bluuebunny/crossref_metadata_2025_split huggingface dataset:
Downregulation of kainate receptors regulating GABAergic transmission in amygdala after early life stress is associated with anxiety-like behavior in rodents
Authors: Englund Jonas , Haikonen Joni , Shteinikov Vasilii , Amarilla Shyrley Paola , Atanasova Tsvetomira , Shintyapina Alexandra , Ryazantseva Maria , Partanen Juha , Voikar Vootele , Lauri Sari E. 
Published: October 2021

AbstractEarly life stress (ELS) is a well-characterized risk factor for mood and anxiety disorders. GABAergic microcircuits in the amygdala are critically implicated in anxiety; however, whether their function is altered after ELS is not known. Here we identify a novel mechanism by which kainate receptors (KARs) modulate feedforward inhibition in the lateral amygdala (LA) and show that this mechanism is downregulated after ELS induced by maternal separation (MS). Specifically, we show that in control rats but not after MS, endogenous activity of GluK1 subunit containing KARs disinhibit LA principal neurons during activation of cortical afferents. GluK1 antagonism attenuated excitability of parvalbumin (PV)-expressing interneurons, resulting in loss of PV-dependent inhibitory control and an increase in firing of somatostatin-expressing interneurons. Inactivation of Grik1 expression locally in the adult amygdala reduced ongoing GABAergic transmission and was sufficient to produce a mild anxiety-like behavioral phenotype. Interestingly, MS and GluK1-dependent phenotypes showed similar gender specificity, being detectable in male but not female rodents. Our data identify a novel KAR-dependent mechanism for cell-type and projection-specific functional modulation of the LA GABAergic microcircuit and suggest that the loss of GluK1 KAR function contributes to anxiogenesis after ELS.
The proteomic architecture of schizophrenia iPSC-derived cerebral organoids reveals alterations in GWAS and neuronal development factors
Authors: Notaras Michael , Lodhi Aiman , Fang Haoyun , Greening David , Colak Dilek 
Published: October 2021

AbstractSchizophrenia (Scz) is a brain disorder that has a typical onset in early adulthood but otherwise maintains unknown disease origins. Unfortunately, little progress has been made in understanding the molecular mechanisms underlying neurodevelopment of Scz due to ethical and technical limitations in accessing developing human brain tissue. To overcome this challenge, we have previously utilized patient-derived Induced Pluripotent Stem Cells (iPSCs) to generate self-developing, self-maturating, and self-organizing 3D brain-like tissue known as cerebral organoids. As a continuation of this prior work, here we provide an architectural map of the developing Scz organoid proteome. Utilizing iPSCs from n = 25 human donors (n = 8 healthy Ctrl donors, and n = 17 Scz patients), we generated 3D cerebral organoids, employed 16-plex isobaric sample-barcoding chemistry, and simultaneously subjected samples to comprehensive high-throughput liquid-chromatography/mass-spectrometry (LC/MS) quantitative proteomics. Of 3,705 proteins identified by high-throughput proteomic profiling, we identified that just ~2.62% of the organoid global proteomic landscape was differentially regulated in Scz organoids. In sum, just 43 proteins were up-regulated and 54 were down-regulated in Scz patient-derived organoids. Notably, a range of neuronal factors were depleted in Scz organoids (e.g., MAP2, TUBB3, SV2A, GAP43, CRABP1, NCAM1 etc.). Based on global enrichment analysis, alterations in key pathways that regulate nervous system development (e.g., axonogenesis, axon development, axon guidance, morphogenesis pathways regulating neuronal differentiation, as well as substantia nigra development) were perturbed in Scz patient-derived organoids. We also identified prominent alterations in two novel GWAS factors, Pleiotrophin (PTN) and Podocalyxin (PODXL), in Scz organoids. In sum, this work serves as both a report and a resource that researchers can leverage to compare, contrast, or orthogonally validate Scz factors and pathways identified in observational clinical studies and other model systems.
MS4A15 drives ferroptosis resistance through calcium-restricted lipid remodeling
Authors: Xin Shan , Mueller Constanze , Pfeiffer Susanne , Kraft Vanessa A. N. , Merl-Pham Juliane , Bao Xuanwen , Feederle Regina , Jin Xiang , Hauck Stefanie M. , Schmitt-Kopplin Philippe , Schick Joel A. 
Published: October 2021

