bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gestures Of Hunger: Uncovering Intentional Gestural Communication In Free-Ranging Hanuman Langurs
Authors: Dasgupta Dishari , Banerjee Arnab , Dutta Akash , Mitra Shohini , Banerjee Debolina , Karar Rikita , Karmakar Srijita , Bhattacharya Aparajita , Ghosh Swastika , Bhattacharjee Pritha , Paul Manabi 
Published: September 2023

ABSTRACTContrary to previous beliefs, intentional gestural communication (IGC) is not exclusive to the hominoid lineage but is also present in other non-human primates. Here, we report the presence of IGC among free-ranging Hanuman langur troop in Dakshineswar, West Bengal, India. These langurs exhibit a food-requesting behaviour wherein they use several gestures to communicate with the humans nearby. Moreover, they can also assess the recipient’s mental state and persistently check if the signal (food request) has been received, waiting until they receive the desired food item. We have identified eight begging gestures used by langurs of all ages, except infants. The most common gesture is by holding cloth (BGc), but provocation-initiated begging (BGpi) and begging by embracing legs (BGe) efficiently direct these events to its success. The frequency of successful begging events is higher in the evening due to increased human interactions. Our findings suggest that ontogenetic ritualization might be at play here among these troop members as this gestural communication has been learned through imitation and reinforced by the reward of receiving food. Moreover, these successful begging events serve as an effective foraging strategy for urban-adapted langurs, allowing them to acquire high-calorie processed food items within a human-modified urban ecosystem.
A common Alu element insertion in the 3’UTR ofTMEM106Bis associated with an increased risk of dementia
Authors: Rodney Alana , Karanjeet Kul , Benzow Kellie , Koob Michael D. 
Published: September 2023

AbstractSequence variants inTMEM106Bhave been associated with an increased risk of developing several different types of dementia. As part of our efforts to generate a set of mouse lines in which we replaced the mouseTmem106bgene with a humanTMEM106Bgene comprised of either a risk or protective haplotype, we conducted an in-depth sequence analysis of these alleles. We identified an AluYb8 insertion in the 3’ untranslated region (3’UTR) of theTMEM106Brisk haplotype. We analyzed transcribedTMEM106Bsequences using RNA-seq data available through the AD Knowledge portal and full genome sequences from the 1000Genomes databases and found that every risk allele analyzed shares this same AluYb8 insertion. The allele frequency of the risk haplotype ranges from 26% to 60% in the populations examined, and the balance of the alleles in each population is the protective haplotype. The primary sequence features of both haplotypes are distinct from the variants found in other primates. We conclude that the risk haplotype arose early in human development with a single Alu-insertion event within a unique haplotype context. Together these two non-ancestral allele variant types now appear to constitute the vast majority of theTMEM106Balleles but neither has come to fully predominate in any modern human population.
A soybean rust effector protease suppresses host immunity and cleaves a 3-deoxy-7-phosphoheptulonate synthase
Authors: Chicowski Aline Sartor , Qi Mingsheng , Variz Haris , Bredow Melissa , Montes Christian , Caiazza Francesco , Dong Haili , Margets Alexandra , Mejias Joffrey , Walley Justin W. , Craik Charles S. , Pedley Kerry F. , Aung Kyaw , Innes Roger , Whitham Steven A. 
Published: September 2023

