies suggest the potential of mosquito-associated microbiota as a source for new biocontrol agents or new insecticidal chemotypes. In this study, we identified a strain ofSerratia marcescensthat has larvicidal activity againstAnopheles dirus, an important malaria vector in Southeast Asia. This bacterium secretes heat-labile larvicidal macromolecules when cultured under static condition at 25°C but not 37°C. Two major protein bands of approximately 55 kDa and 110 kDa were present in spent medium cultured at 25°C but not at 37°C. The Liquid Chromatography-Mass Spectrometry (LC-MS) analyses of these two protein bands identified several proteases and chitinases that were previously reported for insecticidal properties against agricultural insect pests. The treatment with protease and chitinase inhibitors led to a reduction in larvicidal activity, confirming that these two groups of enzymes are responsible for the macromolecule’s toxicity. Taken together, our results suggest a potential use of these enzymes in the development of larvicidal agents againstAnophelesmosquitoes.
Instantaneous movement-unrelated midbrain activity modifies ongoing eye movements
Authors: Buonocore Antimo , Tian Xiaoguang , Khademi Fatemeh , Hafed Ziad M.
Published: June 2020

At any moment in time, new information is sampled from the environment and interacts with ongoing brain state. Often, such interaction takes place within individual circuits that are capable of both mediating the internally ongoing plan as well as representing exogenous sensory events. Here we investigated how sensory-driven neural activity can be integrated, very often in the same neuron types, into ongoing oculomotor commands for saccades. Despite the ballistic nature of saccades, visually-induced action potentials in the superior colliculus (SC), a structure known to drive eye movements, not only occurred intra-saccadically, but they were also associated with highly predictable modifications of ongoing eye movements. Such predictable modifications reflected a simultaneity of movement-related discharge at one SC site and visually-induced activity at another. Our results suggest instantaneous readout of the SC map during movement generation, irrespective of activity source, and they explain a significant component of kinematic variability of motor outputs.
Peripheral blood microbial signatures in COPD
Authors: Morrow Jarrett D. , Castaldi Peter J. , Chase Robert P. , Yun Jeong H. , Lee Sool , Liu Yang-Yu , Hersh Craig P. ,   the COPDGene Investigators
Published: June 2020

Background

The human microbiome has a role in the development of human diseases. Individual microbiome profiles are highly personalized, though many species are shared. Understanding the relationship between the human microbiome and disease may inform future individualized treatments. Specifically, the blood microbiome, once believed sterile, may be a surrogate for some lung and gut microbial characteristics. We sought associations between the blood microbiome and lung-relevant host factors.

Methods

Based on reads not mapped to the human genome, we detected microbial nucleic acid signatures in peripheral blood RNA-sequencing for 2,590 current and former smokers with and without chronic obstructive pulmonary disease (COPD) from the COPDGene study. We used the GATK microbial pipeline PathSeq to infer microbial profiles. We tested associations between the inferred profiles and lung disease relevant phenotypes and examined links to host gene expression pathways.

Results

The four phyla with highest abundance across all subjects were Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. We observed associations between exacerbation phenotypes and the relative abundance ofStaphylococcus, AcidovoraxandCupriavidus. The genusFlavobacteriumwas associated with emphysema and change in emphysema. Our host-microbiome interaction analysis revealed clustering of genera associated with emphysema, systemic inflammation, airway remodeling and exacerbations, through links to lung-relevant host pathways.

Conclusions

This study is the first to identify a bacterial microbiome signature in the peripheral blood of current and former smokers. Understanding the relationships between the systemic microbial populations and lung disease severity may inform novel interventions and aid in the understanding of exacerbation phenotypes.
Silver nanoantibiotics display strong antifungal activity against the emergent multidrug-resistant yeastCandida aurisunder both planktonic and biofilm growing conditions
Authors: Vazquez-Munoz Roberto , Lopez Fernando D. , Lopez-Ribot Jose
Published: June 2020

