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Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 70,838 bioRxiv papers from 309,132 authors.

Most tweeted bioRxiv papers, last 24 hours

412 results found. For more information, click each entry to expand.

1: Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin
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Posted to bioRxiv 23 Jan 2020

Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin
1,120 tweets microbiology

Peng Zhou, Xing-Lou Yang, Xian-Guang Wang, Ben Hu, Lei Zhang, Wei Zhang, Hao-Rui Si, Yan Zhu, Bei Li, Chao-Lin Huang, Hui-Dong Chen, Jing Chen, Yun Luo, Hua Guo, Ren-Di Jiang, Mei-Qin Liu, Ying Chen, Xu-Rui Shen, Xi Wang, Xiao-Shuang Zheng, Kai Zhao, Quan-Jiao Chen, Fei Deng, Lin-Lin Liu, Bing Yan, Fa-Xian Zhan, Yan-Yi Wang, Gengfu Xiao, Zheng-Li Shi

Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.

2: Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV
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Posted to bioRxiv 22 Jan 2020

Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV
243 tweets microbiology

Michael C Letko, Vincent Munster

Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these novel viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent 2019-nCoV, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells and confirm that human ACE2 is the receptor for the recently emerging 2019-nCoV.

3: From SARS-CoV to Wuhan 2019-nCoV Outbreak: Similarity of Early Epidemic and Prediction of Future Trends
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Posted to bioRxiv 25 Jan 2020

From SARS-CoV to Wuhan 2019-nCoV Outbreak: Similarity of Early Epidemic and Prediction of Future Trends
127 tweets microbiology

Zeliang Chen, Wenjun Zhang, Yi Lu, Cheng Guo, Zhongmin Guo, Conghui Liao, Xi Zhang, Yi Zhang, Xiaohu Han, Qianlin Li, Jiahai Lu

The ongoing large-scale pneumonia outbreak in China is caused by the 2019-nCoV, a new coronavirus highly similar to SARS-CoV in the SARS outbreak. The cause and consequence of the outbreak remain largely unknown as it is still in its early stage. As many aspects of the new virus are similar to SARS in 2003, knowledge, patterns and lessons of the SARS-CoV outbreak are valuable resources for responding to the Wuhan 2019-nCoV outbreak. Using epidemiological surveys and analyses from the early stage of the SARS outbreak, we assessed and compared the characteristics of those two outbreaks and predicted the possible outcome for the current 2019-nCoV outbreak. Like the SARS-CoV, the 2019-nCoV has a high human-to-human transmission capability and healthcare workers and family members are high risk populations. Because the early outbreak stage coincides with the Chinese spring festival travel rush, it is a challenge to prevent and control the spread of the virus. In this situation, the emergence and movement of a 2019-nCoV super-spreader is difficult to identify. Using the reported case data so far (as of Jan 23, 2019), a logistic model was built and the cumulative and daily counts of the 2019-nCoV cases were predicted. The cumulative counts of 2019-nCoV cases was estimated about 2-3 times the total number of SARS, and the peak incidence is predicted to be in early or middle February. Regional migration should be limited or prohibited to prevent emergence and movement of a super-spreader. There is an urgent need to establish enhanced surveillance and implement efficient measures nationwide to control this epidemic.

4: Fine-scale genomic analyses of admixed individuals reveal unrecognized genetic ancestry components in Argentina
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Posted to bioRxiv 24 Jan 2020

Fine-scale genomic analyses of admixed individuals reveal unrecognized genetic ancestry components in Argentina
81 tweets genetics

Pierre Luisi, Angelina García, Juan Manuel Berros, Josefina Motti, Darío Demarchi, Emma Alfaro, Eliana Aquilano, Carina Argüelles, Sergio Avena, Graciela Bailliet, Julieta Beltramo, Claudio Bravi, Mariela Cuello, Cristina Dejean, José Edgardo Dipierri, Laura Jurado Medina, José Luis Lanata, Marina Muzzio, María Laura Parolin, Maia Pauro, Paula B. Paz Sepúlveda, Daniela Rodríguez Golpe, María Rita Santos, Marisol Schwab, Natalia Silverio, Jeremias Zubrzycki, Virgina Ramallo, Hernán Dopazo