AbstractFerroptosis is an iron-dependent form of cell death driven by biochemical processes that promote oxidation within the lipid compartment. Calcium (Ca2+) is a signaling molecule in diverse cellular processes such as migration, neurotransmission, and cell death. Here, we uncover a crucial link between ferroptosis and Ca2+through the identification of the novel tetraspanin MS4A15. MS4A15 localizes to the endoplasmic reticulum, where it blocks ferroptosis by depleting luminal Ca2+stores and reprogramming membrane phospholipids to ferroptosis-resistant species. Specifically, prolonged Ca2+depletion inhibits lipid elongation and desaturation, driving lipid droplet dispersion and formation of shorter, more saturated ether lipids that protect phospholipids from ferroptotic reactive species. We further demonstrate that increasing luminal Ca2+levels can preferentially sensitize refractory cancer cell lines. In summary, MS4A15 regulation of anti-ferroptotic lipid reservoirs provides a key resistance mechanism that is distinct from antioxidant and lipid detoxification pathways. Manipulating Ca2+homeostasis offers a compelling strategy to balance cellular lipids and cell survival in ferroptosis-associated diseases.
Loss of Numb promotes hepatic progenitor expansion and intrahepatic cholangiocarcinoma by enhancing Notch signaling
Authors: Shu Yuke , Xu Qing , Xu Yahong , Tao Qing , Shao Mingyang , Cao Xiaoyue , Chen Yuwei , Wu Zhenru , Chen Menglin , Zhou Yongjie , Zhou Ping , Shi Yujun , Bu Hong 
Published: October 2021

AbstractNumb, a stem cell fate determinant, acts as a tumor suppressor and is closely related to a wide variety of malignancies. Intrahepatic cholangiocarcinoma (iCCA) originates from hepatic progenitors (HPCs); however, the role of Numb in HPC malignant transformation and iCCA development is still unclear. A retrospective cohort study indicated that Numb was frequently decreased in tumor tissues and suggests poor prognosis in iCCA patients. Consistently, in a chemically induced iCCA mouse model, Numb was downregulated in tumor cells compared to normal cholangiocytes. In diet-induced chronic liver injury mouse models, Numb ablation significantly promoted histological impairment, HPC expansion, and tumorigenesis. Similarly, Numb silencing in cultured iCCA cells enhanced cell spheroid growth, invasion, metastasis, and the expression of stem cell markers. Mechanistically, Numb was found to bind to the Notch intracellular domain (NICD), and Numb ablation promoted Notch signaling; this effect was reversed when Notch signaling was blocked by γ-secretase inhibitor treatment. Our results suggested that loss of Numb plays an important role in promoting HPC expansion, HPC malignant transformation, and, ultimately, iCCA development in chronically injured livers. Therapies targeting suppressed Numb are promising for the treatment of iCCA.
High-coverage metabolomics uncovers microbiota-driven biochemical landscape of interorgan transport and gut-brain communication in mice
Authors: Lai Yunjia , Liu Chih-Wei , Yang Yifei , Hsiao Yun-Chung , Ru Hongyu , Lu Kun 
Published: October 2021

AbstractThe mammalian gut harbors a complex and dynamic microbial ecosystem: the microbiota. While emerging studies support that microbiota regulates brain function with a few molecular cues suggested, the overall biochemical landscape of the “microbiota-gut-brain axis” remains largely unclear. Here we use high-coverage metabolomics to comparatively profile feces, blood sera, and cerebral cortical brain tissues of germ-free C57BL/6 mice and their age-matched conventionally raised counterparts. Results revealed for all three matrices metabolomic signatures owing to microbiota, yielding hundreds of identified metabolites including 533 altered for feces, 231 for sera, and 58 for brain with numerous significantly enriched pathways involving aromatic amino acids and neurotransmitters. Multicompartmental comparative analyses single out microbiota-derived metabolites potentially implicated in interorgan transport and the gut-brain axis, as exemplified by indoxyl sulfate and trimethylamine-N-oxide. Gender-specific characteristics of these landscapes are discussed. Our findings may be valuable for future research probing microbial influences on host metabolism and gut-brain communication.
Divergent abiotic spectral pathways unravel pathogen stress signals across species
Authors: Zarco-Tejada P. J. , Poblete T. , Camino C. , Gonzalez-Dugo V. , Calderon R. , Hornero A. , Hernandez-Clemente R. , Román-Écija M. , Velasco-Amo M. P. , Landa B. B. , Beck P. S. A. , Saponari M. , Boscia D. , Navas-Cortes J. A. 
Published: October 2021