Candida aurisis an emergent multidrug-resistant pathogenic yeast with an unprecedented ability for a fungal organism to easily spread between patients in clinical settings, leading to major outbreaks in healthcare facilities. The formation of biofilms byC. auriscontributes to infection and its environmental persistence. Most antifungals and sanitizing procedures are not effective againstC. auris,but antimicrobial nanomaterials could represent a viable alternative to combat the infections caused by this emerging pathogen. We have previously described an easy and inexpensive method to synthesize silver nanoparticles (AgNPs) in non-specialized laboratories. Here we have assessed the antimicrobial activity of the resulting AgNPs onC. aurisplanktonic and biofilm growth phases. AgNPs displayed a strong antimicrobial activity against all the stages of allC. aurisstrains tested, representative of four different clades. Under planktonic conditions, MIC values of AgNPs against the different strains were <0.5 μg mL-1; whereas calculated IC50 values for inhibition of biofilms formation were < 2 μg mL-1for all but one of theC. aurisstrains tested. AgNPs were also active against preformed biofilms formed by all differentC. aurisstrains, with IC50 values ranging from 1.2 to 6.2 μg mL-1. Overall, our results indicate potent activity of AgNPs against strains ofC. auris, both under planktonic and biofilm growing conditions, and indicate that AgNPs may contribute to the control of infections caused by this emerging nosocomial threat.
Heat Shock Protein 27 Immune Complex Altered Signaling and Transport (ICAST): Novel Mechanisms of Attenuating Inflammation
Authors: Shi Chunhua , Deng Jingti , Chiu Michael , Chen Yong-Xiang , O’Brien Edward R.
Published: June 2020

Blood levels of heat shock protein (HSP27) and natural IgG auto-antibodies to HSP27 (AAbs) are higher in healthy controls compared to cardiovascular disease patients. Vaccination of mice with recombinant HSP25 (rHSP25, murine ortholog of human rHSP27) increased AAb levels, attenuated atherogenesis and reduced plaque inflammation and cholesterol content. We sought to determine if the HSP27 immune complex (IC) altered MΦ inflammation signaling (Toll Like Receptor 4; TLR4), and scavenger receptors involved in cholesterol uptake (SR-AI, CD-36). Combining a validated polyclonal IgG anti-HSP27 antibody (PAb) with rHSP27 enhanced binding to THP-1 MΦ cell membranes and activation of NF-κB signaling via TLR4, competing away LPS and effecting an anti-inflammatory cytokine profile. Similarly, adding the PAb with rHSP27 enhanced binding to SR-AI and CD-36, as well as lowered oxLDL binding in HEK293 cells separately transfected with SR-AI and CD-36, or THP-1 MΦ. Finally, the PAb enhanced the uptake and internalization of rHSP27 in THP-1 MΦ. Thus, the HSP27 IC potentiates HSP27 cell membrane signaling with receptors involved in modulating inflammation and cholesterol uptake, as well as HSP27 internalization. Going forward, we will explore HSP27 Immune Complex Altered Signaling and Transport (ICAST) as a new anti-inflammatory therapeutic strategyin vivo.
Human Parental Relatedness through Time - Detecting Runs of Homozygosity in Ancient DNA
Authors: Ringbauer Harald , Novembre John , Steinrücken Matthias
Published: June 2020

At present day, human parental relatedness varies substantially across the globe, but little is known about the past. Here we use ancient DNA to provide new insights, leveraging that parental relatedness leaves traces in the offspring’s genome in the form of runs of homozygosity. We present a method to identify such runs in low-coverage ancient DNA data using linkage information from a reference panel of modern haplotypes. As a result, the method facilitates analysis of a much larger fraction of the global ancient DNA record than previously possible. Simulation and experiments show that this new method has power to detect runs of homozygosity longer than 4 centimorgan for ancient individuals with at least 0.3× coverage. We used this new method to analyze sequence data from 1,785 humans from the last 45,000 years. Generally, we detect very low rates of first cousin or closer unions across most ancient populations. Moreover, our results evidence a substantial impact of the adoption of agricultural lifestyles: We find a marked decay in background parental relatedness, co-occurring with or shortly after the advent of sedentary agriculture. We observe this signal, likely linked to increasing local population sizes, across several geographic regions worldwide.
Simultaneous decoding of cardiovascular and respiratory functional changes from pig intraneural vagus nerve signals
Authors: Vallone Fabio , Ottaviani Matteo Maria , Dedola Francesca , Cutrone Annarita , Romeni Simone , Panarese Adele Macrí , Bernini Fabio , Cracchiolo Marina , Gabisonia Khatia , Gorgodze Nikoloz , Mazzoni Alberto , Recchia Fabio A. , Micera Silvestro
Published: June 2020

Bioelectronic medicine is opening new perspectives for the treatment of some major chronic diseases through the physical modulation of autonomic nervous system activity. Being the main peripheral route for electrical signals between central nervous system and visceral organs, the vagus nerve (VN) is one of the most promising targets. Closed-loop neuromodulation would be crucial to increase effectiveness and reduce side effects, but it depends on the possibility of extracting useful physiological information from VN electrical activity, which is currently very limited.