We are at the dawn of the efforts to describe and understand the origins of genetic diversity in Argentina from high-throughput data. This knowledge is a primary step in the intent of deciphering the specific genetic bases of diseases and drug response in the country. Similarly to other populations across the Americas, genetic ancestry in Argentinean populations traces back into African, European and Native American ancestors, reflecting a complex demographic history with multiple migration and admixture events in pre- and post-colonial times. However, little is known about the sub-continental origins of these three main ancestries. We present new high-throughput genotyping data for 87 admixed individuals across Argentina. This data was combined to previously published data for admixed individuals in the region and then compared to different reference panels specifically built to run population structure analyses at a sub-continental level. Concerning the European and African ancestries, we confirmed previous results about their main origins, and we provide new insights into the presence of other origins that reflect historical records. As for the Native American ancestry, leveraging genotype data for archeological samples in the region in order to gain temporal depth in our analyses, we could identify four Native American components segregating in modern Argentinean populations . Three of them are also found in modern South American populations and are specifically represented in Central Chile/Patagonia, Lowlands and Central Andes geographic areas. The fourth one may be specific to the Central Western region of Argentina. Identifying such component has not been straightforward since it is not well represented in any genomic data from the literature. Altogether, we provide useful insights into the multiple population groups from different continents that have contributed to present-days genetic diversity in Argentina. We encourage the generation of massive genotype data locally to further describe the genetic structure in Argentina.

5: Pattern of early human-to-human transmission of Wuhan 2019-nCoV
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Posted to bioRxiv 24 Jan 2020

Pattern of early human-to-human transmission of Wuhan 2019-nCoV
67 tweets microbiology

Julien Riou, Christian L Althaus

On December 31, 2019, the World Health Organization was notified about a cluster of pneumonia of unknown aetiology in the city of Wuhan, China. Chinese authorities later identified a new coronavirus (2019-nCoV) as the causative agent of the outbreak. As of January 23, 2020, 655 cases have been confirmed in China and several other countries. Understanding the transmission characteristics and the potential for sustained human-to-human transmission of 2019-nCoV is critically important for coordinating current screening and containment strategies, and determining whether the outbreak constitutes a public health emergency of international concern (PHEIC). We performed stochastic simulations of early outbreak trajectories that are consistent with the epidemiological findings to date. We found the basic reproduction number, R_0, to be around 2.2 (90% high density interval 1.4--3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of a similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. These findings underline the importance of heightened screening, surveillance and control efforts, particularly at airports and other travel hubs, in order to prevent further international spread of 2019-nCoV.

6: LRRK2 mediates tubulation and vesicle sorting from membrane damaged lysosomes
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Posted to bioRxiv 24 Jan 2020

LRRK2 mediates tubulation and vesicle sorting from membrane damaged lysosomes
56 tweets cell biology

Luis Bonet-Ponce, Alexandra Beilina, Chad Williamson, Eric Lindberg, Jillian H Kluss, Sara Saez-Atienzar, Natalie Landeck, Ravindran Kumaran, Adamantios Mamais, Christopher K.E. Bleck, Yan Li, Mark R Cookson

Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are a cause of familial and sporadic Parkinson disease (PD). Nonetheless, the biological functions of LRRK2 remain incompletely understood. Here, we observed that LRRK2 is recruited to lysosomes that have a ruptured membrane. Using unbiased proteomics, we observed that LRRK2 is able to recruit the motor adaptor protein JIP4 to permeabilized lysosomes in a kinase-dependent manner through the phosphorylation of RAB35 and RAB10. Super-resolution live cell imaging microscopy and FIB-SEM revealed that once at the lysosomal membrane, JIP4 promotes the formation of LAMP1-negative lysosomal tubules that release membranous content from ruptured lysosomes. Released vesicular structures are able to interact with other lysosomes. Thus, we described a new process that uses lysosomal tubulation to release vesicular structures from permeabilized lysosomes. LRRK2 orchestrates this process that we name LYTL (LYsosomal Tubulation/sorting driven by LRRK2) that, given the central role of the lysosome in PD, is likely to be disease relevant.

