bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microinjection‐enabled gene silencing in first instar larvae of western flower thrips, Frankliniella occidentalis, reveals vital genes for larval survival
Authors: Han Jinlong , Rotenberg Dorith 
Published: November 2024

AbstractThe western flower thrips (Frankliniella occidentalis) is a significant agricultural pest, causing severe global yield losses due to extensive feeding damage and the transmission of plant pathogenic viruses. Despite recent advancements in RNA interference (RNAi) in thrips species, its application has been mostly limited to the adult stage. Given the crucial role of first instar larval thrips in acquiring and transmitting orthotospoviruses, achieving gene silencing in these larvae is critical for studying virus entry and acquisition. While thoracic and abdominal injections have proven effective in adult thrips, the low post‐injection survival rate hinders their use in larval thrips. This study addresses this challenge by presenting a microinjection methodology to deliver dsRNA into the hemolymph of first instar larval thrips through the coxa, the first proximal segment of the foreleg. This method significantly improved larval survival rate by preventing detrimental damage to the internal tissues. Significant knockdown of V‐ATPase‐B, cytochrome P450 (CYP3653A2), and apolipophorin‐II/I (ApoLp‐II/I) transcripts was confirmed after 48 and/or 72 h post injection (hpi), corresponding to the first and second instar larval stages, respectively. Silencing CYP3653A2 or ApoLp‐II/I significantly increased larval mortality. These findings demonstrate proof‐of‐principle of gene silencing and associated silencing phenotype (mortality) for first instar larval thrips and highlight the essential role of CYP3653A2 and ApoLp‐II/I in larval vitality. Our RNAi‐based tool offers an opportunity to investigate the molecular mechanisms of thrips‐orthotospovirus interactions, as the virus must be acquired by young larval thrips for successful transmission to plants, thus presenting potential targets for thrips pest management.
The EU's efforts to uphold the international rules‐based order: Mission impossible?
Authors: Wouters Jan 
Published: November 2024

AbstractIt is commonplace today to state that the international rules‐based order is in decline, or at least severely under threat. The European Union has been a steadfast self‐proclaimed defender of such order, with a strong commitment to multilateralism, the United Nations, and international law based on its founding treaties. This contribution asks how deep and consistent the EU's choice for multilateralism is and how the Union is coping with the challenges to the international rules‐based order. It briefly inquires through what instruments, mechanisms, and tools the EU aims to live up to its commitment to multilateralism and to what extent the Union itself consistently respects international law. It ends with the question of how the EU can reinforce its multilateral commitment to the international rules‐based order, in particular through the UN.
Restoration of hair follicle inductive properties by depletion of senescent cells
Authors: Pappalardo Alberto , Kim Jin Yong , Abaci Hasan Erbil , Christiano Angela M. 
Published: November 2024

AbstractSenescent cells secrete a senescence‐associated secretory phenotype (SASP), which can induce senescence in neighboring cells. Human dermal papilla (DP) cells lose their original hair inductive properties when expanded in vitro, and rapidly accumulate senescent cells in culture. Protein and RNA‐seq analysis revealed an accumulation of DP‐specific SASP factors including IL‐6, IL‐8, MCP‐1, and TIMP‐2. We found that combined senolytic treatment of dasatinib and quercetin depleted senescent cells, and reversed SASP accumulation and SASP‐mediated repressive interactions in human DP culture, resulting in an increased Wnt‐active cell population. In hair reconstitution assays, senolytic‐depleted DP cells exhibited restored hair inductive properties by regenerating de novo hair follicles (HFs) compared to untreated DP cells. In 3D skin constructs, senolytic‐depleted DP cells enhanced inductive potential and hair lineage specific differentiation of keratinocytes. These data revealed that senolytic treatment of cultured human DP cells markedly increased their inductive potency in HF regeneration, providing a new rationale for clinical applications of senolytic treatment in combination with cell‐based therapies.
Impacts of an increase in federal assistance for cover cropping: Evidence from the Environmental Quality Incentives Program
Authors: Rosenberg Andrew B. , Pratt Bryan , Szmurlo Daniel 
Published: November 2024

