bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble TREM2 induces microglia dysfunction and brain damage while cleavage-reduced TREM2 shows sustained microglia activation with enhanced myelination in the cuprizone model
Authors: Beckmann Nicolau , Neuhaus Anna , Zurbruegg Stefan , Volkmer Pia , Patino Claudia , Joller Stefanie , Feuerbach Dominik , Doelemeyer Arno , Schweizer Tatjana , Rudin Stefan , Neumann Ulf , Berth Ramon , Frieauff Wilfried , Gasparini Fabrizio , Shimshek Derya 
Published: July 2022

Abstract
Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell-surface immunoreceptor expressed on microglia, osteoclasts, dendritic cells andmacrophages. Heterozygous loss-of-function mutations in TREM2, including mutations enhancing shedding form the cell-surface, have been associated with myelin/neuronal loss and neuroinflammation in neurodegenerative diseases like Alzheimer`s disease and Frontotemporal Dementia. Using the cuprizone model, we investigated the involvement of soluble and cleavage-reduced TREM2 on central myelination processes in cleavage-reduced (TREM2-IPD), soluble-only (TREM2-sol), knock-out (TREM2-KO) and wildtype (WT) mice. In the acute cuprizone model consisting of a five-week intoxication by the copper chelator followed by a four-week recovery all genotypes showed demyelination at the peak of disease reflected by a T2-weighted signal intensity increase in magnetic resonance imaging (MRI), most prominently in the external capsule (EC). During the recovery phase a partial signal reduction in WT and TREM2-IPD was observed, while TREM2-sol and TREM2-KO showed an additional increase in MRI signal in the EC. At week 9 histology revealed no recovery of neuroinflammation as well as of the lysosomal marker LAMP-1 in TREM2-IPD animals, which also displayed enhanced cytokine/chemokine levels in the brain. Despite presenting reduced levels of some cytokines/chemokines, persistent microgliosis and astrocytosis at week 9 was likewise observed in TREM2-sol and to a much lesser extent in TREM2-KO, with both homeostatic (TMEM119) as well as activated (LAMP-1) microglia markers increased. This was accompanied, specifically in the EC, by no myelin recovery, with appearance of myelin debris and axonal pathology, while oligodendrocytes recovered. In the chronic model consisting of 12-week cuprizone administration followed by 3-week recovery TREM2-IPD displayed sustained microgliosis and enhanced remyelination in the recovery phase. Taken together, our data suggest that sustained microglia activation led to increased remyelination, whereas microglia with only soluble TREM2 had reduced phagocytic activity despite efficient lysosomal function leading to a dysfunctional phenotype with improper myelin debris removal, lack of remyelination and axonal pathology following cuprizone intoxication.
Characterisation of a cyclic peptide that blocks the RAS binding domain of phosphoinositide 3-kinase p110α
Authors: Ismail Mohamed , Martin Stephen , George Roger , Houghton Francesca , Kelly Geoff , Wang Xinyue , O’Reilly Nicola , Federico Stefania , Cooley Rachel , Hui Ning Sze , Hancock David , Tavassoli Ali , Downward Julian , Molina-Arcas Miriam 
Published: July 2022

Abstract
p110α is a member of the phosphoinositide 3-kinase (PI3K) enzyme family that functions downstream of RAS. RAS proteins contribute to the activation of p110α by interacting directly with its RAS binding domain (RBD), resulting in the promotion of many cellular functions such as cell growth, proliferation and survival. Previous work from our lab has highlighted the importance of the p110α/RAS interaction in tumour initiation and growth. Here we report the discovery and characterisation of a cyclic peptide inhibitor (cyclo-CRVLIR) that interacts with the p110α-RBD and blocks its interaction with KRAS. cyclo-CRVLIR was discovered by screening a “split-intein cyclisation of peptides and proteins” (SICLOPPS) cyclic peptide library. The primary cyclic peptide hit from the screen initially showed a weak affinity for the p110α-RBD (Kd about 360µM). However, two rounds of amino acid substitution led to cyclo-CRVLIR, with an improved affinity for p110α-RBD in the low µM (Kd 3µM). We show that cyclo-CRVLIR binds selectively to the p110α-RBD but not to KRAS or the structurally-related RAF-RBD. Further, using biophysical, biochemical and cellular assays, we show that cyclo-CRVLIR effectively blocks the p110α/KRAS interaction in a dose dependent manner and reduces phospho-AKT levels in several oncogenic KRAS cell lines.
Dispersive Liquid Liquid Microextraction Extraction for the Determination of Aldehydes in Raw Untreated Water and Wastewater Samples around Gaborone, Botswana
Authors: Mogatsaseno Neo Tebogo , Motladiile Saidy , Sichilongo Kwenga 
Published: July 2022

