@article{17113,
  abstract     = {CRISPR-Cas9 is a powerful tool for genome editing, but the strict requirement for an NGG protospacer-adjacent motif (PAM) sequence immediately next to the DNA target limits the number of editable genes. Recently developed Cas9 variants have been engineered with relaxed PAM requirements, including SpG-Cas9 (SpG) and the nearly PAM-less SpRY-Cas9 (SpRY). However, the molecular mechanisms of how SpRY recognizes all potential PAM sequences remains unclear. Here, we combine structural and biochemical approaches to determine how SpRY interrogates DNA and recognizes target sites. Divergent PAM sequences can be accommodated through conformational flexibility within the PAM-interacting region, which facilitates tight binding to off-target DNA sequences. Nuclease activation occurs ~1000-fold slower than for <jats:italic>Streptococcus pyogenes</jats:italic> Cas9, enabling us to directly visualize multiple on-pathway intermediate states. Experiments with SpG position it as an intermediate enzyme between Cas9 and SpRY. Our findings shed light on the molecular mechanisms of PAMless genome editing.},
  author       = {Hibshman, Grace N. and Bravo, Jack Peter Kelly and Hooper, Matthew M. and Dangerfield, Tyler L. and Zhang, Hongshan and Finkelstein, Ilya J. and Johnson, Kenneth A. and Taylor, David W.},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Unraveling the mechanisms of PAMless DNA interrogation by SpRY-Cas9}},
  doi          = {10.1038/s41467-024-47830-3},
  volume       = {15},
  year         = {2024},
}

@article{17114,
  abstract     = {CRISPR-Cas are adaptive immune systems in bacteria and archaea that utilize CRISPR RNA-guided surveillance complexes to target complementary RNA or DNA for destruction<jats:sup>1–5</jats:sup>. Target RNA cleavage at regular intervals is characteristic of type III effector complexes<jats:sup>6–8</jats:sup>. Here, we determine the structures of the <jats:italic>Synechocystis</jats:italic> type III-Dv complex, an apparent evolutionary intermediate from multi-protein to single-protein type III effectors<jats:sup>9,10</jats:sup>, in pre- and post-cleavage states. The structures show how multi-subunit fusion proteins in the effector are tethered together in an unusual arrangement to assemble into an active and programmable RNA endonuclease and how the effector utilizes a distinct mechanism for target RNA seeding from other type III effectors. Using structural, biochemical, and quantum/classical molecular dynamics simulation, we study the structure and dynamics of the three catalytic sites, where a 2′-OH of the ribose on the target RNA acts as a nucleophile for in line self-cleavage of the upstream scissile phosphate. Strikingly, the arrangement at the catalytic residues of most type III complexes resembles the active site of ribozymes, including the hammerhead, pistol, and Varkud satellite ribozymes. Our work provides detailed molecular insight into the mechanisms of RNA targeting and cleavage by an important intermediate in the evolution of type III effector complexes.},
  author       = {Schwartz, Evan A. and Bravo, Jack Peter Kelly and Ahsan, Mohd and Macias, Luis A. and McCafferty, Caitlyn L. and Dangerfield, Tyler L. and Walker, Jada N. and Brodbelt, Jennifer S. and Palermo, Giulia and Fineran, Peter C. and Fagerlund, Robert D. and Taylor, David W.},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{RNA targeting and cleavage by the type III-Dv CRISPR effector complex}},
  doi          = {10.1038/s41467-024-47506-y},
  volume       = {15},
  year         = {2024},
}

