bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coelimycin inside out — negative feedback regulation by its intracellular precursors
Authors: Kotowska Magdalena , Wenecki Mateusz , Bednarz Bartosz , Ciekot Jarosław , Pasławski Wojciech , Buhl Tomasz , Pawlik Krzysztof J. 
Published: December 2024

Abstract
Coelimycin (CPK) producer Streptomyces coelicolor A3(2) is a well-established model for the genetic studies of bacteria from the genus Streptomyces, renowned for their ability to produce a plethora of antibiotics and other secondary metabolites. Expression regulation of natural product biosynthetic gene clusters (BGCs) is highly complex, involving not only regulatory proteins, like transcription factors, but also the products of the biosynthetic pathway that may act as ligands for some regulators and modulate their activity. Here, we present the evidence that intracellular CPK precursor(s) (preCPK) is involved in a negative feedback loop repressing the CPK BGC. Moreover, we provide a characterization of the cluster-encoded efflux pump CpkF. We show that CpkF is essential for the extracellular CPK production. In order to track down which CPK compounds — intra- or extracellular — are the ones responsible for the feedback signal, a luciferase-based reporter system was applied to compare the activity of 13 CPK gene promoters in the wild-type (WT) and two mutated strains. The first strain, lacking the CPK-specific exporter CpkF (ΔcpkF), was unable to produce the extracellular CPK. The second one did not produce any CPK at all, due to the disruption of the CpkC polyketide synthase subunit (ΔcpkC). All tested promoters were strongly upregulated in ΔcpkC strain, while in the ΔcpkF strain, promoter activity resembled the one of WT. These results lead to the conclusion that the CPK polyketide acts as a silencer of its own production. Supposedly this function is exerted via binding of the preCPK by an unidentified regulatory protein.

Key points
•Intracellular coelimycin precursor takes part in a negative cpk cluster regulation
•CpkF exporter is essential for the extracellular coelimycin production
•Simple method for the analysis of coelimycin P2 production in agar medium

Graphical abstract
History of antineutrophil cytoplasmic autoantibodies
Authors: de Groot Kirsten , Csernok Elena , van der Woude Diane 
Published: December 2024

AbstractAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are autoimmune inflammatory small-vessel disorders with potentially life-threatening organ manifestations. Recent disease definitions and classification criteria allow distinction between granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and non-granulomatous microscopic polyangiitis (MPA). The discovery of ANCA—autoantibodies directed against proteolytic enzymes of neutrophil granules—has enabled earlier diagnosis of AAV and paved the way to stage-adapted treatments. ANCA testing initially relied on different immunofluorescence patterns, i.e., cytoplasmic ANCA (C-ANCA) vs. perinuclear ANCA (P-ANCA), in ethanol-fixed neutrophils. This is nowadays outperformed by well-standardized immunoassays against the ANCA target antigens proteinase 3 (PR3) and myeloperoxidase (MPO) for the diagnosis of small-vessel vasculitides. The discovery of ANCA has contributed substantially to unravelling the pathogenesis of AAV, which comprises neutrophil degranulation, NETosis with concurrently amplified ANCA antigen presentation, and intra- and transmural vascular inflammation involving the alternative complement system in susceptible individuals. There is a genetic disposition concerning certain HLA alleles and polymorphisms of the proteinase 3 gene. Furthermore, epigenetic modifications impact on disease activity and relapse. During follow-up, the ANCA titer is not a reliable mirror of disease activity; however, PR3-ANCA positivity is associated with a greater likelihood of relapse and a better treatment response to rituximab as compared to cyclophosphamide/azathioprine. Within the past 60 years, the discovery of ANCA has revolutionized the ability to diagnose, understand, classify, and treat AAV in a targeted manner.
A brief history of insect neuropeptide and peptide hormone research
Authors: Nässel Dick R. 
Published: December 2024