Abstract
Due to their high solubility, cancer-causing and mutagenic properties, aldehydes have attracted research attention to establish their concentrations in water bodies. In this study, a simple and cheap, dispersive liquid liquid microextraction sample preparation procedure was developed for the determination of aliphatic and aromatic aldehydes in raw untreated water and wastewater in conjunction with using high performance liquid chromatography with diode array detection. The wavelength of detection was 360 nm using acidified water/methanol as a mobile phase and a Waters C18 XBridge column. The targeted aldehydes were propanal, 3-methylbutanal, pentanal, m-tolualdehyde, o-tolualdehyde, hexanal, nonanal and octanal. The recoveries ranged between 71-126.8 %. The method had good linearity with coefficients of determination (R2) values of greater than 0.9801 with linear dynamic ranges of 0.1 - 0.5 μg/mL for all the aldehydes. The method detection limits ranged between 0.02 - 0.15 μg/mL. The method was applied to real water samples obtained from the Gaborone Dam and the Glen Valley Wastewater treatment plant. Out of the analytes, only propanal was detected and quantified in the Glen Valley Wastewater treatment plant. According to the authors ability, results obtained in this study are the first to be reported in literature from Gaborone, Botswana.
Comparison of the gut microflora of common kestrel (Falco tinnunculus) according to differences in sex, age, and physiological condition
Authors: Zhang Kangqing , Gong Xiang , Wang Xinxiang , Sui Jinling 
Published: July 2022

Abstract
Background
Gut microbes play an important role in animal health, and their compositions and changes can reflect the physical condition of animals. However, the gut microbes of most birds, especially raptors, have been poorly investigated. This study used 16S rRNA gene sequencing technology to determine the gut microbiome of rescued common kestrels, compared the composition and diversity of the gut microbiome of common kestrels under different physiological conditions, and analyzed the effects of sex and age on the gut microbes of common kestrels.
Results
The results showed that Proteobacteria and Firmicutes were the dominant bacteria at the phylum level among the gut flora of kestrels. Difference in the physiological condition of kestrels exerted a significant influence on their gut microbe composition. Specifically, compared with the healthy group, the abundance of Lactobacillus in the fracture group increased, and the interaction between functionally similar flora was strengthened; in the pneumonia group, the abundance of potentially pathogenic microorganisms such as Clostridium_sensu_stricto_1 and Paeniclostridium was significantly enhanced (P < 0.05). Moreover, the interaction of differences in physiological condition and sex had a significant impact on the abundance of Proteobacteria and Actinobacteria in the guts of kestrels. In addition, the abundance of Acinetobacter was significantly affected by age, and with increasing age, its abundance also increased.
Conclusions
This study showed that sex, age and physiological condition affected the composition and diversity of the gut microbiome of common kestrels, and specific microorganisms changed in abundance in individuals with bacterial pneumonia or fractures, which provides a new perspective for the disease diagnosis and treatment of wild common kestrels.
Changing landscapes: habitat monitoring and land transformation in a long-time used Mediterranean coastal wetland
Authors: Tomaselli Valeria , Mantino Francesca , Albanese Giuseppe , Tarantino Cristina , Adamo Maria 
Published: July 2022

