bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Taurus Mountains, the hotspot of Western Palearctic biodiversity, is under danger: marble quarries affect wildlife
Authors: Albayrak Tamer , Yılmaz Tamer 
Published: November 2023

AbstractThe Taurus Mountains in the Mediterranean Coastal Basin, considered a biodiversity hotspot, have a rich biodiversity in the Western Palearctic. The number of marble quarries in the Taurus Mountains has dramatically expanded over the past ten years. The objectives of this study are to (i) determine the impacts of quarrying on wildlife; (ii) determine the potential impacts of quarrying on the future of Taurus. A total of 57547 photos and video images were analyzed on 5447 photo-trap days in two areas, the marble quarries and the control areas. Using 97 randomly selected marble quarries, the area they cover and their annual growth rates were determined. The most commonly seen animals were the wolf, fox, lynx, and wild boar in the control area, and the jackal and hare in the marble quarries (p< 0.001). Additionally, we found a significant positive correlation between the distance of the geographical center of the marble quarries and the number of dates of Wolf, Fox and Wild Boar and a negative significant correlation for hare (p< 0.05). A positive correlation was found between the area of marble quarries and the duration of operation (R= 0.89,p< 0.00). The waste from quarries, which makes up 79.7% of the total land used for this purpose, is the greatest cause of habitat degradation. According to calculations, even if no new marble quarries are built as of right now, 7.14% of the Taurus may have disappeared by the year 2027, and by the year 2032, 8.25% of the Taurus ecosystems may have disappeared completely. The Taurus Mountains, a center of Western Palearctic biodiversity, are being threatened by the marble quarries. This study advances our knowledge of how marble quarries may affect wildlife. New strategies must be developed as soon as possible to protect the Taurus Mountains, the hotspot of the Mediterranean basin.Summary Text for Online Table of ContentsWe conducted a one-year photo trap study on the effects of marble quarries on wildlife in the Taurus Mountains, a significant biodiversity hotspot. Our research showed that wild animals prefer areas without marble quarries, and their density rises as they get farther from the quarry’s core. Photograph by Tamer Yılmaz
Cellular Uptake and Fate of Cationic Polymer-Coated Nanodiamonds Delivering siRNA: A Mechanistic Study
Authors: Majer Jan , Kindermann Marek , Pinkas Dominik , Chvatil David , Cigler Petr , Libusova Lenka 
Published: November 2023

ABSTRACTGene silencing using small interfering RNAs (siRNAs) is a selective and promising approach for treatment of numerous diseases. However, broad applications of siRNAs are compromised by their low stability in a biological environment and limited ability to penetrate cells. Nanodiamonds (NDs) coated with cationic polymers can enable cellular delivery of siRNAs. Recently, we developed a new type of ND coating based on a random copolymer consisting of (2-dimethylaminoethyl) methacrylate (DMAEMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) monomers. These hybrid ND-polymer particles (Cop+-FND) provide near-infrared fluorescence, form stable complexes with siRNA in serum, show low toxicity, and effectively deliver siRNA into cellsin vitroandin vivo. Here, we present data on the mechanism of cellular uptake and cell trafficking of Cop+-FND:siRNA complexes and their ability to selectively suppress mRNA levels, as well as their cytotoxicity, viability and colloidal stability. We identified clathrin-mediated endocytosis as the predominant entry mechanism for Cop+-FND:siRNA into U-2 OS human bone osteosarcoma cells, with a substantial fraction of Cop+-FND:siRNA following the lysosome pathway. Cop+-FND:siRNA potently inhibited the target GAPDH gene with negligible toxicity and sufficient colloidal stability. Based on our results, we suggest that Cop+-FND:siRNA can serve as a suitablein vivodelivery system for siRNA.
Influence of Reinforcement and Its Omission on Trial-by-Trial Changes of Response Bias in Perceptual Decision-Making
Authors: Stüttgen Maik C. , Dietl Andrea , Eckert Vanya V. Stoilova , Ferrer Luis de la Cuesta , Blanke Jan-Hendrik , Koß Christina , Jäkel Frank 
Published: November 2023

