bluuebunny/crossref_metadata_2025_split huggingface dataset:
A network of CD163+macrophages monitors enhanced permeability at the blood-dorsal root ganglion barrier
Authors: Lund Harald , Hunt Matthew , Kurtovic Zerina , Sandor Katalin , Fereydouni Noah , Julien Anais , Göritz Christian , Han Jinming , Zhu Keying , Harris Robert A. , Lampa Jon , Haglund Lisbet , Yaksh Tony L. , Svensson Camilla I. 
Published: March 2023

AbstractIn dorsal root ganglia (DRG), macrophages reside in close proximity to sensory neurons, and their functions have largely been explored in the context of pain, nerve injury and repair. In this study, however, we discovered that the majority of macrophages in DRGs are in direct contact with the vasculature where they constantly monitor the circulation, efficiently phagocytosing proteins and macromolecules from the blood. Characterization of the DRG endothelium revealed a specialized vascular network spanning the arteriovenous axis, which gradually transformed from a barrier type endothelium in arteries to a highly permeable endothelium in veins. Macrophage phagocytosis spatially aligned with peak endothelial permeability and we identified caveolar transcytosis as a mechanism regulating endothelial permeability. Profiling of the DRG immune landscape revealed two subsets of perivascular macrophages with distinct transcriptome, turnover and function. CD163 expressing macrophages self-maintained locally, specifically participated in vasculature monitoring, displayed distinct responses during peripheral inflammation and were conserved in mouse and Man. Our work provides a molecular explanation for the permeability of the blood-DRG barrier and identifies an unappreciated role of macrophages as integral components of the DRG-neurovascular unit.
Novel RNA m6A methyltransferase METTL16 inhibitors
Authors: Selberg Simona , Ivanova Larisa , Kotli Mihkel , Herodes Koit , Blokhina Daria , Kankuri Esko , Seli Neinar , Ilves Ivar , Teino Indrek , Saarma Mart , Karelson Mati 
Published: March 2023

AbstractThe overexpression of RNA 6-N-methyladenosine (m6A) methyltransferase METTL16 has oncogenic role in the case of several cancer types, including leukemia, but efficient small-molecule inhibitors are not available. Initially identified by high-throughput virtual screening of the ZINC15 databasein vivosubset, but then confirmed by measuring catalytic activity, two nanomolar-active METTL16 inhibitors, compounds1(IC50= 25.82 ± 17.19 nM) and2(IC50= 60.91 ± 2.75 nM) were found. The inhibitory activity of the compounds was measured using the m6A antibody-based ELISA assay. We also present the results on the effect of these inhibitors on the viability of promyeloblast HL-60 and lymphoblast CCRF-CEM leukemia cell lines. In unstressed growth conditions, both identified METTL16 inhibitors reduced the viability of HL-60 cells by up to 40%. The effect on the viability of CCRF-CEM cells was smaller with no dose dependency observed. In parallel, the level of the m6A as compared to unmodified adenosine in the HL-60 cell mRNAs was significantly reduced by the inhibitor1. Collectively, we herein demonstrate novel METTL16 inhibitors that exert tumor cell-lineage-selective antiproliferative effects.
ATP citrate lyase is an essential player of the metabolic rewiring induced by PTEN loss during T-ALL development
Authors: Andrieu Guillaume P. , Hypolite Guillaume , Balducci Estelle , Costa Caroline , Verhoeyen Els , Nemazanyy Ivan , Panasyuk Ganna , Wellen Kathryn , Macintyre Elizabeth , Asnafi Vahid , Tesio Melania 
Published: March 2023

SummaryAlterations inactivating the tumor suppressor genePTENdrive the development of solid and hematological cancers, such as T-cell acute lymphoblastic leukemia (T-ALL), whereby PTEN loss defines poor-prognosis patients. We investigated the metabolic rewiring induced by PTEN loss in T-ALL, aiming at identifying novel metabolic vulnerabilities. We showed that the enzyme ATP citrate lyase (ACLY) is strictly required for the transformation of thymic immature progenitors and for the growth of human T-ALL, which remain dependent on ACLY activity even upon transformation. Whereas PTEN mutant mice all died within 17 weeks, the concomitant ACLY deletion prevented disease initiation in 70% of the animals, where it prevented the apoptosis of pre-malignant DP thymocytes by up-regulating BCL-2. Transcriptomic and metabolic analysis of primary T-ALL cells next translated our findings to the human pathology, showing that PTEN-altered T-ALL cells selectively activate ACLY and are specifically sensitive to its genetic targeting. ACLY activation thus represents a metabolic vulnerability with therapeutic potential for high-risk T-ALL patients.
Comparative analysis of soybean transcriptional profiles reveals defense mechanisms involved in resistance againstDiaporthe caulivora
Authors: Mena Eilyn , Reboledo Guillermo , Stewart Silvina , Montesano Marcos , de León Inés Ponce 
Published: March 2023