7: Molecular evolution of luciferase diversified bioluminescent signals in sea fireflies (Crustacea:Ostracoda:Cypridinidae)
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Posted to bioRxiv 24 Jan 2020

Molecular evolution of luciferase diversified bioluminescent signals in sea fireflies (Crustacea:Ostracoda:Cypridinidae)
53 tweets evolutionary biology

Nicholai M Hensley, Emily A Ellis, Nicole Y Leung, John Coupart, Alexander Mikhailovsky, Daryl A Taketa, Michael Tessler, David F. Gruber, Anthony W De Tomaso, Trevor J Rivers, Gretchen A Gerrish, Elizabeth Torres, Todd H Oakley

Integrative studies of courtship signals provide rich opportunities to understand how biological diversity originates, but understanding the underlying genetics is challenging. Here we show molecular evolution of a single gene - luciferase - influenced diversification of bioluminescent signals in cypridinid ostracods, including their radiation into dozens of Caribbean species with distinctive courtship displays. We report emission spectra from twenty-one species, thirteen luciferases from transcriptomes, and in vitro assays that confirm function from four exemplar species. We found most sites in luciferase evolved neutrally or under purifying selection, including multiple sites that affect the color of bioluminescence in mutagenesis studies. Twelve sites in cypridinid luciferase evolved under episodic diversifying selection, including five that correlate with changes in kinetics and/or color of bioluminescence, phenotypes that manifest at the organismal level. These results demonstrate how neutral, pleiotropic, and/or selective forces may act on even a single gene and contribute to diversification of phenotypes.

8: BAcTrace a new tool for retrograde tracing of neuronal circuits
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Posted to bioRxiv 25 Jan 2020

BAcTrace a new tool for retrograde tracing of neuronal circuits
47 tweets neuroscience

Sebastian Cachero, Marina Gkantia, Alexander S. Bates, Shahar Frechter, Laura Blackie, Amy Mccarthy, Ben Sutcliffe, Alessio Strano, Yoshinori Aso, Gregory S.X.E. Jefferis

New tools and techniques have enabled many key advances in our understanding of the brain. To elucidate circuit function, it is necessary to identify, record from and manipulate networks of connected neurons. Here we present BAcTrace (Botulinum Activated Tracer), the first fully genetically encoded, retrograde, transsynaptic labelling system. BAcTrace is based on C. botulinum neurotoxin A, Botox, which we have engineered to act as a Trojan horse that jumps retrogradely between neurons to activate an otherwise silent transcription factor. We validate BAcTrace at three connections in the Drosophila olfactory system and show that it enables electrophysiological recordings of connected neurons. Finally, in a challenging circuit with highly divergent connections, we used Electron Microscopy connectomics to show that BAcTrace correctly identifies 12 out of 16 connections.

9: An atlas of cell types in the mammalian epididymis and vas deferens
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Posted to bioRxiv 24 Jan 2020

An atlas of cell types in the mammalian epididymis and vas deferens
41 tweets developmental biology

Vera Rinaldi, Elisa Donnard, Kyle Gellatly, Morten Rasmussen, Alper Kucukural, Onur Yukselen, Manuel Garber, Upasna Sharma, Oliver Rando

Following spermatogenesis in the testis, mammalian sperm continue to mature over the course of approximately 10 days as they transit a long epithelial tube known as the epididymis. The epididymis is comprised of multiple segments/compartments that, in addition to concentrating sperm and preventing their premature activation, play key roles in remodeling the protein, lipid, and RNA composition of maturing sperm. In order to understand the complex roles for the epididymis in reproductive biology, we generated a single cell atlas of gene expression from the murine epididymis and vas deferens. We recovered all the key cell types of the epididymal epithelium, including principal cells, clear cells, and basal cells, along with associated support cells that include fibroblasts, smooth muscle, macrophages and other immune cells. Moreover, our data illuminate extensive regional specialization of principal cell populations across the length of the epididymis, with a substantial fraction of segment-specific genes localized in genomic clusters of functionally-related genes. In addition to the extensive region-specific specialization of principal cells, we find evidence for functionally-specialized subpopulations of stromal cells, and, most notably, two distinct populations of clear cells. Analysis of ligand/receptor expression reveals a network of potential cellular signaling connections, with several predicted interactions between cell types that may play roles in immune cell recruitment and other aspects of epididymal function. Our dataset extends on existing knowledge of epididymal biology, and provides a wealth of information on potential regulatory and signaling factors that bear future investigation.