AbstractDiscrimination performance in perceptual choice tasks is known to reflect both sensory discriminability and non-sensory response bias. In the framework of signal detection theory (SDT), these aspects of discrimination performance are quantified through separate measures, sensitivity (d’) for sensory discriminability and decision criterion (c) for response bias. However, it is unknown how response bias (i.e., criterion) changes at the single-trial level as a consequence of reinforcement history. We subjected rats to a two-stimulus two-response conditional discrimination task with auditory stimuli and induced response bias through unequal reinforcement probabilities for the two responses. We compared three SDT-based criterion learning models in their ability to fit experimentally observed fluctuations of response bias on a trial-by-trial level. These models shift the criterion by a fixed step (1) after each reinforced response, or (2) after each non-reinforced response, or (3) after both. We find that all three models fail to capture essential aspects of the data. Prompted by the observation that steady-state criterion values conformed well to a behavioral model of signal detection based on the generalized matching law, we constructed a trial-based version of this model and find that it provides a superior account of response bias fluctuations under changing reinforcement contingencies.
The Influence of Knee Varus Deformity on the Kinematic and Dynamic Characteristics of Musculoskeletal Models During Gait
Authors: Tabeiy Sina , Karimpour Morad , Shirvani Azizollah , Vaziri Arash Sherafat 
Published: November 2023

AbstractBackgroundMusculoskeletal modeling has paved the way of measuring kinematic and kinetic variables during motions. Nonetheless, since the commonly-used generic models are created based on averaged data; thus, they cannot accurately mimic subjects with skeletal deformities. To overcome this obstacle, one can build personalized models based on subject’s MRI or CT scan data, which is both time and money consuming. The other promising way is to manipulate generic models and create semi-personalized models to match with the individual’s skeletal system at the joint of interest.Research QuestionCan a semi-personalized model reduce marker error in gait analysis? How a semi-personalized model differentiates the ROM of the lower limb joints and muscle activation pattern while having varus deformity?MethodWe developed the varus-valgus tool (freely available on:https://simtk.org/projects/var-val-tool) in MATLAB using OpenSim Application Programming Interface (API) to incorporate varus-valgus deformity in the generic OpenSim models. A 36-year-old female subject with a complaint of knee pain participated in our study. The subject had 6.5 and 11.9 degrees of varus in the right and left leg, respectively. A semi-personalized model of the subject was first created using generic OpenSim models. Then, markers’ error during Inverse Kinematic (IK), joints Range of Motion (ROM) and the activation of Tensor Fasciae Latae (TFL), a knee adductor, and Gracilis, a knee abductor, were calculated and compared between a semi-personalized model and a generic model.ResultsSignificant difference was observed in markers’ error during IK between generic and semipersonalized models (p<0.05). Substantial alterations were found in the ROM of the hip, knee and ankle joints while using semi-personalized model. Moreover, the activation pattern of TFL experienced a dramatic rise whereas Gracilis saw a fall during each gait cycle in semi-personalized models.SignificanceImplementing varus-valgus deformity in the generic models substantially reduces markers’ error which leads to more accurate results. It was observed that semi-personalized models showed different ROM compared to generic ones.
DeepSipred: A deep-learning-based approach on siRNA inhibition prediction
Authors: Liu Bin , Huang Huiya , Liao Weixi , Pan Xiaoyong , Jin Cheng , Yuan Ye 
Published: November 2023

AbstractMotivationThe use of exogenous small interfering RNAs (siRNAs) for gene silencing has become a widespread molecular tool for gene function study and new drug identification. Although the pathway of RNAi to mediate gene expression has been widely investigated, the selection of hyperfunctional siRNA with high inhibition remains challenging.ResultsIn this study, we build a deep-learning-based approach on siRNA inhibition prediction, named DeepSipred. It combines features from sequence context, thermodynamic property, and other expert knowledge together to predict the inhibition more accurately than existing methods. The sequence features from siRNA and local target mRNA are generated via one-hot encoding and pretrained RNA-FM encoding. The convolution layers with multiple kernels in DeepSipred can detect various decisive motifs, which will determine the actual inhibition of siRNA. The thermodynamic features are calculated from Gibbs Free Energy. In addition, the expert knowledge includes those design criteria from previous studies. Benchmarked on large available public datasets, the 10-fold cross-validation results indicate that our predictor achieving the state-of-the-art performance.Contactyuanye_auto@sjtu.edu.cnorchengjin520@sjtu.edu.cn.
Cultural use of tropane alkaloids ofBrugmansiaspecies and cultivars in Colombia depends on local plant growth environment rather than genetic diversity
Authors: Rojas Sofia , Madriñan Santiago , Stahl Mark , Harter Klaus 
Published: November 2023