Abstract
This review briefly summarizes 50 years of research on insect neuropeptide and peptide hormone (collectively abbreviated NPH) signaling, starting with the sequencing of proctolin in 1975. The first 25 years, before the sequencing of the Drosophila genome, were characterized by efforts to identify novel NPHs by biochemical means, mapping of their distribution in neurons, neurosecretory cells, and endocrine cells of the intestine. Functional studies of NPHs were predominantly dealing with hormonal aspects of peptides and many employed ex vivo assays. With the annotation of the Drosophila genome, and more specifically of the NPHs and their receptors in Drosophila and other insects, a new era followed. This started with matching of NPH ligands to orphan receptors, and studies to localize NPHs with improved detection methods. Important advances were made with introduction of a rich repertoire of innovative molecular genetic approaches to localize and interfere with expression or function of NPHs and their receptors. These methods enabled cell- or circuit-specific interference with NPH signaling for in vivo assays to determine roles in behavior and physiology, imaging of neuronal activity, and analysis of connectivity in peptidergic circuits. Recent years have seen a dramatic increase in reports on the multiple functions of NPHs in development, physiology and behavior. Importantly, we can now appreciate the pleiotropic functions of NPHs, as well as the functional peptidergic “networks” where state dependent NPH signaling ensures behavioral plasticity and systemic homeostasis.
Analysis of urine pH and specific gravity in pasture sheep
Authors: Musara Colin , Ndjoze Vati , Matomola Ophelia Chuma , Chitate Frank 
Published: December 2024

Abstract
Urine pH and specific gravity represent the routine objectively verifiable parameters in urinalysis. Urinalysis is presently an underutilised analytical tool in ovine medicine but holds the same potential for predictive, diagnostic and prognostic use in sheep as it does in human and small animal medicine. Urine pH and specific gravity were measured as a health screening tool to ascertain normal physiological ranges in sheep on free-range summer pastures with free access to drinking water. Both sexes, different ages and various breeds including Dorper, Karakul, Damara and cross-breeds were recruited into the study to investigate possible sources of variation. Experimental animals were selected through stratified random sampling using farm records from a population of 69 rams, 135 ewes and 115 lambs. Samples of urine were collected from 60 rams, 60 ewes and 60 lambs by free catch following induction of micturition by transient apnoea. Urine pH was measured by a pH metre whilst urine specific gravity was evaluated with an optical refractometer. The urine pH ranged from 6.81 to 9.08, with a mean of 8.52 ± 0.02 (se). Only one animal had a urine pH value below the existing reference level (7.4–8.5). Concurrent abnormalities of the urine in dipstick analysis included proteinuria and glucosuria. Urine specific gravity varied from 1.003 to 1.050 with a mean of 1.021 ± 0.001 (se). Four sheep, all of them lambs, had urine-specific gravity values above the existing reference level (1.015 to 1.045). The high urine specific gravity was associated with diverse pathological findings including proteinuria, pyuria and glucosuria as well as the presence of urine sediment. Urine pH was influenced by gender and breed and specific gravity by age. The results affirmed that sheep naturally produce alkaline urine and aciduria points to an underlying pathological problem. An association between high urine specific gravity and systemic/urinary system disorders was evident in lambs. Isosthenuria and hyposthenuria were frequently encountered in healthy adult sheep and were considered indices of positive water balance rather than renal dysfunction. Collated data confirmed existing reference levels but revised the upper limit of normal urine pH to 9 instead of 8.5, and the lower limit of normal urine specific gravity to 1.003 instead of 1.015.
Osteoporosis screening using X-ray assessment and osteoporosis self-assessment tool for Asians in hip surgery patients
Authors: Higuchi Ryo , Uemura Keisuke , Kono Sotaro , Mae Hirokazu , Takashima Kazuma , Abe Hirohito , Imagama Takashi , Sakai Takashi , Okada Seiji , Hamada Hidetoshi 
Published: December 2024

Abstract
Objectives
As many patients with osteoporosis remain undiagnosed, we aimed to develop a simple method to efficiently screen for osteoporosis using a combination of anteroposterior hip X-ray assessment and the Osteoporosis Self-Assessment Tool for Asians (OSTA), which is calculated as (body weight − age) × 0.2.