@article{18545,
  abstract     = {Clinical implementation of therapeutic genome editing relies on efficient in vivo delivery and the safety of CRISPR-Cas tools. Previously, we identified PsCas9 as a Type II-B family enzyme capable of editing mouse liver genome upon adenoviral delivery without detectable off-targets and reduced chromosomal translocations. Yet, its efficacy remains insufficient with non-viral delivery, a common challenge for many Cas9 orthologues. Here, we sought to redesign PsCas9 for in vivo editing using lipid nanoparticles. We solve the PsCas9 ribonucleoprotein structure with cryo-EM and characterize it biochemically, providing a basis for its rational engineering. Screening over numerous guide RNA and protein variants lead us to develop engineered PsCas9 (ePsCas9) with up to 20-fold increased activity across various targets and preserved safety advantages. We apply the same design principles to boost the activity of FnCas9, an enzyme phylogenetically relevant to PsCas9. Remarkably, a single administration of mRNA encoding ePsCas9 and its guide formulated with lipid nanoparticles results in high levels of editing in the Pcsk9 gene in mouse liver, a clinically relevant target for hypercholesterolemia treatment. Collectively, our findings introduce ePsCas9 as a highly efficient, and precise tool for therapeutic genome editing, in addition to the engineering strategy applicable to other Cas9 orthologues.},
  author       = {Degtev, Dmitrii and Bravo, Jack Peter Kelly and Emmanouilidi, Aikaterini and Zdravković, Aleksandar and Choong, Oi Kuan and Liz Touza, Julia and Selfjord, Niklas and Weisheit, Isabel and Francescatto, Margherita and Akcakaya, Pinar and Porritt, Michelle and Maresca, Marcello and Taylor, David and Sienski, Grzegorz},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Engineered PsCas9 enables therapeutic genome editing in mouse liver with lipid nanoparticles}},
  doi          = {10.1038/s41467-024-53418-8},
  volume       = {15},
  year         = {2024},
}

@article{17852,
  abstract     = {Metal-metal contacts, though not yet widely realized, may provide exciting opportunities to serve as tunable and functional interfaces in single-molecule devices. One of the simplest components which might facilitate such binding interactions is the ferrocene group. Notably, direct bonds between the ferrocene iron center and metals such as Pd or Co have been demonstrated in molecular complexes comprising coordinating ligands attached to the cyclopentadienyl rings. Here, we demonstrate that ferrocene-based single-molecule devices with Fe-Au interfacial contact geometries form at room temperature in the absence of supporting coordinating ligands. Applying a photoredox reaction, we propose that ferrocene only functions effectively as a contact group when oxidized, binding to gold through a formal Fe<jats:sup>3+</jats:sup> center. This observation is further supported by a series of control measurements and density functional theory calculations. Our findings extend the scope of junction contact chemistries beyond those involving main group elements, lay the foundation for light switchable ferrocene-based single-molecule devices, and highlight new potential mechanistic function(s) of unsubstituted ferrocenium groups in synthetic processes.},
  author       = {Lee, Woojung and Li, Liang and Camarasa-Gómez, María and Hernangómez-Pérez, Daniel and Roy, Xavier and Evers, Ferdinand and Inkpen, Michael S. and Venkataraman, Latha},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Photooxidation driven formation of Fe-Au linked ferrocene-based single-molecule junctions}},
  doi          = {10.1038/s41467-024-45707-z},
  volume       = {15},
  year         = {2024},
}

@article{18153,
  abstract     = {Attention supports decision making by selecting the features that are relevant for decisions. Selective enhancement of the relevant features and inhibition of distractors has been proposed as potential neural mechanisms driving this selection process. Yet, how attention operates when relevance cannot be directly determined, and the attention signal needs to be internally constructed is less understood. Here we recorded from populations of neurons in the anterior cingulate cortex (ACC) of mice in an attention-shifting task where relevance of stimulus modalities changed across blocks of trials. In contrast with V1 recordings, decoding of the irrelevant modality gradually declined in ACC after an initial transient. Our analytical proof and a recurrent neural network model of the task revealed mutually inhibiting connections that produced context-gated suppression as observed in mice. Using this RNN model we predicted a correlation between contextual modulation of individual neurons and their stimulus drive, which we confirmed in ACC but not in V1.},
  author       = {Hajnal, Márton Albert and Tran, Duy and Szabó, Zsombor and Albert, Andrea and Safaryan, Karen and Einstein, Michael and Vallejo Martelo, Mauricio and Polack, Pierre-Olivier and Golshani, Peyman and Orbán, Gergő},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Shifts in attention drive context-dependent subspace encoding in anterior cingulate cortex in mice during decision making}},
  doi          = {10.1038/s41467-024-49845-2},
  volume       = {15},
  year         = {2024},
}

@article{11951,
  abstract     = {The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain.},
  author       = {Ben Simon, Yoav and Käfer, Karola and Velicky, Philipp and Csicsvari, Jozsef L and Danzl, Johann G and Jonas, Peter M},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory}},
  doi          = {10.1038/s41467-022-32559-8},
  volume       = {13},
  year         = {2022},
}

