bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formate-induced CO tolerance and innovative methanogenesis inhibition in co-fermentation of syngas and plant biomass for carboxylate production
Authors: Baleeiro Flávio C. F. , Varchmin Lukas , Kleinsteuber Sabine , Sträuber Heike , Neumann Anke 
Published: July 2022

ABSTRACTProduction of monocarboxylates using microbial communities is highly dependent on local and degradable biomass feedstocks. Syngas or different mixtures of H2, CO, and CO2can be co-fed to a fermenter to alleviate this dependence. To understand the effects of adding these gases during anaerobic fermentation of plant biomass, a series of batch experiments was carried out with different syngas compositions and corn silage (pH 6.0, 32°C). Co-fermentation of syngas with corn silage increased the overall carboxylate yield per gram of volatile solids (VS) by up to 44% (0.36 ± 0.07 g gVS-1; in comparison to 0.23 ± 0.04 g gVS-1with a N2/CO2headspace), despite slowing down biomass degradation. Ethylene and CO exerted a synergistic effect in preventing methanogenesis, leading to net carbon fixation. Less than 12% of the electrons were misrouted to CH4when either 15 kPa CO or 5 kPa CO + 1.5 kPa ethylene was used. CO increased the selectivity to acetate and propionate, which accounted for 86% (electron equivalents) of all products at 49 kPa CO, by favoring lactic acid bacteria and actinobacteria overn-butyrate andn-caproate producers. This happened even when an inoculum pre-acclimatized to syngas and lactate was used. Intriguingly, the effect of CO onn-butyrate andn-caproate production was reversed when formate was present in the broth. The concept of co-fermenting syngas and plant biomass shows promise in two aspects: by making anaerobic fermentation a carbon-fixing process and by increasing the production of propionate and acetate. Testing the concept in a continuous process could improve selectivity ton-butyrate andn-caproate by enriching chain-elongating bacteria adapted to CO and complex biomass.
Metformin protects trabecular meshwork against oxidative injury via activating integrin/ROCK signals
Authors: Xu Lijuan , Zhang Xinyao , Zhao Yin , Cao Yang , Liang Yuanbo 
Published: July 2022

AbstractBackgroundThis study aimed to investigate the protective effect of metformin on the trabecular meshwork (TM) and explore its molecular mechanisms in vivo and in vitro.MethodsOcular hypertension (OHT) mouse models were induced with dexamethasone (DEX) and further treated with metformin to determine its IOP lowering effect. Cultured human TM cells (HTMC) were pre-stimulated with tert-butyl hydroperoxide (tBHP) to induce oxidative damage and then supplemented with metformin for another 24 h. The expression of fibrotic markers and integrin/ROCK signals, including α-SMA, TGF-β, fibronectin, F-actin, integrin beta 1, Rho-associated kinase (ROCK)1/2, AMP-activated protein kinase (AMPK), myosin light chain 1 (MLC 1), and F-actin were determined by western blotting (WB) and immunofluorescence (IF). Reactive oxygen species (ROS) content was analysed using flow cytometry (FCM).ResultsAdministration of metformin reduced the elevated IOP and alleviated the fibrotic activity of aqueous humour outflow in OHT models. Additionally, metformin rearranged the disordered cytoskeleton in the TM both in vivo and in vitro. Furthermore, metformin significantly inhibited ROS production and activated integrin/ROCK signalling induced by tBHP in HTMC.ConclusionMetformin reduced the elevated IOP in steroid-induced OHT mouse models and exerted its protective effects against oxidative injury by regulating cytoskeleton remodelling through the integrin/ROCK pathway. This study provides new insights into metformin use and preclinical evidence for the potential treatment of primary open-angle glaucoma.
A DARPin-based molecular toolset to probe gephyrin and inhibitory synapse biology
Authors: Campbell Benjamin F. N. , Dittmann Antje , Dreier Birgit , Plückthun Andreas , Tyagarajan Shiva K. 
Published: July 2022

