Christopher T. Richards and Enrico A. Eberhard

Muscle force-length dynamics are governed by intrinsic contractile properties, motor stimulation and mechanical load. Although intrinsic properties are well-characterised, physiologists lack in vitro instrumentation accounting for combined effects of limb inertia, musculoskeletal architecture and contractile dynamics. We introduce in vitro virtual-reality (in vitro-VR) which enables in vitro muscle tissue to drive a musculoskeletal jumping simulation. In hardware, muscle force from a frog plantaris was transmitted to a software model where joint torques, inertia and ground reaction forces were computed to advance the simulation at 1 kHz. To close the loop, simulated muscle strain was returned to update in vitro length. We manipulated 1) stimulation timing and, 2) the virtual muscle's anatomical origin. This influenced interactions among muscular, inertial, gravitational and contact forces dictating limb kinematics and jump performance. We propose that in vitro-VR can be used to illustrate how neuromuscular control and musculoskeletal anatomy influence muscle dynamics and biomechanical performance.

Background

Clinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed.

Endogenous viral elements (EVEs) are found in many eukaryotic genomes. Despite considerable knowledge about genomic elements such as transposons (TEs) and retroviruses, we still lack information about nonretroviral EVEs. Aedes aegypti mosquitoes have a highly repetitive genome that is covered with EVEs. Here, we identified 129 nonretroviral EVEs in the AaegL5 version of the A. aegypti genome. These EVEs were significantly associated with TEs and preferentially located in repeat-rich clusters within intergenic regions. Genome-wide transcriptome analysis showed that most EVEs generated transcripts although only around 1.4% were sense RNAs. The majority of EVE transcription was antisense and correlated with the generation of EVE-derived small RNAs. A single genomic cluster of EVEs located in a 143 kb repetitive region in chromosome 2 contributed with 42% of antisense transcription and 45% of small RNAs derived from viral elements. This region was enriched for TE-EVE hybrids organized in the same coding strand. These generated a single long antisense transcript that correlated with the generation of phased primary PIWI-interacting RNAs (piRNAs). The putative promoter of this region had a conserved binding site for the transcription factor Cubitus interruptus, a key regulator of the flamenco locus in Drosophila melanogaster. Here, we have identified a single unidirectional piRNA cluster in the A. aegypti genome that is the major source of EVE transcription fueling the generation of antisense small RNAs in mosquitoes. We propose that this region is a flamenco-like locus in A. aegypti due to its relatedness to the major unidirectional piRNA cluster in Drosophila melanogaster.

Retrospective lineage tracing harnesses naturally occurring mutations in cells to elucidate single cell development. Common single-cell phylogenetic fate mapping methods have utilized highly mutable microsatellite loci found within the human genome. Such methods were limited by the introduction of in vitro noise through polymerase slippage inherent in DNA amplification, which we characterized to be approximately 10–100x higher than the in vivo replication mutation rate. Here, we present RETrace, a method for simultaneously capturing both microsatellites and methylation-informative cytosines to characterize both lineage and cell type, respectively, from the same single cell. An important unique feature of RETrace was the introduction of linear amplification of microsatellites in order to reduce in vitro amplification noise. We further coupled microsatellite capture with single-cell reduced representation bisulfite sequencing (scRRBS), to measure the CpG methylation status on the same cell for cell type inference. When compared to existing retrospective lineage tracing methods, RETrace achieved higher accuracy (88% triplet accuracy from an ex vivo HCT116 tree) at a higher cell division resolution (lowering the required number of cell division difference between single cells by approximately 100 divisions). Simultaneously, RETrace demonstrated the ability to capture on average 150,000 unique CpGs per single cell in order to accurately determine cell type. We further formulated additional developments that would allow high-resolution mapping on microsatellite-stable cells or tissues with RETrace. Overall, we present RETrace as a foundation for multi-omics lineage mapping and cell typing of single cells.

Introduction

Immunotherapy has become the standard of care in advanced non-small cell lung cancer (NSCLC). We aimed to quantify the economic impact, in France, of anti-PD-1 therapy for NSCLC.

A longstanding awareness in generating resistance to common antimicrobial therapies by Gram-negative bacteria has made them a major threat to global health. The application of antimicrobial peptides as a therapeutic agent would be a great opportunity to combat bacterial diseases. Here, we introduce a new antimicrobial peptide (~8.3 kDa) from probiotic strain Lactobacillus acidophilus ATCC 4356, designated acidocin 4356 (ACD). This multifunctional peptide exerts its anti-infective ability against Pseudomonas aeruginosa through an inhibitory action on virulence factors, bacterial killing, and biofilm degradation. Reliable performance over tough physiological conditions and low hemolytic activity confirmed a new hope for the therapeutic setting. Antibacterial kinetic studies using flow cytometry technique showed that the ACD activity is related to the change in permeability of the membrane. The results obtained from molecular dynamic (MD) simulation were perfectly suited to the experimental data of ACD behavior. The structure-function relationship of this natural compound, along with the results of transmission electron microscopy analysis and MD simulation, confirmed the ability of the ACD aimed at enhancing bacterial membrane perturbation. The peptide was effective in the treatment of P. aeruginosa infection in mouse model. The results support the therapeutic potential of ACD for the treatment of Pseudomonas infections.