AbstractBorracheros or Angel Trumpets (Brugmansiaspp.) of theSolanaceaeplant family are known for producing scopolamine and other tropane alkaloids and are widely used by indigenous communities in the Andes for medicinal and ritual purposes. Growing different varieties has increased the popularity ofBrugmansiaspecies in recent years, leading to the promotion of hybridization to get new morphotypes. However, so far no medical or cultural use of plant extracts could be linked to selectedBrugmansiaspecies or cultivars. Moreover, until now there is only limited knowledge about the effect of hybridization on tropane alkaloid contents and/or diversity ofBrugmansiaspecies or cultivars. Here, a liquid chromatography-mass spectrometry (LC-MS) approach was applied to identify and characterize secondary metabolite contents in variousBrugmansiaspecies and hybrids from different geographic origins in Colombia. The analysis of the metabolic data sets revealed that tropane alkaloids and other secondary metabolites accumulate in a leaf and flower specific manner. Although some minor differences were found betweenBrugmansiasubgroups, the only significant difference exists between plants collected in the Sibundoy Valley, where they have been domesticated by indigenous communities since a long time and those, which so far have not been used by humans at all. The different genetic constitutions ofBrugmanciaspecies and cultivars are not the dominating reason for their differences in tropane alkaloid contents and medical and cultural usages, as there is no clear taxonomical signature based on the metabolite properties for species segregation. Instead, their use by indigenous communities during ceremonies and for medical treatment such as wound healing, infection control, rheumatism and arthritis is rather caused by the plasticity of the individual plants to react to the local abiotic and biotic environments by the variation of secondary metabolite composition and by the differences in the bioavailability of the active compounds as result of the extraction method.
Epigenetic predictors of species maximum lifespan and other life history traits in mammals
Authors: Li Caesar Z. , Haghani Amin , Yan Qi , Lu Ake T. , Zhang Joshua , Fei Zhe , Ernst Jason , Yang X. William , Gladyshev Vadim N. , Raj Ken , Seluanov Andrei , Gorbunova Vera , Horvath Steve 
Published: November 2023

AbstractMaximum lifespan is an intrinsic characteristic of a biological species and is defined as the longest time an individual of a species has been reported to survive. By analyzing 15K samples derived from 348 mammalian species representing 25 taxonomic orders we previously identified CpG methylation sites associated with maximum lifespan. Here we present accurate DNA methylation-based (DNAm) predictors of maximum lifespan (r=0.89), average gestation time (r=0.96), and age at sexual maturity (r=0.85). Our DNAm maximum lifespan predictor indicates a potential innate longevity advantage for females over males in 17 mammalian species such as humans, red deer, and cattle. The DNAm maximum lifespan predictions do not vary significantly by caloric restriction and partial reprogramming. Genetic disruptions in the somatotropic axis, which includes growth hormone, IGF-1, and their related receptors, have an impact on DNAm maximum lifespan only in select mouse tissues. Cancer mortality rates in major mammalian orders show no correlation with our epigenetic estimates of life history traits. The DNAm maximum lifespan predictor does not detect variation in lifespan between individuals of the same species, such as between the breeds of dogs. We also present the first prototypes of accurate pan mammalian DNAm predictors of sex and tissue type.Collectively, our findings indicate that maximum lifespan is determined, at least in part, by an epigenetic signature that is an intrinsic property of each species and is distinct from the signatures that relate to individual lifespan, which is unaffected by interventions influencing the mortality risk of individuals.
The proteome of agroinfiltratedNicotiana benthamianais shaped by extensive protein processing
Authors: Zheng Kaijie , Lyu Joy C. , Thomas Emma L. , Schuster Mariana , Sanguankiattichai Nattapong , Ninck Sabrina , Kaschani Farnusch , Kaiser Markus , van der Hoorn Renier A. L. 
Published: November 2023

