bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cortical immune network map identifies distinct microglial transcriptional programs associated with β-amyloid and Tau pathologies
Authors: Patrick Ellis , Olah Marta , Taga Mariko , Klein Hans-Ulrich , Xu Jishu , White Charles C. , Felsky Daniel , Agrawal Sonal , Gaiteri Chris , Chibnik Lori B. , Mostafavi Sara , Schneider Julie A. , Bennett David A. , Bradshaw Elizabeth M. , De Jager Philip L. 
Published: January 2021

AbstractMicroglial dysfunction has been proposed as one of the many cellular mechanisms that can contribute to the development of Alzheimer’s disease (AD). Here, using a transcriptional network map of the human frontal cortex, we identify five modules of co-expressed genes related to microglia and assess their role in the neuropathologic features of AD in 540 subjects from two cohort studies of brain aging. Two of these transcriptional programs—modules 113 and 114—relate to the accumulation of β-amyloid, while module 5 relates to tau pathology. We replicate these associations in brain epigenomic data and in two independent datasets. In terms of tau, we propose that module 5, a marker of activated microglia, may lead to tau accumulation and subsequent cognitive decline. We validate our model further by showing that three representative module 5 genes (ACADVL, TRABD, and VASP) encode proteins that are upregulated in activated microglia in AD.
Weighted gene coexpression network and experimental analyses identify lncRNA SPRR2C as a regulator of the IL-22-stimulated HaCaT cell phenotype through the miR-330/STAT1/S100A7 axis
Authors: Luo Meijunzi , Huang Pan , Pan Yi , Zhu Zhu , Zhou Rong , Yang Zhibo , Wang Chang 
Published: January 2021

AbstractPsoriasis is a chronic inflammatory disease of the skin with highly complex pathogenesis. In this study, we identified lncRNA SPRR2C (small proline-rich protein 2C) as a hub gene with a critical effect on the pathogenesis of psoriasis and response to treatment using both weighted gene coexpression network analysis (WGCNA) and differential expression analysis. SPRR2C expression was significantly upregulated in both psoriatic lesion samples and HaCaT cell lines in response to IL-22 treatment. After SPRR2C knockdown, IL-22-induced suppression of HaCaT proliferation, changes in the KRT5/14/1/10 protein levels, and suppression of the IL-1β, IL-6, and TNF-α mRNA levels were dramatically reversed. In the coexpression network with SPRR2C based on GSE114286, miR-330 was significantly negatively correlated with SPRR2C, while STAT1 and S100A7 were positively correlated with SPRR2C. By binding to miR-330, SPRR2C competed with STAT1 and S100A7 to counteract miR-330-mediated suppression of STAT1 and S100A7. MiR-330 overexpression also reversed the IL-22-induced changes in HaCaT cell lines; in response to IL-22 treatment, miR-330 inhibition significantly attenuated the effects of SPRR2C knockdown. STAT1 and S100A7 expression was significantly upregulated in psoriatic lesion samples. The expression of miR-330 had a negative correlation with the expression of SPRR2C, while the expression of SPRR2C had a positive correlation with the expression of STAT1 and S100A7. Thus, SPRR2C modulates the IL-22-stimulated HaCaT cell phenotype through the miR-330/STAT1/S100A7 axis. WGCNA might uncover additional biological pathways that are crucial in the pathogenesis and response to the treatment of psoriasis.
Transneuronal delivery of hyper-interleukin-6 enables functional recovery after severe spinal cord injury in mice
Authors: Leibinger Marco , Zeitler Charlotte , Gobrecht Philipp , Andreadaki Anastasia , Gisselmann Günter , Fischer Dietmar 
Published: January 2021