AbstractPlant pathogens pose increasing threats to global food security, causing yield losses that exceed 30% in food-deficit regions. Xylella fastidiosa (Xf) represents the major transboundary plant pest and one of the world’s most damaging pathogens in terms of socioeconomic impact. Spectral screening methods are critical to detect non-visual symptoms of early infection and prevent spread. However, the subtle pathogen-induced physiological alterations that are spectrally detectable are entangled with the dynamics of abiotic stresses. Here, using airborne spectroscopy and thermal scanning of areas covering more than one million trees of different species, infections and water stress levels, we reveal the existence of divergent pathogen- and host-specific spectral pathways that can disentangle biotic-induced symptoms. We demonstrate that uncoupling this biotic–abiotic spectral dynamics diminishes the uncertainty in the Xf detection to below 6% across different hosts. Assessing these deviating pathways against another harmful vascular pathogen that produces analogous symptoms, Verticillium dahliae, the divergent routes remained pathogen- and host-specific, revealing detection accuracies exceeding 92% across pathosystems. These urgently needed hyperspectral methods advance early detection of devastating pathogens to reduce the billions in crop losses worldwide.
A dry lunar mantle reservoir for young mare basalts of Chang’e-5
Authors: Hu Sen , He Huicun , Ji Jianglong , Lin Yangting , Hui Hejiu , Anand Mahesh , Tartèse Romain , Yan Yihong , Hao Jialong , Li Ruiying , Gu Lixin , Guo Qian , He Huaiyu , Ouyang Ziyuan 
Published: October 2021

AbstractThe distribution of water in the Moon’s interior carries implications for the origin of the Moon1, the crystallization of the lunar magma ocean2 and the duration of lunar volcanism2. The Chang’e-5 mission returned some of the youngest mare basalt samples reported so far, dated at 2.0 billion years ago (Ga)3, from the northwestern Procellarum KREEP Terrane, providing a probe into the spatiotemporal evolution of lunar water. Here we report the water abundances and hydrogen isotope compositions of apatite and ilmenite-hosted melt inclusions from the Chang’e-5 basalts. We derive a maximum water abundance of 283 ± 22 μg g−1 and a deuterium/hydrogen ratio of (1.06 ± 0.25) × 10–4 for the parent magma. Accounting for low-degree partial melting of the depleted mantle followed by extensive magma fractional crystallization4, we estimate a maximum mantle water abundance of 1–5 μg g−1, suggesting that the Moon’s youngest volcanism was not driven by abundant water in its mantle source. Such a modest water content for the Chang’e-5 basalt mantle source region is at the low end of the range estimated from mare basalts that erupted from around 4.0 Ga to 2.8 Ga (refs. 5,6), suggesting that the mantle source of the Chang’e-5 basalts had become dehydrated by 2.0 Ga through previous melt extraction from the Procellarum KREEP Terrane mantle during prolonged volcanic activity.
Circadian clocks guide dendritic cells into skin lymphatics
Authors: Holtkamp Stephan J. , Ince Louise M. , Barnoud Coline , Schmitt Madeleine T. , Sinturel Flore , Pilorz Violetta , Pick Robert , Jemelin Stéphane , Mühlstädt Michael , Boehncke Wolf-Henning , Weber Jasmin , Laubender David , Philippou-Massier Julia , Chen Chien-Sin , Holtermann Leonie , Vestweber Dietmar , Sperandio Markus , Schraml Barbara U. , Halin Cornelia , Dibner Charna , Oster Henrik , Renkawitz Jörg , Scheiermann Christoph 
Published: October 2021

AbstractMigration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses1,2. Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood3,4. Here, we demonstrate that dendritic cells (DCs) have a circadian migration pattern into LVs, which peaks during the rest phase in mice. This migration pattern is determined by rhythmic gradients in the expression of the chemokine CCL21 and of adhesion molecules in both mice and humans. Chronopharmacological targeting of the involved factors abrogates circadian migration of DCs. We identify cell-intrinsic circadian oscillations in skin lymphatic endothelial cells (LECs) and DCs that cogovern these rhythms, as their genetic disruption in either cell type ablates circadian trafficking. These observations indicate that circadian clocks control the infiltration of DCs into skin lymphatics, a process that is essential for many adaptive immune responses and relevant for vaccination and immunotherapies.
Curvature flows, scaling laws and the geometry of attrition under impacts
Authors: Pál Gergő , Domokos Gábor , Kun Ferenc 
Published: October 2021