10: Definition of the fibroblast adhesome using multiplexed proximity biotinylation
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Posted to bioRxiv 25 Jan 2020

Definition of the fibroblast adhesome using multiplexed proximity biotinylation
38 tweets cell biology

Megan R Chastney, Craig Lawless, Jon D Humphries, Stacey Warwood, Matthew C Jones, David Knight, Claus Jorgensen, Martin J Humphries

Integrin adhesion complexes (IACs) bridge the extracellular matrix to the actin cytoskeleton and transduce signals in response to both chemical and mechanical cues. The composition, interactions, stoichiometry and topological organisation of proteins within IACs are not fully understood. To address this gap, we used multiplexed proximity biotinylation (BioID) to generate an in situ, proximity-dependent adhesome in mouse pancreatic fibroblasts. Integration of the interactomes of 16 IAC-associated baits revealed a network of 147 proteins with 361 proximity interactions. Candidates with underappreciated roles in adhesion were identified, in addition to established IAC components. Bioinformatic analysis revealed five clusters of IAC baits that link to common groups of prey, and which therefore may represent functional modules. The five clusters, and their spatial associations, are consistent with current models of IAC interaction networks and stratification. This study provides a resource to examine proximal relationships within IACs at a global level.

11: Continuous detection of glucose and insulin in live animals
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Posted to bioRxiv 23 Jan 2020

Continuous detection of glucose and insulin in live animals
35 tweets bioengineering

Mahla Poudineh, Caitlin L Maikawa, Eric Yue Ma, Jing Pan, Dan Mamerow, Yan Han, Sam w Baker, Ahmad Beirami, Michael Eisenstein, Seung Kim, Jelena Vuckovic, Eric A. Appel, Hyongsok Tom Soh

Real-time biosensors that can continuously measure circulating biomolecules in vivo would provide valuable insights into a patients health status and their response to therapeutics even when there is considerable variability in pharmacokinetics and pharmacodynamics across patient populations. Unfortunately, current real-time biosensors are limited to a handful of analytes (e.g. glucose and blood oxygen) and are limited in sensitivity (high nanomolar). In this work, we describe a general approach for continuously and simultaneously measuring multiple analytes with picomolar sensitivity and sub-second temporal resolution. As exemplars, we report the simultaneous detection of glucose and insulin at picomolar concentrations in live diabetic rats. Using our system, we demonstrate the capacity to resolve inter-individual differences in the pharmacokinetic responses to insulin and discriminate profiles from different insulin formulations at a high temporal resolution. Critically, our approach is general and could be readily modified to continuously and simultaneously measure other circulating analytes in vivo by swapping the affinity reagents, thus making it a versatile tool for biomedical research.

12: BACTERIAL GROWTH INDUCED BIOCEMENTATION TECHNOLOGY, 'SPACE BRICK' - A PROPOSAL FOR EXPERIMENT AT MICROGRAVITY AND PLANETARY ENVIRONMENTS
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Posted to bioRxiv 23 Jan 2020

BACTERIAL GROWTH INDUCED BIOCEMENTATION TECHNOLOGY, 'SPACE BRICK' - A PROPOSAL FOR EXPERIMENT AT MICROGRAVITY AND PLANETARY ENVIRONMENTS
35 tweets bioengineering

Aloke Kumar, Rashmi Dikshit, Nitin Gupta, Animesh Jain, Arjun Dey, Anuj Nandi, I Venugopal, Koushik Viswanathan, N Sridhara, A Rajendra

We present results of our investigation of microbial induced calcite precipitation for manufacturing 'space bricks and a proposal for study of this activity in low-earth orbit (LEO). Sporosarcina pasteurii, a urease producing bacterial strain was used to consolidate lunar simulant soil (LSS) in the form of a 'brick' with non-trivial strength properties. Potential of a naturally occurring polymer namely, guar gum, as an additive was investigated for enhancement in compressive strength of bio-consolidated samples. Experimental results of bio-brick exhibited an approximate 10-fold increase in compressive strength with guar gum supplementation in soil. We present results of microstructural analysis of the 'space bricks' and also propose a payload design for related experiments in LEO.