Abstract
Zone Umide della Capitanata, located in the northeastern part of the Apulia Region, is one of the most extensive coastal wetlands of the Italian peninsula and one of the largest components of the Mediterranean wetland system. Despite its high ecological importance, this site has been undergoing a variety of pressures intensified in recent decades. This study analyzes and evaluates the changes occurred in this area between 2010 and 2020. Land cover and habitat maps were performed by photointerpretation and on-site surveys, and classified according to the FAO-LCCS and EUNIS taxonomies, respectively. To focus on local dynamics, four subset areas were analyzed separately. A set of landscape metrics was computed to analyze the landscape structure. The anthropogenic pressures affecting the study area were described through the DPSIR (Driving Forces-Pressures-State-Impact-Response) conceptual framework. Numerous changes were identified, deriving from both finest thematic redefinition and anthropogenic pressures. Both class conversions and class modifications were identified and quantified by means of transition matrices. Most of the observed conversions were borne by classes belonging to saltmarshes and to coastal dune systems. In particular, landscape configuration of coastal dune classes was well highlighted by a set of specific landscape metrics. Agriculture practices and changes in water flow pattern turned out to be the main driving forces exerting pressures on these natural systems. Significant differences were found between the four subsets under analysis, thus, indicating that different management strategies lead to different levels of conservation.
Structure and diversity of archaea and methanogenic archaea in sediments of selected freshwater lakes, Antarctic Peninsula
Authors: Buriánková Iva , Rulík Martin , Bábíková Štěpánka , Molíková Anna , Novák David , Lochman Jan , Vítězová Monika 
Published: July 2022

Abstract
This research is the first study focusing to explore the diversity of Archaea and methanogens in sediments of 19 selected lakes nearby the Czech polar station on James Ross Island (JRI), Antarctica. The 16S rRNA gene sequencing provided a general view of a diversity of archaeal members and the mcrA gene sequencing has offered deeper insight into the taxonomical diversity of methanogens. Archaea rarely exceeded 1% of the total prokaryotic community. Genera Methanothrix and Methanosarcina were found as the predominating methanogenic members in the lake samples. For the first time in Antarctica, sequences of representatives belonging to Methanothermobacter sp. and Methanomassiliicoccales, and a high proportion of sequences belonging to Methanoperedens-like archaea, methanotrophs that couples anaerobic methane oxidation to denitrification, were recorded. The presence of the genus Methanobacterium has been also captured for the first time to a such large extent. Individual lakes from one area shared much higher similarity in their methanogenic diversity with the lakes from another area rather than with the lakes within the same area, suggesting that a lake location will be not the main factor influencing the diversity of the methanogens. Our research unambiguously provides evidence that the lakes of the JRI and surrounding islands are a potential source of new archaeal species.
Analysis of the influence of polystyrene microplastics and their derivatives on the DNA of human colon epithelial cells HT29 with the comet assay
Authors: Filipkowski Paweł , Aleksandra Ćwiklińska , Koziara Zuzanna , Parchem Karol , Zedler Łukasz , Ryl Jacek 
Published: July 2022

Abstract
We have been using plastic for almost a century and nowadays a lot of them circulates as pollutants in the environment and still defragmenting to micro and nanoscale. The exposition through the food chain and its precise impact on human health is still not clear. In our study, we tested real food packaging after contact with food products and real thermoinsulation and environmental samples of polystyrene in different model liquids, We used a comet assay, mass spectrometry (MS) of fluids which were in contact with packaging, free styrene measurement by Wijs method according to ISO standard and FTIR of wrap, to get an overview of their possible harmful effects. In the presented study, only low genotoxic effect (5-6% DNA damage) was observed.. In addition, no adverse effects were detected in the mass spectrometry. For analysed coloured polystyrene food packaging materials, we noticed a lower level of free styrene monomers in dairy packages that originally contained products with fruits. Exposure of cells to long-term seasoned polystyrene caused less DNA fragmentation than in the case of samples in saline.. Unfortunately, to this day no one knows how much free styrene and derivatives we eat with our daily food products and from food packaging.Based on our results and knowledge, more attention is needed with regard to polystyrene contamination. In particular, a wider analysis of the impact of interactions with the microbiota and the food matrix, which is in direct contact with the polystyrene packaging, should be carried out.The results of our research show that polystyrene and its derivatives from food packaging can potentially have a negative effect on the DNA of human colon epithelial cells. We recommend seasoning of freshly formed polystyrene products and increasing personal protection in relation to workers of the polystyrene foaming factories This applies primarily to dairy products, readily consumed by children, which are rich in both organic acids and salts, and the presence of these ingredients enhances the genotoxic effects. According to our best knowledge, this is the first study using actual polystyrene food packaging available on the market.
Simultaneous enhancement of iron deficiency tolerance and iron accumulation in rice by combining the knockdown of OsHRZ ubiquitin ligases with the introduction of engineered ferric-chelate reductase
Authors: Kobayashi Takanori , Maeda Keisuke , Suzuki Yutaro , Nishizawa Naoko K. 
Published: July 2022

