bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two notorious nodes: a critical examination of MCMCTree relaxed molecular clock estimates of the bilaterian animals and placental mammals
Authors: Budd Graham E. , Mann Richard P. 
Published: July 2022

AbstractThe popularity of MCMCTree for Bayesian inference of clade origin timings has generated several recent publications with focal results considerably older than the fossils of the clades in question. Here we critically examine two such clades; the animals (with focus on the bilaterians) and the mammals (with focus on the placentals). Each example displays a set of characteristic pathologies which, although much commented on, are rarely corrected for. We conclude that in neither case does the molecular clock analysis provide any evidence for an origin of the clade deeper than what the fossil record might suggest. In addition, both these clades have other features (including, in the case of the placental mammals, proximity to a large mass extinction) that allow us to generate precise expectations of the timings of their origins. Thus, in these instances the fossil record can provide a powerful test of molecular clock methodology, and why it goes astray.
Differential stage-specific mortality as a mechanism for diversification
Authors: Chaparro-Pedraza P. Catalina 
Published: July 2022

AbstractIndividual variability in mortality is widespread in nature. The general rule is that larger organisms have a greater chance of survival than smaller conspecifics. There is growing evidence that differential mortality between developmental stages has important consequences for the ecology and evolution of populations and communities. However, we know little about how it can influence diversification. Using an eco-evolutionary model of diversification that considers individual variability in mortality, we show that commonly observed differences in mortality between juveniles and adults facilitate ecological diversification. We find that juvenile-biased mortality reduces the threshold of minimum resource productivity required for diversification. Diversification is hence less restricted when mortality is more biased towards juveniles than when all individuals experience the same mortality rate. This is because, by altering the population composition, juvenile-biased mortality increases the strength of intraspecific competition. Strong intraspecific competition in turn induces frequency-dependent selection, which drives ecological diversification. Our results demonstrate the strong influence that differential mortality between developmental stages has on diversification, and highlight the need for integrating developmental processes into the theoretical framework of diversification.
Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates
Authors: Zhang Yi-Nan , Paynter Jennifer , Antanasijevic Aleksandar , Allen Joel D. , Eldad Mor , Lee Yi-Zong , Copps Jeffrey , Newby Maddy , He Linling , Chavez Deborah , Frost Pat , Goodroe Anna , Dutton John , Lanford Robert , Chen Christopher , Wilson Ian A. , Crispin Max , Ward Andrew B. , Zhu Jiang 
Published: July 2022

ABSTRACTUncleaved prefusion-optimized (UFO) design can stabilize diverse HIV-1 envelope glycoproteins (Envs). Single-component, self-assembling protein nanoparticles (1c-SApNP) can display 8 or 20 trimeric antigens as multivalent vaccines. Here, we characterized the biophysical, structural, and antigenic properties of 1c-SApNPs that present the BG505 UFO trimer with wildtype and modified glycans. Trimming the glycan shield improved Env recognition by broadly neutralizing antibodies (bNAbs) to the CD4 binding site and other major glycan-containing epitopes. In mice, rabbits, and nonhuman primates, glycan trimming increased the frequency of vaccine responders (FVR) and steered antibody responses away from immunodominant glycan holes and glycan epitopes. The mechanism of vaccine-induced immunity was examined in mice. Compared with the soluble trimer, two large 1c-SApNPs showed 420 times longer retention, 20-32 times greater presentation on follicular dendritic cell dendrites, and up-to-4 times stronger germinal center reactions in lymph node follicles. These findings will inform the next phase of HIV-1 vaccine development.ONE-SENTENCE SUMMARYGlycan trimming of HIV-1 Env immunogens improves the vaccine-induced neutralizing antibody responses in small animals and primates
Stress-induced plasticity of a novel CRHGABA projection disrupts reward behaviors
Authors: Birnie Matthew T. , Short Annabel K. , de Carvalho Gregory B. , Gunn Benjamin G. , Pham Aidan L. , Itoga Christy A. , Xu Xiangmin , Chen Lulu Y. , Mahler Stephen V. , Chen Yuncai , Baram Tallie Z. 
Published: July 2022