AbstractFinancial assistance for cover cropping through the U.S. Department of Agriculture's Environmental Quality Incentives Program (EQIP) has increased more than twentyfold in the past decade and a half. Available support for cover cropping increased further due to the Inflation Reduction Act, which provides significant funding for climate smart practices. In this study, we examine whether increases in available financial assistance lead to significant increases in producer participation in EQIP for cover cropping and whether these increases are additional on the landscape. We focus on the impacts of the National Water Quality Initiative (NWQI), which provides funding for cover crops and several other practices to producers in targeted watersheds on top of normal EQIP levels. We first estimate the impacts of NWQI on enrollment in EQIP using a watershed‐level panel of acres enrolled in EQIP for cover crops. We find that NWQI more than triples EQIP cover crop acreage compared to similar control watersheds. Driving the increase in enrolled acreage is a small increase in the share of applications receiving a contract, as well as a significant increase in the total number of applications received. We then utilize field‐level administrative data on cover cropping to estimate the impact of NWQI on cover crop adoption overall. We find evidence that the impacts of NWQI on cover cropping are largely additional.
The asymmetry in the sagitta of the European eel Anguilla anguilla (Linnaeus, 1758) collected from the Söke District of Aydın Province in Western Anatolia, Türkiye
Authors: Koca Habil Uğur , Cilbiz Mehmet , Güçlü Salim Serkan , Jawad Laith A. 
Published: November 2024

AbstractOtolith features (length, width and weight) of 74 individuals of Anguilla anguilla collected from the Söke District of Aydın Province in Western Anatolia, Türkiye were studied for the first time to evaluate the level of asymmetry in the otolith features selected for this study. The asymmetry value of the otolith length was greater than that of otolith width and otolith weight. The asymmetry value of the three otolith features increased with an increase in the fish's length. The likely cause of asymmetry in the otolith parameters examined has been discussed in relation with the variability in growth provoked by ecological influence associated with the discrepancy in habitat setting and contaminants present in the Söke District of Aydın Province in Western Anatolia, Türkiye.
Elucidating loss‐of‐function mechanisms of monoallelic EPAS1 mutations underlying congenital hypoplastic anaemia in a paediatric anaemia cohort
Authors: Zhang Jiasheng , Sun Jin , Huai Wan , Tang Jie , Chen Jing , Yao Ruen , Yu Tingting 
Published: November 2024

SummaryHIF‐2α, encoded by EPAS1, plays a dominant role in regulating erythropoietin (EPO) production, maintaining the dynamic balance of erythropoiesis. Gain‐of‐function mutations in EPAS1 cause erythrocytosis. However, anaemia caused by EPAS1 loss‐of‐function mutations has been confined to only one case report, and the underlying mechanism remains unclear. Herein, the reanalysis of high‐throughput sequencing data from 311 patients with anaemia identified three monoallelic EPAS1 variants from three unrelated families in a paediatric anaemia cohort. The probands showed highly consistent clinical phenotypes with normocytic and normochromic anaemia, reticulocytopenia and relative deficiency of serum EPO, characterised as congenital hypoplastic anaemia. In vitro studies suggested that defects in steady‐state protein abundance, nuclear localisation and binding with co‐activator in EPAS1 variants lead to impaired EPO transcriptional activation. Therefore, loss‐of‐function mutations in EPAS1 can cause erythroid hypoplasia in an EPO‐dependent manner. This study identified a new causative gene for congenital hypoplastic anaemia and clarified the molecular aetiology of loss‐of‐function EPAS1 mutations.
Autologous stem cell transplantation for multiple myeloma patients whose myeloma‐defining event was SLiM
Authors: Vaxman Iuliana , Kumar Shaji , Cohen Inbar , Shimony Shai , Dispenzieri Angela , Buadi Francis , Dingli David , Muchtar Eli , Kapoor Prashant , Hogan William , Hayman Suzanne , Leung Nelson , Gonsalves Wilson , Kourelis Taxiarchis , Warsame Rahma , Gertz Morie 
Published: November 2024