AbstractSoybean stem canker (SSC) caused by the fungal pathogenDiaporthe caulivorais an important disease affecting soybean production. However, limited information related to the molecular mechanisms underlying soybean resistance toDiaporthespecies is available. In the present work, the defense responses toD. caulivorain two contrasting soybean genotypes were analyzed. We showed thatGénesis5601 is more resistant to fungal infection than Williams, evidenced by significantly smaller lesion length, reduced disease severity and pathogen biomass. Transcriptional profiling was performed in untreated plants and inD. caulivora-inoculated and control-treated tissues at 8 and 48 hours post inoculation (hpi). In total, 2.322 and 1.855 genes were differentially expressed in Génesis 5601 and Williams, respectively. Interestingly, Génesis 5601 exhibited a significantly higher number of upregulated genes compared to Williams at 8 hpi, 1.028 versus 434 genes. Resistance toD. caulivorawas associated with defense activation through transcriptional reprogramming mediating perception of the pathogen by receptors, biosynthesis of phenylpropanoids, hormones, small heat shock proteins and pathogenesis related (PR) genes. These findings provide novel insights into soybean defense molecular mechanisms used to controlD. caulivora, and generate a foundation for development of resistant SSC varieties within soybean breeding programs.
Phase Separation and Ageing of Glycine-Rich Protein from Tick Adhesive
Authors: Ganar Ketan A. , Turbina Polina , Nandy Manali , Chen Chang , Suylen Dennis , van der Beelen Stan , Pascoe Emily Louise , Koenraadt Constantianus J.M. , Dijkgraaf Ingrid , Deshpande Siddharth 
Published: March 2023

AbstractHard ticks feed on their host for multiple days. To ensure firm attachment, they secrete a protein-rich saliva that eventually forms a solid cement cone. The underlying mechanism of this liquid-to-solid transition is not yet understood. This study focuses on the phase transitions of a disordered glycine-rich protein (GRP) that is prominent in tick saliva. We show that GRP undergoes liquid-liquid phase separation via simple coacervation to form biomolecular condensates in salty environments. Cation-pi and pi-pi interactions near the C-terminus promote coacervation while a negatively charged N-terminus prolongs its onset through electrostatic repulsion. Interestingly, GRP condensates exhibit ageing and undergo liquid-to-gel transition to form viscoelastic networks as well as solid-like condensates. Lastly, we provide evidence for protein-rich condensates in natural tick saliva. Our findings provide a starting point to gain insights into the bioadhesion of ticks, develop novel tick control strategies, and towards biomedical applications such as tissue sealants.
A meta-analysis examining how fish biodiversity varies with marine protected area size and age
Authors: Hollitzer Helene A. L. , May Felix , Blowes Shane A. 
Published: March 2023