AbstractDisrupted operations of the reward circuit are thought to underlie major emotional disorders including depression and drug abuse1–3. These disorders commonly arise following early life stress4,5; however, how stress early in life enduringly impacts reward circuit functions to promote disease remains unclear. Here, we discover and characterize a novel stress-sensitive reward-circuit projection connecting the basolateral amygdala (BLA) and nucleus accumbens (NAc) that co-expresses GABA and the stress-reactive neuropeptide corticotropin-releasing hormone (CRH). We then identify a crucial role for this projection in executing the disrupted reward behaviors provoked by early-life adversity (ELA): Chemogenetic and optogenetic stimulations of the CRHGABA BLA→NAc projection in typically reared mice suppressed several reward seeking behaviors, recapitulating deficits resulting from ELA and demonstrating a key contribution of this pathway in the normal operations of the reward circuit. Next, inhibition of the CRHGABA BLA→NAc projection in adult mice that experienced ELA restored typical reward behaviors in these mice, and, in contrast, had little effect in typically reared mice, indicating a selective ELA-induced maladaptive plasticity of this reward-circuit projection. We discover a novel, stress-sensitive, reward inhibiting projection from the BLA→NAc with unique molecular features, which may provide targets for intervention in disabling mental illnesses.
Anatomical and biophysical characterization of intergeneric graft-incompatibility within the Solanoideae
Authors: Thomas Hannah R , Gevorgyan Alice , Frank Margaret H 
Published: July 2022

ABSTRACTInterspecies grafting is a technique that allows beneficial shoot and root combinations from separate species to be combined into a single organism. Despite its relevance to agricultural production, little is known about the determinants of graft compatibility. One hypothesis for compatibility revolves around the taxonomic degree of relatedness between the two plants. To test how phylogenetic distance affects interspecific graft compatibility within the economically important Solanaceae sub-family, Solanoideae, we characterized the anatomical and biophysical integrity of graft junctions for graft combinations made between four species: tomato (Solanum lycopersicum), eggplant (Solanum melongena), pepper (Capsicum annuum), and groundcherry (Physalis pubescens). We analyzed the survival, growth, and junction integrity via bend tests, and imaged the cellular composition of the graft junctions in order to deduce the status of vascular connectivity across the junction. Utilizing these techniques, we were able to quantitatively assess the degree to which each interspecific combination exhibits compatibility. Despite the fact that most of our graft combinations exhibited high survival rates, we show that only tomato and eggplant heterografts are truly compatible. Unlike incompatible grafts, the formation of reconnected vascular tissue within the tomato and eggplant heterografts contributed to biophysically stable grafts that were resistant to snapping. Furthermore, we identified 10 graft combinations that show delayed incompatibility, providing a useful, economically relevant system to pursue deeper work into genetic and genomic determinants of graft compatibility. This work provides new evidence indicating that graft compatibility may be limited to intrageneric combinations within the Solanoideae subfamily. Further research using more extensive graft combinations amongst Solanaceous species can be used to test whether our hypothesis broadly applies to this family.
Exploring Taxonomic and Functional Microbiome of Hawaiian Stream and Spring Irrigation Water Systems Using Illumina and Oxford Nanopore Sequencing Platforms
Authors: Klair Diksha , Dobhal Shefali , Ahmed Amjad , Hassan Zohaib Ul , Uyeda Jensen , Silva Joshua , Wang Koon-Hui , Kim Seil , Alvarez Anne M. , Arif Mohammad 
Published: July 2022