AbstractImpact induced attrition processes are, beyond being essential models of industrial ore processing, broadly regarded as the key to decipher the provenance of sedimentary particles. Here we establish the first link between microscopic, particle-based models and the mean field theory for these processes. Based on realistic computer simulations of particle-wall collision sequences we first identify the well-known damage and fragmentation energy phases, then we show that the former is split into the abrasion phase with infinite sample lifetime (analogous to Sternberg’s Law) at finite asymptotic mass and the cleavage phase with finite sample lifetime, decreasing as a power law of the impact velocity (analogous to Basquin’s Law). This splitting establishes the link between mean field models (curvature-driven partial differential equations) and particle-based models: only in the abrasion phase does shape evolution emerging in the latter reproduce with startling accuracy the spatio-temporal patterns (two geometric phases) predicted by the former.
Individualized stress detection using an unmodified car steering wheel
Authors: Balters Stephanie , Gowda Nikhil , Ordonez Francisco , Paredes Pablo E. 
Published: October 2021

AbstractIn-car passive stress sensing could enable the monitoring of stress biomarkers while driving and reach millions of commuters daily (i.e., 123 million daily commuters in the US alone). Here, we present a nonintrusive method to detect stress solely from steering angle data of a regular car. The method uses inverse filtering to convert angular movement data into a biomechanical Mass Spring Damper model of the arm and extracts its damped natural frequency as an approximation of muscle stiffness, which in turn reflects stress. We ran a within-subject study (N = 22), in which commuters drove a vehicle around a closed circuit in both stress and calm conditions. As hypothesized, cohort analysis revealed a significantly higher damped natural frequency for the stress condition (P = .023, d = 0.723). Subsequent automation of the method achieved rapid (i.e., within 8 turns) stress detection in the individual with a detection accuracy of 77%.
Passing rail traffic reduces bat activity
Authors: Jerem Paul , Mathews Fiona 
Published: October 2021

AbstractRail transport is expanding, with a global increase in infrastructure of up to one-third predicted by 2050. Greater reliance on rail is expected to benefit the environment at a planetary level, by mitigating transport-related carbon emissions. However, smaller-scale, more direct consequences for wildlife are unclear, as unlike roads, railway impacts on animal ecology are rarely studied. As a group, bats frequently interact with transport networks due to their broad distribution and landscape-scale movements. Additionally, their nocturnality, and use of echolocation mean bats are likely to be affected by light and noise emitted by trains. To investigate whether passing trains affect bat activity levels, we monitored the two most abundant UK species using ultrasonic detectors at 12 wooded rail-side sites in southern England. Activity fell by ≥ 30–50% each time a train passed, for at least two minutes. Consequently, activity was reduced for no less than one-fifth of the time at sites with median rail traffic, and two-thirds or more of the time at the busiest site. Such activity changes imply repeated evasive action and/or exclusion from otherwise favourable environments, with potential for corresponding opportunity or energetic costs. Hence, disturbance by passing trains may disadvantage bats in most rail-side habitats.
Increasing urinary podocyte mRNA excretion and progressive podocyte loss in kidney contribute to the high risk of long-term renal disease caused by preterm birth
Authors: Ding Fangrui , Gao Qi , Tian Xiuying , Mo Jiali , Zheng Jun 
Published: October 2021

AbstractPodocyte abnormalities are common mechanism driving the progression of glomerular diseases, which account for most chronic kidney diseases (CKDs). However, the role of podocyte in the mechanism of high-risk long-term CKD caused by prematurity has not been well clarified. In present study, urine samples of 86 preterm infants and 32 full-term infants were collected, and podocyte-specific podocin mRNA levels in urine pellet were applied to indicate urinary podocyte mRNA excretion. In addition, in a preterm animal rat model, preterm rats were identified by delivery 2 days early. From the age of 3 weeks–12 months, urine samples were collected to examine podocyte mRNA excretion by measuring podocyte-specific podocin mRNA levels. Kidney samples at the age of 3 weeks, 2 months, and 12 months were collected from 8, 5 and 6 preterm rats and 9, 6 and 8 full-term rats, respectively, to examine podocyte density and podocyte area by measuring the podocyte specific nuclear marker WT-1 and the podocyte specific marker synaptopodin. As results, a more than threefold increase of urinary podocyte-specific podocin mRNA excretion rate was found in preterm infants compared with full-term infants. In addition, there was negative correlation between gestational age at birth and urinary podocin mRNA excretion. In preterm rats, a reduction in the total number of differentiated podocytes in glomeruli and an increased podocyte podocin mRNA excretion rate in urine were detected at the end of kidney differentiation. Moreover, long-term follow-up data in preterm rats showed there was an increased the risk of renal disease indicated by persistent podocyte mRNA loss, proteinuria, and enlarged glomeruli. In conclusion, increasing podocyte mRNA excretion in urine and podocyte loss in kidney led by prematurity drive the progression of long-term abnormal kidney function and could potentially explain the high risk of long-term CKD in preterm infants.
Implications for conservation and game management of the roadkill levels of the endemic Iberian hare (Lepus granatensis)
Authors: Duarte Jesús , Romero David , Rubio Pablo J. , Farfán Miguel A. , Fa Julia E. 
Published: October 2021