SummaryIn 2014, the International Myeloma Working Group (IMWG) updated the criteria for diagnosing myeloma and added three additional criteria to the traditional Calcium elevation, Renal impairment, Anemia, Bone disease (CRAB) criteria, called the Sixty % marrow plama cells, Light chain ratio >60, Mri demonstates lytic lesions (SLiM) criteria (clonal bone marrow plasma cells ≥60%, involved to uninvolved free light chain ratio (FLCr) ≥100 and >1 focal lesion on magnetic resonance imaging (MRI)). We report on the outcomes of 30 patients who underwent autologous stem cell transplantation (ASCT) where therapy was initiated solely based on SLiM criteria and compared them to a matched cohort of 60 patients whose myeloma‐defining event was CRAB. The SLiM cohort had a shorter median time to neutrophil (15 vs. 16 days, p = 0.049) and platelet (15 vs. 17 days, p = 0.0004) engraftment. The 36‐month overall survival (OS) was 100% in the SLiM group and 93.27% in the control group (95% CI 83.06%–97.42%), with a trend towards longer OS in the SLiM cohort (p = 0.065). The 36‐month progression‐free survival (PFS) was 91.61% in the SLiM (95% CI 69.93%–97.87%) and 65.95% in the control group (95% CI 52.31%–76.53%). There was no difference in the PFS between the cohorts (p = 0.414). ASCT is efficacious and safe in MM patients transplanted only due to SLIM criteria. Early intervention in this asymptomatic cohort did not appear to result in deeper responses or better PFS compared to outcomes in symptomatic patients.
Perceiving visual events uses optical information that reflects dynamics rather than resembles appearance
Authors: Zhang Huiyuan , Bingham Geoffrey P. , Pan Jing Samantha 
Published: November 2024

AbstractThis study investigates the optical information for visual event perception. Events are objects in motion, with properties like shape, weight and surface material influencing the dynamics that shape movements and optics. The progressive transformation of visible textures, known as visual kinaesthetic information, specifies movements and objects. Four experiments tested whether events could be perceived using only visual kinaesthetic information. Participants identified their own walking from point‐light displays (Experiment 1), from simulated environmental texture transformations as a result of their walking (Experiment 2), and from videos shot by a head‐mounted camera during outdoor walking (Experiment 3); and distinguishing strangers from footages captured by their head‐mounted cameras (Experiment 4). In Experiments 2–4, the displays did not resemble the outline of a person or look like walking but revealed the physical relations between the walker and the environment as a result of their movement. Regardless, participants were able to recognize themselves and distinguish strangers. Thus, observers are able to perceive events using visual kinaesthetic information that stems from dynamics. The one‐to‐one correspondences between object property, dynamics, kinematics and optical information are governed by the laws of physics, and unaffected by the event's appearance or viewing perspectives.
Anti‐b diminishes hyperlipidaemia and hepatic steatosis in hamsters and mice by suppressing the mTOR/PPARγ and mTOR/SREBP1 signalling pathways
Authors: Bian Yu , Wu Han , Jiang Weitao , Kong Xue , Xiong Yuting , Zeng Linghua , Zhang Feng , Song Jinglun , Wang Chunlei , Yang Yang , Zhang Xinyue , Zhang Yuning , Pang Ping , Duo Tianqi , Wang Zhuo , Pan Tengfei , Yang Baofeng 
Published: November 2024

Background and PurposeAs a chronic metabolic syndrome, hyperlipidaemia is manifested as aberrantly elevated cholesterol and triglyceride (TG) levels, primarily attributed to disorders in lipid metabolism. Despite the promising outlook for hyperlipidaemia treatment, the need persists for the development of lipid‐lowering agents with heightened efficiency and minimal toxicity. This investigation aims to elucidate the lipid‐lowering effects and potential pharmacodynamic mechanisms of Anti‐b, a novel low MW compound.Experimental ApproachWe employed high‐fat diet (HFD) in hamsters and mice or oleic acid (OA) in cultures of HepG2 cells and LO2 cells to induce hyperlipidaemia models. We administered Anti‐b to assess its therapeutic effects on dyslipidaemia and hepatic steatosis. We used western blotting, RNA sequencing, GO and KEGG analysis, oil red O staining, along with molecular docking and molecular dynamics simulation to elucidate the mechanisms underlying the effects of Anti‐b.Key ResultsAnti‐b exhibited a substantial reduction in HFD‐induced elevation of blood lipids, liver weight to body weight ratio, liver diameter and hepatic fat accumulation. Moreover, Anti‐b demonstrated therapeutic effects in alleviating total cholesterol (TC), TG levels, and lipid accumulation derived from OA in HepG2 cells and LO2 cells. Mechanistically, Anti‐b selectively bound to the mTOR kinase protein and increased mTOR thermal stability, resulting in downregulation of phosphorylation level. Notably, Anti‐b exerted anti‐hyperlipidaemia effects by modulating PPARγ and SREBP1 signalling pathways and reducing the expression level of mSREBP1 and PPARγ proteins.Conclusion and ImplicationsIn conclusion, our study has provided initial data of a novel low MW compound, Anti‐b, designed and synthesised to target mTOR protein directly. Our results indicate that Anti‐b may represent a novel class of drugs for the treatment of hyperlipidemia and hepatic steatosis.
Psilocybin as a novel treatment for chronic pain
Authors: Askey Tate , Lasrado Reena , Maiarú Maria , Stephens Gary J. 
Published: November 2024