AbstractProcessing by proteases irreversibly regulates the fate of plant proteins and hampers the production of recombinant protein in plants, yet only few processing events have been described in agroinfiltratedNicotiana benthamiana, which has emerged as a favorite transient protein expression platform in plant science and molecular pharming. Here, we used in-gel digests and mass spectrometry to monitor the migration and topography of 5,040 plant proteins of agroinfiltratedN. benthamianawithin a protein gel. By plotting the peptides over the gel slices, we generated peptographs that reveal where which part of each protein was detected within the protein gel. These data uncovered that 60% of the detected proteins have proteoforms that migrate at lower than predicted molecular weights, implicating extensive proteolytic processing. For instance, this analysis confirms the proteolytic removal and degradation of autoinhibitory prodomains of most but not all proteases, and revealed differential processing within pectinemethylesterase and lipase families. This analysis also uncovered intricate processing of glycosidases and uncovered that ectodomain shedding might be common for a diverse range of receptor-like kinases. Transient expression of double-tagged candidate proteins confirmed various processing eventsin vivo. This extensive proteomic dataset can be investigated further and demonstrates that most plant proteins are proteolytically processed and implicates an extensive proteolytic machinery shaping the proteome of agroinfiltratedN. benthamiana.
Crystal structure of the GluK1 ligand-binding domain with kainate and the full-spanning positive allosteric modulator BPAM538
Authors: Bay Yasmin , Fransen Stine M. , Pickering Darryl S. , Frydenvang Karla , Francotte Pierre , Pirotte Bernard , Kristensen Anders Skov , Kastrup Jette Sandholm 
Published: November 2023

AbstractKainate receptors play an important role in the central nervous system by mediating postsynaptic excitatory neurotransmission and modulating the release of the inhibitory neurotransmitter GABA through a presynaptic mechanism. To date, only three structures of the ligand-binding domain (LBD) of the kainate receptor subunit GluK1 in complex with positive allosteric modulators have been determined by X-ray crystallography, all belonging to class II modulators. Here, we report a high-resolution structure of GluK1-LBD in complex with kainate and BPAM538, which belongs to the full-spanning class III. One BPAM538 molecule binds at the GluK1 dimer interface, thereby occupying two allosteric binding sites simultaneously. BPAM538 stabilizes the active receptor conformation with only minor conformational changes being introduced to the receptor. Using a calcium-sensitive fluorescence-based assay, a 5-fold potentiation of the kainate response (100 μM) was observed in the presence of 100 μM BPAM538, whereas no potentiation was observed at GluK2.Highlights1.9 Å structure of the kainate receptor GluK1-LBD in complex with kainate and BPAM538The positive allosteric modulator BPAM538 occupies two binding sitesThe binding mode is similar to class III modulators described for AMPA receptorsBPAM538 prefers GluK1 over GluK2
Active-like structure of the ligand-binding domain of GluK2 with L-glutamate and the positive allosteric modulator BPAM344
Authors: Bay Yasmin , Jeppesen Mie Egeberg , Frydenvang Karla , Francotte Pierre , Pirotte Bernard , Pickering Darryl S. , Kristensen Anders Skov , Kastrup Jette Sandholm 
Published: November 2023

AbstractKainate receptors belong to the family of ionotropic glutamate receptors and contribute to the majority of fast excitatory neurotransmission. Consequently, they also play a role in brain diseases. Therefore, understanding how these receptors can be modulated is of importance. Our study provides a dimeric crystal structure of the ligand-binding domain of the kainate receptor GluK2 in complex with L-glutamate and the small molecule positive allosteric modulator, BPAM344, in an active-like conformation. The role of Thr535 and Gln786 for modulation of GluK2 by BPAM344 was investigated using a calcium-sensitive fluorescence-based assay on transiently transfected cells expressing GluK2 and mutants hereof. This study may aid design of tool compounds targeting kainate receptors, elucidating their potential as targets for treatment of brain diseases.
High temporal frequency light response in mouse retina requires FAT3 signaling in bipolar cells
Authors: Avilés Evelyn C. , Wang Sean K. , Patel Sarina , Shi Shuxiang , Lin Lucas , Kefalov Vladimir J. , Goodrich Lisa V. , Cepko Constance L. , Xue Yunlu 
Published: November 2023