@article{12052,
  abstract     = {Directionality in the intercellular transport of the plant hormone auxin is determined by polar plasma membrane localization of PIN-FORMED (PIN) auxin transport proteins. However, apart from PIN phosphorylation at conserved motifs, no further determinants explicitly controlling polar PIN sorting decisions have been identified. Here we present Arabidopsis WAVY GROWTH 3 (WAV3) and closely related RING-finger E3 ubiquitin ligases, whose loss-of-function mutants show a striking apical-to-basal polarity switch in PIN2 localization in root meristem cells. WAV3 E3 ligases function as essential determinants for PIN polarity, acting independently from PINOID/WAG-dependent PIN phosphorylation. They antagonize ectopic deposition of de novo synthesized PIN proteins already immediately following completion of cell division, presumably via preventing PIN sorting into basal, ARF GEF-mediated trafficking. Our findings reveal an involvement of E3 ligases in the selective targeting of apically localized PINs in higher plants.},
  author       = {Konstantinova, N and Hörmayer, Lukas and Glanc, Matous and Keshkeih, R and Tan, Shutang and Di Donato, M and Retzer, K and Moulinier-Anzola, J and Schwihla, M and Korbei, B and Geisler, M and Friml, Jiří and Luschnig, C},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{WAVY GROWTH Arabidopsis E3 ubiquitin ligases affect apical PIN sorting decisions}},
  doi          = {10.1038/s41467-022-32888-8},
  volume       = {13},
  year         = {2022},
}

@article{12208,
  abstract     = {The inadequate understanding of the mechanisms that reversibly convert molecular sulfur (S) into lithium sulfide (Li<jats:sub>2</jats:sub>S) via soluble polysulfides (PSs) formation impedes the development of high-performance lithium-sulfur (Li-S) batteries with non-aqueous electrolyte solutions. Here, we use operando small and wide angle X-ray scattering and operando small angle neutron scattering (SANS) measurements to track the nucleation, growth and dissolution of solid deposits from atomic to sub-micron scales during real-time Li-S cell operation. In particular, stochastic modelling based on the SANS data allows quantifying the nanoscale phase evolution during battery cycling. We show that next to nano-crystalline Li<jats:sub>2</jats:sub>S the deposit comprises solid short-chain PSs particles. The analysis of the experimental data suggests that initially, Li<jats:sub>2</jats:sub>S<jats:sub>2</jats:sub> precipitates from the solution and then is partially converted via solid-state electroreduction to Li<jats:sub>2</jats:sub>S. We further demonstrate that mass transport, rather than electron transport through a thin passivating film, limits the discharge capacity and rate performance in Li-S cells.},
  author       = {Prehal, Christian and von Mentlen, Jean-Marc and Drvarič Talian, Sara and Vizintin, Alen and Dominko, Robert and Amenitsch, Heinz and Porcar, Lionel and Freunberger, Stefan Alexander and Wood, Vanessa},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{On the nanoscale structural evolution of solid discharge products in lithium-sulfur batteries using operando scattering}},
  doi          = {10.1038/s41467-022-33931-4},
  volume       = {13},
  year         = {2022},
}

@article{12217,
  abstract     = {The development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis.},
  author       = {Randriamanantsoa, S. and Papargyriou, A. and Maurer, H. C. and Peschke, K. and Schuster, M. and Zecchin, G. and Steiger, K. and Öllinger, R. and Saur, D. and Scheel, C. and Rad, R. and Hannezo, Edouard B and Reichert, M. and Bausch, A. R.},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids}},
  doi          = {10.1038/s41467-022-32806-y},
  volume       = {13},
  year         = {2022},
}

@article{15133,
  abstract     = {In the evolutionary arms race against phage, bacteria have assembled a diverse arsenal of antiviral immune strategies. While the recently discovered DISARM (Defense Island System Associated with Restriction-Modification) systems can provide protection against a wide range of phage, the molecular mechanisms that underpin broad antiviral targeting but avoiding autoimmunity remain enigmatic. Here, we report cryo-EM structures of the core DISARM complex, DrmAB, both alone and in complex with an unmethylated phage DNA mimetic. These structures reveal that DrmAB core complex is autoinhibited by a trigger loop (TL) within DrmA and binding to DNA substrates containing a 5′ overhang dislodges the TL, initiating a long-range structural rearrangement for DrmAB activation. Together with structure-guided in vivo studies, our work provides insights into the mechanism of phage DNA recognition and specific activation of this widespread antiviral defense system.},
  author       = {Bravo, Jack Peter Kelly and Aparicio-Maldonado, Cristian and Nobrega, Franklin L. and Brouns, Stan J. J. and Taylor, David W.},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{Structural basis for broad anti-phage immunity by DISARM}},
  doi          = {10.1038/s41467-022-30673-1},
  volume       = {13},
  year         = {2022},
}