13: The predictive power of the microbiome exceeds that of genome-wide association studies in the discrimination of complex human disease
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Posted to bioRxiv 02 Jan 2020

The predictive power of the microbiome exceeds that of genome-wide association studies in the discrimination of complex human disease
31 tweets bioinformatics

Braden T. Tierney, Yixuan He, George Church, Eran Segal, Aleksandar D. Kostic, Chirag J. Patel

Over the past decade, studies of the human genome and microbiome have deepened our understanding of the connections between human genes, environments, microbes, and disease. For example, the sheer number of indicators of the microbiome and human genetic common variants associated with disease has been immense, but clinical utility has been elusive. Here, we compared the predictive capabilities of the human microbiome versus human genomic common variants across 13 common diseases. We concluded that microbiomic indicators outperform human genetics in predicting host phenotype (overall Microbiome-Association-Study [MAS] area under the curve [AUC] = 0.79 [SE = 0.03], overall Genome-Wide-Association-Study [GWAS] AUC = 0.67 [SE = 0.02]). Our results, while preliminary and focused on a subset of the totality of disease, demonstrate the relative predictive ability of the microbiome, indicating that it may outperform human genetics in discriminating human disease cases and controls. They additionally motivate the need for population-level microbiome sequencing resources, akin to the UK Biobank, to further improve and reproduce metagenomic models of disease.

14: Bacterial FtsZ induces mitochondrial fission in human cells
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Posted to bioRxiv 24 Jan 2020

Bacterial FtsZ induces mitochondrial fission in human cells
31 tweets cell biology

Anna Spier, Martin Sachse, Nam To Tham, Mariette Matondo, Pascale Cossart, Fabrizia Stavru

Mitochondria are key eukaryotic organelles that evolved from an intracellular bacterium, in a process involving bacterial genome rearrangement and streamlining. As mitochondria cannot form de novo, their biogenesis relies on growth and division. In human cells, mitochondrial division plays an important role in processes as diverse as mtDNA distribution, mitochondrial transport and quality control. Consequently, defects in mitochondrial division have been associated with a wide range of human pathologies. While several protists have retained key components of the bacterial division machinery, none have been detected in human mitochondria, where the dynamin-related protein Drp1, a cytosolic GTPase is recruited to the mitochondrial outer membrane, forming helical oligomers that constrict and divide mitochondria. Here, we created a human codon optimized version of FtsZ, the central component of the bacterial division machinery, and fused it to a mitochondrial targeting sequence. Upon expression in human cells, mt-FtsZ was imported into the mitochondrial matrix, specifically localizing at fission sites prior to Drp1 and significantly increasing mitochondrial fission levels. Our data suggests that human mitochondria have an internal, matrix-localized fission machinery, whose structure is sufficiently conserved as to accommodate bacterial FtsZ. We identified interaction partners of mt-FtsZ, and show that expression of PGAM5, FAM210, SFXN3 and MTCH1 induced mitochondrial fission. Our results thus represent an innovative approach for the discovery of novel critical mitochondrial fission components.

15: Low-N protein engineering with data-efficient deep learning
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Posted to bioRxiv 24 Jan 2020

Low-N protein engineering with data-efficient deep learning
30 tweets synthetic biology

Surojit Biswas, Grigory Khimulya, Ethan C Alley, Kevin M. Esvelt, George M. Church

Protein engineering has enormous academic and industrial potential. However, it is limited by the lack of experimental assays that are consistent with the design goal and sufficiently high-throughput to find rare, enhanced variants. Here we introduce a machine learning-guided paradigm that can use as few as 24 functionally assayed mutant sequences to build an accurate virtual fitness landscape and screen ten million sequences via in silico directed evolution. As demonstrated in two highly dissimilar proteins, avGFP and TEM-1 β-lactamase, top candidates from a single round are diverse and as active as engineered mutants obtained from previous multi-year, high-throughput efforts. Because it distills information from both global and local sequence landscapes, our model approximates protein function even before receiving experimental data, and generalizes from only single mutations to propose high-functioning epistatically non-trivial designs. With reproducible >500% improvements in activity from a single assay in a 96-well plate, we demonstrate the strongest generalization observed in machine-learning guided protein design to date. Taken together, our approach enables efficient use of resource intensive high-fidelity assays without sacrificing throughput. By encouraging alignment with endpoint objectives, low-N design will accelerate engineered proteins into the fermenter, field, and clinic.