AbstractSpinal cord injury (SCI) often causes severe and permanent disabilities due to the regenerative failure of severed axons. Here we report significant locomotor recovery of both hindlimbs after a complete spinal cord crush. This is achieved by the unilateral transduction of cortical motoneurons with an AAV expressing hyper-IL-6 (hIL-6), a potent designer cytokine stimulating JAK/STAT3 signaling and axon regeneration. We find collaterals of these AAV-transduced motoneurons projecting to serotonergic neurons in both sides of the raphe nuclei. Hence, the transduction of cortical neurons facilitates the axonal transport and release of hIL-6 at innervated neurons in the brain stem. Therefore, this transneuronal delivery of hIL-6 promotes the regeneration of corticospinal and raphespinal fibers after injury, with the latter being essential for hIL-6-induced functional recovery. Thus, transneuronal delivery enables regenerative stimulation of neurons in the deep brain stem that are otherwise challenging to access, yet highly relevant for functional recovery after SCI.
Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells
Authors: Ch Ratnasekhar , Rey Guillaume , Ray Sandipan , Jha Pawan K. , Driscoll Paul C. , Dos Santos Mariana Silva , Malik Dania M. , Lach Radoslaw , Weljie Aalim M. , MacRae James I. , Valekunja Utham K. , Reddy Akhilesh B. 
Published: January 2021

AbstractCircadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.
The human endogenous attentional control network includes a ventro-temporal cortical node
Authors: Sani Ilaria , Stemmann Heiko , Caron Bradley , Bullock Daniel , Stemmler Torsten , Fahle Manfred , Pestilli Franco , Freiwald Winrich A. 
Published: January 2021

AbstractEndogenous attention is the cognitive function that selects the relevant pieces of sensory information to achieve goals and it is known to be controlled by dorsal fronto-parietal brain areas. Here we expand this notion by identifying a control attention area located in the temporal lobe. By combining a demanding behavioral paradigm with functional neuroimaging and diffusion tractography, we show that like fronto-parietal attentional areas, the human posterior inferotemporal cortex exhibits significant attentional modulatory activity. This area is functionally distinct from surrounding cortical areas, and is directly connected to parietal and frontal attentional regions. These results show that attentional control spans three cortical lobes and overarches large distances through fiber pathways that run orthogonally to the dominant anterior-posterior axes of sensory processing, thus suggesting a different organizing principle for cognitive control.
Massively parallel cantilever-free atomic force microscopy
Authors: Cao Wenhan , Alsharif Nourin , Huang Zhongjie , White Alice E. , Wang YuHuang , Brown Keith A. 
Published: January 2021

AbstractResolution and field-of-view often represent a fundamental tradeoff in microscopy. Atomic force microscopy (AFM), in which a cantilevered probe deflects under the influence of local forces as it scans across a substrate, is a key example of this tradeoff with high resolution imaging being largely limited to small areas. Despite the tremendous impact of AFM in fields including materials science, biology, and surface science, the limitation in imaging area has remained a key barrier to studying samples with intricate hierarchical structure. Here, we show that massively parallel AFM with >1000 probes is possible through the combination of a cantilever-free probe architecture and a scalable optical method for detecting probe–sample contact. Specifically, optically reflective conical probes on a comparatively compliant film are found to comprise a distributed optical lever that translates probe motion into an optical signal that provides sub-10 nm vertical precision. The scalability of this approach makes it well suited for imaging applications that require high resolution over large areas.
Plasmons in the van der Waals charge-density-wave material 2H-TaSe2
Authors: Song Chaoyu , Yuan Xiang , Huang Ce , Huang Shenyang , Xing Qiaoxia , Wang Chong , Zhang Cheng , Xie Yuangang , Lei Yuchen , Wang Fanjie , Mu Lei , Zhang Jiasheng , Xiu Faxian , Yan Hugen 
Published: January 2021