@article{15134,
  abstract     = {CRISPR-Cas systems are adaptive immune systems that protect prokaryotes from foreign nucleic acids, such as bacteriophages. Two of the most prevalent CRISPR-Cas systems include type I and type III. Interestingly, the type I-D interference proteins contain characteristic features of both type I and type III systems. Here, we present the structures of type I-D Cascade bound to both a double-stranded (ds)DNA and a single-stranded (ss)RNA target at 2.9 and 3.1 Å, respectively. We show that type I-D Cascade is capable of specifically binding ssRNA and reveal how PAM recognition of dsDNA targets initiates long-range structural rearrangements that likely primes Cas10d for Cas3′ binding and subsequent non-target strand DNA cleavage. These structures allow us to model how binding of the anti-CRISPR protein AcrID1 likely blocks target dsDNA binding via competitive inhibition of the DNA substrate engagement with the Cas10d active site. This work elucidates the unique mechanisms used by type I-D Cascade for discrimination of single-stranded and double stranded targets. Thus, our data supports a model for the hybrid nature of this complex with features of type III and type I systems.},
  author       = {Schwartz, Evan A. and McBride, Tess M. and Bravo, Jack Peter Kelly and Wrapp, Daniel and Fineran, Peter C. and Fagerlund, Robert D. and Taylor, David W.},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{Structural rearrangements allow nucleic acid discrimination by type I-D Cascade}},
  doi          = {10.1038/s41467-022-30402-8},
  volume       = {13},
  year         = {2022},
}

@article{18221,
  abstract     = {Synonymous codons translate into chemically identical amino acids. Once considered inconsequential to the formation of the protein product, there is evidence to suggest that codon usage affects co-translational protein folding and the final structure of the expressed protein. Here we develop a method for computing and comparing codon-specific Ramachandran plots and demonstrate that the backbone dihedral angle distributions of some synonymous codons are distinguishable with statistical significance for some secondary structures. This shows that there exists a dependence between codon identity and backbone torsion of the translated amino acid. Although these findings cannot pinpoint the causal direction of this dependence, we discuss the vast biological implications should coding be shown to directly shape protein conformation and demonstrate the usefulness of this method as a tool for probing associations between codon usage and protein structure. Finally, we urge for the inclusion of exact genetic information into structural databases.},
  author       = {Rosenberg, Aviv A. and Marx, Ailie and Bronstein, Alexander},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Codon-specific Ramachandran plots show amino acid backbone conformation depends on identity of the translated codon}},
  doi          = {10.1038/s41467-022-30390-9},
  volume       = {13},
  year         = {2022},
}

@article{11373,
  abstract     = {The actin-homologue FtsA is essential for E. coli cell division, as it links FtsZ filaments in the Z-ring to transmembrane proteins. FtsA is thought to initiate cell constriction by switching from an inactive polymeric to an active monomeric conformation, which recruits downstream proteins and stabilizes the Z-ring. However, direct biochemical evidence for this mechanism is missing. Here, we use reconstitution experiments and quantitative fluorescence microscopy to study divisome activation in vitro. By comparing wild-type FtsA with FtsA R286W, we find that this hyperactive mutant outperforms FtsA WT in replicating FtsZ treadmilling dynamics, FtsZ filament stabilization and recruitment of FtsN. We could attribute these differences to a faster exchange and denser packing of FtsA R286W below FtsZ filaments. Using FRET microscopy, we also find that FtsN binding promotes FtsA self-interaction. We propose that in the active divisome FtsA and FtsN exist as a dynamic copolymer that follows treadmilling filaments of FtsZ.},
  author       = {Radler, Philipp and Baranova, Natalia S. and Dos Santos Caldas, Paulo R and Sommer, Christoph M and Lopez Pelegrin, Maria D and Michalik, David and Loose, Martin},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry},
  publisher    = {Springer Nature},
  title        = {{In vitro reconstitution of Escherichia coli divisome activation}},
  doi          = {10.1038/s41467-022-30301-y},
  volume       = {13},
  year         = {2022},
}