ABSTRACTIrrigation water is a potential source of contamination that carries plant and foodborne human pathogens and provides a niche for survival and proliferation of microbes in agricultural settings. This project investigated bacterial communities and their functions in the irrigation water from wetland taro farms on Oahu, Hawai’i using different DNA sequencing platforms. Irrigation water samples (stream, spring, and tank stored water) were collected from North, East, and West sides of Oahu and subjected to high quality DNA isolation, library preparation and sequencing of the V3-V4 region, full length 16S rRNA, and shotgun metagenome sequencing using Illumina iSeq100, Oxford Nanopore MinION and Illumina NovaSeq, respectively. Illumina reads provided the most comprehensive taxonomic classification at the phylum level where Proteobacteria was identified as the most abundant phyla in river stream source and associated wet taro field water samples. Cyanobacteria was also a dominant phylum from tank and spring water, whereas Bacteroidetes were most abundant in wetland taro fields irrigated with spring water. However, over 50% of the valid short amplicon reads remained unclassified and inconclusive at the species level. Whereas samples sequenced for full length 16S rRNA and shotgun metagenome, clearly illustrated that Oxford Nanopore MinION is a better choice to classify the microbes to the genus and species levels. In terms of functional analyses, only 12% of the genes were shared by two consortia. Total 95 antibiotic resistant genes (ARGs) were detected with variable relative abundance. Description of microbial communities and their functions are essential for the development of better water management strategies to produce safer fresh produce and to protect plant, animal, human and environmental health. This project identified analytical tools to study microbiome of irrigation water.
Complex functional phenotypes of NMDA receptor disease variants
Authors: Iacobucci Gary J , Liu Beiying , Wen Han , Sincox Brittany , Zheng Wenjun , Popescu Gabriela K. 
Published: July 2022

AbstractNMDA receptors have essential roles in the physiology of central excitatory synapses and their dysfunction causes severe neuropsychiatric symptoms. Recently, a series of genetic variants have been identified in patients, however, functional information about these variants is sparse and their role in pathogenesis insufficiently known. Here we investigate the mechanism by which two GluN2A variants may be pathogenic. We use molecular dynamics simulation and single-molecule electrophysiology to examine the contribution of GluN2A subunit-residues, P552 and F652, and their pathogenic substitutions, P552R and F652V, affect receptor functions. We found that P552 and F652 interact during the receptors’ normal activity cycle; the interaction stabilizes receptors in open conformations and is required for a normal electrical response. Engineering shorter side-chains at these positions (P552A and/or F652V) caused a loss of interaction energy and produced receptors with severe gating, conductance, and permeability deficits. In contrast, the P552R sidechain resulted in stronger interaction and produced a distinct, yet still drastically abnormal electrical response. These results identify the dynamic contact between P552 and F652 as a critical step in the NMDA receptor activation, and show that both increased and reduced communication through this interaction cause dysfunction. Results show that subtle differences in NMDA receptor primary structure can generate complex phenotypic alterations whose binary classification is too simplistic to serve as a therapeutic guide.Main findingsTwo NMDA receptor residues whose substitution results in encephalopathies, were found to form new interactions during activation, and the energy provided by this interaction is required for normal receptor gating.Experimental substitutions of these residues that change the strength of their interaction reduce the receptor open probability, unitary conductance, and calcium permeability.Receptors with variations at these positions identified in patients display a broad range of both gain- and loss-of-function changes depending on the stimulation protocol.
Aggressive interactions between smooth-coated otters and water monitor lizards in Singapore
Authors: Bungum Haaken Zhong , Johns Philip 
Published: July 2022