16: A comprehensive atlas of white matter tracts in the chimpanzee
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Posted to bioRxiv 25 Jan 2020

A comprehensive atlas of white matter tracts in the chimpanzee
29 tweets neuroscience

Katherine L Bryant, Longchuan Li, Rogier B Mars

Chimpanzees ( Pan troglodytes ) are, along with bonobos, the closest living relatives of humans. The advent of diffusion tractography in recent years has allowed a resurgence of comparative neuroanatomical studies in humans and other primate species. Here, we offer, in comparative perspective, the first chimpanzee white matter atlas, coupled with surface projection maps of these major white matter tracts, constructed from in vivo chimpanzee diffusion-weighted scans. Comparative white matter atlases provide a useful tool for identifying neuroanatomical differences and similarities between humans and other primate species. Until now, comprehensive fascicular atlases have been created for humans ( Homo sapiens ), rhesus macaques ( Macaca mulatta ), and several other nonhuman primate species, but never in a nonhuman ape. Information on chimpanzee neuroanatomy is essential for understanding the anatomical specializations of white matter organization that are unique to the human lineage.

17: High-throughput screens of PAM-flexible Cas9 variants for gene knock-out and transcriptional modulation
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Posted to bioRxiv 23 Jan 2020

High-throughput screens of PAM-flexible Cas9 variants for gene knock-out and transcriptional modulation
27 tweets bioengineering

Mateusz Legut, Zharko Daniloski, Xinhe Xue, Dayna McKenzie, Xinyi Guo, Hans-Hermann Wessels, Neville E. Sanjana

A key limitation of the commonly-used CRISPR enzyme S. pyogenes Cas9 is the strict requirement of an NGG protospacer-adjacent motif (PAM) at the target site, which reduces the number of accessible genomic loci. This constraint can be limiting for genome editing applications that require precise Cas9 positioning. Recently, two Cas9 variants with a relaxed PAM requirement (NG) have been developed (xCas9 and Cas9-NG) but their activity has been measured at only a small number of endogenous sites. Here we devised a high-throughput Cas9 pooled competition screen to compare the performance of both PAM-flexible Cas9 variants and wild-type Cas9 at thousands of genomic loci and across 3 modalities (gene knock-out, transcriptional activation and suppression). We show that PAM flexibility comes at a substantial cost of decreased DNA targeting and cutting. Of the PAM-flexible variants, we found that Cas9-NG outperforms xCas9 regardless of genome engineering modality or PAM. Finally, we combined xCas9 mutations with those of Cas9-NG, creating a stronger transcriptional modulator than existing PAM-flexible Cas9 variants.

18: Climate change will drive novel cross-species viral transmission
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Posted to bioRxiv 25 Jan 2020

Climate change will drive novel cross-species viral transmission
24 tweets ecology

Colin J. Carlson, Gregory F Albery, Cory Merow, Christopher H Trisos, Casey M. Zipfel, Evan A Eskew, Kevin J Olival, Noam Ross, Shweta Bansal