Abstract
Iron is an essential micronutrient for living organisms, but its solubility is extremely low under alkaline conditions. Plants often suffer from iron deficiency chlorosis in calcareous soils, which consist of approximately 30% of the world’s cultivated area, severely limiting plant productivity. Iron deficiency anemia is also a widespread problem in humans, especially in Asian and African people who take up iron mainly from staple foods containing low iron concentrations. Transgenic manipulation of genes involved in plant iron uptake, translocation, and storage has made improvements in enhancing iron deficiency tolerance or iron accumulation in edible parts, but these two properties have been characterized separately. We previously produced transgenic rice lines, with concomitant improvement of iron deficiency tolerance and grain iron accumulation by knocking-down OsHRZ ubiquitin ligases, which negatively regulate iron deficiency response and iron accumulation in rice. In the present report, we aimed to further improve the iron deficiency tolerance and grain iron accumulation of OsHRZ knockdown rice by the simultaneous introduction of the engineered ferric-chelate reductase gene Refre1/372 under the control of the OsIRT1 promoter for further enhancement of iron uptake. We obtained several transgenic rice lines with repressed OsHRZ expression and induced Refre1/372 expression. These lines showed a variable degree of iron deficiency tolerance in calcareous soils, with increased iron accumulation in brown seeds under both iron-deficient and iron-sufficient soil cultures. Selected OsHRZ knockdown plus Refre1/372 lines showed better growth compared with that of singly introduced OsHRZ knockdown or Refre1/372 lines in calcareous soils under both non-submerged and submerged conditions. After submerged calcareous soil cultivation, these OsHRZ knockdown plus Refre1/372 lines accumulated 2.5–4.3 times and 17–23 times more iron concentrations than that of non-transformants in brown rice and straw, respectively, which was comparable or superior to a single OsHRZ knockdown line. Our results indicate that the combined introduction of OsHRZ knockdown and OsIRT1 promoter-Refre1/372 is highly effective in further improving the iron deficiency tolerance without compromising the iron accumulation of the OsHRZ knockdown effects.
Aberrant GATA3 expression in Large B-cell Lymphoma with IRF4 rearrangement: a pitfall in the pathological diagnosis, a case report
Authors: Lu Min-ya , Teng Li-song , Wang Zhe , Teng Xiao-dong , Wang Zhao-ming 
Published: July 2022

Abstract
Background Large B-cell lymphoma (LBCL) with interferon regulatory factor 4 (IRF4) rearrangement (LBCL-IRF4) is a rare entity of LBCL with a specific clinical presentation. Notably, it is defined by the presence of an IRF4 rearrangement. Case presentationHere, we describe a case of a 2-years-old child presenting with a LBCL-IRF4 located in the left tonsil, with characteristic histologic appearance and the phenotype of neoplastic cells. The histologic analysis showed the monomorphic atypical lymphoid cells were medium size or large, positive for CD20, CD79a, MUM-1, GATA3, and Ki-67 was about 80%; Fluorescence in situ hybridization (FISH) analysis confirmed the presence of an IRF4 rearrangement. The patient was followed up for 18 months with no evidence of recurrence after being treated with 1 cycles of R-CHOP.ConclusionMorphologically, LBCL-IRF4 has predominantly diffuse or follicular pattern with a large number of necrosis, and a high proliferation rate, all of these suggest that the tumor is highly invasive. But actually LBCL-IRF4 usually performs a favorable outcome after therapy. Furthermore, LBCL-IRF4 with GATA3 positive have never been reported.
The core metabolome and exudation dynamics of three phylogenetically distinct plant species
Authors: Brecht Sarah , Zhalnina Kateryna , Kosina Suzanne , Northen Trent , Sasse Joelle 
Published: July 2022

