Top 10 Biorxiv Papers Today


3.036 Mikeys
#1. Remodeling of Crossbridges Controls Peptidoglycan Crosslinking Levels in Bacterial Cell Walls
Sean Pidgeon, Alexis Apostolos, Marcos M Pires
Cell walls are barriers found in almost all known bacterial cells. These structures establish a controlled interface between the external environment and vital cellular components. A primary component of cell wall is a highly crosslinked matrix called peptidoglycan (PG). PG cross-linking, carried out by transglycosylases and transpeptidases, is necessary for proper cell wall assembly. Transpeptidases, targets of b-lactam antibiotics, stitch together two neighboring PG stem peptides (acyl-donor and acyl-acceptor strands). We recently described a novel class of cellular PG probes that were processed exclusively as acyl-donor strands. Herein, we have accessed the other half of the transpeptidase reaction by developing probes that are processed exclusively as acyl-acceptor strands. The critical nature of the crossbridge on the PG pep-tide was demonstrated in live bacterial cells and surprising promiscuity in crossbridge primary sequence was found in various bacterial species. Additionally, acyl-acceptor probes provided insight into...
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biorxivpreprint: Remodeling of Crossbridges Controls Peptidoglycan Crosslinking Levels in Bacterial Cell Walls https://t.co/ae3usDPVyu #bioRxiv
biorxiv_micrbio: Remodeling of Crossbridges Controls Peptidoglycan Crosslinking Levels in Bacterial Cell Walls https://t.co/9ce0kGFwxo #biorxiv_micrbio
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3.004 Mikeys
#2. Astral Microtubules Regulate Formation of the Cytokinetic Cleavage Furrow in Fission Yeast
Samantha ER Dundon, Thomas D Pollard
Microtubules of the mitotic spindle direct cytokinesis in metazoans but this has not been documented in fungi. We report evidence that astral microtubules help coordinate cytokinetic furrow formation in fission yeast. The temperature-sensitive cps1-191 strain (Liu et al., 1999) with a D277N substitution in β-glucan synthase 1 (Cps1/Bgs1) was reported to arrest with an unconstricted contractile ring. We discovered that rings in cps1-191 cells do constrict slowly and that an S338N mutation in the mto2 gene is required with the bgs1-D277N mutation to reproduce the cps1-191 phenotype. Complexes of Mto2 and Mto1 with γ-tubulin regulate microtubule assembly. Deletion of Mto1 along with the bgs1-D277N mutation also gives the cps1-191 phenotype, which is not observed in mto2-S338N or mto1Δ cells expressing bgs1+. Both mto2-S338N and mto1Δ cells nucleate fewer astral microtubules than normal and have higher levels of Rho1-GTP at the division site than wild-type cells. We report multiple conditions that sensitize mto1Δ and mto2-S338N cells...
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biorxivpreprint: Astral Microtubules Regulate Formation of the Cytokinetic Cleavage Furrow in Fission Yeast https://t.co/ttY3yB9ExL #bioRxiv
biorxiv_cellbio: Astral Microtubules Regulate Formation of the Cytokinetic Cleavage Furrow in Fission Yeast https://t.co/GIkl3Muo4f #biorxiv_cellbio
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2.619 Mikeys
#3. Exposure to nicotine vapor causes short-term increases in impulsive choice in rats.
Rodolfo J. Flores, Fatima Z. Alshbool, Priscilla Giner, Laura E. O'Dell, Ian A. Mendez
Previous studies have shown that exposure to nicotine smoke increases impulsivity. Surprisingly, research investigating the effects of electronic cigarette nicotine vapor exposure on impulsivity has not been conducted. Therefore, the present study examined the effects of nicotine vapor exposure on impulsive choice. Twenty-four adult male rats were trained in the delay discounting task to choose between small immediate food rewards or larger food rewards with delayed deliveries. After 24 days of training in the delay discounting task, rats were passively exposed to vapor containing either 0, 12, or 24 mg/mL of nicotine for 10 days. To monitor exposure to nicotine, serum cotinine levels were assessed on exposure days 1, 5, and 10 using enzyme-linked immunosorbent assay (ELISA). Following vapor exposure, rats were retrained in the delay discounting task until stable performance was achieved, and the effects of nicotine vapor exposure on choice preference were assessed. Rats that were exposed to 12 and 24 mg/mL nicotine vapor...
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biorxivpreprint: Exposure to nicotine vapor causes short-term increases in impulsive choice in rats. https://t.co/WIMbtr82fz #bioRxiv
DLydonStaley: RT @biorxivpreprint: Exposure to nicotine vapor causes short-term increases in impulsive choice in rats. https://t.co/WIMbtr82fz #bioRxiv
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2.609 Mikeys
#4. Complex spikes encode reward expectation signals during visuomotor association learning
Naveen Sendhilnathan, Anna E Ipata, Michael E Goldberg
Climbing fiber input to Purkinje cells has been thought to instruct learning related changes in simple spikes and cause behavioral changes through an error-based learning mechanism. Although, this framework explains simple motor learning, it cannot be extended to learning higher-order skills. Recently the cerebellum has been implicated in a variety of cognitive tasks and reward-based learning. Here we show that when a monkey learns a new visuomotor association, complex spikes predict the time of the beginning of the trial in a learning independent manner as well as encode a learning contingent reward expectation signal after the stimulus onset and reward delivery. These complex spike signals are unrelated to and were unlikely to instruct the reward based signal found in the simple spikes. Our results provide a more general role of complex spikes in learning and higher-order processing while gathering evidence for their participation in reward based learning.