Between 10,000 and 600,000 species of mammal virus are estimated to have the potential to spread in human populations, but the vast majority are currently circulating in wildlife, largely undescribed and undetected by disease outbreak surveillance [1,2,3]. In addition, changing climate and land use drive geographic range shifts in wildlife, producing novel species assemblages and opportunities for viral sharing between previously isolated species [4,5]. In some cases, this will inevitably facilitate spillover into humans [6,7] - a possible mechanistic link between global environmental change and emerging zoonotic disease [8]. Here, we map potential hotspots of viral sharing, using a phylogeographic model of the mammal-virus network, and projections of geographic range shifts for 3,870 mammal species under climate change and land use scenarios for the year 2070. Shifting mammal species are predicted to aggregate at high elevations, in biodiversity hotspots, and in areas of high human population density in Asia and Africa, sharing novel viruses between 3,000 and 13,000 times. Counter to expectations, holding warming under 2 C within the century does not reduce new viral sharing, due to greater range expansions - highlighting the need to invest in surveillance even in a low-warming future. Most projected viral sharing is driven by diverse hyperreservoirs (rodents and bats) and large-bodied predators (carnivores). Because of their unique dispersal capacity, bats account for the majority of novel viral sharing, and are likely to share viruses along evolutionary pathways that could facilitate future emergence in humans. Our findings highlight the urgent need to pair viral surveillance and discovery efforts with biodiversity surveys tracking range shifts, especially in tropical countries that harbor the most emerging zoonoses.

19: Neurons in Visual Cortex are Driven by Feedback Projections when their Feedforward Sensory Input is Missing
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Posted to bioRxiv 25 Jan 2020

Neurons in Visual Cortex are Driven by Feedback Projections when their Feedforward Sensory Input is Missing
22 tweets neuroscience

Andreas J Keller, Morgane M Roth, Massimo Scanziani

We sense our environment through pathways linking sensory organs to the brain. In the visual system, these feedforward pathways define the classical feedforward receptive field (ffRF), the area in space where visual stimuli excite a neuron. The visual system also uses visual context, the visual scene surrounding a stimulus, to predict the content of the stimulus, and accordingly, neurons have been found that are excited by stimuli outside their ffRF. The mechanisms generating excitation to stimuli outside the ffRF are, however, unclear. Here we show that feedback projections onto excitatory neurons in mouse primary visual cortex (V1) generate a second receptive field driven by stimuli outside the ffRF. Stimulating this feedback receptive field (fbRF) elicits slow and delayed responses compared to ffRF stimulation. These responses are preferentially reduced by anesthesia and, importantly, by silencing higher visual areas (HVAs). Feedback inputs from HVAs have scattered receptive fields relative to their putative V1 targets enabling the generation of the fbRF. Neurons with fbRFs are located in cortical layers receiving strong feedback projections and are absent in the main input layer, consistent with a laminar processing hierarchy. The fbRF and the ffRF are mutually antagonistic since large, uniform stimuli, covering both, suppress responses. While somatostatin-expressing inhibitory neurons are driven by these large stimuli, parvalbumin and vasoactive-intestinal-peptide-expressing inhibitory neurons have antagonistic fbRF and ffRF, similar to excitatory neurons. Therefore, feedback projections may enable neurons to use context to predict information missing from the ffRF and to report differences in stimulus features across visual space, regardless if excitation occurs inside or outside the ffRF. We have identified a fbRF which, by complementing the ffRF, may contribute to predictive processing.

20: Genomic and phenotypic evolution of Escherichia coli in a novel citrate-only resource environment
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Posted to bioRxiv 23 Jan 2020

Genomic and phenotypic evolution of Escherichia coli in a novel citrate-only resource environment
22 tweets evolutionary biology

Zachary D. Blount, Rohan Maddamsetti, Nkrumah A Grant, Sumaya T Ahmed, Tanush Jagdish, Brooke A Sommerfeld, Alice Tillman, Jeremy P Moore, Joan L Slonczewski, Jeffrey E. Barrick, Richard E. Lenski

Evolutionary innovations allow populations to colonize new, previously inaccessible ecological niches. We previously reported that aerobic growth on citrate (Cit++) evolved in a population of Escherichia coli during adaptation to a minimal glucose medium containing citrate (DM25). Cit+ can grow in citrate-only medium (DM0), which is a novel environment for E. coli . To study adaptation to this new niche, we evolved one set of Cit+ populations for 2,500 generations in DM0 and a control set in DM25. We identified numerous parallel mutations, many mediated by transposable elements. Several lineages evolved multi-copy amplifications containing the maeA gene, constituting up to ~15% of the genome. We also found substantial cell death in ancestral and evolved clones. Our results demonstrate the importance of copy-number variation and transposable elements in the refinement of the Cit+ trait. However, the observed mortality suggests a persistent evolutionary mismatch between E. coli physiology and a citrate-only environment.

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