bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynorphin / kappa-opioid receptor regulation of excitation-inhibition balance toggles afferent control of prefrontal cortical circuits in a pathway-specific manner
Authors: Yarur Hector E. , Casello Sanne M. , Tsai Valerie S. , Enriquez-Traba Juan , Kore Rufina , Wang Huikun , Arenivar Miguel , Tejeda Hugo A. 
Published: August 2023

AbstractThe medial prefrontal cortex (mPFC) controls behavior via connections with limbic excitatory afferents that engage various inhibitory motifs to shape mPFC circuit function. The dynorphin (Dyn) / kappa-opioid receptor (KOR) system is highly enriched in the mPFC, and its dysregulation is implicated in neuropsychiatric disorders. However, it is unclear how the Dyn / KOR system modulates excitatory and inhibitory circuits that are integral for mPFC information processing and behavioral control. Here, we provide a circuit-based framework wherein mPFC Dyn / KOR signaling regulates excitation-inhibition balance by toggling which afferents drive mPFC neurons. Dyn / KOR regulation of afferent inputs is pathway-specific. Dyn acting on presynaptic KORs inhibits glutamate release from afferent inputs to the mPFC, including the basolateral amygdala (BLA), paraventricular nucleus of the thalamus, and contralateral cortex. The majority of excitatory synapses to mPFC neurons, including those from the ventral hippocampus (VH), do not express presynaptic KOR, rendering them insensitive to Dyn / KOR modulation. Dyn / KOR signaling also suppresses afferent-driven recruitment of specific inhibitory sub-networks, providing a basis for Dyn to disinhibit mPFC circuits. Specifically, Dyn / KOR signaling preferentially suppresses SST interneuron- relative to PV interneuron-mediated inhibition. Selective KOR action on afferents or within mPFC microcircuits gates how distinct limbic inputs drive spiking in mPFC neurons. Presynaptic Dyn / KOR signaling decreases KOR-positive input-driven (e.g. BLA) spiking of mPFC neurons. In contrast, KOR-negative input recruitment of mPFC neurons is enhanced by Dyn / KOR signaling via suppression of mPFC inhibitory microcircuits. Thus, by acting on distinct circuit elements, Dyn / KOR signaling shifts KOR-positive and negative afferent control of mPFC circuits, providing mechanistic insights into the role of neuropeptides in shaping mPFC function. Together, these findings highlight the utility of targeting the mPFC Dyn / KOR system as a means to treat neuropsychiatric disorders characterized by dysregulation in mPFC integration of long-range afferents with local inhibitory microcircuits.
Molecular neurobiology of loss: a role for basolateral amygdala extracellular matrix
Authors: Smail Marissa A. , Smith Brittany L. , Shukla Rammohan , Alganem Khaled , Eby Hunter M. , Bollinger Justin L. , Parikh Ria K. , Chambers James B. , Reigle James K. , Moloney Rachel D. , Nawreen Nawshaba , Wohleb Eric S. , Pantazopoulos Harry , McCullumsmith Robert E. , Herman James P. 
Published: August 2023

AbstractPsychological loss is a common experience that erodes well-being and negatively impacts quality of life. The molecular underpinnings of loss are poorly understood. Here, we investigate the mechanisms of loss using an environmental enrichment removal (ER) paradigm in male rats. The basolateral amygdala (BLA) was identified as a region of interest, demonstrating differential Fos responsivity to ER and having an established role in stress processing and adaptation. A comprehensive multi-omics investigation of the BLA, spanning multiple cohorts, platforms, and analyses, revealed alterations in microglia and the extracellular matrix (ECM). Follow-up studies indicated that ER decreased microglia size, complexity, and phagocytosis, suggesting reduced immune surveillance. Loss also substantially increased ECM coverage, specifically targeting perineuronal nets surrounding parvalbumin interneurons, suggesting decreased plasticity and increased inhibition within the BLA following loss. Behavioral analyses suggest that these molecular effects are linked to impaired BLA salience evaluation, leading to a mismatch between stimulus and reaction intensity. These loss-like behaviors could be rescued by depleting BLA ECM during the removal period, helping us understand the mechanisms underlying loss and revealing novel molecular targets to ameliorate its impact.
SCARB1 in extracellular vesicles promotes NPC metastasis by co-regulating M1 and M2 macrophage function
Authors: Chen Wenhui , Bao Lili , Ren Qianqian , Zhang Zixiang , Yi Lu , Lei Wei , Yang Zhiyuan , Lu Yingna , You Bo , You Yiwen , Gu Miao 
Published: August 2023