AbstractSmooth-coated otters (Lutrogale perspicillata) and Malayan water monitor lizards (Varanus salvator) occupy similar habitats and and interact regularly in Singapore’s waterways. These interactions have a range of potential outcomes and are sometimes lethal. Few formal behavioral studies exist for either species. We analyzed interactions between otters and monitor lizards by gleaning data from publicly available videos from citizen scientists to examine what factors influence aggressive and defensive behaviors, and what influences vigilance in otters. Behavioral sequence analysis revealed no obvious monitor lizard behavior that predicted otter aggression towards monitors. We found that the presence and number of otter pups is positively associated with otter aggression. Otters also tended to be more vigilant in groups with more pups, and more vigilant on land than water. Monitor lizards displayed aggressive and defensive behaviors more frequently than did otters, regardless of whether the otters were aggressive towards lizards. These observations suggests that otters vary their aggression and vigilance levels depending on the context of each interaction.
Comparative study of bacterial SPOR domains identifies functionally important differences in glycan binding affinity
Authors: Yahashiri Atsushi , Kaus Gabriela M. , Popham David L. , Houtman Jon C.D. , Weiss David S. 
Published: July 2022

AbstractBacterial SPOR domains target proteins to the divisome by binding septal peptidoglycan (PG) at sites where cell wall amidases have removed stem peptides. These PG structures are referred to as denuded glycans. Although all characterized SPOR domains bind denuded glycans, whether there are differences in affinity is not known. Here we use isothermal titration calorimetry (ITC) to determine the relative PG glycan binding affinity (Kd) of four Escherichia coli SPOR domains and one Cytophaga hutchinsonii SPOR domain. We found that the Kd values ranged from approximately 1 µM for E. coli DamXSPOR and C. hutchinsonii CHU2221SPOR to about 10 µM for E. coli FtsNSPOR. To ask whether these differences in PG binding affinity are important for SPOR domain protein function, we constructed and characterized a set of DamX and FtsN “swap” proteins. As expected, all SPOR domain swap proteins localized to the division site, and in the case of FtsN all of the heterologous SPOR domains supported cell division. But for DamX only the high-affinity SPOR domain from CHU2221 supported normal function in cell division. In summary, different SPOR domains bind denuded PG glycans with different affinity, which appears to be very important for the function of some SPOR domain proteins (e.g., DamX) but not others (e.g., FtsN).ImportanceSPOR domain proteins are prominent components of the cell division apparatus in a wide variety of bacteria. The primary function of SPOR domains is to target proteins to the division site, which they accomplish by binding to septal peptidoglycan. But whether SPOR domains have any functions beyond septal targeting is unknown. Here we show that SPOR domains vary in their PG binding affinities and, at least in the case of the E. coli cell division protein DamX, having a high-affinity SPOR domain contributes to proper function.
Reconstruction and analysis of thermodynamically-constrained models reveal metabolic responses of a deep-sea bacterium to temperature perturbations
Authors: Dufault-Thompson Keith , Nie Chang , Jian Huahua , Wang Fengping , Zhang Ying 
Published: July 2022

AbstractMicrobial acclimation to different temperature conditions can involve broad changes in cell composition and metabolic efficiency. A systems-level view of these metabolic responses in non-mesophilic organisms, however, is currently missing. In this study, thermodynamically-constrained genome-scale models were applied to simulate the metabolic responses of a deep-sea psychrophilic bacterium, Shewanella psychrophila WP2, under suboptimal (4°C), optimal (15°C), and supraoptimal (20°C) growth temperatures. The models were calibrated with experimentally determined growth rates of WP2. Gibbs free energy change of reactions (ΔrG’), metabolic fluxes, and metabolite concentrations were predicted using random simulations to characterize temperature-dependent changes in the metabolism. The modeling revealed the highest metabolic efficiency at the optimal temperature, and it suggested distinct patterns of ATP production and consumption that could lead to the lower metabolic efficiency under suboptimal or supraoptimal temperatures. The modeling also predicted rearrangement of fluxes through multiple metabolic pathways, including the glycolysis pathway, Entner-Doudoroff pathway, tricarboxylic acid (TCA) cycle, and the electron transport system, and these predictions were corroborated through comparisons to WP2 transcriptomes. Furthermore, predictions of metabolite concentrations revealed the potential conservation of reducing equivalents and ATP in the suboptimal temperature, consistent with experimental observations from other psychrophiles. Taken together, the WP2 models provided mechanistic insights into the metabolism of a psychrophile in response to different temperatures.ImportanceMetabolic flexibility is a central component of any organism’s ability to survive and adapt to changes in environmental conditions. This study represents the first application of thermodynamically-constrained genome-scale models in simulating the metabolic responses of a deep-sea psychrophilic bacterium to varying temperatures. The models predicted differences in metabolic efficiency that were attributed to changes in metabolic pathway utilization and metabolite concentration during growth under optimal and non-optimal temperatures. Experimental growth measurements were used for model calibration, and temperature-dependent transcriptomic changes corroborated the model-predicted rearrangement of metabolic fluxes. Overall, this study highlights the utility of modeling approaches in studying the temperature-driven metabolic responses of an extremophilic organism.
Rapid monitoring for ecological persistence
Authors: Song Chuliang , Simmons Benno I. , Fortin Marie-Josée , Gonzalez Andrew , Kaiser-Bunbury Christopher N. , Saavedra Serguei 
Published: July 2022