AbstractMarine Protected Areas (MPAs) are a well-established conservation practice worldwide, but their effectiveness in protecting or replenishing fish biodiversity remains uneven. Understanding the patterns of this heterogeneity is central to general guidelines for MPA design and can ultimately provide guidance on how to maximize MPA potential. Here, we examine associations between the degree of protection, duration of protection, and protected area size, with fish biodiversity inside of protected areas relative to that of sites nearby, but outside of protected areas. We quantitatively synthesize 116 published estimates of species richness from 72 marine protected areas, and 38 estimates of Shannon entropy from 21 marine protected areas. We show that species richness is on average 18% (95% confidence intervals: 10% to 29%) higher in protected areas relative to areas open to fishing; and, on average Shannon entropy is 13% (95% confidence intervals: −2% to 31%) higher within protected areas relative to outside. We find no relationship between the degree or duration of protection with the ratio of species richness inside versus outside of protected areas; both fully and partially protected areas contribute to the accumulation of species inside protected areas, and protected areas of all ages contribute similarly on average to biodiversity conservation. In contrast to our expectations, increasing protected area size was associated with a decreased ratio of species richness sampled at sites inside versus outside the protected area, possibly due, for example, to insufficient enforcement and/or low compliance. Finally, we discuss why meta-analyses such as ours that summarize effect sizes of local scale biodiversity responses, that is, those at a single site, can only give a partial answer to the question of whether larger protected areas harbor more species than comparable unprotected areas.
Sensing the rainbow: genetic and physiological responses to light quality in Ostreococcus, an ecologically important photosynthetic picoeukaryote
Authors: Sands Elizabeth , Davies Sian , Puxty Richard John , Bouget François-Yves , Scanlan David John , Carré Isabelle Alice 
Published: March 2023

AbstractPhytoplankton is exposed to dramatic variations in light quality as it moves up and down the water column or encounters the presence of sediments in the water. We investigated the potential impact onOstreococcus,a key marine photosynthetic picoeukaryote, by analysing changes in its transcriptome, pigment content and photophysiology after acclimation to monochromatic red, green or blue light. The clade B species RCC809, isolated from the deep Atlantic Ocean, responded to blue light by accelerating cell division at the expense of storage reserves, and by increasing the relative level of blue-light absorbing pigments. In contrast, it responded to red and green light by increasing its potential for photoprotection. In contrast, the clade A species OTTH0595, which originates from a shallow water environment, showed no difference in photosynthetic properties and minor differences in carotenoid contents between light qualities. These results demonstrate that light quality can have a major influence on the physiology of eukaryotic phytoplankton, and suggest that different light quality environments can drive selection for diverse patterns of responsiveness and environmental niche partitioning.HighlightWe characterise the effects of light quality on the transcriptome and photophysiology ofOstreococcus, a photosynthetic picoeukaryote, and show that responses are distinct between two ecotypes originating from different environments.
FLASH-RT does not affect chromosome translocations and junction structures beyond that of CONV-RT dose-rates
Authors: Barghouth Paul G. , Melemenidis Stavros , Montay-Gruel Pierre , Ollivier Jonathan , Viswanathan Vignesh , Jorge Patrik G. , Soto Luis A. , Lau Brianna C. , Sadeghi Cheyenne , Edlabadkar Anushka , Manjappa Rakesh , Wang Jinghui , Bouteiller Marie Le , Surucu Murat , Yu Amy , Bush Karl , Skinner Lawrie , Maxim Peter G. , Loo Billy W. , Limoli Charles L. , Vozenin Marie-Catherine , Frock Richard L. 
Published: March 2023

AbstractThe molecular and cellular mechanisms driving the enhanced therapeutic ratio of ultra-high dose-rate radiotherapy (FLASH-RT) over slower conventional (CONV-RT) radiotherapy dose-rate remain to be elucidated. However, attenuated DNA damage and transient oxygen depletion are among several proposed models. Here, we tested whether FLASH-RT under physioxic (4% O2) and hypoxic conditions (≤2% O2) reduces genome-wide translocations relative to CONV-RT and whether any differences identified revert under normoxic (21% O2) conditions. We employed high-throughput rejoin and genome-wide translocation sequencing (HTGTS-JoinT-seq), usingS. aureusandS. pyogenesCas9 “bait” DNA double strand breaks (DSBs), to measure differences in bait-proximal repair and their genome-wide translocations to “prey” DSBs generated by electron beam CONV-RT (0.08-0.13Gy/s) and FLASH-RT (1×102-5×106Gy/s), under varying ionizing radiation (IR) doses and oxygen tensions. Normoxic and physioxic irradiation of HEK293T cells increased translocations at the cost of decreasing bait-proximal repair but were indistinguishable between CONV-RT and FLASH-RT. Although no apparent increase in chromosome translocations was observed with hypoxia-induced apoptosis, the combined decrease in oxygen tension with IR dose-rate modulation did not reveal significant differences in the level of translocations nor in their junction structures. Thus, Irrespective of oxygen tension, FLASH-RT produces translocations and junction structures at levels and proportions that are indistinguishable from CONV-RT.
Potassium transporter OsHAK18 mediates shoot-to-root circulation of potassium and sodium and source-to-sink translocation of soluble sugar in rice
Authors: Peng Lirun , Xiao Huojun , Li Ran , Zeng Yang , Gu Mian , Moran Nava , Yu Ling , Xu Guohua 
Published: March 2023