IMPORTANCE Multidrug-resistant bacteria are a major threat to global health, and the Pseudomonas bacterium with the ability to form biofilms is considered one of the main causative agents of nosocomial infections. Traditional antibiotics have failed because of increased resistance. Thus, finding new biocompatible antibacterial drugs is essential. Antimicrobial peptides are produced by various organisms as a natural defense mechanism against pathogens, inspiring the possible design of the next generation of antibiotics. In this study, a new antimicrobial peptide was isolated from Lactobacillus acidophilus ATCC 4356, counteracting both biofilm and planktonic cells of Pseudomonas aeruginosa. A detailed investigation was then conducted concerning the functional mechanism of this peptide by using fluorescence techniques, electron microscopy, and in silico methods. The antibacterial and antibiofilm properties of this peptide may be important in the treatment of Pseudomonas infections.

London’s leading real estate agents Daniel Cobb have revealed top 10 simple tricks to add values to your home and sell it faster, The Sun reported.

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Many people see buy-to-rent as an attractive income investment in a time of low rates and stock market volatility. But if you are considering investing in property - or improving your returns on a buy-to-rent you already own - it's important to do things right.

भगवान विष्णु ने नरसिंह का अवतार लेकर हिरण्कश्यपु का वध करके अपने प्रिय भक्त प्रह्रलाद की जान बचाई थी। भगवान विष्णु ने पृथ्वी पर कई अलग-अलग अवतार लेकर अपने भक्तों को मुसीबतों से बचाया है।

A review of two-factor authentication methods, which involve websites sending confirmation texts to your phone, has found that millions of people may risk having their online accounts hacked

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A team of researchers at the Massachusetts Institute of Technology (MIT) has demonstrated that single-celled microorganisms such as Escherichia coli and Saccharomyces cerevisiae that normally do not inhabit hydrogen-rich environments can survive and grow in a 100% hydrogen atmosphere. “There’s a diversity of habitable worlds out there, and we have confirmed that Earth-based life can [...]

In an exclusive interview, climate activist Greta Thunberg has told New Scientist that the coronavirus pandemic shows we can act quickly in an emergency

The Simpsons has done it again, this time predicting the COVID-19 pandemic and murder hornets. Here are some other instances of The Simpsons predicting the future.

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The 39-year-old star has fired back at Vogue editor Sally Singer after a piece reflecting on the 2007 Met Gala which criticised her low cut

Scientists have presented a non-contact method for detecting the state of charge and any defects in lithium-ion batteries.

Scientists have developed a method that combines different resolution levels in a computer simulation of biological membranes. Their algorithm backmaps a large-scale model that includes features, such as membrane curvature, to its corresponding coarse-grained molecular model. This has allowed them to zoom in on toxin-induced membrane budding and to simulate a full-sized mitochondrial lipid membrane. Their approach opens the way to whole-cell simulations at a molecular level.

A recent study has described new states that can be found in super-cold atom experiments, which could have applications for quantum technology.

BBC News looks at what we know and don't know about the Earth's changing climate.

Stephanie Labbé, goalkeeper for the Canada's soccer team, and her long-time girlfriend Georgia Simmerling, a vital member for Canada's team pursuit in track cycling, have already qualified for the Tokyo Games. But the COVID-19 lockdown measures have rocked them. This Olympic couple had planned to retire. Now, instead of facing four months until retirement they face 16 months.

The Simpsons may have predicted 2020's pandemic and murder hornets

Plague Inc. is an app and online game in which users play the role of a disease set on infecting the world with a pathogen.

Fans think The Simpsons predicted everything from Trump's presidency to coronavirus

Bill Oakley dug up notes from more than 25 years ago that showed the writers' intentions for that particular scene

Thirty years on from Kelsey Grammer's remarkable cartoon debut, Louis Chilton looks at the legacy of one of the most endearing felons in fiction

Clausen previously alleged he was dismissed over his 'perceived disability and age'

People have noted a certain timeliness in a clip from the 1993 episode 'Marge in Chains'

Deep recessions have long shadows and already there is a gaping hole opening up in our pandemic response

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The great recession was followed by Brexit, the election of Donald Trump and the rise of authoritarianism particularly in Europe.

Big economic events have big political consequences.

Beckingham's older brother Pegg has been a "sound board" for him as he navigates the industry

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Forget a virtual haircut, all you need is this foolproof, three-step hack

Lizzie Edmonds speaks to travel expert Simon Calder about whether we should book summer holidays and how travel will be different

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Odion Ighalo believes Victor Osimhen has huge potential, with the Manchester United striker praising his compatriot as the "future of Nigerian football."

Victor Osimhen has opened up about why he rejected Arsenal as a teenager... and why he will use the same reasoning when it comes to his next move.

EXCLUSIVE: Quite a week for Netflix’s film division, which tonight won a ferocious auction for the Simon Kinberg spec script Here Comes The Flood. I’m told that the deal mid seven figures, an extremely high amount for a script that has no talent attached to it, but the kind of roles that attract stars. Deadline […]

While potential for finishing the 2019-2020 NBA season remains in doubt, the folks at NBA 2K have moved forward with simulating the results. The 2K Sim playoffs have completed their conference championships and are ready to “play” the final round. In...

«C’est mon rêve de jouer dans la LNH. C’est mon rêve de jouer à Montréal. C’est mon rêve préféré.»

Simi Valley two-sport athlete Chase Aurand learned a valuable history lesson amid the coronavirus outbreak: 'Don't take going to practice for granted.'

The Britain's Got Talent judges come crashing into tonight's auditions when Simon can't work the breaks - leaving David to claim he has whiplash