AbstractNeuroscience currently requires the use of antibodies to study synaptic proteins, where antibody binding is used as a correlate to define the presence, plasticity, and regulation of synapses. Gephyrin is an inhibitory synaptic scaffolding protein used to mark GABAergic and glycinergic postsynaptic sites. Despite the importance of gephyrin in modulating inhibitory transmission, its study is currently limited by the tractability of available reagents. Designed Ankyrin Repeat Proteins (DARPins) are a class of synthetic protein binder derived from diverse libraries by in vitro selection, and tested by high-throughput screening to produce specific binders. In order to generate a functionally diverse toolset for studying inhibitory synapses, we screened a DARPin library against gephyrin mutants representing both phosphorylated and dephosphorylated states. We validated the robust use of anti-gephyrin DARPin clones for morphological identification of gephyrin clusters in rodent neuron culture and brain tissue, discovering previously overlooked clusters. This DARPin-based toolset includes clones with heterogenous gephyrin binding modes that allowed for identification of the most extensive gephyrin interactome to date, and defined novel classes of putative interactors, creating a framework for understanding gephyrin’s non-synaptic functions. This study demonstrates anti-gephyrin DARPins as a versatile platform for studying inhibitory synapses in an unprecedented manner.
In-depth study of tomato and weed viromes reveals undiscovered plant virus diversity in an agroecosystem
Authors: Rivarez Mark Paul Selda , Pecman Anja , Bačnik Katarina , Maksimović Carvalho Ferreira Olivera , Vučurović Ana , Seljak Gabrijel , Mehle Nataša , Gutiérrez-Aguirre Ion , Ravnikar Maja , Kutnjak Denis 
Published: July 2022

AbstractBackgroundIn agroecosystems, viruses are well known to influence crop health and a few cause phytosanitary and economic problems, but their diversity in non-crop plants and role outside the disease perspective is less known. An extensive virome exploration that includes both crop and diverse weed plants is therefore needed to better understand roles of viruses in agroecosystems. Such unbiased exploration is possible through viromics, which could generate biological and ecological insights from immense high-throughput sequencing (HTS) data.ResultsHere, we implemented HTS-based viromics to explore viral diversity in tomatoes and weeds in farming areas at a nation-wide scale. We detected 125 viruses, including 79 novel species, wherein 65 were found exclusively in weeds. This spanned 21 higher-level plant virus taxa dominated by Potyviridae, Rhabdoviridae, and Tombusviridae, and four non-plant virus families. We detected viruses of non-plant hosts and viroid-like sequences, and demonstrated infectivity of a novel tobamovirus in plants of Solanaceae family. Diversities of predominant tomato viruses were variable, in some cases, comparable to that of global isolates of same species. We phylogenetically classified novel viruses, and showed links between a subgroup of phylogenetically-related rhabdoviruses to their taxonomically-related host plants. Ten classified viruses detected in tomatoes were also detected in weeds, which might indicate possible role of weeds as their reservoirs, and that these viruses could be exchanged between the two compartments.ConclusionsWe showed that even in relatively well studied agroecosystems, such as tomato farms, a large part of very diverse plant viromes can still be unknown and is mostly present in understudied non-crop plants. The overlapping presence of viruses in tomatoes and weeds implicate possible presence of virus reservoir and possible exchange between the weed and crop compartments, which may influence weed management decisions. The observed variability and widespread presence of predominant tomato viruses and the infectivity of a novel tobamovirus in solanaceous plants, provided foundation for further investigation of virus disease dynamics and their effect on tomato health. The extensive insights we generated from such in-depth agroecosystem virome exploration will be valuable in anticipating possible emergences of plant virus diseases, and would serve as baseline for further post-discovery characterization studies.
High Frequency Oscillations (250-500Hz) in Animal Models of Alzheimer’s Disease and Two Animal Models of Epilepsy
Authors: Lisgaras Christos Panagiotis , Scharfman Helen E. 
Published: July 2022