AbstractHigh-affinity potassium (K+) transporters HAK/KUP/KT have been identified in all genome-sequenced terrestrial plants. They play important role in K+acquisition, translocation and enhancing salt tolerance. Here we report that the plasma-membrane-located OsHAK18 functions in K+and sodium (Na+) circulation and sugar translocation in rice. OsHAK18 is expressed mainly, though not exclusively, in vascular tissues and particularly in the phloem. Knockout (KO) ofOsHAK18reduced K+concentration in phloem sap and in the root but increased K+accumulation in the shoot of both Nipponbare and Zhonghua11 cultivars, while overexpression (OX) ofOsHAK18driven by its endogenous promoter increased K+concentration in phloem sap and in roots, and promoted Na+retrieval from shoot to root under salt stress. Split-root experimental analysis of rubidium (Rb+) uptake and circulation indicated thatOsHAK18-OX promoted Rb+translocation from shoot to root. In addition,OsHAK18-KO increased whileOsHAK18-OX reduced soluble sugar content in the shoot and affected oppositely the sugar concentration in the phloem and its content in the root. Moreover,OsHAK18-OX increased dramatically grain yield and physiological K+utilization efficiency. Taken together, our results suggest that – unlike other OsHAKs analyzed heretofore – OsHAK18 is critical to K+and Na+re-circulation from shoot to root and enhances the source-to-sink translocation of a photo-assimilate.One sentence summaryRice potassium transporter OsHAK18 mediates shoot-to-root circulation of potassium and sodium and source-to-sink translocation of soluble sugar which improves potassium use efficiency and grain yield.
Shaping and interpretation of Dpp morphogen gradient by endocytic trafficking
Authors: Rasouliha Sheida Hadji , Aguilar Gustavo , Reinger Cindy , Matsuda Shinya 
Published: March 2023

AbstractDpp/BMP is a morphogen that controls patterning and growth in the Drosophila wing disc. Endocytic trafficking has been proposed to control extracellular Dpp spreading or removal, and Dpp signaling. However, how Dpp morphogen gradient is shaped and interpreted by endocytic trafficking remains unclear due to the lack of tools to visualize Dpp distribution at the physiological level. Here we generate functional fluorescent protein taggeddppalleles to visualize both extracellular and intracellular Dpp distribution. Using these alleles, we found that, while Dynamin-mediated internalization of Dpp is required for Dpp signal activation, Rab5-mediated trafficking is not required for Dpp spreading or signaling as proposed before but for shutting off Dpp signaling through downregulating activated receptors. We provide evidence that Dpp signaling is terminated at Multivesicular body (MVB) likely through sorting activated receptors into intraluminal vesicles (ILVs) rather than Rab7-mediated lysosomal degradation. We further found that blocking MVB formation expanded Dpp signaling gradient without affecting extracellular Dpp gradient, thus compromising extracellular Dpp gradient interpretation. These results indicate that extracellular Dpp gradient is shaped by Dynamin-mediated internalization of Dpp and interpreted by duration of Dpp signaling.
Risk Assessment and Monitoring of Certain Pollutants in Natural Honeys Imported from Different Countries and Marketing in KSA
Authors: Osman Khaled A. , Elsayed Mohamed Hala H. , Salama Maher S. 
Published: March 2023

AbstractThe physicochemical and antimicrobial properties, as well as metals and pesticide residue contents in honeys imported from different countries and marketing in KSA were investigated. The results indicated that the chemical composition of some of these honeys violated the most national and international guidelines. Also, honey samples showed greater antimicrobial activities against all the osmophilic microorganisms especiallyAspergillus flavus. Pb and Cd were not detected in all the tested samples, while Cu levels were below the guideline value of 5 mg/kg. However, Zn, Fe, and Ni levels in most the tested samples did not comply with the legislation values of 5, 15, and 0.01-1.00 mg/kg, respectively, and may pose a health risk to consumers. Also, Mn was found in higher levels which can be attributed either to the production stages of honey or the region from where the honey has been taken. Regarding the pesticide residues, some residues were detected in honeys imported from Germany, Australia, and Turkey; however, the hazardous indices for all the detected residues were less than one, indicating that these residues could not pose a health risk. It can be concluded that natural honeys should be free of any objectionable metals and pesticides.
A systematic review of ambient heat and sleep in a warming climate
Authors: Chevance Guillaume , Minor Kelton , Vielma Constanza , Campi Emmanuel , O’Callaghan-Gordo Cristina , Basagaña Xavier , Ballester Joan , Bernard Paquito 
Published: March 2023