Abstract
Root exudates are plant-derived, exported metabolites that likely shape root-associated microbial communities by acting as nutrients and signals. However, root exudation dynamics are unclear and thus also, if changes in exudation are reflected in changes in microbiome structure. Here, we assess commonalities and differences between exudates of different plant species, diurnal exudation dynamics, as well as the accompanying methodological aspects of exudate sampling.
We find that exudates should be collected for hours rather than days as many metabolite abundances saturate over time, that growth in sterile, nonsterile, or sugar-supplemented environments significantly alters exudate profiles (sugar-supplemented: more carbohydrates, less organic acids, organoheterocyclic compounds). Brachypodium distachyon grown in. nonsterile conditions further display distinct root morphology compared to sterile or sugar-supplemented conditions. A comparison of Arabidopsis thaliana, Brachypodium distachyon, and Medicago truncatula shoot, root, and exudate metabolite profiles revealed clear differences between these species, but also a core metabolome for tissues and exudates. Exudate profiles also exhibit a diurnal signature. These findings add to the methodological and conceptual groundwork for future exudate studies to improve understanding of plant-microbe interactions.
Using Video-based Examiner Score Comparison and Adjustment (VESCA) to compare the influence of examiners at different sites in a distributed Objective Structured Clinical Exam (OSCE). Do Hawks Nest with Doves?
Authors: Yeates Peter , Maluf Adriano , Cope Natalie , McCray Gareth , McBain Stuart , Beardow Dominic , Fuller Richard , McKinley Bob 
Published: July 2022

Abstract
Purpose: Ensuring equivalence of examiners’ judgements within distributed objective structured clinical exams (OSCEs) is key to both fairness and validity but is hampered by lack of cross-over in the performances which different groups of examiners observe. This study develops a novel method called Video-based Examiner Score Comparison and Adjustment (VESCA) using it to compare examiners scoring from different OSCE sites for the first time.Materials/ Methods: Within a summative 16 station OSCE, volunteer students were videoed on each station and all examiners invited to score station-specific comparator videos in addition to usual student scoring. Linkage provided through the video-scores enabled use of Many Facet Rasch Modelling (MFRM) to compare 1/ examiner-cohort and 2/ site effects on students’ scores.Results: Examiner-cohorts varied by 6.9% in the overall score allocated to students of the same ability. Whilst only a tiny difference was apparent between sites, examiner-cohort variability was greater in one site than the other. Adjusting student scores altered their rank position by up to 3 deciles.Conclusions: Whilst comparatively limited examiner participation rates may limit interpretation of score adjustment in this instance, this study demonstrates the feasibility of using VESCA for quality assurance purposes in large scale distributed OSCEs.
Evaluating and Predicting a City’s Water Resources Carrying Capacity Using a Multiple Linear Regression Model
Authors: Zhang Ziying , Yin zhiwei , Chen Yuyao , Chen Jialun 
Published: July 2022

Abstract
To identify the status of the water resources carrying capacity in Taizhou City in China, this paper selected 17 evaluation indicators and used principal component analysis to analyze the factors influencing that capacity. Then, an evaluation model was established to assess the water resources carrying capacity in the same city from 2011 to 2020, and a multiple linear regression model was established to predict the total water consumption from 2021 to 2026. The results show that as Taizhou has constructed a water-saving society, its water resources carrying capacity has gradually increased. From 2021 to 2026, Taizhou's total water consumption is predicted to show a downward trend each year. Based on the comprehensive evaluation and prediction results of water resources carrying capacity, the paper proposed water resources management and control measures for Taizhou, providing scientific support for the rational development and utilization of water resources.