AbstractThe devastating soybean rust (SBR) pathogen,Phakopsora pachyrhizi, encodes many secreted proteins, but only two have been functionally characterized for their roles in rust virulence. Here, we demonstrate that transient expression ofP. pachyrhizieffector candidate 15 (PpEC15), an aspartic protease, leads to enhanced bacterial growthin planta, suppression of callose deposition, reduced expression of plant defense-related marker genes and suppression of pathogen-associated molecular pattern (PAMP)-induced reactive oxygen species (ROS). Stable expression ofPpEC15 in soybean suppresses PAMP-induced ROS production and enhances bacterial growth, indicating that, collectively,PpEC15 suppresses host and non-host innate immune responses. Yeast-two-hybrid and proximity labeling identified putativePpEC15 interacting partners including a peptide-chain release factor (PCRF), a NAC83 (NAM, ATAF, and CUC) transcription factor, and a DAHP (3-deoxy-7-phosphoheptulonate) synthase. We further show thatPpEC15 can cleave DAHP but does not cleave PCRF or NAC83. Virus-induced gene silencing of NAC83, PCRF and DAHP altered PAMP-induced ROS production and salicylic acid production, indicating that these proteins may be involved in immune signaling. Collectively, our data show thatPpEC15 is conserved acrossP. pachyrhiziisolates and other economically important rust species and is involved in the suppression of plant basal defense responses. Understanding the role ofPpEC15 inP. pachyrhizivirulence will provide a foundation for designing targeted intervention strategies to generate rust-resistant crops.
Association of secondary metabolite gene clusters with host-specific lineages of the cereal blast fungusPyricularia oryzae
Authors: Mehta Khyati , Navarro-Muñoz Jorge C. , Bakore Sayali , Collemare Jérôme , Patkar Rajesh 
Published: September 2023

AbstractFungal plant pathogens constantly evolve and deploy novel peptide and metabolite effectors to break down plant resistance and adapt to new host plants. The blast fungal pathogenPyricularia oryzaeis a single species subdivided into multiple host-specific lineages that have evolved through gain and/or loss of virulence and/or effector related genes through chromosomal rearrangement. Here, we mined 68 genomes ofP. oryzae, belonging to six host-specific lineages, to identify secondary metabolite (SM) biosynthetic gene clusters (BGCs) likely associated with potential metabolite effectors involved in host specialization. A similarity network analysis grouped a total of 4501 BGCs into 283 gene cluster families (GCFs), based on the content and architecture of the BGCs. While most of the GCFs were present in all theP. oryzaelineages, two (BGC-O1 and BGC-O2) were found specifically in theOryzalineage and one (BGC-TLE) was found in the lineage specific toTriticum, LoliumandEleusinehosts. Further analysis of the phylogenetic relationships between core biosynthetic genes confirmed that BGC-O1, which comprises a reducing polyketide synthase gene (MGG_08236) and four putative tailoring genes, was present only in theOryzalineage. Importantly, most genes, including MGG_08236, from the BGC-O1 were expressed specifically during pathogenesis. We propose that theOryzalineage-specific BGC-O1 produces a metabolite effector likely involved in specialization ofP. oryzaeto the rice host. In addition, we identified five SM genes under positive or balancing selection only in theOryzalineage, suggesting a role in the interaction with rice specifically. Our findings highlight the importance of further mining novel metabolite effectors in specialization and virulence of the blast fungus to different cereal hosts.
The crystal and cryo-EM structures of PLCγ2 reveal dynamic inter-domain recognitions in autoinhibition
Authors: Shin Young-Cheul , Plummer-Medeiros Ashlee Marie , Mungenast Alison , Choi Hyeong-wook , TenDyke Karen , Zhu Xiaojie , Shepard Jennifer , Zhuang Ningning , Hu Liang , Qian Dongming , Song Kangkang , Xu Chen , Wang John , Poda Suresh B , Liao Maofu , Chen Yu 
Published: September 2023

Abstract/SummaryPhospholipase C gamma 2 (PLCγ2) plays important roles in cell signaling downstream of various membrane receptors. PLCγ2 contains a multi-domain inhibitory region critical for its regulation, while it has remained unclear how these domains contribute to PLCγ2 activity modulation. Here we determined three structures of human PLCγ2 in autoinhibited states, which reveal dynamic interactions at the autoinhibition interface, involving the conformational flexibility of the SH3 domain in the inhibitory region, and its previously unknown interaction with a C-terminal helical domain in the core region. We also determined a structure of PLCγ2 bound to the kinase domain of fibroblast growth factor receptor 1 (FGFR1), which demonstrates the recognition of FGFR1 by the nSH2 domain in the inhibitory region of PLCγ2. Our results provide new structural insights into PLCγ2 regulation that will facilitate future mechanistic studies to understand the entire activation process.
TRPM2-CaMKII signaling drives excessive GABAergic synaptic inhibition following ischemia
Authors: Burch Amelia M. , Garcia Joshua D. , O’Leary Heather , Haas Ami , Orfila James E. , Tiemeier Erika , Chalmers Nicholas , Smith Katharine R. , Quillinan Nidia , Herson Paco S. 
Published: September 2023