AbstractPlasmons in two-dimensional (2D) materials beyond graphene have recently gained much attention. However, the experimental investigation is limited due to the lack of suitable materials. Here, we experimentally demonstrate localized plasmons in a correlated 2D charge-density-wave (CDW) material: 2H-TaSe2. The plasmon resonance can cover a broad spectral range from the terahertz (40 μm) to the telecom (1.55 μm) region, which is further tunable by changing thickness and dielectric environments. The plasmon dispersion flattens at large wave vectors, resulted from the universal screening effect of interband transitions. More interestingly, anomalous temperature dependence of plasmon resonances associated with CDW excitations is observed. In the CDW phase, the plasmon peak close to the CDW excitation frequency becomes wider and asymmetric, mimicking two coupled oscillators. Our study not only reveals the universal role of the intrinsic screening on 2D plasmons, but also opens an avenue for tunable plasmons in 2D correlated materials.
Single-neuron dynamical effects of dendritic pruning implicated in aging and neurodegeneration: towards a measure of neuronal reserve
Authors: Kirch Christoph , Gollo Leonardo L. 
Published: January 2021

AbstractAging is a main risk factor for neurodegenerative disorders including Alzheimer's disease. It is often accompanied by reduced cognitive functions, gray-matter volume, and dendritic integrity. Although age-related brain structural changes have been observed across multiple scales, their functional implications remain largely unknown. Here we simulate the aging effects on neuronal morphology as dendritic pruning and characterize its dynamical implications. Utilizing a detailed computational modeling approach, we simulate the dynamics of digitally reconstructed neurons obtained from Neuromorpho.org. We show that dendritic pruning affects neuronal integrity: firing rate is reduced, causing a reduction in energy consumption, energy efficiency, and dynamic range. Pruned neurons require less energy but their function is often impaired, which can explain the diminished ability to distinguish between similar experiences (pattern separation) in older people. Our measures indicate that the resilience of neuronal dynamics is neuron-specific, heterogeneous, and strongly affected by dendritic topology and the position of the soma. Based on the emergent neuronal dynamics, we propose to classify the effects of dendritic deterioration, and put forward a topological measure of “neuronal reserve” that quantifies the resilience of neuronal dynamics to dendritic pruning. Moreover, our findings suggest that increasing dendritic excitability could partially mitigate the dynamical effects of aging.
Ultra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function
Authors: Stephens Matthew , Liao Shan , von der Weid Pierre-Yves 
Published: January 2021

AbstractTLR4 location, and bacterial species-derived lipopolysaccharides, play a significant role in the downstream activation of transcription factors, accessory molecules, and products. Here, this is demonstrated through the use of classically-activated and alternatively-activated macrophages. We show that, when polarized, human macrophages differentially express and localize TLR4, resulting in biased recognition and subsequent signalling of LPS derived from Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica. Analysis of activation demonstrated that in classically activated macrophages, P. aeruginosa signals from the plasma membrane via TLR4 to p65 dependent on TAK1 and TBK1 signalling. E. coli signals dependent or independent of the endosome, utilizing both TAK1- and TBK1-signalling to induce P65 and IRF3 inducible genes and cytokines. S. enterica however, only induces P65 and IRF3 phosphorylation through signalling via the endosome. This finding outlines clear signalling mechanisms by which innate immune cells, such as macrophages, can distinguish between bacterial species and initiate specialized responses through TLR4.
Test–retest reliability of laser evoked pain perception and fMRI BOLD responses
Authors: Bi Yanzhi , Hou Xin , Zhong Jiahui , Hu Li 
Published: January 2021

AbstractPain perception is a subjective experience and highly variable across time. Brain responses evoked by nociceptive stimuli are highly associated with pain perception and also showed considerable variability. To date, the test–retest reliability of laser-evoked pain perception and its associated brain responses across sessions remain unclear. Here, an experiment with a within-subject repeated-measures design was performed in 22 healthy volunteers. Radiant-heat laser stimuli were delivered on subjects’ left-hand dorsum in two sessions separated by 1–5 days. We observed that laser-evoked pain perception was significantly declined across sessions, coupled with decreased brain responses in the bilateral primary somatosensory cortex (S1), right primary motor cortex, supplementary motor area, and middle cingulate cortex. Intraclass correlation coefficients between the two sessions showed “fair” to “moderate” test–retest reliability for pain perception and brain responses. Additionally, we observed lower resting-state brain activity in the right S1 and lower resting-state functional connectivity between right S1 and dorsolateral prefrontal cortex in the second session than the first session. Altogether, being possibly influenced by changes of baseline mental state, laser-evoked pain perception and brain responses showed considerable across-session variability. This phenomenon should be considered when designing experiments for laboratory studies and evaluating pain abnormalities in clinical practice.
Sustainable production of camptothecin from an Alternaria sp. isolated from Nothapodytes nimmoniana
Authors: Mohinudeen I. A. H. Khwajah , Kanumuri Rahul , Soujanya K. N. , Shaanker R. Uma , Rayala Suresh Kumar , Srivastava Smita 
Published: January 2021