AbstractDistant metastasis is currently the main factor affecting the prognosis of nasopharyngeal carcinoma (NPC), and understanding the mechanisms of metastasis and identifying reliable therapeutic targets are critical for improving prognosis and achieving clinical translation. Macrophages, as important immune cells in the tumor microenvironment (TME), have been shown to regulate metastasis. And extracellular vesicles (EVs) secreted by stromal cells and tumor cells play the important role in intercellular communication in the tumor microenvironment. However, the role of NPC-EVs on macrophages and their function in regulating macrophages to affect metastasis has not been fully clarified. In this study, we report that NPC-EVs can be uptake by macrophages and alter macrophage polarization, for the first time, we identified the genes implicated in these regulatory functions: SCARB1, HAAO, and CYP1B1. Moreover, we found that SCARB1 was positively associated with metastasis and poor prognosis of NPC. Interestingly, we found that SCARB1-rich EVs promoted M1 macrophages ferroptosis to decrease M1 macrophages infiltration by upregulating the HAAO level while decreasing phagocytosis of M2 macrophages by upregulating the CYP1B1 level. Finally, we identified the SCARB1-binding gene KLF9, which is involved in the transcription of HAAO and CYP1B1. Our findings showed that SCARB1-EVs promoted metastasis by co-regulating M1 and M2 macrophage function. The related mechanism will provide a new therapeutic strategy to help patients with NPC improve their prognosis.
Igneous meteorites suggest Aluminium-26 heterogeneity in the early Solar Nebula
Authors: Krestianinov Evgenii , Amelin Yuri , Yin Qing-Zhu , Cary Paige , Huyskens Magdalena H. , Miller Audrey , Dey Supratim , Hibiya Yuki , Tang Haolan , Young Edward D. , Pack Andreas , Di Rocco Tommaso 
Published: August 2023

AbstractThe short-lived radionuclide aluminium-26 (26Al) isotope is a major heat source for early planetary melting. The aluminium-26 – magnesium-26 (26Al-26Mg) decay system also serves as a high-resolution relative chronometer. In both cases, however, it is critical to establish whether 26Al was homogeneously or heterogeneously distributed throughout the solar nebula. Here we report a precise lead-207 – lead-206 (207Pb-206Pb) isotopic age of 4565.56 ± 0.12 million years (Ma) for the andesitic achondrite Erg Chech 002. Our analysis, in conjunction with published 26Al-26Mg data, reveals that the initial 26Al/27Al in the source material of this achondrite was notably higher than in various other well-preserved and precisely dated achondrites. Here we demonstrate that the current data clearly indicate spatial heterogeneity of 26Al by a factor of 3-4 in the precursor molecular cloud or the protoplanetary disk of the Solar System, likely associated with the late infall of stellar materials with freshly synthesized radionuclides.
Delayed gut microbiota maturation in the first year of life is a hallmark of pediatric allergic disease
Authors: Hoskinson Courtney , Dai Darlene L. Y. , Del Bel Kate L. , Becker Allan B. , Moraes Theo J. , Mandhane Piushkumar J. , Finlay B. Brett , Simons Elinor , Kozyrskyj Anita L. , Azad Meghan B. , Subbarao Padmaja , Petersen Charisse , Turvey Stuart E. 
Published: August 2023

AbstractAllergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune programming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxidative activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (βindirect = −2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.
Loss of LCMT1 and biased protein phosphatase 2A heterotrimerization drive prostate cancer progression and therapy resistance
Authors: Rasool Reyaz ur , O’Connor Caitlin M. , Das Chandan Kanta , Alhusayan Mohammed , Verma Brijesh Kumar , Islam Sehbanul , Frohner Ingrid E. , Deng Qu , Mitchell-Velasquez Erick , Sangodkar Jaya , Ahmed Aqila , Linauer Sarah , Mudrak Ingrid , Rainey Jessica , Zawacki Kaitlin P. , Suhan Tahra K. , Callahan Catherine G. , Rebernick Ryan , Natesan Ramakrishnan , Siddiqui Javed , Sauter Guido , Thomas Dafydd , Wang Shaomeng , Taylor Derek J. , Simon Ronald , Cieslik Marcin , Chinnaiyan Arul M. , Busino Luca , Ogris Egon , Narla Goutham , Asangani Irfan A. 
Published: August 2023

AbstractLoss of the tumor suppressive activity of the protein phosphatase 2A (PP2A) is associated with cancer, but the underlying molecular mechanisms are unclear. PP2A holoenzyme comprises a heterodimeric core, a scaffolding A subunit and a catalytic C subunit, and one of over 20 distinct substrate-directing regulatory B subunits. Methylation of the C subunit regulates PP2A heterotrimerization, affecting B subunit binding and substrate specificity. Here, we report that the leucine carboxy methyltransferase (LCMT1), which methylates the L309 residue of the C subunit, acts as a suppressor of androgen receptor (AR) addicted prostate cancer (PCa). Decreased methyl-PP2A-C levels in prostate tumors is associated with biochemical recurrence and metastasis. Silencing LCMT1 increases AR activity and promotes castration-resistant prostate cancer growth. LCMT1-dependent methyl-sensitive AB56αCme heterotrimers target AR and its critical coactivator MED1 for dephosphorylation, resulting in the eviction of the AR-MED1 complex from chromatin and loss of target gene expression. Mechanistically, LCMT1 is regulated by S6K1-mediated phosphorylation-induced degradation requiring the β-TRCP, leading to acquired resistance to anti-androgens. Finally, feedforward stabilization of LCMT1 by small molecule activator of phosphatase (SMAP) results in attenuation of AR-signaling and tumor growth inhibition in anti-androgen refractory PCa. These findings highlight methyl-PP2A-C as a prognostic marker and that the loss of LCMT1 is a major determinant in AR-addicted PCa, suggesting therapeutic potential for AR degraders or PP2A modulators in prostate cancer treatment.
Downregulation of transposable elements extends lifespan in Caenorhabditis elegans
Authors: Sturm Ádám , Saskői Éva , Hotzi Bernadette , Tarnóci Anna , Barna János , Bodnár Ferenc , Sharma Himani , Kovács Tibor , Ari Eszter , Weinhardt Nóra , Kerepesi Csaba , Perczel András , Ivics Zoltán , Vellai Tibor 
Published: August 2023

AbstractMobility of transposable elements (TEs) frequently leads to insertional mutations in functional DNA regions. In the potentially immortal germline, TEs are effectively suppressed by the Piwi-piRNA pathway. However, in the genomes of ageing somatic cells lacking the effects of the pathway, TEs become increasingly mobile during the adult lifespan, and their activity is associated with genomic instability. Whether the progressively increasing mobilization of TEs is a cause or a consequence of ageing remains a fundamental problem in biology. Here we show that in the nematode Caenorhabditis elegans, the downregulation of active TE families extends lifespan. Ectopic activation of Piwi proteins in the soma also promotes longevity. Furthermore, DNA N6-adenine methylation at TE stretches gradually rises with age, and this epigenetic modification elevates their transcription as the animal ages. These results indicate that TEs represent a novel genetic determinant of ageing, and that N6-adenine methylation plays a pivotal role in ageing control.
γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection
Authors: Quintana Juan F. , Sinton Matthew C. , Chandrasegaran Praveena , Lestari Agatha Nabilla , Heslop Rhiannon , Cheaib Bachar , Ogunsola John , Ngoyi Dieudonne Mumba , Kuispond Swar Nono-Raymond , Cooper Anneli , Mabbott Neil A. , Coffelt Seth B. , MacLeod Annette 
Published: August 2023