Methods
One hundred Japanese women (age: 73 ± 11 years, body weight: 54.4 ± 11.1 kg) who underwent hip surgery, anteroposterior hip X-ray, and DXA were included. Based on the DXA results of the total proximal femur, 35 cases were diagnosed with osteoporosis. Fifteen orthopaedic surgeons visually inspected the hip X-ray images and scored the suspicion of osteoporosis on a scale of 1–4 (1: very unlikely, 4: very suspicious), which is referred to as “pred-score.” In addition, OSTA was calculated as a continuous variable (OSTA score). Osteoporosis was screened using the pred-score and OSTA score, and both scores were analyzed using the receiver operating characteristic curves.

Results
The area under the curves (AUCs) of the pred-score and OSTA score were 0.626–0.875 and 0.817 across surgeons, respectively. When both scores were used, the AUC for screening osteoporosis ranged from 0.821 to 0.915 across surgeons. Significant improvement from AUCs calculated with the pred-score or OSTA score was found in 11 surgeons (73.3%).

Conclusion
The combination of X-ray assessment and OSTA can be used to screen for osteoporosis and has the potential to be used as a new simple screening tool in daily clinical practice.
Biological control of pests of stored cereals with the predatory mites Blattisocius tarsalis and Cheyletus malaccensis
Authors: del Arco Lidia , Castañé Cristina , Riudavets Jordi 
Published: December 2024

AbstractNumerous arthropod pest species can cause significant losses in the quantity and quality of stored products. Currently, the most common pest control strategy is the use of a limited number of authorized synthetic insecticides. However, the overuse of these insecticides has led to an increase in pesticide resistance, reducing their effectiveness. Biological control using natural enemies offers an effective alternative to prevent insect populations from reaching pest status. Generalist predatory mites are noted for their potential as biocontrol agents as they can prey on a large variety of pest species and are easy to manage and apply. We evaluated the suitability of three predatory mites, Blattisocius tarsalis, Cheyletus malaccensis, and Amblyseius swirskii, for controlling several insect pests that are usually present in stored cereals. Prey acceptance and predation rates were assessed in experiments in which a known number of preys were offered to mite females in different arenas. Blattisocius tarsalis and C. malaccensis exhibited broad polyphagous behavior on insect pests commonly found in stored rice and other cereals. In contrast, A. swirskii was ineffective against these pest species. The efficacy of B. tarsalis and C. malaccensis, individually or in combination, in controlling populations of Oryzaephilus surinamensis and Sitotroga cerealella in medium-size arenas was also evaluated. Whether individually or in combination, both predatory mites reduced populations of O. surinamensis or of S. cerealella by half. These results suggest that periodic releases of these predatory mites could maintain these pest populations under control.
Phenotypic and Molecular Screening for Yellow Rust Resistance in Chinese Wheat Hybrids as Impacted by Selection
Authors: Iftikhar Zainab , Arif Muhammad , Iqbal Aamir , Munir Iqbal , Zhang Sheng Quan , Zhao Chang Ping , Ali Sajid 
Published: December 2024

AbstractExploring the potential of novel sources of wheat material is immensely important to combat the ever-changing pathogen causing wheat rust disease, associated with huge losses worldwide. This study focused on assessing rust (YR) resistance in Chinese wheat hybrids, combining molecular markers and field testing over two years with estimation of the impact of selection. Out of 416 hybrids, 108 were selected based on disease scoring parameters, showing negative genetic advancement for rust severity and coefficient of infection. The maximum rust severity reached 100% for four hybrids during the year 2017–18 whereas 70% for three hybrids during the year 2018–19. The maximum coefficient of infection was observed for four hybrids which were 100% (2017–18), whereas 70% for three hybrids (2018–19). Molecular genotyping with a set of five yellow rust resistance genes linked markers revealed that the most frequent molecular markers was Yr18/Lr34 (among the YR markers), present in 92 out of 108 hybrids. All the five Yr genes were present only in 18 hybrids. Yr18 was the most common resistance gene detected in 85% hybrids, while Yr17 was the least detected gene (57%). Notably, the average coefficient of infection (ACI) was not directly associated with the number of resistant genes. Considering the overall performance, the hybrid lines 17BH002, 17BH057, 17BH073, 17BH109, 17BH123, 17BH128, 17BH190, 18BH026 and 17BH155 had an overall low yellow rust severity and co-efficient of infection and could be considering promising lines for further utilization. Clustering based on rust resistance genes categorized hybrids into five main clusters for YR resistance genes, showing variability among these valuable genetic resources. The observed variability in this study can be utilized for future breeding programs focused on developing resistant wheat varieties.
Parasitoids of the invasive cotton mealybug, Phenacoccus solenopsis Tinsley (Hemiptera, Pseudococcidae), in Iraq
Authors: Khudhair Ahmed Hasan , Kareem Ali A. , Watson Gillian W. , Kresslein Robert L. , Beasley Jordan , Topakcı Nurdan , Polaszek Andrew 
Published: December 2024