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biorxiv_neursci: Complex spikes encode reward expectation signals during visuomotor association learning https://t.co/9c2qFFBrLs #biorxiv_neursci
biorxivpreprint: Complex spikes encode reward expectation signals during visuomotor association learning https://t.co/rp3truOLKs #bioRxiv
NeuroLuyckx: RT @biorxiv_neursci: Complex spikes encode reward expectation signals during visuomotor association learning https://t.co/9c2qFFBrLs #bior…
geewhiz_ephys: RT @biorxiv_neursci: Complex spikes encode reward expectation signals during visuomotor association learning https://t.co/9c2qFFBrLs #bior…
yasuyotanaka: RT @biorxiv_neursci: Complex spikes encode reward expectation signals during visuomotor association learning https://t.co/9c2qFFBrLs #bior…
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2.355 Mikeys
#5. Tumor microtubes connect pancreatic cancer cells in an Arp2/3 complex-dependent manner
Casey J Latario, Lori W Schoenfeld, Charles L Howarth, Laura E Pickrell, Fatema Begum, Dawn A Fischer, Olivera Grbovic-Huezo, Steven D Leach, Yolanda Sanchez, Kerrington D Smith, Henry N Higgs
Actin-based tubular connections between cells have been observed in many cell types. Termed "tunneling nanotubes (TNTs)", "membrane nanotubes", "tumor microtubes (TMTs)", or "cytonemes", these protrusions interconnect cells in dynamic networks. Structural features in these protrusions vary between cellular systems, including tubule diameter and presence of microtubules. We find tubular protrusions, which we classify as TMTs, in a pancreatic cancer cell line, DHPC-018. TMTs are present in DHPC-018-derived tumors in mice, as well as in a mouse model of pancreatic cancer and a sub-set of primary human tumors. DHPC-018 TMTs have heterogeneous diameter (0.39 - 5.85 μm, median 1.92 μm) and contain actin filaments, microtubules, and cytokeratin 19-based intermediate filaments. The actin filaments are cortical within the protrusion, as opposed to TNTs, in which filaments run down the center of the tube. TMTs are dynamic in length, but are long-lived (median > 60 min). Inhibition of actin polymerization, but not microtubules, results in...
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biorxivpreprint: Tumor microtubes connect pancreatic cancer cells in an Arp2/3 complex-dependent manner https://t.co/eKt3s4Vg7P #bioRxiv
biorxiv_cellbio: Tumor microtubes connect pancreatic cancer cells in an Arp2/3 complex-dependent manner https://t.co/U9bEtqH8X9 #biorxiv_cellbio
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2.355 Mikeys
#6. Gli1+ mesenchymal stromal cells modulate epithelial metaplasia in lung fibrosis
Monica Cassandras, Chaoqun Wang, Jaymin Kathiriya, Tatsuya Tsukui, Peri Matatia, Michael Matthay, Paul Wolters, Ari Molofsky, Dean Sheppard, Hal Chapman, Tien Peng
Organ fibrosis is often accompanied by aberrant epithelial reprogramming, culminating in a transformed barrier composed of scar and metaplastic epithelium. Understanding how the scar promotes an abnormal epithelial response could better inform strategies to reverse the fibrotic damage. Here we show that Gli1+ mesenchymal stromal cells (MSCs), previously shown to contribute to myofibroblasts in the scar, promote metaplastic differentiation of airway progenitors into KRT5+ basal cells in vitro and in vivo. During fibrotic repair, Gli1+ MSCs integrate hedgehog activation to promote metaplastic KRT5 differentiation by upregulating BMP antagonism in the progenitor niche. Restoring the balance towards BMP activation attenuated metaplastic KRT5+ differentiation while promoting adaptive alveolar differentiation. Finally, fibrotic human lungs demonstrate altered BMP activation in the metaplastic epithelium. These findings show that Gli1+ MSCs integrate hedgehog signaling as a rheostat to control BMP activation in the progenitor niche to...