ABSTRACTObjectiveTo test the hypothesis that high frequency oscillations (HFOs) between 250 and 500Hz occur in mouse models of Alzheimer’s disease (AD) and thus are not unique to epilepsy.MethodsExperiments were conducted in three mouse models of AD: Tg2576 mice that simulate a form of familial AD, presenilin 2 knock-out (PS2KO) mice, and the Ts65Dn model of Down’s syndrome. We recorded HFOs using wideband (0.1-500Hz, 2kHz) intra-hippocampal and cortical surface EEG at 1month until 24months-old during wakefulness, slow wave sleep (SWS) and rapid eye movement (REM) sleep. Interictal spikes (IIS) and seizures were also analyzed for the possible presence of HFOs. Comparisons were made to the intra-hippocampal kainic acid and pilocarpine models of epilepsy.ResultsWe describe for the first time that hippocampal and cortical HFOs are a new EEG abnormality in AD mouse models. HFOs occurred in all transgenic mice but no controls. They were also detectable as early as 1month of age and prior to amyloid-β plaque neuropathology. HFOs were most frequent during SWS (vs. REM or wakefulness). Notably, HFOs in the AD and epilepsy models were indistinguishable in both spectral frequency and duration. HFOs also occurred during IIS and seizures in the AD models, although with altered spectral properties compared to isolated HFOs.SignificanceOur data demonstrate that HFOs, an epilepsy biomarker with high translational value, are not unique to epilepsy and thus not disease specific. Our findings also strengthen the idea of hyperexcitability in AD and its significant overlap with epilepsy. HFOs in AD mouse models may serve as an EEG biomarker which is detectable from the scalp and thus amenable to non-invasive detection in people at risk for AD.KEY POINTSHigh frequency oscillations (HFOs, 250-500Hz) occur in mouse models of Alzheimer’s diseaseHFOs are detectable from the hippocampus and overlying cortexHFOs are most frequent during slow wave sleepHFOs in AD mouse models resemble HFOs in two animal models of epilepsyHFOs can be detected during interictal spikes and seizures in the AD models
Intestinal Epithelial Heat Shock Protein 25/27 integrates host and microbial drivers of mucosal restitution following inflammatory injury
Authors: Cham Candace M. , Messer Jeannette S. , Lake Joash , Zhu Xiaorong , Tao Yun , He Lei , Weber Christopher R. , Lin Fanfei , Dai Zhanghan , Tong Jinlu , Temelkova Sara , Rubin David T. , Liu Cambrian , Chang Eugene B. 
Published: July 2022

AbstractMucosal healing following inflammatory injury is poorly understood and often neglected, despite being the best indicator of long-term outcomes in inflammatory bowel diseases. We report here that the enigmatic small molecular weight heat shock protein, Hsp25 (the human form is Hsp27), plays a vital role in converging microbial and host factors to promote pSTAT3-mediated mucosal healing. In wild type mice, the proximal-to-distal gradient of intestinal epithelial cell (IEC) Hsp25 expression is dependent on microbial cues. Patients with left-sided ulcerative colitis, however, show reduced levels of Hsp27 expression in both uninvolved and involved areas compared to normal colons of non-IBD patients. In mice with global or IEC-specific Hsp25 gene-targeted deletion, impaired mucosal healing with development of hallmarks of chronic disease are observed following DSS-induced or TNBS-induced colitis, whereas mucosal restitution is accelerated in IEC-specific overexpressing Hsp25 transgenic mice. In colonic IECs derived from these murine lines, Hsp25 binds and stabilizes a phospho-STAT3/YAP nuclear complex stimulated by IL-22 to sustain its wound healing gene programming. Thus, our findings provide insight into the mechanism of action of IEC Hsp25/27 in integrating host and microbial drivers of mucosal restitution, which can be leveraged to develop novel approaches for achieving and maintaining remission in complex immune disorders like IBD.
Odd-Even Oddball Task: Evaluating Event-Related Potentials (ERPs) during Word Discrimination Compared to Speech-Token and Tone Discrimination
Authors: Voola Marcus , Nguyen An T. , Marinovic Welber , Rajan Gunesh , Tavora-Vieira Dayse 
Published: July 2022