AbstractThe Iberian hare (Lepus granatensis) is an important small game species endemic to the Iberian Peninsula for which the incidence of roadkill is unknown. We surveyed Iberian hare–vehicle accidents on road networks in southern Spain, focusing on roads that mainly run through favorable habitats for this species: Mediterranean landscapes with plots of arable crops, olive groves, and vineyards. We recorded roadkills over a 5-month period, estimated hare accident densities on roads, and compared these numbers to hare hunting yields in adjoining hunting estates. We also analyzed the spatial patterns of and potential factors influencing hare roadkills. We detected the existence of black spots for hare roadkills in areas with high landscape heterogeneity that also included embankments and nearby crossroads and had high traffic intensity. Hare roadkill levels ranged from 5 to 25% of the annual harvest of hares killed on neighboring hunting estates. We suggest that road collisions should be considered in Iberian hare conservation in addition to hunting, since they may represent an additive source of mortality. Game managers should address the issue of hare roadkill in harvest planning to compensate for hare accidents, adjusting hunting quotas to account for this unnatural source of mortality. Our results suggest future directions for applied research in road ecology, including further work on demographic compensation and roadkill mitigation.
Premature birth carries a higher risk of nephrotic syndrome: a cohort study
Authors: Chen Chih-Chia , Yu Tsung , Chou Hsin-Hsu , Chiou Yuan-Yow , Kuo Pao-Lin 
Published: October 2021

AbstractThe pathogenesis of nephrotic syndrome is unclear. We conducted a nationwide population-based cohort study to examine the associations between preterm births and subsequent development of NS. NS was defined as ≥ 3 records with ICD-9-CM codes for NS in hospital admission or outpatient clinic visits. To avoid secondary nephrotic syndrome or nephritis with nephrotic range proteinuria, especially IgA nephropathy, we excluded patients with associated codes. A total of 78,651 preterm infants (gestational age < 37 weeks) and 786,510 matched term infants born between 2004 and 2009 were enrolled and followed until 2016. In the unadjusted models, preterm births, maternal diabetes, and pregnancy induced hypertension were associated with subsequent NS. After adjustment, preterm births remained significantly associated with NS (p = 0.001). The risk of NS increased as the gestational age decreased (p for trend < 0.001). Among the NS population, preterm births were not associated with more complications (Hypertension: p = 0.19; Serious infections: p = 0.63, ESRD: p = 0.75) or a requirement for secondary immunosuppressants (p = 0.61). In conclusion, preterm births were associated with subsequent NS, where the risk increased as the gestational age decreased. Our study provides valuable information for future pathogenesis studies.
Heat insulation effect in solar radiation of polyurethane powder coating nanocomposite
Authors: Azemati Ali Akbar , Koloor Seyed Saeid Rahimian , Khorasanizadeh Hossain , Petrů Michal , Sheikhzadeh Ghanbar Ali , Safi Mahdi , Hadavand Behzad Shirkavand 
Published: October 2021

AbstractThis study aims to improve polyurethane-based coating by modified zirconium oxide and aluminum oxide nanoparticles for preparing thin polymeric heat insulation coatings. In the first step, the nanoparticles were chemically modified with the silane coupling agent. Then, three different weight percent of modified nanoparticles (1, 3, and 5% w/w) were mixed with polyurethane, to prepare the nanocomposites, which were coated on metallic plate samples. Then, these plates are used to measure the radiation heat transfer coefficients, absorption coefficient in a region of short wavelengths (UV/VIS/NIR), the emissivity coefficient, and thermography of the samples in a region of long wavelengths (IR). Results showed that by adding the modified nanoparticles to the polyurethane matrix, absorption was decreased and the emissivity coefficient was increased. According to the thermography results, it was observed that the surface temperature of both samples with 3% w/w of nanoparticles had the minimum temperature compare to others. Minimum heat surface observed for 3% w/w of modified nano zirconium oxide.