AbstractCamptothecin the third most in demand alkaloid, is commercially extracted in India from the endangered plant, Nothapodytes nimmoniana. Endophytes, the microorganisms that reside within plants, are reported to have the ability to produce host–plant associated metabolites. Hence, our research aims to establish a sustainable and high camptothecin yielding endophyte, as an alternative source for commercial production of camptothecin. A total of 132 endophytic fungal strains were isolated from different plant parts (leaf, petiole, stem and bark) of N. nimmoniana, out of which 94 were found to produce camptothecin in suspension culture. Alternaria alstroemeriae (NCIM1408) and Alternaria burnsii (NCIM1409) demonstrated camptothecin yields up to 426.7 ± 33.6 µg/g DW and 403.3 ± 41.6 µg/g DW, respectively, the highest reported production to date. Unlike the reported product yield attenuation in endophytes with subculture in axenic state, Alternaria burnsii NCIM1409 could retain and sustain the production of camptothecin up to ~ 200 μg/g even after 12 continuous subculture cycles. The camptothecin biosynthesis in Alternaria burnsii NCIM1409 was confirmed using 13C carbon labelling (and cytotoxicity analysis on different cancer cell lines) and this strain can now be used to develop a sustainable bioprocess for in vitro production of camptothecin as an alternative to plant extraction.
Unusual derivatives from Hypericum scabrum
Authors: Soroury Sara , Alilou Mostafa , Gelbrich Thomas , Tabefam Marzieh , Danton Ombeline , Ebrahimi Samad N. , Kaiser Marcel , Hamburger Matthias , Stuppner Hermann , Moridi Farimani Mahdi 
Published: January 2021

AbstractThree new compounds (1–3) with unusual skeletons were isolated from the n-hexane extract of the air-dried aerial parts of Hypericum scabrum. Compound 1 represents the first example of an esterified polycyclic polyprenylated acylphloroglucinol that features a unique tricyclo-[4.3.1.11,4]-undecane skeleton. Compound 2 is a fairly simple MPAP, but with an unexpected cycloheptane ring decorated with prenyl substituents, and compound 3 has an unusual 5,5-spiroketal lactone core. Their structures were determined by extensive spectroscopic and spectrometric techniques (1D and 2D NMR, HRESI-TOFMS). Absolute configurations were established by ECD calculations, and the absolute structure of 2 was confirmed by a single crystal determination. Plausible biogenetic pathways of compounds 1–3 were also proposed. The in vitro antiprotozoal activity of the compounds against Trypanosoma brucei rhodesiense and Plasmodium falciparum and cytotoxicity against rat myoblast (L6) cells were determined. Compound 1 showed a moderate activity against T. brucei and P. falciparum, with IC50 values of 3.07 and 2.25 μM, respectively.
Leg amputation modifies coordinated activation of the middle leg muscles in the cricket Gryllus bimaculatus
Authors: Owaki Dai , Aonuma Hitoshi , Sugimoto Yasuhiro , Ishiguro Akio 
Published: January 2021