ABSTRACTFollowing an ischemic insult to the brain, there is an acute loss of GABAergic inhibitory synapses and an increase in excitatory/ inhibitory (E/I) imbalance that drives neuronal hyperexcitability. It is unknown whether this E/I imbalance persists at delayed timepoints and contributes to chronic impairments in memory and long-term potentiation (LTP) in the hippocampus following ischemic brain injury. Here, we reveal a shift to reduced E/I ratio in hippocampal CA1 neurons via a persistent increase in postsynaptic GABAAreceptor mediated inhibitory responses and clustering days after a global ischemic insult. This enhancement of postsynaptic inhibitory function and clustering required activation of the Ca2+-permeable TRPM2 ion channel and the Ca2+-dependent kinase, CaMKII. Thus, we propose a mechanism in which acute downregulation of GABAAreceptors is followed by a strengthening of inhibitory synapses at delayed periods after ischemia. Targeting this mechanism has therapeutic potential to recover hippocampal plasticity and cognitive function post-ischemia.GRAPHICAL ABSTRACT
Identification of an H-Ras nanocluster disrupting peptide
Authors: Manoharan Ganesh babu , Steffen Candy Laura , Pavic Karolina , Yeste-Vázquez Alejandro , Knuuttila Matias , Arora Neha , Zhou Yong , Härmä Harri , Gaigneaux Anthoula , Grossmann Tom N. , Abankwa Daniel Kwaku 
Published: September 2023

AbstractThe Ras-MAPK pathway is critical to regulate cell proliferation and differentiation. Its dysregulation is implicated in the onset and progression of numerous types of cancers. To be active, Ras proteins are membrane anchored and organized into nanoclusters, which realize high-fidelity signal transmission across the plasma membrane. Nanoclusters therefore represent potential drug targets. However, targetable protein components of signalling nanoclusters are poorly established.We previously proposed that the nanocluster scaffold galectin-1 (Gal1) enhances H-Ras nanoclustering by stabilizing stacked dimers of H-Ras and Raf via a direct interaction of dimeric Gal1 with the Ras binding domain (RBD) in particular of B-Raf. Here, we provide further supportive evidence for this model. We establish that the B-Raf preference emerges from divergent regions of the Raf RBDs that were proposed to interact with Gal1. We then identify the L5UR peptide, which disrupts this interaction by binding with low micromolar affinity to the B-Raf-RBD. Its 23-mer core fragment is thus sufficient to interfere with Gal1-enhanced H-Ras nanocluster, reduce MAPK-output and cell viability inHRAS-mutant cancer cell lines.Our data therefore suggest that the interface between Gal1 and the RBD of B-Raf can be targeted to disrupt Gal1-enhanced H-Ras nanoclustering. Collectively, our results support that Raf-proteins are integral components of active Ras nanoclusters.
Genome-wide Perturbation Analysis Screening System for Exosomes-Related Genes Based on the CRISPR/Cas9 Platform
Authors: Lu Lu , Yin Jianxin , Chen Ning , Guo Xiaofei , Han Chunle , Wang Miao , Du Huanqing , Li Huifang , Pan Xingang , Gao Mengya , Wang Na , Qi Dongli , Wang Jianhong , Dong Fengwei , Li Tianshi , Ge Xiaohu 
Published: September 2023