AbstractPsychedelic drugs are under active consideration for clinical use and have generated significant interest for their potential as anti‐nociceptive treatments for chronic pain, and for addressing conditions like depression, frequently co‐morbid with pain. This review primarily explores the utility of preclinical animal models in investigating the potential of psilocybin as an anti‐nociceptive agent. Initial studies involving psilocybin in animal models of neuropathic and inflammatory pain are summarised, alongside areas where further research is needed. The potential mechanisms of action, including targeting serotonergic pathways through the activation of 5‐HT2A receptors at both spinal and central levels, as well as neuroplastic actions that improve functional connectivity in brain regions involved in chronic pain, are considered. Current clinical aspects and the translational potential of psilocybin from animal models to chronic pain patients are reviewed. Also discussed is psilocybin's profile as an ideal anti‐nociceptive agent, with a wide range of effects against chronic pain and its associated inflammatory or emotional components.
E3 Ubiquitin Ligase Ring Finger Protein 2 Alleviates Cerebral Ischemia–Reperfusion Injury by Stabilizing Mesencephalic Astrocyte‐Derived Neurotrophic Factor Through Monoubiquitination
Authors: Shen Yujun , Wang Jinfeng , Liang Junxing , Chen Ying , Wu Xueyan , Ren Zhenhua , Zhou Jiangning , Feng Lijie , Shen Yuxian 
Published: November 2024

ABSTRACTAimCerebral ischemic stroke (IS) is one of the leading causes of morbidity and mortality globally. However, the mechanisms underlying IS injury remain poorly understood. Ring finger protein 2 (RNF2), the member of the polycomb family (PcG), has been implicated in diverse biological and pathological conditions. However, whether RNF2 plays a role in IS progression is not clarified. This study aims to investigate the potential effects of RNF2 on IS.MethodsThe effects of RNF2 were studied in human postmortem IS brains, a rat model of IS, tunicamycin (TM)‐induced mouse neuroblastoma neuro2a (N2a) cells, and oxygen–glucose deprivation/reperfusion (OGD/R)‐induced SH‐SY5Y cells.ResultsHere, we demonstrated that RNF2 was markedly upregulated both in human postmortem IS brains and ischemic rat brains and RNF2 overexpression alleviated brain injury induced by middle cerebral artery occlusion by reducing neuron apoptosis. Mechanistically, we found that RNF2 is an E3 ubiquitin ligase for the mesencephalic astrocyte‐derived neurotrophic factor (MANF), which confers protection against brain ischemia. RNF2 interacted with MANF and promoted the monoubiquitination of MANF, consequently facilitating its stability and nuclear localization.ConclusionCollectively, RNF2 is identified as a critical inhibitor of IS injury by stabilizing MANF through monoubiquitination, suggesting that RNF2 is a potential therapeutic target for IS.
Pharmacogenetic‐guided dosing for fluoropyrimidine (DPYD) and irinotecan (UGT1A1*28) chemotherapies for patients with cancer (PACIFIC‐PGx): A multicenter clinical trial
Authors: Glewis Sarah , Lingaratnam Senthil , Lee Benjamin , Campbell Ian , IJzerman Maarten , Fagery Mussab , Harris Sam , Georgiou Chloe , Underhill Craig , Warren Mark , Campbell Robert , Jayawardana Madawa , Silva S. Sandun M. , Martin Jennifer H. , Tie Jeanne , Alexander Marliese , Michael Michael 
Published: November 2024