AbstractAfrican trypanosomes colonise the skin to ensure parasite transmission. However, how the skin responds to trypanosome infection remains unresolved. Here, we investigate the local immune response of the skin in a murine model of infection using spatial and single cell transcriptomics. We detect expansion of dermal IL-17A-producing Vγ6+ cells during infection, which occurs in the subcutaneous adipose tissue. In silico cell-cell communication analysis suggests that subcutaneous interstitial preadipocytes trigger T cell activation via Cd40 and Tnfsf18 signalling, amongst others. In vivo, we observe that female mice deficient for IL-17A-producing Vγ6+ cells show extensive inflammation and limit subcutaneous adipose tissue wasting, independently of parasite burden. Based on these observations, we propose that subcutaneous adipocytes and Vγ6+ cells act in concert to limit skin inflammation and adipose tissue wasting. These studies provide new insights into the role of γδ T cell and subcutaneous adipocytes as homeostatic regulators of skin immunity during chronic infection.
Functionalization and higher-order organization of liposomes with DNA nanostructures
Authors: Zhang Zhao , Feng Zhaomeng , Zhao Xiaowei , Jean Dominique , Yu Zhiheng , Chapman Edwin R. 
Published: August 2023

AbstractSmall unilamellar vesicles (SUVs) are indispensable model membranes, organelle mimics, and drug and vaccine carriers. However, the lack of robust techniques to functionalize or organize preformed SUVs limits their applications. Here we use DNA nanostructures to coat, cluster, and pattern sub-100-nm liposomes, generating distance-controlled vesicle networks, strings and dimers, among other configurations. The DNA coating also enables attachment of proteins to liposomes, and temporal control of membrane fusion driven by SNARE protein complexes. Such a convenient and versatile method of engineering premade vesicles both structurally and functionally is highly relevant to bottom-up biology and targeted delivery.
Next generation synthetic memory via intercepting recombinase function
Authors: Short Andrew E. , Kim Dowan , Milner Prasaad T. , Wilson Corey J. 
Published: August 2023

AbstractHere we present a technology to facilitate synthetic memory in a living system via repurposing Transcriptional Programming (i.e., our decision-making technology) parts, to regulate (intercept) recombinase function post-translation. We show that interception synthetic memory can facilitate programmable loss-of-function via site-specific deletion, programmable gain-of-function by way of site-specific inversion, and synthetic memory operations with nested Boolean logical operations. We can expand interception synthetic memory capacity more than 5-fold for a single recombinase, with reconfiguration specificity for multiple sites in parallel. Interception synthetic memory is ~10-times faster than previous generations of recombinase-based memory. We posit that the faster recombination speed of our next-generation memory technology is due to the post-translational regulation of recombinase function. This iteration of synthetic memory is complementary to decision-making via Transcriptional Programming – thus can be used to develop intelligent synthetic biological systems for myriad applications.
Hippocampal subfield vulnerability to α-synuclein pathology precedes neurodegeneration and cognitive dysfunction
Authors: Dues Dylan J. , Nguyen An Phu Tran , Becker Katelyn , Ma Jiyan , Moore Darren J. 
Published: August 2023

AbstractCognitive dysfunction is a salient feature of Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). The onset of dementia reflects the spread of Lewy pathology throughout forebrain structures. The mere presence of Lewy pathology, however, provides limited indication of cognitive status. Thus, it remains unclear whether Lewy pathology is the de facto substrate driving cognitive dysfunction in PD and DLB. Through application of α-synuclein fibrils in vivo, we sought to examine the influence of pathologic inclusions on cognition. Following stereotactic injection of α-synuclein fibrils within the mouse forebrain, we measured the burden of α-synuclein pathology at 1-, 3-, and 6-months post-injection within subregions of the hippocampus and cortex. Under this paradigm, the hippocampal CA2/3 subfield was especially susceptible to α-synuclein pathology. Strikingly, we observed a drastic reduction of pathology in the CA2/3 subfield across time-points, consistent with the consolidation of α-synuclein pathology into dense somatic inclusions followed by neurodegeneration. Silver-positive degenerating neurites were observed prior to neuronal loss, suggesting that this might be an early feature of fibril-induced neurotoxicity and a precursor to neurodegeneration. Critically, mice injected with α-synuclein fibrils developed progressive deficits in spatial learning and memory. These findings support that the formation of α-synuclein inclusions in the mouse forebrain precipitate neurodegenerative changes that recapitulate features of Lewy-related cognitive dysfunction.
A soil productivity system reveals most Brazilian agricultural lands are below their maximum potential
Authors: Greschuk Lucas T. , Demattê José A. M. , Silvero Nélida E. Q. , Rosin Nícolas Augusto 
Published: August 2023