AbstractInsects alter their walking pattern in order to respond to demands of an ever-changing environment, such as varying ground surface textures. They also exhibit resilient and flexible ability to retain the capacity to walk even after substantial changes in their body properties, e.g. leg amputation. While the motor control paradigm governing the inter-leg coordination in such adaptive walking has been extensively described in past studies, the mechanism remains unknown. Here, we examined this question by using the cricket (Gryllus bimaculatus), which shows a tetrapod/tripod gait on a flat surfaces, like many other insects. We performed leg amputation experiments to investigate modifications of leg movements and coordination of muscle activities. We simultaneously recorded (1) the leg movements, locomotion velocity, and body rotation and (2) the leg movements and leg muscles activities before and after leg amputation. Crickets displayed adaptive coordination of leg movement patterns in response to amputations. The activation timings of levator muscles in both middle legs tended to synchronize in phase when both legs were amputated at the coxatrochanteral joint. This supports the hypothesis that an intrinsic contralateral connection within the mesothoracic ganglion exists, and that mechanosensory feedback from the legs override this connection, resulting in the anti-phase movement of a normal gait.
A system dynamics model for pests and natural enemies interactions
Authors: Sokame Bonoukpoè Mawuko , Tonnang Henri E. Z. , Subramanian Sevgan , Bruce Anani Y. , Dubois Thomas , Ekesi Sunday , Calatayud Paul-André 
Published: January 2021

AbstractStemborers (Busseola fusca, Sesamia calamistis and Chilo partellus), the fall armyworm (Spodoptera frugiperda) and associated parasitoids constitute an interacting system in maize fields in Kenya. This work aims at developing and evaluating models that represent the evolution of those interactions by applying system thinking and system dynamics approaches with its archetypes [causal loop diagram (CLD), reinforcing (R) and balancing (B)] to analyse the population of these multi-species systems. The software Vensim PLE 8.0.9 was used to implement the models and carry out the simulations of single- and multi-species systems. The results showed that when a single pest species with its associated parasitoids interact with the host plant, the species was able to establish and sustain by cyclical relationship between populations of the pest and the associated parasitoids. However, in multi- pest species systems, dominance of S. frugiperda and C. partellus over B. fusca and S. calamistis was observed, but without extinction. However, there was a likelihood for B. fusca being displaced by C. partellus. Overall, the models predict the co-existence of fall armyworm with stemborer species as an additional pest of maize in Africa that need to be considered henceforth in designing IPM strategies in maize.
Shared and unique metabolic features of the malignant and benign thyroid lesions determined with use of 1H HR MAS NMR spectroscopy
Authors: Skorupa Agnieszka , Ciszek Mateusz , Chmielik Ewa , Boguszewicz Łukasz , Oczko-Wojciechowska Małgorzata , Kowalska Małgorzata , Rusinek Dagmara , Tyszkiewicz Tomasz , Kluczewska-Gałka Aneta , Czarniecka Agnieszka , Jarząb Barbara , Sokół Maria 
Published: January 2021

AbstractThe purpose of this work was to investigate the distinct and common metabolic features of the malignant and benign thyroid lesions in reference to the non-transformed tissue from the contralateral gland (chronic thyroiditis and colloid goiter). 1H HR MAS NMR spectra of 38 malignant lesions, 32 benign lesions and 112 samples from the non-tumoral tissue (32 from chronic thyroiditis and 80 samples from colloid goiter) were subjected both to multivariate and univariate analysis. The increased succinate, glutamine, glutathione, serine/cysteine, ascorbate, lactate, taurine, threonine, glycine, phosphocholine/glycerophosphocholine and decreased lipids were found in both lesion types in comparison to either colloid goiter or chronic thyroiditis. The elevated glutamate and choline, and reduced citrate and glucose were additionally evident in these lesions in reference to goiter, while the increased myo-inositol—in comparison to thyroiditis. The malignant lesions were characterized by the higher alanine and lysine levels than colloid goiter and thyroiditis, while scyllo-inositol was uniquely increased in the benign lesions (not in cancer) in comparison to both non-tumoral tissue types. Moreover, the benign lesions presented with the unique increase of choline in reference to thyroiditis (not observed in the cancerous tissue). The metabolic heterogeneity of the non-tumoral tissue should be considered in the analysis of metabolic reprogramming in the thyroid lesions.