AbstractPhenacoccus solenopsis Tinsley (Hemiptera, Pseudococcidae) is an invasive mealybug globally, having originated in North America. During routine rearing of this pest in a plant nursery in Karbala, Iraq in June 2023, three species of parasitoid wasps (Hymenoptera, Chalcicoidea) emerged from the mealybug colonies, or were extracted as pupae from parasitised mealybugs. They were identified using both morphology and DNA sequencing as Aenasius arizonensis (Girault), Cheiloneurus nankingensis Li and Zu (Encyrtidae), and Marietta pictus (André) (Aphelinidae). The latter two species represent new country records for Iraq. All three species are diagnosed and illustrated below, with summaries of their distributions and biology. The importance of having databases available of barcodes and other diagnostic sequence data is emphasised in the context of biological control programmes.
Do labour productivity, capital productivity and education influence the technical efficiency of entrepreneurial outcomes? Evidence from europe
Authors: Silva Pedro Mendonça , Moutinho Victor Ferreira , Gaspar Pedro Miguel 
Published: December 2024

AbstractThe differences in Labour and Capital Productivity and Education in Europe were used to provide a comprehensive evaluation of the performance of technical efficiency of entrepreneurship activities and new firm creation. For this purpose, two distinct methodologies were used: a non-parametric Data Envelopment Analysis (DEA) and a parametric Stochastic Frontier Analysis (SFA). Firstly, to obtain the ranking for assessing entrepreneurship efficiency, two outputs (birth rate and total early-stage entrepreneurial activity) were combined, and four inputs (long-term unemployment rate, household disposable income ratio S80/S20; young people neither in employment nor in education or training and employment rate of recent graduates) were applied. In the second step, two estimators were used to examine the effect of capital productivity, labour productivity, non-qualified labour, and population share of education on the technical efficiency score of entrepreneurial outcomes. The estimators were the Tobit regression, including random effects and mixed effects models, and the quantile regression model. The results for technical efficiency in the first step reveal that during 2008–2014 and after this period, 2015–2019, the European countries of Lithuania, Estonia and the Netherlands present the highest efficiency scores according to the DEA-CRS model. Applying the SFA technique, Belgium, Germany, and Malta show the highest levels of inefficiency during both periods of financial crisis. The second stage results demonstrate that there was a negative and significant effect of capital productivity on the efficiency scores of entrepreneurial outcomes in the periods of financial crises. This statistical evidence mirrors the observed decrease in average EU investments in fixed capital, structural changes in the labour market, and structural changes in education level in the active and inactive population, particularly in countries with economic growth, during the sub-periods between 2008 and 2019 under consideration.
Influence of the Reduction Rate of Slag from Oxidation Process of Cu–Fe–Pb Alloy During Reduction (De-coppering) on Its Viscosity
Authors: Madej Piotr 
Published: December 2024