AbstractFood production is extremely dependent on the soil. Brazil plays an important role in the global food production chain. Although only 30% of the total Brazilian agricultural areas are used for crop and livestock, the full soil production potential needs to be evaluated due to the environmental and legal impossibility to expand agriculture to new areas. A novel approach to assess the productive potential of soils, called “SoilPP” and based on soil analysis (0–100 cm) - which express its pedological information - and machine learning is presented. Historical yields of sugarcane and soybeans were analyzed, allowing to identify where it is still possible to improve crop yields. The soybean yields were below the estimated SoilPP in 46% of Brazilian counties and could be improved by proper management practices. For sugarcane, 38% of areas can be improved. This technique allowed us to understand and map the food yield situation over large areas, which can support farmers, consultants, industries, policymakers, and world food security planning.
Analysis of starch grains trapped in human dental calculus in Áspero, Peru during the Initial Formative Period (3000–1800 BCE)
Authors: Yseki Marco , Pezo-Lanfranco Luis , Machacuay Marco , Novoa Pedro , Shady Ruth 
Published: August 2023

AbstractThe objective of this research is to identify the plants consumed and to determine their dietary importance in Áspero, an urban center on the coast of the Supe Valley, Peru. Consequently, starch grains trapped in the human dental calculus of nine individuals were recovered, while the results from one individual from the Sacred City of Caral, located in the interior of Supe Valley, are presented. Eight species of food plants were identified, among them C3 plants: sweet potato, squash, potato, chili pepper, algarrobo, manioc and bean and C4 plant: maize. Previous isotopic analysis indicates that C3 plants formed the foundation of the diet at Áspero and Caral. Our results indicate a high ubiquity of C3 plants like sweet potato (100%) and squash (90%) suggesting, with caution, that these taxa were an important C3 source in the menu. Maize, C4 plant, showed a similar ubiquity (100%) to sweet potato and squash, however, previous isotopic analysis indicate that maize was a marginal food in Áspero and Caral. These results support that the absence and abundance of starch grains cannot be employed to directly infer the frequency of intake of C3 and C4 plants within a small population, as suggested by previous studies.
Ultrasensitive miniaturized planar microwave sensor for characterization of water–alcohol mixtures
Authors: Javadizadeh Saeed , Badieirostami Majid , Shahabadi Mahmoud 
Published: August 2023

AbstractDesigning a low-cost, compact, yet sensitive planar microwave sensor for complex permittivity measurement is highly desired for numerous applications though quite challenging. Here, in this research, an ultrasensitive planar microwave sensor is proposed which is based on an electric LC structure. The core sensor was fabricated on an FR-4 substrate using a simple fabrication process, then integrated within a polymethylmethacrylate microfluidic channel for straightforward liquid delivery to the sensing region. The resonance frequency of the bare sensor was designed to occur at 4.14 GHz while empty and shifted to 0.88 GHz when deionized water flows into the channel. The sensor response has been characterized for different mixture ratios of methanol and ethanol with deionized water. Next, the complex permittivity of the resulted binary mixtures has been extracted by the Debye model through a least square fitting method. The calculated average sensitivity is 1.45% which stands above most of sensors reported in the literature. Besides, the sensor has a small footprint with dimensions of 3.6 × 3.8 mm$$^2$$

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making it a suitable candidate for integration with point-of-care testing devices.