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biorxivpreprint: Gli1+ mesenchymal stromal cells modulate epithelial metaplasia in lung fibrosis https://t.co/mmeOfi2DjE #bioRxiv
biorxiv_cellbio: Gli1+ mesenchymal stromal cells modulate epithelial metaplasia in lung fibrosis https://t.co/tJtSc6EDRG #biorxiv_cellbio
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2.355 Mikeys
#7. Determining the content of vesicles captured by golgin tethers using LOPIT-DC
John Jae Hee Shin, Sean Munro, Kathryn Susan Lilley, Oliver M Crook, Alicia Borgeaud, Jerome Cattin-Ortola, Seu-Yeu Peak-Chew, Jessica Chadwick
The internal organisation of the cell depends on tethers at destination organelles to selectively capture incoming transport vesicles to facilitate SNARE-mediated fusion. The golgin long coiled- coil proteins function as tethers that contributes to this specificity at the Golgi (1). Golgin-97, golgin-245 and GCC88 golgins of the trans-Golgi capture vesicles derived from endosomes, which serve to recycle the critical Golgi machinery required to deliver lysosomal hydrolases and to maintain exocytosis. Retrograde trafficking from endosomes to the trans-Golgi network (TGN) is a complex process that involves the sorting of transmembrane cargo proteins into distinct transport vesicles by adaptors from multiple pathways. The content of these distinct vesicles, which golgin they target and the factors that mediate this targeting are not well understood. The major challenges that have limited advances in these areas is the transient nature of vesicle tethering, and the redundancies in their mechanisms that confound experimental dissection....
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biorxivpreprint: Determining the content of vesicles captured by golgin tethers using LOPIT-DC https://t.co/WIa8B4T0tI #bioRxiv
biorxiv_cellbio: Determining the content of vesicles captured by golgin tethers using LOPIT-DC https://t.co/e4NPPDCBqq #biorxiv_cellbio
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2.353 Mikeys
#8. Family permutation profiling identifies a dynamic protein domain as functionally tolerant to increased conformational entropy
Joshua T Atkinson, Alicia M Jones, Vikas Nanda, Jonathan J Silberg
To investigate whether adenylate kinase (AK) homologs differ in their functional tolerance to mutational lesions that alter dynamics, we subjected three homologs having a range of thermostabilities to random circular permutation and evaluated where new protein termini were non-disruptive to activity using a cellular selection and deep mutational scanning. Analysis of the positional tolerance to new termini, which increase local conformational entropy by breaking peptide bonds, showed that bonds were either functionally sensitive to cleavage across all three homologs, differentially sensitive, or uniformly tolerant. The mobile AMP binding domain, which displays the highest calculated contact energies (frustration), presented the greatest tolerance to new termini across all AKs. In contrast, retention of function in the lid and core domains was more dependent upon AK melting temperature. Thus, regions of high energetic frustration tolerated increases in conformational entropy in a manner that was less dependent on thermostability...
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biorxivpreprint: Family permutation profiling identifies a dynamic protein domain as functionally tolerant to increased conformational entropy https://t.co/FenwasZIeJ #bioRxiv
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2.268 Mikeys
#9. Nonlinear stimulus representations in neural circuits with approximate excitatory-inhibitory balance
Cody Baker, Vicky Zhu, Robert Rosenbaum
Balanced excitation and inhibition is widely observed in cortical recordings. How does this balance shape neural computations and stimulus representations? This problem is often studied using computational models of neuronal networks in a dynamically balanced state. However, these balanced network models predict a linear relationship between stimuli and population responses, in contrast to the nonlinearity of cortical computations. We show that every balanced network architecture admits some stimuli that break the balanced state and these breaks in balance push the network into a ''semi-balanced state'' characterized by excess inhibition to some neurons, but an absence of excess excitation. The semi-balanced state is unavoidable in networks driven by multiple stimuli, is more consistent with experimental data, has a direct mathematical relationship to artificial neural networks, and permits nonlinear stimulus representations and nonlinear computations.
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biorxiv_neursci: Nonlinear stimulus representations in neural circuits with approximate excitatory-inhibitory balance https://t.co/s5t2Y3aeqy #biorxiv_neursci
biorxivpreprint: Nonlinear stimulus representations in neural circuits with approximate excitatory-inhibitory balance https://t.co/ZuTHtQUkob #bioRxiv
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2.268 Mikeys
#10. Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval
Koral Goltseker, Hen Handrus, Segev Barak
Relapse to alcohol abuse is often caused by exposure to potent alcohol-associated cues. Therefore, disruption of the cue-alcohol memory can prevent relapse. It is believed that memories destabilize and become prone for updating upon their reactivation through retrieval, and then re-stabilize within 6 h during a reconsolidation process. We recently showed that relapse to cocaine seeking could be prevented by counterconditioning the cocaine-cues with aversive outcomes following cocaine-memory retrieval, in a place conditioning paradigm. However, to better model addiction-related behaviors, self-administration models are necessary. Here, we demonstrate that relapse to alcohol seeking can be prevented by aversive counterconditioning conducted during alcohol-memory reconsolidation, in conditioned place preference (CPP) and operant self-administration paradigms, in mice and rats, respectively. We found that the reinstatement of alcohol-CPP was abolished only when aversive counterconditioning with water-flooding was given shortly after...
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biorxiv_neursci: Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval https://t.co/7aUsdzDGDY #biorxiv_neursci
biorxivpreprint: Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval https://t.co/PVhlq7PKUZ #bioRxiv
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