AbstractBackgroundEarlier reviews documented the effects of a broad range of climate change outcomes on sleep but have not yet evaluated the effect of ambient temperature. This systematic review aims to identify and summarize the literature on ambient temperature and sleep outcomes in a warming world.MethodsFor this systematic review, we searched online databases (PubMed, Scopus, JSTOR, GreenFILE, GeoRef and PsycARTICLES) together with relevant journals for studies published before February 2023. We included articles reporting associations between objective indicators of ambient temperature and valid sleep outcomes measured in real-life environments. We included studies conducted among adults, adolescents, and children. A narrative synthesis of the literature was then performed.FindingsThe present systematic review shows that higher outdoor or indoor ambient temperatures, expressed either as daily mean or night-time temperature, are negatively associated with sleep quality and quantity worldwide. The negative effect of higher ambient temperatures on sleep is stronger in the warmest months of the year, among vulnerable populations and in the warmest areas of the world. This result appears consistent across several sleep indicators and measures.InterpretationAlthough this work identified several methodological limitations of the extant literature, a strong body of evidence from both this systematic review and previous experimental studies converge on the negative impact of elevated temperatures on sleep quality and quantity. In absence of solid evidence on fast adaptation to the effects of heat on sleep, rising temperatures induced by climate change pose a planetary threat to human sleep and therefore human health, performance and wellbeing.
Validation of an open-source smartphone step counting algorithm in clinical and non-clinical settings
Authors: Straczkiewicz Marcin , Keating Nancy L. , Thompson Embree , Matulonis Ursula A. , Campos Susana M. , Wright Alexi A. , Onnela Jukka-Pekka 
Published: March 2023

AbstractBackgroundStep counts are increasingly used in public health and clinical research to assess wellbeing, lifestyle, and health status. However, estimating step counts using commercial activity trackers has several limitations, including a lack of reproducibility, generalizability, and scalability. Smartphones are a potentially promising alternative, but their step-counting algorithms require robust validation that accounts for temporal sensor body location, individual gait characteristics, and heterogeneous health states.ObjectiveOur goal was to evaluate an open-source step-counting method for smartphones under various measurement conditions against step counts estimated from data collected simultaneously from different body locations (“internal” validation), manually ascertained ground truth (“manual” validation), and step counts from a commercial activity tracker (Fitbit Charge 2) in patients with advanced cancer (“wearable” validation).MethodsWe used eight independent datasets collected in controlled, semi-controlled, and free-living environments with different devices (primarily Android smartphones and wearable accelerometers) carried at typical body locations. Five datasets (N=103) were used for internal validation, two datasets (N=107) for manual validation, and one dataset (N=45) used for wearable validation. In each scenario, step counts were estimated using a previously published step-counting method for smartphones that uses raw sub-second level accelerometer data. We calculated mean bias and limits of agreement (LoA) between step count estimates and validation criteria using Bland-Altman analysis.ResultsIn the internal validation datasets, participants performed 751.7±581.2 (mean±SD) steps, and the mean bias was -7.2 steps (LoA -47.6, 33.3) or -0.5%. In the manual validation datasets, the ground truth step count was 367.4±359.4 steps while the mean bias was -0.4 steps (LoA -75.2, 74.3) or 0.1 %. In the wearable validation dataset, Fitbit devices indicated mean step counts of 1931.2±2338.4, while the calculated bias was equal to -67.1 steps (LoA -603.8, 469.7) or a difference of 0.3 %.ConclusionsThis study demonstrates that our open-source step counting method for smartphone data provides reliable step counts across sensor locations, measurement scenarios, and populations, including healthy adults and patients with cancer.