Here, we present a new decoding algorithm properly detecting different functional changes from VN signals. They were recorded using intraneural electrodes in anaesthetized pigs during cardiovascular and respiratory challenges mimicking increases in arterial blood pressure, tidal volume and respiratory rate. A novel decoding algorithm was developed combining discrete wavelet transformation, principal component analysis, and ensemble learning made of classification trees. It robustly achieved high accuracy levels in identifying different functional changes and discriminating among them. We also introduced a new index for the characterization of recording and decoding performance of neural interfaces. Finally, by combining an anatomically validated hybrid neural model and discrimination analysis, we provided new evidence suggesting a functional topographical organization of VN fascicles. This study represents an important step towards the comprehension of VN signaling, paving the way to the development of effective closed-loop bioelectronic systems.
Ancient Admixture into Africa from the ancestors of non-Africans
Authors: Cole Christopher B. , Zhu Sha Joe , Mathieson Iain , Prüfer Kay , Lunter Gerton
Published: June 2020

Genetic diversity across human populations has been shaped by demographic history, making it possible to infer past demographic events from extant genomes. However, demographic inference in the ancient past is difficult, particularly around the out-of-Africa event in the Late Middle Paleolithic, a period of profound importance to our species’ history. Here we presentSMCSMC, a Bayesian method for inference of time-varying population sizes and directional migration rates under the coalescent-with-recombination model, to study ancient demographic events. We find evidence for substantial migration from the ancestors of present-day Eurasians into African groups between 40 and 70 thousand years ago, predating the divergence of Eastern and Western Eurasian lineages. This event accounts for previously unexplained genetic diversity in African populations, and supports the existence of novel population substructure in the Late Middle Paleolithic. Our results indicate that our species’ demographic history around the out-of-Africa event is more complex than previously appreciated.
Smoking and the risk of COVID-19 in a large observational population study
Authors: Israel Ariel , Feldhamer Elan , Lahad Amnon , Levin-Zamir Diane , Lavie Gil
Published: June 2020

BACKGROUND

Smokers are generally more susceptible to infectious respiratory diseases and are at higher risk of developing severe complications from these infections. Conflicting reports exist regarding the impact of smoking on the risk of Coronavirus disease 2019 (COVID-19).

METHODS

We carried out a population-based study among over 3,000,000 adult members of Clalit Health Services, the largest health provider in Israel. Since the beginning of the disease outbreak, and until May 16, 2020, over 145,000 adults underwent RT-PCR testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and 3.3% had positive results. We performed a case-control study among patients who underwent SARS-CoV-2 testing, to assess the impact of smoking on infection incidence and severity. Individuals with positive tests were matched in a 1:5 ratio to individuals tested negative, of the same sex, age, and ethnicity/religion. Conditional logistic regressions were performed to evaluate odds ratios for current and previous smoking on the risk of testing positive. Multivariable logistic regressions were performed among patients infected with COVID-19 to estimate the association between smoking and fatal or severe disease requiring ventilation. Regressions were performed with and without adjustment for preexisting medical conditions.

RESULTS

Current smokers (9.8%) were significantly less prevalent among members tested positive compared to the general population (19.4%, P<0.001), and to matched members tested negative (18.2%, P<0.001). Current smoking was associated with significantly reduced odds ratio (OR) for testing positive OR=0.447 (95% confidence interval (CI) 0.400-0.501). Among patients tested positive, there was no evidence of significantly increased risk of developing severe or fatal disease.