AbstractEffective conservation of ecological communities requires accurate and up-to-date information about whether species are persisting or declining to extinction. The persistence of ecological communities is largely supported by its structured architecture of species interactions, known as an ecological network. While the persistence of the network supporting the whole community is the most relevant scale for conservation, in practice, we can only monitor small subsets of these networks due to logistical sampling constraints. There is therefore an urgent need to establish links between the small snapshots of data conservationists are able to collect, and the ‘big picture’ conclusions about ecosystem health demanded by policy makers, scientists and societies. Here we show that the persistence of small subnetworks in isolation — that is, their persistence when considered separately from the larger network of which they are a part — is a reliable probabilistic indicator of the persistence of the network as a whole. Our results are general across both antagonistic and mutualistic interaction networks. Empirically, we show that our theoretical predictions are supported by data on invaded networks in restored and unrestored areas, even in the presence of environmental variability. Our work suggests that coordinated action to aggregate information from incomplete sampling can provide a means to rapidly assess the persistence of entire ecological networks and the expected success of restoration strategies. This could significantly improve our ability to monitor progress towards achieving policy targets, such as those enshrined in the UN Convention on Biological Diversity.
Aesthetic and physiological effects of naturalistic multimodal music listening
Authors: Czepiel Anna , Fink Lauren K. , Seibert Christoph , Scharinger Mathias , Kotz Sonja A. 
Published: July 2022

AbstractCompared to audio only (AO) conditions, audiovisual (AV) information can enhance the aesthetic experience of a music performance. However, such beneficial multimodal effects have yet to be studied in naturalistic music performance settings. Further, peripheral physiological correlates of aesthetic experiences are not well-understood. Here, participants were invited to a concert hall for piano performances of Bach, Messiaen, and Beethoven, which were presented in two conditions: AV and AO. They rated their aesthetic experience (AE) after each piece (Experiment 1 and 2), while peripheral signals (cardiorespiratory measures, skin conductance, and facial muscle activity) were continuously measured (Experiment 2). Factor scores of AE were significantly higher in the AV condition in both experiments. LF/HF ratio, a heart rhythm that represents activation of the sympathetic nervous system, was higher in the AO condition, suggesting increased arousal, likely caused by less predictable sound onsets in the AO condition. We present partial evidence that breathing was faster and facial muscle activity was higher in the AV condition, suggesting that observing a performer’s movements likely enhances motor mimicry in these more voluntary peripheral measures. Further, zygomaticus (‘smiling’) muscle activity was a significant predictor of AE. Thus, we suggest physiological measures are related to AE, but at different levels: the more involuntary measures (i.e., heart rhythms) may reflect more sensory aspects, while the more voluntary measures (i.e., muscular control of breathing and facial responses) may reflect the liking aspect of an AE. In summary, we replicate and extend previous findings that AV information enhances AE in a naturalistic music performance setting. We further show that a combination of self-report and peripheral measures benefit a meaningful assessment of AE in naturalistic music performance settings.