AbstractThe use of tonal and speech token auditory oddball tasks has been used abundantly in past literature; however, it has been argued that tasks using non-word sounds fail to capture the higher-level ability to interpret and discriminate stimuli based on meaning which are critical to language comprehension. As such this study aims to examine how neural signals associated with discrimination and evaluation-processes (P3b) from semantic stimuli compare with those elicited by pure tones and speech tokens.This study comprises of two experiments, both containing thirteen adults (Exp 1: (Mean(SD)age = 25.20(3.89) years and Exp 2: Mean(SD)age = 25.3(3.79) years) with normal hearing in both ears (PTA ≤ 20dB HL). Scalp electroencephalography and auditory event related potentials was recorded in free field whilst they completed three different oddball tasks: 1) Tones, 2) Speech tokens and 3) Odd/Even numbers. In experiment two, the duration of each stimulus was the same.P3b peak latency was significantly different between all three tasks, in both experiments. P3b amplitude was identified to be sensitive to reaction time, with tasks that have a large reaction time variability resulting in the P3b amplitude to be smeared out, thereby reducing the amplitude size.The findings from this study highlight the need to take into consideration all factors of the task before attributing any effects to any additional process such as semantic processing and mental effort. Furthermore, it highlights the need for more cautious interpretation of P3b results in auditory oddball tasks.
Event-Related Potentials of Single Sided Deaf Cochlear Implant Users – Using a Semantic Oddball Paradigm in Noise
Authors: Voola Marcus , Wedekind Andre , Nguyen An T. , Marinovic Welber , Rajan Gunesh , Tavora-Vieira Dayse 
Published: July 2022

AbstractObjectiveIn individuals with single sided deafness (SSD), which is characterised by a profound hearing loss in one ear and normal hearing in the contralateral ear, binaural input is no longer present. A cochlear implant (CI) is the only way to restore functional hearing in the profoundly deaf ear, with previous literature demonstrating improvements in speech in noise intelligibility with the provision of a CI. However, we currently have a limited understanding of the neural processes involved (e.g., how the brain integrates the electrical signal produced by the CI with the acoustic signal produced by the normal hearing ear) and how the modulation of these processes with CI contributes to improved speech in noise intelligibility. Using a semantic oddball paradigm presented in the presence of background noise, this study aims to investigate how the provision of CI impacts speech in noise perception of SSD CI users.MethodHigh density electroencephalography (EEG) from twelve SSD-CI participants was recorded whilst they completed a semantic acoustic oddball task. All participants completed the oddball task in three different free field conditions with the speech and noise coming from different speakers. The three tasks were 1) with the CI-On in background noise, 2) with the CI-Off in background noise and 3) with the CI-On without background noise (Control). We examined task-performance (RT, subjective listening effort, and accuracy) and measured N2N4 and P3b event-related brain potentials (ERPs) linked to the discrimination and evaluation of task relevant stimuli. Speech in noise and sound localisation abilities was also measured.ResultsReaction time was significantly different between all tasks with CI-On (M(SE) = 809(39.9) ms) having faster RTs than CI-Off (M(SE) = 845(39.9) ms) and Control (M(SE) = 785(39.9) ms) being the fastest condition. The Control condition exhibited a significantly shorter N2N4 and P3b area latency when compared to the other two conditions. However, despite these differences noticed in RTs and area latency, we observed similar results between all three conditions for N2N4 and P3b difference area.ConclusionThe inconsistency between the behavioural and neural results suggest that EEG may not be a reliable measure of cognitive effort. This rationale is further supported by the different explanations used in past studies to explain N2N4 and P3b effects. Future studies should look to alternative measures of auditory processing (e.g., pupillometry) to get a deeper understanding of the underlying auditory processes that facilitate speech in noise intelligibility.
An improved graph representation learning method for drug-target interaction prediction over heterogeneous biological information graph
Authors: Zhao Bo-Wei , Su Xiao-Rui , You Zhu-Hong , Hu Peng-Wei , Hu Lun 
Published: July 2022