@article{12585,
  abstract     = {Glaciers in High Mountain Asia generate meltwater that supports the water needs of 250 million people, but current knowledge of annual accumulation and ablation is limited to sparse field measurements biased in location and glacier size. Here, we present altitudinally-resolved specific mass balances (surface, internal, and basal combined) for 5527 glaciers in High Mountain Asia for 2000–2016, derived by correcting observed glacier thinning patterns for mass redistribution due to ice flow. We find that 41% of glaciers accumulated mass over less than 20% of their area, and only 60% ± 10% of regional annual ablation was compensated by accumulation. Even without 21st century warming, 21% ± 1% of ice volume will be lost by 2100 due to current climatic-geometric imbalance, representing a reduction in glacier ablation into rivers of 28% ± 1%. The ablation of glaciers in the Himalayas and Tien Shan was mostly unsustainable and ice volume in these regions will reduce by at least 30% by 2100. The most important and vulnerable glacier-fed river basins (Amu Darya, Indus, Syr Darya, Tarim Interior) were supplied with >50% sustainable glacier ablation but will see long-term reductions in ice mass and glacier meltwater supply regardless of the Karakoram Anomaly.},
  author       = {Miles, Evan and McCarthy, Michael and Dehecq, Amaury and Kneib, Marin and Fugger, Stefan and Pellicciotti, Francesca},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{Health and sustainability of glaciers in High Mountain Asia}},
  doi          = {10.1038/s41467-021-23073-4},
  volume       = {12},
  year         = {2021},
}

@article{15137,
  abstract     = {Characteristic properties of type III CRISPR-Cas systems include recognition of target RNA and the subsequent induction of a multifaceted immune response. This involves sequence-specific cleavage of the target RNA and production of cyclic oligoadenylate (cOA) molecules. Here we report that an exposed seed region at the 3′ end of the crRNA is essential for target RNA binding and cleavage, whereas cOA production requires base pairing at the 5′ end of the crRNA. Moreover, we uncover that the variation in the size and composition of type III complexes within a single host results in variable seed regions. This may prevent escape by invading genetic elements, while controlling cOA production tightly to prevent unnecessary damage to the host. Lastly, we use these findings to develop a new diagnostic tool, SCOPE, for the specific detection of SARS-CoV-2 from human nasal swab samples, revealing sensitivities in the atto-molar range.},
  author       = {Steens, Jurre A. and Zhu, Yifan and Taylor, David W. and Bravo, Jack Peter Kelly and Prinsen, Stijn H. P. and Schoen, Cor D. and Keijser, Bart J. F. and Ossendrijver, Michel and Hofstra, L. Marije and Brouns, Stan J. J. and Shinkai, Akeo and van der Oost, John and Staals, Raymond H. J.},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{SCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation}},
  doi          = {10.1038/s41467-021-25337-5},
  volume       = {12},
  year         = {2021},
}

@article{9778,
  abstract     = {The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons. To directly test cooperativity and associativity, we made paired recordings between single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain slices. By stimulating non-overlapping mossy fiber inputs converging onto single CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly, mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only minimal PTP after combined pre- and postsynaptic high-frequency stimulation with intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels, group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire of synaptic computations, implementing a brake on mossy fiber detonation and a “smart teacher” function of hippocampal mossy fiber synapses.},
  author       = {Vandael, David H and Okamoto, Yuji and Jonas, Peter M},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {general physics and astronomy, general biochemistry, genetics and molecular biology, general chemistry},
  number       = {1},
  publisher    = {Springer},
  title        = {{Transsynaptic modulation of presynaptic short-term plasticity in hippocampal mossy fiber synapses}},
  doi          = {10.1038/s41467-021-23153-5},
  volume       = {12},
  year         = {2021},
}

@article{15142,
  abstract     = {Bacteria and archaea employ CRISPR (clustered, regularly, interspaced, short palindromic repeats)-Cas (CRISPR-associated) systems as a type of adaptive immunity to target and degrade foreign nucleic acids. While a myriad of CRISPR-Cas systems have been identified to date, type I-C is one of the most commonly found subtypes in nature. Interestingly, the type I-C system employs a minimal Cascade effector complex, which encodes only three unique subunits in its operon. Here, we present a 3.1 Å resolution cryo-EM structure of the <jats:italic>Desulfovibrio vulgaris</jats:italic> type I-C Cascade, revealing the molecular mechanisms that underlie RNA-directed complex assembly. We demonstrate how this minimal Cascade utilizes previously overlooked, non-canonical small subunits to stabilize R-loop formation. Furthermore, we describe putative PAM and Cas3 binding sites. These findings provide the structural basis for harnessing the type I-C Cascade as a genome-engineering tool.},
  author       = {O’Brien, Roisin E. and Santos, Inês C. and Wrapp, Daniel and Bravo, Jack Peter Kelly and Schwartz, Evan A. and Brodbelt, Jennifer S. and Taylor, David W.},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  keywords     = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary},
  publisher    = {Springer Nature},
  title        = {{Structural basis for assembly of non-canonical small subunits into type I-C Cascade}},
  doi          = {10.1038/s41467-020-19785-8},
  volume       = {11},
  year         = {2020},
}

