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Currently indexing 66,973 bioRxiv papers from 294,811 authors.

Most tweeted bioRxiv papers, last 24 hours

Results 1 through 20 out of 174


1: The nucleus measures shape deformation for cellular proprioception and regulates adaptive morphodynamics

Valeria Venturini, Fabio Pezzano et al.

37 tweets (posted 05 Dec 2019) cell biology

The physical microenvironment regulates cell behavior during tissue development and homeostasis. How single cells decode information about their geometrical shape under mechanical stress and physical space constraints within their local environment remains largely unknown. Here we show that the nucleus, the biggest cellular organelle, functions as a non-dissipative cellular shape deformation gauge that enables cells to continuously measure shape variations on the time scale of seconds. Inner nuclear membrane unfolding together with the relative spatial intracellular positioning of the nucleus provides physical information on the amplitude and type of cellular shape deformation. This adaptively activates a calcium-dependent mechano-transduction pathway, controlling the level of actomyosin contractility and migration plasticity. Our data support that the nucleus establishes a functional module for cellular proprioception that enables cells to sense shape variations for adapting cellular behaviour to their microenvironment.


2: Late life metformin treatment limits cell survival and shortens lifespan by triggering an aging-associated failure of energy metabolism.

Lilia Espada, Alexander Dakhovnik et al.

32 tweets (posted 03 Dec 2019) physiology

The diabetes drug metformin is to be clinically tested in aged humans to achieve health span extension, but little is known about responses of old non-diabetic individuals to this drug. By in vitro and in vivo tests we found that metformin shortens life span and limits cell survival when provided in late life, contrary to its positive early life effects. Mechanistically, metformin exacerbates aging-associated mitochondrial dysfunction towards respiratory failure, aggravated by the inability of old cells to upregulate gl...


3: The nucleus acts as a ruler tailoring cell responses to spatial constraints

Alexis Lomakin, Cedric Cattin et al.

29 tweets (posted 05 Dec 2019) cell biology

The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. Here, we found that cells measure the degree of spatial confinement using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, upregulating cell contractili...


4: Single-cell mass-spectrometry quantifies the emergence of macrophage heterogeneity

Harrison Specht, Edward Emmott et al.

26 tweets (posted 09 Jun 2019) systems biology

The fate and physiology of individual cells are controlled by protein interactions. Yet, our ability to quantitatively analyze proteins in single cells has remained limited. To overcome this barrier, we developed SCoPE2. It lowers cost and hands-on time by introducing automated and miniaturized sample preparation while substantially increasing quantitative accuracy. These advances enabled us to analyze the emergence of cellular heterogeneity as homogeneous monocytes differentiated into macrophage-like cells in the absen...


5: Dopamine modulates the size of striatal projection neuron ensembles

Marta Maltese, Jeffrey R March et al.

26 tweets (posted 05 Dec 2019) neuroscience

Dopamine (DA) is a critical modulator of brain circuits that control voluntary movements, but our understanding of its influence on the activity of target neurons in vivo remains limited. Here, we use two-photon Ca2+ imaging to simultaneously monitor the activity of direct and indirect-pathway spiny projection neurons (SPNs) in the striatum of behaving mice during acute and prolonged manipulations of DA signaling. We find that, contrary to prevailing models, DA does not modulate activity rates in either pathway strongly...


6: Combining antibiotics with antivirulence compounds is effective and can reverse selection for antibiotic resistance in Pseudomonas aeruginosa

Chiara Rezzoagli, Martina Archetti et al.

21 tweets (posted 05 Dec 2019) microbiology

Antibiotics are losing efficacy due to the rapid evolution and spread of resistance. Treatments targeting bacterial virulence factors have been considered as alternatives because they target virulence instead of pathogen viability, and should therefore exert weaker selection for resistance than conventional antibiotics. However, antivirulence treatments rarely clear infections, which compromises their clinical applications. Here, we explore the potential of combining antivirulence drugs with antibiotics against the oppo...


7: Combining machine learning and a universal acoustic feature-set yields efficient automated monitoring of ecosystems

Sarab S Sethi, Nick S Jones et al.