CONCLUSION

The risk of infection by COVID-19 appears to be reduced by half among current smokers. This intriguing finding may reveal unique infection mechanisms present for COVID-19 which may be targeted to combat the disease and reduce its infection rate.
Rapid systematic review on clinical evidence of chloroquine and hydroxychloroquine in COVID-19: critical assessment and recommendation for future clinical trials
Authors: Wang Yitong , Liang Shuyao , Qiu Tingting , Han Ru , Dabbous Monique , Nowotarska Anna , Toumi Mondher
Published: June 2020

Purpose

This study aims to critically assess the published studies of Chloroquine (CQ) and hydroxychloroquine (HCQ) for the treatment of COVID-19 and provide recommendations for future clinical trials for the COVID-19 pandemic.

Method

A rapid systematic review was conducted by searching the PubMed, Embase, and China National Knowledge Infrastructure databases on April 13, 2020. Three clinical trial registry platforms, includingClinicalTrials.gov, the EU Clinical Trials Register, and the Chinese Clinical Trial Register were also complementarily searched.

Results

A total of 10 clinical studies were identified, including 3 randomized controlled trials (RCTs), 1 comparative nonrandomized trial, 5 single-arm trials, and 1 interim analysis. The heterogeneity among studies of the baseline disease severity and reported endpoints made a pooled analysis impossible. CQ and HCQ (with or without azithromycin) showed significant therapeutic benefit in terms of virologic clearance rate, improvement in symptoms and imaging findings, time to clinical recovery, and length of hospital stay in 1 RCT, 4 single-arm trials, and the interim analysis, whereas no treatment benefit of CQ or HCQ was observed in the remaining 4 studies. Limitations of the included studies ranged from small sample size, to insufficient information concerning baseline patient characteristics, to potential for selection bias without detailing the rationale for exclusion, and presence of confounding factors.

Conclusion

Based on the studies evaluated, there still lacked solid evidence supporting the efficacy and safety of HCQ and CQ as a treatment for COVID-19 with or without azithromycin. This emphasized the importance of robust RCTs investing HCQ/CQ to address the evidence uncertainties.
After the break: DSB end processing in mouse meiosis
Authors: Brick Kevin , Pratto Florencia , Camerini-Otero R. Daniel
Published: June 2020

The exchange of genetic information between parental chromosomes in meiosis is an integral process for the creation of gametes. To generate a crossover, hundreds of DNA double-strand breaks (DSBs) are introduced in the genome of each meiotic cell by the SPO11 protein. The nucleolytic resection of DSB-adjacent DNA is a key step in meiotic DSB repair, but this process has remained understudied. In this issue of Genes & Development, Yamada and colleagues (pp. 806–818) capture some of the first details of resection and DSB repair intermediates in mouse meiosis using a method that maps blunt-ended DNA after ssDNA digestion. This yields some of the first genome-wide insights into DSB resection and repair in a mammalian genome and offers a tantalizing glimpse of how to quantitatively dissect this difficult to study, yet integral, nuclear process.
The dynamic stimulus of social media marketing on purchase intention of Indonesian airline products and services
Authors: Moslehpour Massoud , Dadvari Alaleh , Nugroho Wahyudi , Do Ben-Roy
Published: May 2020

Purpose

The present paper aims to explore the antecedents and consequences of social media marketing (SMM) subsets on consumers’ purchase intentions of Indonesian airline products and services. We propose a research framework to empirically test the influence and interaction of factors, including entertainment (ENT), and interaction (INT) through the effect of trust (TR), and perceived value (PV) as mediators on purchase intention (PI).

Design/methodology/approach

The study employs an online survey to collect data. We collect 301 qualified questionnaires and employ structural equation modeling (SEM) to test the proposed model. The research findings enrich our understanding of the mediating role of TR and PV. Trust and perceived value significantly mediate the relationship between SMM factors and PI during initial stages of decision-making toward purchasing airline products and services.

Findings

Research findings provide support for most hypotheses regarding the significant influence of the variables proposed in the model. Furthermore, trust mediates the relationship between two of the SMM factors (INT and ENT) and purchase intention. Notably, perceived value mediates the link between entertainment and purchase intention.

Originality/value

This study successfully offers a model to examine the influence of social media marketing on Indonesian consumers’ purchasing intentions of airline products and services. Social media marketing components progressively impact the fundamentals of purchase intention, creating a new marketing communication style. These changes generate new opportunities and challenges for companies. This study provides a better understanding of how social media factors influence Indonesian consumers’ initial decision to purchase airline products and services.