Abstract
The production of copper based on a direct-to-blister flash smelting process made it necessary to introduce the technology for the reduction of flash smelting slag and subsequent refining of the resulting Cu–Fe–Pb alloy. Refining of Cu–Fe–Pb alloy produces a converter slag containing 7 ÷ 25 wt pct Cu, 3 ÷ 20 wt pct Fe , and 15 ÷ 45 wt pct Pb. This material is directed to the reduction (de-coppering) process, which allows the recovery of copper in the form of Cu–Pb alloy as well as the removal of lead from the copper material cycle in the form of lead-bearing material. The copper recovery rate in the form of Cu–Pb alloy depends on a number of factors, of which one of the primary ones is the viscosity of the medium (slag), which determines the rate of coalescence and sedimentation of the reduced metal droplets. The investigations on how the degree of reduction of metal oxides from the converter slag affects its viscosity are presented in the study. Viscosity tests were conducted in the range of 1000 ÷ 1450 °C and showed that the main factor affecting viscosity is the Cu2O content in the slag. Slags directed to the reduction process with a high Cu2O content have a lower viscosity than slags after the reduction process, which is due to a decrease in the copper oxide content of the slag. The viscosity of slags after reduction depends on the PbO content, the higher the PbO content the lower the slag viscosity. Furthermore, studies have shown that the viscosity of slags can be reduced by adding CaO to the slag.
Flexibilisering in de jeugdgezondheidszorg: passende zorg voor alle kinderen
Authors: Kocken Paul L. , Theunissen Meinou H. C. , Bezem Janine , Huizing Arjan , van der Ploeg Kitty C. B. P. , Lanting Caren I. , Blanson Henkemans Olivier A. 
Published: December 2024

SamenvattingDe jeugdgezondheidszorg (JGZ) ziet een toename van complexere problematiek bij kinderen, met name gerelateerd aan leefstijl en mentale gezondheid. Daarnaast is er een tekort aan jeugdartsen en -verpleegkundigen in de JGZ. Om extra zorg te kunnen leveren aan kinderen die dit het meeste nodig hebben, worden in JGZ-organisaties professionals vrijgemaakt. Dit geschiedt door een flexibelere uitvoering van aantal en vorm van de contactmomenten, en herschikking van taken tussen disciplines. Dit onderzoek vergelijkt drie JGZ-organisaties in de mate waarin zij flexibel werken. Inzicht wordt gegeven in het aandeel basiszorg- en extra zorgactiviteiten door de JGZ, en de inzet van de verschillende JGZ-disciplines (jeugdartsen, jeugdverpleegkundigen, consultatiebureauassistentes en doktersassistentes). We maken gebruik van een steekproef uit het digitaal dossier JGZ van kinderen in de leeftijd van 0–12 jaar (n = 15.776). De meest geflexibiliseerde organisatie heeft de meeste kinderen in extra zorg en de minst geflexibiliseerd JGZ-organisatie de minste kinderen. De delegatie van taken van de jeugdarts naar de jeugdverpleegkundige is vooral zichtbaar bij het verrichten van extra zorg door de organisatie met een focus op taakherschikking. De meest geflexibiliseerde organisatie heeft de hoogste ureninzet van jeugdartsen in de extra zorgactiviteiten, vooral bij 0–4-jarigen. Concluderend kunnen flexibilisering van contact (frequentie en vorm) en vrijere inzet van disciplines (taakherschikking) leiden tot meer inzet van extra zorg in de JGZ. Daarmee kunnen deze een rol spelen in het leveren van passende zorg. Verder onderzoek is echter nodig om het totaalbeeld te krijgen van factoren die, naast flexibilisering, de geboden JGZ-zorg bepalen.
The Faraoskop event: a significant moment in the history of foraging in the western cape, South Africa?
Authors: Parkington John , Loftus Emma , Manhire Antony , Webley Lita 
Published: December 2024

Abstract
Here we make the case that the interment of twelve skeletons in a small Western Cape rock shelter should be viewed as a single event. We present evidence of the partially disarticulated, clearly overlapping arrangement of human remains and the radiocarbon dating results from the individuals that point to a hasty but coordinated burial at a critical moment in the prehistory of the Cape. The moment was marked by the earliest appearance of the pastoralist lifestyle in an area previously dominated by hunting and gathering (Sadr PLoS ONE 10(8):e0134215, 2015). Because, as others show (Dlamini et al., this volume), these interments are associated with peri-mortem violence, the demonstration of contemporaneity and entanglement implies a rare occurrence of so many deaths at a time when conflict between pastoralists and hunter-gatherers in the area seems likely. In describing the circumstances of bone recovery, the positioning of body parts and the associated radiocarbon ages, we lay the platform for further micro-stratigraphic, biological, genetic and isotopic studies of the twelve individuals and some contemplation on the nature of the event.