@article{7707,
  abstract     = {The growing sample size of genome-wide association studies has facilitated the discovery of gene-environment interactions (GxE). Here we propose a maximum likelihood method to estimate the contribution of GxE to continuous traits taking into account all interacting environmental variables, without the need to measure any. Extensive simulations demonstrate that our method provides unbiased interaction estimates and excellent coverage. We also offer strategies to distinguish specific GxE from general scale effects. Applying our method to 32 traits in the UK Biobank reveals that while the genetic risk score (GRS) of 376 variants explains 5.2% of body mass index (BMI) variance, GRSxE explains an additional 1.9%. Nevertheless, this interaction holds for any variable with identical correlation to BMI as the GRS, hence may not be GRS-specific. Still, we observe that the global contribution of specific GRSxE to complex traits is substantial for nine obesity-related measures (including leg impedance and trunk fat-free mass).},
  author       = {Sulc, Jonathan and Mounier, Ninon and Günther, Felix and Winkler, Thomas and Wood, Andrew R. and Frayling, Timothy M. and Heid, Iris M. and Robinson, Matthew Richard and Kutalik, Zoltán},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Quantification of the overall contribution of gene-environment interaction for obesity-related traits}},
  doi          = {10.1038/s41467-020-15107-0},
  volume       = {11},
  year         = {2020},
}

@article{7999,
  abstract     = {Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70–79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3–51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal. },
  author       = {Trejo Banos, D and McCartney, DL and Patxot, M and Anchieri, L and Battram, T and Christiansen, C and Costeira, R and Walker, RM and Morris, SW and Campbell, A and Zhang, Q and Porteous, DJ and McRae, AF and Wray, NR and Visscher, PM and Haley, CS and Evans, KL and Deary, IJ and McIntosh, AM and Hemani, G and Bell, JT and Marioni, RE and Robinson, Matthew Richard},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Bayesian reassessment of the epigenetic architecture of complex traits}},
  doi          = {10.1038/s41467-020-16520-1},
  volume       = {11},
  year         = {2020},
}

@article{8138,
  abstract     = {Directional transport of the phytohormone auxin is a versatile, plant-specific mechanism regulating many aspects of plant development. The recently identified plant hormones, strigolactones (SLs), are implicated in many plant traits; among others, they modify the phenotypic output of PIN-FORMED (PIN) auxin transporters for fine-tuning of growth and developmental responses. Here, we show in pea and Arabidopsis that SLs target processes dependent on the canalization of auxin flow, which involves auxin feedback on PIN subcellular distribution. D14 receptor- and MAX2 F-box-mediated SL signaling inhibits the formation of auxin-conducting channels after wounding or from artificial auxin sources, during vasculature de novo formation and regeneration. At the cellular level, SLs interfere with auxin effects on PIN polar targeting, constitutive PIN trafficking as well as clathrin-mediated endocytosis. Our results identify a non-transcriptional mechanism of SL action, uncoupling auxin feedback on PIN polarity and trafficking, thereby regulating vascular tissue formation and regeneration.},
  author       = {Zhang, J and Mazur, E and Balla, J and Gallei, Michelle C and Kalousek, P and Medveďová, Z and Li, Y and Wang, Y and Prat, Tomas and Vasileva, Mina K and Reinöhl, V and Procházka, S and Halouzka, R and Tarkowski, P and Luschnig, C and Brewer, PB and Friml, Jiří},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  number       = {1},
  pages        = {3508},
  publisher    = {Springer Nature},
  title        = {{Strigolactones inhibit auxin feedback on PIN-dependent auxin transport canalization}},
  doi          = {10.1038/s41467-020-17252-y},
  volume       = {11},
  year         = {2020},
}