18 tweets (posted 05 Dec 2019) ecology

Natural habitats are being impacted by human pressures at an alarming rate. Monitoring these ecosystem-level changes often requires labour-intensive surveys that are unable to detect rapid or unanticipated environmental changes. Here we developed a generalisable, data-driven solution to this challenge using eco-acoustic data. We exploited a convolutional neural network to embed ecosystem soundscapes from a wide variety of biomes into a common acoustic space. In both supervised and unsupervised modes, this allowed us to ...


8: Plant Small RNA Species Direct Gene Silencing in Pathogenic Bacteria as well as Disease Protection


18 tweets (posted 03 Dec 2019) plant biology

Plant small RNAs (sRNAs) and/or double-stranded RNAs (dsRNAs) trigger RNA interference (RNAi) in interacting eukaryotic pathogens or parasites. However, it is unknown whether this phenomenon could operate in bacterial phytopathogens, which lack a eukaryoticlike RNAi machinery. Here, we first show that Arabidopsis-encoded inverted repeat transgenes trigger silencing of Pseudomonas syringae heterologous reporter and endogenous virulence-associated genes during infection. Antibacterial Gene Silencing (AGS) of the latter wa...


9: On the discovery of population-specific state transitions from multi-sample multi-condition single-cell RNA sequencing data

Helena L Crowell, Charlotte Soneson et al.

16 tweets (posted 26 Jul 2019) bioinformatics

Single-cell RNA sequencing (scRNA-seq) has quickly become an empowering technology to profile the transcriptomes of individual cells on a large scale. Many early analyses of differential expression have aimed at identifying differences between subpopulations, and thus are focused on finding markers for cell populations either in a single sample or across multiple samples. More generally, such methods can compare expression levels in multiple sets of cells, thus leading to cross-condition analyses. However, given the eme...


10: Clair: Exploring the limit of using a deep neural network on pileup data for germline variant calling

Ruibang Luo, Chak-Lim Wong et al.

16 tweets (posted 05 Dec 2019) bioinformatics

Single-molecule sequencing technologies have emerged in recent years and revolutionized structural variant calling, complex genome assembly, and epigenetic mark detection. However, the lack of a highly accurate small variant caller has limited the new technologies from being more widely used. In this study, we present Clair, the successor to Clairvoyante, a program for fast and accurate germline small variant calling, using single molecule sequencing data. For ONT data, Clair achieves the best precision, recall and spee...


11: The smfBox: an open-source platform for single-molecule FRET

Benjamin Ambrose, James Baxter et al.

14 tweets (posted 05 Dec 2019) biophysics

Single-molecule Förster Resonance Energy Transfer (smFRET) is a powerful technique capable of resolving both relative and absolute distances within and between structurally dynamic biomolecules. High instrument costs, and a lack of open-source hardware and acquisition software have limited smFRET's broad application by non-specialists. Here, we present the smfBox, a cost-effective confocal smFRET platform, providing detailed build instructions, open-source acquisition software, and full validation, thereby democratising...


12: Plants emit informative airborne sounds under stress

I. Khait, Ohad Lewin-Epstein et al.

14 tweets (posted 28 Dec 2018) plant biology

Stressed plants show altered phenotypes, including changes in color, smell, and shape. Yet, the possibility that plants emit airborne sounds when stressed – similarly to many animals – has not been investigated. Here we show, to our knowledge for the first time, that stressed plants emit airborne sounds that can be recorded remotely, both in acoustic chambers and in greenhouses. We recorded ∼65 dBSPL ultrasonic sounds 10 cm from tomato and tobacco plants, implying that these sounds could be detected by some organisms fr...


13: Local axonal conduction delays underlie precise timing of a neural sequence

Robert Egger, Yevhen Tupikov et al.

11 tweets (posted 05 Dec 2019) neuroscience

Sequential activation of neurons has been observed during various behavioral and cognitive processes and is thought to play a critical role in their generation. Here, we studied a circuit in the songbird forebrain that drives the performance of adult courtship song. In this region, known as HVC, neurons are sequentially active with millisecond precision in relation to behavior. Using large-scale network models, we found that HVC sequences could only be accurately produced if sequentially active neurons were linked with ...


14: Tracking selective rehearsal and active inhibition of memory traces in directed forgetting

Marie-Christin Fellner, Gerd T. Waldhauser et al.