AbstractAs reported previously, exosomes have significant impacts on the physiological and pathological statein vivo. Exosomes have been extensively studied as a drug delivery carrier and some exosomes drugs have been undergoing clinical research. The mechanisms of exosome production, transport, and secretion remain to be studied in depth. Thus, here, we developed a novel CRISPR-UMI-based gene screening system, with which we can reveal the exosomes biogenesis, transport, and uptake mechanisms on a genome-wide scale. This system consists of two parts: one is a gene knockout component; the other part is a unique molecular identifiers (UMI) labeling component that can label the exosomes produced by the knockout cells, in which each sgRNA corresponds to a specific UMI. In this way, by detecting the UMI loaded in the exosomes, we can trace the knockout gene. In this study, we first verified the function of each component using plasmids and lentiviruses respectively. Next, we simulated the infection of cells with lentiviral libraries using a single lentivirus to validate the functionality of the screening system. Finally, we constructed a CRISPR-UMI-based library targeting 15 genes (genes with clear effects on exosomes biogenesis) to further validate the reliability of the screening system. The development of this screening system is of indispensable importance for the in-depth study of the mechanisms of exosome production and secretion, as well as for the improvement of exosomes production and the advancement of exosomes industrialization.
Does the stress axis mediate behavioural flexibility in a social cichlid,Neolamprologus pulcher?
Authors: Fischer Stefan , Ferlinc Zala , Hirschenhauser Katharina , Taborsky Barbara , Fusani Leonida , Tebbich Sabine 
Published: September 2023

AbstractBehavioural flexibility plays a major role in the way animals cope with novel situations, and physiological stress responses are adaptive and highly efficient mechanisms to cope with unpredictable events. Previous studies investigating the role of stress responses in mediating behavioural flexibility were mostly done in laboratory rodents using stressors and cognitive challenges unrelated to the ecology of the species. To better understand how stress mediates behavioural flexibility in a natural context, direct manipulations of the stress response and cognitive tests in ecologically relevant contexts are needed. To this aim, we pharmacologically blocked glucocorticoid receptors (GR) in adultNeolamprologus pulcherusing a minimally invasive application of a GR antagonist. GR blockade prevents the recovery after a stressful event, which we predicted to impair behavioural flexibility. After the application of the GR antagonist, we repeatedly exposed fish to a predator and tested their behavioural flexibility using a detour task, i.e. fish had to find a new, longer route to the shelter when the shortest route was blocked. While the latencies to find the shelter were not different between treatments, GR blocked fish showed more failed attempts during the detour tasks than control fish. Furthermore, weak performance during the detour tasks was accompanied by an increase of fear related behaviours. This suggests that blocking GR changed the perception of fear and resulted in an impaired behavioural flexibility. Therefore, our results support a causal link between the capacity to recover from stressors and behavioural flexibility inN. pulcherwith potential consequences for an effective and adaptive coping with changing environments.
Novel laminarin-binding CBMs in multimodular proteins of marineBacteroidotafeature prominently in phytoplankton blooms
Authors: Zühlke Marie-Katherin , Ficko-Blean Elizabeth , Bartosik Daniel , Terrapon Nicolas , Jeudy Alexandra , Jam Murielle , Wang Fengqing , Welsch Norma , Larocque Robert , Jouanneau Diane , Eisenack Tom , Thomas François , Trautwein-Schult Anke , Teeling Hanno , Becher Dörte , Schweder Thomas , Czjzek Mirjam 
Published: September 2023

AbstractThe ß-(1,3)-glucan laminarin functions as storage polysaccharide in marine stramenophiles such as diatoms. Laminarin is abundant, water-soluble and structured simply, making it an attractive substrate for marine bacteria. As a consequence, many marine bacteria have developed competitive strategies to scavenge and decompose laminarin, which involves carbohydrate-binding modules (CBMs) as key players. We therefore functionally and structurally characterized two yet unassigned domains as laminarin-binding CBMs in multimodular proteins from our model bacteriumChristiangramia forsetiiKT0803T, hereby unveiling the novel laminarin-binding CBM families CBMxx and CBMyy (official CAZy numbering will be provided upon acceptance of the manuscript in a peer-reviewed journal). We discovered four CBMxx repeats in a surface glycan-binding protein (SGBP) and a single CBMyy combined with a glycoside hydrolase module from family 16 (GH16_3). Our analyses revealed that both modular proteins have an elongated shape, and that the GH16_3 displayed a higher flexibility than the SGBP. While motility of both polypeptide chains may facilitate recognition and/or degradation of laminarin, constraints in the SGBP may support docking of laminarin onto the bacterial surface. The exploration of bacterial metagenome-assembled genomes (MAGs) from phytoplankton blooms in the North Sea revealed that both laminarin-binding CBM families are widely distributed among marineBacteroidota, illustrating the high adaptability of modularity in sugar-binding and -degrading proteins. High expression of CBMxx- and CBMyy-containing proteins during phytoplankton blooms further underpins their importance in marine laminarin usage.
Learnt representations of proteins can be used for accurate prediction of small molecule binding sites on experimentally determined and predicted protein structures
Authors: Carbery Anna , Buttenschoen Martin , Skyner Rachael , von Delft Frank , Deane Charlotte M. 
Published: September 2023