AbstractPACIFIC‐PGx evaluated the feasibility of implementing pharmacogenetics (PGx) screening in Australia and the impact of DPYD/UGT1A1 genotype‐guided dosing on severe fluoropyrimidine (FP) and irinotecan‐related toxicities and hospitalizations, compared to historical controls. This prospective single arm trial enrolled patients starting FP/irinotecan for any cancer between 7 January 2021 and 25 February 2022 from four Australian hospitals (one metropolitan, three regional). During the accrual period, 462/487 (95%) consecutive patients screened for eligibility for DPYD and 50/109 (46%) for UGT1A1 were enrolled and genotyped (feasibility analysis), with 276/462 (60%) for DPYD and 30/50 (60%) for UGT1A1 received FP/irinotecan (safety analysis). DPYD genotyping identified 96% (n = 443/462) Wild‐Type, 4% (n = 19/462) Intermediate Metabolizers (50% dose reduction), and 0% Poor Metabolizers. UGT1A1 genotyping identified 52% (n = 26/50) Wild‐Type, 40% (n = 20/50) heterozygous, and 8% (n = 4/50) homozygous (30% dose reduction). Key demographics for the FP/irinotecan safety cohorts included: age range 23–89/34–74 years, male 56%/73%, Caucasian 83%/73%, lower gastrointestinal cancer 50%/57%. Genotype results were reported prior to cycle‐1 (96%), average 5–7 days from sample collection. PGx‐dosing for DPYD variant allele carriers reduced high‐grade toxicities compared to historic controls (7% vs. 39%; OR = 0.11, 95% CI 0.01–0.97, p = 0.024). High‐grade toxicities among Wild‐Type were similar (14% vs. 14%; OR = 0.99, 95% CI 0.64–1.54, p = 0.490). PGx‐dosing reduced FP‐related hospitalizations (−22%) and deaths (−3.7%) compared to controls. There were no high‐grade toxicities or hospitalizations for UGT1A1*28 homozygotes. PGx screening and prescribing were feasible in routine oncology care and improved patient outcomes. Findings may inform expanded PGx programs within cancer and other disease settings.
Syndication in science: Curated collaboration
Authors: Hurry David B. , Izmailova Elena S. , Davies Simon , Harari Olivier , Stoch S. Aubrey , Wagner John A. 
Published: November 2024

AbstractDevelopment and validation of digital measures require dedicated clinical studies, which can be conducted by a single study sponsor or a precompetitive collaboration. In this perspective, we propose an alternative model, data syndication, a curated collaboration, which foresees a technology provider being a founding member with biopharmaceutical sponsors and other stakeholders joining. Its main advantages are the speed of the study startup and the opportunity for real‐time data streaming.
Parental childhood adversity and emotional functioning: Associations with child's emotion regulation
Authors: Zreik Ghadir , Haimov Iris , Szepsenwol Ohad 
Published: November 2024

AbstractObjectiveWe examined the unique associations of different childhood stressors (economic hardship, unpredictability, low parental sensitivity, and adverse childhood experiences) with parents' emotion regulation and mentalizing, and whether parental difficulties in these domains translate into emotion regulation difficulties in their children.BackgroundMaladjustment caused by early exposure to adversity may transfer to future generations by undermining the parenting quality of the exposed individuals.MethodA sample of 562 parents to 3‐ to 6‐year‐old children completed an online questionnaire.ResultsChildhood experiences of early‐life unpredictability and insensitive parental care were uniquely associated with parental emotion regulation and mentalizing difficulties. Examining the mediated paths linking parents' exposure to specific childhood stressors with their children's emotion regulation difficulties indicated that parental experiences of early‐life unpredictability and insensitive parental care are indirectly associated with greater emotion regulation difficulties in their children, through greater parental emotion regulation difficulties and prementalizing modes.ConclusionsThis study points to the unique role of specific childhood stressors—namely, unpredictability and insensitive parenting—in the intergenerational transmission of emotion regulation problems.ImplicationsThe findings have important implications for intervention programs aimed at working with young children and their parents to mitigate the intergenerational transmission of adversity to the next generations.