AbstractVision is initiated by the reception of light by photoreceptors and subsequent processing via downstream retinal neurons. Proper cellular organization depends on the multi-functional tissue polarity protein FAT3, which is required for amacrine cell connectivity and retinal lamination. Here we investigated the retinal function ofFat3mutant mice and found decreases in physiological and perceptual responses to high frequency flashes. These defects did not correlate with abnormal amacrine cell wiring, pointing instead to a role in bipolar cell subtypes that also express FAT3. The role of FAT3 in the response to high temporal frequency flashes depends upon its ability to transduce an intracellular signal. Mechanistically, FAT3 binds to the synaptic protein PTPσ, intracellularly, and is required to localize GRIK1 to OFF-cone bipolar cell synapses with cone photoreceptors. These findings expand the repertoire of FAT3’s functions and reveal its importance in bipolar cells for high frequency light response.
Cannabinoid receptor type 2 expression in mouse brain: from mapping to regulation in microglia under inflammatory conditions
Authors: Grabon Wanda , Ruiz Anne , Gasmi Nadia , Degletagne Cyril , Georges Béatrice , Belmeguenai Amor , Bodennec Jacques , Rheims Sylvain , Marcy Guillaume , Bezin Laurent 
Published: November 2023

ABSTRACTSince its detection in the brain, the cannabinoid receptor type 2 (CB2) has been deemed a promising therapeutic target for various neurological and psychiatric disorders. However, precise brain mapping of CB2 expression is currently lacking. Using magnetic cell sorting, calibrated reverse transcription-quantitative PCR, and single-nucleus RNA-seq, we revealed the low level of CB2 expression in all brain regions examined, mainly by a few microglial cells and by neurons in an even lower proportion. Upon lipopolysaccharide stimulation to simulate non-sterile neuroinflammatory conditions, we demonstrated that the inflammatory response was associated with a transient reduction in CB2 mRNA levels in the brain tissue, particularly in microglia. This result, confirmed in the BV2 microglial cells, contrasts with the positive correlation observed between CB2 mRNA levels and the inflammatory response upon stimulation by interferon-gamma, which models sterile inflammatory conditions. Thus, discrete brain CB2 expression may be upregulated or downregulated depending on the inflammatory context.
Effect of Schizophrenia linkedDRD2gene mutations and correlation of social behavior with biochemical changes in a post-weaning isolated mouse model
Authors: Mukesh Nivedhitha , Divi Pavan Kumar , Maikap Shimantika , Mohapatra Saswati , Rajan Muskaan , Kanthimath Sanjana , Mishra Nishant , Kar Karunakar , Anand Bibin G , Annamneedi Anil 
Published: November 2023

AbstractNeurological disorders encompass a diverse range of conditions that affect individuals cognitive, emotional, and social functioning. Though these disorders are multifactorial, genetic factors play a significant role in the pathogenesis. Especially, synaptic gene mutations or synaptic protein dysfunction are shown to be closely associated with neuropathology. This study aims at understanding the critical role of synaptic compartment by conducting comprehensive analysis of existing synaptic gene mutations responsible for the development of three significant disorders in the Indian population: autism spectrum disorder (ASD), epilepsy and schizophrenia (SZ). Ourin-silicoanalysis predicts that mutations in synaptic genesRPL10(rs387906727),GABRA1(rs121434579) andDRD2(rs1801028) corresponding to ASD, epilepsy and SZ respectively, are deleterious. Of these, SZ-related mutations inDRD2(D(2) dopamine receptor) are deleterious and due to its genetic association also with ASD as well sociosexual behavior, this study focuses on DRD2.In silicoanalysis using molecular docking revealed an abnormal interaction between D(2) dopamine receptor and neuronal calcium sensor 1, which may hamper neurotransmitter regulation. We further employed a post-weaning social isolation mice model of SZ to investigate the D(2) dopamine receptor expression levels in hippocampus and social behavioral changes. We observed a reduced immunofluorescent intensities of D(2) dopamine receptor and NCS1 compared to group-housed controls in hippocampus and a trend towards an impaired sociosexual behavior characterized by anogenital sniffing in a male-female social interaction test. Altogether, our study helps to further our understanding of synaptic signaling in the context of SZ and decode the probable mechanism by which disrupted synaptic signaling and protein-protein interaction may lead to the disease pathology and further aid in identifying novel therapeutic targets.