AbstractProtein-ligand binding site prediction is a useful tool for understanding the functional behaviour and potential drug-target interactions of a novel protein of interest. However, most binding site prediction methods are tested by providing crystallised ligand-bound (holo) structures as input. This testing regime is insufficient to understand the performance on novel protein targets where experimental structures are not available. An alternative option is to provide computationally predicted protein structures, but this is not commonly tested. However, due to the training data used, computationally-predicted protein structures tend to be extremely accurate, and are often biased toward a holo conformation. In this study we describe and benchmark IF-SitePred, a protein-ligand binding site prediction method which is based on the labelling of ESM-IF1 protein language model embeddings combined with point cloud annotation and clustering. We show that not only is IF-SitePred competitive with state-of-the-art methods when predicting binding sites on experimental structures, but it performs better on proxies for novel proteins where low accuracy has been simulated by molecular dynamics. Finally, IF-SitePred outperforms other methods if ensembles of predicted protein structures are generated.
Nutrient availability influencesE. colibiofilm properties and the structure of purified curli amyloid fibers
Authors: Siri Macarena , Vázquéz-Dávila Mónica , Bidan Cécile M. 
Published: September 2023

ABSTRACTBacterial biofilms are highly adaptable and resilient to challenges. Nutrient availability can induce changes in biofilm growth, biomass, morphology, architecture and mechanical properties. Bacterial extracellular matrix plays a major role in achieving biofilm stability under different environmental conditions. Curli amyloid fibers are determining for the architecture and stiffness ofE. colibiofilms, but how this major matrix component adapts to different environmental cues remains unclear.Here, we investigated for the first time the effect of nutrient availability on both i) biofilm materials properties and ii) the structure and properties of curli amyloid fibers extracted from the biofilms. For this, we culturedE. coliW3110, which main matrix component is curli fibers. We quantified the size, mass and water content of the resulting biofilms and estimated their mechanical properties by microindentation. The curli amyloid fibers were then purified from the biofilms and their molecular structure and properties were studied by spectroscopic techniques. Our results show that the availability of nutrients in the substrate influences the yield of curli fibers, their structural composition and chemical stability, and suggest that these molecular features contribute to the stiffness of the biofilms. Biofilms grown on substrates with high nutrient concentration are softer, contain less curli fibers, and these fibers exhibit low β-sheet content and chemical stability.Our multiscale study sheds new light on the relationship between the molecular structure of bacterial matrix and the macroscopic properties of biofilms. This knowledge will benefit the development of both anti-biofilm strategies and biofilm-based materials.Graphical abstract
Dynamic atP5CS2 Filament Facilitates Substrate Channeling
Authors: Guo Chen-Jun , Zhang Tianyi , Leng Qingqing , Zhou Xian , Zhong Jiale , Liu Ji-Long 
Published: September 2023

AbstractIn plants, the rapid accumulation of proline is a common response to combat abiotic stress. Delta-1-pyrroline-5-carboxylate synthase (P5CS) is a rate-limiting enzyme in proline synthesis, catalyzing the initial two-step conversion from glutamate to proline. Here, we determine the first structure of plant P5CS. Our results show that Arabidopsis thaliana P5CS2 (atP5CS2) can form enzymatic filaments in a substrate-sensitive manner. The destruction of atP5CS filaments by mutagenesis leads to a significant reduction in enzymatic activity. Furthermore, separate activity tests on two domains reveals that filament-based substrate channeling is essential for maintaining the high catalytic efficiency of atP5CS. Our study demonstrates the unique mechanism for the efficient catalysis of P5CS, shedding light on the intricate mechanisms underlying plant proline metabolism and stress response. Therefore these findings provide potential avenues for crop genetically modified breeding.