11 tweets (posted 05 Dec 2019) neuroscience

Selectively remembering or forgetting newly encountered information is essential for goal-directed behavior. It is still an open question, however, whether intentional forgetting is an active process based on the inhibition of unwanted memory traces or whether it occurs passively through reduced recruitment of selective rehearsal. Here we show that intentional control of memory encoding relies on both, enhanced active inhibition and decreased selective rehearsal, and that these two processes can be separated in time and...


15: Material aging causes centrosome weakening and disassembly during mitotic exit

Matthaeus Mittasch, Vanna M. Tran et al.

11 tweets (posted 05 Dec 2019) cell biology

Centrosomes must resist microtubule-mediated forces for mitotic chromosome segregation. During mitotic exit, however, centrosomes are deformed and fractured by those same forces, which is a key step in centrosome disassembly. How the functional material properties of centrosomes change throughout the cell cycle, and how they are molecularly tuned remain unknown. Here, we used optically-induced flow perturbations to determine the molecular basis of centrosome strength and ductility in C. elegans embryos. We found that bo...


16: Endocrine autoimmune disease as a fragility of immune-surveillance against hypersecreting mutants

Yael Korem Kohanim, Avichai Tendler et al.

9 tweets (posted 17 Nov 2019) immunology

Many endocrine organs show prevalent autoimmune diseases (AID) such as type-1-diabetes and Hashimoto's-thyroiditis. The fundamental origins of these diseases is unclear. Here we address AID from the viewpoint of feedback control. Endocrine tissues maintain their mass by feedback-loops that balance cell proliferation and removal according to input signals related to the hormone function. Such feedback is unstable to mutant cells that mis-sense the signal, and therefore hyper-proliferate and hyper-secrete the hormone. We ...


17: Effects of feeding treatment on growth rate and performance of primiparous Holstein dairy heifers

Yannick Le Cozler, Julien Jurquet et al.

8 tweets (posted 08 Sep 2019) zoology

The objective of this study was to investigate effects of feeding-rearing programs that aim for first calving at 20-27 months (mo) of age on growth, reproduction and production performance of Holstein cows at nulliparous and primiparous stages. We hypothesised that, in a seasonal autumn-calving strategy, heifers born late in the season could catch up to the growth of heifers born earlier and be inseminated during the same period, at a body weight (BW) of at least 370 kg. This approach would result in first calving age a...


18: Barcoding and demultiplexing Oxford Nanopore native RNA sequencing reads with deep residual learning

Martin Smith, Tansel Ersavas et al.

8 tweets (posted 04 Dec 2019) genomics

Nanopore sequencing has enabled sequencing of native RNA molecules without conversion to cDNA, thus opening the gates to a new era for the unbiased study of RNA biology. However, a formal barcoding protocol for direct sequencing of native RNA molecules is currently lacking, limiting the efficient processing of multiple samples in the same flowcell. A major limitation for the development of barcoding protocols for direct RNA sequencing is the error rate introduced during the base-calling process, especially towards the 5...


19: Enabling high-accuracy long-read amplicon sequences using unique molecular identifiers and Nanopore sequencing

Soeren Michael Karst, Ryan Ziels et al.

7 tweets (posted 24 May 2019) molecular biology

High-throughput amplicon sequencing of large genomic regions represents a challenge for existing short-read technologies. Long-read technologies can in theory sequence large genomic regions, but they currently suffer from high error rates. Here, we report a high-throughput amplicon sequencing approach that combines unique molecular identifiers (UMIs) with Oxford Nanopore sequencing to generate single-molecule consensus sequences of large genomic regions. We demonstrate the approach by generating nearly 10,000 full-lengt...


20: Direct RNA sequencing reveals m6A modifications on adenovirus RNA are necessary for efficient splicing

Alexander M. Price, Katharina E. Hayer et al.

7 tweets (posted 05 Dec 2019) molecular biology

Adenovirus is a nuclear replicating DNA virus reliant on host RNA processing machinery. Processing and metabolism of cellular RNAs can be regulated by METTL3, which catalyzes the addition of N6-methyladenosine (m6A) to mRNAs. While m6A-modified adenoviral RNAs have been previously detected, the location and function of this mark within the infectious cycle is unknown. Since the complex adenovirus transcriptome includes overlapping spliced units that would impede accurate m6A mapping using short-read sequencing, we profi...