ABSTRACTThe prediction task of the relationships between drugs and targets plays a significant role in the process of new drug discovery. Computational-based strategies for predicting drug-target interactions (DTIs) are regarded as a high-efficiency way. Moreover, recent studies adopted a graph neural network (GNN) to discover underlying DTIs and achieved better performance. Although these inductive methods can straightway learn biomolecules’ latent representations, they have an over-smoothing phenomenon in the course of obtaining the rich neighborhood information of each node in the biological information network, which further leads to a consistent feature representation of each node. To address the above issues, a novel model, called iGRLDTI, is proposed to precisely identify new DTIs based on an improved graph representation learning strategy. Specifically, iGRLDTI first constructs a biological information graph (BIG) by calculating the biological knowledge of drugs and targets with the relationships between them. Then, an improved graph representation learning strategy is designed to capture the enriched feature representations of drugs and targets. Finally, the Gradient Boosting Decision Tree classifier is applied to predict potential DTIs. Experimental results demonstrate that iGRLDTI yields better performance by comparing it with other state-of-the-art models on the benchmark dataset. Besides, our case studies denote that iGRLDTI can successfully identify unknown DTIs according to the improved feature representations of drugs and targets.
KIPEs3: Automatic annotation of biosynthesis pathways
Authors: Rempel Andreas , Choudhary Nancy , Pucker Boas 
Published: July 2022

AbstractFlavonoids and carotenoids are pigments involved in stress mitigation and numerous other processes. Both pigment classes can contribute to flower and fruit coloration. Flavonoid aglycones and carotenoids are produced by a pathway that is largely conserved across land plants. Glycosylations, acylations, and methylations of the flavonoid aglycones can be species-specific and lead to a plethora of biochemically diverse flavonoids. We previously developed KIPEs for the automatic annotation of biosynthesis pathways and presented an application on the flavonoid aglycone biosynthesis.KIPEs3 is an improved version with additional features and the potential to identify not just the core biosynthesis players, but also candidates involved in the decoration steps and in the transport of flavonoids. Functionality of KIPEs3 is demonstrated through the analysis of the flavonoid biosynthesis inArabidopsis thalianaNd-1,Capsella grandiflora, andDioscorea dumetorum. We demonstrate the applicability of KIPEs to other pathways by adding the carotenoid biosynthesis to the repertoire. As a technical proof of concept, the carotenoid biosynthesis was analyzed in the same species andDaucus carota. KIPEs3 is available as an online service to enable access without prior bioinformatics experience.KIPEs3 facilitates the automatic annotation and analysis of biosynthesis pathways with a consistent and high quality in a large number of plant species. Numerous genome sequencing projects are generating a huge amount of data sets that can be analyzed to identify evolutionary patterns and promising candidate genes for biotechnological and breeding applications.
The circadian clock controls temporal and spatial patterns of floral development in sunflower
Authors: Marshall Carine M. , Thompson Veronica L. , Creux Nicky M. , Harmer Stacey L. 
Published: July 2022

AbstractBiological rhythms are ubiquitous. They can be generated by circadian oscillators, which produce daily rhythms in physiology and behavior, as well as by developmental oscillators such as the segmentation clock, which produces modular developmental units in a periodic fashion. Here, we show that the circadian clock controls the timing of late-stage floret development, or anthesis, in domesticated sunflower. In these plants, what appears to be a single inflorescence consists of up to thousands of individual florets tightly packed onto a capitulum disk. While early floret development occurs continuously across capitula to generate iconic spiral phyllotaxy, during anthesis floret development occurs in discrete ring-like pseudowhorls with up to hundreds of florets undergoing simultaneous maturation. We demonstrate circadian regulation of floral organ growth and show that the effects of light on this process are time-of-day dependent. Disruption of circadian rhythms in floral organ development causes loss of pseudowhorl formation. Thus, we show that the sunflower circadian clock acts in concert with environmental response pathways to tightly synchronize the anthesis of hundreds of florets each day, generating spatial patterns on the developing capitulum disk. This coordinated mass release of floral rewards at predictable times of day likely promotes pollinator visits and plant reproductive success.